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.

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.

Social cognitive heterogeneity in schizophrenia: A cluster analysis.

This study examined social cognitive heterogeneity in Norwegian sample of individuals with schizophrenia (n = 82). They were assessed with three social cognitive tests: Emotion in Biological Motion (emotion processing), Relationships Across Domains (social perception), and Movie for the Assessment of Social Cognition (theory of mind). Hierarchical and k-means cluster analyses using standardized scores on these three tests provided two clusters. The first cluster (68 %) had mild social cognitive impairments (<0.5 standard deviations below healthy comparison participants). The second cluster (32 %) had severe social cognitive impairments (>2 standard deviations below healthy comparison participants). Validity of the two social cognitive subgroups was indicated by significant differences in functioning, symptom load and nonsocial cognition. Our study shows that social cognitive tests can be used for clinical and cognitive subtyping. This is of potential relevance for treatment.

The factor structure of social cognition in schizophrenia: Weak evidence for separable domains.

This study examined the factor structure of social cognition in a Norwegian sample of individuals diagnosed with schizophrenia (n = 83). Eight variables from three social cognitive tests from three theoretical domains were included: emotion processing, social perception and theory of mind. Factor analysis with maximum likelihood extraction and oblique rotation resulted in two factors using Kaiser's criterion. Although the two-factor model had better fit than a unifactorial model, it did not represent the data well. Two social cognitive variables did not load on either factor. The two extracted factors did not correspond to an expected distinction between low and high level of processing or between affective and cognitive processes. A non-negligible number of nonredundant residuals between observed and computed correlations suggested poor model fit. In conclusion, this study failed to identify separable dimensions of social cognition in spite of including measures from different theoretical domains.

Cognitive Heterogeneity across Schizophrenia and Bipolar Disorder: A Cluster Analysis of Intellectual Trajectories.

OBJECTIVE: Cognitive dysfunction cut across diagnostic categories and is present in both schizophrenia and bipolar disorder, although with considerable heterogeneity in both disorders. This study examined if distinct cognitive subgroups could be identified across schizophrenia and bipolar disorder based on the intellectual trajectory from the premorbid phase to after illness onset. METHOD: Three hundred and ninety-eight individuals with schizophrenia (n = 223) or bipolar I disorder (n = 175) underwent clinical and neuropsychological assessment. Hierarchical and k-means cluster analyses using premorbid (National Adult Reading Test) and current IQ (Wechsler Abbreviated Scale of Intelligence) estimates were performed for each diagnostic category, and the whole sample collapsed. Resulting clusters were compared on neuropsychological, functional, and clinical variables. Healthy controls (n = 476) were included for analyses of neuropsychological performance. RESULTS: Cluster analyses consistently yielded three clusters: a relatively intact group (36% of whole sample), an intermediate group with mild cognitive impairment (44%), and an impaired group with global deficits (20%). The clusters were validated by multinomial logistic regression and differed significantly for neuropsychological, functional, and clinical measures. The relatively intact group (32% of the schizophrenia sample and 42% of the bipolar sample) performed below healthy controls for speeded neuropsychological tests. CONCLUSIONS: Three cognitive clusters were identified across schizophrenia and bipolar disorder using premorbid and current IQ estimates. Groups differed for clinical, functional, and neuropsychological variables, implying their meaningfulness. One-third of the schizophrenia sample belonged to the relatively intact group, highlighting that neuropsychological assessment is needed for the precise characterization of the individual.

Cognitive Performance in Early-Onset Schizophrenia and Attention-Deficit/Hyperactivity Disorder: A 25-Year Follow-Up Study.

Early-Onset Schizophrenia (EOS) and Attention Deficit-Hyperactivity Disorder (ADHD) are early- onset neurodevelopmental disorders associated with cognitive deficits. The current study represents the first attempt to compare these groups on a comprehensive cognitive test battery in a longitudinal design over 25 years in order to enhance our knowledge of particular patterns resulting from the interaction between normal maturational processes and different illness processes of these disorders. In the baseline study, 19 adolescents with schizophrenia were compared to 20 adolescents with ADHD and 30 healthy controls (HC), all between 12 and 18 years of age. After 13 years (T2) and after 25 years (T3) they were re-evaluated with the cognitive test battery. A cognitive Composite Score was used in a linear mixed model. The EOS group had a significant cognitive stagnation or deterioration from T1 to T2 compared to HC. However, the EOS group had the most positive change from T2 to T3, supporting a stable level of cognitive performance over the 25 year span. The ADHD group improved or had similar development as the HC group from T1 to T2. They continued to improve significantly compared to the HC group from T2 to T3. Individuals in the EOS group performed more impaired on the cognitive composite score compared to the HC group and the ADHD group at all three time points. Results might indicate a neurodevelopmental pathway of EOS with subnormal cognitive development specific in adolescence. In comparison, the ADHD group had a more consistent cognitive maturation supporting a maturational delay hypothesis of ADHD.

The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia.

BACKGROUND: Cognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases. METHODS: We combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results were then meta-analyzed across all samples. A genome-wide association studies (GWAS) of cognition was conducted in schizophrenia cases. RESULTS: PRS for both population IQ (P = 4.39 × 10-28) and EA (P = 1.27 × 10-26) were positively correlated with cognition in those with schizophrenia. In contrast, there was no association between cognition in schizophrenia cases and PRS for schizophrenia (P = .39), BD (P = .51), or MDD (P = .49). No individual variant approached genome-wide significance in the GWAS. CONCLUSIONS: Cognition in schizophrenia cases is more strongly associated with PRS that index cognitive traits in the general population than PRS for neuropsychiatric disorders. This suggests the mechanisms of cognitive variation within schizophrenia are at least partly independent from those that predispose to schizophrenia diagnosis itself. Our findings indicate that this cognitive variation arises at least in part due to genetic factors shared with cognitive performance in populations and is not solely due to illness or treatment-related factors, although our findings are consistent with important contributions from these factors.

Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.

Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected ("concordant") direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants that demonstrated the counterintuitive ("discordant") relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education, and/or schizophrenia at p < 5 × 10-8. Pleiotropic analysis successfully identified more than 100 loci that were not significant in the input GWASs. Many of these have been validated by larger, more recent single-phenotype GWASs. Leveraging the joint genetic correlations of cognitive ability, education, and schizophrenia, we were able to dissociate two distinct biological mechanisms-early neurodevelopmental pathways that characterize concordant allelic variation and adulthood synaptic pruning pathways-that were linked to the paradoxical positive genetic association between education and schizophrenia. Furthermore, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia but also to the broader biological dimensions implicated in both general health outcomes and psychiatric illness.

A randomized controlled trial of training of affect recognition (TAR) in schizophrenia shows lasting effects for theory of mind.

Schizophrenia is characterized by social cognitive impairments that predict functioning. Social cognitive training aims to target these impairments. Although it can improve the targeted social cognitive domain, it is unclear if the training generalizes to non-targeted domains and to functioning, with lasting effects. This randomized controlled trial examined the effect of a targeted facial affect recognition training program, Training of Affect Recognition (TAR), in persons with schizophrenia. Individuals with schizophrenia were randomized to receive treatment as usual and TAR (n = 24) or treatment as usual (n = 24) after assessments with a comprehensive protocol at baseline (T1). Participants were reassessed immediately after the intervention period (T2: after 8 weeks) and at 3-month follow-up (T3). The protocol included tests of social cognition (facial or body affect recognition, theory of mind), nonsocial cognition (Matrics Consensus Cognitive Battery), clinical symptoms (Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia), functioning (self-reported, social or nonsocial functional capacity), self-esteem, self-efficacy and insight. Linear mixed models yielded a significant group × time interaction effect for a non-targeted social cognitive domain (theory of mind) and a trend-level effect for social functional capacity with the intervention group performing better over time. No beneficial effects on nonsocial cognition, other measures of functioning, clinical symptoms, or self-esteem/self-efficacy appeared for the TAR program. This study provides evidence for transfer and durability effects of facial affect recognition training to theory of mind, but also highlights the need for additional treatments to achieve functional benefits.

Multi-Trait Analysis of GWAS and Biological Insights Into Cognition: A Response to Hill (2018).

Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88) presented a critique of our recently published paper in Cell Reports entitled 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' (Lam et al., Cell Reports, Vol. 21, 2017, 2597-2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229-237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from 'inflation in the FDR [false discovery rate]', as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88), and are not 'more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence'.

Emotion perception, non-social cognition and symptoms as predictors of theory of mind in schizophrenia.

BACKGROUND: Theory of mind (ToM) can be divided into cognitive and affective ToM, and a distinction can be made between overmentalizing and undermentalizing errors. Research has shown that ToM in schizophrenia is associated with non-social and social cognition, and with clinical symptoms. In this study, we investigate cognitive and clinical predictors of different ToM processes. METHODS: Ninety-one individuals with schizophrenia participated. ToM was measured with the Movie for the Assessment of Social Cognition (MASC) yielding six scores (total ToM, cognitive ToM, affective ToM, overmentalizing errors, undermentalizing errors and no mentalizing errors). Neurocognition was indexed by a composite score based on the non-social cognitive tests in the MATRICS Consensus Cognitive Battery (MCCB). Emotion perception was measured with Emotion in Biological Motion (EmoBio), a point-light walker task. Clinical symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Seventy-one healthy control (HC) participants completed the MASC. RESULTS: Individuals with schizophrenia showed large impairments compared to HC for all MASC scores, except overmentalizing errors. Hierarchical regression analyses with the six different MASC scores as dependent variables revealed that MCCB was a significant predictor of all MASC scores, explaining 8-18% of the variance. EmoBio increased the explained variance significantly, to 17-28%, except for overmentalizing errors. PANSS excited symptoms increased explained variance for total ToM, affective ToM and no mentalizing errors. DISCUSSION: Both social and non-social cognition were significant predictors of ToM. Overmentalizing was only predicted by non-social cognition. Excited symptoms contributed to overall and affective ToM, and to no mentalizing errors.

Right unilateral electroconvulsive therapy does not cause more cognitive impairment than pharmacologic treatment in treatment-resistant bipolar depression: A 6-month randomized controlled trial follow-up study.

OBJECTIVES: Electroconvulsive therapy is an effective treatment for bipolar depression, but there are concerns about whether it causes long-term neurocognitive impairment. METHODS: In this multicenter randomized controlled trial, in-patients with treatment-resistant bipolar depression were randomized to either algorithm-based pharmacologic treatment or right unilateral electroconvulsive therapy. After the 6-week treatment period, all of the patients received maintenance pharmacotherapy as recommended by their clinician guided by a relevant treatment algorithm. Patients were assessed at baseline and at 6 months. Neurocognitive functions were assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, and autobiographical memory consistency was assessed using the Autobiographical Memory Interview-Short Form. RESULTS: Seventy-three patients entered the trial, of whom 51 and 26 completed neurocognitive assessments at baseline and 6 months, respectively. The MATRICS Consensus Cognitive Battery composite score improved by 4.1 points in both groups (P = .042) from baseline to 6 months (from 40.8 to 44.9 and from 41.9 to 46.0 in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively). The Autobiographical Memory Interview-Short Form consistency scores were reduced in both groups (72.3% vs 64.3% in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively; P = .085). CONCLUSIONS: This study did not find that right unilateral electroconvulsive therapy caused long-term impairment in neurocognitive functions compared to algorithm-based pharmacologic treatment in bipolar depression as measured using standard neuropsychological tests, but due to the low number of patients in the study the results should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00664976.

Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets.

Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability ("g"), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum). Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth.

Body language reading of emotion in schizophrenia: Associations with symptoms and functional outcome.

Our aim was to explore how body language reading of emotion relates to neurocognition, symptoms and functional outcome in schizophrenia. Fifty-four individuals with schizophrenia and eighty-four healthy controls participated in the study. Emotion perception was assessed with a point-light display (PLD) task, the Emotion in Biological Motion (EmoBio) test, neurocognition was measured with the MATRICS Consensus Cognitive Battery (MCCB), and functioning was indexed by one measure of functional capacity and by one self-report questionnaire. Clinical symptoms were assessed with a five factor Positive and Negative Syndrome Scale (PANSS) symptoms model. Participants with schizophrenia had impaired body language reading of emotions compared to healthy controls (Cohen's d = 0.69). In participants with schizophrenia, emotion perception was associated with neurocognition (r = 0.42), functional capacity (r = 0.27) and disorganization symptoms (r = -0.27). Mediation analyses showed that disorganization symptoms mediated the effects of emotion perception and neurocognition, respectively, on social functional capacity. These results suggest that in individuals with schizophrenia, reduced emotion perception from body movements has negative consequences for functional outcome, but that the effect is mediated through disorganization symptoms.

Early clinical recovery in first-episode psychosis: Symptomatic remission and its correlates at 1-year follow-up.

The aim was to gain more knowledge about early clinical recovery in first-episode psychosis (FEP). The interrelationship between symptomatic remission, poor global functioning and neurocognitive impairment was investigated. FEP participants (n =91) from the TOP study were investigated at baseline and 1-year follow-up. Symptomatic remission was defined by internationally standardized criteria. Poor global functioning was defined as GAF-F score ≤60. Neurocognitive impairment was defined as 1.5 standard deviation below healthy controls on a neuropsychological composite score. Finally, early clinical recovery was defined as symptomatic remission during the last 6 months and functional remission (1. GAF-F score ≥61, 2. at least 50% study/employment, and 3. living independently). At 1-year follow-up 26% were in symptomatic remission, predicted by duration of untreated psychosis and baseline positive symptoms. Significantly fewer in the symptomatic remission group had poor global functioning compared to the non-remission group, with no difference in the rate of neurocognitive impairment. Finally, 14% were considered in early clinical recovery. They had the same rate of neurocognitive impairment as the remaining group. These findings imply that symptomatic remission and early clinical recovery can already be identified at 1-year follow-up, and that this is relatively independent of neurocognitive impairment.

Impairment in emotion perception from body movements in individuals with bipolar I and bipolar II disorder is associated with functional capacity.

BACKGROUND: Individuals with bipolar disorder present with moderate impairments in social cognition during the euthymic state. The impairment extends to theory of mind and to the perception of emotion in faces and voices, but it is unclear if emotion perception from body movements is affected. The main aim of this study was to examine if participants with bipolar disorder perform worse than healthy control participants on a task using point-light displays of human full figures moving in a manner indicative of a basic emotion (angry, happy, sad, fearful, neutral/no emotion). A secondary research question was whether diagnostic subtypes (bipolar I, bipolar II) and history of psychosis impacted on this type of emotion perception. Finally, symptomatic, neurocognitive, and functional correlates of emotion perception from body movements were investigated. METHODS: Fifty-three individuals with bipolar I (n = 29) or bipolar II (n = 24) disorder, and 84 healthy control participants were assessed for emotion perception from body movements. The bipolar group also underwent clinical, cognitive, and functional assessment. Research questions were analyzed using analyses of variance and bivariate correlations. RESULTS: The bipolar disorder group differed significantly from healthy control participants for emotion perception from body movements (Cohen's d = 0.40). Analyses of variance yielded no effects of sex, diagnostic subtype (bipolar I, bipolar II), or history of psychosis. There was an effect of emotion, indicating that some emotions are easier to recognize. The lack of a significant group × emotion interaction effect points, however, to this being so regardless of the presence of bipolar disorder. Performance was unrelated to manic and depressive symptom load but showed significant associations with neurocognition and functional capacity. CONCLUSIONS: Individuals with bipolar disorder had a small but significant impairment in the ability to perceive emotions from body movement. The impairment was global, i.e., affecting all emotions and equally present for males and females. The impairment was associated with neurocognition and functional capacity, but not symptom load. Our findings identify pathopsychological factors underlying the functional impairment in bipolar disorder and suggest the consideration of social cognition training as part of the treatment for bipolar disorder.

A genetic association study of CSMD1 and CSMD2 with cognitive function.

The complement cascade plays a role in synaptic pruning and synaptic plasticity, which seem to be involved in cognitive functions and psychiatric disorders. Genetic variants in the closely related CSMD1 and CSMD2 genes, which are implicated in complement regulation, are associated with schizophrenia. Since patients with schizophrenia often show cognitive impairments, we tested whether variants in CSMD1 and CSMD2 are also associated with cognitive functions per se. We took a discovery-replication approach, using well-characterized Scandinavian cohorts. A total of 1637 SNPs in CSMD1 and 206 SNPs in CSMD2 were tested for association with cognitive functions in the NCNG sample (Norwegian Cognitive NeuroGenetics; n=670). Replication testing of SNPs with p-value<0.001 (7 in CSMD1 and 3 in CSMD2) was carried out in the TOP sample (Thematically Organized Psychosis; n=1025) and the BETULA sample (Betula Longitudinal Study on aging, memory and dementia; n=1742). Finally, we conducted a meta-analysis of these SNPs using all three samples. The previously identified schizophrenia marker in CSMD1 (SNP rs10503253) was also included. The strongest association was observed between the CSMD1 SNP rs2740931 and performance in immediate episodic memory (p-value=5×10-6, minor allele A, MAF 0.48-0.49, negative direction of effect). This association reached the study-wide significance level (p⩽1.2×10-5). SNP rs10503253 was not significantly associated with cognitive functions in our samples. In conclusion, we studied n=3437 individuals and found evidence that a variant in CSMD1 is associated with cognitive function. Additional studies of larger samples with cognitive phenotypes will be needed to further clarify the role of CSMD1 in cognitive phenotypes in health and disease.

A sequence variant associating with educational attainment also affects childhood cognition.

Only a few common variants in the sequence of the genome have been shown to impact cognitive traits. Here we demonstrate that polygenic scores of educational attainment predict specific aspects of childhood cognition, as measured with IQ. Recently, three sequence variants were shown to associate with educational attainment, a confluence phenotype of genetic and environmental factors contributing to academic success. We show that one of these variants associating with educational attainment, rs4851266-T, also associates with Verbal IQ in dyslexic children (P = 4.3 × 10-4, ß = 0.16 s.d.). The effect of 0.16 s.d. corresponds to 1.4 IQ points for heterozygotes and 2.8 IQ points for homozygotes. We verified this association in independent samples consisting of adults (P = 8.3 × 10-5, ß = 0.12 s.d., combined P = 2.2 x 10-7, ß = 0.14 s.d.). Childhood cognition is unlikely to be affected by education attained later in life, and the variant explains a greater fraction of the variance in verbal IQ than in educational attainment (0.7% vs 0.12%,. P = 1.0 × 10-5).

Neurocognition and Duration of Psychosis: A 10-year Follow-up of First-Episode Patients.

A substantial proportion of schizophrenia-spectrum patients exhibit a cognitive impairment at illness onset. However, the long-term course of neurocognition and a possible neurotoxic effect of time spent in active psychosis, is a topic of controversy. Furthermore, it is of importance to find out what predicts the long-term course of neurocognition. Duration of untreated psychosis (DUP), accumulated time in psychosis the first year after start of treatment, relapse rates and symptoms are potential predictors of the long-term course. In this study, 261 first-episode psychosis patients were assessed neuropsychologically on one or more occasions. Patients were tested after remission of psychotic symptoms and reassessed 1, 2, 5, and 10 years after inclusion. The neurocognitive battery consisted of California Verbal Learning Test, Wisconsin Card Sorting Test, Controlled Oral Word Association Task, Trail Making A and B, and Finger Tapping. We calculated a composite score by adding the z-scores of 4 tests that were only moderately inter-correlated, not including Finger Tapping. Data were analyzed by a linear mixed model. The composite score was stable over 10 years. No significant relationship between psychosis before (DUP) or after start of treatment and the composite score was found, providing no support for the neurotoxicity hypothesis, and indicating that psychosis before start of treatment has no significant impact on the course and outcome in psychosis. We found no association between symptoms and the neurocognitive trajectory. Stable remission during the first year predicted neurocognitive functioning, suggesting that the early clinical course is a good predictor for the long-term course.