Genomic insights into the shared and distinct genetic architecture of cognitive function and schizophrenia.

Cognitive impairment is a major determinant of functional outcomes in schizophrenia, however, understanding of the biological mechanisms underpinning cognitive dysfunction in the disorder remains incomplete. Here, we apply Genomic Structural Equation Modelling to identify latent cognitive factors capturing genetic liabilities to 12 cognitive traits measured in the UK Biobank. We identified three broad factors that underly the genetic correlations between the cognitive tests. We explore the overlap between latent cognitive factors, schizophrenia, and schizophrenia symptom dimensions using a complementary set of statistical approaches, applied to data from the latest schizophrenia genome-wide association study (Ncase = 53,386, Ncontrol = 77,258) and the Thematically Organised Psychosis study (Ncase = 306, Ncontrol = 1060). Global genetic correlations showed a significant moderate negative genetic correlation between each cognitive factor and schizophrenia. Local genetic correlations implicated unique genomic regions underlying the overlap between schizophrenia and each cognitive factor. We found substantial polygenic overlap between each cognitive factor and schizophrenia and biological annotation of the shared loci implicated gene-sets related to neurodevelopment and neuronal function. Lastly, we show that the common genetic determinants of the latent cognitive factors are not predictive of schizophrenia symptoms in the Norwegian Thematically Organized Psychosis cohort. Overall, these findings inform our understanding of cognitive function in schizophrenia by demonstrating important differences in the shared genetic architecture of schizophrenia and cognitive abilities.

Measuring the concurrent validity of the norwegian versions of the psychotic symptom rating scales (PSYRATS) and the positive scale from the positive and negative syndrome scale (PANSS).

PURPOSE: The Positive and Negative Syndrome Scale (PANSS) is one of the most commonly used assessment tools for measuring psychotic symptoms. The Psychotic Symptom Rating Scales (PSYRATS) is another instrument created specifically to assess delusions and auditory hallucinations. However, research on the concurrent validity of PSYRATS with PANSS is limited. There are also inconsistent findings regarding the association between the PSYRATS scales and the PANSS positive scale. The present study aims to add to the understanding of the concurrent validity of these measures, while also incorporating a broader measure of psychiatric symptoms (the symptom scale from the Global Assessment of Functioning Scale - split version, GAF-S). MATERIALS AND METHODS: Spearman's Rank Order Correlations (rho) were calculated for scores from the PANSS positive scale, PSYRATS and GAF-S in a sample of 148 participants with psychotic disorders at three time points. RESULTS: The findings indicate concurrent validity between PSYRATS and PANSS, while the PSYRATS scales were not consistently correlated with GAF-S. CONCLUSIONS: PSYRATS may be a valid assessment tool for evaluating psychotic symptoms. The utility of PSYRATS in research and clinical practice should be investigated further.

Neurocognitive function and delusion severity in schizophrenia spectrum disorders.

The role of basic neurocognitive function in delusions is unclear despite the association to difficulties in reasoning and decision-making. We investigated 812 individuals with schizophrenia spectrum disorders (SSD) using a broad neuropsychological test battery encompassing motor and mental processing speed, working memory, learning and memory, and executive function. Premorbid and current intellectual function was assessed with NART and WASI. Delusion level and other clinical symptoms were measured with the PANSS and GAF. Hierarchical and k-means cluster analysis using standardized scores showed the presence of two separate clusters where the group with the higher delusion level (n = 291) was characterized by more severe neurocognitive deficits (>1.5 standard deviations below the healthy control mean), higher PANSS scores, lower GAF scores, and lower intelligence levels compared to the cluster with mild impairments (n = 521). We conclude that a higher delusion level is related to neurocognitive deficits across domains. Further, the validity of the two separate clusters was indicated by significant differences in clinical symptoms, everyday function, and intellectual ability. Compared to those with mild delusion levels, SSD patients with higher delusion levels seem particularly disadvantaged, with co-occurring general symptoms and lower daily function, underscoring the need for clinical and psychosocial support programs. A limitation of this study is the cross sectional design. Longitudinal studies are needed to determine the causal relationship between delusions and neurocognitive function.

Unraveling the shared genetics of common epilepsies and general cognitive ability.

Objective: Cognitive impairment is prevalent among individuals with epilepsy, and it is possible that genetic factors can underlie this relationship. Here, we investigated the potential shared genetic basis of common epilepsies and general cognitive ability (COG). Methods: We applied linkage disequilibrium score (LDSC) regression, MiXeR and conjunctional false discovery rate (conjFDR) to analyze different aspects of genetic overlap between COG and epilepsies. We used the largest available genome-wide association study data on COG (n = 269,867) and common epilepsies (n = 27,559 cases, 42,436 controls), including the broad phenotypes 'all epilepsy', focal epilepsies and genetic generalized epilepsies (GGE), and as well as specific subtypes. We functionally annotated the identified loci using a variety of biological resources and validated the results in independent samples. Results: Using MiXeR, COG (11.2k variants) was estimated to be almost four times more polygenic than 'all epilepsy', GGE, juvenile myoclonic epilepsy (JME), and childhood absence epilepsy (CAE) (2.5k - 2.9k variants). The other epilepsy phenotypes were insufficiently powered for analysis. We show extensive genetic overlap between COG and epilepsies with significant negative genetic correlations (-0.23 to -0.04). COG was estimated to share 2.9k variants with both GGE and 'all epilepsy', and 2.3k variants with both JME and CAE. Using conjFDR, we identified 66 distinct loci shared between COG and epilepsies, including novel associations for GGE (27), 'all epilepsy' (5), JME (5) and CAE (5). The implicated genes were significantly expressed in multiple brain regions. The results were validated in independent samples (COG: p = 1.0 × 10-14; 'all epilepsy': p = 5.6 × 10-3). Significance: Our study demonstrates a substantial genetic basis shared between epilepsies and COG and identifies novel overlapping genomic loci. Enhancing our understanding of the relationship between epilepsies and COG may lead to the development of novel comorbidity-targeted epilepsy treatments.

The relationship between visual hallucinations, functioning, and suicidality over the course of illness: a 10-year follow-up study in first-episode psychosis.

Visual hallucinations in psychosis are under-researched despite associations with increased illness severity, functional impairments, and suicidality in the few existing studies. Further, there are no long-term longitudinal studies, making it impossible to conclude if these associations are state or trait phenomena. In the current prospective longitudinal study, 184 individuals with first-episode psychosis were assessed with semi-structured clinical interviews and self-report questionnaires at baseline and 10-year follow-up. Participants were grouped based on lifetime experience of visual hallucinations: before or at baseline (VH+/+), first during follow-up (VH-/+), or never (VH-/-). Associations with functioning, suicide attempts, childhood trauma and other markers of illness severity were tested using multinomial logistic regression analysis. At baseline, the VH+/+ group (37.5%), but not VH-/+ (12.5%), had poorer functioning, higher symptom severity, a lower age at onset, and included more individuals with a history of multiple suicide attempts than the VH-/- group (50%). At follow-up, the VH-/+ group, but not VH+/+, had poorer functioning and higher symptom severity than the VH-/- group. However, the number of participants who committed multiple suicide attempts during the follow-up period was again significantly higher in the VH+/+ group. There was no association with childhood trauma. Hence, visual hallucinations are associated with impaired functioning and higher symptom severity, but only in the short-term. However, visual hallucinations that arise early in the course of illness are a risk indicator for repeated suicide attempts throughout the illness course. These findings highlight the relevance of assessing visual hallucinations and monitoring their development over time.

Cognitive and inflammatory heterogeneity in severe mental illness: Translating findings from blood to brain.

Recent findings link cognitive impairment and inflammatory-immune dysregulation in schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, heterogeneity and translation between the periphery and central (blood-to-brain) mechanisms remains a challenge. Starting with a large SZ, BD and healthy control cohort (n = 1235), we aimed to i) identify candidate peripheral markers (n = 25) associated with cognitive domains (n = 9) and elucidate heterogenous immune-cognitive patterns, ii) evaluate the regulation of candidate markers using human induced pluripotent stem cell (iPSC)-derived astrocytes and neural progenitor cells (n = 10), and iii) evaluate candidate marker messenger RNA expression in leukocytes using microarray in available data from a subsample of the main cohort (n = 776), and in available RNA-sequencing deconvolution analysis of postmortem brain samples (n = 474) from the CommonMind Consortium (CMC). We identified transdiagnostic subgroups based on covariance between cognitive domains (measures of speed and verbal learning) and peripheral markers reflecting inflammatory response (CRP, sTNFR1, YKL-40), innate immune activation (MIF) and extracellular matrix remodelling (YKL-40, CatS). Of the candidate markers there was considerable variance in secretion of YKL-40 in iPSC-derived astrocytes and neural progenitor cells in SZ compared to HC. Further, we provide evidence of dysregulated RNA expression of genes encoding YKL-40 and related signalling pathways in a high neuroinflammatory subgroup in the postmortem brain samples. Our findings suggest a relationship between peripheral inflammatory-immune activity and cognitive impairment, and highlight YKL-40 as a potential marker of cognitive functioning in a subgroup of individuals with severe mental illness.

A good life with psychosis: rate of positive outcomes in first-episode psychosis at 10-year follow-up.

BACKGROUND: More knowledge about positive outcomes for people with first-episode psychosis (FEP) is needed. An FEP 10-year follow-up study investigated the rate of personal recovery, emotional wellbeing, and clinical recovery in the total sample and between psychotic bipolar spectrum disorders (BD) and schizophrenia spectrum disorders (SZ); and how these positive outcomes overlap. METHODS: FEP participants (n = 128) were re-assessed with structured clinical interviews at 10-year follow-up. Personal recovery was self-rated with the Questionnaire about the Process of Recovery-15-item scale (total score ⩾45). Emotional wellbeing was self-rated with the Life Satisfaction Scale (score ⩾5) and the Temporal Experience of Pleasure Scale (total score ⩾72). Clinical recovery was clinician-rated symptom-remission and adequate functioning (duration minimum 1 year). RESULTS: In FEP, rates of personal recovery (50.8%), life satisfaction (60.9%), and pleasure (57.5%) were higher than clinical recovery (33.6%). Despite lower rates of clinical recovery in SZ compared to BD, they had equal rates of personal recovery and emotional wellbeing. Personal recovery overlapped more with emotional wellbeing than with clinical recovery (χ2). Each participant was assigned to one of eight possible outcome groups depending on the combination of positive outcomes fulfilled. The eight groups collapsed into three equal-sized main outcome groups: 33.6% clinical recovery with personal recovery and/or emotional wellbeing; 34.4% personal recovery and/or emotional wellbeing only; and 32.0% none. CONCLUSIONS: In FEP, 68% had minimum one positive outcome after 10 years, suggesting a good life with psychosis. This knowledge must be shared to instill hope and underlines that subjective and objective positive outcomes must be assessed and targeted in treatment.

Sex differences in social cognition among individuals with schizophrenia and in healthy control participants: a secondary analysis of published data.

PURPOSE: Sex differences are present among individuals experiencing schizophrenia. Whether these differences extend to social cognition is unclear. In this study, we investigated sex differences in emotion perception, social perception and theory of mind (ToM). METHODS: We examined sex differences between males and females with schizophrenia on five social cognitive tests. Healthy male and female control participants were included to examine if any sex difference was illness-specific. Emotion perception was measured with Pictures of Facial Affect (PFA) and Emotion in Biological Motion (EmoBio); social perception with the Relationships Across Domains Test (RAD); and ToM with the Movie for the Assessment of Social Cognition (MASC) and Hinting Task. RESULTS: Two-way analyses of variance revealed overall group differences for all tests, with healthy controls outperforming individuals with schizophrenia. Significant sex effects were present for PFA and Hinting Task. There were no significant interaction effects. Within-group independent samples t-tests yielded one significant sex difference, i.e., among healthy controls for PFA. CONCLUSIONS: Females had better facial emotion perception than males. This sex difference was statistically significant among healthy controls and medium-large among individuals experiencing schizophrenia. There were no significant sex differences for other social cognitive domains. The study did not find evidence for a general female advantage in social cognition.

Long-term course of cognitive functioning in bipolar disorder: A ten-year follow-up study.

INTRODUCTION: Cognitive impairments are common in bipolar disorder (BD), but the long-term course remains understudied. Longitudinal data on cognitive functioning from the start of the first treatment could help clarify pathophysiological processes that shape the illness outcome. We here aim to investigate the 10-year cognitive course in BD compared to healthy controls (HC) and the effects of clinical symptoms on cognitive trajectories. METHODS: Fifty-six BD participants recruited within their first year of treatment and 108 HC completed clinical and cognitive assessments at baseline and 10-year follow-up. We derived eight cognitive domain scores and a cognitive composite score, which were further investigated using linear mixed model analyses. Correlation analyses were used to assess associations between the composite score and depressive, manic and psychotic symptoms. RESULTS: BD participants performed poorer than HCs in all domains except mental speed and verbal fluency. Verbal learning and memory, verbal fluency and the composite score improved over time in both BD participants and HC, while short-term memory, mental speed, psychomotor speed and working memory were stable. We found no significant correlations between cognition and symptom level at either time point in BD participants. CONCLUSIONS: We found evidence of long-term cognitive stability or improvement in BD participants from first treatment to 10-year follow-up. Though the BD group was impaired in all domains except mental speed and verbal fluency, the change in cognitive functioning was parallel to that of HCs. These findings are not consistent with the notion of neuroprogression in BD.

Altered Sex Differences in Hippocampal Subfield Volumes in Schizophrenia.

BACKGROUND AND HYPOTHESIS: The hippocampus is a heterogenous brain structure that differs between the sexes and has been implicated in the pathophysiology of psychiatric illnesses. Here, we explored sex and diagnostic group differences in hippocampal subfield volumes, in individuals with schizophrenia spectrum disorder (SZ), bipolar disorders (BD), and healthy controls (CTL). STUDY DESIGN: One thousand and five hundred and twenty-one participants underwent T1-weighted magnetic resonance imaging (SZ, n = 452, mean age 30.7 ±â€…9.2 [SD] years, males 59.1%; BD, n = 316, 33.7 ±â€…11.4, 41.5%; CTL, n = 753, 34.1 ±â€…9.1, 55.6%). Total hippocampal, subfield, and intracranial volumes were estimated with Freesurfer (v6.0.0). Analysis of covariance and multiple regression models were fitted to examine sex-by-diagnostic (sub)group interactions in volume. In SZ and BD, separately, associations between volumes and clinical as well as cognitive measures were examined between the sexes using regression models. STUDY RESULTS: Significant sex-by-group interactions were found for the total hippocampus, dentate gyrus, molecular layer, presubiculum, fimbria, hippocampal-amygdaloid transition area, and CA4, indicating a larger volumetric deficit in male patients relative to female patients when compared with same-sex CTL. Subgroup analyses revealed that this interaction was driven by males with schizophrenia. Effect sizes were overall small (partial η < 0.02). We found no significant sex differences in the associations between hippocampal volumes and clinical or cognitive measures in SZ and BD. CONCLUSIONS: Using a well-powered sample, our findings indicate that the pattern of morphological sex differences in hippocampal subfields is altered in individuals with schizophrenia relative to CTL, due to higher volumetric deficits in males.

Intra- and inter-individual cognitive variability in schizophrenia and bipolar spectrum disorder: an investigation across multiple cognitive domains.

There is substantial cognitive heterogeneity among patients with schizophrenia (SZ) and bipolar disorders (BD). More knowledge about the magnitude and clinical correlates of performance variability could improve our understanding of cognitive impairments. Using double generalized linear models (DGLMs) we investigated cognitive mean and variability differences between patients with SZ (n = 905) and BD spectrum disorders (n = 522), and healthy controls (HC, n = 1170) on twenty-two variables. The analysis revealed significant case-control differences on 90% of the variables. Compared to HC, patients showed larger intra-individual (within subject) variability across tests and larger inter-individual (between subject) variability in measures of fine-motor speed, mental processing speed, and inhibitory control (SZ and BD), and in verbal learning and memory and intellectual functioning (SZ). In SZ, we found that lager intra -and inter (on inhibitory control and speed functions) individual variability, was associated with lower functioning and more negative symptoms. Inter-individual variability on single measures of memory and intellectual function was additionally associated with disorganized and positive symptoms, and use of antidepressants. In BD, there were no within-subject associations with symptom severity. However, greater inter-individual variability (primarily on inhibitory control and speeded functions) was associated with lower functioning, more negative -and disorganized symptoms, earlier age at onset, longer duration of illness, and increased medication use. These results highlight larger individual differences in patients compared to controls on various cognitive domains. Further investigations of the causes and correlates of individual differences in cognitive function are warranted.

Genomic Insights into the Shared and Distinct Genetic Architecture of Cognitive Function and Schizophrenia.

Cognitive impairment is a major determinant of functional outcomes in schizophrenia, and efforts to understand the biological basis of cognitive dysfunction in the disorder are ongoing. Previous studies have suggested genetic overlap between global cognitive ability and schizophrenia, but further work is needed to delineate the shared genetic architecture. Here, we apply genomic structural equation modelling to identify latent cognitive factors capturing genetic liabilities to 12 cognitive traits measured in the UK Biobank (UKB). We explore the overlap between latent cognitive factors, schizophrenia, and schizophrenia symptom dimensions using a complementary set of statistical approaches, applied to data from the latest schizophrenia genome-wide association study (Ncase = 53,386, Ncontrol = 77,258) and the Thematically Organised Psychosis study (Ncase = 306, Ncontrol = 1060). We identified three broad factors (visuo-spatial, verbal analytic and decision/reaction time) that underly the genetic correlations between the UKB cognitive tests. Global genetic correlations showed a significant but moderate negative genetic correlation between each cognitive factor and schizophrenia. Local genetic correlations implicated unique genomic regions underlying the overlap between schizophrenia and each cognitive factor. We found evidence of substantial polygenic overlap between each cognitive factor and schizophrenia but show that most loci shared between the latent cognitive factors and schizophrenia have unique patterns of association with the cognitive factors. Biological annotation of the shared loci implicated gene-sets related to neurodevelopment and neuronal function. Lastly, we find that the common genetic determinants of the latent cognitive factors are not predictive of schizophrenia symptom dimensions. Overall, these findings inform our understanding of cognitive function in schizophrenia by demonstrating important differences in the shared genetic architecture of schizophrenia and cognitive abilities.

Tobacco smoking related to childhood trauma mediated by cognitive control and impulsiveness in severe mental disorders.

BACKGROUND: People with severe mental disorders (SMDs) show an increased prevalence of tobacco smoking compared to the general population. Tobacco smoking and other adult adverse health behaviors have been associated with traumatic experiences in childhood. In the present study we investigated the relationship between childhood trauma and tobacco smoking in people with SMDs, including the possible mediating role of cognitive- and personality characteristics, i.e. cognitive control, impulsiveness, affective lability and self-esteem. METHODS: Enrolled in the study were 871 participants with schizophrenia (SCZ, N = 484) and bipolar (BD, N = 387) spectrum disorders. We assessed tobacco smoking behavior (yes/no and amount), and history of childhood trauma with the Childhood Trauma Questionnaire. Data on cognitive control, impulsiveness, affective lability, and self-esteem were available in subsamples. We performed linear and logistic regressions, and conducted mediation analyses in PROCESS. All analyses were as standard adjusted for age, sex, and diagnostic group. RESULTS: Experience of one or more subtypes of childhood trauma was significantly associated with smoking tobacco in SMDs (p = 0.002). There were no significant associations between childhood trauma and amount of tobacco smoking. Cognitive control and impulsiveness were significant mediators between childhood trauma and tobacco smoking. CONCLUSIONS: These findings indicate the experience of childhood trauma as a predisposing factor for tobacco smoking in SMDs. Cognitive control and impulsiveness were suggested as mediating mechanisms, indicating the importance of considering inhibition related self-regulatory aspects in efforts to improve health behavior in individuals with SMDs and childhood trauma.

Telomere length and verbal learning in bipolar disorders.

INTRODUCTION: Recent studies indicate accelerated ageing processes, shorter telomere length and poorer cognitive functioning in patients with bipolar disorder. The neurobiology underlying cognitive function in bipolar disorder is yet to be established. We anticipated that accelerated ageing as indicated by shortened telomere length, would be associated with reduced cognitive performance in bipolar disorder, particularly for ageing sensitive functions such as memory and learning. METHODS: The study consisted of 647 participants (bipolar disorder [n = 246] and healthy controls [n = 401]). All participants underwent a standardized neuropsychological test battery, including working memory, executive functioning, processing speed, verbal learning, and verbal memory. Leucocyte telomere length was measured via blood and determined by quantitative real-time Polymerase Chain Reaction (qPCR) providing a telomere to single copy ratio (T/S ratio). The T/S ratio was used as an estimate of the mean telomere length of each participant. All analyses were adjusted for medication, Daily Defined Dose (DDD), chronological age, sex, and ethnicity. RESULTS: Patients had shorter telomere lengths than healthy controls (Cohen's d = 0.11, p = 0.01). Within patients', a positive association was observed for verbal learning and telomere length (ß = 0.14, p = 0.025), along with a trend for verbal memory and telomere length (ß = 0.11, p = 0.07). No other associations were observed for telomere length and cognitive functioning in the patient or the control group (p > 0.1). CONCLUSION: Our study may suggest poorer brain health in bipolar disorder as indexed by shorter telomere length and reduced learning correlates. However, the role of telomere length on cognitive functioning in bipolar disorder seems limited.

Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy.

Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex mental traits as distinct constructs. We applied the 'pleiotropy-informed' multivariate omnibus statistical test to genome-wide association studies of 35 measures of neuroticism and cognitive function from the UK Biobank (n = 336,993). We identified 431 significantly associated genetic loci with evidence of abundant shared genetic associations, across personality and cognitive function domains. Functional characterization implicated genes with significant tissue-specific expression in all tested brain tissues and brain-specific gene sets. We conditioned independent genome-wide association studies of the Big 5 personality traits and cognitive function on our multivariate findings, boosting genetic discovery in other personality traits and improving polygenic prediction. These findings advance our understanding of the polygenic architecture of these complex mental traits, indicating a prominence of pleiotropic genetic effects across higher order domains of mental function such as personality and cognitive function.

Early identification of treatment non-response in first-episode psychosis.

BACKGROUND: Approximately one-third of patients with psychotic disorders does not respond to standard antipsychotic treatments. Consensus criteria for treatment resistance (TR) may aid the identification of non-response and subsequent tailoring of treatments. Since consensus criteria require stability of clinical status, they are challenging to apply in first-episode psychosis (FEP). This study aims to investigate (a) if an adaptation of consensus criteria can be used to identify FEP patients with early signs of TR (no early clinical recovery-no-ECR) after 1 year in treatment and (b) to what extent differences in antipsychotic treatments differentiate between outcome groups. METHODS: Participants with FEP DSM-IV schizophrenia spectrum disorders were recruited during their first treatment. A total of 207 participated in the 1-year follow-up. Remission and recovery definitions were based on adaptations of the "Remission in Schizophrenia Working Group" criteria and TR on adaptations of the "Treatment Response and Resistance in Psychosis" (TRRIP) working group criteria. RESULTS: 97 participants (47%) could be classified as no-ECR, 61 (30%) as ECR, and 49 (23%) as with partial ECR (P-ECR). Statistically significant baseline predictors of no-ECR matched previously identified predictors of long-term TR. Only 35 no-ECR participants had two adequate treatment trials and met the full TRRIP criteria. 21 no-ECR participants were using the same medication over the follow-up year despite the lack of significant effects. CONCLUSION: The difference in the percentage of FEP participants classified as no-ECR versus TR indicates that we may underestimate the prevalence of early TR when using consensus criteria.

Visual processing deficits in patients with schizophrenia spectrum and bipolar disorders and associations with psychotic symptoms, and intellectual abilities.

Objective: Low-level sensory disruption is hypothesized as a precursor to clinical and cognitive symptoms in severe mental disorders. We compared visual discrimination performance in patients with schizophrenia spectrum disorder or bipolar disorder with healthy controls, and investigated associations with clinical symptoms and IQ. Methods: Patients with schizophrenia spectrum disorder (n = 32), bipolar disorder (n = 55) and healthy controls (n = 152) completed a computerized visual discrimination task. Participants responded whether the latter of two consecutive grids had higher or lower spatial frequency, and discrimination thresholds were estimated using an adaptive maximum likelihood procedure. Case-control differences in threshold were assessed using linear regression, F-test and post-hoc pair-wise comparisons. Linear models were used to test for associations between visual discrimination threshold and psychotic symptoms derived from the PANSS and IQ assessed using the Matrix Reasoning and Vocabulary subtests from the Wechsler Abbreviated Scale of Intelligence (WASI). Results: Robust regression revealed a significant main effect of diagnosis on discrimination threshold (robust F = 6.76, p = .001). Post-hoc comparisons revealed that patients with a schizophrenia spectrum disorder (mean = 14%, SD = 0.08) had higher thresholds compared to healthy controls (mean = 10.8%, SD = 0.07, ß = 0.35, t = 3.4, p = .002), as did patients with bipolar disorder (12.23%, SD = 0.07, ß = 0.21, t = 2.42, p = .04). There was no significant difference between bipolar disorder and schizophrenia (ß = -0.14, t = -1.2, p = .45). Linear models revealed negative associations between IQ and threshold across all participants when controlling for diagnostic group (ß = -0.3, t = -3.43, p = .0007). This association was found within healthy controls (t = -3.72, p = .0003) and patients with bipolar disorder (t = -2.53, p = .015), and no significant group by IQ interaction on threshold (F = 0.044, p = .97). There were no significant associations between PANSS domain scores and discrimination threshold. Conclusion: Patients with schizophrenia spectrum or bipolar disorders exhibited higher visual discrimination thresholds than healthy controls, supporting early visual deficits among patients with severe mental illness. Discrimination threshold was negatively associated with IQ among healthy controls and bipolar disorder patients. These findings elucidate perception-related disease mechanisms in severe mental illness, which warrants replication in independent samples.

Retrospectively assessed childhood trauma experiences are associated with illness severity in mental disorders adjusted for symptom state.

Converging evidence suggests that childhood trauma is a causal factor in schizophrenia (SZ) and in bipolar disorders (BD). Here, we investigated whether retrospective reports are associated with severity of illness, independent of current symptom state in a large sample of participants with SZ or BD. We included 1260 individuals (SZ [n = 461], BD [n = 352]), and healthy controls; HC [n = 447]) recruited from the same catchment area. A history of childhood trauma was obtained with the Childhood Trauma Questionnaire (CTQ). Diagnosis and episodes were obtained with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Clinical symptoms (state) were assessed with the Positive and Negative Syndrome scale (PANSS), the Calgary Depression Scale (CDSS). Trait related illness characteristics were assessed with age at illness onset, number of episodes, and lifetime suicide attempts. Patients who reported multiple types of childhood trauma experiences had significantly more severe illness course including an earlier illness onset, more mood episodes, and increased risk of at least one suicide attempt, also after adjusting for current symptom state. Retrospective assessed childhood trauma experiences are associated with illness severity in mental disorders adjusted for symptom state. Our results strengthen the role of childhood trauma in development of psychopathology.

The trajectory of two negative symptom dimensions in first-episode psychosis and the role of cannabis use: A 10-year follow-up study.

OBJECTIVE: To investigate the trajectories of diminished expression and apathy over 10 years. Further, to explore the effects of baseline- and persistent cannabis use on the development of diminished expression and apathy during follow-up, while controlling other potential sources and predictors of secondary negative symptoms. METHODS: 351 participants with a first episode of non-affective psychosis were examined at baseline and invited to follow-up at one year and 10 years. The trajectories of diminished expression and apathy were investigated using linear mixed models. Subsequently, cannabis use and other potential predictors and sources of secondary negative symptoms were added to the model to investigate the respective impact on their trajectories. RESULTS: The severity of both diminished expression and apathy decreased during the follow-up period after the first episode of psychosis, with the most improvement observed from baseline to 1-year follow-up. Cannabis use at baseline was associated with a long-lasting higher symptom load for diminished expression, but not apathy. Introducing persistent cannabis use to the model further strengthened the association with diminished expression. CONCLUSION: Both cannabis use at baseline and persistent cannabis use after a first episode of psychosis were associated with more severe symptoms of diminished expression. Our results imply a causal relationship between cannabis use and diminished expression and suggest that measures to reduce cannabis use both before and after psychosis onset may reduce expressive negative symptoms.

Vocational rehabilitation augmented with cognitive behavioral therapy or cognitive remediation for individuals with schizophrenia: a 5-year follow-up study.

INTRODUCTION: Although employment is an important part of recovery for individuals with schizophrenia spectrum disorders, the employment rate for this group remains low. Increasing evidence supports the use of augmented vocational rehabilitation (VR) programs to improve occupational outcome. The aim of this study is to explore 5-year follow-up registry data from the JUMP study, a VR program for individuals with schizophrenia spectrum disorders, specifically with regard to competitive employment outcome and predictors of competitive employment. The VR was augmented with either cognitive remediation (CR) or elements from cognitive behavior therapy (CBT). METHODS: One hundred and forty eight participants with schizophrenia spectrum disorders from six Norwegian counties received 10 months VR augmented with either CR (n = 64) or CBT (n = 84). Both competitive and sheltered workplaces were used. Assessments were conducted at baseline, at post intervention and at 2-year follow-up. Data on employment status at 5-year follow-up was obtained by registry. RESULTS: At 5-year follow-up 55.4% were engaged in working activity, of which 22.3% had obtained competitive employment. A further 18.2% had work placements in competitive workplaces. Number of received intervention hours and competitive employment at 2-year follow-up emerged as significant predictors of competitive employment. IQ and intervention type in marginal favor of CBT were predictors on trend level. CONCLUSION: To the best of our knowledge, this is the first study investigating competitive employment at 5-year follow-up for individuals with schizophrenia spectrum disorders. The results add to existing evidence that competitive employment is attainable for this group.