Dissertations / Theses on the topic 'Schizophrenia – Risk factors'
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Lee, Heeyoung. "Protective and risk factors in adolescents with schizophrenia /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/7263.
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Eriksson, Åsa. "Risk factors for criminal offending among men with schizophrenia." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-666-2/.
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Suvisaari, Jaana. "Incidence and risk factors of schizophrenia in Finland." Helsinki : University of Helsinki, 1999. http://ethesis.helsinki.fi/julkaisut/laa/kansa/vk/suvisaari/.
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Roberts, Seth. "Season of Birth and Risk for Schizophrenia." VCU Scholars Compass, 2008. http://scholarscompass.vcu.edu/etd/1633.
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Background: Schizophrenia is a chronic, debilitating mental disorder characterized by positive (e.g., hallucinations, delusions) and negative (e.g., catatonia, flat affect) signs and symptoms. Many studies suggest that individuals born in winter or spring months are at increased risk for schizophrenia. Study Objectives: 1) To determine whether season of birth affects risk for schizophrenia in the Irish Study of High Density Schizophrenia Families (ISHDSF). 2) To examine, by computer simulation, power to detect genetic associations with schizophrenia under a variety of conditions and using different analytic strategies. 3) To test whether specific genes are associated with schizophrenia in the Irish Case Control Schizophrenia Study (ICCSS), using different analytic strategies to account for season of birth. Methods: A case-control design was used to examine the relationship between schizophrenia and season of birth. Cases were individuals from the ISHDSF diagnosed with schizophrenia. Controls were the general population of Ireland, with data provided by Ireland’s Central Statistics Office (CSO). The birth frequencies for each month or quarter were compared in the two groups by a chi square test. Computer simulations were conducted to examine power to detect schizophrenia susceptibility loci using either all cases or only cases born in high-risk months, under different conditions and models for how genetic risk and season of birth interact to influence risk for schizophrenia. Data for six genetic markers from the ICCSS were analyzed for evidence of association, using all cases, and then using only cases born in high-risk months. Setting and Study Participants: ISHDSF families were ascertained through inpatient psychiatric care facilities serving >95% of the Irish population. Diagnoses were established using DSM-III-R criteria, and birthdates were recorded for all individuals. The Irish CSO provided aggregate, population-level data for number of births in Ireland by month for the years 1976-2000 and by quarter for the years 1900-2000. The ICCSS is a sample of schizophrenic and control individuals who have been genotyped at many loci across the genome. Schizophrenics were ascertained through in- and outpatient psychiatric facilities, had diagnoses verified by an expert, and their birthdates recorded. Controls were selected from several sources, e.g. blood donation centers, and denied any lifetime history of schizophrenia. For each subject in the ICCSS, all four grandparents were born in Ireland or the United Kingdom. Results: Number of births in each month was compared for schizophrenics in the ISHDSF and general population controls, resulting in a chi square of 19.44 (p value ~ 0.054, 11 df). Simulations revealed that, in some circumstances, power to detect genetic associations was increased by restricting cases to those born in high-risk months. Analysis of data from the ICCSS revealed that restricting cases to high-risk birth months increased the evidence for association for three of six markers tested, two of which were associated with the gene FBXL21. Conclusions: Birth in the months of March, April, or May appears to be associated with elevated risk for schizophrenia in the ISHDSF. In attempting to find susceptibility loci for schizophrenia, restricting genetic association analyses to schizophrenics born in high-risk months may result in increased power to detect genetic association in some circumstances.
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Spencer, Michelle Kerry. "Examining the use of dynamic risk factors to predict high risk behaviours in people with schizophrenia." Thesis, University of Warwick, 2009. http://wrap.warwick.ac.uk/3261/.
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The following thesis discusses aspects of risk management within a dynamic framework. It focuses on risk management with people with schizophrenia, as they are considered to be at more risk than the general population both of harming others and harming themselves. The literature review summarises current research into suicide risk factors in the schizophrenia population. People with a diagnosis other than schizophrenia, such as schizoaffective disorder, are not included in the review. Studies that are dealing with factors that are open to change (dynamic), or that indicate or trigger imminent acute risk, are discussed. The literature is evaluated in terms of its methodologies, its findings and its place within a dynamic risk framework. Recommendations are made for future research. The main research paper explores a developing methodology to produce a high risk behaviour signature, utilising the concepts of early warning signs, psychosis relapse signatures, functional analysis and a dynamic risk model conceptualised from the sexual offending field. Support was found for staff’s ability to agree on relevance at a crude level for early warning signs of high risk behaviours compared to dummy signs, the occurrence of early warning signs, and the occurrence of high risk behaviour. Results are discussed further within the context of dynamic assessments of risk. The reflective review discusses philosophical, clinical and research reflections relating to the thesis. Three main themes are considered: the philosophical underpinnings of research; the impact of the process of research; clinical and ethical implications of research.
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Morgan, Vera Anne. "Intellectual disability co-occurring with schizophrenia and other psychiatric illness : epidemiology, risk factors and outcome." University of Western Australia. School of Psychiatry and Clinical Neurosciences, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0209.
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(Truncated abstract) The aims of this thesis are: (i) To estimate the prevalence of psychiatric illness among persons with intellectual disability and, conversely, the prevalence of intellectual disability among persons with a psychiatric illness; (ii) To describe the disability and service utilisation profile of persons with conjoint disorder; (iii) To examine, in particular, intellectual disability co-occurring with schizophrenia; and (iv) To explore the role of hereditary and environmental (specifically obstetric) risk factors in the aetiology of (i) intellectual disability and (ii) intellectual disability co-occurring with psychiatric illness. This thesis has a special interest in the relationship between intellectual disability and schizophrenia. Where data and sample sizes permit, it explores that relationship at some depth and has included sections on the putative nature of the link between intellectual disability and schizophrenia in the introductory and discussion chapters. To realise its objectives, the thesis comprises a core study focusing on aims (i) (iii) and a supplementary study whose focus is aim (iv). It also draws on work from an ancillary study completed prior to the period of candidacy...This thesis found that, overall, 31.7% of persons with an intellectual disability had a psychiatric illness; 1.8% of persons with a psychiatric illness had an intellectual disability. The rate of schizophrenia, but not bipolar disorder or unipolar major depression, was greatly increased among cases of conjoint disorder: depending on birth cohort, 3.7-5.2% of individuals with intellectual disability had co-occurring schizophrenia. Down syndrome was much less prevalent among conjoint disorder cases despite being the most predominant cause of intellectual disability while pervasive developmental disorder was over-represented. Persons with conjoint disorder had a more severe clinical profile including higher mortality rates than those with a single disability. The supplementary study confirmed the findings in the core body of work with respect to the extent of conjoint disorder, its severity, and its relationship with pervasive development disorder and Down syndrome. Moreover, the supplementary study and the ancillary influenza study indicated a role for neurodevelopmental insults including obstetric complications in the adverse neuropsychiatric outcomes, with timing of the insult a potentially critical element in defining the specific outcome. The supplementary study also added new information on familiality in intellectual disability. It found that, in addition to parental intellectual disability status and exposure to labour and delivery complications at birth, parental psychiatric status was an independent predictor of intellectual disability in offspring as well as a predictor of conjoint disorder. In conclusion, the facility to collect and integrate records held by separate State administrative health jurisdictions, and to analyse them within the one database has had a marked impact on the capacity for this thesis to estimate the prevalence of conjoint disorder among intellectually disabled and psychiatric populations, and to understand more about its clinical manifestations and aetiological underpinnings.
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Pukall, Monica G. "Postnatal risk factors in the etiology of schizophrenia : association with good premorbid adjustment." Thesis, McGill University, 1999. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=30728.
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Research shows distinct premorbid subtypes in schizophrenia. While family history of schizophrenia and obstetric complications are associated with poor premorbid adjustment, risk factors associated with good premorbid adjustment, characterizing most patients, remain unidentified. Both childhood trauma and premorbid substance use appear to increase vulnerability to schizophrenia. The goals of this study were to determine the association among family history, obstetric complications, childhood trauma, and premorbid substance use; and secondly, to assess whether trauma and premorbid substance use are associated with good premorbid schizophrenia. Trauma and substance use were assessed in 26 schizophrenia patients whose mothers were asked about family history of schizophrenia and obstetric complications. Results suggest that childhood trauma may co-occur with a family history of schizophrenia; high premorbid cannabis consumption was significantly associated with an absence of family history. Childhood trauma and premorbid substance use, however, did not consistently predict a good premorbid adjustment profile.
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Davie, Brenda J. "Suicidality among individuals with schizophrenia, the interaction of personality and known risk factors." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ30938.pdf.
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Pukall, Monica G. "Postnatal risk factors in the etiology of schizophrenia, association with good premorbid adjustment." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/MQ64433.pdf.
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Thompson, Rhiannon. "Genetic and functional investigation of FXYD6 and MAP2K7 as risk factors in schizophrenia." Thesis, University of Glasgow, 2013. http://theses.gla.ac.uk/4157/.
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Schizophrenia is a debilitating psychiatric disorder with a prevalence of around 1% worldwide. It is an extraordinarily complex syndrome, which encompasses multiple psychological domains leading to the impairment of a range of symptoms. These symptoms are categorised as positive symptoms, negative symptoms and cognitive deficits. The profile of cognitive deficits is broad and severe, and is likely to be present in most, if not all patients. Despite cognitive enhancement being recognised as an important treatment target in schizophrenia, the discovery of an effective treatment has been met with difficulty. The degree of psychosis is subject to numerous genetic and environmental factors. Family, twin and adoption studies show schizophrenia is unequivocally a genetic disorder, however the genetics behind schizophrenia are indisputably complex as it is not characterised by a single causative gene. A number of candidate genes have been implicated in schizophrenia. Recent genetic association studies have found an association for two genes, FXYD6 and MAP2K7, as risk factors in the susceptibility to schizophrenia. However the roles of these genes in the underlying mechanisms of the symptoms of schizophrenia are unknown. To address this I utilise two mouse models, one containing homozygous disruption of Fxyd6 (Fxyd6-/-) and one heterozygous for Map2k7 (Map2k7+/-). I employ a range of molecular and behavioural tests to investigate the roles FXYD6 and MAP2K7 in schizophrenia- like phenotypes in these mice. FXYD proteins are a family of seven single-span transmembrane proteins, all thought to be regulators of the Na+ K+ ATPase pump in a tissue-specific fashion. Up until now, FXYD6 function and its role in the risk to schizophrenia remain unclear. To address this I firstly investigated the association between FXYD6 and schizophrenia in a Northern European population using a genetic association study. However from this study I was unable to confirm an allelic or haplotypic association between FXYD6 and schizophrenia. Furthermore there was also no evidence for a role of epistatic interactions between FXYD6 and MAP2K7 in the risk of schizophrenia. A putative functional link for FXYD6 in schizophrenia was explored further using Fxyd6-/- mice. The in situ hybridisation technique was utilised to reveal the expression of Fxyd6 in the mouse brain. Fxyd6 is interestingly expressed in the prefrontal cortex and hippocampus, two brain regions associated with schizophrenia and learning and memory. In addition, I have shown for the first time that disruption of Fxyd6 results in a significant deficit in Na+ K+ ATPase activity in the forebrain, confirming that FXYD6 is a modulator of mouse brain Na+ K+ ATPase activity. Anxiety- like behaviours and hyperlocomotion were explored Fxyd6-/- mice. However activity in plus maze and open field tests, and response to amphetamine or ketamine was not altered in comparison to wildtype mice. Nonetheless subtle deficits observed in prepulse inhibition suggest potential deficits in neurotransmission in Fxyd6-/- mice may be present. Interestingly, Fxyd6-/- mice displayed deficits in working memory at delays of 5 seconds, indicating cognitive deficits. The molecular characterisation and insight into the phenotype of Fxyd6-/- mice are encouraging to investigate the role of FXYD6 in underlying mechanisms of schizophrenia-like symptoms further. MAP2K7 belongs to the family of Map Kinases which have key roles in the regulation of a diverse range of cellular processes such as gene expression, apoptosis and synaptic plasticity. The brain expression of Map2k7 was previously unknown, however this study utilised the in situ hybridisation technique to show expression in regions associated with schizophrenia, including the PFC and the hippocampus. For the reason that the homozygous disruption of Map2k7 is embryonically lethal, mice heterozygous for the disruption Map2k7 were used to explore the role of MAP2K7 in the susceptibility to schizophrenia. RTqPCR confirmed a modest but significant reduction of Map2k7 in these mice. The heterozygous deletion of Map2k7 results in alteration of glutamate receptor Grin1 expression, a receptor reported to have altered expression in schizophrenia. Furthermore, Map2k7+/- mice display cognitive deficits, as observed by increased perseverative responding in the working memory task. Despite not exhibiting deficits in PPI, social behaviours or neurochemical deficits in GABAergic markers, Map2k7+/- mice revealed altered sensitivity to amphetamine, suggesting alterations in dopaminergic circuitry. In conclusion, this study provides an insight in to the functional roles of FXYD6 and MAP2K7. Although the roles of FXYD6 and MAP2K7 as risk factors in schizophrenia still requires further elucidation, these results provide evidence of a putative role for both genes in some areas of the underlying neuronal activity associated with schizophrenia-associated symptoms. Furthermore, results from this study suggest both strains of mice are potential rodent models of cognitive impairments.
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Hubbard, Leon. "Common and rare genetic risk factors for schizophrenia and their associations with cognition." Thesis, Cardiff University, 2014. http://orca.cf.ac.uk/73174/.
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Individuals with schizophrenia have severe cognitive impairments that impact upon their ability to function within society. Better understanding the genetic mechanisms underlying schizophrenia and cognition provides an opportunity for targeted pharmacological intervention. This thesis investigates common and rare genetic variation in schizophrenia and their associations with cognitive ability in schizophrenia cases and healthy controls. Polygenic risk of schizophrenia and bipolar disorder predicted ability on tests of cognitive domains affected in schizophrenia, performance, verbal and full scale IQ in healthy controls. Increased polygenic risk of schizophrenia was robustly associated with lower performance IQ at different training thresholds in two independent cognition samples. There was no consistent association between bipolar polygenic risk and cognition. Common genetic differences between schizophrenia and bipolar disorder were associated with verbal and full scale IQ. I investigated the hypothesis that 155 gene-sets across six biological categories relating to cognition, brain function and structure were enriched for SNPs influencing general cognitive ability. Schizophrenia polygenic pathway scores for gene-sets were not associated with general cognitive ability in schizophrenia patients, or performance IQ in healthy individuals. Separately, neither gene-sets vi nor general categories were enriched for common SNPs showing association with general cognitive ability in schizophrenia cases. Associations between rare CNVs and general cognitive ability were tested in schizophrenia cases. Cases with a known pathogenic CNV performed approximately one standard deviation below other schizophrenia cases on the MATRICS composite score. In addition, increases in the number of genes hit by large (>100kb) and rare (frequency <1%) CNVs were associated with lower general cognitive ability. However, the number of genes hit in gene-sets previously mentioned was not associated with the MATRICS composite score. These findings indicate genetic variation in schizophrenia is associated with cognitive ability in schizophrenia cases and healthy controls, providing direction for future research.
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Filatova, S. (Svetlana). "Incidence of schizophrenia and associations of schizophrenia and schizotypy with early motor developmental milestones." Doctoral thesis, Oulun yliopisto, 2017. http://urn.fi/urn:isbn:9789526217178.
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Abstract Schizophrenia is a complex mental health disorder and its etiology can be investigated based on different theoretical prerequisites. The present thesis examines schizophrenia from the neurodevelopmental and psychosis continuum perspectives. Neurodevelopmental theories of schizophrenia see abnormalities in the developing nervous system as early predictors of vulnerability to the disease. Schizophrenia can be seen also as a progressive disorder and a continuum of symptomatology from personality traits (schizotypy) to full-blown schizophrenia. The aim of the present thesis is to study incidence of schizophrenia; prevalence of schizotypy; and associations between schizophrenia and schizotypy with early motor developmental milestones. The research design includes prospective cohort studies and systematic review, and meta-analysis. In two successive Northern Finland Birth Cohorts (NFBC) studies, 20 years apart (1966 and 1986), the incidence of schizophrenia remained the same, but the incidence of other psychoses and therefore all psychoses was higher in NFBC 1986. In NFBC 1966, mean schizotypy scores were among the lowest and the highest scores among 24 general population studies. When early motor developmental milestones were investigated in the meta-analyses (3 to 5 studies), a significant small effect size for walking, sitting, and standing unsupported was found with respect to adult schizophrenia. When schizotypy outcome was studied in the NFBC 1966, later achievement of turning from back to tummy, touching thumb with index finger, standing up, sitting unsupported, and walking with support were found to be associated with an increase in schizotypy scales and varied somewhat by gender. To conclude, there have been changes in the incidence of all psychoses but not in schizophrenia between the two NFBCs. This is in line with other studies on the trends of incidence of psychoses, which highlights the role of changes in diagnostic systems and practices that can influence rates. In this project, mean schizotypy scores were both among the highest and the lowest estimates in the studies on schizotypy in the general population. Early motor developmental milestones were both predictors of schizophrenia and schizotypy, and thus this finding supports both the neurodevelopmental and psychosis continuum approaches to the aetiology of schizophreniaTiivistelmä Skitsofrenia on monimuotoinen mielenterveyden häiriö, jonka etiologiaa voidaan tutkia erilaisissa teoreettisissa viitekehyksissä. Tämä väitöskirja tutkii skitsofreniaa neurologisen kehityksen ja psykoosin jatkumon näkökulmista. Skitsofrenian neurokehitykselliset teoriat pitävät kehittyvän keskushermoston poikkeavuuksia varhaisina skitsofrenian alttiuden ennustajina. Skitsofreniaa voidaan pitää myös progressiivisena sairautena ja oireiden jatkumona persoonallisuuden piirteistä (skitsotypaalisuudesta) täysimittaiseen skitsofreniaan. Tämän väitöskirjatutkimuksen tavoitteena on tutkia skitsofrenian ilmaantuvuutta, skitsotypaalisten piirteiden yleisyyttä ja skitsofrenian ja skitsotypaalisten piirteiden yhteyttä varhaiseen motoriseen kehitykseen. Tutkimusasetelmina ovat prospektiiviset syntymäkohortit, systemaattinen katsaus ja meta-analyysi. Kahdessa peräkkäisessä 20 vuoden välein kerätyssä Pohjois-Suomen syntymäkohortissa (1966 ja 1986) skitsofrenian ilmaantuvuus pysyi samana, mutta muiden psykoosien ja siten kaikkien psykoosien ilmaantuvuudet olivat korkeampia vuoden 1986 syntymäkohortissa. Vuoden 1966 syntymäkohortissa negatiivisen skitsotypaalisuuden piirteet olivat korkeita ja positiivisen skitsotypaalisuuden piirteet alhaisia verrattuna 24 muuhun väestöaineistoon. Varhaisen motorisen kehityksen ja aikuisiän skitsofrenian välistä yhteyttä tutkittiin meta-analyysin (3–5 tutkimusta) avulla. Tilastollisesti merkitsevä pieni negatiivinen yhteys löytyi aikuisiän skitsofrenian ja kävelemään, istumaan ja seisomaan oppimisen välillä. Pohjois-Suomen vuoden 1966 syntymäkohortissa skitsotypaaliset piirteet liittyivät hitaampaan vatsalleen kääntymisen, peukalo-etusormi otteen, seisomisen, tuetta istumisen ja tuen kanssa kävelemisen oppimiseen. Näissä yhteyksissä oli vaihtelua tutkittavan sukupuolen mukaan. Yhteenvetona voidaan todeta, että psykoosien ilmaantuvuus on kasvanut Pohjois-Suomen syntymäkohorteissa, mutta skitsofrenian ei. Tämä on linjassa aikaisempien tutkimusten kanssa. On kuitenkin huomioitava myös diagnostisten järjestelmien ja käytäntöjen merkitys näiden muutosten arvioimisessa. Varhainen motorinen kehitys ennusti sekä skitsofreniaa että skitsotypaalisia piirteitä. Havainto tukee sekä neurokehityksellistä että psykoosin jatkumoon liittyvää lähestymistapaa skitsofrenian etiologiassa
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Keskinen, E. (Emmi). "Parental psychosis, risk factors and protective factors for schizophrenia and other psychosis:the Northern Finland Birth Cohort 1966." Doctoral thesis, Oulun yliopisto, 2015. http://urn.fi/urn:isbn:9789526210483.
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Abstract The aim of this study was to investigate whether risk factors for psychosis are different among those with and without parental psychosis, and to study the interaction between parental psychosis and risk factors. Protective factors for psychosis were also examined. Data from the Northern Finland Birth Cohort 1966 (N = 10,458) was used. Biological risk factors in particular increased the risk for schizophrenia and other psychosis among those with parental psychosis. In the same group, the risk for schizophrenia was increased if the achievement of holding the head up and touching the thumb with the index finger was delayed. A new born’s large size, advanced maternal age and mother’s antenatal depressed mood had interactions with parental psychosis regarding risk for schizophrenia and the mother’s smoking during pregnancy regarding risk for other psychosis. Parental psychosis and delayed touching the thumb with the index finger had an interaction regarding risk for schizophrenia and other psychosis. Several variables were associated with the decreased risk for psychosis in the total sample. In the parental psychosis group, only a mother’s non-depressed mood and a mother’s working outside the home or studying associated to remaining unaffected. This study is one of the few studies to investigate risk factors for psychosis among those with and without parental psychosis and to examine interactions between parental psychosis and risk factors. This study showed that many risk factors increased the risk for schizophrenia and other psychosis only among those with parental psychosis. Hence, parental psychosis might even explain part of the association between some risk factors. Surprisingly few protective factors were found among those with parental psychosis. Further studies on the protective factors for psychosis are important in order to prevent psychosis in individuals at high riskTiivistelmä Tämän tutkimuksen tavoitteena oli selvittää, eroavatko psykoosien riskitekijät henkilöillä, joiden vanhemmalla oli psykoosi verrattuna niihin joiden vanhemmalla ei ollut psykoosia sekä tutkia vanhemman psykoosin ja riskitekijöiden yhdysvaikutusta. Myös psykoosilta suojaavia tekijöitä tutkittiin. Tutkimusaineistona oli Pohjois-Suomen vuoden 1966 syntymäkohortti (N = 10458). Erityisesti biologiset tekijät lisäsivät skitsofrenian ja muiden psykoosien riskiä henkilöillä, joiden vanhemmalla oli psykoosi. Viivästynyt pään kannattelun ja pinsettiotteen oppiminen lisäsivät skitsofreniariskiä henkilöillä joiden vanhemmalla oli psykoosi. Vastasyntyneen suurella koolla, äidin korkealla iällä ja raskaudenaikaisella masentuneella mielialalla oli yhdysvaikutus vanhemman psykoosin kanssa skitsofreniariskin osalta ja äidin raskaudenaikaisella tupakoinnilla muiden psykoosien riskin osalta. Vanhemman psykoosilla ja viivästyneellä pinsettiotteen oppimisella oli yhdysvaikutus sekä skitsofrenian että muiden psykoosien riskin osalta. Koko aineistossa useat tekijät liittyivät alentuneeseen psykoosiriskiin. Vain äidin ei-masentunut mieliala ja työskentely kodin ulkopuolella tai opiskelu suojasivat psykoosilta henkilöitä, joiden vanhemmalla oli psykoosi. Tämä on yksi harvoista tutkimuksista, jossa on tutkittu psykoosien riskitekijöitä erikseen henkilöillä, joiden vanhemmalla oli tai ei ollut psykoosia sekä vanhempien psykoosin ja riskitekijöiden yhdysvaikutusta. Useat riskitekijät lisäsivät skitsofreniariskiä ainoastaan henkilöillä, joiden vanhemmalla oli psykoosi, joten vanhemman psykoosi voisi selittää osan psykoosien riskitekijöistä. Psykoosilta suojaavia tekijöitä löydettiin yllättävän vähän niillä, joiden vanhemmalla oli psykoosi. Suojaavien tekijöiden tutkiminen on tärkeää, jotta suuressa psykoosiriskissä olevien sairastumista voidaan ennaltaehkäistä
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Zammit, Stanley. "An investigation into the use of cannabis and tobacco as risk factors for schizophrenia." Thesis, Cardiff University, 2004. http://orca.cf.ac.uk/48919/.
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Masse, Marjolaine. "Risk factors for premorbid cannabis use and the relationship between cannabis use and schizophrenia symptoms." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=95187.
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Cannabis use increases the risk for psychosis with a dose response relationship; the risk is particularly strong before age 15. Factors precipitating use and explaining total amount used in patients are unknown. It is likewise unknown whether patients and controls differ on predictor profiles. The amount of variance in psychotic symptoms explained by premorbid cannabis use and the unique contribution of cannabis use when controlling for risk factors for schizophrenia is also unknown. The results show that some risk factors found in the community apply to both groups in the same way, and others did not. Total amount, intensity and duration of marijuana use were also associated with positive symptoms in patients. No mediation effects of marijuana use variables on more distal predictors of schizophrenia symptoms were found. Results are discussed in the context of a hypothesis of common neural networks for both schizophrenia and substance misuse.L'usage de cannabis accroit proportionnellement le risque de développer la psychose. Ce risque est particulièrement élevé chez les moins de 15 ans. Les facteurs prédisposant à l'usage prémorbide, et expliquant le montant utilisé par les patients sont inexplorés, conséquemment, on ignore si ces groupes ont des prédispositions différentes. La variation dans les symptômes expliquée par ces facteurs d'usage et la contribution unique du cannabis, lorsque les facteurs de risques pour la psychose sont contrôlés, sont également inconnus. Les résultats démontrent que certains facteurs de risque s'appliquent aux deux populations et d'autres pas. Le montant, l'intensité et la durée de l'usage sont associés avec les symptômes positifs chez les patients. Aucun effet de médiation de l'usage de marijuana sur les facteurs de prédisposition à la schizophrénie n'a été observé. Les résultats sont examinés dans le contexte d'une hypothèse de réseaux neuronaux communs à la schizophrénie et l'usage de cannabis.
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Stålberg, Gabriella. "Vulnerability and Social Functioning in Schizophrenia." Doctoral thesis, Uppsala universitet, Psykiatri, Akademiska sjukhuset, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-209626.
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This thesis offers a broad approach in elucidating biological risk factors, as well as psychological and social functioning in schizophrenia. The aims are as follows: (I) investigate the association between birth characteristics and schizophrenia, (II) study the association between levels of neurotransmitter neuropeptide Y (NPY) in cerebrospinal fluid (CSF), social function and longitudinal outcome in schizophrenia, (III) compare social functioning of patients with schizophrenia with their biological siblings and (IV) explore how siblings to patients with schizophrenia perceive the sibling relationship and their role. Paper I was a cohort analysis of 11,360 same-sexed twins in which obstetric records were used. Low birth weight and small head circumference were associated with later development of schizophrenia. To some extent the results persisted in the within-pair analyses conducted on 82 pairs discordant for schizophrenia. Fifty-six patients with schizophrenia were included in paper II. Levels of NPY in CSF correlated to social competence at index admission. For each standard deviation increase in baseline NPY, there was a concomitant increased risk of being unemployed, having moderate or severe symptoms or recent hospitalization at the 3-year follow-up. In paper III, social functioning was investigated using the Swedish version of the videotaped test Assessment of Interpersonal Problem Solving Skills (AIPSS) in 70 participants (25 patients with schizophrenia, 20 siblings and 25 randomly selected controls). The patients presented severe deficits in social functioning. The siblings expressed subtle impairments in nonverbal language but did not generally differ from the controls. To explore the siblings’ perspective on schizophrenia a qualitative study was conducted with interviews of 16 siblings in paper IV. A unifying major theme was an emotional sibling bond. Siblings developed several coping patterns, including avoidance, isolation, normalization, care giving and grieving. A third major theme consisted of the fear of inheriting schizophrenia. In conclusion, fetal growth, altered levels of NPY in CSF and subtle impairments in nonverbal social behavior might be important risk factors in schizophrenia. Patients with schizophrenia revealed extensive impaired social functioning, and from the siblings’ perspective, a brother or sister’s diagnosis of schizophrenia seems to have a profound psychological impact on the siblings.
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Nilsson, Emma. "Genetic epidemiological studies of adverse pregnancy outcomes and the role of schizophrenia /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-590-9/.
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Stokes, Paul Robert Alexander. "Investigating the effects of gnetic and environmental risk factors for schizophrenia on the human dopaminergic system." Thesis, Imperial College London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.530447.
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Dickson, Marguerite Mulryan. "Genetic and psychiatric treatment related risk factors for type 2 diabetes in schizophrenia and schizoaffective disorder patients." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2009r/dickson.pdf.
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Alaräisänen, A. (Antti). "Risk factors and pathways leading to suicide with special focus in schizophrenia:the Northern Finland 1966 Birth Cohort Study." Doctoral thesis, University of Oulu, 2010. http://urn.fi/urn:isbn:9789514262630.
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Abstract The aim of this study was to investigate risk factors, developmental pathways and the rate of attempted or accomplished suicide in a longitudinal population-based prospective birth cohort. The Northern Finland 1966 Birth Cohort (NFBC 1966) consists of 12,068 pregnant women with expected dates of delivery in 1966, and their 12,058 live-born children. The data used here was collected prospectively for 10,934 individuals who were alive and resident in Finland at the age of 16. This study utilized an extensive data set collected in antenatal clinics at mid-pregnancy, by postal questionnaire at the age of 14 years and through national registers. A total of 121 suicide attempts (57 males) and 69 suicides (56 males) had occurred by the end of 2005. A single-parent family was a risk factor for attempted suicides and grand multiparity for suicides in male offspring. Adolescent regular smoking was associated with an increased risk of suicide attempts in both genders and for suicide among males. Good school performance at age 16 years was associated with an increased risk of suicide in psychosis cases, whereas in persons who did not develop psychosis it was associated with a lower suicide risk. The suicide rate in new-onset schizophrenia followed until the age of 39 was 7%. Over two thirds of the suicides took place during the first 3 years of the illness. This was the first study of suicide rates in a prospectively followed population-based birth cohort of individuals with schizophrenia. This study replicated association between some early family-related risk factors for attempted and accomplished suicide, and also presented data for previously unstudied early factors, namely maternal antenatal depression, smoking and unwanted pregnancy This study has clarified the association between adolescent smoking and later suicide risk. It also revealed the association between good school performance and elevated risk of suicide in psychotic people, in contrast to its protective effect in the non-psychotic population. However, even though there were significant antenatal and developmental risk factors, a later psychiatric disorder seems to be the major risk factor for both attempted and accomplished suicide. Nevertheless, suicide usually seems to be a long multifactorial process that begins in early life and has complex trajectories in adolescence or early midlifeTiivistelmä Tämän tutkimuksen tarkoitus oli tutkia itsemurhien esiintyvyyttä, riskitekijöitä, siihen johtavia kehityspolkuja yleisväestöön perustuvassa prospektiivisessa pitkittäistutkimuksessa. Pohjois-Suomen vuoden 1966 syntymäkohorttiin kuului alun perin 12,068 raskaana olevaa naista joiden laskettu aika oli vuonna 1966, ja heidän 12,058 elävänä syntynyttä lastaan, kohortin jäsenet. Tässä tutkimuksessa käytetty aineisto on kerätty 11,017 kohortin jäsenestä, jotka olivat elossa ja asuivat Suomessa 16-vuotiaana. Käytetty aineisto on kerätty äitiysneuvoloissa, 14-vuotiaana tehdyssä postikyselyssä ja kansallisista rekistereistä. Kaikkiaan 121 itsemurhayritystä (joista 57 miehillä) ja 69 itsemurhaa (56 miehillä) tapahtui vuoden 2005 loppuun mennessä. Yhden vanhemman perhe syntymän aikaan oli riski myöhemmälle itsemurhayritykselle ja syntyminen monilapsiseen perheeseen (yli viisi lasta) oli riski itsemurhalle. Tupakointi 14-vuotiaana ennusti itsemurhayrityksiä kummallakin sukupuolella sekä itsemurhia miehillä. Hyvä koulumenestys 16-vuotiaana liittyi kohonneeseen itsemurhavaaraan niillä jotka myöhemmin sairastuivat psykoosiin, kun muilla se liittyi alentuneeseen vaaraan. Skitsofreniaan sairastuneista 7 % teki itsemurhan ja yli kaksi kolmannesta skitsofreniaan sairastuneiden itsemurhista tapahtui kolmen vuoden kuluessa sairastumisesta. Tämä tutkimus vahvisti aikaisempia havaintoja varhaisista riskitekijöistä itsemurhayrityksiin ja itsemurhiin. Tässä tutkimuksessa tutkittiin myös kokonaan uusia varhaisia riskitekijöitä, joita ei ole ennen tutkittu suhteessa itsemurhaan tai itsemurhayrityksiin, kuten äidin raskaudenaikainen masennus ja tupakointi sekä ei-toivottu raskaus. Tämän tutkimuksen avulla saatiin myös uutta tietoa teini-iässä aloitetun tupakoinnin suhteesta itsemurhiin ja -yrityksiin. Tutkimus paljasti hyvän koulumenestyksen lisäävän riskiä itsemurhaan henkilöillä jotka sairastuvat myöhemmin psykoosiin. Tämä oli ensimmäinen tutkimus, jossa skitsofreniaa sairastavien henkilöiden itsemurhakuolleisuutta selvitettiin yleisväestöön pohjautuvassa syntymäkohortissa. Vaikka tutkimuksessa tuli ilmi sekä syntymän, että nuoruuden aikaisia varhaisia riskitekijöitä, myöhempi psykiatrinen sairaus on merkittävin itsemurhan ja -yritysten riskitekijä. Siitä huolimatta itsemurha on aina monitekijäinen prosessi, joka voi alkaa jo ennen syntymää ja johon myöhemmät elämänvaiheet vaikuttavat
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Stenson, Gillian. "Impact of environmental risk factors for schizophrenia on the developing brain : characterisation of the effects of polyIC and THC on functional neural systems and behaviour." Thesis, University of Strathclyde, 2012. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=19517.
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Cannabis abuse can produce deficits in cognition and has been implicated as a 'late' environmental risk factor in the pathogenesis of the poly-factorial disorder schizophrenia. Evidence suggests an age-related susceptibility to the deleterious effects of cannabis as early onset of use may increase the vulnerability of the brain to the adverse consequences of cannabis abuse. Animal models are crucial for exploration of mechanistic and causative theories, and long-term behavioural consequences of adolescent cannabis abuse in a controlled experimental environment. This thesis evaluates the vulnerability of the adolescent/peripubertal brain to Δ⁹-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, and explores the potential interplay between this schizophrenia-related 'late' environmental risk factor and an 'early' environmental risk factor (prenatal infection - maternal immune activation (MIA)) on functional neural systems and behaviours relevant to schizophrenia. Cannabinoid CB1 receptor ontogeny (activated in the brain by the receptor ligand THC) within important cognitive substrates, the prefrontal cortex (PFC) and hippocampus, was investigated to delineate a period of neurodevelopmental vulnerability for peripubertal THC treatment. CB1 receptor ligand binding revealed that the PFC and hippocampus follow differential late maturational trajectories throughout the peripubertal period. The 'vulnerability window' for peripubertal THC treatment was defined as post-natal day (PD) 35-56 to encompass the dynamic peripubertal ontogenetic patterns of the CB1 receptor in both these regions. Furthermore, age-related alterations in cerebral metabolism and regional functional connectivity profiles were evident in the hippocampus and important neuromodulatory nuclei including the ventral tegmental area, dorsal raphe, locus coeruleus and the diagonal band of Broca. Acute THC administration (5mg/kg) produced hypometabolism in the thalamus and an altered functional connectivity profile between thalamic nuclei and the PFC, hippocampus and the nucleus accumbens. THC-induced anomalistic neural activity was evident in key neuromodulatory nuclei and produced perturbed functional connectivity within acetylcholine, noradrenaline, and dopamine neural pathways. Acute THC treatment resulted in alterations in cerebral metabolism in the amygdala and aberrant functional connectivity profiles between amygdaloid nuclei and the hippocampus, PFC and nucleus accumbens. There appeared to be an age-related sensitivity to THC in several thalamic, neuromodulatory and amygdaloid nuclei. Peripubertal low-dose intermittent THC (3.5mg/kg, 3 times a week), mimetic of light, recreational adolescent cannabis use, produced long-term cognitive inflexibility, as measured by the attentional-set shifting task, perturbed cerebral metabolism in the dorsolateral orbital cortex andhizophrenia. Cannabinoid CB1 receptor ontogeny (activated in the brain by the receptor ligand THC) within important cognitive substrates, the prefrontal cortex (PFC) and hippocampus, was investigated to delineate a period of neurodevelopmental vulnerability for peripubertal THC treatment. CB1 receptor ligand binding revealed that the PFC and hippocampus follow differential late maturational trajectories throughout the peripubertal period. The 'vulnerability window' for peripubertal THC treatment was defined as post-natal day (PD) 35-56 to encompass the dynamic peripubertal ontogenetic patterns of the CB1 receptor in both these regions. Furthermore, age-related alterations in cerebral metabolism and regional functional connectivity profiles were evident in the hippocampus and important neuromodulatory nuclei including the ventral tegmental area, dorsal raphe, locus coeruleus and the diagonal band of Broca. the nucleus accumbens core and altered functional coupling between both regions and neural substrates subserving reward-related learning including prefrontal, septal and amygdala subfields. High-dose daily THC (7mg/kg) throughout the peripubertal period, mimetic of heavy daily cannabis abuse, did not precipitate any schizophrenia-related behaviours in adulthood. MIA induced by prenatal exposure to the immune-stimulating agent polyriboinosinic-polyribocytidilic acid (PolyIC) did not produce any schizophrenia-related phenotypes in adulthood. However, prenatal PolyIC exposure produced residual hypermetabolism within discrete components of the prefrontal cortex dorsolateral orbital and cingulate cortices and hypometabolism within the CA3 subfield of the hippocampus. The functional connectivity signatures of all these regions indicated a unified MIA effect of aberrant mesocorticolimbic functional coupling in adulthood. Furthermore, chronic intermittent treatment with low-dose THC durnia. Cannabinoid CB1 receptor ontogeny (activated in the brain by the receptor ligand THC) within important cognitive substrates, the prefrontal cortex (PFC) and hippocampus, was investigated to delineate a period of neurodevelopmental vulnerability for peripubertal THC treatment. CB1 receptor ligand binding revealed that the PFC and hippocampus follow differential late maturational trajectories throughout the peripubertal period. The 'vulnerability window' for peripubertal THC treatment was defined as post-natal day (PD) 35-56 to encompass the dynamic peripubertal ontogenetic patterns of the CB1 receptor in both these regions. Furthermore, age-related alterations in cerebral metabolism and regional functional connectivity profiles were evident in the hippocampus and important neuromodulatory nuclei including the ventral tegmental area, dorsal raphe, locus coeruleus and the diagonal band of Broca. ing the peripubertal period caused an increase in sensitivity to amphetamine (indicative of aberrant mesolimbic dopamine transmission) in PolyIC-trea compared to PBS-treated offspring, suggestive of a synergistic effect of these two environmental risk factors. In conclusion, the findings presented in this thesis have provided clear evidence of dose-specific detrimental effects of 'adolescent' THC exposure on behaviour and the functional neural systems that may underpin these deficits which impact on behaviour and neural systems into adulthood.
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Mungly, Shazia. "The Prevalence Of Metabolic Disorders And Their Associated Risk Factors In Forensic Patients With Schizophrenia Spectrum Disorders On Clozapine Compared To Haloperidol At Valkenberg Hospital." Master's thesis, Faculty of Health Sciences, 2019. http://hdl.handle.net/11427/31076.
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Background: Various studies have shown that people with serious mental illness have an increased risk for metabolic syndrome with prevalence ranging from 28.7% to 60%. Given the amount of evidence suggesting a link between clozapine and metabolic syndrome, several guidelines have recommended regular clinical monitoring of metabolic syndrome in patients on clozapine. Aim: To determine the screening, prevalence and associated risk factors of metabolic disorders in forensic patients with schizophrenia spectrum disorders who are on clozapine (study group) compared to patients on haloperidol (control group). Methods: It is a retrospective, folder review of forensic male adult patients at Valkenberg Hospital, Observatory Cape Town. Results: There were 45 patients in the study group and 23 patients in the control group. Eight patients (17.8%) in the study group (Clozapine) met criteria for metabolic syndrome according to the NCEP-ATP III criteria and none of the patients in the control group (Haloperidol) did (χ 2 (1) = 4.441, p = .035 V = .257). Patients who had a diagnosis of schizoaffective disorder were also on mood stabilisers in addition to clozapine. Again, while none of the patients on Haloperidol met the criteria for Metabolic syndrome, 6 (24%) of the 25 patients on concurrent Clozapine and sodium valproate did, (χ 2 (1) = 6.051, p = .023 V = .359). In terms of metabolic disorders, a significantly higher proportion of patients in the study group has hypertension and hyperlipidaemia (p = .003 and p = .021 respectively). Less than 25% of all patients were fully screened for metabolic syndrome. There was a very low rate of screening of blood tests: fasting glucose, total cholesterol, trigylcerides, High Density Lipoprotein(HDL) or Low-Density Lipoprotein (LDL). Conclusion: The prevalence of metabolic syndrome was higher in the clozapine group than haloperidol group, which is unsurprising since clozapine is usually associated with a higher risk of metabolic syndrome. However, the prevalence on metabolic syndrome in this study sample was relatively low compared to other studies. This could be due to the low rate of screening of each criteria of metabolic syndrome. Screening for metabolic syndrome should be regularly performed by health professionals in patients with serious mental illness. Further studies are needed to investigate the risk of metabolic syndrome for patients who are on a combination of clozapine and mood stabilisers.
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Prats, Balado Claudia. "Genetic risk factors in Schizophrenia and Neurodevelopmental disorders: Association and epistatic analyses of Neuritin-1 gene and white matter related genes = Factores genéticos en esquizofrenia y enfermedades del neurodesarrollo: análisis de asociación y epistáticos en el gen Neuritina-1 y en genes relacionados con la materia blanca." Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/456897.
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Nowadays, it is estimated that about 450 million people suffer from a mental or behavioural disorder in the world. According to World health organization (WHO), 33% of the years lived with disability (YLD) are due to psychiatric disorders. In this regard, psychotic disorders including schizophrenia (SZ), remain one of the most mysterious and costliest mental disorders in terms of human suffering and social expenditure.
In recent years, the field of molecular genetics has been uncovering evidence of the complex polygenetic architecture of SZ and related disorders. In addition, GWAS studies have identified several genes associated with SZ, which have been shown to converge in complex and identifiable molecular pathways related to synaptic plasticity, neurotransmission and connectivity processes. Also, these studies have reported an important genetic overlap across several psychiatric disorders such as Schizophrenia (SZ), Bipolar disorder (BPD), Major Depressive Disorder (MDD) or Autism Spectrum Disorders (ASD), which adds to the consideration of common pathophysiological mechanisms among these disorders. In this sense, a growing body of evidence has established that connectivity and synaptic plasticity, modulated by neuronal activity, is an inherent feature of brain function during both development and adulthood.
The present dissertation hypothesizes that genetic variability of genes involved in either synaptic plasticity (NRN1, BDNF and DTNBP1) and/or white matter related pathways (and their interactions) will be associated with SSD. In addition, due to the clinical, cognitive, neuroimaging and genetic overlap observed across different psychiatric disorders, we also hypothesize that the studied genetic variability will be also associated with other neurodevelopmental psychiatric disorders, such as ASD and BPD. In this sense, four studies have been carried out. The first three studies, analyse genetic variability at Neuritin-1 gene (NRN1) and its relationship with the risk for developing SSD and BPD, and also with some clinical and cognitive phenotypes both in patients and in healthy subjects from the general population. Moreover, in these studies we also analyzed whether NRN1 action is modulated by other genes such as BDNF and DTNBP1. The fourth study analyses the integrative effects of a set of white matter related genes (Oligodendrocyte/myelination related genes - OMR) and its contribution to both SSD and ASD. Our results focused on the genetic variability at NRN1 gene, suggest that genetic variability of NRN1 gene has an impact on the risk for developing SSD/BPD and also on the presence of depressive symptoms in the general population. Its pleiotropic effect is also evidenced by its effect on different phenotypes: such as cognitive performance and age at onset. Moreover, our genexgene interaction results suggest that NRN1 action is modulated by the BDNF and DTNBP1 genes. On the other hand, the results of the fourth study suggest that some of the OMR genetic risk variants seem to be shared across SZ-ASD continuum. The fact that some OMR genes are marginally associated with both disorders and also, due to their involvement in the detected epistatic effects, seem to support the notion that dysregulation in myelination processes may underlie susceptibility to develop ASD or SSD. To conclude, further genetic studies are needed to elucidate the biological background underlying mental disorders, which can ultimately lead to better treatment in order to improve the quality life of the patients.Actualmente, se estima que alrededor de 450 millones de personas en el mundo sufren de un trastorno mental o de la conducta. Según la Organización Mundial de la Salud (OMS), el 33% de los años vividos con discapacidad (YLD) se asocian a trastornos psiquiátricos. En este sentido, los trastornos psicóticos, incluyendo la esquizofrenia (EQ), siguen siendo uno de los trastornos mentales más desconocidos y costosos en términos de sufrimiento humano y gasto social. En los últimos años, el campo de la genética molecular ha estado descubriendo evidencias acerca de la compleja arquitectura poligénica de la EQ y de otros trastornos relacionados. Además, los estudios GWAS han identificado varios genes asociados con EQ, los cuales se ha demostrado que convergen en vías moleculares complejas e identificables relacionados con la plasticidad sináptica, la neurotransmisión y los procesos de conectividad. Además, estos estudios han informado de un importante solapamiento genético a través de varios trastornos psiquiátricos como la esquizofrenia (EQ), el trastorno bipolar (TB), el trastorno depresivo mayor (TDM) o los trastornos del espectro autista (TEA), lo que se suma a la consideración de mecanismos fisiopatológicos comunes en estos trastornos. En este sentido, el creciente cuerpo de evidencias ha establecido que la conectividad y la plasticidad sináptica modulada por la actividad neuronal, es una característica inherente de la función cerebral durante el desarrollo y la edad adulta. La presente tesis plantea la hipótesis de que la variabilidad genética en genes implicados en la plasticidad sináptica (NRN1, BDNF y DTNBP1) y/o en las vías relacionadas con la materia blanca (y sus interacciones) se asociarán con Trastornos del Espectro de la Esquizofrenia (TEE). Además, debido al solapamiento clínico, cognitivo, de neuroimagen y genético observado a través de los diferentes trastornos psiquiátricos, también hipotetizamos que la variabilidad genética estudiada se asocia con otros trastornos psiquiátricos del neurodesarrollo, como el TEE y TEA. En este sentido, se han llevado a cabo cuatro estudios. Los tres primeros estudios analizan la variabilidad genética del gen Neuritin-1 (NRN1) y su relación con el riesgo de desarrollar TEE y TB, así como algunos fenotipos clínicos y cognitivos tanto en pacientes como en sujetos sanos de la población general. Además, en estos estudios también analizamos si la acción de NRN1 es modulada por otros genes como BDNF y DTNBP1. El cuarto estudio analiza los efectos integradores de un conjunto de genes relacionados con la materia blanca (genes relacionados con Oligodendrocitos/mielinización - OMR) y su contribución a TEE y TEA. Nuestros resultados centrados en la variabilidad genética del gen NRN1, sugieren que su variabilidad genética tendría un impacto en el riesgo de desarrollar TEE / TB y también en la presencia de síntomas depresivos en la población general. Este efecto pleiotrópico también se ve respaldado por sus efectos sobre otros fenotipos: como el rendimiento cognitivo y la edad de inicio. Además, nuestros resultados de interacción genéticas (gxg) sugieren que la acción de NRN1 es modulada por los genes BDNF y DTNBP1. Por otro lado, los resultados del cuarto estudio sugieren que algunas de las variantes de riesgo genético de los genes OMR parecen ser compartidas a través de del continuum TEE-TEA. El hecho de que algunos genes OMR estén ligeramente asociados con ambos trastornos, así como también, debido a su participación en los efectos epistáticos detectados, parece apoyar la noción de que la desregulación en los procesos de mielinización podría ser subyacente a la susceptibilidad para desarrollar TEE o TEA. Para concluir, se necesitan más estudios genéticos que ayuden a descifrar el trasfondo biológico subyacente a los trastornos mentales, lo que en última instancia puede conducir a un mejor tratamiento con el fin de mejorar la calidad de vida de los pacientes.
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Mitjans, Niubó Marina. "Genetic Risk Factors for the Lack of Response to Clinical Treatment in Mental Disorders: an Approach from Pharmacogenetics." Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/289981.
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Severe mental disorders, such as Major Depressive Disorder (MDD), Bipolar Disorder (BD) and Schizophrenia (SCZ), represent a huge burden to society, reflecting the limited efficacy of current drug treatments. Although the progress in development of pharmacological treatments is one of the great successes of modern psychiatry, it should not be forgotten that a very high percentage of patients do not receive and/or seek the proper treatment for their disease. Individual differences in clinical response to psychotropic drugs have long been recognized as a fundamental problem in the treatment of the seriously mentally ill patient. This variability in individual response ranges from patients who experience complete symptom remission to a subset of patients often describes as “treatment refractory”, as well as a marked variability in susceptibility to adverse drug effects. In this sense, the overall objective of pharmacogenetics is to determine the genetic basis of the variability in drug efficacy and safety, and to use this information to benefit the patient detecting a priori those patients that could not respond to a drug and/or present drug side effects. The present dissertation hypothesizes that lack of response to psychotropic drugs will be associated to genetic variability at genes coding for proteins involved directly or indirectly in the mechanism of action of these drugs. In this sense three different studies have been carried out. The first study analyses genetic variability at genes of the endocannabinoid system in clinical response and/or remission to citalopram treatment in MDD patients. The second study analyses genetic variability at genes related to phosphoinositide (PI), glycogen synthetase kinase-3 (GSK3), hypothalamic-pituitary-adrenal (HPA) and glutamatergic pathways in clinical response to lithium in BD patients. The third study analyses genetic variability at genes related to neurotrophic factors and HPA in clinical response to clozapine in patients with SCZ. Our results focused in the analyses of genetic variability at genes coding for proteins involved in the mechanism of action of psychotropic drugs let us to detect some minor and moderate effects of genetic variants that could explain, at least, part of the lack of response to these drugs. The results of our study in relation to citalopram response in MDD showed that genetic variability at genes related to the endocannabinoid system could play a role in the understanding of clinical response to this drug treatment. Specifically, we found an association between CNR1 gene and clinical remission at 12th week and an effect of CNR1 gene on longitudinal response (along the 12th week follow-up). The results of our study in relation to lithium response in BD showed that genetic variability at INPP1, IMPA2, GSK3B and GRIK2 genes could play a role in the understanding of lithium response. Finally, the results in relation to clozapine response in SCZ showed that genetic variants at FKBP5 and NTRK2 genes may play a role in clozapine response. The detection of individual genetic differences in the response to psychotropic drugs may provide new strategies for the treatment of mental disorders, as well as, new knowledge about the aetiology of these disorders.Los trastornos mentales graves, como son la depresión mayor (DM), el trastorno bipolar (TB) y la esquizofrenia (SCZ), se han convertido en los últimos años en un importante problema de salud en los países desarrollados. Aunque el avance alcanzado en el desarrollo de tratamientos farmacológicos ha constituido uno de los grandes logros de la psiquiatría moderna, no debemos olvidar que hay un porcentaje muy alto de pacientes que no reciben el tratamiento adecuado para su enfermedad. En este sentido, la farmacogenética tiene como objetivo identificar y caracterizar los factores genéticos que se encuentran en la base de las diferencias existentes entre individuos en la respuesta clínica al tratamiento farmacológico. La presente tesis pretende estudiar variación genética basada en genes que codifican para moléculas implicadas directamente o indirectamente en los mecanismos de acción del tratamiento con citalopram (DM), carbonato de litio (TB) y clozapina (SCZ) que nos explicará parte del riesgo para la no respuesta clínica y la no remisión del episodio tratado farmacológicamente. Los resultados nos permitieron identificar variación genética asociada a la respuesta al tratamiento. Concretamente, nuestros resultados indicaron que variabilidad genética relacionada con el sistema endocannabinoide se asociaba con la respuesta a citalopram en DM. Por otro lado, genes involucrados con el sistema de fosfoinositoles podrían explican parte de la variación en la respuesta al litio en el TB. En referencia al estudio de la respuesta a clozapina en pacientes con SCZ, los resultados sugieren que variantes genéticas en los genes FKBP5 y NTRK2 pueden jugar un papel en la respuesta. En este sentido, nuestro estudio proporciona evidencia de la implicación del eje hipotálamo-pituitario-adrenal (HPA) y de factores neurotróficos en la modulación de la respuesta a clozapina. La detección de diferencias genéticas individuales en la respuesta a los fármacos psicotrópicos puede proporcionar nuevas estrategias para el tratamiento de trastornos mentales, así como, nuevos conocimientos sobre la etiología de estos trastornos.
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Rothärmel, Maud. "La résistance pharmacologique dans les pathologies psychiatriques : Exemple de la dépression, la schizophrénie et l'autisme. Identification of potential genetic risk factors for bipolar disorder by whole-exome sequencing Les traitements pharmacologiques dans les troubles du spectre de l’autisme Troubles de l’humeur ? Quand recourir à la stimulation magnétique transcrânienne ? Repeated transcranial magnetic stimulation (rTMS) to improve electroconvulsive therapy (ECT) in TReatment-Resistant Depression : a report of two cases." Thesis, Normandie, 2019. http://www.theses.fr/2019NORMR125.
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Le problème de la pharmacorésistance est un phénomène courant en médecine et qui n’épargne pas la psychiatrie. Au même titre qu’on parle « d’épilepsie résistante », on parle de « dépression ou de schizophrénie résistante ». L’autisme est une situation un peu différente dans la mesure où il n’existe pas de traitement de référence pour les troubles du neurodéveloppement. Ces trois troubles, néanmoins, constituent des enjeux majeurs de santé publique tant du point de vue économique que sociétal, avec d’importantes répercussions fonctionnelles pour les patients. Après nous être interrogés dans une première partie sur la définition même de la pharmacorésistance dans la dépression, la schizophrénie et l’autisme et sur les mécanismes physiopathologiques possiblement impliqués dans leur genèse, nous avons recherché ce qui pouvait être commun à ces troubles. Cette démarche nous a permis de comprendre comment optimiser leurs traitements. Différentes techniques d’optimisation des traitements sont à la disposition des cliniciens et incluent la potentialisation des médicaments entre eux ou encore la potentialisation des médicaments par des techniques de neurostimulation (l’électroconvulsivothérapie, ECT, la stimulation magnétique transcrânienne répétitive, rTMS, ou la stimulation transcrânienne à courant continu, tDCS). Dans une seconde partie de ce travail, nous avons étudié différentes approches d’optimisation des traitements : l’utilisation de la clozapine dans les troubles du comportement à type d’agressivité dans l’autisme ; l’utilisation de la tDCS dans les troubles des fonctions exécutives toujours dans l’autisme ; la potentialisation de la clozapine par l’ECT dans la schizophrénie résistante et enfin la potentialisation de l’ECT par la rTMS dans la dépression résistante. Les résultats encourageants que nous avons obtenus nous amènent à réfléchir sur les mécanismes d’action de ces techniques de potentialisation, notamment l’ECT et sur l’élaboration de protocoles nous permettant de confirmer nos résultatsDrug resistance is a common problem in medicine, that also concerns psychiatry. As there are resistant epilepsies, there are resistant depression or schizophrenia. Autism is in a slightly different situation as there is no reference treatment for neurodevelopmental disorders. These three disorders constitue major public health issues from both the economic and social perspective with important functional impact of the disease. After focusing on the definition of drug resistance in depression, schizophrenia and autism and on the hypothetical underlying pathophysiological processes, we investigated what could be common to these disorders. This allowed us to understand how to optimize their treatments. Several augmentation methods are possible, such as the potentiation of drugs between them or the potentiation of drugs by neurostimulation (electroconvulsive therapy, ECT, repetitive transcranial magnetic stimulation, rTMS, transcranial direct current stimulation, tDCS). In the second part of this work, we studied the effects of different ways to optimizing treatments : the use of clozapine on aggressive behaviors for patients with autism spectrum disorders (ASD) ; the use of tDCS on executive functions in patients with ASD ; the clozapine augmentation strategie by ECT in ultra-resistant schizophrenia and the ECT augmentation strategie by rTMS in treatment-resistant depression. Our encouraging results led us to focus on the mechanisms of these potentiation strategies, including ECT and on the development of new protocols to confirm our results
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Roisko, R. (Riikka). "Parental Communication Deviance as a risk factor for thought disorders and schizophrenia spectrum disorders in offspring:The Finnish Adoptive Family Study." Doctoral thesis, Oulun yliopisto, 2014. http://urn.fi/urn:isbn:9789526206066.
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Abstract Both genetic and biological and psychosocial environmental risk factors contribute to the aetiology of schizophrenia spectrum disorders. Among the much studied environmental risk indicators are parental Communication Deviance (CD) and the winter or spring birth of a child. Genetic and environmental risk factors do not function in isolation from each other, but gene-environment interactions play a major role in the aetiology of psychotic disorders. The aim of this doctoral thesis is to investigate the role of parental CD as a risk factor (together with other risk indicators) for thought disorders and schizophrenia spectrum disorders in an adoptive child. A systematised review was performed concerning the association between parental Communication Deviance and schizophrenia spectrum and thought disorders in offspring. A meta-analysis could only be performed for the association of parental CD with schizophrenia spectrum disorders in offspring. A large overall effect size was found (0.79, 95%CI 0.21–1.37). The studies included in the systematised review suggest that frequent parental CD and thought disorders in the offspring are connected with each other. The two original studies are based on the data derived from the total sample of the Finnish Adoptive Family Study (n=382). First, the association between parental Communication Deviance scored from individual and family Rorschach protocols and the characteristics of the adoptive child and the parents themselves was investigated. The variability of CD in the adoptive parents in individual and family Rorschach situations was most closely associated with the characteristics of the parents themselves. The association of an adoptive child’s thought and schizophrenia spectrum disorders with the child’s genetic risk for schizophrenia spectrum disorders, winter or spring birth, and parental Communication Deviance, and their interactions was also explored. The adoptive child’s thought disorders were associated only with parental CD. None of the risk indicators or their interactions predicted the adoptee’s schizophrenia spectrum diagnosis. In conclusion, the results indicate that the amount of Communication Deviance is a stable trait of an individual. It may be considered as a risk indicator for schizophrenia spectrum disorders in offspring and, with a lower level of confidence, also for thought disorders in offspringTiivistelmä Skitsofreniaspektrin sairauksien varsinaisia syytekijöitä ei tunneta, mutta niillä on lukuisia sekä perimään että biologiseen ja psykososiaaliseen ympäristöön liittyviä riskitekijöitä. Nykytietämyksen mukaan riskitekijät eivät vaikuta sairauden syntyyn itsenäisesti, vaan perimän ja ympäristön vuorovaikutuksella on merkittävä osuus. Paljon tutkittuja ympäristöön liittyviä riskitekijöitä ovat lapsen talvi- tai kevätsyntymä ja vanhempien hajanainen kommunikaatio. Tässä väitöskirjassa tutkitaan vanhempien hajanaista kommunikaatiota adoptiolapsen ajatushäiriöiden ja skitsofreniaspektrin sairauksien riskitekijänä. Vanhempien hajanaisen kommunikaation ja lapsen skitsofreniaspektrin sairauksien ja ajatushäiriöiden yhteydestä laadittiin systemaattinen katsaus. Meta-analyysi voitiin tehdä vain skitsofreniaspektrin sairauksiin liittyen. Vanhempien hajanaisen kommunikaation ja lapsen skitsofreniaspektrin sairauksien välisellä yhteydellä havaittiin olevan suuri efektikoko (0,79, 95 % luottamusväli 0,21–1,37). Katsaukseen sisällytetyt tutkimukset viittaavat siihen, että vanhempien hajanaisella kommunikaatiolla ja lapsen ajatushäiriöillä on myös yhteys. Väitöskirjan alkuperäistutkimukset perustuvat Suomalaisen adoptiolapsiperhetutkimuksen aineistoon (n= 382). Aluksi tutkittiin vanhempien yksilö- ja perhe-Rorschach-tilanteissa mitatun hajanaisen kommunikaation määrän ja lapsen ja vanhempien ominaisuuksien välistä yhteyttä. Hajanaisen kommunikaation määrän vaihtelu selittyi pääosin vanhempien ominaisuuksilla. Seuraavaksi tutkittiin adoptiolapsen ajatushäiriöiden ja skitsofreniaspektrin sairauksien yhteyttä lapsen skitsofreniaspektrin sairauksille altistavan perimän, talvi- tai kevätsyntymän ja vanhempien hajanaisen kommunikaation kanssa. Huomioon otettiin myös riskitekijöiden yhteisvaikutukset. Mikään riskitekijä tai niiden yhteisvaikutus ei ollut yhteydessä lapsen skitsofreniaspektrin sairauteen. Lapsen ajatushäiriöt olivat yhteydessä ainoastaan vanhempien hajanaiseen kommunikaatioon. Tutkimuksen tulokset osoittavat, että vanhempien hajanainen kommunikaatio on kohtalaisen muuttumaton piirre, joka on lapsen skitsofreniaspektrin sairauksien riskitekijä. Tulokset viittaavat myös siihen, että vanhempien hajanainen kommunikaatio voi olla lapsen ajatushäiriöiden riskitekijä
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Badowska, Dorota [Verfasser], Moritz [Akademischer Betreuer] Rossner, Hannelore [Akademischer Betreuer] Ehrenreich, André [Akademischer Betreuer] Fischer, Michael [Akademischer Betreuer] Hoerner, and Mikael [Akademischer Betreuer] Simons. "Schizophrenia risk factor Tcf4 and gene-environment interaction in mice / Dorota Badowska. Gutachter: Hannelore Ehrenreich ; André Fischer ; Michael Hoerner ; Mikael Simons. Betreuer: Moritz Rossner." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2015. http://d-nb.info/1067626573/34.
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Burt, Melissa. "Investigating the effect of prenatal immune activation, a risk factor for Schizophrenia, on hippocampal n-methyl-d- aspartate receptor function in a rodent model." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119491.
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N-methyl-D-aspartate receptor (NMDAR) hypofunction has been hypothesized as a pathological change accounting for many of the symptoms of schizophrenia, including cognitive deficits. Although the etiology of schizophrenia is still not known, prenatal infection has been identified as an early-life environmental risk factor. While the onset of psychosis commonly occurs in early adulthood, cognitive deficits can be present earlier. Exposure to risk factors during adolescence, such as stress, is hypothesized to precipitate the onset of psychosis. Recent findings suggest stress may impact cognition through the modulation of NMDAR function and plasticity in the hippocampus, a vulnerable structure in schizophrenia. Therefore, prenatal infection may increase vulnerability to schizophrenia through the modulation of hippocampal NMDAR function. In order to examine this we utilized a rodent model of prenatal immune activation and investigated hippocampal NMDAR function using behavioral, electrophysiological and molecular techniques in both adolescent and adult offspringFor all of the experiments in this thesis, we examined the male offspring from pregnant rats administered lipopolysaccharide (LPS), a bacterial endotoxin, or saline control on gestational days 15 and 16. In Chapter 2 we investigated the effects of prenatal LPS exposure on hippocampal and NMDAR associated learning and memory in adolescent and adult offspring. Using NMDAR associated behavioral tasks we found alterations in adolescent, but not adult offspring. Specifically, adolescent prenatal LPS offspring had subtle long-term spatial memory impairment and enhanced spatial reversal learning; both tasks which are associated with hippocampal NMDAR-dependent synaptic plasticity, long-term depression (LTD). Next, in Chapter 3 we used electrophysiological techniques to investigate the effects of prenatal LPS exposure on in vitro hippocampal NMDAR synaptic function and LTD in adolescent offspring and tested if this may be differentially affected by exposure to stress. We found NMDAR-dependent LTD was abolished in prenatal LPS offspring, which was supported by a significant decrease in both field and whole cell measures of NMDAR synaptic function. However, restraint stress repaired the abolished LTD in prenatal LPS offspring, and treatment with the stress hormone corticosterone (CORT) augmented LTD in prenatal LPS offspring but not in controls. In Chapter 4, similar experiments were performed in adult offspring. However, hippocampal NMDAR synaptic function was not significantly altered in either basal or CORT conditions in adult prenatal LPS offspring compared to controls, suggesting the effects observed in adolescence are transiently expressed. Finally, in Chapter 5 we investigated the effects of prenatal LPS exposure on hippocampal reelin and glutamic acid decarboxylase 67 (GAD67) expression in juvenile and adolescent offspring. Both reelin and GAD67 expression are reduced in schizophrenia and preclinical studies suggest they could modulate NMDAR-mediated synaptic plasticity. Using immunohistochemistry, we found a decrease in reelin+ cells at postnatal day (P)14 and decrease in GAD67+ cells at P14 and P28 in the hippocampus of prenatal LPS offspring compared to controls. The results from this thesis demonstrate that prenatal exposure to LPS transiently alters NMDAR function in the hippocampus of rat offspring during adolescence. Prenatal LPS causes NMDAR hypofunction under basal conditions, but increased NMDAR function in response to stress during adolescence. Also, the decreased hippocampal expression of reelin and GAD67 in juvenile prenatal LPS offspring could impact normal NMDAR development. Therefore, prenatal infection could be increasing vulnerability to schizophrenia during adolescence at the level of the NMDAR and interacting with a second risk factor, stress. These results may provide insight into how prenatal infection could increase risk for schizophrenia.L'hypofonctionnement des récepteurs au N-methyl-D-aspartate (NMDA) est une des principales hypothèses pour expliquer les symptômes de la schizophrénie, en particulier les déficits cognitifs. Bien que les causes de la schizophrénie soient méconnues, une infection durant la grossesse est un des facteurs de risque qui a été identifié. Alors que la maladie ne se manifeste qu'à l'âge adulte, les déficits cognitifs peuvent apparaitre avant. Des études suggèrent que le stress affecte les capacités cognitives via les récepteurs NMDA et la plasticité synaptique dans l'hippocampe. Par conséquent, l'infection prénatale pourrait augmenter la vulnérabilité à la schizophrénie par une modulation des récepteurs NMDA dans l'hippocampe, dont les conséquences seraient observables à l'adolescence et à l'âge adulte. Afin d'étudier cette hypothèse nous avons évalué la fonction des récepteurs NMDA dans l'hippocampe de rats adultes et adolescents suite à une infection prénatale. Nous avons utilisé un modèle d'activation du système immunitaire chez la rate gestant : une dose de lipopolysaccharide (LPS) est injectée à des rates à 15 et 16 jours de gestation et les effets sur la progéniture ont été étudiés. Les effets de cette exposition au LPS sur les fonctions cognitives sont présentés dans le chapitre 2. Les rats adolescents exposés au LPS ont montré des déficits de mémoire spatiale à long terme et une augmentation de la réversion de l'apprentissage spatial. Les rats adultes n'ont présenté aucun déficit. Ces deux tâches étant associées à la fonction des récepteurs NMDA dans la plasticité synaptique et à la dépression synaptique à long terme (LTD) dans l'hippocampe, nous avons dans le troisième chapitre étudié l'effet de l'exposition au LPS sur la transmission synaptique liée aux récepteurs NMDA et sur la LTD dans l'hippocampe des rats adolescents. De plus, nous avons étudié la relation entre le stress et l'exposition au LPS. Nous avons montré que l'exposition au LPS abolit la LTD. Cet effet est associé à une diminution de la fonction des récepteurs NMDA puisque les potentiels de champ dépendant des récepteurs NMDA ainsi que les courants NMDA furent diminués. Un stress de contention permet de rétablir les déficits de LTD observés dans le groupe exposé au LPS alors qu'un traitement à la corticostérone augmente la LTD seulement chez les animaux du groupe LPS. Aucune altération de la fonction des récepteurs NMDA et de la plasticité synaptique n'a été observée chez l'animal adulte (chapitre 4). Par conséquent une exposition au LPS affecte les fonctions des récepteurs NMDA hippocampiques de façon transitoire pendant l'adolescence.Dans le chapitre 5, nous avons étudié l'effet de l'exposition au LPS sur l'expression de la reelin et de la GAD 67 chez le rat juvénile et adolescent. L'expression de ces deux protéines est réduite chez les schizophrènes et des études suggèrent que cela affecte la plasticité synaptique en modulant les récepteurs NMDA. Nous avons observé une diminution du nombre de cellules exprimant la reelin et la GAD67 dans l'hippocampe à 14 et 28 jours chez les rats du groupe LPS. L'ensemble de nos résultats montrent que l'exposition prénatale au LPS cause des altérations de la fonction des récepteurs NMDA de l'hippocampe de façon transitoire durant l'adolescence. Elle induit un hypofonctionnement des récepteurs NMDA et augmente l'effet du stress sur leur fonction ainsi que sur la LTD pendant l'adolescence. De plus, la diminution de l'expression de la reelin et de la GAD67 observée dans l'hippocampe chez les rats juvéniles et adolescents exposés au LPS suggère que ces changements pourraient avoir un impact sur le développement des récepteurs NMDA. En conclusion, nos résultats soutiennent l'hypothèse que l'infection prénatale augmente la vulnérabilité à la schizophrénie à l'adolescence et élucident une partie des mécanismes par lesquels l'infection prénatale augmente les risques de développer la schizophrénie.
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Chaumette, Boris. "Identification de facteurs biologiques de la transition psychotique." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCB046/document.
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La psychose est un syndrome apparaissant progressivement à l’adolescence chez des individus à risque selon un processus dynamique appelé transition psychotique. Ces individus à risque sont repérables cliniquement mais les données biologiques actuelles sont insuffisantes pour expliquer l’apparition de la psychose. Au cours de cette thèse, nous avons cherché à identifier les facteurs biologiques responsables de ce processus. Les hypothèses permettant d’expliquer la transition psychotique privilégient l’interaction gène x environnement, sous-tendue par des mécanismes épigénétiques. Nous avons mené une étude des modifications de la méthylation de l’ADN et de la transcription à l’aide de techniques de biologie moléculaire et de bio-informatique à l’échelle pan-génomique. La transition psychotique semble être liée à des modifications de méthylation et de transcription de gènes impliqués dans des mécanismes comme le guidage axonal ou la régulation du stress oxydatif. Ces modifications longitudinales pourraient refléter l’influence de l’environnement. Les facteurs environnementaux pourraient déréguler l’axe biologique du stress dès les phases précoces de la maladie, comme le suggère l’augmentation de la sécrétion de cortisol basal que nous avons montré chez les individus à risque. En outre, il est probable que des spécificités au niveau des gènes et des processus régulant l’épigénome soient également impliquées dans cette réponse individuelle à l’environnement. Nous avons montré l’importance du métabolisme mono-carboné au moins dans un sous-groupe spécifique de patients. Ces résultats doivent être répliqués et étendus dans d’autres paradigmes pour valider l’implication de ces processus dans la transition psychotique. En cas de confirmation, ces voies biologiques pourraient s’avérer être des pistes intéressantes pour développer des thérapeutiques ciblées et relever le défi de la prévention de la psychose chez des individus à risquePsychosis is a progressive mental disorder which normally occurs during adolescence in at-risk subjects following a dynamic process termed “psychotic transition”. These at-risk subjects are clinically identifiable but biological data are still insufficient in explaining the onset of psychosis. Throughout this thesis, we aim to identify biological factors implicated in this pathophysiological process. Current hypotheses explaining the psychotic transition favor the interaction between genes and the environment mediated by epigenetic mechanisms. We conducted studies examining methylomic and transcriptomic changes during psychotic transition using molecular biology and bioinformatics techniques at a whole genome scale. Our results suggest that psychotic transition may be linked to methylomic and transcriptomic changes in genes implicated in axon guidance or oxidative stress. These longitudinal changes could be related to environmental factors. Some of these factors could deregulate the hormonal stress response at the earliest phases of psychosis. Indeed, our results show that secretion of basal cortisol is increased in prodromal individuals. Moreover, it is likely that genes and processes regulating epigenetic modifications are also implicated in the individual response to the environment. We have shown the importance of the one-carbon metabolism for at least one sub-group of patients affected by psychosis. Our results should be replicated using other paradigms in order to definitively validate the implication of these various actors in the psychotic transition. If confirmed, knowledge of these biological mechanisms could lead to the development of targeted therapeutics to prevent psychosis in at-risk individuals
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Yerabham, Antony Sravan Kumar [Verfasser], Carsten [Gutachter] Korth, and Georg [Gutachter] Groth. "Investigations of the structural organization of the Disrupted-in-Schizophrenia 1 (DISC1) protein, a major risk factor for mental illness / Antony Sravan Kumar Yerabham ; Gutachter: Carsten Korth, Georg Groth." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2017. http://d-nb.info/1138114480/34.
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Tang, Chao-Jung, and 湯昭容. "The Related Factors of High Risk Behavior for Patient with Schizophrenia." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/64978899018658917707.
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碩士國立臺灣大學
護理學研究所
90
ABSTRACT The purpose of this study was to explore the related factors of high-risk sexual behaviors of patients with schizophrenia. A descriptive correlation study design was used. Structured questionnaires were filled by the investigator through interviews. A purposive sample of 208 patients of schizophrenia came from outpatient psychiatric departments of a medical center and a psychiatric hospital in central Taiwan. Descriptive and inferential statistics were used for data analysis. Major findings of this study included: 1. Patients practiced as much as 7 high-risk sexual behaviors. 55.8% of patients had practiced high-risk sexual behaviors. Causal sex happened with 46.2% of patients. Substance related high-risk sexual behavior sex happened with 25.5% of patients. 2. The characteristics of patients practiced high-risk sexual behaviors were male, had history of substance use, were frequently hospitalized, perceived the impact of psychotropic medications on their sexual feelings, experienced more severe positive symptoms, experienced less severe negative symptoms, had first sexual experience in their early age, had multiple sexual partners, had history of HIV-infection or other sexual transmitted diseases. 3. The characteristics of patients practiced causal sex were male, married, had history of substance abuse, were frequently hospitalized, were diagnosed with schizophrenia in their early age, had more severe positive symptoms, had first sexual experience in their early age, had multiple partners, had history of HIV-infection or other sexual transmitted diseases. 4. The characteristics of patients practice substance related high-risk sexual behaviors were had history of substance use, perceived the impact of psychotropic medications on their sexual feelings, had less severe negative symptoms, had first sexual experience in their early age, had multiple sexual partners, infrequently used condoms, had history of HIV infection or other sexual transmitted diseases. 5. The HIV/AIDS related knowledge was positively correlated with attitudes towards HIV/AIDS. Patients with more positive attitudes towards HIV/AIDS practiced less high-risk sexual behaviors and less casual sex. 6. Statistically significant correlates of a higher high-risk sexual practice included frequent hospitalization, more sexual partners, more positive symptoms, and less negative symptoms. 7. Statistically significant correlates of a higher casual sex included male, not married, and more sexual partners. 8. Statistically significant correlates of a higher substance-related sexual practice included more sexual partners, less negative symptoms, and had history of HIV infection and other sexual transmitted diseases. The implications of this study were threefold. First, the results can be used to increase the assessment and understanding of mental health professionals of high-risk sexual behaviors of patients with schizophrenia. Secondly, the results provide a guideline for psychiatric nurses in designing and implementing nursing care related to sexual behaviors. Lastly, patients can be educated to increase their knowledge and practice of safe sex. Future educational and administrative efforts should focus on improving quality of nursing care related to sexual health of patients with schizophrenia.
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KUO, HUI-WEN, and 郭惠雯. "A Study of Schizophrenia Risk Factors for Rehospitalization in One Year." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/78221492500538148557.
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碩士國立臺北護理健康大學
健康事業管理研究所
101
Background: The prevalence rate of psychiatric disorders was 53‰ in Taiwan. Both in the acute psychiatric ward or chronic psychiatric ward, most patients were schizophrenia. In acute psychiatric ward, 58% patients were schizophrenia. In chronic psychiatric ward, 80% patients were schizophrenia. Schizophrenia was a chronic and lifelong mental illness. As patients with schizophrenia often relapse, it consumed a lot of social and medical resources. Objectives: The purpose of this study was to investigate the risk factors affecting the rehospitalization in patients with schizophrenia within one year after discharged. In the present study, it was hoped to be a reference for caregivers making better care plans in order to prevent relapse and rehospitalization for patients with schizophrenia. Methods: The study cohort was retrieved from the National Health Insurance Research Database published by the National Health Research Institutes, and it was composed by 5,284 schizophrenic patients who admitted and discharged in 2007. Patients who was younger than 18 years old were excluded from the study. Rehospitalization was considered as the primary outcome variable in this study. In the present study, it used the Kaplan-Meier method to estimate the Survival curve and the multivariate Cox proportional hazards regression model to identify risk factors. Data was analyzed with SAS version 9.2 for Windows. Results: The one-year rehospitalization rate was estimated at 57.49%, and the mean time to rehospitalization was 218.39 days (SE= 2.028 ). The present study found the risk of rehospitalization reduced with age (HR=0.994, 95% CI=0.990-0.997). Compared to employees of public or private enterprises or institutions, there were significantly higher risks of rehospitalization, which included farmer or fishermen(HR=1.290, 95% CI=1.034-1.609), low income households(HR=1.545, 95% CI=1.261-1.893) and who were unemployed and qualify as dependents(HR=1.335, 95% CI=1.090-1.634) or insured by administrative office in the village, township, city or area(HR=1.385, 95% CI=1.146-1.674). Compared to patients lived in highly urbanized town, those lived in ordinary town (HR=1.147, 95% CI=1.003-1.313) or in aging town (HR=1.446, 95% CI=1.144-1.828) had higher risk of rehospitalization. Additionally, there were significantly higher risks of rehospitalization, if the number of previous hospitalizations for psychiatric was over 2 times (HR=1.563, 95% CI=1.426-1.714). Furthermore, the risk of rehospitalization also increased with the cumulative days of previous hospitalizations for psychiatric. Conclusions: The present study found risk factors of affecting the rehospitalization in patients with schizophrenia included type of identity, urbanization stratification, the number of previous hospitalizations for psychiatric, and the cumulative days of previous hospitalizations for psychiatric. The present study suggested that caregivers should enhance the patients’ social skill training and the support from families. The present study also suggested that the health policy makers should make people acquainted with psychiatric.
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Cheng, Chin-Chi, and 鄭沁綺. "The Survey of the Risk Factors for Metabolic Syndrome in Schizophrenia." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/12422917004010335251.
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碩士高雄醫學大學
行為科學研究所碩士班
95
Objective: The metabolic syndrome has been recognized as a side effect of antipsychotic treatment. ApoE polymorphism was associated with lipid metabolism in the metabolic syndrome. The study explored the relationship of schizophrenia and metabolic syndrome and predicted the prevalence about the risk of metabolic syndrome in the atypical antipsychotic treatment. Further, we explored the relationship between the ApoE genotypes and metabolic syndrome in schizophrenic patients. Method: This is a retrospective and chart review study. Total of 111 Taiwanese patients met the DSM III-R criteria for schizophrenia and schizoaffective disorder. All individuals were collected the data of age, onset age, gender, height, weight, blood pressure, fasting glucose, triglyceride, cholesterol level, ApoE genotype and the type of antipsychotics. Logistic regression and structural equation modeling were used to identify the relationship of cause and effect. Results: The logistic regression and structural equation modeling revealed that atypical antipsychotics negative directly influenced hypertension (β=-.18, p =0.049), triglyceride (β=-.31, p<0.001) and cholesterol (β=-.21, p =0.026) of plasma. The atypical antipsychotics compared with conventional antipsychotics individuals less hypertension and hyperlipidemia. In the study, the atypical antipsychotics showed indirect influence with the variable of body mass index. Conclusion: Our findings showed atypical antipsychotics compared with conventional antipsychotics individuals decreases risk of hypertension and hyperlipidemia, especially predominant on triglyceride plasma level. The atypical antipsychotic did not directly influenced body mass index (BMI), but indirectly influenced BMI by the variables of hypertension and triglyceride.
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Cheng, Liang-Chih, and 鄭良志. "An Investigation of the Risk Factors for Prediction Pneumonia among Schizophrenia Inpatients." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/9kx6u9.
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碩士義守大學
醫務管理學系
106
Backgroubd and purpose: Schizophrenia regards as severe mental disorder diseases. Ever increaing patients are treated with medications mainly, though 2nd generation antipsychotic Clozapine has less extrapyramidal symptoms still left serious adverse effect, including pneumonia. This thesis focus on study of Clozapine Induced Pneumonia and other risk factors. Materials and Methods: This thesis investigate on how Schizophrenia patients after taking Clozapine and other factors might lead to pneumonia. The research main focus includes variable factors of population, medications, blood tests and physical assesments. Use study of Chart review method was used to collect inpatients from southern Taiwan mental hospital. Results and Conclusions: 217 hospitalized patients data retracted from central of disease control (CDC) archives during period of 1-9-2013 till 2-28- 2018. Logistic Regression analysis shown 80 Schizophrenia patient taken Clozapine developed penumonia (β = 2.71，p ＜ .05), 15 times more than those without; male (β = 2.02，p ＜ .05) and blood sugar (β = -0.13，p ＜ .05) also positive related which considerd as risk factors, furthermore, male pneumonia complications is 7.55 times more than female; one degree of blood sugar increment, pneumonia complications increase 1.33 times. Besides, Chi-square test results show that drug interactions are associated with pneumonia (χ2 = 5.20，p ＜ .05); Two sample t test indicated that Clozapine cause low WBC count (t = -3.70，p ＜ .001) , low neutrophil (t = -5.40，p ＜ .001). This research concluded that special attention should be given to male inpatients with schizophrenia, taking Clozapine drugs, generating drug interactions, and closely monitoring blood glucose, white blood cell count, and neutrophil numbers to prevent the development of pneumonia.
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Tseng, Chiu-Yu, and 曾秋玉. "Exploration of Risk Factors of Glycemic Control in Patients with Schizophrenia and Diabetes." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/63382940854827245168.
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碩士高雄醫學大學
藥學系碩士在職專班
105
Background: In recent years, many studies have found that sleep quality and glycemic control are highly correlated, but few studies have extensively investigated the relations of glycemic control, sleep quality and drugs. Especially in many patients with schizophrenia are not only using a single anti- psychotropic drugs but also using mood stabilizers. Objective: This study was aimed to investigate the relations of glycemic control efficacy, quality of sleep, drugs and physiological diseases in hospitalized patients with schizophrenia and Diabetes. Also analysis the result to predict the risk factors mainly affects glycemic control. Methods: This study is a retrospective case-control study and conducted schizophrenia inpatients with diabetes in a hospital in the central region of Taiwan during the period from 2013 to 2014. The patients were divided into the good glycemic control group (glycated hemoglobin, HbA1c<7%) and the poor glycemic control group (HbA1c≧7 %). The information including the use of drugs (antipsychotics, antidiabetic drug, hypnotics and mood stabilizers), biochemical tests, disease status and other related factors that affect blood glucose control were collected from their medical records. Data was analyzed using logistic regression and tested with Chi-Square test. Results: A total of 183 schizophrenia patients with diabetes were enrolled in this study. Among them, 89 patients were poor glycemic control group and 94 patients were good glycemic control group with an average age of 52.9±11.8 years old. Patients in poor glycemic control group with diabetes mellitus was longer than those in good glycemic control (8.79±3.31 vs 6.21±2.58) and had a significant difference (p<0.001). In terms of disease, it had the higher percentage of poor glycemic control group with high blood pressure (38.2% vs 23.4%) and hyperlipidemia (33.7% vs 13.8%), and significant differences were observed. In the case of drug use, the poor glycemic control group resulted in a higher proportion of clozapine (46.1% vs 27.7%) and mood stabilizer (33.7% vs 14.9%) use, and significant differences were observed. In the treatment of diabetes with metformin, the poor glycemic control group had a lower proportion of it’s use (23.6% vs 69.1%), and significant differences were observed. After adjusting for other factors, the multiple logistic regression analysis results showed that the risk of poor glycemic control increased by 1.29-fold for each additional year with diabetes year (95% CI=1.12~1.51, p=0.001). The body mass index (BMI) for every additional unit increased the risk of poor glycemic control increased by 1.38 -fold (95% CI =1.18-1.63, p<0.001). Sleep less than 5 hours compared to sleep more than 7 hours , the risk of poor glycemic control increased by 4.31-fold (95% CI=1.49-12.53, p=0.007). Co-administration of clozapine and mood stabilizer compared to non-users , the risk of poor glycemic control increased by 8.22-fold (95% CI=2.01-33.54, p=0.003). With the use of metformin compared to non-users, the risk of poor glycemic control was increased by 0.16-fold (95% CI=0.06-0.38, p<0.001). Conclusion: This study revealed that BMI (>27.7), sleep time (<5 hours), diabetes extended disease duration, and combined use of clozapine and emotional stabilizers are main risk factors of poor glycemic control. And the use of metformin can reduce the chance of 84% of poor glycemic control. These findings provide medical care information for hospitalized schizophrenia patients with diabetic, so as to provide pharmaceutical care to control blood glucose level.
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Liang, Yu-Min, and 梁鈺敏. "Risk Factors Associated with the Relapse of Schizophrenia－Application of the Survival analysis of Cox ProportionalHazards Model." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/11714947329028966912.
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碩士高雄醫學大學
行為科學研究所碩士班
94
Objective：The aim of this study was to use the method of the survival analysis of cox proportional hazards models to explore the risk factors of relapse in schizophrenia, according to several articles about this issues , the risk factors associated with the relapse in schizophrenia were investigated from the anamnesis. Methods：Cases consisted of 94 patients who were diagnosed as schizophrenia （295.0-295.9）by psychiatrists from one of the teaching hospital in southern Taiwan. All of these patients were required to have the condition of first hospitalization after the onset. During the five years of observation （2001-2005）, 52（55.32％）patients who were hospitalized once more due to the illness relapse belonged to the group of relapse；the remainders of 42 patients（44.68％）belonged to the group of not being relapsed. According to the literatures, patient＇s anamnesis of prognosis, nursing records, assessment of social workers and the measurements of COTE were turned into variables. Then, the survival analysis of COX proportional risk model was used to find out the hazard factors in predicting relapse in schizophrenia. Moreover, hazard ratio（HR）and 95 ％ Cl for HR would indicate the degree of relapse. Results：The results showed that if the first child or usually conflicts with the family was 4.8 times higher than the patients who never involves in a conflict（p＝0.004）；95％ Cl for HR would be 0.071-0.613；if the patient who is the first child of the family was 2.95 times higher to be illness relapse than other siblings（p＝0.049）. The relapse rate of patient who conflicted with family members was 4.8 times higher than whom didn＇t（p＝0.004）. 95％ Cl for HR was 0.071-0.613; the first child was 2.95 times higher than the other ranking children （p＝0.049）, and the 95％ Cl for HR would be 0.116-0.995.The social work assessment showed that the worse relationship with the father would result higher illness relapse （p＝0.027）. Conclusion：If the patient who is the first child and usually conflicts with family or if the patient has worse relationship with the father are the hazardous factors to cause illnss relapse in schizophrenia. The results can be a helpful reference for planning intervention and prevention programs for the prevention of relapse in schizophrenia.
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Cheng-Chen and 張正辰. "Variability of waist circumference measurements at three sites and its relationship with cardiovascular risk factors in patients with schizophrenia." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/11267723539853484015.
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碩士中山醫學大學
醫學研究所
98
Objective：1. To compare the magnitude of waist circumference (WC) measured at 3 sites (immediately above the iliac crest, midpoint between the lowest rib and the iliac crest, umbilical level) in males and females. 2. To examine the correlation of WC with lipid profiles, glucose and metabolic syndrome. Methods and Materials： Patients with the DSM-IV diagnosis of schizophrenia, regular follow-up at an outpatient clinic were recruited. After explaining the purpose of the study and obtaining patient’s agreement, the following data are collected: age, gender, education level, marital status, height, weight, and smoking. WC was measured using an inelastic plastic tape at each site. Fasting venous blood samples were collected for lipid and glucose analyses. Differences in WC across sites were tested using repeated measures ANOVA, adjusted for multiple comparisons. Linear regression methods were used to model the relation between fat values measured and WC, with separate calculations performed for each of the 3 sites, adjusting of age and smoking. Results：Our sample consisted of 45 men and 35 women (29-52 years).Both in men and women, the mean WC for all sites were significantly different from each other, with the exception of the iliac crest and umbilical site. WC values at 3 sites were significantly correlated with triglyceride, high-density lipoprotein in men. Midline WC had higher correlation with fasting glucose, diastolic blood pressure, cholesterol/high-density lipoprotein ratio, and metabolic syndrome in men. In women, only iliac crest WC had higher correlation with systolic blood pressure and cholesterol/high-density lipoprotein ratio. Conclusion and Suggestion: The magnitude of WC is influenced by measurement site in both genders. Adopting a standard measurement protocol in schizophrenic patients will facilitate the interpretation and clinical utility of WC for evaluation of cardiovascular risk.
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Shumar, Erik. "Associations between Homelessness and Psychiatric Symptom Severity and How Homelessness Interacts with Risk Factors among First-Admission Psychiatric Patients." Thesis, 2014. https://doi.org/10.7916/D8FJ2DZV.
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Individuals who experience homelessness are exposed to stressors that have the potential to precipitate mental and physical health complications that can present serious threats to multiple areas of these individuals' lives. Although the path to becoming and remaining homeless is different for every individual, there may be some commonality specific to homelessness that makes certain individuals who experience homelessness more vulnerable than other individuals to the expression and potentially devastating course of psychopathology. Guided by the diathesis-stress model, the intent of this study is to explore the question, following a first hospitalization for mental illness ("schizophrenia spectrum disorder" or "other diagnosis"), what are the associations of homelessness with psychiatric symptom severity and how do risk factors of family history of mental illness, low intelligence, housing independence, hopelessness, and lack of social support interact with homelessness? To answer this question, a secondary analysis was performed on data from the Suffolk County Mental Health Project, a longitudinal study that sought to investigate the course of schizophrenia in an epidemiologic sample of first-admission patients. A sub-sample of 548 cases taken from the parent study were further subdivided into two cohorts; individuals diagnosed with schizophrenia spectrum disorder and those diagnosed with non-schizophrenia mental illness. A multilevel analysis was conducted for four different outcome variables, measuring psychotic, disorganized, and depressive symptoms as well as global functioning, in order to determine whether or not there is a significant association between homelessness and the severity of psychiatric symptomatology. Through the continued use of multilevel analytic models and interaction plots, significant confounding variables were examined to determine whether or not they facilitated interactions with homelessness. Homelessness was found to produce a small, but significant effect, for both cohorts across all four outcome variables. Additionally, applied to different outcome variables, the five confounding variables were also found to have small-to-medium-sized, significant interactions with homelessness. The results of this study provide additional statistical support to other studies looking at similar populations.
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Motta, Carolina Dall'Antónia da. "Uncovering the endophenotypic factors on the impact of functional outcomes in schizophrenia: studies on different genetic risk samples from the Portuguese Population." Doctoral thesis, 2020. http://hdl.handle.net/10316/92414.
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Tese no âmbito do Doutoramento em Psicologia, especialidade em Psicologia
Clínica apresentada à Faculdade de Psicologia
e Ciências de Educação da Universidade de Coimbra.The administration of neurophysiological, neurocognitive and behavioral measures as endophenotypes in studies about schizophrenia is in vogue, particularly the inquiry on their interrelationships and their impact on patient’s functional outcome. To this date, increasingly large Portuguese samples with genetic risk to schizophrenia (patients and families) have been integrated into studies about candidate genes to schizophrenia or linkage studies relating schizophrenia to other severe mental illnesses. The inclusion of Portuguese samples gained significant interest for being genetically homogenous in comparison to other western populations. However, despite cognitive abilities being also largely inheritable and relevant to the understanding of schizophrenia, the profile of cognitive deficits in schizophrenia has not been sufficiently explored in our national samples. The use of neurocognitive assessment in schizophrenia has the potential to yield innovations in the multidisciplinary treatment and intervention for affected patients and families, and future research that heighten our understanding about what stands between the genotype and the phenotype regarding this complex and impairing disease. The work hereby presented provides an empirical contribute to the understanding of the endophenotypic aspects involved in schizophrenia, and to the discussion of the implications to research, new intervention targets and psychosocial approaches for families and patients. We studied several putative neurocognitive endophenotypes of that illness by developing an in-depth investigation of the neurocognitive and social cognition in schizophrenia in Portuguese samples of patients affected with schizophrenia, first-degree relatives, and controls. We dove below the cloudy waters of clinical heterogeneity of symptoms to attempt to provide a characterization of schizophrenia – both on an endophenotypic and functional level – in an objective and comprehensive approach. By empirically tracing a latent neurocognitive profile and characterizing the underlying processes of the clinical and biological underpinnings of schizophrenia, we expected to contribute to a more coherent systematization of schizophrenia and treatment/rehabilitation. As a by-product of this research, we also aimed to provide specific and psychometrically sound tools for neurocognitive assessment and performance-based skills assessment relevant to practitioners and researchers working in several disciplinary fields with Portuguese-speaking populations.
A administração de medidas neurofisiológicas, neurocognitivas e comportamentais para a avaliação de variáveis endofenotípicas nos estudos sobre a esquizofrenia é uma área que tem adquirido um progressivo destaque, particularmente no que toca o questionamento sobre as inter-relações entre estas variáveis e o seu impacto na capacidade funcional dos doentes. Até a data, diversos estudos sobre genes candidatos à esquizofrenia ou estudos de ligação relacionando a esquizofrenia a outras doenças mentais graves integraram grandes amostras portuguesas de sujeitos em risco genético para esquizofrenia (pacientes e famílias). A inclusão destas amostras relaciona-se com o facto da população portuguesa ser geneticamente mais homogénea em comparação com outras populações ocidentais. No entanto, e apesar das capacidades cognitivas serem, em grande parte, também hereditárias e relevantes para a compreensão da esquizofrenia, o perfil dos défices cognitivos na esquizofrenia não tem sido suficientemente explorado em amostras nacionais. O uso da avaliação neurocognitiva na esquizofrenia tem o potencial de introduzir inovação no tratamento e potenciar intervenções multidisciplinares direcionadas para pacientes e famílias afetadas, bem como o potencial de fomentar futuras investigações orientadas para o aumento da nossa compreensão sobre o que existe entre o genótipo e o fenótipo desta doença tão complexa e invalidante. O trabalho aqui apresentado é um contributo para a compreensão dos aspetos endofenotípicos subjacentes à esquizofrenia, bem como para a discussão das suas implicações para a investigação, para o estabelecimento de alvos específicos de intervenção e para o desenvolvimento abordagens psicossociais específicas para famílias e pacientes que sofrem de esquizofrenia. Estudámos diversos endofenótipos neurocognitivos putativos da doença, encontrados na literatura, desenvolvendo uma investigação aprofundada da neurocognição e da cognição social na esquizofrenia, em amostras portuguesas de pacientes diagnosticados com esquizofrenia, parentes em primeiro grau e controlos. Mergulhámos para além das águas conturbadas pela heterogeneidade clínica dos sintomas para tentar proporcionar uma caracterização da esquizofrenia – tanto ao nível endofenotípico quanto funcional – recorrendo a abordagens objetivas e metodologicamente abrangentes. Ao traçar empiricamente um perfil neurocognitivo latente e ao caracterizar os processos clínicos e biológicos subjacentes da esquizofrenia, esperámos poder contribuir para uma futura sistematização mais coerente da esquizofrenia, bem como para o seu tratamento e reabilitação. Como um subproduto deste trabalho, procurámos, ainda, fornecer ferramentas específicas e psicometricamente robustas para a avaliação neurocognitiva e para a avaliação de habilidades baseadas no desempenho, que se mostrassem relevantes para profissionais e investigadores atuantes em diversas áreas disciplinares junto de populações falantes da língua portuguesa.
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"Environmental Stimuli Activates Early Growth Response 3 (EGR3), an Immediate Early Gene Residing at the Center of a Biological Pathway Associated with Risk for Schizophrenia." Doctoral diss., 2020. http://hdl.handle.net/2286/R.I.63032.
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abstract: Schizophrenia, a debilitating neuropsychiatric disorder, affects 1% of the population. This multifaceted disorder is comprised of positive (hallucinations/psychosis), negative (social withdrawal/anhedonia) and cognitive symptoms. While treatments for schizophrenia have advanced over the past few years, high economic burdens are still conferred to society, totaling more than $34 billion in direct annual costs to the United States of America. Thus, a critical need exists to identify the factors that contribute towards the etiology of schizophrenia. This research aimed to determine the interactions between environmental factors and genetics in the etiology of schizophrenia. Specifically, this research shows that the immediate early gene, early growth response 3 (EGR3), which is upregulated in response to neuronal activity, resides at the center of a biological pathway to confer risk for schizophrenia. While schizophrenia-risk proteins including neuregulin 1 (NRG1) and N-methyl-D-aspartate receptors (NMDAR’s) have been identified upstream of EGR3, the downstream targets of EGR3 remain relatively unknown. This research demonstrates that early growth response 3 regulates the expression of the serotonin 2A-receptor (5HT2AR) in the frontal cortex following the physiologic stimulus, sleep deprivation. This effect is translated to the level of protein as 8 hours of sleep-deprivation results in the upregulation of 5HT2ARs, a target of antipsychotic medications. Additional downstream targets were identified following maximal upregulation of EGR3 through electroconvulsive stimulation (ECS). Both brain-derived neurotrophic factor (BDNF) and its epigenetic regulator, growth arrest DNA-damage-inducible 45 beta (GADD45B) are upregulated one-hour following ECS in the hippocampus and require the presence of EGR3. These proteins play important roles in both cellular proliferation and dendritic structural changes. Next, the effects of ECS on downstream neurobiological processes, hippocampal cellular proliferation and dendritic structural changes were examined. Following ECS, hippocampal cellular proliferationwas increased, and dendritic structural changes were observed in both wild-type and early growth response 3 knock-out (Egr3-/-) mice. Effects in the number of dendritic spines and dendritic complexity following ECS were not found to require EGR3. Collectively, these results demonstrate that neuronal activity leads to the regulation of schizophrenia risk proteins by EGR3 and point to a possible molecular mechanism contributing risk for schizophrenia.Dissertation/Thesis
Doctoral Dissertation Neuroscience 2020
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Σταθοπούλου, Αναστασία. "Ενδομήτρια έκθεση στον καπνό του τσιγάρου, κίνδυνος εκδήλωσης σχιζοφρένειας και βαρύτητα θετικών/αρνητικών αποτελεσμάτων." Thesis, 2014. http://hdl.handle.net/10889/7994.
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Η προγεννητική έκθεση στον καπνό του τσιγάρου προκαλεί χρόνια εμβρυϊκή υποξία, απορρύθμιση της ομαλής λειτρουγίας του ενδοκρινικού συστήματος, και διαταραχή της νευροανάπτυξης του εμβρύου, η οποία σχετίζεται με εγκεφαλική δυσλειτουργία, τα οποία δυνητικά θα μπορούσαν να προκαλέσουν ευαλωτότητα για σχιζοφρένεια.. Συνολικά 212 ασθενείς με σχιζοφρένεια ηλικίας 14-30 ετών, και 212 αντίστοιχοι μάρτυρες μελετήθηκαν. Η προγεννητική έκθεση στον καπνό του τσιγάρου των ασθενών με σχιζοφρένεια συγκρίθηκε με εκείνη των μαρτύρων εφαρμόζοντας ανάλυση λογιστικής παλινδρόμησης και έλεγχο για διάφορους παράγοντες που αλληλεπιδρούν και συμβάλλουν στην έκβαση της επίδρασης. Εστίες ενδιαφέροντος ήταν η σύγκριση της συχνότητας καπνίσματος της μητέρας και του πατέρα μεταξύ ασθενών και μαρτύρων, καθώς επίσης και η σοβαρότητα των θετικών και αρνητικών συμπτωμάτων μεταξύ των απογόνων καπνιζόντων και μη καπνιζόντων γονέων. Επιπλέον, διερευνήθηκε η σχετική συχνότητα των υποτύπων σχιζοφρένειας μεταξύ των ασθενών καπνιστών και μη καπνιστών γονέων. Μεταξύ των μητέρων των ασθενών με σχιζοφρένεια και των μαρτύρων, 92 (43,4%) και 46 (21,7%) κάπνιζαν, αντίστοιχα. Το κάπνισμα της μητέρας κατά την εγκυμοσύνη είχε μια σημαντικά μοναδική συνεισφορά στην αύξηση του κινδύνου για την ανάπτυξη της σχιζοφρένειας (p = 0,001), καθώς και μεγαλύτερη σοβαρότητα των αρνητικών συμπτωμάτων (p = 0,023). Ταυτόχρονα, λογιστική ανάλυση παλινδρόμησης έδειξε ότι το κάπνισμα της μητέρας κατά την εγκυμοσύνη είχε σημαντικά μοναδική συνεισφορά στην αύξηση κινδύνου για την ανάπτυξη της σχιζοφρένειας με πιθανή αναλογία=2.32, 95%CI=1.41-3.81, p=0.001 και τη συχνότητα των μη-παρανοϊκών υποτύπων με πιθανή αναλογία= 2.94,95%CI=1.50-5.76, p=0.002. Το κάπνισμα του πατέρα δεν είχε σημαντική επίδραση στον κίνδυνο εκδήλωσης σχιζοφρένειας, ούτε στη σοβαρότητα των αρνητικών συμπτωμάτων. Τα ευρήματα υποδεικνύουν ότι το κάπνισμα της μητέρας κατά τη διάρκεια της εγκυμοσύνης θέτει τους απογόνους σε αυξημένο κίνδυνο για σχιζοφρένεια μετέπειτα στη ζωη τους, με αυξημένη σοβαρότητα των αρνητικών συμπτωμάτων. Λαμβάνοντας υπόψη την ευρεία πρακτική του καπνίσματος κατά την εγκυμοσύνη, η έκθεση του εμβρύου στον καπνό θα μπορούσε να είναι ένας σημαντικός αποτρέψιμος τροποποιήσιμος νευροαναπτυξιακός παράγοντας που αυξάνει την ευαλωτότητα για την εκδήλωση σχιζοφρένειας.Prenatal exposure to cigarette smoke causes chronic fetal hypoxia, dysregulation of endocrine equilibrium, and disruption of fetal neurodevelopment associated with brain malfunction, all of which potentially could induce vulnerability to schizophrenia. A total of 212 schizophrenia patients aged 14-30 years, and 212 matched controls were studied. Prenatal tobacco smoke exposure of the schizophrenia patients was compared to that of the normal controls by applying logistic regression analysis and controlling for several confounding factors The outcomes of interest were comparison of the frequency of maternal and paternal smoking between patients and controls as well as the severity of positive and negative symptoms between the offspring of smoking and nonsmoking parents. Furthermore, we investigated the relative frequency of subtypes of schizophrenia among offspring of smoking and non-smoking parent. Among the mothers of schizophrenia patients and controls, 92 (43.4%) and 46 (21.7%) smoked, respectively. Maternal smoking during pregnancy had a significant unique contribution on increasing the risk for development of schizophrenia (p=0.001), and a greater severity of negative symptoms (p=0.023). Simultaneously, logistic regression analysis showed that maternal smoking during pregnancy had significantly unique contribution to increased risk for the development of schizophrenia with possible ratio = 2.32, 95% CI = 1.41-3.81, p = 0.001 and frequency of non-paranoid subtypes as potential ratio = 2.94,95% CI = 1.50-5.76, p = 0.002. Paternal smoking did not have a significant effect on the risk of schizophrenia, or severity of negative symptoms. The findings suggest that maternal smoking during pregnancy puts offspring at an increased risk for later schizophrenia, with increased severity of negative symptoms. Given the wide practice of smoking during pregnancy, fetal exposure to tobacco smoke could be a major preventable neurodevelopmental factor that increases vulnerability to schizophrenia.
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Auerbach, Isabelle. "Kindliche Traumatisierung, elterliche Erziehungsstile, familiäre Vorbelastung und Geburtsrisikofaktoren bei Patienten mit Schizophrenie." Doctoral thesis, 2012. http://hdl.handle.net/11858/00-1735-0000-0006-B2F6-0.
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Shing-Chia, Chen. "Heterogeneity and Risk factors of Aggressive Acts among Schizophrenic Inpatients." 2005. http://www.cetd.com.tw/ec/thesisdetail.aspx?etdun=U0001-0108200519064200.
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Chen, Shing-Chia, and 陳杏佳. "Heterogeneity and Risk factors of Aggressive Acts among Schizophrenic Inpatients." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/38296465019485419625.
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博士國立臺灣大學
護理學研究所
93
Background: Psychiatric inpatients’ aggressive acts can occur frequently and are recognized as a significant problem in psychiatric settings. Understanding of aggressive acts in clinical settings is still incomplete and the clinical care of aggressive acts remains unsatisfactory. It is therefore crucial to establish objective measures and to develop insights into the heterogeneity and related risk factors of aggressive acts, for improvement in the management and prevention of aggressive acts. Objective: The purpose of this study has a many-fold intention depicted as follows: to describe and characterize schizophrenic inpatients’ aggressive acts, to identify and specify heterogeneity in their structure, and to look for and set up risk factors for prevention. This study investigates four major issues: (1) Establishing an objective behavior rating scale for measuring aggressive acts; (2) Understanding the characteristics and incidence of aggressive acts by inpatients with schizophrenia; (3) Exploration of the heterogeneous structure of aggressive acts by inpatients with schizophrenia; and (4) Identifying the risk factors of aggressive acts of inpatients with schizophrenia. Method: The “Two-Stage Model of suicide and violence” coined by Plutchik, van Praag, and Conte and MacArthur’s “Violence Risk Assessment Model” have been incorporated in developing the conceptual framework of this study. At first, by back translation, an English version of the violence scale (VS) was translated into Chinese (VS-C) with counts scaling, including three categories of aggressive acts: (1) towards property (AggP), (2) towards others (AggO), and (3) towards self (AggS). The content validity, construct validity, and internal consistency of VS-C were examined. Prospective panel design was used for data collection. Patients fulfilling the DSM-IV criteria of schizophrenia in the acute psychiatric ward of a university teaching hospital were recruited over a one-year period (April 2001 to March 2002) as study subjects, after signing informed consent. The sample size was 107. Aggressive acts were rated daily using the VS-C by participant observation during the hospitalization period. The raw counts of aggressive acts were summed weekly as a data unit. The risk factors of schizophrenic inpatients’ aggressive acts were measured using “Past Month History of Aggressive Acts”, “State-Trait Anger Expression Inventory”, “Patients’ Basic Demographic and Clinical Data”, “Ward Restriction Scale”, and “Psychiatric Symptoms Checklist”. The heterogeneous structure of aggressive acts was assessed by three indicators: (1) the concurrence of specific categories and types of aggressive acts in the initial week after hospitalization, (2) the correlation of the severity of aggressiveness among specific categories and types between past-month and initial-week aggressive acts, and (3) the concordance of specific categories between past-month and initial-week aggressive acts in sensitivity, specificity, and positive and negative predictive value. The software applications SPSS12.0, S-PLUS6.0, and LISREL8.43 were used for statistical analysis. The statistical methods included descriptive statistics, Chi-square test, Pearson’s correlation, Confirmatory Factor Analysis (CFA), Receiver Operating Characteristic (ROC) curves analysis, multiple regression model and interaction analysis. Results: There was a Poisson distribution and over-dispersion on aggressive acts found in this study. The VS-C with 16 items showed an acceptable quality, but lacked a high internal consistency value (Cronbach’s α = .67). A shorter version of the VS-C could be drawn with one latent variable of 6 items sharing a core meaning labeled as “common outward aggressive acts.” In this study, participating subjects had a mean age of 33.4 (SD = 11.9). The majority of them was single (68.2%), female (69.2%), unemployed (73.8%), and had an Eastern religious affiliation (57.9%). The average duration of their hospitalization was 4 weeks (SD = 2.4, range = 2 to 13). About one quarter of them were involuntarily admitted (26.2%). The mean age of the onset of initial nonspecific symptoms was 24.1 years old. Ninety-one out of 107 patients (85.0%) had a history of past-month aggressive acts, and 63 patients (58.9%) exhibited aggressive acts (mean = 10, SD = 9.8, range = 1 to 46) in the initial week after admission. The past-month incidence rate of aggressive acts was in the order of AggO (70.1%), AggP (44.9%), and AggS (32.7%). The initial-week incidence rate of aggressive acts was in the order of AggO (47.7%), AggP (27.1%), and AggS (14.0%). The category AggO occurred more frequently than the other two categories. All aggressive acts decreased during the treatment course of patients’ hospitalization. The incidence rate of aggressive acts that decreased the most, over weeks, were “loud verbal arguments with another person”, “low grade hostility”, and “used property in a threatening manner without damage”. The incidence rate of aggressive acts decreased to 33.3%, 26.8%, and 16.9% in the following second, third, and forth week respectively during hospitalization. Most patients’ aggressive acts were quickly decreased in two weeks. The study subjects’ aggressive acts were heterogeneous as evidenced by: (1) a high concurrent rate of AggO with AggP (r = .52), especially with physical AggP (r = .51), whereas only physical AggO was concurrent with AggS (r = .24) in the initial week after hospitalization, (2) a high significant correlation of the severity of aggressive acts between corresponding categories of past-month and initial-week aggressive acts (toward property, r= .46 ; toward others, r = .50; toward self, r = .41; and Past-month AggP with AggO, r = .34, and Past-month AggO with AggP, r = .43), whereas the correlation between aggressive acts toward self and the other two categories were all low, and (3) a high concordance rate of corresponding categories of past-month and initial-week aggressive acts (toward property, 72.0%; toward person, 72.6%; toward self, 70.7%). The concordance between past-month AggP and initial-week AggO (64.7%), past-month AggO and initial-week AggP (64.6%) were also high, whereas the concordance between aggressive acts towards the self and other two categories were low. The risk factors of weekly averages of AggP during hospitalization were weekly averages of past-month AggP, and positive and negative psychiatric symptoms. The risk factors of weekly averages of AggO during hospitalization were weekly averages of past-month AggO, affective psychiatric symptom, and the interaction of weekly averages of past-month AggO and gender factor. The risk factors of weekly averages of AggS during hospitalization were only the weekly averages of past-month AggS. Apparently, the risk factors of these three categories of aggressive acts were different. Globally, the risk factors that significantly predict the single latent factors of “common outward aggressive acts.” were the corresponding category of past-month aggressive acts, psychiatric symptoms, and gender factor. Discussion: The strength of this study on aggressive acts of inpatients with schizophrenia was a prospective observation study design using an objective measure. Previous studies of patients’ aggressive acts mainly used retrospective reports, which might underestimate the occurrence of patients’ aggressive acts, and which provided a cross-sectional data only. This study revealed information on aggressive acts occurring weekly after admission into the psychiatric ward. In addition, to identify the risk factors of aggressive acts and consider their developmental directions to predict the formation of aggressive acts. This brings insight into the dynamic nature of aggressive acts of schizophrenia inpatients. Further, the incidence rate of aggressive acts decreased of 83.1% after 4 weeks of admission. This information is useful for emphasizing prevention and management of aggressive acts of inpatients with schizophrenia after admission. The specific category of initial-week aggressive acts was accurately predicted around seventy percent of the time by the corresponding category occurring in the past month prior to admission. This evidence is crucial for clinical psychiatric service in the prevention of aggressive acts. AggP was also predicted by high level of the positive and low level of the negative psychiatric symptoms; the AggO was also predicted by high level of the affective psychiatric symptoms. Male patients with a past-month history of AggO predict AggO more accurately than the same for female patients. Gender has no effect on the prediction of the other two categories of AggP and AggS. The risk factors of aggressive acts among schizophrenic inpatients occurring during hospitalization did not include the personality variable of an anger trait. This might be due to the fact that the acute phase of illness might reduce the effect of the anger trait on aggressive acts. The anger trait may play a role on aggressive acts that occur in the stabilized state of illness. This needs to be studied further.
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Badowska, Dorota. "Schizophrenia risk factor Tcf4 and gene-environment interaction in mice." Doctoral thesis, 2014. http://hdl.handle.net/11858/00-1735-0000-0022-5DCD-B.
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Tseng, Pei-Hsin, and 曾姵馨. "Risk and determined factars of developing Dementia in patients with Schizophrenia." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/90548900711352052784.
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碩士中山醫學大學
醫療產業科技管理學系碩士班
103
Background:As the global population aging, advances in medical technology, the elderly population is growing ensue a rapid increase in dementia and schizophrenia patients. World Health Organization in April 2012 report released by the Global dementia, estimated in 2010 of 35.6 million worldwide with dementia, with 7.7 million annual increase rate of growth, that is, about every four seconds on a new diseased person. According to the study,schizophrenia patients may got hypertension, diabetes,cerebrovascular disease , metabolic syndrome related comorbidities .And reduce healthy management ability.Schizophrenia patients will significantly increase the risk of dementia,In this study, we use"National Health Insurance Research Database" to analyzethat if schizophrenia patient will developdementia or not.Schizophrenia patients will significantly increase the risk of dementia, Objective: Schizophrenia and dementia are important diseases in the medical field. The study was designed to investigate the risk factors of schizophrenia , related factors of dementia and whether the elderly patients with schizophrenia will increase the risks of dementia or not. Methods:The study used 2005 from the National Health Insurance data and randomly selected one million representative samples of the large-scale data .The database is from 2000 to 2010 , all the medical data of this study conducted a case-control study. By age, gender and comorbidity to pair up. After pairing , experimental group are 8497 people ,and there are 33,988 in control groupe. Conducting descriptive statistics and logistic regression with SPSS 18.0 to analyze patients with schizophrenia increasing the risks of dementia. Results:The studies showed that patients who have gender, schizophrenia, cerebrovascular disease , chronic liver disease, diabetes, hypertension, hyperlipidemia, alcoholic diseases are significant differences. Statistics showed that patients with comorbid disease and schizophrenia increases the risk of dementia.Cerebrovascular disease, chronic liver disease, diabetes, hypertension, hyperlipidemia, and alcoholic diseases, included as control variables,. Schizophrenia patients will significantly increase the risk of dementia, the risk (RR=3.84). We can find that patients who are under 65 years old will significantly increase the risk of dementia, and the risk is higher than the population over 65 years old. In ages among 50-59 ,with the highest risk. Men’s schizophrenia patients will significantly increase the risk of dementia, and the risk is higher than the female population. Conclusion:The study found that patients with schizophrenia may increase the risk of dementia, patients with chronic diseases particularly increase the risk of dementia, hyper-aged society in Taiwan, people with schizophrenia and dementia increasing. It should be early detection , giving diagnosis and treatment.
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Dragomir, Elena Alice. "Évaluation de l'impact clinique et économique du développement d'un traitement pour la schizophrénie." Thèse, 2010. http://hdl.handle.net/1866/4818.
Full textAbstract:
Contexte : Les stratégies pharmacologiques pour traiter la schizophrénie reçoivent une attention croissante due au développement de nouvelles pharmacothérapies plus efficaces, mieux tolérées mais plus coûteuses. La schizophrénie est une maladie chronique présentant différents états spécifiques et définis par leur sévérité.
Objectifs : Ce programme de recherche vise à: 1) Évaluer les facteurs associés au risque d'être dans un état spécifique de la schizophrénie, afin de construire les fonctions de risque de la modélisation du cours naturel de la schizophrénie; 2) Développer et valider un modèle de Markov avec microsimulations de Monte-Carlo, afin de simuler l'évolution naturelle des patients qui sont nouvellement diagnostiqués pour la schizophrénie, en fonction du profil individuel des facteurs de risque; 3) Estimer le coût direct de la schizophrénie (pour les soins de santé et autres non reliés aux soins de santé) dans la perspective gouvernementale et simuler l’impact clinique et économique du développement d’un traitement dans une cohorte de patients nouvellement diagnostiqués avec la schizophrénie, suivis pendant les cinq premières années post-diagnostic.
Méthode : Pour le premier objectif de ce programme de recherche, un total de 14 320 patients nouvellement diagnostiqués avec la schizophrénie ont été identifiés dans les bases de données de la RAMQ et de Med-Echo. Les six états spécifiques de la schizophrénie ont été définis : le premier épisode (FE), l'état de dépendance faible (LDS), l’état de dépendance élevée (HDS), l’état stable (Stable), l’état de bien-être (Well) et l'état de décès (Death). Pour évaluer les facteurs associés au risque de se trouver dans chacun des états spécifiques de la schizophrénie, nous avons construit 4 fonctions de risque en se basant sur l'analyse de risque proportionnel de Cox pour des risques compétitifs. Pour le deuxième objectif, nous avons élaboré et validé un modèle de Markov avec microsimulations de Monte-Carlo intégrant les six états spécifiques de la schizophrénie. Dans le modèle, chaque sujet avait ses propres probabilités de transition entre les états spécifiques de la schizophrénie. Ces probabilités ont été estimées en utilisant la méthode de la fonction d'incidence cumulée. Pour le troisième objectif, nous avons utilisé le modèle de Markov développé précédemment. Ce modèle inclut les coûts directs de soins de santé, estimés en utilisant les bases de données de la Régie de l'assurance maladie du Québec et Med-Echo, et les coûts directs autres que pour les soins de santé, estimés à partir des enquêtes et publications de Statistique Canada.
Résultats : Un total de 14 320 personnes nouvellement diagnostiquées avec la schizophrénie ont été identifiées dans la cohorte à l'étude. Le suivi moyen des sujets était de 4,4 (± 2,6) ans. Parmi les facteurs associés à l’évolution de la schizophrénie, on peut énumérer l’âge, le sexe, le traitement pour la schizophrénie et les comorbidités. Après une période de cinq ans, nos résultats montrent que 41% des patients seront considérés guéris, 13% seront dans un état stable et 3,4% seront décédés. Au cours des 5 premières années après le diagnostic de schizophrénie, le coût direct moyen de soins de santé et autres que les soins de santé a été estimé à 36 701 $ canadiens (CAN) (95% CI: 36 264-37 138). Le coût des soins de santé a représenté 56,2% du coût direct, le coût de l'aide sociale 34,6% et le coût associé à l’institutionnalisation dans les établissements de soins de longue durée 9,2%. Si un nouveau traitement était disponible et offrait une augmentation de 20% de l'efficacité thérapeutique, le coût direct des soins de santé et autres que les soins de santé pourrait être réduit jusqu’à 14,2%.
Conclusion : Nous avons identifié des facteurs associés à l’évolution de la schizophrénie. Le modèle de Markov que nous avons développé est le premier modèle canadien intégrant des probabilités de transition ajustées pour le profil individuel des facteurs de risque, en utilisant des données réelles. Le modèle montre une bonne validité interne et externe. Nos résultats indiquent qu’un nouveau traitement pourrait éventuellement réduire les hospitalisations et le coût associé aux établissements de soins de longue durée, augmenter les chances des patients de retourner sur le marché du travail et ainsi contribuer à la réduction du coût de l'aide sociale.Aim: Pharmacological strategies for schizophrenia have received increasing attention due to the development of new therapies more effective, better tolerated but more expensive. Schizophrenia is a chronic illness with various states of illness. Objectives: This research program aimed: 1) to evaluate the factors associated with the risk of being in a specific state of schizophrenia in order to construct the risk functions of the course of schizophrenia modeling; 2) to develop and validate a Markov model with Monte-Carlo micro-simulations in order to simulate the natural course of patients who have been newly diagnosed with schizophrenic based upon the individual risk factors profile; and 3) to estimate the direct healthcare and non-healthcare cost of schizophrenia and to simulate clinical and economic impact of developing a new treatment, in a cohort of patients newly diagnosed with schizophrenia, over the first 5 years following their diagnosis. Methods: For the first objective of this research program, a total of 14,320 newly diagnosed patients with schizophrenia were identified based on data from the RAMQ and Med-Echo databases. Six disorder states of schizophrenia were defined: first episode (FE), low dependency state (LDS), high dependency state (HDS), Stable state (Stable), Well state (Well) and Death state (Death). To evaluate factors associated to the risk of being in each disease state, we constructed 4 risk functions based on the Cox proportional hazard analysis for competing risks. For the second objective, a Markov model with Monte-Carlo microsimulations with the six specific states of schizophrenia was developed and validated. In the model, each subject had his own probabilities of transition between specific states, which were estimated based on the cumulative incidence function. For the third objected, we used the Markov model we previously developed. The model includes direct healthcare costs estimated from the Régie de l’assurance maladie du Québec and Med-Echo databases and direct non-healthcare costs estimated from the surveys and publications of Statistics Canada. Results: A total of 14,320 individuals were identified in the study cohort as newly diagnosed patients with schizophrenia. The mean follow-up of the subjects was of 4.4 (± 2.6) years. The age, the sex, the schizophrenia treatment, and having comorbidities are factors that are associated with the schizophrenia course. After a five-year period, our results show that 41% of patients will be considered as having recovered, 13% will be in stable condition and 3.4% of patients will have died. The mean direct healthcare and non-healthcare cost of schizophrenia over the first 5 years following diagnosis was estimated $36,701 Canadian (CAN) (95% CI: 36,264 to 37,138). The direct healthcare cost accounted for 56.2% of the total cost, welfare assistance for 34.6% and long term care facilities for 9.2%. On the direct healthcare cost, hospitalisation cost accounted for 64.6%, medical cost for 11.4% and drug-related cost for 24%. In the case where a new treatment with 20% increase of effectiveness will be available, the direct healthcare and non-healthcare costs can be reduced up to 14.2%. Conclusion: We have identified factors associated with the schizophrenia’s specific states, The Markov model we have developed is the first Canadian model incorporating transition probabilities adjusted for individual risk factor profiles using real-life data. The model shows a good internal and external validity. Based on the cost estimates, our results indicate that a new treatment could possibly reduce hospitalization and long-term care facility costs while potentially enabling patients to return to active employment that would in turn contribute to the reduction of the welfare assistance cost.
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Lin, Chia-Jung, and 林嘉容. "Explore the Moderation and Mediation Effects among those Risk Factors of the Treatment of Schizophrenia:A Longitudinal Study." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/57607287032319739600.
Full textAbstract:
碩士淡江大學
數學學系碩士班
98
Schizophrenia is a complex and heterogeneous psychosis. The durations of antipsychotic trial for drug treatment of schizophrenia recommend to at least 42 days. Efficacy and drug safety were assessed on days 0, 14, 28, and 42. Therefore, the data structure is a longitudinal dependent data. We have published 20 papers to explore the relationship between the treatment effects of schizophrenia and some potential prognostic/risk factors. Those factors can be classified into three major areas: genes, disease related factors and patients’ personal characteristics. Efficacy was measured by the PANSS and/or other clinical evaluation forms like Clinical Global Impression (CGI), named dependent variables. We used GEE method’s generalized linear models/other non-parametric methods to explore the possible moderation effects and/ the mediation effects among those aforementioned risk factors. One of the primary study purposes of evaluating the treatment effects of schizophrenia is to figure out the changes of each response variable with respect to time. Therefore, to explore the moderation effect, we focus on the moderation effect on the treatment time to each response variable. Accordingly, to explore the mediation effect, we used the GEE method’s generalized linear model to adjust the time effect. Some other nonparametric methods, such as Chi-Square Test, Kruskal-Wallis Test, Kolmogorov-Smirnov Test, or Kendall’s bivariates correlations, were used to explore the mediation effect of those risk factors to each response variable according to the characteristics of risk factors. In conclusion, the relationships between treatment week and those nine response variables were influenced by the genetic factors; the disease related factors influence the relationships between treatment week and the response variables (except CGI); the patients’ characteristic factors were influence on the relationships between treatment week and four indicators ( CGI, PANSS negative score, PANSS total score, and response ). Further analyses on the partial/complete mediator, we found that some genetic and disease related factors were partial mediators. And, body weight was the only complete mediator of sex to PANSS negative score.
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Mei-Kuei and 吳梅桂. "The risk factors of cardiovascular disease and the effect of diet and physical activity program in clozapine-treated schizophrenic obesity." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/81974959043939493828.
Full textAbstract:
博士中山醫學大學
營養學研究所
96
Schizophrenia has a prevalence of 1 percent in all cultures and is equally common in men and women. It is a devastating mental illness that impairs mental and social functioning. Clozapine is effective in treating not only the positive symptoms of schizophrenia, but also in reducing negative symptoms and cognitive deficits. Several studies have reported significant weight gain with clozapine and the largest weight gains seen with antipsychotic drug and had a significantly higher mean BMI value and rate of obesity than patients treated with other SGAs. Obese patients with schizophrenia being treated with clozapine (OSC) and non-psychiatric obese (OB) are often assumed to share the same physiological changes in obesity. In fact, the obese patients with schizophrenia being treated with clozapine was different from non-psychiatric obese in physiological change. Although the anthropometric parameters in the OB and OSC groups were similar, in the OSC group the waist-to-hip ratio (WHR), insulin levels and HOMA index were significantly higher, while insulin sensitivity, cholesterol, low-density lipoprotein (LDL) cholesterol, TC/HDL-C, LDL-C/HDL-C, IGF-1 and IGF-1/IGFBP-3 molar ratio were lower, than those of the OB group. Significant weight gain can lead to health complications such as cardiovascular disease, hypertension, dyslipidemia, stroke, gallbladder disease, osteoarthritis, sleep apnea, respiratory problems, certain cancers, and type 2 diabetes. Compliance with prescribed antipsychotic medication is low and weight gain contributes to psychotropic non-compliance. The intervention program of dietary control and regular physical activity in obese patients with schizophrenia being treated with clozapine can showed a significant decrease in body weight, BMI, body fat percentage, and waist and hip girths. In addition, participating patients showed improved metabolic profiles of triglyceride, insulin, IGFBP-3 levels, and the IGF-1 to IGFBP3 molar ratio. In conclusion, the obese patients with schizophrenia being treated with clozapine was different from non-psychiatric obese in physiological 3 change. The obese patients with schizophrenia being treated with clozapine group was characterized by impaired glucose–insulin homeostasis, abnormal lipid profiles and hormonal changes in the GH-IGF-IGFBP axis and in leptin. By way of the program of dietary control and regular physical activity can significantly reduce body weight and improve metabolic profiles of insulin, triglyceride, and IGFBP-3 among obese inpatients taking clozapine for the treatment of schizophrenia.
50
Chen, Po-Yu, and 陳柏妤. "Family history of obesity related metabolic diseases as the risk factor of metabolic disturbances in schizophrenic patients receiving antipsychotics." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/61122088915656095016.
Full textAbstract:
碩士國立臺灣大學
臨床醫學研究所
96
Objective: Obesity and diabetes mellitus are common side effects during antipsychotics treatment. These side effects may predispose cardiovascular diseases and decrease antipsychotics compliance in schizophrenic patients. Higher prevalence of metabolic diseases in schizophrenic patients was frequently reported in many countries. However, there are not many studies of the prevalence of metabolic diseases in community patients in Taiwan. Different effects on metabolic disease among various antipsychotics have been broadly discussed. However, clinical risk factors focusing on patient aspects still need to be further clarified. Family history was demonstrated as an important risk factor for metabolic diseases in general population. However, whether family history us also important for antipsychotics related metabolic disease is still an unresolved question. Our study aimed to provide reference for prevalence of metabolic disease in community schizophrenic patient in our country. Furthermore, this study examined the influence of family history on the metabolic outcomes related to antipsychotics treatments Methods: Volunteer schizophrenic patients were recruited during a disease screening activity, sponsored by Taipei Public Health Bureau. Schizophrenic who live in community and half-way houses were invited. Personal interview for clinical information were performed. All patients receive anthropometric measurements and fasting blood sampling to evaluate metabolic disease status. Prevalence of metabolic diseases among our patients was described. Multiple logistic regression model was use to define the metabolic family histories risk on various metabolic outcomes. Results: Totally 307 patients were included in this study. Our analysis revealed prevalence in these patients were 60% for overweight, 30% for obese, 33.01% for metabolic syndrome, 33.66% for hypertension, 10.46% for diabetes mellitus and 9.48% in hypercholesterolemia. Most of these prevalence rates were higher than general population. Males tend to have hypertension. Females were found to have more diabetes and central obesity. Antipsychotics effects on metabolic diseases were not significant distinct in our study. Family history of DM elevated the risk to 2.35 in overweight, 2.01 in obesity, 2.07 in central obesity and 3.31 in DM. In addition, family history of DM increases 4.95 kg of mean body weight and 2.11 of body mass index. Family history of DM could be a predictor for overweight, obesity, central obesity and DM when patient receiving antipsychotics and as a reference for medical decision. Also, our study found interaction between antipsychotics and family history of DM , comparing to those without family history of DM, typical and second-generation antipsychotics generated more prominent risks for central obesity. Other metabolic disease family histories didn’t showed significant correlation with the metabolic outcomes in schizophrenic patients receiving antipsychotics. There are several limitations of this study. First of all, only current drug information was available. Second, there are many kinds of drugs in this study and the sample size for single drug is too small to clarify the specific drug effect. Also, information about family history was self-reported .It may be under estimated due to impaired cognitive function of schizophrenic patients. Conclusion: The prevalence of metabolic diseases for schizophrenic patients in community was higher than the general population. Specific gender differences were found. Family history of DM predicts overweight, obesity, central obesity and DM in schizophrenic patient with antipsychotics treatments.