scholarly journals A Longitudinal Approach to Biological Psychiatric Research: The PsyCourse Study

2017 ◽  
Author(s):  
Monika Budde ◽  
Heike Anderson-Schmidt ◽  
Katrin Gade ◽  
Daniela Reich-Erkelenz ◽  
Kristina Adorjan ◽  
...  
Keyword(s):  
Psychotic Disorders ◽  
Diagnostic Group ◽  
Psychiatric Research ◽  
Risk Scores ◽  
Psychotic Symptoms ◽  
Diagnostic Systems ◽  
Global Functioning ◽  
Polygenic Risk ◽  
First Results ◽  
Present Design

In current diagnostic systems, schizophrenia and bipolar disorder are still conceptualized as distinct categorical entities. Recently, both clinical and genetic evidence have challenged this Kraepelinian dichotomy. There are only few longitudinal studies addressing the potential overlaps between these conditions. Here, we present design and first results of the PsyCourse study, an ongoing transdiagnostic study of the affective-to-psychotic continuum that combines longitudinal deep phenotyping and dimensional assessment of psychopathology with an extensive collection of biomaterial. Within the DSM-IV framework, we compare two broad diagnostic groups: one consisting of predominantly affective and one of predominantly psychotic disorders. Depressive, manic, and psychotic symptoms as well as global functioning over time were analyzed. Furthermore, we explore the effects of polygenic risk scores for schizophrenia on diagnostic group membership and address their effects on non-participation in follow-up visits. While phenotypic results show differences in both current psychotic and manic symptoms, depressive symptoms did not vary between both groups. Polygenic risk scores for schizophrenia significantly explained part of the variability of the diagnostic group. Furthermore, there was a trend that a higher polygenic loading for schizophrenia was associated with attrition. Because of its unique properties, the PsyCourse study presents a prime resource for the interrogation of complex genotype-phenotype relationships.

The use of Polygenic Risk Scores to Inform Aetiology of Mood and Psychotic Disorders

2017 ◽  
Vol 41 (S1) ◽  
pp. S166-S166
Author(s):  
J. Harrison ◽  
S. Mistry
Keyword(s):  
Bipolar Disorder ◽  
Genetic Basis ◽  
Psychotic Disorders ◽  
Mental Illnesses ◽  
Risk Scores ◽  
Psychotic Symptoms ◽  
Polygenic Risk ◽  
Genetic Overlap ◽  
Competing Interest

IntroductionPolygenic risk scores (PRS) incorporate many small genetic markers that are associated with conditions. This technique was first used to investigate mental illnesses in 2009. Since then, it has been widely used.ObjectivesWe wanted to explore how PRS have been used to the study the aetiology of psychosis, schizophrenia, bipolar disorder and depression.AimsWe aimed to conduct a systematic review, identifying studies that have examined associations between PRS for bipolar disorder, schizophrenia/psychosis and depression and psychopathology-related outcome measures.MethodsWe searched EMBASE, Medline and PsychInfo from 06/08/2009 to 14/03/2016. We hand-searched the reference lists of related papers.ResultsAfter removing duplicates, the search yielded 1043 publications. When irrelevant articles were excluded, 33 articles remained. We found 24 studies using schizophrenia PRS, three using bipolar PRS and nine using depression PRS. Many studies successfully used PRS to predict case/control status. Some studies showed associations between PRS and diagnostic sub-categories. A range of clinical phenotypes and symptoms has been explored. For example, specific PRS are associated with cognitive performance in schizophrenia, psychotic symptoms in bipolar disorder, and frequency of episodes of depression. PRS have also demonstrated genetic overlap between mental illnesses. It was difficult to assess the quality of some studies as not all reported sufficient methodological detail.ConclusionsPRS have enabled us to explore the polygenic architecture of mental illness and demonstrate a genetic basis for some observed features. However, they have yet to give insights into the biology, which underpin mental illnesses.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Polygenic Risk Scores for Bipolar Disorders Associated With Worse Global Functioning

2020 ◽  
Vol 87 (9) ◽  
pp. S211
Author(s):  
Alexandre Paim Diaz ◽  
Gabriel Fries ◽  
Joao Quevedo ◽  
Consuelo Walss-Bass ◽  
Marsal Sanches ◽  
...  
Keyword(s):  
Bipolar Disorders ◽  
Risk Scores ◽  
Global Functioning ◽  
Polygenic Risk

scholarly journals Genetic risk for bipolar disorder and schizophrenia predicts structure and function of the ventromedial prefrontal cortex

2021 ◽  
Vol 46 (4) ◽  
pp. E441-E450
Author(s):  
Christoph Abé ◽  
Predrag Petrovic ◽  
William Ossler ◽  
William H. Thompson ◽  
Benny Liberg ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Prefrontal Cortex ◽  
Genetic Risk ◽  
Psychotic Disorders ◽  
Structure And Function ◽  
Ventromedial Prefrontal Cortex ◽  
Risk Scores ◽  
Polygenic Risk ◽  
And Function ◽  
Structural Brain

Background: Bipolar disorder is highly heritable and polygenic. The polygenic risk for bipolar disorder overlaps with that of schizophrenia, and polygenic scores are normally distributed in the population. Bipolar disorder has been associated with structural brain abnormalities, but it is unknown how these are linked to genetic risk factors for psychotic disorders. Methods: We tested whether polygenic risk scores for bipolar disorder and schizophrenia predict structural brain alterations in 98 patients with bipolar disorder and 81 healthy controls. We derived brain cortical thickness, surface area and volume from structural MRI scans. In post-hoc analyses, we correlated polygenic risk with functional hub strength, derived from resting-state functional MRI and brain connectomics. Results: Higher polygenic risk scores for both bipolar disorder and schizophrenia were associated with a thinner ventromedial prefrontal cortex (vmPFC). We found these associations in the combined group, and separately in patients and drug-naive controls. Polygenic risk for bipolar disorder was correlated with the functional hub strength of the vmPFC within the default mode network. Limitations: Polygenic risk is a cumulative measure of genomic burden. Detailed genetic mechanisms underlying brain alterations and their cognitive consequences still need to be determined. Conclusion: Our multimodal neuroimaging study linked genomic burden and brain endophenotype by demonstrating an association between polygenic risk scores for bipolar disorder and schizophrenia and the structure and function of the vmPFC. Our findings suggest that genetic factors might confer risk for psychotic disorders by influencing the integrity of the vmPFC, a brain region involved in self-referential processes and emotional regulation. Our study may also provide an imaging–genetics vulnerability marker that can be used to help identify individuals at risk for developing bipolar disorder.

scholarly journals Negative and disorganized symptoms mediate the relationship between verbal learning and global functioning in adolescents with early-onset psychosis

2020 ◽  
Vol 29 (12) ◽  
pp. 1693-1703 ◽  
Author(s):  
Runar Elle Smelror ◽  
Bjørn Rishovd Rund ◽  
Vera Lonning ◽  
Kjetil Nordbø Jørgensen ◽  
Kirsten Wedervang-Resell ◽  
...  
Keyword(s):  
Early Onset ◽  
Psychotic Disorders ◽  
Five Factor Model ◽  
Verbal Learning ◽  
Psychotic Symptoms ◽  
Point Estimate ◽  
Neurocognitive Deficits ◽  
Global Functioning ◽  
Mediation Effects ◽  
The Relationship

Abstract Neurocognitive deficits are associated with impaired global functioning and psychotic symptoms. However, whether symptoms can mediate the relationship between neurocognition and global functioning in adolescent psychosis is unclear. Here, we investigated if symptoms assessed with the Positive And Negative Syndrome Scale (PANSS), mediated the relationship between neurocognitive performance and global functioning in adolescents with non-affective early-onset psychotic disorders (EOP). Sixty-one adolescent EOP patients (age 12–18 years) from 2 Norwegian clinical cohorts were included. Linear regression models were applied to investigate associations between neurocognitive domains from the MATRICS Consensus Cognitive Battery (MCCB) and global functioning. PANSS symptoms were analyzed using the Wallwork/Fortgang five-factor model. Using the INDIRECT macro for SPSS, mediation effects were tested using bootstrapping with 95% bias corrected confidence intervals. Verbal learning was positively associated with global functioning (P < 0.001) and negatively associated with the disorganized symptom factor (P = 0.002), controlling for age, sex and cohort. Testing of indirect effects, controlling for age, sex and cohort, showed that the Negative (point estimate = 1.56, 95% CI 0.22, 3.47) and Disorganized (point estimate = 1.24, 95% CI 0.05, 3.69) symptom factors significantly mediated the relationship between verbal learning and global functioning. We found that verbal learning, negative and disorganized symptoms influenced global functioning in adolescents with EOP, while reality-distorted positive symptoms did not. These results suggest that assessing these domains in EOP is helpful for planning treatment and rehabilitation programs focusing on functional outcome.

scholarly journals Associations between polygenic liability for schizophrenia and level of psychosis and mood-incongruence in bipolar disorder

2017 ◽  
Author(s):  
Judith Allardyce ◽  
Ganna Leonenko ◽  
Marian Hamshere ◽  
Antonio F. Pardiñas ◽  
Liz Forty ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Logistic Regression ◽  
Multinomial Logistic Regression ◽  
Bipolar Affective Disorder ◽  
Research Network ◽  
Risk Scores ◽  
Psychotic Symptoms ◽  
P Value ◽  
Polygenic Risk ◽  
Psychotic Features

AbstractImportanceBipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed to understand the underlying disease processes/mechanisms.ObjectivesTo investigate the relationship between common-variant liability for schizophrenia, indexed by polygenic risk scores (PRS) and psychotic presentations of BD, using clinical descriptions which consider both occurrence and level of mood-incongruent psychotic features.DesignCase-control design: using multinomial logistic regression, to estimate differential associations of PRS across categories of cases and controls.Settings & Participants4399 BDcases, mean [sd] age-at-interview 46[12] years, of which 2966 were woman (67%) from the BD Research Network (BDRN) were included in the final analyses, with data for 4976 schizophrenia cases and 9012 controls from the Type-1 diabetes genetics consortium and Generation Scotland included for comparison.ExposureStandardised PRS, calculated using alleles with an association p-value threshold < 0.05 in the second Psychiatric Genomics Consortium genome-wide association study of schizophrenia, adjusted for the first 10 population principal components and genotyping-platform.Main outcome measureMultinomial logit models estimated PRS associations with BD stratified by (1) Research Diagnostic Criteria (RDC) BD subtypes (2) Lifetime occurrence of psychosis.(3) Lifetime mood-incongruent psychotic features and (4) ordinal logistic regression examined PRS associations across levels of mood-incongruence. Ratings were derived from the Schedule for Clinical Assessment in Neuropsychiatry interview (SCAN) and the Bipolar Affective Disorder Dimension Scale (BADDS).ResultsAcross clinical phenotypes, there was an exposure-response gradient with the strongest PRS association for schizophrenia (RR=1.94, (95% C.1.1.86, 2.01)), then schizoaffective BD (RR=1.37, (95% C.I. 1.22, 1.54)), BD I (RR= 1.30, (95% C.I. 1.24, 1.36)) and BD II (RR=1.04, (95% C.1. 0.97, 1.11)). Within BD cases, there was an effect gradient, indexed by the nature of psychosis, with prominent mood-incongruent psychotic features having the strongest association (RR=1.46, (95% C.1.1.36, 1.57)), followed by mood-congruent psychosis (RR= 1.24, (95% C.1. 1.17, 1.33)) and lastly, BD cases with no history of psychosis (RR= 1.09, (95% C.1. 1.04, 1.15)).ConclusionWe show for the first time a polygenic-risk gradient, across schizophrenia and bipolar disorder, indexed by the occurrence and level of mood-incongruent psychotic symptoms.

scholarly journals S92. REASONS TO START SMOKING CANNABIS: A CASE CONTROL-ANALYSIS FROM THE EUGEI STUDY

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S69-S69
Author(s):  
Edoardo Spinazzola ◽  
Victoria Rodriguez ◽  
Diego Quattrone ◽  
Giulia Trotta ◽  
Marta Di Forti ◽  
...  
Keyword(s):  
Regression Models ◽  
Psychotic Disorders ◽  
Case Control ◽  
Cannabis Use ◽  
Risk Scores ◽  
First Episode ◽  
Control Analysis ◽  
Multinomial Regression ◽  
Polygenic Risk ◽  
Patterns Of Use

Abstract Background Studies have shown that cannabis can increase the risk of psychosis from 1.7 to 3.9 times. Both frequency and potency seem to contribute to differences in the incidence of psychosis across Europe. Despite this evidence, sceptics argue that that the association between cannabis use and psychotic disorders could be explained by: (a) subjects who start experiencing psychosis use cannabis as a form of self-medication; (b) the co-morbid effect of other psychotogenic drugs (e.g., amphetamines); or (c) there is a common genetic vulnerability between cannabis use and psychosis. Thus, we aim to analyse: 1) reported reasons to start using cannabis, 2) if these predict differences in patterns of use (frequency and potency), 3) the association of both reasons to start and pattern of use with PRS for Schizophrenia, as it can explain whether patients with a higher genetic burden also start smoking cannabis after experiencing a higher psychological discomfort. Methods Using data from the multicentric EUGEI First-Episode Psychosis (FEP) case-control study we examined differences in reasons to start using cannabis between cases and controls. Data were obtained from the Cannabis Experiences Questionnaire modified version. Logistic regression models were used to test if reason to start predicted different patterns of use. Finally, we used regression to test if Polygenic risk scores for schizophrenia (SZ PRS) explained variance in reasons to start. Results Up to 85% of controls compared to 68% of FEP started using cannabis because either friends or family were using it. Instead, 18% of cases started using cannabis to feel better compared 5% of controls, reporting the 13.4% of cases and 10.3% of controls having start due to “other reasons”. Regression models showed that being a case was positively associated with starting use in order to feel better (RRR 4.67, z=7.58, p&lt;0.001), remaining significant after adjusting for gender, age, ethnicity or site. We did not find evidence of an association between start using cannabis “to feel better” and potency nor in cases or controls. We found an association for both cases and controls between those who started smoking to feel better and the frequency of use following a gradient from “more than once a week” to “daily”. Using cannabis “to feel better” was associated with a 4 times increase in the risk (RRR=4.45 95% CI 1.85 – 10.72) of using it daily in controls and 3 times increase (RRR= 3.11 95% CI 1.81 – 5.35) in FEP. Multinomial regression showed that reasons to start did not change according to Schizophrenia PRS, with those starting because a family member was using cannabis (RRR =1 95% CI 0.38 – 2.62) and those starting to feel better (RRR = 1.05 95% CI 0.47 – 2.33) not being at higher polygenic risk compared with those starting because their friends were using cannabis. Discussion These preliminary findings show that a higher proportion of patients with psychosis than controls start using cannabis as a way to make them feel better, although they are a minority. Furthermore, both cases and controls that started smoking “to feel better” presented higher chances to start smoking more frequently. Lastly, PRS did not predict the reasons to start smoking cannabis.

scholarly journals Co-occurring Hydrocephalus and Polygenic Risk in Autism Spectrum Disorder: A Danish Population-based Cohort Study

2020 ◽  
Author(s):  
Tina Nørgaard Munch ◽  
Paula Hedley ◽  
Christian Munch Hagen ◽  
Marie Bækvad-Hansen ◽  
Jonas Bybjerg-Grauholm ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Psychiatric Disorders ◽  
Population Based ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Psychiatric Research ◽  
Risk Scores ◽  
Danish Population ◽  
Polygenic Risk ◽  
Population Controls

Abstract Background The association between autism spectrum disorder and hydrocephalus is not well understood, despite demonstrated links between autism spectrum disorder and cerebrospinal fluid abnormalities. Based on the hypothesis that autism spectrum disorder and hydrocephalus may, at least in some cases, be two manifestations of a shared congenital brain pathology, we investigated the potential association between autism spectrum disorder and hydrocephalus in a large Danish population-based cohort, and whether the polygenic risk scores for autism spectrum disorder changed as a function of the presence of hydrocephalus. Methods Patients and controls were obtained from the Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH2012 case-cohort, which includes all patients with selected psychiatric disorders born in Denmark 1981–2005 along with randomly selected population controls (end of follow-up, December 31, 2016). The associations between individual psychiatric disorders and hydrocephalus were estimated using binary logistic regression with adjustment for age and sex. Polygenic risk scores for autism spectrum disorder were used to compare the genetic architecture of autism spectrum disorder as a function of the presence of hydrocephalus. Results The cohort consisted of 86,571 individuals, of which 14,654 were diagnosed with autism spectrum disorder, 28,606 were population controls, and the remaining were diagnosed with other psychiatric disorders. We identified 201 hydrocephalus cases; 68 among autism spectrum disorder patients and 40 among controls (OR 3.77, 95% CI 2.48–5.78). The autism spectrum disorder-hydrocephalus association was significant over the entire subgroup spectrum of autism spectrum disorder. The presence of hydrocephalus did not markedly influence the polygenic risk scores in patients with autism spectrum disorder, which may indicate overlapping genetic architectures or other common aetiology. Conclusions Given the very strong association, we suggest that patients with autism spectrum disorder should be evaluated for co-occurring hydrocephalus on a routine basis as timely neurosurgical intervention is important. Further clarification of the genetic aetiology of both diseases, may help in elucidating shared genetic pathways between autism spectrum disorder and hydrocephalus, and it may elucidate the role of abnormal CSF dynamics in the pathogenesis of autism spectrum disorders.

scholarly journals Psychotic-like experiences, polygenic risk scores for schizophrenia and structural properties of the salience, default mode and central-executive networks in healthy participants from UK Biobank

2019 ◽  
Author(s):  
C. Alloza ◽  
M. Blesa-Cábez ◽  
M.E. Bastin ◽  
J.W. Madole ◽  
C.R. Buchanan ◽  
...  
Keyword(s):  
Cortical Thickness ◽  
Large Population ◽  
Central Executive ◽  
Auditory Hallucinations ◽  
Risk Scores ◽  
Psychotic Symptoms ◽  
Polygenic Risk ◽  
Default Mode ◽  
Healthy Participants ◽  
Clinical Populations

AbstractSchizophrenia is a highly heritable disorder with considerable phenotypic heterogeneity. Hallmark psychotic symptoms can be considered as existing on a continuum from non-clinical to clinical populations. Assessing genetic risk and psychotic-like experiences (PLEs) in non-clinical populations and their associated neurobiological underpinnings can offer valuable insights into symptom-associated brain mechanisms without the potential confounds of the effects of schizophrenia and its treatment. We leveraged a large population-based cohort (UKBiobank) including information on PLEs, polygenic risk scores for schizophrenia (PRSSZ) and multi-modal brain imaging in combination with network neuroscience. Morphometric (cortical thickness, volume) and water diffusion (fractional anisotropy) properties of the regions and pathways belonging to the salience, default-mode and central-executive networks were computed. We hypothesized that these anatomical concomitants of functional dysconnectivity would be negatively associated with PRSSZ and PLEs. PRSSZ was significantly associated with a latent measure of cortical thickness across the salience network (r = −0.069, p = 0.010) and PLEs showed a number of significant associations with properties of the salience and default mode networks (involving the insular cortex, supramarginal gyrus and pars orbitalis, pFDR < 0.050); with the cortical thickness of the insula largely mediating the relationship between PRSSZ and auditory hallucinations. These results are consistent with the hypothesis that higher genetic liability for schizophrenia is related to subtle disruptions in brain structure and predisposes to PLEs even among healthy participants. In addition, our study suggests that networks engaged during auditory hallucinations show structural associations with PLEs in the general population.

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