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.

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.

Inflammation and cognition in severe mental illness: patterns of covariation and subgroups.

A potential relationship between dysregulation of immune/inflammatory pathways and cognitive impairment has been suggested in severe mental illnesses (SMI), such as schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, multivariate relationships between peripheral inflammatory/immune-related markers and cognitive domains are unclear, and many studies do not account for inter-individual variance in both cognitive functioning and inflammatory/immune status. This study aimed to investigate covariance patterns between inflammatory/immune-related markers and cognitive domains and further elucidate heterogeneity in a large SMI and healthy control (HC) cohort (SZ = 343, BD = 289, HC = 770). We applied canonical correlation analysis (CCA) to identify modes of maximum covariation between a comprehensive selection of cognitive domains and inflammatory/immune markers. We found that poor verbal learning and psychomotor processing speed was associated with higher levels of interleukin-18 system cytokines and beta defensin 2, reflecting enhanced activation of innate immunity, a pattern augmented in SMI compared to HC. Applying hierarchical clustering on covariance patterns identified by the CCA revealed a high cognition-low immune dysregulation subgroup with predominantly HC (24% SZ, 45% BD, 74% HC) and a low cognition-high immune dysregulation subgroup predominantly consisting of SMI patients (76% SZ, 55% BD, 26% HC). These subgroups differed in IQ, years of education, age, CRP, BMI (all groups), level of functioning, symptoms and defined daily dose (DDD) of antipsychotics (SMI cohort). Our findings suggest a link between cognitive impairment and innate immune dysregulation in a subset of individuals with severe mental illness.

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.

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.

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.

Course of intellectual functioning in schizophrenia and bipolar disorder: a 10-year follow-up study.

BACKGROUND: Intellectual functioning (IQ) is lower in schizophrenia patients compared to healthy controls, with bipolar patients intermediate between the two. Declines in IQ mark the onset of schizophrenia, while stability is generally found post-onset. There are to date few studies on long-term IQ development in bipolar disorder. This study presents 10-year follow-up data on IQ, including premorbid IQ estimates, to track the developmental course from pre-onset levels to long-term outcomes in both patient groups compared to healthy controls. METHODS: We included 139 participants with schizophrenia, 76 with bipolar disorder and 125 healthy controls. Mixed model analyses were used to estimate developmental slopes for IQ scores from estimated premorbid level (NART IQ) through baseline (WASI IQ) measured within 12 months post-onset, to 10-year follow-up (WASI IQ), with pairwise group comparisons. The best fit was found using a model with a breakpoint at baseline assessment. RESULTS: Only the schizophrenia group had significant declines from estimated premorbid to baseline IQ levels compared to controls. When comparing patient groups, schizophrenia patients had steeper declines than the bipolar group. Increases in IQ were found in all groups over the follow-up period. CONCLUSIONS: Trajectories of IQ from premorbid level to 10-year follow-up indicated declines from estimated premorbid level to illness onset in both patient groups, followed by increases during the follow-up period. Schizophrenia patients had a steeper decline than bipolar patients. During follow-up, increases indicate developmental improvement for both patient groups, but with a maintained lag compared to healthy controls due to lower premorbid levels.

Theory of mind in schizophrenia: a comparison of subgroups with low and high IQ.

BACKGROUND: Social cognitive impairment is common in schizophrenia, but it is unclear if it is present in individuals with high IQ. This study compared theory of mind (ToM) in schizophrenia participants with low or high IQ to healthy controls. METHODS: One hundred and nineteen participants (71 healthy controls, 17 high IQ (IQ ≥115), and 31 low IQ (IQ ≤95) schizophrenia participants) were assessed with the Movie for the Assessment of Social Cognition, providing scores for total, cognitive, and affective ToM, along with overmentalizing, undermentalizing, and no-mentalizing errors. IQ was measured with Wechsler Abbreviated Scale of Intelligence; clinical symptoms with the Positive and Negative Syndrome Scale. RESULTS: Healthy controls performed better than the low IQ schizophrenia group for all ToM scores, and better than the high IQ schizophrenia group for the total score and under- and no-mentalizing errors. The high IQ group made fewer overmentalizing errors and had better total and cognitive ToM than the low IQ group. Their number of overmentalizing errors was indistinguishable from healthy controls. CONCLUSION: Global ToM impairment was present in the low IQ schizophrenia group. Overmentalizing was not present in the high IQ group and appears related to lower IQ. Intact higher-level reasoning may prevent the high IQ group from making overmentalizing errors, through self-monitoring or inhibition. We propose that high IQ patients are chiefly impaired in lower-level ToM, whereas low IQ patients also have impaired higher-level ToM. Conceivably, this specific impairment could help explain the lower functioning reported in persons with intact IQ.

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.

Affective lability and social functioning in severe mental disorders.

Social functioning is impaired in severe mental disorders despite clinical remission, illustrating the need to identify other mechanisms that hinder psychosocial recovery. Affective lability is elevated and associated with an increased clinical burden in psychosis spectrum disorders. We aimed to investigate putative associations between affective lability and social functioning in 293 participants with severe mental disorders (schizophrenia- and bipolar spectrum), and if such an association was independent of well-established predictors of social impairments. The Affective Lability Scale (ALS-SF) was used to measure affective lability covering the dimensions of anxiety-depression, depression-elation and anger. The interpersonal domain of the Social Functioning Scale (SFS) was used to measure social functioning. Correlation analyses were conducted to investigate associations between affective lability and social functioning, followed by a hierarchical multiple regression and follow-up analyses in diagnostic subgroups. Features related to premorbid and clinical characteristics were entered as independent variables together with the ALS-SF scores. We found that higher scores on all ALS-SF subdimensions were significantly associated with lower social functioning (p < 0.005) in the total sample. For the anxiety-depression dimension of the ALS-SF, this association persisted after controlling for potential confounders such as premorbid social functioning, duration of untreated illness and current symptoms (p = 0.019). Our results indicate that elevated affective lability may have a negative impact on social functioning in severe mental disorders, which warrants further investigation. Clinically, it might be fruitful to target affective lability in severe mental disorders to improve psychosocial outcomes.

A randomized controlled trial of Goal Management Training for executive functioning in schizophrenia spectrum disorders or psychosis risk syndromes.

BACKGROUND: Executive functioning is essential to daily life and severely impaired in schizophrenia and psychosis risk syndromes. Goal Management Training (GMT) is a theoretically founded, empirically supported, metacognitive strategy training program designed to improve executive functioning. METHODS: A randomized controlled parallel group trial compared GMT with treatment as usual among 81 participants (GMT, n = 39 versus Wait List Controls, n = 42) recruited from an early intervention for psychosis setting. Computer generated random allocation was performed by someone independent from the study team and raters post-intervention were unaware of allocation. The primary objective was to assess the impact of GMT administered in small groups for 5 weeks on executive functioning. The secondary objective was to explore the potential of the intervention in influencing daily life functioning and clinical symptoms. RESULTS: GMT improved self-reported executive functioning, measured with the Behavior Rating Inventory of Executive Function - Adult version (BRIEF-A), significantly more than treatment as usual. A linear mixed model for repeated measures, including all partial data according to the principle of intention to treat, showed a significant group x time interaction effect assessed immediately after intervention (post-test) and 6 months after intervention (follow-up), F = 8.40, p .005, r .37. Improvement occurred in both groups in objective executive functioning as measured by neuropsychological tests, functional capacity, daily life functioning and symptoms of psychosis rated by clinicians. Self-reported clinical symptoms measured with the Symptoms Check List (SCL-10) improved significantly more after GMT than after treatment as usual, F = 5.78, p .019, r .29. Two participants withdrew due to strenuous testing and one due to adverse effects. CONCLUSIONS: GMT had clinically reliable and lasting effects on subjective executive function. The intervention is a valuable addition to available treatment with considerable gains at low cost. TRIAL REGISTRATION: Registered at clinicaltrials.gov NCT03048695 09/02/2017.

Premorbid characteristics of patients with DSM-IV psychotic disorders.

INTRODUCTION: Psychotic disorder not otherwise specified (PNOS) is considered part of the psychosis spectrum, together with schizophrenia spectrum disorders (SSD) and psychotic bipolar spectrum disorders (PBD). The atypical clinical presentations of PNOS conditions may lead to uncertainty regarding treatment choices and expected outcomes. PNOS is understudied, and little is known about patients' premorbid characteristics including premorbid adjustment, prevalence of early cannabis use and childhood trauma. Knowledge about early illness phases can increase our understanding of this diagnostic group. METHODS: We included 1099 participants from the Norwegian TOP-study; 688 with narrow SSD diagnoses (schizophrenia, schizoaffective disorder, schizophreniform disorder), 274 with PBD (psychotic bipolar 1 and bipolar NOS) and 137 with PNOS diagnosed with the SCID-I for DSM-IV. Participants were assessed with the Premorbid Adjustment Scale (PAS) divided into the areas of premorbid academic and social functioning. We obtained information on age at first exposure to cannabis and use of cannabis before the age of 16. The participants also provided information regarding early traumatic experiences using the Childhood Trauma Questionnaire (CTQ). RESULTS: Participants with PNOS and SSD had poorer premorbid academic functioning than those with PBD (F2, 1029 = 7.81, p < 0.001, pη2 = 0.015). Premorbid social adjustment was significantly worse in the SSD group compared to the PBD group (F2, 1024 = 3.10, p = 0.045, pη2 = 0.006), with PNOS in the middle position. Significantly more of the participants with PNOS (17.5%) and SSD (11.5%) used cannabis before the age of 16 compared with PBD (5.3%, Wald χ2 = 6.86, p = 0.03). There were no significant differences between the three groups regarding mean CTQ scores or in the proportion of participants who had experienced at least one type of childhood adversity. CONCLUSIONS: Participants with PNOS appear as more similar to participants with SSD than to those with PBD regarding early premorbid adjustment and early cannabis use. The results indicate that many conditions classified as PNOS have functional impairments and problematic substance use from an early age. The prevalence of childhood adversities are high in all three groups.

Significant association between intracranial volume and verbal intellectual abilities in patients with schizophrenia and a history of birth asphyxia.

BACKGROUND: The etiology of schizophrenia (SZ) is proposed to include an interplay between a genetic risk for disease development and the biological environment of pregnancy and birth, where early adversities may contribute to the poorer developmental outcome. We investigated whether a history of birth asphyxia (ASP) moderates the relationship between intracranial volume (ICV) and intelligence in SZ, bipolar disorder (BD) and healthy controls (HC). METHODS: Two hundred seventy-nine adult patients (18-42 years) on the SZ and BD spectrums and 216 HC were evaluated for ASP based on information from the Medical Birth Registry of Norway. Participants underwent structural magnetic resonance imaging (MRI) to estimate ICV and intelligence quotient (IQ) assessment using the Wechsler Abbreviated Scale of Intelligence (WASI). Multiple linear regressions were used for analyses. RESULTS: We found a significant three-way interaction (ICV × ASP × diagnosis) on the outcome variable, IQ, indicating that the correlation between ICV and IQ was stronger in patients with SZ who experienced ASP compared to SZ patients without ASP. This moderation by ASP was not found in BD or HC groups. In patients with SZ, the interaction between ICV and a history of the ASP was specifically related to the verbal subcomponent of IQ as measured by WASI. CONCLUSIONS: The significant positive association between ICV and IQ in patients with SZ who had experienced ASP might indicate abnormal neurodevelopment. Our findings give support for ICV together with verbal intellectual abilities as clinically relevant markers that can be added to prediction tools to enhance evaluations of SZ risk.

Correction: Genome-wide analysis reveals extensive genetic overlap between schizophrenia, bipolar disorder, and intelligence.

A correction to this paper has been published and can be accessed via a link at the top of the paper.

Genome-wide analysis reveals extensive genetic overlap between schizophrenia, bipolar disorder, and intelligence.

Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders associated with cognitive impairment, which is considered a major determinant of functional outcome. Despite this, the etiology of the cognitive impairment is poorly understood, and no satisfactory cognitive treatments exist. Increasing evidence indicates that genetic risk for SCZ may contribute to cognitive impairment, whereas the genetic relationship between BD and cognitive function remains unclear. Here, we combined large genome-wide association study data on SCZ (n = 82,315), BD (n = 51,710), and general intelligence (n = 269,867) to investigate overlap in common genetic variants using conditional false discovery rate (condFDR) analysis. We observed substantial genetic enrichment in both SCZ and BD conditional on associations with intelligence indicating polygenic overlap. Using condFDR analysis, we leveraged this enrichment to increase statistical power and identified 75 distinct genomic loci associated with both SCZ and intelligence, and 12 loci associated with both BD and intelligence at conjunctional FDR < 0.01. Among these loci, 20 are novel for SCZ, and four are novel for BD. Most SCZ risk alleles (61 of 75, 81%) were associated with poorer cognitive performance, whereas most BD risk alleles (9 of 12, 75%) were associated with better cognitive performance. A gene set analysis of the loci shared between SCZ and intelligence implicated biological processes related to neurodevelopment, synaptic integrity, and neurotransmission; the same analysis for BD was underpowered. Altogether, the study demonstrates that both SCZ and BD share genetic influences with intelligence, albeit in a different manner, providing new insights into their genetic architectures.

G-estimation of causal pathways in vocational rehabilitation for adults with psychotic disorders - a secondary analysis of a randomized trial.

BACKGROUND: Vocational rehabilitation (VR) has increasingly become an important intervention targeting poor occupational functioning in schizophrenia. The Norwegian Job Management Program (JUMP), sought to enhance occupational outcomes by augmenting VR with either cognitive behavioral therapy (CBT) techniques aiming to improve psychotic symptoms or cognitive remediation (CR) aiming to improve cognition. CBT is standard treatment in schizophrenia, but recent meta-analyses question the effect of CBT on negative psychotic symptoms. It is of interest to study the causal role of psychotic symptoms and cognitive functioning on occupational functioning. METHODS: Data from the JUMP VR - program, was reanalyzed with a causal inference method to assess the causal effects of reduced symptoms / improved neurocognitive functioning on occupational functioning measured by number of working hours per week. Participants (N = 131) had been randomized to either VR + CBT (N = 68) or VR + CR (N = 63). Large improvements in number of working hours were demonstrated in both intervention groups (nonsignificant group difference). G-estimation was used to assess the strength and nature of the causal effects, adjusted for time-varying confounding and selection - bias from loss to follow-up. RESULTS: Significant causal effects of reduction in each of four dimensions of symptoms and improved neurocognition respectively, on number of working hours were found (separate models). The effect of negative symptoms was the strongest and increased in magnitude during the whole observation period, while the effect of two other symptoms and neurocognition was constant. Adjusted for confounding (including potential feedback), the causal effect of a hypothetical change in negative symptoms equal to the average improvement in the CBT group corresponded to an increase in working hours of 3.2 h per week (95% CI: 1.11, 5.35). CONCLUSION: High performance of g-estimation in a small psychiatric data set with few repeated measures and time-varying confounding and effects, was demonstrated. Augmented vocational rehabilitation showed causal effects of intervention targets with the strongest and increasing effect from negative symptoms on number of working hours. Combination of therapy and activation (indirect and direct approach) might explain improvement in both cognition and negative symptoms, and shed some light on effective ingredients for improved treatment of negative symptoms.

Obstetric complications and intelligence in patients on the schizophrenia-bipolar spectrum and healthy participants.

BACKGROUND: Whether severe obstetric complications (OCs), which harm neural function in offspring, contribute to impaired cognition found in psychiatric disorders is currently unknown. Here, we sought to evaluate how a history of severe OCs is associated with cognitive functioning, indicated by Intelligence Quotient (IQ). METHODS: We evaluated the associations of a history of OCs and IQ in 622 healthy controls (HC) and 870 patients on the schizophrenia (SCZ) - bipolar disorder (BIP) spectrum from the ongoing Thematically Organized Psychosis study cohort, Oslo, Norway. Participants underwent assessments using the NART (premorbid IQ) and the WASI (current IQ). Information about OCs was obtained from the Medical Birth Registry of Norway. Multiple linear regression models were used for analysis. RESULTS: Severe OCs were equally common across groups. SCZ patients with OCs had lower performances on both premorbid and current IQ measures, compared to those without OCs. However, having experienced more than one co-occurring severe OC was associated with lower current IQ in all groups. CONCLUSIONS: Severe OCs were associated with lower IQ in the SCZ group and in the BIP and HC groups, but only if they had experienced more than one severe OC. Low IQ might be a neurodevelopmental marker for SCZ; wherein, severe OCs influence cognitive abilities and increase the risk of developing SCZ. Considering OCs as a variable of neurodevelopmental risk for severe mental illness may promote the development of neuroprotective interventions, improve outcome in vulnerable newborns and advance our ability to make clinical prognoses.

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.

Improvement in verbal learning over the first year of antipsychotic treatment is associated with serum HDL levels in a cohort of first episode psychosis patients.

To investigate whether changes in serum lipids are associated with cognitive performance in first episode psychosis (FEP) patients during their first year of antipsychotic drug treatment. One hundred and thirty-two antipsychotic-treated FEP patients were included through the TOP study along with 83 age- and gender-matched healthy controls (HC). Information regarding cognitive performance, psychotic symptoms, lifestyle, body mass index, serum lipids [total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides] and antipsychotic treatment was obtained at baseline and after 1 year. The cognitive test battery is comprised of assessments for verbal learning, processing speed, working memory, verbal fluency, and inhibition. Mixed-effects models were used to study the relationship between changes over time in serum lipids and cognitive domains, controlling for potential confounders. There was a significant group by HDL interaction effect for verbal learning (F = 11.12, p = 0.001), where an increase in HDL levels was associated with improvement in verbal learning in FEP patients but not in HC. Practice effects, lifestyle, and psychotic symptoms did not significantly affect this relationship. Antipsychotic-treated FEP patients who increased in HDL levels during the first year of follow-up exhibited better verbal learning capacity. Further investigations are needed to clarify the underlying mechanisms.

Do sleep disturbances contribute to cognitive impairments in schizophrenia spectrum and bipolar disorders?

Sleep disturbances and cognitive impairments are both frequent across psychotic disorders, with debilitating effects on functioning and quality of life. This study aims to investigate if sleep disturbances are related to cognitive impairments in schizophrenia spectrum (SCZ) and bipolar disorders (BD), if this relationship varies between different sleep disturbances (insomnia, hypersomnia or delayed sleep phase (DSP)) and lastly, if this relationship differs between clinical groups and healthy controls (HC). We included 797 patients (SCZ = 457, BD = 340) from the Norwegian Centre for Mental Disorders Research (NORMENT) study in Norway. Sleep disturbances were based on items from the Inventory of Depressive Symptoms-Clinician rated scale (IDS-C). Their relationship with several cognitive domains was tested using separate ANCOVAs. A three-way between-groups ANOVA was conducted to test if the relationship with cognitive impairments varies between different sleep disturbances. These analyses revealed significantly poorer processing speed and inhibition in those with any sleep disturbance versus those without, also after adjusting for several covariates. The relationship between sleep disturbances and cognition was similar across SCZ and BD, and there were significant effects of insomnia and hypersomnia on both processing speed and inhibition. No association between sleep disturbances and cognition was found in HC. Sleep disturbances contribute to cognitive impairments in psychotic disorders. Processing speed and inhibition is poorer in patients with sleep disturbances. Impairments in these domains are related to insomnia and hypersomnia. These findings suggest that treating sleep disturbances is important to protect cognitive functioning, alongside cognitive remediation in psychotic disorders.