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.

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.

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.

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.

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.

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.

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'.

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.

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.

Independent evidence for an association between general cognitive ability and a genetic locus for educational attainment.

Cognitive deficits and reduced educational achievement are common in psychiatric illness; understanding the genetic basis of cognitive and educational deficits may be informative about the etiology of psychiatric disorders. A recent, large genome-wide association study (GWAS) reported a genome-wide significant locus for years of education, which subsequently demonstrated association to general cognitive ability ("g") in overlapping cohorts. The current study was designed to test whether GWAS hits for educational attainment are involved in general cognitive ability in an independent, large-scale collection of cohorts. Using cohorts in the Cognitive Genomics Consortium (COGENT; up to 20,495 healthy individuals), we examined the relationship between g and variants associated with educational attainment. We next conducted meta-analyses with 24,189 individuals with neurocognitive data from the educational attainment studies, and then with 53,188 largely independent individuals from a recent GWAS of cognition. A SNP (rs1906252) located at chromosome 6q16.1, previously associated with years of schooling, was significantly associated with g (P = 1.47 × 10(-4) ) in COGENT. The first joint analysis of 43,381 non-overlapping individuals for this a priori-designated locus was strongly significant (P = 4.94 × 10(-7) ), and the second joint analysis of 68,159 non-overlapping individuals was even more robust (P = 1.65 × 10(-9) ). These results provide independent replication, in a large-scale dataset, of a genetic locus associated with cognitive function and education. As sample sizes grow, cognitive GWAS will identify increasing numbers of associated loci, as has been accomplished in other polygenic quantitative traits, which may be relevant to psychiatric illness.

Working memory networks and activation patterns in schizophrenia and bipolar disorder: comparison with healthy controls.

BACKGROUND: Schizophrenia and bipolar disorder are severe mental disorders with overlapping genetic and clinical characteristics, including cognitive impairments. An important question is whether these disorders also have overlapping neuronal deficits. AIMS: To determine whether large-scale brain networks associated with working memory, as measured with functional magnetic resonance imaging (fMRI), are the same in both schizophrenia and bipolar disorder, and how they differ from those in healthy individuals. METHOD: Patients with schizophrenia (n = 100) and bipolar disorder (n = 100) and a healthy control group (n = 100) performed a 2-back working memory task while fMRI data were acquired. The imaging data were analysed using independent component analysis to extract large-scale networks of task-related activations. RESULTS: Similar working memory networks were activated in all groups. However, in three out of nine networks related to the experimental task there was a graded response difference in fMRI signal amplitudes, where patients with schizophrenia showed greater activation than those with bipolar disorder, who in turn showed more activation than healthy controls. Secondary analysis of the patient groups showed that these activation patterns were associated with history of psychosis and current elevated mood in bipolar disorder. CONCLUSIONS: The same brain networks were related to working memory in schizophrenia, bipolar disorder and controls. However, some key networks showed a graded hyperactivation in the two patient groups, in line with a continuum of neuronal abnormalities across psychotic disorders.

Occupational outcome in bipolar disorder is not predicted by premorbid functioning and intelligence.

OBJECTIVES: Bipolar disorder (BD), over the long term, can manifest a variety of outcomes depending on a number of different conditions. There is a need for further knowledge regarding preventive factors as well as predictors of the disabling course of the disorder. Studies regarding the impact on functional outcome of premorbid and current general intellectual function [intelligence quotient (IQ)] and premorbid functioning in BD patients are sparse. The present study addressed the role of premorbid functioning [assessed with the Premorbid Adjustment Scale (PAS)], intelligence, course of illness, and sociodemographics on occupational outcome in BD. METHODS: Bipolar disorder patients were recruited consecutively from psychiatric units (outpatient and inpatient) in four major hospitals in Oslo, Norway [(N = 226: 64.4% bipolar I disorder (BD-I); 30.1% bipolar II disorder (BD-II); 5.5% bipolar disorder not otherwise specified (BD-NOS); 38.6% males]. The associations between current IQ, premorbid IQ [assessed using the National Adult Reading Test (NART)], PAS, clinical and sociodemographic characteristics, and receipt of disability benefit were analysed using descriptive statistics and logistic regression analyses. RESULTS: The number of hospitalizations for depressive episodes and illness duration was associated with a higher risk of receipt of disability benefit. PAS, premorbid and current IQ, as well as decline in IQ, did not explain the higher risk of receipt of disability benefits. CONCLUSIONS: Severe clinical course of BD was associated with receipt of disability benefit. Occupational outcome was unrelated to PAS, premorbid and current IQ, as well as decline in IQ. This suggests that the persistence of severe clinical symptoms, rather than global cognitive functioning, determines occupational outcome in BD and emphasizes the protective potential of early and continuous clinical treatment.

Neurocognitive profiles in treatment-resistant bipolar I and bipolar II disorder depression.

BACKGROUND: The literature on the neuropsychological profiles in Bipolar disorder (BD) depression is sparse. The aims of the study were to assess the neurocognitive profiles in treatment-resistant, acutely admitted BD depression inpatients, to compare the neurocognitive functioning in patients with BD I and II, and to identify the demographic and clinical illness characteristics associated with cognitive functioning. METHODS: Acutely admitted BD I (n = 19) and BD II (n = 32) inpatients who fulfilled the DSM-IV-TR criteria for a major depressive episode were tested with the MATRICS Consensus Cognitive Battery (MCCB), the Wechsler Abbreviated Scale of Intelligence, the National Adult Reading Test, and a battery of clinical measures. RESULTS: Neurocognitive impairments were evident in the BD I and BD II depression inpatients within all MCCB domains. The numerical scores on all MCCB-measures were lower in the BD I group than in the BD II group, with a significant difference on one of the measures, category fluency. 68.4% of the BD I patients had clinically significant impairment (>1.5 SD below normal mean) in two or more domains compared to 37.5% of the BD II patients (p = 0.045). A significant reduction in IQ from the premorbid to the current level was seen in BD I but not BD II patients. Higher age was associated with greater neurocognitive deficits compared to age-adjusted published norms. CONCLUSIONS: A high proportion of patients with therapy-resistant BD I or II depression exhibited global neurocognitive impairments with clinically significant severity. The cognitive impairments were more common in BD I compared to BD II patients, particularly processing speed. These findings suggest that clinicians should be aware of the severe neurocognitive dysfunction in treatment-resistant bipolar depression, particularly in BD I. TRIAL REGISTRATION: NCT00664976.

Social functioning in first contact mania: clinical and neurocognitive correlates.

PURPOSE: To study social functioning, and its relationship with clinical and neurocognitive variables, in patients having their first treatment contact for a manic episode. METHODS: A total of 55 first contact mania patients, 34 with a first manic episode (FM) and 21 with previously untreated manic episodes (PM), and 110 healthy control subjects matched for age, sex and education to the patient group, completed the Social Functioning Scale (SFS), a self-reported assessment of social functioning. The patients also completed a broad neuropsychological test battery. RESULTS: Both patient groups scored significantly lower on self-rated social functioning compared to healthy controls, with PM patients reporting significantly lower functioning than FM patients. There were no significant correlations between clinical symptoms and social functioning. On a trend level, a reduced SFS score was associated with more cannabis use, higher levels of depression and more depressive episodes as well as an earlier age at onset. There was no significant association between social function and neurocognition. CONCLUSIONS: Social dysfunction was present in patients with BD at first treatment contact-the main predictors of which being the severity of clinical symptoms.

Social cognition and clinical insight in schizophrenia and bipolar disorder.

The association between clinical insight and social cognition assessed with an emotion perception task was investigated in schizophrenia (n = 29) and bipolar I disorder (n = 19). Persons with schizophrenia had reduced auditory emotion perception compared with individuals with bipolar I disorder, but levels of visual emotion perception and clinical insight were comparable. In the schizophrenia group, clinical insight was moderately associated with auditory and visual emotion perception (r = 0.36-0.44) and negative symptoms (r = -0.33). Better insight was associated with better social cognition and fewer negative symptoms. In the bipolar I disorder group, clinical insight showed small associations with social cognition (largest r = -0.28) and moderate to large associations with positive, negative, manic, and depressive symptoms. Poorer insight was associated with higher symptom load. Social cognition seems to be of importance for clinical insight in schizophrenia, whereas symptoms are important in bipolar I disorder.

Occupational functioning, symptoms and neurocognition in patients with psychotic disorders: investigating subgroups based on social security status.

PURPOSE: Reported employment rates for patients with psychosis are low, but vary partly depending on illness phase. Illness-related factors such as neurocognition and negative symptoms are associated with occupational functioning, while external factors may also act as barriers for employment. The current study investigated the relationship between neurocognition, symptoms and employment using a threefold division of employment status: employed, receiving temporary benefits and receiving disability benefits. The latter group was divided into two based on level of social functioning. METHODS: A total of 155 patients with broad DSM-IV schizophrenia spectrum disorder were assessed with clinical, neurocognitive and social and occupational functioning measures. Group differences were analyzed with ANOVAs and hierarchical regression analysis. RESULTS: Thirteen percent were employed, 52 % received temporary benefits and 35 % received disability benefits. There were no differences in symptom level and neurocognitive functioning between groups. Among patients on disability benefits, the subgroup with higher social functioning had fewer negative and general symptoms and a trend for better neurocognition compared with those with lower social functioning, thus being more similar to employed patients. Negative symptoms and executive functioning explained 26 % of the variance in social functioning for patients receiving disability benefits. CONCLUSIONS: The association between neurocognition and employment may not be as strong as previously assumed, due to external factors that may influence this relationship. Patients on disability benefits rated high on social functioning showed similarities with employed patients. This could imply that these patients have some work capacity. This issue needs further investigation.

Sex-dependent association of common variants of microcephaly genes with brain structure.

Loss-of-function mutations in the genes associated with primary microcephaly (MCPH) reduce human brain size by about two-thirds, without producing gross abnormalities in brain organization or physiology and leaving other organs largely unaffected [Woods CG, et al. (2005) Am J Hum Genet 76:717-728]. There is also evidence suggesting that MCPH genes have evolved rapidly in primates and humans and have been subjected to selection in recent human evolution [Vallender EJ, et al. (2008) Trends Neurosci 31:637-644]. Here, we show that common variants of MCPH genes account for some of the common variation in brain structure in humans, independently of disease status. We investigated the correlations of SNPs from four MCPH genes with brain morphometry phenotypes obtained with MRI. We found significant, sex-specific associations between common, nonexonic, SNPs of the genes CDK5RAP2, MCPH1, and ASPM, with brain volume or cortical surface area in an ethnically homogenous Norwegian discovery sample (n = 287), including patients with mental illness. The most strongly associated SNP findings were replicated in an independent North American sample (n = 656), which included patients with dementia. These results are consistent with the view that common variation in brain structure is associated with genetic variants located in nonexonic, presumably regulatory, regions.

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.

Neurocognitive functioning in patients recently diagnosed with bipolar disorder.

OBJECTIVES: Cognitive dysfunction in bipolar disorder (BD) is well established in the literature; however, there are few studies of neurocognition in patients early in the course of the illness. In this study we compare neurocognitive function in a cohort of first-contact mania patients with a healthy control group matched for age, gender, and education. METHODS: Patients with a first manic episode (FM) (n = 34) or previous untreated manic episodes (PM) (n = 21) were neuropsychologically tested following their first treated manic episode. A total of 110 matched healthy control comparison subjects were also tested. The following cognitive domains were evaluated: verbal and visual learning and memory, attention, processing speed, executive functioning, and IQ. Results were corrected for speed of processing differences and were compared with previously reported results for multiple-episode BD patients. RESULTS: BD patients early in their disease course showed impairments in psychomotor speed, attention, learning and memory, executive functioning, and IQ. When controlling for speed of processing, measures of visuoconstructive reasoning and motor dexterity remained statistically significant. Eighteen percent of FM and 16% of PM patients were found to have clinically significant neurocognitive impairment. No significant relationship between clinical symptoms and neurocognition was found. The first-contact mania patients studied were found to have smaller neurocognitive deficits compared to multiple-episode patients in previous studies. CONCLUSIONS: Neurocognitive dysfunction is present in early BD and is clinically significant for a proportion of patients. Our findings also suggest that neurocognitive dysfunction may increase with illness progression.