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Lim, Keane, Max Lam, Hailiang Huang, Jianjun Liu y Jimmy Lee. "Genetic liability in individuals at ultra-high risk of psychosis: A comparison study of 9 psychiatric traits". PLOS ONE 15, n.º 12 (2 de diciembre de 2020): e0243104. http://dx.doi.org/10.1371/journal.pone.0243104.
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Individuals at ultra-high risk (UHR) of psychosis are characterised by the emergence of attenuated psychotic symptoms and deterioration in functioning. In view of the high non-psychotic comorbidity and low rates of transition to psychosis, the specificity of the UHR status has been called into question. This study aims to (i) investigate if the UHR construct is associated with the genetic liability of schizophrenia or other psychiatric conditions; (ii) examine the ability of polygenic risk scores (PRS) to discriminate healthy controls from UHR, remission and conversion status. PRS was calculated for 210 youths (nUHR = 102, nControl = 108) recruited as part of the Longitudinal Youth at Risk Study (LYRIKS) using nine psychiatric traits derived from twelve large-scale psychiatric genome-wide association studies as discovery datasets. PRS was also examined to discriminate UHR-Healthy control status, and healthy controls from UHR remission and conversion status. Result indicated that schizophrenia PRS appears to best index the genetic liability of UHR, while trend level associations were observed for depression and cross-disorder PRS. Schizophrenia PRS discriminated healthy controls from UHR (R2 = 7.9%, p = 2.59 x 10−3, OR = 1.82), healthy controls from non-remitters (R2 = 8.1%, p = 4.90 x 10−4, OR = 1.90), and converters (R2 = 7.6%, p = 1.61 x 10−3, OR = 1.82), with modest predictive ability. A trend gradient increase in schizophrenia PRS was observed across categories. The association between schizophrenia PRS and UHR status supports the hypothesis that the schizophrenia polygenic liability indexes the risk for developing psychosis.
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Zhou, Yifang, Jie Liu, Naomi Driesen, Fay Womer, Kaiyuan Chen, Ye Wang, Xiaowei Jiang et al. "White Matter Integrity in Genetic High-Risk Individuals and First-Episode Schizophrenia Patients: Similarities and Disassociations". BioMed Research International 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/3107845.
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White matter (WM) neuroimaging studies have shown varied findings at different stages of schizophrenia (SZ). Understanding these variations may elucidate distinct markers of genetic vulnerability and conversion to psychosis. To examine the similarities and differences in WM connectivity between those at-risk for and in early stages of SZ, a cross-sectional diffusion tensor imaging study of 48 individuals diagnosed with first-episode SZ (FE-SZ), 37 nonpsychotic individuals at a high genetic risk of SZ (GHR-SZ), and 67 healthy controls (HC) was conducted. Decreased fractional anisotropy (FA) in the corpus callosum (CC), anterior cingulum (AC), and uncinate fasciculus (UF) was observed in both the GHR-SZ and FE-SZ groups, while decreased FAs in the superior longitudinal fasciculus (SLF) and the fornix were only seen in the FE-SZ participants. Additionally, both GHR-SZ and FE-SZ showed worse executive performance than HC. The left SLF III FA was significantly positively correlated with hallucinations, and right SLF II was positively correlated with thought disorder. The presence of shared WM deficits in both FE-SZ and GHR-SZ individuals may reflect the genetic liability to SZ, while the disparate FA changes in the FE-SZ group may represent symptom-generating circuitry that mediates perceptual and cognitive disturbances of SZ and ultimately culminates in the onset of psychotic episodes.
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Schultze-Lutter, F., C. Michel, S. J. Schmidt, B. G. Schimmelmann, N. P. Maric, R. K. R. Salokangas, A. Riecher-Rössler et al. "EPA guidance on the early detection of clinical high risk states of psychoses". European Psychiatry 30, n.º 3 (marzo de 2015): 405–16. http://dx.doi.org/10.1016/j.eurpsy.2015.01.010.
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AbstractThe aim of this guidance paper of the European Psychiatric Association is to provide evidence-based recommendations on the early detection of a clinical high risk (CHR) for psychosis in patients with mental problems. To this aim, we conducted a meta-analysis of studies reporting on conversion rates to psychosis in non-overlapping samples meeting any at least any one of the main CHR criteria: ultra-high risk (UHR) and/or basic symptoms criteria. Further, effects of potential moderators (different UHR criteria definitions, single UHR criteria and age) on conversion rates were examined. Conversion rates in the identified 42 samples with altogether more than 4000 CHR patients who had mainly been identified by UHR criteria and/or the basic symptom criterion ‘cognitive disturbances’ (COGDIS) showed considerable heterogeneity. While UHR criteria and COGDIS were related to similar conversion rates until 2-year follow-up, conversion rates of COGDIS were significantly higher thereafter. Differences in onset and frequency requirements of symptomatic UHR criteria or in their different consideration of functional decline, substance use and co-morbidity did not seem to impact on conversion rates. The ‘genetic risk and functional decline’ UHR criterion was rarely met and only showed an insignificant pooled sample effect. However, age significantly affected UHR conversion rates with lower rates in children and adolescents. Although more research into potential sources of heterogeneity in conversion rates is needed to facilitate improvement of CHR criteria, six evidence-based recommendations for an early detection of psychosis were developed as a basis for the EPA guidance on early intervention in CHR states.
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Gee, Dylan G. y Tyrone D. Cannon. "Prediction of conversion to psychosis: review and future directions". Revista Brasileira de Psiquiatria 33, suppl 2 (octubre de 2011): s129—s142. http://dx.doi.org/10.1590/s1516-44462011000600002.
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This article reviews recent findings on predictors of conversion to psychosis among youth deemed at ultra high risk (UHR) based on the presence of subpsychotic-intensity symptoms or genetic risk for psychosis and a recent decline in functioning. Although transition rates differ between studies, the most well powered studies have observed rates of conversion to full psychosis in the 30-40% range over 2-3 years of follow-up. Across studies, severity of subthreshold positive symptoms, poorer social functioning, and genetic risk for schizophrenia appear to be consistent predictors of conversion to psychosis, with algorithms combining these indicators achieving positive predictive power > 80%. Nevertheless, a substantial fraction of UHR cases do not convert to psychosis. Recent work indicates that UHR cases who present with lower levels of negative symptoms and higher levels of social functioning are more likely to recover symptomatically and no longer meet criteria for an at-risk mental state. In general, it appears that about 1/3 of UHR cases convert to psychosis, about 1/3 do not convert but remain symptomatic and functionally impaired, and about 1/3 recover symptomatically and functionally. Continued efforts to detect early risk for psychosis are critical for informing early intervention and provide increasing promise of delaying or even preventing the onset of psychosis.
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Bechdolf, A., B. Nelson, S. M. Cotton, A. Chanen, A. Thompson, P. Conus, A. R. Yung, M. Berk y P. D. McGorry. "A Pilot Study of at-risk Criteria for Bipolar Disorders in Help Seeking Adolescents and Young Adults". European Psychiatry 24, S1 (enero de 2009): 1. http://dx.doi.org/10.1016/s0924-9338(09)70354-2.
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Introduction:We have developed ultra-high risk criteria for bipolar affective disorder (bipolar at-risk - BAR) which include general criteria such as being in the peak age range of the onset of the disorder and a combination of specific criteria including sub-threshold mania, depressive symptoms, cyclothymic features and genetic risk. In the current study, the predictive and discriminant validity of these criteria were tested in help seeking adolescents and young adults.Method:This medical file-audit study was conducted at ORYGEN Youth Health (OYH), a public mental health program for young people aged between 15 and 24 years and living in metropolitan Melbourne, Australia. BAR criteria were applied to the intake assessments of all non-psychotic patients who were being treated in OYH on 31 January.08. All entries were then checked for conversion criteria. Hypomania/mania related additions or alterations to existing treatments or initiation of new treatment by the treating psychiatrist served as conversion criteria to mania.Results:The BAR criteria were applied to 173 intake assessments. Of these, 22 patients (12.7%) met BAR criteria. The follow-up period of the sample was 265.5 days on average (SD 214.7). There were significantly more cases in the BAR group (22.7%, n = 5) than in the non-BAR group (0.7%, n = 1) who met conversion criteria (p < .001).Conclusions:These findings support the notion that people who develop a first episode of mania can be identified during the prodromal phase. The proposed criteria need further evaluation in prospective clinical trials.
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Kaymaz, N., M. Drukker, R. Lieb, H. U. Wittchen, N. Werbeloff, M. Weiser, T. Lataster y J. van Os. "Do subthreshold psychotic experiences predict clinical outcomes in unselected non-help-seeking population-based samples? A systematic review and meta-analysis, enriched with new results". Psychological Medicine 42, n.º 11 (20 de enero de 2012): 2239–53. http://dx.doi.org/10.1017/s0033291711002911.
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BackgroundThe base rate of transition from subthreshold psychotic experiences (the exposure) to clinical psychotic disorder (the outcome) in unselected, representative and non-help-seeking population-based samples is unknown.MethodA systematic review and meta-analysis was conducted of representative, longitudinal population-based cohorts with baseline assessment of subthreshold psychotic experiences and follow-up assessment of psychotic and non-psychotic clinical outcomes.ResultsSix cohorts were identified with a 3–24-year follow-up of baseline subthreshold self-reported psychotic experiences. The yearly risk of conversion to a clinical psychotic outcome in exposed individuals (0.56%) was 3.5 times higher than for individuals without psychotic experiences (0.16%) and there was meta-analytic evidence of dose–response with severity/persistence of psychotic experiences. Individual studies also suggest a role for motivational impairment and social dysfunction. The evidence for conversion to non-psychotic outcome was weaker, although findings were similar in direction.ConclusionsSubthreshold self-reported psychotic experiences in epidemiological non-help-seeking samples index psychometric risk for psychotic disorder, with strong modifier effects of severity/persistence. These data can serve as the population reference for selected and variable samples of help-seeking individuals at ultra-high risk, for whom much higher transition rates have been indicated.
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Lawrie, Stephen M., Majella Byrne, Patrick Miller, Ann Hodges, Robert A. Clafferty, David G. Cunningham Owens y Eve C. Johnstone. "Neurodevelopmental indices and the development of psychotic symptoms in subjects at high risk of schizophrenia". British Journal of Psychiatry 178, n.º 6 (junio de 2001): 524–30. http://dx.doi.org/10.1192/bjp.178.6.524.
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BackgroundNeurological ‘soft signs’ and minor physical anomalies (MPAs) are reported to be more frequent in patients with schizophrenia than in controls.AimsTo determine whether these disturbances are genetically mediated, and whether they are central to the genesis of symptoms or epiphenomena.MethodWe obtained ratings in 152 individuals who were antipsychotic drug-free and at high risk, some of whom had experienced psychotic symptoms, as well as 30 first-episode patients and 35 healthy subjects.ResultsMPAs and Neurological Evaluation Scale (NES) ‘sensory integration abnormalities’ were more frequent in high-risk subjects than in healthy controls, but there were no reliable differences between high-risk subjects with and without psychotic symptoms. MPAs were most frequent in high-risk subjects with least genetic liability and NES scores showed no genetic associations.ConclusionsThe lack of associations with psychotic symptoms and genetic liability to schizophrenia suggests that soft signs and physical anomalies are non-specific markers of developmental deviance that are not mediated by the gene(s) for schizophrenia.
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Crush, Eloise, Louise Arseneault, Andrea Danese, Sara R. Jaffee y Helen L. Fisher. "Using discordant twin methods to investigate an environmentally mediated pathway between social support and the reduced likelihood of adolescent psychotic experiences". Psychological Medicine 50, n.º 11 (15 de agosto de 2019): 1898–905. http://dx.doi.org/10.1017/s0033291719001983.
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AbstractBackgroundSocial support has been shown to be associated with a reduced likelihood of developing psychotic experiences in the general population and even amongst those at high risk due to exposure to multiple forms of victimisation (poly-victimised). However, it is unclear whether this association is merely due to the confounding effects of shared environmental and genetic influences, or reverse causality. Therefore, we investigated whether social support has a unique environmentally mediated effect on adolescent psychotic experiences after accounting for familial factors, including genetic factors, and also prior psychopathology.MethodsParticipants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 UK-born twins. Adolescents were interviewed at age 18 about psychotic experiences and victimisation exposure since age 12, and their perceptions of social support. Prior childhood mental health problems and psychotic symptoms were assessed at age 12. The discordant twin method was used to disentangle the relative family-wide and unique-environmental effects of social support on psychotic experiences in the general population and among poly-victimised adolescents.ResultsPerceived social support, particularly from friends, was found to have a unique environmentally mediated buffering effect on adolescent psychotic experiences in the whole sample and in the high-risk poly-victimised group.ConclusionsThe protective effects of social support on adolescent psychotic experiences cannot be accounted for by shared environmental or genetic factors, nor by earlier psychopathology. Our findings suggest that early intervention programmes focused on increasing perceptions of social support have the potential to prevent the emergence of psychotic experiences amongst adolescents.
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COSWAY, R., M. BYRNE, R. CLAFFERTY, A. HODGES, E. GRANT, J. MORRIS, S. S. ABUKMEIL et al. "Sustained attention in young people at high risk for schizophrenia". Psychological Medicine 32, n.º 2 (febrero de 2002): 277–86. http://dx.doi.org/10.1017/s0033291701005050.
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Background. Sustained attention has been found to be impaired in individuals suffering from schizophrenia and their close relatives. This has led to the hypothesis that impaired sustained attention is an indicator of vulnerability to schizophrenia.Methods. The Edinburgh High Risk Study used the Continuous Performance Test-Identical Pairs version (CPT-IP) to assess sustained attention in 127 high risk participants, 30 controls and 15 first-episode schizophrenic patients. A second assessment was completed by 59 high risk and 18 control participants 18 months to 2 years after the first.Results. No differences in attentional capacity were found between the high risk and control groups and there was no association between genetic liability to schizophrenia and poor performance on the CPT-IP. Additionally, no association between occurrence of psychotic symptoms in the high risk group and impaired attentional capacity was found.Conclusions. The results suggest that deficits in sustained attention are not indicative of a genetic vulnerability to schizophrenia, and are not associated with the occurrence of psychotic symptoms.
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Rek-Owodziń, Katarzyna y Anna Konopka. "Cognitive-behavioral therapy in ultra high risk states of psychosis (UHR)". Archives of Psychiatry and Psychotherapy 25, n.º 1 (22 de marzo de 2023): 7–13. http://dx.doi.org/10.12740/app/152940.
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Ultra-high risk of psychosis (UHR) is a condition associated with a higher risk of developing schizophrenia or another psychotic disorder as compared to the general population. Three groups of symptoms are reported to be related to UHR states: attenuated psychotic symptoms (APS), brief limited intermittent psychotic symptoms (BLIPS) and genetic risk and deterioration syndrome (GDR). In addition, specific cognitive deficits within attention, verbal and visual memory, executive functions and processing speed are all described as linked to UHR. UHR individuals also manifest negative cognitive beliefs and attribution biases, which affect their everyday lives. Hence, a first-line treatment recommended in UHR states is cognitive-behavioral therapy (CBT), whose effectiveness has been assessed across different studies. In this paper we describe the characteristics of UHR states, including specific cognitive difficulties they are linked with, alongside therapeutic recommendations and specificity of dedicated cognitive-behavioral treatment options.
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Ciarleglio, Adam J., Gary Brucato, Michael D. Masucci, Rebecca Altschuler, Tiziano Colibazzi, Cheryl M. Corcoran, Francesca M. Crump et al. "A predictive model for conversion to psychosis in clinical high-risk patients". Psychological Medicine 49, n.º 07 (28 de junio de 2018): 1128–37. http://dx.doi.org/10.1017/s003329171800171x.
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AbstractBackgroundThe authors developed a practical and clinically useful model to predict the risk of psychosis that utilizes clinical characteristics empirically demonstrated to be strong predictors of conversion to psychosis in clinical high-risk (CHR) individuals. The model is based upon the Structured Interview for Psychosis Risk Syndromes (SIPS) and accompanying clinical interview, and yields scores indicating one's risk of conversion.MethodsBaseline data, including demographic and clinical characteristics measured by the SIPS, were obtained on 199 CHR individuals seeking evaluation in the early detection and intervention for mental disorders program at the New York State Psychiatric Institute at Columbia University Medical Center. Each patient was followed for up to 2 years or until they developed a syndromal DSM-4 disorder. A LASSO logistic fitting procedure was used to construct a model for conversion specifically to a psychotic disorder.ResultsAt 2 years, 64 patients (32.2%) converted to a psychotic disorder. The top five variables with relatively large standardized effect sizes included SIPS subscales of visual perceptual abnormalities, dysphoric mood, unusual thought content, disorganized communication, and violent ideation. The concordance index (c-index) was 0.73, indicating a moderately strong ability to discriminate between converters and non-converters.ConclusionsThe prediction model performed well in classifying converters and non-converters and revealed SIPS measures that are relatively strong predictors of conversion, comparable with the risk calculator published by NAPLS (c-index = 0.71), but requiring only a structured clinical interview. Future work will seek to externally validate the model and enhance its performance with the incorporation of relevant biomarkers.
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Zhang, T. H., H. J. Li, K. A. Woodberry, L. H. Xu, Y. Y. Tang, Q. Guo, H. R. Cui et al. "Two-year follow-up of a Chinese sample at clinical high risk for psychosis: timeline of symptoms, help-seeking and conversion". Epidemiology and Psychiatric Sciences 26, n.º 3 (8 de abril de 2016): 287–98. http://dx.doi.org/10.1017/s2045796016000184.
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Background.Chinese psychiatrists have gradually started to focus on those who are deemed to be at ‘clinical high-risk (CHR)’ for psychosis; however, it is still unknown how often those individuals identified as CHR from a different country background than previously studied would transition to psychosis. The objectives of this study are to examine baseline characteristics and the timing of symptom onset, help-seeking, or transition to psychosis over a 2-year period in China.Method.The presence of CHR was determined with the Structured Interview for Prodromal Syndromes (SIPS) at the participants' first visit to the mental health services. A total of 86 (of 117) CHR participants completed the clinical follow-up of at least 2 years (73.5%). Conversion was determined using the criteria of presence of psychotic symptoms (in SIPS). Analyses examined baseline demographic and clinical predictors of psychosis and trajectory of symptoms over time. Survival analysis (Kaplan–Meier) methods along with Log-rank tests were performed to illustrate the relationship of baseline data to either conversion or non-conversion over time. Cox regression was performed to identify baseline predictors of conversion by the 2-year follow-up.Results.In total 25 (29.1%) of 86 completers transitioned to a psychotic disorder over the course of follow-up. Among the CHR sample, the mean time between attenuated symptom onset and professional help-seeking was about 4 months on average, and converters developed fully psychotic symptoms about 12 months after symptom onset. Compared with those CHR participants whose risk syndromes remitted over the course of the study, converters had significantly longer delays (p = 0.029) for their first visit to a professional in search of help. At baseline assessment, the conversion subgroup was younger, had poorer functioning, higher total SIPS positive symptom scores, longer duration of untreated prodromal symptoms, and were more often given psychosis-related diagnoses and subsequently prescribed antipsychotics in the clinic.Conclusions.Chinese CHR identified primarily by a novel clinical screening approach had a 2-year transition rate comparable with those of specialised help-seeking samples world-wide. Early clinical intervention with this functionally deteriorating clinical population who are suffering from attenuated psychotic symptoms, is a next step in applying the CHR construct in China.
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Fiksinski, A. M., E. J. Breetvelt, Y. J. Lee, E. Boot, N. Butcher, L. Palmer, E. W. C. Chow, R. S. Kahn, J. A. S. Vorstman y A. S. Bassett. "Neurocognition and adaptive functioning in a genetic high risk model of schizophrenia". Psychological Medicine 49, n.º 6 (1 de agosto de 2018): 1047–54. http://dx.doi.org/10.1017/s0033291718001824.
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AbstractBackgroundIdentifying factors that influence the functional outcome is an important goal in schizophrenia research. The 22q11.2 deletion syndrome (22q11DS) is a unique genetic model with high risk (20–25%) for schizophrenia. This study aimed to identify potentially targetable domains of neurocognitive functioning associated with functional outcome in adults with 22q11DS.MethodsWe used comprehensive neurocognitive test data available for 99 adults with 22q11DS (n = 43 with schizophrenia) and principal component analysis to derive four domains of neurocognition (Verbal Memory, Visual and Logical Memory, Motor Performance, and Executive Performance). We then investigated the association of these neurocognitive domains with adaptive functioning using Vineland Adaptive Behavior Scales data and a linear regression model that accounted for the effects of schizophrenia status and overall intellectual level.ResultsThe regression model explained 46.8% of the variance in functional outcome (p < 0.0001). Executive Performance was significantly associated with functional outcome (p = 0.048). Age and schizophrenia were also significant factors. The effects of Executive Performance on functioning did not significantly differ between those with and without psychotic illness.ConclusionThe findings provide the impetus for further studies to examine the potential of directed (early) interventions targeting Executive Performance to improve long-term adaptive functional outcome in individuals with, or at high risk for, schizophrenia. Moreover, the neurocognitive test profiles may benefit caregivers and clinicians by providing insight into the relative strengths and weaknesses of individuals with 22q11DS, with and without psychotic illness.
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Oliver, Dominic, Thomas J. Reilly, Ottone Baccaredda Boy, Natalia Petros, Cathy Davies, Stefan Borgwardt, Philip McGuire y Paolo Fusar-Poli. "What Causes the Onset of Psychosis in Individuals at Clinical High Risk? A Meta-analysis of Risk and Protective Factors". Schizophrenia Bulletin 46, n.º 1 (20 de junio de 2019): 110–20. http://dx.doi.org/10.1093/schbul/sbz039.
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AbstractTwenty percent of individuals at clinical high risk for psychosis (CHR-P) develop the disorder within 2 years. Extensive research has explored the factors that differentiate those who develop psychosis and those who do not, but the results are conflicting.The current systematic review and meta-analysis comprehensively addresses the consistency and magnitude of evidence for non-purely genetic risk and protective factors associated with the risk of developing psychosis in CHR-P individuals. Random effects meta-analyses, standardized mean difference (SMD) and odds ratio (OR) were used, in combination with an established stratification of evidence that assesses the association of each factor and the onset of psychotic disorders (from class I, convincing evidence to class IV weak evidence), while controlling for several types of biases.A total of 128 original controlled studies relating to 26 factors were retrieved. No factors showed class I-convincing evidence. Two further factors were associated with class II-highly suggestive evidence: attenuated positive psychotic symptoms (SMD = 0.348, 95% CI: 0.280, 0.415) and global functioning (SMD = −0.291, 95% CI: −0.370, −0.211). There was class III-suggestive evidence for negative psychotic symptoms (SMD = 0.393, 95% CI: 0.317, 0.469). There was either class IV-weak or no evidence for all other factors.Our findings suggest that despite the large number of putative risk factors investigated in the literature, only attenuated positive psychotic symptoms, global functioning, and negative psychotic symptoms show suggestive evidence or greater for association with transition to psychosis. The current findings may inform the refinement of clinical prediction models and precision medicine in this field.
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Johnstone, Eve C., Klaus P. Ebmeier, Patrick Miller, David G. C. Owens y Stephen M. Lawrie. "Predicting schizophrenia: findings from the Edinburgh High-Risk Study". British Journal of Psychiatry 186, n.º 1 (enero de 2005): 18–25. http://dx.doi.org/10.1192/bjp.186.1.18.
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BackgroundThe hypothesis that schizophrenia is neurodevelopmental was investigated in a prospective study of young people with a postulated 10–15% risk for the development of schizophrenia.AimsTo determine premorbid variables distinguishing high-risk people who will go on to develop schizophrenia from those who will not.MethodA high-risk sample of 163 young adults with two relatives with schizophrenia was recruited. They and 36 controls were serially examined. Baseline measures were compared between those who did develop schizophrenia, a well control group, a well high-risk group and high-risk participants with partial or isolated psychotic symptoms.ResultsOf those at high risk, 20 developed schizophrenia within 2½ years. More experienced isolated or partial psychotic symptoms. Those who developed schizophrenia differed from those who did not on social anxiety, withdrawal and other schizotypal features. The whole high-risk sample differed from the control group on developmental and neuropsychological variables.ConclusionsThe genetic component of schizophrenia affects many more individuals than will develop the illness, and partial impairment can be found in them. Highly significant predictors of the development of schizophrenia are detectable years before onset.
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Byrne, Majella, Bobby A. Clafferty, Richard Cosway, Elizabeth Grant, Ann Hodges, Heather C. Whalley, Stephen M. Lawrie, David G. Cunningham Owens y Eve C. Johnstone. "Neuropsychology, genetic liability, and psychotic symptoms in those at high risk of schizophrenia." Journal of Abnormal Psychology 112, n.º 1 (2003): 38–48. http://dx.doi.org/10.1037/0021-843x.112.1.38.
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de la Fuente-Sandoval, Camilo, Pablo León-Ortiz, Mariana Azcárraga, Rafael Favila, Sylvana Stephano y Ariel Graff-Guerrero. "Striatal glutamate and the conversion to psychosis: a prospective 1H-MRS imaging study". International Journal of Neuropsychopharmacology 16, n.º 2 (17 de abril de 2012): 471–75. http://dx.doi.org/10.1017/s1461145712000314.
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Abstract Increased glutamate levels in the associative-striatum have been described in subjects at ultra-high risk for psychosis (UHR); nevertheless, it is unclear whether this abnormality predicts the conversion to psychosis. Nineteen subjects at UHR and 26 controls were studied using proton magnetic resonance spectroscopy. Subjects at UHR were clinically followed for 2 yr. Seven UHR subjects (37%) transitioned to a psychotic disorder and the remaining 12 did not exhibit psychotic symptoms at the most recent follow-up. The psychosis transition group had higher glutamate levels compared to both non-transition and control groups (p = 0.02 and p < 0.01, respectively; effect size 1.39). These pilot findings suggest that the conversion to psychosis is associated with increased glutamate levels in the associative-striatum.
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Hengartner, M. P., K. Heekeren, D. Dvorsky, S. Walitza, W. Rössler y A. Theodoridou. "Checking the predictive accuracy of basic symptoms against ultra high-risk criteria and testing of a multivariable prediction model: Evidence from a prospective three-year observational study of persons at clinical high-risk for psychosis". European Psychiatry 45 (septiembre de 2017): 27–35. http://dx.doi.org/10.1016/j.eurpsy.2017.05.026.
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AbstractBackground:The aim of this study was to critically examine the prognostic validity of various clinical high-risk (CHR) criteria alone and in combination with additional clinical characteristics.Methods:A total of 188 CHR positive persons from the region of Zurich, Switzerland (mean age 20.5 years; 60.2% male), meeting ultra high-risk (UHR) and/or basic symptoms (BS) criteria, were followed over three years. The test battery included the Structured Interview for Prodromal Syndromes (SIPS), verbal IQ and many other screening tools. Conversion to psychosis was defined according to ICD-10 criteria for schizophrenia (F20) or brief psychotic disorder (F23).Results:Altogether n = 24 persons developed manifest psychosis within three years and according to Kaplan–Meier survival analysis, the projected conversion rate was 17.5%. The predictive accuracy of UHR was statistically significant but poor (area under the curve [AUC] = 0.65, P < .05), whereas BS did not predict psychosis beyond mere chance (AUC = 0.52, P = .730). Sensitivity and specificity were 0.83 and 0.47 for UHR, and 0.96 and 0.09 for BS. UHR plus BS achieved an AUC = 0.66, with sensitivity and specificity of 0.75 and 0.56. In comparison, baseline antipsychotic medication yielded a predictive accuracy of AUC = 0.62 (sensitivity = 0.42; specificity = 0.82). A multivariable prediction model comprising continuous measures of positive symptoms and verbal IQ achieved a substantially improved prognostic accuracy (AUC = 0.85; sensitivity = 0.86; specificity = 0.85; positive predictive value = 0.54; negative predictive value = 0.97).Conclusions:We showed that BS have no predictive accuracy beyond chance, while UHR criteria poorly predict conversion to psychosis. Combining BS with UHR criteria did not improve the predictive accuracy of UHR alone. In contrast, dimensional measures of both positive symptoms and verbal IQ showed excellent prognostic validity. A critical re-thinking of binary at-risk criteria is necessary in order to improve the prognosis of psychotic disorders.
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Mittal, Vijay A., Mary E. Saczawa, Deborah Walder, Rachel Willhite y Elaine Walker. "Prenatal exposure to viral infection and conversion among adolescents at high-risk for psychotic disorders". Schizophrenia Research 99, n.º 1-3 (febrero de 2008): 375–76. http://dx.doi.org/10.1016/j.schres.2007.11.037.
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Padula, Maria Carmela, Marie Schaer, Marco Armando, Corrado Sandini, Daniela Zöller, Elisa Scariati, Maude Schneider y Stephan Eliez. "Cortical morphology development in patients with 22q11.2 deletion syndrome at ultra-high risk of psychosis". Psychological Medicine 48, n.º 14 (17 de enero de 2018): 2375–83. http://dx.doi.org/10.1017/s0033291717003920.
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AbstractBackgroundPatients with 22q11.2 deletion syndrome (22q11DS) present a high risk of developing psychosis. While clinical and cognitive predictors for the conversion towards a full-blown psychotic disorder are well defined and largely used in practice, neural biomarkers do not yet exist. However, a number of investigations indicated an association between abnormalities in cortical morphology and higher symptoms severities in patients with 22q11DS. Nevertheless, few studies included homogeneous groups of patients differing in their psychotic symptoms profile.MethodsIn this study, we included 22 patients meeting the criteria for an ultra-high-risk (UHR) psychotic state and 22 age-, gender- and IQ-matched non-UHR patients. Measures of cortical morphology, including cortical thickness, volume, surface area and gyrification, were compared between the two groups using mass-univariate and multivariate comparisons. Furthermore, the development of these measures was tested in the two groups using a mixed-model approach.ResultsOur results showed differences in cortical volume and surface area in UHR patients compared with non-UHR. In particular, we found a positive association between surface area and the rate of change of global functioning, suggesting that higher surface area is predictive of improved functioning with age. We also observed accelerated cortical thinning during adolescence in UHR patients with 22q11DS.ConclusionsThese results, although preliminary, suggest that alterations in cortical volume and surface area as well as altered development of cortical thickness may be associated to a greater probability to develop psychosis in 22q11DS.
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McHugh, M. J., P. D. McGorry, A. R. Yung, A. Lin, S. J. Wood, J. A. Hartmann y B. Nelson. "Cannabis-induced attenuated psychotic symptoms: implications for prognosis in young people at ultra-high risk for psychosis". Psychological Medicine 47, n.º 4 (8 de noviembre de 2016): 616–26. http://dx.doi.org/10.1017/s0033291716002671.
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BackgroundCannabis use shows a robust dose-dependent relationship with psychosis risk among the general population. Despite this, it has been difficult to link cannabis use with risk for transitioning to a psychotic disorder among individuals at ultra-high risk (UHR) for psychosis. The present study examined UHR transition risk as a function of cannabis use characteristics which vary substantially between individuals including age of first use, cannabis abuse severity and a history of cannabis-induced attenuated psychotic symptoms (APS).MethodParticipants were 190 UHR individuals (76 males) recruited at entry to treatment between 2000 and 2006. They completed a comprehensive baseline assessment including a survey of cannabis use characteristics during the period of heaviest use. Outcome was transition to a psychotic disorder, with mean time to follow-up of 5.0 years (range 2.4–8.7 years).ResultsA history of cannabis abuse was reported in 58% of the sample. Of these, 26% reported a history of cannabis-induced APS. These individuals were 4.90 (95% confidence interval 1.93–12.44) times more likely to transition to a psychotic disorder (p = 0.001). Greater severity of cannabis abuse also predicted transition to psychosis (p = 0.036). However, this effect was mediated by higher abuse severity among individuals with a history of cannabis-induced APS.ConclusionsFindings suggest that cannabis use poses risk in a subpopulation of UHR individuals who manifest cannabis-induced APS. Whether this reflects underlying genetic vulnerability requires further study. Nevertheless, findings reveal an important early marker of risk with potentially significant prognostic utility for UHR individuals.
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Chakirova, G., K. A. Welch, TWJ Moorhead, A. C. Stanfield, J. Hall, P. Skehel, V. J. Brown et al. "Orbitofrontal morphology in people at high risk of developing schizophrenia". European Psychiatry 25, n.º 6 (octubre de 2010): 366–72. http://dx.doi.org/10.1016/j.eurpsy.2010.03.001.
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AbstractBackgroundAbnormalities of orbitofrontal cortex (OFC) sulcogyral patterns have been reported in schizophrenia, but it is not known if these predate psychosis.MethodsHundred and forty-six subjects at high genetic risk of schizophrenia, 34 first episode of schizophrenia patients (SZ) and 36 healthy controls were scanned and clinically assessed. Utilising the classification system proposed by Chiavaras, we categorised OFC patterns and compared their distribution between the groups, as well as between those high risk subjects who did, and did not develop schizophrenia. The relationship between OFC pattern and schizotypy was explored in high risk subjects.ResultsWe refined Chiavaras’ classification system, with the identification of a previously unreported variant of OFC surface structure. There were significant differences in distribution of OFC patterns between high risk subjects who did or did not develop schizophrenia as well as between the first episode of schizophrenia group and healthy controls. Within the high risk group, possession of OFC Type III was associated with higher ratings on the Structured Inventory for Schizotypy (SIS) psychotic factor.ConclusionsOur results suggest that OFC Type III is associated with psychotic features before the development of schizophrenia. Characterisation of OFC morphology may have a role in the identification of those at greatest risk of developing schizophrenia.
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Isvoranu, Adela-Maria, Sinan Guloksuz, Sacha Epskamp, Jim van Os y Denny Borsboom. "Toward incorporating genetic risk scores into symptom networks of psychosis". Psychological Medicine 50, n.º 4 (14 de marzo de 2019): 636–43. http://dx.doi.org/10.1017/s003329171900045x.
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AbstractBackgroundPsychosis spectrum disorder is a heterogeneous, multifactorial clinical phenotype, known to have a high heritability, only a minor portion of which can be explained by molecular measures of genetic variation. This study proposes that the identification of genetic variation underlying psychotic disorder may have suffered due to issues in the psychometric conceptualization of the phenotype. Here we aim to open a new line of research into the genetics of mental disorders by explicitly incorporating genes into symptom networks. Specifically, we investigate whether links between a polygenic risk score (PRS) for schizophrenia and measures of psychosis proneness can be identified in a network model.MethodsWe analyzed data from n = 2180 subjects (controls, patients diagnosed with a non-affective psychotic disorder, and the first-degree relatives of the patients). A network structure was computed to examine associations between the 42 symptoms of the Community Assessment of Psychic Experiences (CAPE) and the PRS for schizophrenia.ResultsThe resulting network shows that the PRS is directly connected to the spectrum of positive and depressive symptoms, with the items conspiracy and no future being more often located on predictive pathways from PRS to other symptoms.ConclusionsTo our knowledge, the current exploratory study provides a first application of the network framework to the field of behavior genetics research. This allows for a novel outlook on the investigation of the relations between genome-wide association study-based PRSs and symptoms of mental disorders, by focusing on the dependencies among variables.
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Schultze-Lutter, F. "Prevention strategies in clinical high-risks states for psychotic disorders: weighing up costs and benefits". European Psychiatry 66, S1 (marzo de 2023): S30—S31. http://dx.doi.org/10.1192/j.eurpsy.2023.118.
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AbstractToday, the indicated prevention of psychosis prior to its first episode is mainly based on clinical high-risk of psychosis (CHR) criteria, namely ultra-high risk criteria and basic symptom criteria. These are associated with conversion-to-psychosis rates of about 30% within three years. Thus, many patients meeting CHR criteria will not progress to psychosis over a medium-term period, and the cost-benefit evaluation of CHR states is always complicated by the largely unknown individual psychosis risk of CHR patients. In consequence, for the lesser risk of adverse events, treatment recommendations commonly favour non-pharmacological strategies, in particular cognitive-behavioural psychotherapy. Yet, individual risk estimation in identified CHR patients is increasingly done with help of machine learning algorithms, which might help to identify CHR patients who would greatly benefit from an additional pharmacological intervention with low-dose antipsychotics. The presentation will discuss the evidence-base of such a multistep, machine learning informed prevention strategy.Disclosure of InterestNone Declared
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Barbato, Mariapaola, David L. Penn, Diana O. Perkins, Scott W. Woods, Lu Liu y Jean Addington. "Metacognitive Functioning in Individuals at Clinical High Risk for Psychosis". Behavioural and Cognitive Psychotherapy 42, n.º 5 (21 de marzo de 2013): 526–34. http://dx.doi.org/10.1017/s1352465813000167.
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Background: Metacognition has been described as the knowledge of our own cognitive processes. Metacognitive deficits are common in schizophrenia, but little is known about metacognition before the onset of full-blown psychosis. Aims: This study aimed to longitudinally characterize metacognition in a sample of individuals at clinical high risk (CHR) for psychosis, and to determine if metacognition was related to later conversion to psychosis. Method: Participants (153 CHR individuals; 68 help seeking controls, HSC) were part of the large multi-site PREDICT study, which sought to determine predictors of conversion to psychosis. They were tested at baseline and 6 months using the Meta-Cognitions Questionnaire (MCQ) that has five sub-scales assessing different domains of metacognition. Results: Results of the mixed-effect models demonstrated significantly poorer scores at baseline for the CHR group compared to the HSC group in Negative beliefs about uncontrollability, Negative beliefs and the overall MCQ score. At the 6-month assessment, no difference was observed in metacognition between the two groups, but both groups showed improvement in metacognition over time. Those who later converted to psychosis had poorer performance on metacognitive beliefs at baseline. Conclusions: A poorer performance in metacognition can be seen as a marker of developing a full blown psychotic illness and confirms the potential value of assessing metacognitive beliefs in individuals vulnerable for psychosis.
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Kelleher, I. y M. Cannon. "Psychotic-like experiences in the general population: characterizing a high-risk group for psychosis". Psychological Medicine 41, n.º 1 (19 de mayo de 2010): 1–6. http://dx.doi.org/10.1017/s0033291710001005.
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Recent research shows that psychotic symptoms, or psychotic-like experiences (PLEs), are reported not only by psychosis patients but also by healthy members of the general population. Healthy individuals who report these symptoms are considered to represent a non-clinical psychosis phenotype, and have been demonstrated to be at increased risk of schizophrenia-spectrum disorder. Converging research now shows that this non-clinical psychosis phenotype is familial, heritable and covaries with familial schizophrenia-spectrum disorder. A review of the research also shows that the non-clinical phenotype is associated extensively with schizophrenia-related risk factors, including social, environmental, substance use, obstetric, developmental, anatomical, motor, cognitive, linguistic, intellectual and psychopathological risk factors. The criterion and construct validity of the non-clinical psychosis phenotype with schizophrenia demonstrates that it is a valid population in which to study the aetiology of psychosis. Furthermore, it suggests shared genetic variation between the clinical and non-clinical phenotypes. Much remains to be learned about psychosis by broadening the scope of research to include the non-clinical psychosis phenotype.
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Lawrie, Stephen M., Heather C. Whalley, Suheib S. Abukmeil, Julia N. Kestelman, Lorna Donnelly, Patrick Miller, Jonathan J. K. Best, David G. Cunningham Owens y Eve C. Johnstone. "Brain structure, genetic liability, and psychotic symptoms in subjects at high risk of developing schizophrenia". Biological Psychiatry 49, n.º 10 (mayo de 2001): 811–23. http://dx.doi.org/10.1016/s0006-3223(00)01117-3.
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Omelchenko, M. A. "Clinical High Risk Psychosis: Issues of Diagnostics and Therapy". Psychiatry 18, n.º 2 (22 de julio de 2020): 82–91. http://dx.doi.org/10.30629/2618-6667-2020-18-2-82-91.
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The aim of the review: the analysis of modern Russian and foreign literature dedicated to the problem of determining diagnostic criteria for clinical high risk of psychosis (CHR-P) and outlining the therapeutic approaches based on the pathogenic mechanisms of their development. Material and method: the publications found by searching queries for keywords in Russian and English in the MEDLINE/PubMed and eLIBRARY databases for the time period from 2010 to 2020 were then analyzed. Conclusion: the review presents a modern definition of the CHR-P group, along with a clarification of individual diagnostic criteria, which include attenuated psychotic symptoms (APS), brief limited intermittent psychotic symptoms (BLIPS), genetic risk with deterioration of premorbid functioning, as well as basic symptoms (BS). We found heterogeneity of the CHR-P group with different levels of manifestation and outcomes and indicated the involvement of different pathogenic mechanisms in their formation. These findings determine the development of various approaches to treatment, which involve the assessment of the ratio of potential benefits and the risks of side effects. The obtained data, on the one hand, attest to the prospective viability of the therapeutic approach to the patients with CHR-P with the possibility of influencing the course of the disease, delaying its manifestation and improving long-term outcomes, and, on the other hand, the lack of universal standards of therapy at present. Tactics of treatment are determined basing on an individual approach to the patient with a comprehensive psychopathological assessment of complaints, clinical state and its dynamics.
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Abarca, Maximiliano, Humberto Pizarro, Rebeca Nuñez y Marcelo Arancibia. "Physical exercise as an intervention in people at clinical high-risk for psychosis: A narrative review". Medwave 23, n.º 08 (15 de septiembre de 2023): e2724-e2724. http://dx.doi.org/10.5867/medwave.2023.08.2724.
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The concept of clinical high risk for psychosis has favored research in the neurobiology of the stages prior to psychosis, as well as in preventive interventions. This group is made up of young people with: (1) psychotic symptoms of less intensity or less frequency during a brief time or having genetic history of psychotic disorders associated to a significant deterioration in functioning. The few existing interventions for this population have a low level of evidence. Physical activity and exercise have been shown to be part of the therapy for multiple psychiatric disorders, while a sedentary lifestyle would be a factor that favors psychosis. Indeed, people in clinical high risk for psychosis present a worse physical condition associated with a greater sedentary lifestyle and unhealthy habits. It has been proposed that exercise generates a positive biological effect on the hippocampus and surrounding areas, regions that would be involved in the pathophysiology of psychosis. Some experimental studies have shown a decrease in psychotic symptoms in patients with clinical high risk for psychosis who have followed physical exercise guidelines, as well as morphofunctional changes in brain structures. Although there are barriers to the implementation of this intervention, it is safe and feasible. It is necessary to conduct a greater number of experimental studies on a larger scale to measure its efficacy, generating scientific evidence that will eventually allow physical exercise to be included in clinical practice guidelines as a systematic recommendation for clinical high risk for psychosis.
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Kounali, Daphne, Sarah Sullivan, Jon Heron, Jon McLeod, Mary Cannon, David Cotter, David Mongan, Glyn Lewis, Peter Jones y Stanley Zammit. "M110. PREDICTING RISK OF PSYCHOSIS IN A GENERAL POPULATION SAMPLE". Schizophrenia Bulletin 46, Supplement_1 (abril de 2020): S176—S177. http://dx.doi.org/10.1093/schbul/sbaa030.422.
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Abstract Background At present clinical high-risk states for psychosis are determined by specialist mental health services using clinical tools such as the CAARMS, which largely rely on the detection of attenuated psychotic symptoms. However, the positive predictive value (PPV) of the CAARMS for transition to psychosis is only 25% in help seeking populations and as low as 5% in general population, non-help seeking samples. There is therefore a clear need to improve the prediction of psychotic disorder using other (non-symptom related) markers of risk. Our aim was to derive a risk prediction tool to determine risk of psychotic disorder using a large, population-based birth-cohort. Methods We used data from the ALSPAC birth cohort, with data on a comprehensive range of predictors ascertained from early childhood through early adulthood, and on psychotic disorder up to age 24 (imputed up to N≈7000 with any data on psychotic experiences). We use a two-stage risk prediction model, where different sets of predictors are used for outcomes of increasing severity. In the first stage, we predicted a clinical need for care in those who had self-reported psychotic-like experiences prior to age 17 years. We assumed that most of this need for care subsample would be help-seeking and that they therefore provide a more accessible risk-enriched sample for the second stage of our prediction model, where more difficult to measure predictors are included for estimating the risk of new onset psychotic disorder. Here we report on the first stage of our prediction model where we predict a clinical need for care (defined as presence of frequent and distressing interviewer-rated psychotic experiences) at age 17–24 years in participants who self-reported any psychotic-like experiences prior to age 17. The prediction set consisted of sixty-one features across 4 domains: socio-demographic (12 features); cognitive (10 features); non-psychotic psychopathology (24 features); behavioural (10 features). We used machine-learning methods for predictor selection and model fitting, employing resampling to assess and validate model calibration and discrimination. Results 13% of participants who self-reported psychotic experiences by age 17 were found to have a clinical need for care between ages 17–24, and 3.5% met criteria for newly ascertained psychotic disorder at 24 years. Use of two different machine learning methods for feature selection (random forests with a 10-fold cross-validation and elastic nets employing shrinkage) yielded similar results, although the elastic nets/ridge regression produced a more parsimonious model. The features selected included: adolescent self-harm, and childhood IQ, attention, processing speed and external locus of control. The AUC reduced very little compared to that of a model with 61 characteristics. This simpler model showed improved calibration and optimism-corrected predictive performance of AUC=0.73, sensitivity=0.75, specificity=0.60, and PPV=0.22. Discussion Our risk calculator is comparable in performance to those produced in studies of prodromal psychosis in high-risk samples. This first-stage model achieved promising predictive performance. We are currently developing a prognostic score for psychotic disorder in those with a clinical need for care and augment the predictor set with genetic, lipidomic and proteomic markers and further cognitive tests. We will then assess the model’s clinical utility and variation in predictive performance using linkage of ALSPAC data to clinical health care records with the aim to externally validate in other cohort studies.
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Binbay, T., M. Drukker, K. Alptekin, H. Elbi, F. Aksu Tanık, F. Özkınay, H. Onay, N. Zağlı y J. van Os. "Evidence that the wider social environment moderates the association between familial liability and psychosis spectrum outcome". Psychological Medicine 42, n.º 12 (16 de abril de 2012): 2499–510. http://dx.doi.org/10.1017/s0033291712000700.
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BackgroundFamilial liability to both severe and common mental disorder predicts psychotic disorder and psychotic symptoms, and may be used as a proxy in models examining interaction between genetic risk and the environment at individual and contextual levels.MethodIn a representative general population sample (n=4011) in Izmir, Turkey, the full spectrum of expression of psychosis representing (0) no symptoms, (1) subclinical psychotic experiences, (2) low-impact psychotic symptoms, (3) high-impact psychotic symptoms and (4) full-blown clinical psychotic disorder was assessed in relation to mental health problems in the family (proxy for familial liability) and the wider social environment. Quality of the wider social environment was assessed in an independent sample using contextual measures of informal social control, social disorganization, unemployment and low income, aggregated to the neighbourhood level.ResultsThe association between familial liability to severe mental illness and expression of psychosis spectrum was stronger in more deprived neighbourhoods [e.g. this association increased from β=0.33 (p=0.01) in low-unemployment neighbourhoods to β=0.92 (p<0.001) in high-unemployment neighbourhoods] and in neighbourhoods high in social control, while neighbourhood variables did not modify the association between familial liability to common mental disorder and the psychosis outcome. Neighbourhood variables mediated urbanicity effects.ConclusionsContextual effects may be important in moderating the expression of psychosis liability in populations, representing a specific pathway independent of the link between common mental disorder and psychosis.
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Chaumette, B., C. Jiao y Q. He. "Resilience Factors Preventing Schizophrenia in Ultra-high Risk Patients: Lessons from Genetics". European Psychiatry 65, S1 (junio de 2022): S9—S10. http://dx.doi.org/10.1192/j.eurpsy.2022.49.
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Over the past decades, researchers and psychiatrists in the field of psychosis have moved from a conception of a chronic presentation to a more dynamic paradigm. Accordingly, schizophrenia is now conceptualized as a progressive illness that typically emerges during late adolescence and follows different stages: early vulnerability, ultra-high risk state, first episode of psychosis, and chronic disease. Only one-quarter of the ultra-high risk patients will convert to a full-blown psychotic episode within 3 years while the others, called non-converters, will remain at-risk, develop other psychiatric disorders, or fully recover. The reasons for this differential outcome are not yet understood but this concept opens the way to scientific research to determine the protective factors involved in resilience for non-converters. Based on the Gene X Environment interaction model, schizophrenia results from genetic vulnerability and environmental aggressions which can have an impact on the epigenome and gene expression. Recent studies have shown that genetic variants play a role in the resilience of psychosis. Polygenic risk scores, computed as the addition of genetic polymorphisms, can modulate the effects of genetic at-risk deletions (i.e. del22q11) that predispose to psychosis and may also influence the cognitive symptoms of ultra-high risk patients. Resilience, defined as the ability to withstand adversity, is not only related to external skills or psychotherapeutic care but could also be explained by internal molecular factors. Identifying the genetic factors of resilience might help to stratify the risk and to develop precision medicine in psychiatry. Disclosure No significant relationships.
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Xu, Jiayuan, Qiaojun Li, Wen Qin, Mulin Jun Li, Chuanjun Zhuo, Huaigui Liu, Feng Liu, Junping Wang, Gunter Schumann y Chunshui Yu. "Neurobiological substrates underlying the effect of genomic risk for depression on the conversion of amnestic mild cognitive impairment". Brain 141, n.º 12 (14 de noviembre de 2018): 3457–71. http://dx.doi.org/10.1093/brain/awy277.
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Abstract Depression increases the conversion risk from amnestic mild cognitive impairment to Alzheimer’s disease with unknown mechanisms. We hypothesize that the cumulative genomic risk for major depressive disorder may be a candidate cause for the increased conversion risk. Here, we aimed to investigate the predictive effect of the polygenic risk scores of major depressive disorder-specific genetic variants (PRSsMDD) on the conversion from non-depressed amnestic mild cognitive impairment to Alzheimer’s disease, and its underlying neurobiological mechanisms. The PRSsMDD could predict the conversion from amnestic mild cognitive impairment to Alzheimer’s disease, and amnestic mild cognitive impairment patients with high risk scores showed 16.25% higher conversion rate than those with low risk. The PRSsMDD was correlated with the left hippocampal volume, which was found to mediate the predictive effect of the PRSsMDD on the conversion of amnestic mild cognitive impairment. The major depressive disorder-specific genetic variants were mapped into genes using different strategies, and then enrichment analyses and protein–protein interaction network analysis revealed that these genes were involved in developmental process and amyloid-beta binding. They showed temporal-specific expression in the hippocampus in middle and late foetal developmental periods. Cell type-specific expression analysis of these genes demonstrated significant over-representation in the pyramidal neurons and interneurons in the hippocampus. These cross-scale neurobiological analyses and functional annotations indicate that major depressive disorder-specific genetic variants may increase the conversion from amnestic mild cognitive impairment to Alzheimer’s disease by modulating the early hippocampal development and amyloid-beta binding. The PRSsMDD could be used as a complementary measure to select patients with amnestic mild cognitive impairment with high conversion risk to Alzheimer’s disease.
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Schürhoff, F., A. Laguerre, H. Fisher, B. Etain, A. Méary, C. Soussy, A. Szöke y M. Leboyer. "Self-reported childhood trauma correlates with schizotypal measures in schizophrenia but not bipolar pedigrees". Psychological Medicine 39, n.º 3 (30 de junio de 2008): 365–70. http://dx.doi.org/10.1017/s0033291708003905.
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BackgroundStrong evidence supports the association between childhood trauma and psychotic disorders. In two different high-risk populations, we looked for a correlation between the magnitude of schizotypal dimensions and the importance of self-reported childhood trauma.MethodA sample of 138 unaffected first-degree relatives was recruited (67 relatives of schizophrenic probands and 71 relatives of bipolar probands). The relationship between schizotypal dimensions and childhood trauma scores was analyzed by partial correlations.ResultsA positive correlation was found between childhood trauma scores and total schizotypal scores in first-degree relatives of schizophrenic subjects but not in first-degree relatives of bipolar probands. This correlation was primarily due to a strong association with the positive dimension of schizotypy.ConclusionsThe significant correlation between childhood trauma and schizotypal dimensions in subjects at high genetic risk for schizophrenia suggests that susceptibility genes for schizophrenia may interact with childhood trauma to induce the emergence of schizotypal dimensions, mainly positive psychotic features.
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Bang, Minji, Jin Young Park, Kyung Ran Kim, Su Young Lee, Yun Young Song, Jee In Kang, Eun Lee y Suk Kyoon An. "Psychotic conversion of individuals at ultra‐high risk for psychosis: The potential roles of schizotypy and basic symptoms". Early Intervention in Psychiatry 13, n.º 3 (8 de diciembre de 2017): 546–54. http://dx.doi.org/10.1111/eip.12518.
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Fusar-Poli, P., M. Byrne, S. Badger, L. R. Valmaggia y P. K. McGuire. "Outreach and support in South London (OASIS), 2001–2011: Ten years of early diagnosis and treatment for young individuals at high clinical risk for psychosis". European Psychiatry 28, n.º 5 (junio de 2013): 315–26. http://dx.doi.org/10.1016/j.eurpsy.2012.08.002.
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AbstractIntroduction:Prevention of psychosis has become a major objective of modern clinical psychiatry. An increasing number of new services have been established in Europe and in the world. The OASIS team has become an established model where clinical practice and research are fully integrated in the field of preventative interventions in psychosis.Method:Comprehensive analysis of different clinical and service measures describing the 2001–2011 implementation of the OASIS team.Results:Over the last decade, the OASIS team has received a total of 1102 referrals, mostly young males from ethnic minorities. After the assessment, 35% were diagnosed with an At Risk Mental State (ARMS) while 32% were already psychotic. Within the ARMS, 70% met the inclusion criteria for the attenuated psychotic symptoms subgroup, 1% met the inclusion criteria for the genetic deterioration syndrome, 9% met inclusion criteria for a brief and self-limited intermittent psychotic episode and the others met inclusion criteria for more than one subgroup. Most of them had at least one comorbid diagnosis, mainly relating to anxiety and depressive domains. The majority of the OASIS clients received cognitive behavioural therapy alone or in combination with antidepressants/antipsychotics. Over the 2-year follow-up time, 44 subjects (15.2%) developed a frank psychotic episode.Conclusions:The OASIS service represents one of the largest and most established prodromal services in the world. The burden of research evidence and the translational impact produced on the clinical practice support the OASIS as a model for the development of similar services.
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Fusar-Poli, P., M. Cappucciati, G. Rutigliano, T. Y. Lee, Q. Beverly, I. Bonoldi, J. Lelli et al. "Towards a Standard Psychometric Diagnostic Interview for Subjects at Ultra High Risk of Psychosis: CAARMS versus SIPS". Psychiatry Journal 2016 (2016): 1–11. http://dx.doi.org/10.1155/2016/7146341.
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Background. Several psychometric instruments are available for the diagnostic interview of subjects at ultra high risk (UHR) of psychosis. Their diagnostic comparability is unknown.Methods. All referrals to the OASIS (London) or CAMEO (Cambridgeshire) UHR services from May 13 to Dec 14 were interviewed for a UHR state using both the CAARMS 12/2006 and the SIPS 5.0. Percent overall agreement, kappa, the McNemar-Bowkerχ2test, equipercentile methods, and residual analyses were used to investigate diagnostic outcomes and symptoms severity or frequency. A conversion algorithm (CONVERT) was validated in an independent UHR sample from the Seoul Youth Clinic (Seoul).Results. There was overall substantial CAARMS-versus-SIPS agreement in the identification of UHR subjects (n=212, percent overall agreement = 86%; kappa = 0.781, 95% CI from 0.684 to 0.878; McNemar-Bowker test = 0.069), with the exception of the brief limited intermittent psychotic symptoms (BLIPS) subgroup. Equipercentile-linking table linked symptoms severity and frequency across the CAARMS and SIPS. The conversion algorithm was validated in 93 UHR subjects, showing excellent diagnostic accuracy (CAARMS to SIPS: ROC area 0.929; SIPS to CAARMS: ROC area 0.903).Conclusions. This study provides initial comparability data between CAARMS and SIPS and will inform ongoing multicentre studies and clinical guidelines for the UHR psychometric diagnostic interview.
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Çukurova, M. y A. Özdemir. "The Investigation of Cognitive Functions and Clinical High Risk Status for Psychosis in First-Degree Relatives of Patients with Substance Induced Psychotic Disorder". European Psychiatry 65, S1 (junio de 2022): S203. http://dx.doi.org/10.1192/j.eurpsy.2022.533.
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Introduction The etiology of substance-induced psychotic disorder (SIPD) is an important research area to study. Objectives It is aimed to investigate clinical risk status for psychosis, schizotypal features and neurocognitive functions in siblings of the patients who have been diagnosed as SIPD and who have no family history of psychotic spectrum disorder. Methods This study included 41 healthy siblings of patients who have been diagnosed as SIPD according to DSM-V and 41 healthy controls without family history of psychiatric disorders (matched on age, gender, and years of education). The data collected with sociodemographic and clinical data form, Digid Span Test, Trail Making Test A, Trail Making Test B, Verbal Fluency Test and Stroop Test, Comprehensive Assesment of At-Risk Mental States (CAARMS) and Structured Interview for Schizotypy-Revised. Results It is determined that %41.5 of siblings and %7.3 of healthy controls are in one of the clinical high risk groups for psychosis according to CAARMS. There is significant difference in Trail Making Test A error and Trail Making Test B error and correction, verbal fluency test- lexical fluency-perseveration mean scores between siblings of patients and healthy controls. Conclusions Siblings of patients with SIPD have more schizotypal features than healthy control group and they take part more frequent in one of high risk group for psychosis. Schizotypal features are known as trait factor and show genetic predisposition. Siblings who are in high risk groups have more schizotypal features and it may point that predisposition to psychosis is more related to underlying genetic predisposition than environmental factors and social stressors. Disclosure No significant relationships.
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Dahdouh Guermouche, A., J. Prados, M. Guipponi, F. Bena, L. Stenz, B. Semaoune, S. Antonarakis y H. Hamamy. "Consangunity and psychosis in Algeria. A family study". European Psychiatry 30, S2 (noviembre de 2015): S85. http://dx.doi.org/10.1016/j.eurpsy.2015.09.373.
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Several studies have affirmed the existence of a strong and complex genetic component in the determination of psychotic disorders. However, the genetic architecture of these disorders remains poorly understood. GWAS studies conducted over the past decade have identified some associations to low effect, and the major part of this heritability remains unexplained, thus calling into question the hypothesis of “common disease – common variant” for model involving a large number of rare variants. Family studies of extended pedigrees selected from geographical isolate can be a powerful approach in identifying rare genetic variants of complex diseases such as psychotic disorders. Here, we studied four multigenerational families in which co-exist psychotic and mood disorders and a high rate of consanguinity, identified in the northwest of Algeria. This case-control study aimed to characterize new rare genetic variants responsible for psychosis. These families have received complete clinical and genealogical investigations, genome wide analysis that were performed in the laboratory of medical genetics in the university hospital of Geneva. A genome wide research CNVs using Agilent Human Genome CGH Microarray Kit 44 K, covering 45 subjects including 20 patients and in a control population of 55 individuals. Three CNVs that had never been reported to date have been identified in one of four families and validated by two techniques. It is the dup 4q26, and 16q23.1 del del21q21. These CNVs are transmitted by either parent line, suggesting a cumulative effect on the risk of psychotic disorders. Further analyzes using pan-genomic linkage analysis using GWAS chip (Illumina Human 660 W-Quad v1.0 Breadchip) and complete WES (by GAIIx Illumina/HiSeq 2000) were performed in some related individuals to search other mutations may explain the appearance of the phenotype in this population.
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Addington, Jean, Jacqueline Stowkowy, Lu Liu, Kristin S. Cadenhead, Tyrone D. Cannon, Barbara A. Cornblatt, Thomas H. McGlashan et al. "Clinical and functional characteristics of youth at clinical high-risk for psychosis who do not transition to psychosis". Psychological Medicine 49, n.º 10 (4 de septiembre de 2018): 1670–77. http://dx.doi.org/10.1017/s0033291718002258.
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AbstractBackgroundMuch of the interest in youth at clinical high risk (CHR) of psychosis has been in understanding conversion. Recent literature has suggested that less than 25% of those who meet established criteria for being at CHR of psychosis go on to develop a psychotic illness. However, little is known about the outcome of those who do not make the transition to psychosis. The aim of this paper was to examine clinical symptoms and functioning in the second North American Prodrome Longitudinal Study (NAPLS 2) of those individuals whose by the end of 2 years in the study had not developed psychosis.MethodsIn NAPLS-2 278 CHR participants completed 2-year follow-ups and had not made the transition to psychosis. At 2-years the sample was divided into three groups – those whose symptoms were in remission, those who were still symptomatic and those whose symptoms had become more severe.ResultsThere was no difference between those who remitted early in the study compared with those who remitted at one or 2 years. At 2-years, those in remission had fewer symptoms and improved functioning compared with the two symptomatic groups. However, all three groups had poorer social functioning and cognition than healthy controls.ConclusionsA detailed examination of the clinical and functional outcomes of those who did not make the transition to psychosis did not contribute to predicting who may make the transition or who may have an earlier remission of attenuated psychotic symptoms.
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Tepper, Ángeles, Analía Cuiza, Luz María Alliende, Carlos Mena, Juan Pablo Ramirez-Mahaluf, Barbara Iruretagoyena, Claudia Ornstein et al. "Functional Dysconnectivity in Ventral Striatocortical Systems in 22q11.2 Deletion Syndrome". Schizophrenia Bulletin 48, n.º 2 (21 de diciembre de 2021): 485–94. http://dx.doi.org/10.1093/schbul/sbab139.
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Abstract 22q11.2 deletion syndrome (22q11.2DS) is a genetic neurodevelopmental disorder that represents one of the greatest known risk factors for psychosis. Previous studies in psychotic subjects without the deletion have identified a dopaminergic dysfunction in striatal regions, and dysconnectivity of striatocortical systems, as an important mechanism in the emergence of psychosis. Here, we used resting-state functional MRI to examine striatocortical functional connectivity in 22q11.2DS patients. We used a 2 × 2 factorial design including 125 subjects (55 healthy controls, 28 22q11.2DS patients without a history of psychosis, 10 22q11.2DS patients with a history of psychosis, and 32 subjects with a history of psychosis without the deletion), allowing us to identify network effects related to the deletion and to the presence of psychosis. In line with previous results from psychotic patients without 22q11.2DS, we found that there was a dorsal to ventral gradient of hypo- to hyperstriatocortical connectivity related to psychosis across both patient groups. The 22q11.2DS was additionally associated with abnormal functional connectivity in ventral striatocortical networks, with no significant differences identified in the dorsal system. Abnormalities in the ventral striatocortical system observed in these individuals with high genetic risk to psychosis may thus reflect a marker of illness risk.
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Okutucu, Fatma Tuygar. "DiGeorge Syndrome With Atypical Psychotic Symptoms: The Need for a Multidisciplinary Methodology". Psychiatric Annals 53, n.º 9 (septiembre de 2023): 432–35. http://dx.doi.org/10.3928/00485713-20230824-02.
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DiGeorge syndrome (DGS), known as 22q11.2 deletion syndrome or velocardiofacial syndrome, is one of the most common microdeletion syndromes in humans. Developmental delay, intellectual disability, congenital cardiac and gross vessel anomalies, hypocalcemia, and hearing loss may be seen and characterized by dysmorphic facial features. The syndrome has high risk for psychiatric disorders, specifically intellectual disability and psychotic disorders. Dysmorphic features may be overlooked and the diagnosis may be delayed for years. We explore a case of DGS with intellectual disability and atypical psychotic symptoms. A 19-year-old female patient had atypical psychotic symptoms, dysmorphic facial features, and unilateral hearing loss. Intellectual disability was detected in the IQ test evaluation. A detailed investigation and genetic evaluation resulted in a diagnosis of DGS. This case report highlights the variable clinical presentation of DGS in each patient and the need for a multidisciplinary methodology to diagnose and treat it. [ Psychiatr Ann . 2023;53(9):432–435.]
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Moreno, L., J. Valero, A. M. Gaviria y A. Labad. "Is attention related with pathological personality in siblings of psychotic patients?" European Psychiatry 26, S2 (marzo de 2011): 1455. http://dx.doi.org/10.1016/s0924-9338(11)73160-1.
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IntroductionImpaired sustained and selective attention have been seen as vulnerability factors to psychotic disorders. Relatives of psychotic patients are a risk population for psychosis, and previous studies have shown that they displayed more attentional deficits compared with healthy controls. Additionally, relatives have more pathological personality and schizotypy, the least considered also to be the expression of the genetic vulnerability to schizophrenia. There are few studies that relate attention to personality factors in relatives of psychotic patients.AimsTo compare attentional performance of siblings of psychotic patients with those of healthy controls, taking into account their pathological and schizotypal personality.MethodsThe Spanish version of the SPQ and the DAPP-BQ were administered to a sample of 51 subjects that were divided into four groups by a hierarchical cluster analysis: siblings with high pathological personality (SHPP), siblings with low pathological personality (SLPP), controls with high pathological personality (CHPP), and controls with low pathological personality (CLPP). In all the subjects we assessed a sustained attention index (SUA) and a selective attention index (SEA). We compared the performance of the four groups on these attentional indexes.ResultsWe found that SHPP had worse performance on sustained attention compared with CLPP. Specifically this difference was in the reaction time item of the SUA.ConclusionsThe high schizotypy and pathological personality had an influence on sustained attentional performance in the siblings of patients with psychosis, but not in the healthy controls.
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Kebir, O., B. Chaumette y M. O. Krebs. "Longitudinal study of methylome profiles in subjects with psychosis and/or schizophrenia". European Psychiatry 33, S1 (marzo de 2016): S30. http://dx.doi.org/10.1016/j.eurpsy.2016.01.855.
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BackgroundSchizophrenia is a complex disorder involving both genetic and environmental factors. Epigenetic is a growing theory to explain these interactions at a molecular level. It is well-known that schizophrenia begins with prodromal symptoms and patients undergoing subthreshold symptoms are named ultra-high risk (UHR) subjects. Therapeutic and prognostic attitude remain challenging for this population. According to the model of the gene-environment interactions, the psychotic transition in adolescence could be related to epigenetic changes during the psychotic transition.MethodsWe designed and performed the first longitudinal study about whole-genome DNA methylation changes. Thirty-nine UHR patients were recruited in specialized center C’JAAD - Centre Hospitalier Ste Anne - Paris (France). During follow-up, 14 of them became psychotic (converters) according to the validated scale CAARMS. Initial and final methylation were investigated by Infinium Human Methylation450 BeadChip for 450,000 CpG after bisulfite conversion.ResultsThe psychotic transition was not associated with global methylation changes. Linear models failed to identify CpG and genes significantly associated with psychotic transition after Bonferroni correction. Analyses of the top results provided a cluster, which could classify perfectly converters and non-converters. These genes of interest are over-represented in biological pathways with relevance for psychotic physiopathology. Individual analyses highlighted the biological heterogeneity of the psychotic transition.ConclusionImproving physiopathological understanding of psychotic transition is a current challenge to identify biomarkers and to develop targeted preventive interventions available in clinical practice for UHR subjects. The epigenetic processes and in particular DNA methylation could be interesting factors.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Richter, Anja, Evangelos Vassos, Matthew J. Kempton, Mark van der Gaag, Lieuwe de Haan, Barnaby Nelson, Anita Riecher-Rössler et al. "S175. CLINICAL OUTCOMES IN PEOPLE AT HIGH RISK FOR PSYCHOSIS RELATED TO INTERACTIONS BETWEEN POLYGENIC RISK SCORES AND CHILDHOOD ADVERSITY". Schizophrenia Bulletin 46, Supplement_1 (abril de 2020): S104. http://dx.doi.org/10.1093/schbul/sbaa031.241.
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Abstract Background Genetic vulnerability to psychosis is polygenic, involving multiple genes with small individual effects (Psychiatric Genomics Consortium (PGC), 2014). The risk of psychosis is also related to environmental factors, such as childhood trauma (Lardinois et al, 2011). Although the onset of psychosis is thought to result from the interaction of genetic and environmental risk factors (Walker & Diforio, 1997), the extent to which the influence of childhood trauma depends on genetic susceptibility remains unclear. We sought to address this issue in a large prospective study of people at clinical high risk (CHR) for psychosis. These individuals present with psychotic and affective symptoms, and are at increased risk of developing both schizophreniform and affective psychoses. Methods We studied subjects of European ancestry, drawn from EU-GEI, a large multi-centre prospective study of people at CHR for psychosis. At baseline, DNA was obtained from subjects who met the CAARMS criteria for the CHR state (n=266) and healthy controls (HC; n=42). Childhood trauma was assessed using the childhood trauma questionnaire (CTQ), which comprises 5 subdomains: emotional abuse, physical abuse, sexual abuse, physical neglect, and emotional neglect. Polygenic risk scores (PRSs) for schizophrenia (SCZ), bipolar disorder (BD) and major depressive disorder (MDD) were constructed separately, using results from meta-analyses by the corresponding Disorder Working Groups of the PGC. The CHR subjects were clinically monitored for up to 5 years and clinical outcomes were assessed in terms of transition to psychosis (as defined by the CAARMS), remission from the CHR state (subject no longer meets CAARMS inclusion criteria) and level of functioning (GAF Disability Scale). Logistic regression models were used to investigate the association between each PRSs and childhood trauma as predictors of transition and remission, adjusted by population stratification using the first 10 principal components, age, sex and site. All findings are reported at p<0.017, Bonferroni-corrected for the 3 PRSs. Results Within the CHR sample, the onset of psychosis during follow up was related to interactions between the BD PRS and the total childhood trauma score (OR=0.959, 95% CI 0.930–0.988, p=0.006), and between the BD PRS and physical abuse (OR=0.787, 95% CI 0.689–0.900, p<0.001). Remission from the CHR state was related to an interaction between the SCZ PRS and childhood sexual abuse (OR: 1.110, 95% CI 1.004–1.226, p=0.041). Discussion These data indicate that clinical outcomes in CHR subjects are related to interactions between the polygenic risk for psychotic disorders and childhood adversity. The measurement of interactions between genomic and environmental risk factors may help to predict individual outcomes in people at high risk in a clinical setting.
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Addington, J. y M. Barbato. "The role of cognitive functioning in the outcome of those at clinical high risk for developing psychosis". Epidemiology and Psychiatric Sciences 21, n.º 4 (30 de julio de 2012): 335–42. http://dx.doi.org/10.1017/s204579601200042x.
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Although it is well established that cognitive impairment is a common feature of schizophrenia, only recently has cognitive functioning been prospectively studied in individuals at clinical high risk (CHR) for developing psychosis. To date, both cross-sectional and longitudinal studies have been conducted in the CHR population and in the context of later conversion to psychosis. A comprehensive review of the literature suggests that CHR individuals have general and specific baseline cognitive deficits compared to healthy controls. As a group, their cognitive course, tends to remain stable over time and in this way does not differ from healthy controls. For those who go on to develop a full-blown psychotic illness compared to those who do not convert, there appeared to be minimal differences at baseline with respect to cognition, although over time the converters may show deterioration in certain cognitive abilities compared to the non-converters. However, for many cognitive domains results are mixed, and may result from methodological limitations.
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Fonseca-Pedrero, E., M. Debbané, M. Schneider, D. Badoud y S. Eliez. "Schizotypal traits in adolescents with 22q11.2 deletion syndrome: validity, reliability and risk for psychosis". Psychological Medicine 46, n.º 5 (16 de diciembre de 2015): 1005–13. http://dx.doi.org/10.1017/s0033291715002500.
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BackgroundVery little is known about the phenotypic expression of schizotypal traits in individuals with 22q11.2 deletion syndrome (22q11DS). The main purpose was to analyse the factorial structure, internal consistency and temporal stability of schizotypal traits, as well as their associations with prodromal states and clinical psychotic symptoms in adolescents with 22q11DS.MethodThe sample comprised 61 adolescents with 22q11DS (mean = 14.95 years, s.d. = 2.13; n = 24 at follow-up). An age-matched comparison group (n = 61, mean = 15.44 years, s.d. = 1.76) was also included. The Schizotypal Personality Questionnaire (SPQ), the Structured Interview for Prodromal Syndromes, the Positive and Negative Syndrome Scale, and the Brief Psychiatric Rating Scale were used.ResultsAdolescents with 22q11DS scored higher than the control group on the interpersonal dimension and suspiciousness subscale of the SPQ. The analysis of the internal structure of the SPQ in the sample of 22q11DS participants yielded a three-component solution (cognitive–perceptual, interpersonal, and disorganized). In addition, internal consistency coefficients ranged between 0.63 and 0.91. The schizotypal traits were highly stable across a 3.6-year interval, and ranged from 0.50 to 0.63. Self-reported schizotypal traits correlated with interview-based ratings of prodromal states and psychotic symptoms.ConclusionsThese results indicate that the SPQ may be a valid tool to assess schizotypal traits in adolescents with 22q11DS. The identification of a reliable self-report instrument for use in individuals with learning disabilities and at genetic high risk for psychosis could be useful in clinical and research settings. Assessment of schizotypal traits may be used as a distal risk marker and in a close-in strategy in high-risk genetic samples to enhance the possibility of early detection of psychosis.
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WAHLBERG, K. E., L. C. WYNNE, H. OJA, P. KESKITALO, H. ANAIS-TANNER, P. KOISTINEN, T. TARVAINEN et al. "Thought Disorder Index of Finnish adoptees and communication deviance of their adoptive parents". Psychological Medicine 30, n.º 1 (enero de 2000): 127–36. http://dx.doi.org/10.1017/s0033291799001415.
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Background. Diverse forms of thought disorder, as measured by the Thought Disorder Index (TDI), are found in many conditions other than schizophrenia. Certain thought disorder categories are primarily manifest during psychotic schizophrenic episodes. The present study examined whether forms of thought disorder qualify as trait indicators of vulnerability to schizophrenia in persons who are not clinically ill, and whether these features could be linked to genetic or environmental risk or to genotype–environment interactions. The Finnish Adoptive Study of Schizophrenia provided an opportunity to disentangle these issues.Methods. Rorschach records of Finnish adoptees at genetic high risk but without schizophrenia-related clinical diagnoses (N = 56) and control adoptees at low genetic risk (N = 95) were blindly and reliably scored for the Thought Disorder Index (TDI). Communication deviance (CD), a measure of the rearing environment, was independently obtained from the adoptive parents.Results. The differences in total TDI between high-risk and control adoptees were not statistically significant. However, TDI subscales for Fluid Thinking and Idiosyncratic Verbalization were more frequent in high-risk adoptees. When Rorschach CD of the adoptive rearing parents was introduced as a continuous predictor variable, the odds ratio for the Idiosyncratic Verbalization component of the TDI of the high-risk adoptees was significantly higher than for the control adoptees.Conclusions. Specific categories of subsyndromal thought disorder appear to qualify as vulnerability indicators for schizophrenia. Genetic risk and rearing-parent communication patterns significantly interact as a joint effect that differentiates adopted-away offspring of schizophrenic mothers from control adopted-away offspring.
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Salokangas, R., T. Svirskis, M. Heinimaa, J. Klosterkötter, S. Ruhrmann, H. Graf von Reventlow, D. Linszen, P. Dingemans, M. Birchwood y P. Patterson. "Subjective quality of life and its changes in patients at-risk for psychosis results of the EPOS study". European Psychiatry 26, S2 (marzo de 2011): 2039. http://dx.doi.org/10.1016/s0924-9338(11)73742-7.
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ObjectivesIn the European Prediction of Psychosis Study (EPOS) a large sample of young patients at high risk of psychosis (HR) were examined and their conversion rate to psychosis during 18 months follow-up was estimated. This presentation describes quality of life (QoL) and its changes in patients at risk of psychosis who did or did not convert to psychosis.MethodsIn all, 245 young HR patients were recruited and followed for 9 and 18 months. Risk of psychosis was defined by occurrence of basic symptoms (BS), attenuated psychotic symptoms (ATP), brief, limited or intermittent psychotic symptoms (BLIPS) or familial risk plus reduced functioning (FR-RF). QoL was assessed at baseline and at 9 and 18 months’ follow-ups, and analysed in the HR-patients who converted (HR-P; n = 40) or did not converted to psychosis (HR-NP; n = 205).ResultsThere were no differences in the course of QoL between the HR-P and HR-NP patients. Of the inclusion criteria, only BS associated with poor QoL at baseline. Among HR-NP subjects, depressive symptoms associated with QoL at baseline and predicted poor QoL at 9 and 18 month follow-ups.ConclusionsQoL of the HR-NP patients is as poor as that of the HR-P. From the QoL point of view, all HR patients require intensive treatment intervention from the first contact on. Especially, depressive disorders need to be treated vigorously.
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Carr, Vaughan, Sean Halpin, Namson Lau, Sian O'Brien, Jane Beckmann y Terry Lewin. "A Risk Factor Screening and Assessment Protocol for Schizophrenia and Related Psychosis". Australian & New Zealand Journal of Psychiatry 34, n.º 1_suppl (febrero de 2000): A170—A180. http://dx.doi.org/10.1177/000486740003401s26.
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Objective The Psychological Assistance Service (PAS) opened in Newcastle, New South Wales in 1997 as a clinical service for the assessment and treatment of young people at high risk of psychosis and those experiencing a first psychotic episode. The aim of this paper is to describe the assessment protocol of PAS, which is strongly influenced by the neurodevelopmental perspective on early onset psychosis. Method The systematic assessment of patients referred to PAS using a protocol over a 2 week period is described. The protocol includes a narrative history, structured diagnostic interview, quantitative assessment of symptoms and other clinical features, a neurological examination and comprehensive neuropsychological test battery. Results The clinic has received over 250 referrals in a 2 year period and accepted 116 patients for a full assessment, of whom 60 were deemed to be ‘at-risk’ of psychosis and 56 were experiencing their first psychotic episode. Both groups were similar with respect to gender and there were minor age differences. The first-episode group experienced more reality distortion, schizotypal and negative symptoms. While both groups showed some neuropsychological and neurological impairment, there were no statistically significant differences between the groups on these variables except for a test of executive functioning in which the first-episode group was more impaired than the ‘at-risk’ group. A low rate of conversion to psychosis occurred in the ‘at-risk’ group. Conclusions The minor differences between the two groups may have been related to relatively small sample sizes, although some similarities between the groups were to be expected. The low rate of conversion to psychosis in the ‘at-risk’ group is discussed. Further analyses using larger samples are necessary to determine the validity of the various ‘at-risk’ categories and this will involve following a sufficiently large sample over an adequate time. The most efficient way of doing this would be to pool data across centres with comparable early intervention programs.