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Dissertations / Theses on the topic 'Major depressive disorder'
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Quiring, Jason Matthew. "Early intervention and major depressive disorder /." view abstract or download file of text, 2002. http://wwwlib.umi.com/cr/uoregon/fullcit?p3055704.
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Thesis (Ph. D.)--University of Oregon, 2002.Typescript. Includes vita and abstract. Includes bibliographical references (leaves 114-123). Also available for download via the World Wide Web; free to University of Oregon users.
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Sheppard, Leyland Curtis. "Processing of the depressive schema in major depressive disorder." Thesis, University of Cambridge, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.621919.
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Mullins, Niamh Aine. "Dissecting the genetics of major depressive disorder." Thesis, King's College London (University of London), 2017. https://kclpure.kcl.ac.uk/portal/en/theses/dissecting-the-genetics-of-major-depressive-disorder(cc98809b-0603-4dd8-b88c-ea9c8a6afbbd).html.
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Major depressive disorder (MDD) is a leading cause of disability worldwide and a major contributor to early mortality from suicide. It is a common psychiatric illness with a wellestablished heritability. MDD is an extremely heterogeneous disorder in terms of symptoms, genetics and environmental risk factors. This thesis uses genetic and environmental data from case-control, clinical trial and population samples to dissect the heterogeneity of MDD. Gene-environment interactions were tested in the Radiant UK recurrent depression sample using polygenic risk scores (PRS), which reflect genetic liability for MDD based on many common variants. No interactions were found between PRS and adult adverse events. Interactions between PRS and childhood trauma showed an inverse association with MDD status, as cases who experienced more severe trauma tended to have a lower PRS. The current selection pressures on genetic variants associated with MDD and other psychiatric disorders were investigated in the Icelandic population by testing whether PRS are associated with number of offspring. There was no evidence that risk alleles for depression are under selection, whereas higher PRS for autism were associated with fewer children and higher PRS for ADHD were associated with having more children. Genome-wide association studies on suicide attempt were conducted comparing 6,569 attempters versus 17,232 non-attempters from MDD, bipolar disorder and schizophrenia cases in the Psychiatric Genomics Consortium. This identified three genome-wide significant loci for suicide attempt in mood disorders, which will be replicated in independent samples. Finally, blood mRNA levels of SAT1, PTEN, MAP3K3 and MARCKS have been reported as biomarkers for suicidality and here, an independent test in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study did not support the validity of the proposed biomarkers. The availability of phenotypic, genetic and environmental data provides abundant opportunities to leverage the heterogeneity of depression to better understand its complex aetiology.
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Williamson, Sarah Elisabeth. "STin2 RISK GENOTYPES FOR MAJOR DEPRESSIVE DISORDER." Thesis, The University of Arizona, 2009. http://hdl.handle.net/10150/197262.
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Hung, Chi-Fa. "Medical diseases and obesity in major depressive disorder." Thesis, King's College London (University of London), 2015. https://kclpure.kcl.ac.uk/portal/en/theses/medical-diseases-and-obesity-in-major-depressive-disorder(07dc80a9-c3cf-448a-83e0-ad2644640a4d).html.
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The association between major depressive disorder (MDD) and various physical diseases is well recognized. However, previous studies have mainly focused on depression in physically ill individuals. My thesis aims to investigate the reverse direction, i.e. the occurrence of physical diseases including obesity in individuals with MDD. First, I found evidence for higher prevalence rates for eight out of the 16 common physical diseases studied here in depressed people compared to controls with no history of MDD. Affected and unaffected siblings of the depressed subjects showed a similar pattern. The diseases that were significantly more common in depressed subjects were hypertension, hypercholesterolemia, myocardial infarction, asthma, allergic rhinitis/ hay fever, gastric ulcer, osteoarthritis and thyroid disease. In addition, factor and correlational analyses showed that groups of physical diseases tended to cluster together in families where one or more individuals suffered from depression. The most striking of these was a ‘metabolic syndrome’ cluster, which was associated with high body mass index (BMI). Second, I explored personality factors as possible mediators of the link between MDD and physical diseases. Neuroticism, as measured by the Eysenck Personality Questionnaire, was associated with an increased number of self-reported physical diseases in individuals with MDD. Among individual diseases, only asthma had a modest but significant association with MDD. However, we did not find a familial correlation between neuroticism and asthma, suggesting that the phenotypic association between neuroticism and asthma is unlikely to have a genetic component. Third, a new statistical tool was used to estimate the proportion of phenotypic variance of complex diseases/ traits that can be explained by common tag single nucleotide polymorphisms (SNPs), termed “SNP heritability”. Analysis indicated that a substantial proportion of phenotype variance of both BMI and MDD was explained by common genetic variants. There was also suggestive evidence for a substantial genetic correlation between BMI and MDD, although the estimates had large standard errors. This imprecision almost certainly reflects the fact that, although the samples used here were large, even greater sample sizes are required for analyses of SNP heritability. Fourth, I used 32 SNPs identified from a published meta-analysis of genome-wide association studies (GWAS) on BMI to construct both weighted and un-weighted genetic risk scores (GRS) for BMI. Perhaps surprisingly, only 1.27% of the variance of BMI score was explained by the GRSs derived from these SNPs. Subsequent analyses showed that neither GRS alone, nor GRS combined with ‘traditional’ risk factors, can provide, in our present state of knowledge, a useful tool to discriminate the presence or absence of obesity in depressed people. Fifth, Mendelian randomization (MR) was used to attempt to disentangle the causal relationship between increased BMI and MDD. Although conventional regression analysis suggested a strong association between increased BMI and MDD, MR analysis failed to support the hypothesis that increased BMI is a causal factor in the development of MDD. Finally, I further explored the association between MDD and physical diseases by reviewing published genome wide association study (GWAS) data on MDD to examine whether identified risk loci for MDD overlapped with loci implicated in physical diseases. I then analysed our own GWAS data on depression to examine the presence of case/control differences at loci where there had been physical disease ‘hits’ in published studies. Analyses indicated that the SNP rs1342326, near the IL33 gene, which was genome-wide significant in a GWAS on asthma, was over-represented in individuals with MDD. However, MR analysis did not support a causal relationship between suffering from asthma and having MDD. These results could suggest a single point of genetic overlap between asthma and MDD that might contribute to the observed phenotypic overlap between the two disorders, and highlight the need for further studies in larger samples. In summary, the analyses presented in this thesis show that the relationship between MDD and physical diseases/ obesity is complicated, but suggests that genetic factors play a role in the overlap between depression and BMI and, by implication, diseases associated with high BMI. Only one non-BMI associated disease, asthma, has an identifiable polymorphism that is also associated with depression and withstands correction for multiple testing. Further larger scale studies searching for disease associated variants are vital in order to understand the pathogenesis of the co-occurrence between MDD and physical diseases/ obesity. These will include genome-wide and, eventually, deep sequencing studies of very large cohorts such as the UK Biobank.
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Withall, Adrienne Lee. "Cognitive function and recovery in major depressive disorder." Thesis, The University of Sydney, 2006. https://hdl.handle.net/2123/28184.
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The term ‘depression’ is used to refer to conditions ranging from non-clinical low mood to severe clinical conditions often resulting in hospitalization (American Psychiatric Association, 1994). Most people will experience low mood at some time during their lives however Major Depressive Disorder (MDD) is much more severe and very common, being experienced by approximately one in five persons. MDD is also associated with significantly impaired daily function (Andrews, Henderson, & Hall, 2001; Bland, 1997). Depression is also a chronic illness that is predicted to become the second leading cause of world-wide disability by the year 2020, second only to ischaemic heart disease (Lewis &
Araya, 2001).
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Smolkina, Milana. "Epidemiological and genetic associations between Cannabis Use Disorder and Major Depressive Disorder." Thesis, King's College London (University of London), 2019. https://kclpure.kcl.ac.uk/portal/en/theses/epidemiological-and-genetic-associations-between-cannabis-use-disorder-and-major-depressive-disorder(aae240ea-e4b3-4c30-8fc0-fba14831b3a1).html.
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Background: Cannabis is the most commonly used illicit drug in the United Kingdom and worldwide. It is associated with a number of negative outcomes, which includes developing Cannabis Use Disorder (CUD). Individuals who meet criteria for CUD are at heightened risk for experiencing Major Depressive Disorder (MDD), the leading cause of disability worldwide. While this association has frequently been reported, the underlying mechanisms remain controversial. Aims of thesis: This thesis aims to investigate the degree of co-morbidity between lifetime rates of CUD and MDD, test whether this co-morbidity is accounted for by shared covariates, and test different twin models to investigate the sources (environmental or genetic) of and mechanisms underlying this co-morbidity. Methods: Data analysis was conducted on a sample of 3824 Australian twins and their non-twin siblings. Epidemiological analyses, using multivariable logistic regressions, tested whether CUD and MDD were significantly co-morbid in this sample, and to what extent covariates influenced this relationship. Twin models – bivariate correlated liabilities, discordant twin and co-morbidity models – examined whether the co-morbidity between the disorders could be explained by a) shared genetic and environmental factors, b) causal processes, and c) 13 different models of co-morbidity. Results: The epidemiological analyses found that MDD and CUD were significantly co-morbid in this sample: meeting diagnostic criteria for one disorder more than doubled the odds of meeting criteria for the other (odds ratio = 2.23, 95% confidence interval = 1.84–2.70). This co-morbidity could not be fully attributed to various psychiatric, trauma-related, parental, peer and demographic covariates. Bivariate twin analyses found that – when separated into genetic and environmental correlations – the only significant correlation between MDD and CUD was genetic (r =.41, 95% confidence interval = .24–.60). A possible causal relationship could not be excluded, because MDD and CUD were significantly associated (odds ratio = 2.83, 95% confidence interval = 1.12–7.19) in monozygotic twins discordant for both disorders. Co-morbidity model analyses indicated that the direction of influence was from CUD to MDD, and that CUD risk factors may cause MDD symptoms, particularly in individuals at high risk of CUD.
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Farmer, Caroline. "Understanding poor help-seeking rates for major depressive disorder." Thesis, University of Exeter, 2013. http://hdl.handle.net/10871/14620.
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The principal aim of this thesis was to further understanding of the factors influencing decisions to seek treatment for Major Depressive Disorder. A review of the literature (Chapter 2) revealed a number of factors associated with help-seeking for mental health disorders. However, there was no existing theoretical model of decisions to seek treatment for MDD, and there was limited understanding of the psychological and emotional processes involved in seeking treatment for depressive symptoms. In Study 1 (Chapter 3), a qualitative study explored participants’ accounts of seeking treatment for MDD, which resulted in the development of a theoretical model of help-seeking. This model highlighted the role of identity and goals in decisions to seek treatment for MDD. Subsequent studies in this thesis sought to test predictions made by this model. Study 2 (Chapter 4) explored the relationship between identity and goal conflict and depressed individuals’ acknowledgement of depressive symptoms and perceived need for treatment. Findings of this study suggested that greater identity conflict, but not goal, conflict was associated with reduced acknowledgement of depressive symptoms and less perceived need for treatment. Study 3 (Chapter 5) sought to replicate this relationship, and also tested the extent to which identity as a depressed person and socio-cognitive models of health behaviour could predict (i) intentions to seek treatment for depression and (ii) current treatment seeking. This study found that identity conflict was associated with reduced acknowledgement of depressive symptoms, but failed to replicate the relationship between identity conflict and perceived need for treatment for depression. However, greater identity as a depressed person was associated with both current treatment seeking and greater intentions to seek help. Analyses demonstrated that the Theory of Planned Behaviour and the Health Belief Model predicted current help-seeking and help-seeking intentions, but identity as a depressed person explained an additional significant proportion of the variance. A unified model, drawing on these two theories and incorporating identity was found to be the best fit in accounting for intentions to seek help for depression. The findings of Study 4 (Chapter 6) demonstrated that identity as a depressed person was also a significant predictor of prospective help-seeking behaviour for MDD. In this study, the majority of factors from the Theory of Planned Behaviour and Health Belief Model, extended to include identity, predicted help-seeking behaviour indirectly via intentions to seek help. However, intentions to seek help only predicted a small proportion of the variance in help-seeking behaviour, and the findings revealed that a subsample of factors, including identity, directly predicted help-seeking behaviour. The final study sought to use an online focus group to develop a measure of symptom avoidance in depressed individuals. This study faced methodological difficulties, and Chapter 7 reflects on the use of online focus groups to explore patient experiences of illness. The findings of this study highlighted participant experiences of using an online focus group method to discuss personal experiences of MDD, and this chapter provides specific guidance for other researchers planning to use this method in the context of health research. The implications of the findings of this thesis are discussed in Chapter 8, alongside recommendations for future help-seeking research.
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Zeng, Yanni. "The identification of risk factors for major depressive disorder." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28702.
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For complex traits, population genetic studies ask: to what extent do genetic variation and environmental variation influence, determine and predict phenotypic variation? More specifically, researchers ask two questions. First, how much of the phenotypic variation is genetic in origin? Second, if the genetic component of a trait has been ascertained, then by what mechanisms do the causal variants contribute to the genetic variation that impacts on the phenotype? Previous studies have indicated a polygenic structure for many complex traits, which means that the genetic variation in those traits is the result of the cumulative effect from hundreds or even thousands of genetic variants. To further decipher the polygenic genetic architecture of a complex trait, genetic studies aim to identify the number, the location in the genome, and the distribution of the effect sizes of causal variants, as well as their individual and interacting effects. Linkage analysis and genome-wide association studies (GWAS), either based on single variants or sets of variants categorized by functional annotations, can be applied to map the potentially causal variants in the genome. The identification of disease-associated loci, however, is only the starting point in identifying causal variants. Causal variants are usually difficult to distinguish from the large number of variants in linkage disequilibrium (LD) within the associated loci, and may be in incomplete LD with genotyped variants. Computational prediction integrated with multi-level ‘Omic’ data will help the prioritization of candidate causal variants, which then become important targets for experimental validation (Chapter 1). Major depressive disorder (MDD) is a complex trait, contributes the second most important burden to global disease. Both genetic and environmental components have been suggested for this disorder in previous studies, although a clear partitioning of the contribution of each component and the identification of major contributing components is yet to be achieved. In efforts to map causal genetic variants, genome-wide association studies of MDD have identified few significant associations so far. The polygenic architecture combined with the widespread clinical and genetic heterogeneity of MDD between populations may impede the identification of causal variants (Chapter 2). In this thesis, I will present three studies; the first study estimated the proportions of the phenotypic variation that are genetic or familial environmental in origin in two depression definitions(chapter 3), followed by two studies where distinct (non- GWAS) methods were used to identify candidate causal genetic variants for MDD (chapter 4,5). In detail, in chapter 3, a variance component analysis was applied to GS:SFHS (Generation Scotland: Scottish Family Health Study) to investigate the relative genetic and environmental contributions to diagnosed major depressive disorder (MDD) and self-declared depression (SDD). Models for MDD and SDD that simultaneously included genetic and environmental effects suggested that narrow-sense heritability could be inflated by the environments shared by nuclear family members. The most parsimonious models selected for both MDD and SDD included SNP and pedigree-associated genetic effects and the effect of the common environment of couples. In chapter 4, I integrated pathway analysis and multi-level regional heritability analyses in a pipeline designed to identify MDD-associated pathways. The pipeline was applied to two independent GWAS studies (GS:SFHS and PGC1-MDD). The NETRIN1 signalling pathway showed the most consistent association with MDD across the two samples. Polygenic risk scores (PRSs) from this pathway showed predictive accuracy better than whole-genome PRSs when using AUC statistics, logistic regression and the linear mixed model. In chapter 5, genome-wide Haplotype-block-based regional heritability mapping (HRHM) was applied to identify haplotype blocks significantly contributing to MDD. A haplotype block across a 24kb region within the TOX2 gene reached genotype-wide significance in GS:SFHS. Single-SNP and haplotype based association tests were used to localize the association signal within the region identified by HRHM, and demonstrated that five out of nine genotyped SNPs and two haplotypes were significantly associated with MDD. The results were replicated in the UK-Ireland group in PGC2-MDD. The brain expression of TOX2 and brain-specific LncRNA RP1-269M15.3 were also significantly regulated by MDD-associated SNPs within the identified haplotype block. The three studies highlight the value of the application of multiple population genetics and bioinformatics methods to multiple family-based and population-based cohorts in identification of risk factors for MDD.
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Lavanty, Brittany. "Describing Emotions: Major Depressive Disorder and Conceptual Metaphor Theory." Case Western Reserve University School of Graduate Studies / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1428942943.
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Chan, C. S. J. "The cognitive vulnerability to depressive rumination in people diagnosed with major depressive disorder." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1336874/.
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This research project focuses on the cognitive process of rumination and its association to depression. Part one of the project is a literature review, which aimed to provide a comprehensive summary of the current state of research on the relations between rumination and the major cognitive processes in people with depression. A systematic search identified 25 studies in the existing literature which fulfilled the basic requirements of studying rumination and at least one other cognitive process with valid measure(s) or experimental manipulations in people with a diagnosis of major depressive disorder. These studies covered 8 domains of cognitive deficits and biases related to rumination. They included overgeneralised memory, memory biases, thinking biases, attentional biases, inhibitory deficits, impairments in general resource allocation, maladaptive thought control strategies, and problem-solving deficits. The review investigated the conclusions made by these studies in terms of their suggestions on the interrelations between depressive symptoms, rumination, the cognitive process in question. Particular attention was paid to each study's conceptualisation of rumination, and whether it addressed subcomponents of rumination which underlie its negative effects. Part two consisted of the empirical paper. The empirical study focussed on the ability of one particular hypothesis - the mood-as-input model -to explain the mechanisms underlying the perseverative thinking style which characterised depressive rumination. Using a rumination interview paradigm, it compared participants with major depressive disorder (MDD) with healthy controls for the extent of their perseverative thinking during the rumination task. The performance of each participant in both the depressed and control group was also measured and contrasted across two experimental conditions. In each these conditions, participants were asked to adopt either an 'as-much-as-can' or a 'feel-like-continuing' stop-rule as guidelines for decision making on how and when to terminate the task. Results indicated that the interaction of depressive symptoms and 'stop-rule' significantly influenced perseveration in all participants. Participants' changes of mood during the rumination task, as well as their spontaneous selection of stop-rule in their daily life were also explored. Finally, the critical appraisal in part three offered a reflection on the my motivations for undertaking this research and some reasons for the important decisions made in the process. It also provided further discussions on the designs and methodologies of the experimental study, and the research and clinical implications of its findings.
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Serra, Blasco Maria. "Neurotoxicity of major depressive disorder: a neuroimaging and neuropsychological study." Doctoral thesis, Universitat Autònoma de Barcelona, 2015. http://hdl.handle.net/10803/310597.
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Introducció
El trastorn depressiu major (TDM), caracteritzat per sentiments de tristesa i/o apatia, malestar físic i dèficits cognitius, presenta un 50% de recaigudes i un 20% de cronificació. Les teories etiològiques més integradores postulen que les alteracions de matèria gris i els dèficits cognitius facilitarien la recurrència/cronifiació del episodi. No obstant, les àrees afectades són inconsistents entre els estudis, complicant la millora dels tractaments. A més, les estratègies terapèutiques per als pacients resistents als tractaments (DRT) són escasos, afetcant generalment la cognició, i dificultant una complerta recuperació. Així, es requereixen noves vies d'estudi centrades en la prevenció de la recurrència/cronificació dels pacients a través de la detecció de variables predictores individuals que optimitzin les opcions terapèutiques.
Objectius
E1: Investigar l'afectació de matèria gris cerebral en diferents estadis de la malaltia depressiva i determinar l'efecte de les carcateristiques clíniques en el seu volum.
E2: Determinar els canvis metabòlics cerebrals que ocorren al aturar l'estimulació cerebral profunda (ECP) del cortex cingulat anterior subgenual (CASg) en pacients amb DRT.
E3: Evaluar les funcions cognitives en pacients amb DRT abans i després de l'ECP del còrtex CASg).
E4: Examinar el potencial predictiu de les dades cliniques i de neuroimatge estructural en el curs del TDM.
Mètodes
Es compara el volum de matèria gris (VMG) entre pacients amb TDM en diferents estadis de la malaltia amb controls sans a través de la tècnia de morfometria basada en el voxel (E1). Els pacients ressonats es contacten als 5 anys i es divideixen en 4 grups segons l'evolució clínica que han tingut. Es fa un anàlisi de regressió amb les dades cliniques i de neuroimatge basals com a variables predictores del curs observat (E3). Finalment s'administra una bateria neuropicològica abans i després de l'ECP del CAsg en pacients amb DRT, agafant com a grup control pacients amb un primer episodi (E2). A més, se'ls realitza una tomografia per emissió de positrons després d'un període d'estabilitat clínica amb el neuroestimulador on versus off.
Resultats
Els pacients amb DRT exhibien menor VMG frontotemporal. El VMG en l'insula dreta i el cortex prefrontal medial dret correlaciona negativament amb la duració de la malaltia (E1). En el tercer estudi s'observà que el VMG explicava un 20% més de variància que les dades clíniques soles a l'hora de predir el curs clínic dels pacients, essent el gir cingulat anterior l'àrea amb més poder predictiu. Aquesta àrea, a més, mostra un descens en la seva activitat metabòlica quan s'apaga el neuroestimulador en pacients amb DRT que havien respòs clinicament (E2). Per últim, l'ECP no empitjora cap funció cognitiva en aquests pacients i l'evaluació neuropsicològica mostra una millora mnèsica posterior a l'intervenció (E3).
Conclusions
Els pacients amb DRT tenen menors VMG frontotemporolimbics, els quals estan associats amb la durada de malaltia, suggerint efectes nocius del trastorn depressiu per se en la matèria gris. A més, el VMG tindria un valor afegit a la informació purament clínica a l'hora de predir la resposta clínica dels pacients a llarg termini. La part dorsal del còrtex cingulat anterior dret es relaciona amb la resposta al tractament. Finalment, l'estudi neuropsicològic dóna suport a la seguretat cognitiva de ECP del CASg, contribuïnt en la seva implantació com a alternativa terapèutica pels pacients amb DRT.
Limitacions
El seguiment de primers episodis respondria millor si les reduccions de VMG són resultat de la depressió o si ja estaven presents d'un inici, incidint en el curs del trastorn. Quant a l'estudi longitudinal, la diferència en l'estadi del TDM basal podria ser un factor confusor. En l'estudi neuropsicològic i metabòlic dels pacients intervinguts caldria tenir en compte el reduït tamany de la mostra.Introduction Major depressive disorder (MDD) is characterized by feelings of sadness and/or apathy, physical disturbances and cognitive impairment. After the first episode, 50% of patients relapse and up to 20% become chronic. Current etiological theories postulate that structural alterations and cognitive impairments would ease recurrence and chronicity. However, the brain areas implied are inconsistent throughout studies, hindering the characterization of MDD pathophysiological models and slowing the finding of new treatments. In addition, therapeutic strategies for patients with treatment resistant depression (TRD) are scarce and generally have a negative impact on cognition, preventing them from a complete recovery. Thus, new studies determining individual variables predicting clinical trajectories such as chronicity are needed. Objectives: E1: To investigate structural brain abnormalities at different stages of the illness and to determine the effect of clinical characteristics on brain GMV. E2: To determine the cerebral metabolism changes during a switch-off of electrical stimulation in implanted patients with TRD who had achieved clinical improvement. E3: To evaluate cognitive function of TRD patients before and after DBS of the SCG. E4: To examine the prognostic potential of clinical and sMRI data in the long-term clinical outcomes of MDD. Methods Voxel-based morphometry (VBM) was used to compare 66 MDD patients at different illness stages with 32 healthy controls. GMV were also correlated with patients clinical characteristics (E1). 66 MDD patients were contacted at 5 years after MRI scan and split in 4 groups depending on their clinical trajectories during that time (n=49). Regression analysis with clinical and neuroimaging data as predictive variables and clinical outcomes as dependent variable was carried out (E4). Finally, a neuropsychological battery was administered before and after DBS of subgenual cingulate gyrus (SCG) in TRD patients, with a control group of first episode patients (E3). In addition, clinically stable TRD patients underwent a positron emission tomography (PET) analysis comparing active versus inactive DBS (E2). Results VBM showed a significant group effect in right superior frontal gyrus, left medial frontal gyrus and left cingulate gyrus. Patients whose condition was treatment resistant/chronic exhibited the smallest volumes in frontotemporal areas. Longer illness duration was negatively correlated with decreases in right medial frontal cortex and left insula (E1). Third study showed that GMV explained a 20% more of variance when joined to clinical characteristics predicting long-term clinical outcomes. Anterior cingulate gyrus was the area adding more value to the prediction. In addition, such cingulate area showed a metabolic decrease in TRD patients who were clinically stable when the stimulation was stopped. Finally, neuropsychological assessment of TRD patients show no impairment of cognitive functioning after DBS, but a memory improvement (E2). Conclusions Frontotemporolimbic areas were smaller in the patients with severe depression and were associated with duration of illness, but not with medication patterns, suggesting negative effects of long-lasting MDD on grey matter. In addition, GMV may demonstrated an added value to clinical information of depressive patients in terms of predicting their long-term clinical outcome (E4). Right dorsal anterior cingulate gyrus seems to be closely related to treatment response (E2). Finally, neuropsychological performance of patients after DBS (E3) supported the cognitive safety of this new technique adding a valuable information for its future implementation as a therapeutic alternative for TRD patients. Limitations A longitudinal study would be more appropriate to ascertain whether volume reductions in chronic patients are a result of enduring MDD effects or the cause of a more severe disorder. Regarding the longitudinal study (E4), differences in illness stage at baseline could lead to confusion. The results of second and third study should be interpreted cautiously given the small sample size.
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Green, Sophie. "The neural basis of disorders of social knowledge : Major Depressive Disorder and Frontotemporal Dementia." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/the-neural-basis-of-disorders-of-social-knowledge-major-depressive-disorder-and-frontotemporal-dementia(c5d16402-8a89-4143-b5fd-16c6fb386485).html.
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A fronto-temporo-mesolimbic integration model of moral cognition proposed that the experience of self- and other-blaming feelings is dependent upon integration of different forms of representations including: 1) differentiated conceptual representations about social behaviours served by the anterior temporal lobe, 2) sequential representations about the consequences of social actions in the ventral frontal lobes, and 3) motivational state representations in mesolimbic regions. Here, I use this model to investigate overgeneral forms of self-blaming feelings, such as self-contempt in remitted Major Depressive Disorder (MDD), and inappropriate social behaviour of patients with Frontotemporal Lobar Degeneration (FTLD). Individuals with remitted MDD demonstrated an increased proneness to experience overgeneral self-blaming feelings (self-contempt bias). This was associated with decreased conceptual differentiation when evaluating one's own social behaviour relative to that of others, combined with the tendency to find one's own behaviours more unpleasant than that of other people. An fMRI study revealed that compared to a control group, people with remitted MDD exhibited decreased functional connectivity across a fronto-temporo-limbic network that was selective for self-blaming relative to other-blaming feelings. These findings provide a neural mechanism for self-blaming biases, thereby helping to understand vulnerability to MDD. In the FTLD study, we demonstrated a double dissociation between deficits in conceptual and sequential social knowledge in patients with Semantic (SD) and Frontotemporal Dementia (FTD) respectively. This could partly explain the inappropriate social behaviours occurring in both of these groups. These results shed new light on the basis of self-blaming biases in MDD and inappropriate social behaviour in FTLD, and provide a platform for future investigations of these disorders from this perspective.
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Barrera, Alinne Z. "Risk factors associated with major depressive disorder among adolescent Latinas." Diss., Connect to online resource, 2006. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3219199.
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Mamdani, Firoza. "A genomic investigation of major depressive disorder and antidepressant response." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=106256.
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Major depressive disorder (MDD) is a common and complex disorder with consistent evidence of genetic influence on predisposition. The search for susceptibility genes has proved to be an arduous task with studies having ever increasing sample numbers still not leading to replicable findings. It is generally believed that the failure of common genetic studies to identify replicable genetic associations is a consequence of the multifactorial and heterogeneous nature of MDD. This etiological heterogeneity may also explain significant variability in treatment response. Accordingly, while effective treatments for MDD are available, approximately half of the patients fail to respond to conventional antidepressant treatment. We hypothesized that peripheral gene expression could help us better understand illness heterogeneity and mechanisms of antidepressant response, possibly helping to identify biomarkers. To test this hypothesis, we have prospectively followed, and treated with the antidepressant citalopram for eight weeks, a cohort of medication naive individuals with MDD. RNA and DNA from pre- and post-treatment blood samples of this cohort were used to perform high-throughput pharmacogenomic and genetic studies to identify genes involved in treatment response and in the pathophysiology of MDD. Significant gene expression alterations in immune related genes were observed after citalopram treatment, pointing to a possible mode of action of the treatment response, as well as possible biomarkers for future treatment response. Additionally, we identified copy number variable regions differentiating MDD and controls and having a significant impact on gene expression. These results provide important additional information which can be used to identify the genomic and molecular underpinnings of MDD and antidepressant response.La dépression majeure est un trouble complexe et commun dans la population et pour laquelle il existe des évidences suggérant de manière consistante une influence génétique sur sa prédisposition. La recherche pour des gènes de susceptibilité pour la DM s'est avérée particulièrement compliquée avec des études ayant des échantillons de plus en plus grands mais qui ont révélé des résultats non reproductibles. Il est généralement accepté que l'absence de réplication des résultats obtenus dans des études génétiques classiques est une conséquence du caractère multifactoriel et hétérogène de la DM. Cette hétérogénéité clinique peut aussi expliquer la variabilité significative observée dans la réponse aux antidépresseurs. Ainsi, même s'il existe des traitements disponibles, seulement autour de la moitié de patients traités répondent aux traitements antidépresseurs conventionnels. Notre hypothèse de départ était que l'expression génique dans du tissus périphérique pourrait nous aider à comprendre d'avantage l'hétérogénéité de la maladie et les mécanismes de réponse aux antidépresseurs, ainsi qu'aider à l'identification de biomarqueurs. Pour tester cette hypothèse, nous avons suivi prospectivement et traité avec l'antidépresseur citalopram, un échantillon de patients avec DM pendant huit semaines, cette cohorte n'avait jamais sous médication préalablement. ARN et ADN extraits à partir d'échantillons sanguins collectés avant et après le traitement ont été utilisés pour effectuer des analyses pharmacogénomiques et génétiques dans le but d'identifier des gènes impliques dans la réponse au traitement ou dans la physiopathologie de la DM. Des changements significatifs en termes de niveaux d'expression génique ont été observés pour des gènes impliqués dans la réponse immunitaire après le traitement au citalopram, indiquant un possible mode d'action pour la réponse au traitement mais aussi des possibles biomarqueurs pour la réponse. De plus, nous avons identifié des régions avec des variations au niveau du nombre de copies permettant la différentiation des patients et des sujets témoins et qui ont un impact significatif sur les niveaux d'expression génique. Ces résultats apportent des informations supplémentaires importantes pour l'identification des bases génétiques et moléculaires de la DM et de la réponse aux antidépresseurs.
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Stelzhammer, Viktoria. "Major depressive disorder : molecular profiling to aid drug target discovery." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607830.
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Park, Rebecca Jane. "Autobiographical memory and rumination in adolescents with major depressive disorder." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620548.
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Engelbrecht, Albertus Hermanus. "Biological markers for major depressive disorder in children and adolescents." Thesis, Cape Technikon, 1986. http://hdl.handle.net/20.500.11838/1481.
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Thesis (Masters Diploma (Technology)--Cape Technikon, Cape Town, 1986Child psychiatrists have become increasingly aware of the existence. of affective disorders in prepubertal and pubertal patients. This has led to the investigation of possible biological factors contributing to the disorders. Due to the lack of availability of human brain material, different parameters have been investigated in the periphery in order to obtain information regarding the aetiology of major depressive disorder. The neurotransmitters, NA, 5-HT and DA have been implicated in depression. Levels of the metabolites of these transmitters have been measured in plasma, urine and CSF of adult depressed patients. Two other peripheral "tools" used in the study of major depressive disorder are blood platelets and lymphocytes. The former contain cr 2 -adrenoceptors and imipramine binding sites (indicative of 5-HT uptake into the platelet) and the latter S-adrenoceptors. Platelets have been widely used as a model for indirectly evaluating changes in central cr2-adrenoceptor and imipramine binding whereas lymphocytes have been used to measure changes in S-adrenoceptor binding and activity in adults with major depressive disorder.
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Holmes, Sophie. "Neuroinflammation in Major Depressive Disorder and schizophrenia : a PET study." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/neuroinflammation-in-major-depressive-disorder-and-schizophrenia-a-pet-study(d47b0905-a16c-46d7-b383-44491c9fa371).html.
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Background: Mounting evidence suggests that inflammation is involved in the pathophysiology of both Major Depressive Disorder (MDD) and schizophrenia. The presence of inflammation in the brain, however, is less clear. Microglial activation, a measure of neuroinflammation, can be quantified using PET ligands that bind to the Translocator Protein (TSPO) which is overexpressed by activated microglia. Previous PET studies using TSPO radioligands have shown some evidence for neuroinflammation in both MDD and schizophrenia. However some of these studies have been confounded by antidepressant/antipsychotic medication, low numbers and mild severity. We aimed to address some of these issues and investigate the relationship between neuroinflammation and peripheral inflammation, medication status, symptom severity and cognitive function. Method: Fourteen patients in a Major Depressive Episode (MDE) of at least moderate severity, sixteen patients with a diagnosis of schizophrenia of at least moderate severity and a total of eighteen age and gender-matched healthy volunteers underwent a 60 minute dynamic PET scan with the TSPO radioligand [11C](R)-PK11195 on the High Resolution Research Tomograph (HRRT). Parametric maps of binding potential (BPND) were generated using the simplified reference tissue model and a grey matter cerebellum input function. All of the MDD patients were antidepressant-free for at least eight months prior to scanning. Of the sixteen schizophrenia patients, eight were antipsychotic-free (for at least twelve months) and eight were on a long-acting injection of risperidone or paliperidone. All patients and healthy volunteers were medically healthy and had drug or alcohol abuse within the previous year. Results: We found a 26% mean increase in BPND values, indicative of microglial activation, in MDD patients compared to healthy volunteers. Exploratory analysis revealed significantly higher [11C](R)-PK11195 binding in the anterior cingulate cortex (ACC). We found no significant correlations between [11C](R)-PK11195 binding and peripheral markers of inflammation or with symptom severity. We also found a mean 27% increase in BPND values in the schizophrenia patients compared to healthy volunteers. There were significant correlations between [11C](R)-PK11195 and negative symptoms across multiple brain regions. When breaking the cohort down according to medication status, there was no difference between antipsychotic-free patients and healthy volunteers. However, mean BPND values were 30% higher in the ACC. The medicated patients exhibited higher BPND values than healthy volunteers, with a mean increase of 48%. Exploratory t-tests revealed significant increases in dorsolateral prefrontal cortex and ACC.Conclusions: Our findings are largely consistent with previous PET findings of increased microglial activation in a sample of antidepressant-free patients in a moderate-to-severe MDE, suggesting that neuroinflammation is present in MDD. We also investigated neuroinflammation in antipsychotic-free patients for the first time and found no evidence of microglial activation. However it is likely that the subgroup sample was underpowered. The medicated patients exhibited a 48% increase in [11C](R)-PK11195 binding compared to controls, suggesting that either medication or duration of illness might potentiate microglial activation. Our findings also point to an association between neuroinflammation and the negative symptoms of schizophrenia. The PET findings from both cohorts are largely overlapping, suggesting that neuroinflammation is not specific to either disorder but rather a common mechanism. This could reflect a common aetiology and/or an overlap in symptoms. Our findings suggest that inflammation could be used as a potential biomarker as well as a target for novel treatment strategies in both MDD and schizophrenia.
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Krus, Hansson Eric. "Default Mode Network and Its Role in Major Depressive Disorder." Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-16211.
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This essay investigates the relationship between a malfunctioning Default Mode Network (DMN) and the diagnosis of Major Depressive Disorder (MDD). A deeper understanding of how the DMN affects those brain processes which are implicated in MDD may offer new approaches to reduce the suffering of the very large number of MDD-afflicted patients. The MDD-DMN relationship has been investigated by studying scientific articles within the field of cognitive neuroscience and searching the articles for clues on how a malfunctioning DMN might correlate with the diagnosis of MDD. The essay concludes that there is much experimental evidence in support of there being a strong coupling between a malfunctioning DMN and the diagnosis of MDD.
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Ordway, Gregory A. "A Double Hit Stress Rodent Model of Major Depressive Disorder." Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/8638.
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Social defeat is an ethologically relevant stressor that utilizes the natural establishment of social rank in male rodents and has been shown to be relevant to major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). In the present study, we wished to establish a social defeat stress model in combination with the chronic unpredictable stress model, which is considered a mild stressor to the rodent. In this way, we create a “double hit” model that may more accurately mimic severe stress that is common in both MDD and PTSD. In the present study, residents established dominance over the intruder for 10 consecutive days. In addition, social defeat stress was followed by another stressor given at random times during each day, i.e. chronic unpredictable stress. These unpredictable stressors included 30 min restraint, 1 h shaking/crowding, a cold water swim, a warm water swim or a tipped cage for 24 h. In one cohort of animals, brain tissue was taken 24 h after the last stressor for DNA. In a second cohort, animals were tested on a sucrose preference test in which two bottles containing 0.8% sucrose was placed on their cages for 3 consecutive days (days 8-10 of social defeat stress), and the total amount of sucrose was calculated relative to total volume consumed. Brain tissue analyses revealed significantly elevated DNA oxidation in white matter comparing stressed animals to non-stressed controls, consistent with what has been found in post-mortem white matter from MDD subjects. Further, animals given the social defeat + chronic unpredictable stress demonstrated a deficit in sucrose preference, a natural reward, revealing that these animals were anhedonic as compared to controls. Stressed animals also demonstrated fear of the intruder in a social interaction test performed one day after the social defeat/chronic unpredictable stress was complete. Therefore, it appears that social defeat plus chronic unpredictable stress produces a phenotype relevant to clinical data in humans.
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Hernandez, Liza J., Katherine C. Burgess, J. D. Wherry, Attila Szebeni, Katalin Szebeni, Gregory A. Ordway, and Russell W. Brown. "A Double Hit Stress Rodent Model of Major Depressive Disorder." Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/968.
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Social defeat is an ethologically relevant stressor that utilizes the natural establishment of social rank in male rodents and has been shown to be relevant to major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). In the present study, we wished to establish a social defeat stress model in combination with the chronic unpredictable stress model, which is considered a mild stressor to the rodent. In this way, we create a “double hit” model that may more accurately mimic severe stress that is common in both MDD and PTSD. In the present study, residents established dominance over the intruder for 10 consecutive days. In addition, social defeat stress was followed by another stressor given at random times during each day, i.e. chronic unpredictable stress. These unpredictable stressors included 30 min restraint, 1 h shaking/crowding, a cold water swim, a warm water swim or a tipped cage for 24 h. In one cohort of animals, brain tissue was taken 24 h after the last stressor for DNA. In a second cohort, animals were tested on a sucrose preference test in which two bottles containing 0.8% sucrose was placed on their cages for 3 consecutive days (days 8-10 of social defeat stress), and the total amount of sucrose was calculated relative to total volume consumed. Brain tissue analyses revealed significantly elevated DNA oxidation in white matter comparing stressed animals to non-stressed controls, consistent with what has been found in post-mortem white matter from MDD subjects. Further, animals given the social defeat + chronic unpredictable stress demonstrated a deficit in sucrose preference, a natural reward, revealing that these animals were anhedonic as compared to controls. Stressed animals also demonstrated fear of the intruder in a social interaction test performed one day after the social defeat/chronic unpredictable stress was complete. Therefore, it appears that social defeat plus chronic unpredictable stress produces a phenotype relevant to clinical data in humans.
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Hadjiyannakis, Katholiki Kathy. "Specific depressive symptoms as risk factors for the onset of major depressive disorder in adolescence /." view abstract or download file of text, 2003. http://wwwlib.umi.com/cr/uoregon/fullcit?p3080587.
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Thesis (Ph. D.)--University of Oregon, 2003.Typescript. Includes vita and abstract. Includes bibliographical references (leaves 142-146). Also available for download via the World Wide Web; free to University of Oregon users.
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Sendi, Shahbaz. "Biomarkers of major depressive disorder : a study of the interaction of genetic, neuroimaging and endocrine factors, and the effects of childhood adversity, in major depressive disorder." Thesis, King's College London (University of London), 2016. http://kclpure.kcl.ac.uk/portal/en/theses/biomarkers-of-major-depressive-disorder(743a993b-8c01-46be-8707-855dc01bc355).html.
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My thesis consisted of two studies. The first study was a part of a wider study; within this, we investigated the modulation of amygdala structure by the val66met BDNF (Brain Derived Neurotrophic Factor) polymorphism. Structural Magnetic Resonance Imaging (MRI) scans were obtained at 1.5 T in 87 Major Depressive Disorder (MDD) patients and 74 age, gender, and verbal IQ matched healthy controls. We used Freesurfer version 5.1.0 to examine the grey matter amygdala volume. In the second study, we investigated neuroendocrine abnormalities˗˗ Hypothalamus-Pituitary-Adrenal Axis (HPA) axis changes˗˗ in MDD and their relation to early life stress (ELS). In total 112 subjects took part, consisting of MDD patients with (n=28) and without (n=15) a history of ELS and healthy controls with (n=26) and without (n=43) a history of ELS. The cortisol awakening response (CAR) was used as an index of HPA axis activity. In both studies, the data were analyzed using Statistical Package for Social Science (SPSS version 22). In the first study, we did not find any modulatory effect of the val66met polymorphism on the grey matter of right and left amygdala volumes. In the second study, we showed that the CAR was most elevated in those who were both depressed and had a history of ELS, which supports the argument that the effects of early life stress and MDD on the HPA axis may be additive.
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Nouzová, Eva. "Eye movements as diagnostic trait markers for adult major depressive disorder." Thesis, University of Aberdeen, 2016. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=230162.
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Diagnosis of Major Depressive Disorder (MDD) is currently symptom-based and no externally validated tests are available for routine use to confirm clinical diagnoses. Eye movement abnormalities in schizophrenia (SCZ) and bipolar disorder (BPAD) have been consistently reported and their potential as a biological trait marker highlighted. Only a limited amount of research has been conducted in MDD. Eye movement performance of MDD patients (n = 99; F:M = 55:44; Mdn age = 48) was investigated using picture free-viewing, smooth pursuit and fixation stability tasks and recorded using a non-invasive EyeLink1000 infra-red eye tracker. Performance was compared with identical measures from SCZ, BPAD, Primary Care depression (DEP) and control participants. Analysis was conducted using analyses of variance and machine learning using Probabilistic Neural Networks (PNN). We discovered a unique MDD specific eye movement phenotype, which differentiated patients with MDD from other diagnostic groups with remarkable accuracy. MDDs generated a markedly poor smooth pursuit performance, characterised by small signal-to-noise ratio, small tracking gain and large positional error. Patients also exhibited a slow average saccade velocity during free-viewing and pursuit, and poor fixation maintenance on a centralised target. A PNN classifier delineated MDD from controls with exceptional statistical sensitivity (100%) and specificity (99%), independent of state or demographics. MDD was delineated from SCZ and BPAD in all models with above 89% sensitivity and 95% specificity. MDD and DEP patients were delineated with remarkable statistical sensitivity (90%) and specificity (98%). This emerging evidence suggests possible subtypes consistent with clinical features. Testretest reliability was high for a majority of performance measures; however some measures were less robust. Brief neuropsychology assessment advocated the role of frontal lobes in oculomotor behaviour. This preliminary evidence argues for a specific MDD oculomotor dysfunction and represents potential for a diagnostically applicable biological trait marker.
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Garriock, Holly Ann. "Genetics of Major Depressive Disorder in Treatment Resistance and Tryptophan Depletion." Diss., Tucson, Arizona : University of Arizona, 2006. http://etd.library.arizona.edu/etd/GetFileServlet?file=file:///data1/pdf/etd/azu%5Fetd%5F1462%5F1%5Fm.pdf&type=application/pdf.
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Horwitz-Martin, Rachelle (Rachelle Laura). "Vocal modulation features in the prediction of major depressive disorder severity." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/93072.
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Thesis: S.M., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2014."September 2014." Cataloged from PDF version of thesis.
Includes bibliographical references (pages 113-115).
This thesis develops a model of vocal modulations up to 50 Hz in sustained vowels as a basis for biomarkers of neurological disease, particularly Major Depressive Disorder (MDD). Two model components contribute to amplitude modulation (AM): AM from respiratory muscles and from interaction between formants and frequency modulation in the fundamental frequency harmonics. Based on the modulation model, we test three methods to extract the envelope of the third formant from which features are extracted using sustained vowels from the 2013 AudioNisual Emotion Challenge. Using a Gaussian-Mixture-Model-based predictor, we evaluate performance of each feature in predicting subjects' Beck MDD severity score by the root mean square error (RMSE), mean absolute error (MAE), and Spearman correlation between the actual Beck score and predicted score. Our lowest MAE and RMSE values are 8.46 and 10.32, respectively (Spearman correlation=0.487, p<0.001), relative to the mean MAE of 10.05 and mean RMSE of 11.86.
by Rachelle L. Horwitz.
S.M.
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Limon, Amanda Miguela. "Acculturative stress, generalized anxiety and major depressive disorder among Latino subgroups." Thesis, California State University, Long Beach, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10116153.
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Research has demonstrated that acculturative stress is an important influence on anxiety and depression in Latinos, however methodological issues limit generalizability of findings. The present study examines Latino subgroup (i.e., Cuban, Puerto Rican, Mexican) differences in the influence of acculturative stress on Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD). Secondary data analysis of data from 2,554 Latino immigrants in the National Latino and Asian American Study (NLAAS) included stratified hierarchical logistic regression. The NLAAS collected data via in-person interviews at the participants' homes by bilingual interviewers in the participants’ language of choice. Acculturative stress was significantly related to MDD for Other Latinos (p < .001), and to GAD for Mexicans (p = .040). Results provide empirical evidence for the need to disaggregate Latino subgroups. Subgroup heterogeneity may introduce important contextual factors that should be accounted for when exploring their mental health, particularly when examining acculturative stress.
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Wigmore, Eleanor May. "Regional brain volumes and antidepressant treatment resistance in major depressive disorder." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31291.
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Major depressive disorder (MDD) is a heritable and highly debilitating condition with antidepressants, first-line treatment, demonstrating low to modest response rates. No current biological mechanism substantially explains MDD but both neurostructural and neurochemical pathways have been suggested. Further explication of these may aid in identifying subgroups of MDD that are better defined by their aetiology. Specifically, genetic stratification provides an array of tools to do this, including the intermediate phenotype approach which was applied in this thesis. This thesis explores genetic overlap with regional brain volume and MDD and the genetic and non-genetic components of antidepressant response. The first study utilised the most recent published data from ENIGMA (Enhancing Neuroimaging Genetics through Meta-analysis) Consortium's genome-wide association study (GWAS) of regional brain volume to examine shared genetic architecture between seven subcortical brain volumes and intracranial volume (ICV) and MDD. This was explored using linkage disequilibrium score regression (LDSC), polygenic risk scoring (PRS) techniques, Mendelian randomisation (MR) analysis and BUHMBOX (Breaking Up Heterogeneous Mixture Based On Cross-locus correlations). Results indicated that hippocampal volume was positively genetically correlated with MDD (rg= 0.46, P= 0.02), although this did not survive multiple comparison testing. Additionally, there was evidence for genetic subgrouping in Generation Scotland: Scottish Family Health Study (GS:SFHS) MDD cases (P=0.00281), however, this was not replicated in two other independent samples. This study does not support a shared architecture for regional brain volumes and MDD, however, provided some evidence that hippocampal volume and MDD may share genetic architecture in a subgroup of individuals, albeit the genetic correlation did not survive multiple testing correction and genetic subgroup heterogeneity was not replicated. To explore antidepressant treatment resistance, the second study utilised prescription data in (GS:SFHS) to define a measure of (a) treatment resistance (TR) and (b) stages of resistance (SR) by inferring antidepressant switching as non-response. GWAS were conducted separately for TR in GS:SFHS and the GENDEP (Genome-based Therapeutic Drugs for Depression) study and then meta-analysed (meta-analysis n=4,213, cases=358). For SR, a GWAS on GS:SFHS only was performed (n=3,452). Additionally, gene-set enrichment, polygenic risk scoring (PRS) and genetic correlation analysis were conducted. No significant locus, gene or gene-set was associated with TR or SR, however power analysis indicated that this analysis was underpowered. Pedigree-based correlations identified genetic overlap with psychological distress, schizotypy and mood disorder traits. Finally, the role of neuroticism, psychological resilience and coping styles in antidepressant resistance was investigated. Univariate, moderation and mediation models were applied using logistic regression and structural equation modelling techniques. In univariate models, neuroticism and emotion-orientated coping demonstrated significant negative association with antidepressant resistance, whereas resilience, task-orientated and avoidance-orientated coping demonstrated significant positive association. No moderation of the association between neuroticism and TR was detected and no mediating effect of coping styles was found. However, resilience was found to partially mediate the association between neuroticism and TR. Whilst the first study does not indicate a genetic overlap between regional brain volumes and MDD, it demonstrates the utility of the intermediate approach in complex disease. Antidepressant resistance was associated with neuroticism both genetically and phenotypically, indicating its role as an intermediate phenotype. Nonetheless, larger sample sizes are needed to adequately address the components of antidepressant resistance. Further work in antidepressant non-response may help to identify biological mechanisms responsible in MDD pathology and help stratify individuals into more tractable groups.
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Feng, Shengchuang. "Association between Reward Sensitivity and Smoking Status in Major Depressive Disorder." Thesis, Virginia Tech, 2017. http://hdl.handle.net/10919/79954.
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Chronic nicotine use has been linked to increased sensitivity to nondrug rewards as well as improvement in mood among individuals with depression, and these effects have been hypothesized to be mediated through alternations in striatal dopamine activity. Similarly, chronic nicotine use is hypothesized to influence the mechanisms by which healthy and depressed individuals learn about rewards in their environment. However, the specific behavioral and neural mechanisms by which nicotine influences the learning process is poorly understood. Here, we use a probabilistic learning task, functional magnetic resonance imaging and neurocomputational analyses, to show that chronic smoking is associated with higher reward sensitivity, along with lower learning rate and striatal prediction error signal. Further, we show that these effects do not differ between individuals with and without major depressive disorder (MDD). In addition, a negative correlation between reward sensitivity and striatal prediction error signal was found among smokers, consistent with the suggestion that enhanced tonic dopamine associated with increased reward sensitivity leads to an attenuation of phasic dopamine activity necessary for updating of reward value during learning.Master of Science
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Bickham, Grace Antia. "Major Depressive Disorder: Precursors, Predictors, and Coping Mechanism Among Undergraduate Students." ScholarWorks, 2015. https://scholarworks.waldenu.edu/dissertations/743.
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Major depressive disorder (MDD) is common among college students. The disease perpetuates depressive symptoms and potentially leads to chronic depressive episodes. Existing literature has shown that students who use both cognitive and behavioral maladaptive coping skills are more prone to endure depressive symptoms and poorer academic performance. Despite these known associations, little research has examined the relationship between coping skills and self-efficacy in response to warning signs of MDD in college students. This study sought to fill the gaps in the research of MDD related to precursors, predictors, and coping mechanisms among undergraduate students in a national sample of U.S. college students. Secondary data (N = 6,713) were analyzed from the Healthy Minds Study 2012, which used the Patient Health Questionnaire-9 (PHQ-9) with a test-retest reliability. Social learning and social cognitive theories were used as the theoretical frameworks to focus on problems such as management of life activities, academic success, and maladaptive beliefs. Analyses of the data from the cross-sectional survey using multiple linear and logistic regressions indicated a statistically significant relationship between depressive symptoms and the potential predictive factors of MDD. These findings contribute positively to social change by informing the work of therapists and program developers, who may use these results to create programs that reduce depressive symptoms among undergraduates.
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Jones, Julia H. "Cost Outcomes for Major Depressive Disorder and Bipolar Disorder Across Professional License Types and Modalities." BYU ScholarsArchive, 2017. https://scholarsarchive.byu.edu/etd/6332.
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The purpose of this study was to compare outcomes for patients with Bipolar Disorder or Major Depressive Disorder based on severity of diagnosis. This study also compared psychotherapy providers and therapy modalities on total cost, number of sessions, and dropout. Our data set (N=136,439) came from Cigna, a national health care company. Results showed significant differences by severity of diagnosis. The comparison of providers showed that psychologists had higher costs and session numbers, while the other providers were not significantly different. However, all providers successfully provided low cost treatment on both MDD and BD. There is no support for the idea that one profession is more successful at providing low cost treatment for MDD and BD. Family therapy did significantly better on all outcomes except dropout rate when compared to individual or mixed (individual and family sessions) therapy. It is a low-cost option when treating MDD and BD, regardless of severity.
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Moody, Lara. "Evidence of Executive Dysfunction in Co-occurring Substance Use Disorder and Major Depressive Disorder or Antisocial Personality Disorder." Thesis, Virginia Tech, 2014. http://hdl.handle.net/10919/78165.
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Background and Aims: Executive dysfunction is pervasive in substance-dependent individuals (Verdejo-GarcÃa, Bechara, Recknor, & Perez-Garcia, 2006). As many as four-fifths of individuals in treatment for substance use disorders (SUDs) have co-existing lifetime psychopathology. Executive function deficits are tied to markers of decreased quality of life including increases in negative life events (Green, Kern, Braff, & Mintz, 2000), maladaptive social functioning (Kurtz, Moberg, Ragland, Gur, & Gur, 2005) and worsened treatment outcomes (Czuchry & Dansereau, 2003). Despite evidence of executive dysfunction across several mental disorders, few studies investigate how the co-occurrence of psychopathologies in SUDs impacts executive functioning.
Methods: Here, we compare measures of executive function (i.e., the Iowa Gambling Test, Letter Number Sequencing Test, Stroop Test, Wisconsin Card Sorting Test, Continuous Performance Test, Towers Test, and Delay Discounting Test) in individuals with a) substance use disorder, b) substance use disorder and co-occurring major depressive disorder, c) substance use disorder and co-occurring antisocial personality disorder, d) substance use disorder and co-occurring major depressive disorder and antisocial personality disorder and e) no substance use disorder or co-occurring psychopathology.
Results: Regression models of respective executive function measure outcomes as a function of education, income, age, and group membership indicated that the Delay Discounting Test and Continuous Performance Test were the only significant overall models (F(4, 313) = 12.699, p < 0.001 and F(4, 307) = 2.659, p = 0.033, respectively).
Conclusions: Overall the Delay Discounting Test and Continuous Performance Test were the most sensitive to differences between substance use and psychopathology profiles assessed.Master of Science
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Workman, Clifford. "The role of moral cognition and emotions in remitted major depressive disorder." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-moral-cognition-and-emotions-in-remitted-major-depressive-disorder(e1c3b588-b506-47c2-a579-4ccedf1f113b).html.
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Background: The aim of this thesis was to investigate the relationship of moral cognition and emotions to the pathophysiology of major depressive disorder (MDD). Patients with MDD may experience excessive guilt or self-blaming biases despite recovery from the depressed state. Since guilt is a moral emotion thought to motivate altruistic behaviours, it has been hypothesized that elevated self-blame in MDD may result in pathological increases to altruism in some patients. The relationship of self-blame to altruistic choices in individuals with remitted MDD (rMDD), however, has not been established. Guilt has been shown to activate the subgenual cingulate and adjacent septal region (SCSR) which is of known importance to the pathophysiology of MDD. Since MDD is thought to arise from network-level dysfunctions, and moral cognition and emotions are hypothesized to emerge from network-level binding, investigating resting-state SCSR functional connectivity in rMDD patients and healthy control (HC) participants could reveal networks of potential relevance both to MDD and to moral cognition and emotions. Chapter 2: We investigated whether melancholic rMDD patients could be distinguished from non-melancholic and HC groups on the basis of resting-state functional connectivity to an SCSR seed region. Lower SCSR-amygdala connectivity distinguished the melancholic rMDD group from non-melancholic and HC groups. Chapter 3: We investigated whether patients who remained resilient to recurring depressive episodes were distinguishable from recurring episode MDD and HC groups on the basis of resting-state connectivity to an SCSR seed region. Lower interhemispheric SCSR connectivity distinguished the resilient MDD patients from the recurring episode MDD and HC groups. Chapter 4: We measured explicit and implicit preferences for social options with and without altruistic motivations relative to selfish options in the rMDD and HC groups during emotion priming to modulate feelings of guilt. The rMDD patients explicitly preferred prosocial options (i.e., social options and altruism directed towards friends or colleagues) less than HC participants. Regardless of group, guilt priming increased explicit and implicit preferences for altruism towards strangers. Chapter 5: We investigated whether explicit and/or implicit preferences for prosocial options during guilt priming were correlated with resting-state connectivity to an SCSR seed region, and whether this relationship could distinguish the rMDD and HC groups. Across all participants, implicit prosocial choice preference negatively correlated with connectivity between the SCSR and right temporoparietal junction (TPJ). The relationship of SCSR-TPJ connectivity to implicit preferences for social options and for altruism towards friends and colleagues was weaker in the rMDD group compared to the HC group, particularly for implicit altruism. Conclusions: We identified resting-state SCSR networks associated with vulnerability to melancholia and with resilience to recurring depressive episodes. Patients with rMDD explicitly preferred options entailing social withdrawal, a symptom associated with MDD vulnerability. Irrespective of group, guilt motivated altruism towards strangers but not friends and colleagues. Implicit prosociality was negatively associated with connectivity in a social agency network, and the comparatively weak relationships between connectivity and implicit choice preferences in rMDD patients may reflect a vulnerability factor for MDD.
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Post, Loren M. "Understanding PTSD and Major Depressive Disorder Co-occurrence: Structural Relations Among Disorder Constructs and Trait and Symptom Dimensions." Cleveland, Ohio : Case Western Reserve University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1257991628.
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Thesis(M.A.)--Case Western Reserve University, 2010Title from PDF (viewed on 2010-01-28) Department of Psychology Includes abstract Includes bibliographical references and appendices Available online via the OhioLINK ETD Center
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Strong, Vanessa April. "The management of major depressive disorder in cancer patients : a randomised trial." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/29385.
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MDD in cancer patients demands attention as it is a major determinant of quality of life, is associated with non-adherence to treatment, with greater functional impairment or disability, with increased medical costs and is associated with suicide and with an increased risk of death from all causes. However, there is only limited evidence to inform its treatment. In this thesis I describe the development of a nurse-delivered psychiatrist supervised multi-component intervention (problem-solving therapy, coordination of antidepressant drug treatment with primary care, and active monitoring and follow up of the patient’s progress) for the management of MDD in cancer patients and its evaluation in a randomised controlled clinical trial (RCT). 200 Outpatients with varied cancer diagnoses and stages, meeting criteria for MDD were randomly assigned in a single-centre two-arm RCT to receive either optimised usual care or optimised usual care plus the intervention. A clinically and statistically significantly better outcome was observed for patients who had received the intervention (difference of adjusted mean Symptom Check-List-20 score of 0.34; 95% CI 0.13 to 0.55) three months after trial entry. This trial provides evidence of efficacy. Further research is needed to test the efficacy of multi-component interventions for patients with poor prognosis cancers and to test the effectiveness of the intervention in normal clinical practice in a range of settings.
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Victoria, Michelle Renee. "Adult Outpatients With Major Depressive Disorder Forming Positive Responses During Challenging Events." Thesis, Walden University, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3597909.
Full textAbstract:
Previous empirical research demonstrated that major depressive disorder (MDD) had a profound impact on adults. What remained unaddressed in the research was the ability of those with MDD to form positive responses during challenging life events. The purpose of this exploratory quantitative study was to examine the cognitive ability of MDD patients to form positive responses on a standardized psychological assessment. This study, guided by Beck's cognitive theory of depression, was designed to determine whether depressed individuals were prone to negativity and had decreased ability to form positive responses to challenging situations. A 2x2 ANOVA was used to analyze 116 participants who voluntarily completed the Changes in Outlook Questionnaire (CiOQ). Results indicated that the group diagnosed with MDD scored significantly lower than a control group on the positive response scale of the CiOQ and that men diagnosed with MDD scored significantly lower than women diagnosed with MDD on the positive response scale of the CiOQ. This research has positive social change implications in that practitioners may use the findings in developing more effective treatments to help those with MDD to learn to form positive responses in the midst of challenging life events. Practitioners may also develop their ability to recognize when men with MDD are depressed by using the CiOQ to obtain written responses from individuals who do not verbalize depression. This research may also be useful for future research and application within the field.
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D'Iuso, Debora Anna. "A closer look at cognitive and interpersonal variables in major depressive disorder." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=122973.
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AbstractMajor Depressive Disorder (MDD) causes significant distress and has major societal implications. For example, it is one of the costliest disorders in Canada (Stephens & Joubert, 2001). While, Cognitive Behavior Therapy (CBT) has proven to be effective for the treatment of depression (Butler, Chapman, Forman, & Beck, 2006; Dobson, 1989; Fava et al., 2004), few studies have examined its mechanisms of change (Castonguay, Hayes, Goldfried, & DeRubeis, 1995). Theoretically, CBT targets maladaptive cognitions, and coping strategies. Recently, the interpersonal functioning of depressed individuals has also been highlighted in CBT. One of the objectives of this thesis is to gain an understanding of the association between coping, cognitive errors and interpersonal behaviors among individuals with depression. This dissertation consists of three manuscripts. The first manuscript focused on examining the association between cognitive errors and interpersonal behaviors. The second manuscript assessed the association between coping strategies and interpersonal functioning. Lastly, the third manuscript examined whether cognitive processes serve to mediate the relationship between interpersonal functioning and depression. Results and clinical implications for each study were discussed in the context of improving psychotherapy outcome.La dépression majeure (MDD) cause une détresse importante et a des implications majeures pour notre société. Par exemple, c'est l'un des troubles les plus coûteux au Canada (Fava & Kendler, 2000). La thérapie cognitivo-comportementale (TCC) a une efficacité démontrée pour le traitement de la dépression (Butler, Chapman, Forman, & Beck, 2006; Dobson, 1989; Fava et al, 2004) ; cependant, peu d'études ont examiné comment le changement se produit. En principe, la TCC vise à changer les cognitions et les stratégies de coping inadaptées; récemment, l'importance du fonctionnement interpersonnel a également été soulignée. Un des objectifs de cette thèse est de mieux comprendre le lien entre le coping, les erreurs cognitives et les comportements interpersonnels chez les individus souffrant de dépression. Cette thèse comprend trois articles. Le premier article examine l'association entre les erreurs cognitives et les comportements interpersonnels. Le second article évalue l'association entre le coping et le fonctionnement interpersonnel. Enfin, le troisième article examine les médiations possibles entre les processus cognitifs, le fonctionnement interpersonnel et la dépression. Les résultats et les implications cliniques pour chaque étude seront discutés dans le but d'améliorer les résultats de la psychothérapie.
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DeFeo, Graig C. "Risk Factors for Recurrent Major Depressive Disorder in a Nationally Representative Sample." Thesis, University of South Florida, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=1569946.
Full textAbstract:
The public use version of the National Comorbidity Survey – Replication (NCS-R) dataset was used (N = 995) to investigate risk factors for recurrent major depressive disorder (MDD) that are evident before recovery from the first major depressive episode (MDE) by comparing persons diagnosed with MDD who experienced a single MDE to persons with recurrent MDD.
Multiple logistic regression analyses assessed the independent risk of recurrent MDD for each of the following risk factors: an early age of onset (<30 years old), absence of a life stress trigger, chronic first episode, childhood parental loss, parental maltreatment, parental depression, comorbid anxiety disorder, and comorbid substance disorder. The relative excess risk due to interaction (RERI) assessed the risk of recurrent MDD associated with the interaction of an early onset with three childhood-based vulnerabilities: a) parental depression, b) parental loss, and c) parental maltreatment.
There was a statistically significant risk of recurrent MDD found for the following risk factors: early onset, stress trigger absent, childhood parental loss, parental maltreatment, parental depression, and anxiety disorder; marginally significant results suggested an increased risk of recurrent MDD for substance disorder. There was a significant increased risk found for the interaction of an early onset with parental depression and similar non-significant trends were found for the interactions of early onset with parental loss and early onset with parental maltreatment.
An early onset, the absence of a life stress trigger, and the presence of parental loss, parental maltreatment, parental depression, a comorbid anxiety disorder, and a comorbid substance disorder each confer greater risk of recurrent MDD among persons that have not yet recovered from their first lifetime MDE. The presence of an early onset combined with a childhood-based vulnerability such as parental depression, parental loss, or parental maltreatment, indicate an especially high risk of recurrent MDD. These findings may inform the development of a screening tool to assess risk for recurrent MDD and early intervention to prevent recurrent MDD. Future research should employ a longitudinal research design to replicate and expand upon these findings.
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Shaikh, Aamir. "Levels of PARP1-immunoreactivity in the Human Brain in Major Depressive Disorder." Digital Commons @ East Tennessee State University, 2020. https://dc.etsu.edu/honors/547.
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MDD is a severe and debilitating disorder that is associated with a growing global economic burden due to reduced workplace productivity along with increased healthcare resource utilization. Furthermore, depression markedly enhances the risk for suicide, mortality that is especially worrisome given that 30% of depressed individuals have an inadequate response to current antidepressants. This inadequacy of antidepressants necessitates the discovery of a better understanding of the pathobiology of MDD. Most current antidepressants work through monoamine neurotransmitters, and their relative efficacy in depression led to the now dated monoamine-deficiency hypothesis. The limited usefulness of antidepressants has led to a reinvigorated search for other pathologies in depression that might yield clues for the development of better drug treatments. In this regard, a strong association has been found between oxidative stress and MDD. Our lab recently found increased DNA oxidation and elevated poly(ADP)ribose polymerase (PARP1) gene expression in the brain from donors that had MDD at the time of death. Besides DNA damage repair, PARP1 mediates several downstream inflammatory effects that may contribute to pathology in MDD. In fact, our lab has demonstrated that PARP-1 inhibition produces antidepressant-like effects in rodents, suggesting that PARP-1 inhibitors hold promise as a novel antidepressant drug. While our lab had previously demonstrated elevated PARP1 gene expression in the frontal cortex in MDD, whether PARP1 protein levels were also increased in depression had not been verified. My thesis research was performed to determine whether PARP1 protein expression was also elevated in the brain in MDD. I studied primarily the hippocampus because it is part of the limbic (mediating emotion) system of the brain and because previous research has shown numerous other pathologies in the hippocampus. My study was carried out simultaneously as others in our lab were measuring PARP1 protein levels in frontal cortex in MDD. This latter work was important since the lab’s previous work had observed elevated PARP1 gene expression in the frontal cortex, rather than in the hippocampus which was not previously studied. Hippocampal and frontal cortical brain sections were cut from frozen blocks of both MDD and psychiatrically normal control brain donors for these studies. PARP1 protein levels were estimated by assisted-imaging software. The findings herein demonstrate that levels of PARP1 immunoreactivity are significantly elevated in the frontal cortex of MDD donors as compared to control donors. However, there was no change in PARP1 immunoreactivity in the hippocampus in MDD.
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Ryan, Elizabeth T. "Sudden Gains and Sudden Losses in Cognitive Therapy for Major Depressive Disorder." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1354636220.
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Hill, Emma Louise. "A novel decentering and perspective broadening training intervention for major depressive disorder." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.707975.
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Gedik, Huseyin. "Investigation on Genetic Modifiers of Age at Onset of Major Depressive Disorder." VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/4994.
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Major Depressive Disorder (MDD) is a complex multifactorial disorder, which would lead to disability. Environmental and genetic factors are involved in MDD etiology. The aim of this project was to identify loci modifying age at onset (AAO) of MDD using survival models after adjusting for Childhood Sexual Abuse (CSA). To achieve this aim, a dataset was made available by the China Oxford and VCU Experimental Research on Genetic Epidemiology (CONVERGE) consortium. The study population had 5,220 controls and 5,282 cases with MDD. We performed two univariate association analyses using Cox Proportional Hazard (Cox PH) models. These two are Full Sample (FS), cases and controls, and only the Case Cohort (CC). No genome-wide significant associations were found in univariate analyses. Subsequent gene set enrichment analysis showed that there were significant enrichments in neurological Gene Ontology terms and some novel non-neural pathways. These findings may allow us to better understand MDD pathology.
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Choi, Ki Sueng. "Characterizing structural neural networks in major depressive disorder using diffusion tensor imaging." Diss., Georgia Institute of Technology, 2013. http://hdl.handle.net/1853/50353.
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Diffusion tensor imaging (DTI) is a noninvasive MRI technique used to assess white matter (WM) integrity, fiber orientation, and structural connectivity (SC) using water diffusion properties. DTI techniques are rapidly evolving and are now having a dramatic effect on depression research. Major depressive disorder (MDD) is highly prevalent and a leading cause of worldwide disability. Despite decades of research, the neurobiology of MDD remains poorly understood. MDD is increasingly viewed as a disorder of neural circuitry in which a network of brain regions involved in mood regulation is dysfunctional. In an effort to better understand the neurobiology of MDD and develop more effective treatments, much research has focused on delineating the structure of this mood regulation network. Although many studies have focused on the structural connectivity of the mood regulation network, findings using DTI are highly variable, likely due to many technical and analytical limitations. Further, structural connectivity pattern analyses have not been adequately utilized in specific clinical contexts where they would likely have high relevance, e.g., the use of white matter deep brain stimulation (DBS) as an investigational treatment for depression. In this dissertation, we performed a comprehensive analysis of structural WM integrity in a large sample of depressed patients and demonstrated that disruption of WM does not play a major role in the neurobiology of MDD. Using graph theory analysis to assess organization of neural network, we elucidated the importance of the WM network in MDD. As an extension of this WM network analysis, we identified the necessary and sufficient WM tracts (circuit) that mediate the response of subcallosal cingulate cortex DBS treatment for depression; this work showed that such analyses may be useful in prospective target selection. Collectively, these findings contribute to better understanding of depression as a neural network disorder and possibly will improve efficacy of SCC DBS.
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Aragam, Nagesh Ramarao. "Genome-Wide Association Analysis of Major Depressive Disorder and Its Related Phenotypes." Digital Commons @ East Tennessee State University, 2011. https://dc.etsu.edu/etd/1368.
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Major Depressive Disorder (MDD) is a complex and chronic disease that ranks fourth as cause of disability worldwide. Thirteen to 14 million adults in the U.S. are believed to have MDD and an estimated 75% attempt suicide making MDD a major public health problem. Recently several genome-wide association (GWA) studies of MDD have been reported; however, few GWA studies focus on the analysis for MDD related phenotypes such as neuroticism and age at onset of MDD. The purpose of this study is to determine risk factors for MDD, identify genome-wide genetic variants affecting neuroticism and age at onset as quantitative traits, and detect gender differences influencing neuroticism.
Bivariate and multiple logistic regression analyses were performed on 1,738 MDD cases and 1,618 non-MDD controls to determine phenotypic risk factors for MDD. Multiple linear regression analyses in PLINK software were used for GWA analyses for neuroticism and age at onset of MDD with 437,547 Single Nucleotide Polymorphisms (SNPs).
Gender (OR: 1.43; 95% CI: 1.24 - 1.64) and a family history (OR: 2.88; 95% CI: 2.48 - 3.35) were significantly associated with an increased risk of MDD, which supports the findings of prior studies. Through GWA analysis 34 SNPs were identified to be associated with neuroticism (p < 10-4). The best SNP was rs4806846 within the TMPRSS9 gene (p = 7.79 x10-6). Furthermore, 46 SNPs were found showing significant gene x gender interactions for neuroticism with p<10-4. The best SNP showing gene x gender interaction was rs2430132 (p = 5.37x10-6) in HMCN1 gene. In addition, GWA analysis showed that several SNPs within 4 genes (GPR143, ASS1P4, MXRA5 and MAGEC1/2) were significantly associated with age at onset of MDD (p < 5x10-7).
This study confirmed previous findings that MDD is associated with an increased prevalence in women (about 43% more compared to men) and is highly heritable among first degree relatives. Several novel genetic loci were identified to be associated with neuroticism and age at onset. Gender differences were found in genetic influence of neuroticism. These findings offer the potential for new insights into the pathogenesis of MDD.
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DeFeo, Graig Charles. "Risk Factors for Recurrent Major Depressive Disorder in a Nationally Representative Sample." Scholar Commons, 2014. https://scholarcommons.usf.edu/etd/5351.
Full textAbstract:
The public use version of the National Comorbidity Survey - Replication (NCS-R) dataset was used (N = 995) to investigate risk factors for recurrent major depressive disorder (MDD) that are evident before recovery from the first major depressive episode (MDE) by comparing persons diagnosed with MDD who experienced a single MDE to persons with recurrent MDD.
Multiple logistic regression analyses assessed the independent risk of recurrent MDD for each of the following risk factors: an early age of onset (old), absence of a life stress trigger, chronic first episode, childhood parental loss, parental maltreatment, parental depression, comorbid anxiety disorder, and comorbid substance disorder. The relative excess risk due to interaction (RERI) assessed the risk of recurrent MDD associated with the interaction of an early onset with three childhood-based vulnerabilities: a) parental depression, b) parental loss, and c) parental maltreatment.
There was a statistically significant risk of recurrent MDD found for the following risk factors: early onset, stress trigger absent, childhood parental loss, parental maltreatment, parental depression, and anxiety disorder; marginally significant results suggested an increased risk of recurrent MDD for substance disorder. There was a significant increased risk found for the interaction of an early onset with parental depression and similar non-significant trends were found for the interactions of early onset with parental loss and early onset with parental maltreatment.
An early onset, the absence of a life stress trigger, and the presence of parental loss, parental maltreatment, parental depression, a comorbid anxiety disorder, and a comorbid substance disorder each confer greater risk of recurrent MDD among persons that have not yet recovered from their first lifetime MDE. The presence of an early onset combined with a childhood-based vulnerability such as parental depression, parental loss, or parental maltreatment, indicate an especially high risk of recurrent MDD. These findings may inform the development of a screening tool to assess risk for recurrent MDD and early intervention to prevent recurrent MDD. Future research should employ a longitudinal research design to replicate and expand upon these findings.
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Victoria, Michelle Renee. "Adult Outpatients With Major Depressive Disorder Forming Positive Responses During Challenging Events." ScholarWorks, 2011. https://scholarworks.waldenu.edu/dissertations/1082.
Full textAbstract:
Previous empirical research demonstrated that major depressive disorder (MDD) had a profound impact on adults. What remained unaddressed in the research was the ability of those with MDD to form positive responses during challenging life events. The purpose of this exploratory quantitative study was to examine the cognitive ability of MDD patients to form positive responses on a standardized psychological assessment. This study, guided by Beck's cognitive theory of depression, was designed to determine whether depressed individuals were prone to negativity and had decreased ability to form positive responses to challenging situations. A 2x2 ANOVA was used to analyze 116 participants who voluntarily completed the Changes in Outlook Questionnaire (CiOQ). Results indicated that the group diagnosed with MDD scored significantly lower than a control group on the positive response scale of the CiOQ and that men diagnosed with MDD scored significantly lower than women diagnosed with MDD on the positive response scale of the CiOQ. This research has positive social change implications in that practitioners may use the findings in developing more effective treatments to help those with MDD to learn to form positive responses in the midst of challenging life events. Practitioners may also develop their ability to recognize when men with MDD are depressed by using the CiOQ to obtain written responses from individuals who do not verbalize depression. This research may also be useful for future research and application within the field.
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Li, Yihan. "Patterns of symptoms in major depressive disorder and genetics of the disorder using low-pass sequencing data." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:110887ce-fa6a-4a86-8063-d3de0d85d0d6.
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My thesis aims at identifying both genetic and environmental causes of major depressive disorder (MDD), using a large case-control study: 6,000 Chinese women with recurrent MDD and 6,000 controls. One of the major challenges for conducting genetic research on MDD is disease heterogeneity. The first question addressed is how different MDD is from highly comorbid anxiety disorders. I examine how anxiety disorders predict clinical features of depression and the degree of heterogeneity in their predictive pattern. The second question addressed is whether clinically defined MDD is a single disorder, or whether it consists of multiple subtypes. Results are then compared with and interpreted in the context of Western studies. Furthermore, latent class analysis and factor analysis results are also used in association analysis to explore more genetically homogeneous subtypes. Genetic data were derived using a novel strategy, low pass whole genome sequence analysis. Using genotypes imputed from the sequence data, I show that a cluster of single nucleotide polymorphisms (SNPs) is significantly associated with a binary disease phenotype including only cases with = 4 episodes of MDD, suggesting that recurrence might be an indication of genetic predisposition. The third issue examined is the contribution of rare variants to disease susceptibility. Again using sparse sequence data, I identified exonic sequence variants and performed gene-based analysis by comparing the number of variants between cases and controls in every gene. Furthermore I performed gene enrichment test by combining P values of SNP association tests at different minor allele frequency ranges. Overall, I did not find convincing evidence that rare variants aggregately contribute to disease susceptibility. However, the gene-based analysis resulted in an unexpected finding: cases have an excess of variants in all thirteen-protein coding mitochondrial genes, which was due to copy number differences in the mitochondrial genome. Both human phenotypic data as well as mice experimental data show that the increase in the mitochondrial copy number in cases is due to chronic stress.
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Bylsma, Lauren M. "Examining emotional reactivity to daily events in major and minor depression." [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002571.
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Rytsälä, Heikki. "Functional and work disability and treatment received by patients with major depressive disorder." Helsinki : University of Helsinki, 2006. http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/rytsala/.
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