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Objectives A consensus definition of clinical recovery in first-episode psychosis (FEP) is required to improve knowledge about recovery rates in this population. To propose criteria for a future consensus definition, this study aims to investigate rates of clinical recovery when using a standard definition (full psychotic symptom remission and adequate functioning for minimum one year) across both affective and nonaffective FEP groups (bipolar spectrum and schizophrenia spectrum disorders). Second, we aim to explore changes in rates when altering the standard definition criteria. Third, to examine the extent to which healthy controls meet the functioning criteria. Study design In total, 142 FEP participants and 117 healthy controls preselected with strict criteria, were re-assessed with structured clinical interviews at 10-year follow-up. Study results A total of 31.7% were in clinical recovery according to the standard definition, with significantly higher recovery rates in bipolar (50.0%) than in schizophrenia spectrum disorders (22.9%). Both groups’ recovery rates decreased equally when extending duration and adding affective symptom remission criteria and increased with looser functioning criteria. In healthy controls, 18.8% did not meet the standard criteria for adequate functioning, decreasing to 4.3% with looser criteria. Conclusions Findings suggest that clinical recovery is common in FEP, although more in bipolar than in schizophrenia spectrum disorders, also when altering the recovery criteria. We call for a future consensus definition of clinical recovery for FEP, and suggest it should include affective symptom remission and more reasonable criteria for functioning that are more in line with the general population.

Apathy is prevalent in first-episode psychosis (FEP) and associated with reduced global functioning. Investigations of the trajectory of apathy and its early predictors are needed to develop new treatment interventions. We here measured the levels of apathy over the first 10 years of treatment in FEP and in healthy controls (HC). We recruited 198 HC and 198 FEP participants. We measured apathy with the Apathy Evaluation Scale, self-report version, psychotic symptoms with the Positive and Negative Syndrome Scale, depression with the Calgary Depression Scale for Schizophrenia, functioning with the Global Assessment of Functioning Scale, and also estimated the duration of untreated psychosis (DUP). The longitudinal development of apathy and its predictors were explored using linear mixed models analyses. Associations to functioning at 10 years were investigated using multiple hierarchical linear regression analyses. In HC, mean apathy levels were low and stable. In FEP, apathy levels decreased significantly during the first year of treatment, followed by long-term stability. High individual levels of apathy at baseline were associated with higher apathy levels during the follow-up. Long DUP and high baseline levels of depression predicted higher apathy levels at follow-ups. The effect of DUP was persistent, while the effect of baseline depression decreased over time. At 10 years, apathy was statistically significantly associated with reduced functioning. The early phase of the disorder may be critical to the development of apathy in FEP. Electronic supplementary material The online version of this article (10.1007/s00406-020-01112-3) contains supplementary material, which is available to authorized users.

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.

Background Cardiometabolic risk is increased in severe mental disorders (SMDs), and there appears to be a relationship between childhood trauma and cardiometabolic risk, possibly related to adverse health behavior. The current study examined the association between childhood trauma and serum lipids and adiposity in SMDs and the potential mediating role of cognitive and personality characteristics. Methods Participants with schizophrenia and bipolar spectrum disorders (N = 819) were included, cardiometabolic risk factors (serum lipids, body mass index, and waist circumference) were measured, and history of childhood trauma was assessed by the Childhood Trauma Questionnaire. Cognitive and personality characteristics were available in subsamples, with assessments of cognitive control, impulsiveness, self-esteem, and affective lability. Linear regressions and mediation analyses with Hayes’ PROCESS were performed, adjusting for age, sex, antipsychotic agent propensity of metabolic side-effect, and diagnostic group. Results Experience of three or more subtypes of childhood trauma was positively associated with waist circumference in patients with SMDs (p = 0.014). There were no other significant associations between trauma variables and lipid or adiposity measures in the total sample. Cognitive control was a significant mediator between experience of one or two subtypes of childhood trauma and waist circumference. Conclusions The results indicate childhood trauma as a predisposing factor for increased waist circumference in individuals with SMDs. Poorer cognitive control, suggestive of adverse health behavior, might be a mediating factor of the association, and the findings indicate the potential importance of increased focus on these factors in prevention and treatment regimens targeting cardiometabolic health.

Cognitive impairments are considered core features in schizophrenia and other psychotic disorders. Cognitive impairments are, to a lesser degree, also documented in healthy first-degree relatives. Although recent studies have shown (negative) genetic correlations between schizophrenia and general cognitive ability, the association between polygenic risk for schizophrenia and individual cognitive phenotypes remains unclear. We here investigated the association between a polygenic score for schizophrenia (SCZPGS) and six well-defined cognitive domains, in addition to a composite measure of cognitive ability and a measure of premorbid intellectual ability in 731 participants with a psychotic disorder and 851 healthy controls. We also investigated the association between a PGS for general cognitive ability (COGPGS) and the same cognitive domains in the same sample. We found no significant associations between the SCZPGS and any cognitive phenotypes, in either patients with a psychotic disorder or healthy controls. For COGPGS we observed stronger associations with cognitive phenotypes in healthy controls than in participants with psychotic disorders. In healthy controls, the association between COGPGS (at the p value threshold of ≥0.01) and working memory remained significant after Bonferroni correction (β = 0.12, p = 8.6 × 10−5). Altogether, the lack of associations between SCZPGS and COGPGS with cognitive performance in participants with psychotic disorders suggests that either environmental factors or unassessed genetic factors play a role in the development of cognitive impairments in psychotic disorders. Working memory should be further studied as an important cognitive phenotype.

BackgroundThe experience of childhood trauma is linked to more severe symptoms and poorer functioning in severe mental disorders; however, the mechanisms behind this are poorly understood. We investigate the relationship between childhood trauma and sleep disturbances in severe mental disorders including the role of sleep disturbances in mediating the relationship between childhood trauma and the severity of clinical symptoms and poorer functioning.MethodsIn total, 766 participants with schizophrenia-spectrum (n = 418) or bipolar disorders (n = 348) were assessed with the Childhood Trauma Questionnaire. Sleep disturbances were assessed through the sleep items in the self-reported Inventory of Depressive Symptoms. Clinical symptoms and functioning were assessed with The Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale. Mediation analyses using ordinary least squares regression were conducted to test if sleep disturbances mediated the relationship between childhood trauma and the severity of clinical symptoms and poorer functioning.ResultsSymptoms of insomnia, but not hypersomnia or delayed sleep phase, were significantly more frequent in participants with childhood trauma experiences compared to those without. Physical abuse, emotional abuse, and emotional neglect were significantly associated with insomnia symptoms. Insomnia symptoms partly mediate the relationship between childhood trauma and the severity of positive and depressive/anxiety symptoms, in addition to poorer functioning.ConclusionWe found frequent co-occurrence of childhood trauma history and current insomnia in severe mental disorders. Insomnia partly mediated the relationship between childhood trauma and the severity of clinical symptoms and functional impairment.

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. Electronic supplementary material The online version of this article (10.1007/s00406-019-01017-w) contains supplementary material, which is available to authorized users.

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.

We investigate negative symptoms over a 1-year follow-up period with the objective to see how groups defined according to level of symptom severity are related to cognition. Eighty-seven participants with first-episode psychosis (FEP) and matched healthy controls were assessed at baseline and follow-up. FEP participants were sub-grouped based on negative symptom items from the Positive and Negative Syndrome Scale (PANSS-R) with either no, mild, transitory or sustained symptoms over one year. Following an overall MANOVA, groups were compared on cognitive domains and a cognitive composite using ANOVAs. Cognitive course was explored with a MANOVA. We found a group effect on cognition. Participants who sustained negative symptoms were significantly outperformed by participants with no negative symptoms on executive functions and processing speed, and by those with mild or transitory symptoms on verbal learning and memory. Participants with sustained negative symptoms performed significantly poorer on the cognitive composite than those with no or mild negative symptoms. The group with no negative symptoms did not differ significantly from healthy controls on any cognitive measure, and the groups did not differ in cognitive course. Early course of negative symptoms is associated with cognition and could guide clinicians when evaluating need for cognitive assessment.

Background: Sleep disturbances are prevalent in severe mental disorders but their type and frequency across diagnostic categories has not been investigated in large scale studies. Methods: Participants with Schizophrenia spectrum disorders (SCZ, (N = 617)), Bipolar disorders (BD, (N = 440)), and Healthy Controls (HC, (N = 173)) were included in the study. Sleep disturbances (insomnia, hypersomnia and delayed sleep phase) were identified based on items from the Inventory of Depressive Symptoms – Clinician rated scale. Clinical symptoms were assessed with the Positive and Negative Syndrome scale and level of functioning with the Global assessment of Functioning scale. Results: The rate of any sleep disturbance was 78% in SZ, 69% in BD and 39% in HC. Insomnia was the most frequently reported sleep disturbance across all groups. Both diagnostic groups reported significantly more of any sleep disturbances than HC (P

Aim Lack of insight into illness is frequent in psychotic disorders and seen as part of their primary pathology. The recognition of symptoms as psychotic, and beliefs about treatment alternatives, is also influenced by socio-cultural factors. Here we examined clinical insight into illness and beliefs about psychosis in immigrants in their first episode of psychosis compared with a reference group. Methods A total of 277 first-episode psychosis participants were recruited to this cross-sectional study; 40 first- and 40 second-generation immigrants from Europe, Americas and Oceania (n = 37), Asia including Turkey (n = 28) or Africa (n = 15). The Birchwood Insight Scale was used to measure clinical insight and ‘The Attitudes and Beliefs about Mental Health Problems’ schizophrenia version to assess socio-cultural beliefs. Results Immigrants did not differ from the reference sample in clinical insight. After controlling for education level, first-generation immigrants were less likely to recognize psychotic symptoms (odds ratio (OR) 2.9; Wald = 8.977, degrees of freedom (d.f.) 1, P = 0.003) and viewed hospitalization (OR 5.2; Wald = 20.388, d.f. 1, P = 0.001) and treatment by a psychiatrist (OR 4.9; Wald = 6.609, d.f. 1, P = 0.01)) as less beneficial than the reference group. Immigrants from Asia held more alternative explanations (OR 0.3; Wald = 6.567, d.f. 1, P = 0.010). There were significantly stronger associations between clinical insight and socio-cultural beliefs in the reference group. Conclusions Socio-cultural beliefs about psychosis in immigrants in first-episode psychosis call for more tailored information to this group, and emphasize the importance of treatment interventions involving both a cultural and personal perspective of insight.

Background Sleep disturbances are prevalent in people with psychosis and are related to several negative outcomes. Recent research indicates that sleep disturbances contribute to the development of psychosis and is therefore an important treatment target. Despite this, a study found that sleep problems in people with psychosis were mostly assessed informally and treated with non-recommended interventions. However, it is uncertain whether these findings reflect local practise or rather status quo for how sleep disturbances in the context of psychosis are approached across different treatment sites. We aimed to replicate this study and investigate how sleep disturbances in people with psychosis are viewed, assessed and treated by clinicians across several mental health services, and the clinicians' perceived barriers to sleep treatment. Methods A total of 204 clinicians completed an e-mail survey about sleep problems and psychosis. Results The main findings were highly consistent with previous research; the clinicians found sleep problems in patients with psychosis to be highly prevalent and with negative consequences. However, structured assessments and the use of recommended treatment interventions were rare. This apparent paradox may at least partly be explained by the clinicians' perceived barriers to sleep treatment, including their declared lack of knowledge about sleep assessment and sleep treatment, and beliefs that sleep treatment is (too) demanding in this population. Conclusion Many patients with psychosis across several treatment sites receive less than optimal sleep treatment. Increasing clinicians' knowledge about adequate sleep treatment and its feasibility for patients with psychotic disorders is therefore imperative.

Background: Apathy and depression are prevalent in first-episode psychosis (FEP), have overlapping clinical features and are linked to social dysfunction, with indications that persisting symptoms have an even more negative impact. Our objective was to investigate the prevalence of persisting depression (PD), persisting apathy (PA), to what extent they overlap and their relative associations to functioning during a one-year follow-up. Methods: One hundred and twenty-five participants with a FEP were recruited, and 88 (70%) were reassessed at follow-up. Functional outcome was assessed with the Global Assessment of Functioning Scale-split version, functioning sub-scale, apathy with the Apathy Evaluation Scale, Clinician version (AES-C), and depression with the Calgary Depression Scale for Schizophrenia (CDSS). Persisting depression was defined as a CDSS sum-score > 7 at baseline and follow-up, and persisting apathy as an AES-C sum-score ≥ 27 at baseline and follow-up. Multiple linear regression analyses were used to investigate symptoms' contributions to functioning. Differences in functioning between groups were explored with Kruskal-Wallis test and Mann-Whitney U test. Results: We found PD in 17 (19%) and PA in 28 (32%) of participants. The likelihood of PD was increased if PA was also present (p = 0.008, phi = 0.28). Ten participants (11%) experienced overlapping PD and PA. Participants with PD (r = −0.38, p = 0.004), PA (r = −0.51, p

Background A potential link between increase in total cholesterol and triglycerides and clinical improvement has been observed during antipsychotic drug treatment in chronic schizophrenia patients, possibly due to drug related effects on lipid biosynthesis. We examined whether changes in serum lipids are associated with alleviation of psychosis symptoms after one year of antipsychotic drug treatment in a cohort of first-episode psychosis (FEP) patients. Methods A total of 132 non-affective antipsychotic-treated FEP patients were included through the Norwegian Thematically Organized Psychosis (TOP) project. Data on antipsychotic usage, serum lipids (total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides (TG)), body mass index (BMI) and clinical state were obtained at baseline and after 12 months. The Positive and Negative Syndrome Scale (PANSS) was used to assess psychotic symptoms. Mixed-effects models were employed to examine the relationship between serum lipids and psychotic symptoms while controlling for potential confounders including BMI. Results An increase in HDL during one year of antipsychotic treatment was associated with reduction in PANSS negative subscores (B = − 0.48, p = 0.03). This relationship was not affected by concurrent change in BMI (adjusted HDL: B = − 0.54, p = 0.02). No significant associations were found between serum lipids, BMI and PANSS positive subscores. Conclusion We found that an increase in HDL level during antipsychotic treatment is associated with improvement in negative symptoms in FEP. These findings warrant further investigation to clarify the interaction between lipid pathways and psychosis.

BackgroundFirst-episode psychosis (FEP) patients show structural brain abnormalities. Whether the changes are progressive or not remain under debate, and the results from longitudinal magnetic resonance imaging (MRI) studies are mixed. We investigated if FEP patients showed a different pattern of regional brain structural change over a 1-year period compared with healthy controls, and if putative changes correlated with clinical characteristics and outcome.MethodMRIs of 79 FEP patients [SCID-I-verified diagnoses: schizophrenia, psychotic bipolar disorder, or other psychoses, mean age 27.6 (s.d. = 7.7) years, 66% male] and 82 healthy controls [age 29.3 (s.d. = 7.2) years, 66% male] were acquired from the same 1.5 T scanner at baseline and 1-year follow-up as part of the Thematically Organized Psychosis (TOP) study, Oslo, Norway. Scans were automatically processed with the longitudinal stream in FreeSurfer that creates an unbiased within-subject template image. General linear models were used to analyse longitudinal change in a wide range of subcortical volumes and detailed thickness and surface area estimates across the entire cortex, and associations with clinical characteristics.ResultsFEP patients and controls did not differ significantly in annual percentage change in cortical thickness or area in any cortical region, or in any of the subcortical structures after adjustment for multiple comparisons. Within the FEP group, duration of untreated psychosis, age at illness onset, antipsychotic medication use and remission at follow-up were not related to longitudinal brain change.ConclusionsWe found no significant longitudinal brain changes over a 1-year period in FEP patients. Our results do not support early progressive brain changes in psychotic disorders.

thinking is important in modern understanding of neurocognitive abilities, and a symptom of thought disorder in psychosis. In patients with psychosis, we assessed if socio-developmental background influences abstract thinking, and the association with executive functioning and clinical psychosis symptoms.Participants (n = 174) had a diagnosis of psychotic or bipolar disorder, were 17-65 years, intelligence quotient (IQ) 70, fluent in a Scandinavian language, and their full primary education in Norway. Immigrants (N = 58) were matched (1:2) with participants without a history of migration (N = 116). All participants completed a neurocognitive and clinical assessment. Socio-developmental background was operationalised as human developmental index (HDI) of country of birth, at year of birth. Structural equation modelling was used to assess the model with best fit.The model with best fit, χThis study found that socio-developmental background influences abstract thinking in psychosis by indirect effect through executive functioning. We should take into account socio-developmental background in the interpretation of neurocognitive performance in patients with psychosis, and prioritise cognitive remediation in treatment of immigrant patients.

Background Mood stabilizers like lithium and anticonvulsants are used in bipolar and related psychotic disorders. There is a lack of knowledge of the relationship of these medications and cognition in the psychosis spectrum. We studied the association between serum concentration of mood stabilizers and cognitive performance in a well-characterized sample of bipolar and schizophrenia spectrum disorders. Methods Serum concentrations of valproate, lamotrigine, and lithium were analyzed for associations to performance on neuropsychological tests in six cognitive domains in individuals with bipolar disorder (n = 167) and in a combined sample of individuals with bipolar or schizophrenia spectrum disorders (n = 217). Linear regression with adjustments for gender, age, and symptom levels of depression, mania, and psychosis were applied for the association analyses. Results There were negative associations between serum levels of valproate and short term delayed recall (bipolar: p = 0.043; combined: p = 0.044) and working memory (bipolar: p = 0.043). A positive association was suggested between serum level of lithium and working memory (bipolar: p = 0.039). There were no other significant relationships between serum levels of valproate, lamotrigine, or lithium and neuropsychological test performance in neither the bipolar disorder nor the combined group. Conclusions Serum levels of mood stabilizers were unrelated to cognitive performance in most domains, indicating that higher dose does not lead to broader cognitive impairments in bipolar and related psychotic disorder patients. However, worsened memory with increasing levels of valproate suggests cautious dosing of anticonvulsants, while increasing lithium level seems to be associated with improved memory. The findings should be interpreted with caution due to the explorative, naturalistic design.

Antipsychotics are effective in treating psychosis and mood episodes; however, the effect on cognition is less known. We investigated the association between serum levels of second-generation antipsychotics (SGAs) and cognitive performance in psychosis spectrum disorders in a naturalistic setting.A total of 495 patients with a DSM-IV Schizophrenia and Other Psychotic Disorders (SCZ, n = 373) or Bipolar Disorder (BD, n = 122) diagnosis treated with olanzapine, quetiapine, aripiprazole or risperidone were tested neuropsychologically with concurrent measurement of the serum concentration of the drug. Linear regression was used for association analyses.Attention was positively associated with the olanzapine concentration (standardised beta (β) coefficient = 0.19, P = .006), and short-term verbal memory and verbal fluency were negatively associated with the quetiapine (β = -0.24, P = .004) and risperidone (β = -0.37, P = .007) concentrations respectively.The present results suggest that SGA serum concentration is associated with better attention (small effect size), and worse verbal memory (small effect size) and verbal fluency (medium effect size). These findings are in line with the notion that SGAs affect aspects of cognitive function, and suggest careful dosing in patients with severe memory and executive problems.

Objective: To investigate potential risk factors for medication non-adherence in patients with schizophrenia and bipolar disorder. Method: A total of 255 patients underwent clinical assessments, neurocognitive testing and blood sampling. The patients were divided into groups of ‘No’, ‘Partial’ or ‘Full’ adherence. Relationships to different risk factors were analyzed. Results: In schizophrenia, use of illicit substances, alcohol and poor insight were related to worse adherence. Schizophrenia patients with No adherence did better on tests of executive functioning, verbal learning and memory and had higher IQ than patients with better adherence. There were higher levels of autonomic side effects in the non-adherence group, but body mass index was lower in the Partial adherence group than in the Full adherence group. In the bipolar disorder patients, there was an association between the use of illicit substances and alcohol and poor adherence. We found no relationship between adherence behavior and neurocognition in the bipolar disorder group. Conclusion: Substance use is an important risk factor for non-adherence in patients with schizophrenia and bipolar disorder. Poor insight is also a risk factor in schizophrenia. The results suggest that cognitive dysfunction is not a risk factor for non-adherence in these diagnostic groups.

To investigate sex differences in neurocognition and social functioning in schizophrenia and bipolar disorder and the possible role of sex as a moderator of this relationship.Participants with schizophrenia (60 women/94 men), bipolar I disorder (55 women/51 men), and healthy controls (158 women/182 men) were assessed with an extensive neuropsychological test battery and a social functioning questionnaire.We found significant main effects of sex for neuropsychological tests (p.001, η² = 0.10) and social functioning (p.001, η² = 0.05), with men scoring below women. Women performed better than men for all neuropsychological tests (except attention and working memory). Both clinical groups performed below healthy controls for all neuropsychological tests (except attention). Post hoc comparisons of persons with schizophrenia and healthy controls yielded significant interaction effects (p.05) for three neuropsychological tests (California Verbal Learning Test II [CVLT-II], Color-Word Interference, and Interference/Switching), with men with schizophrenia being disproportionally disadvantaged compared with their female counterparts. Regression analyses investigating sex as a moderator between neurocognition and social functioning showed that neurocognition predicted social functioning in schizophrenia, whereas sex predicted social functioning in healthy controls. Sex was not a moderator in any of the three groups.This study is the first to find neurocognitive sex differences for bipolar disorder and replicated previous findings for schizophrenia. The data did not support the hypothesis that sex is a moderator between neurocognition and social functioning. Clinical implications include the use of different cognitive remediation strategies based on sex.

Hellvin, T., Sundet, K.,Vaskinn, A., Simonsen, C.,Ueland, T., Andreassen, O.A. & Melle, I. (2010). Validation of the Norwegian version of the Social Functioning Scale (SFS) for schizophrenia and bipolar disorder. Scandinavian Journal of Psychology 51, 525–533. Studies of social functioning in severe mental disorders are disadvantaged by the multitude of different assessment instruments in use. The present study aims to establish reliability and validity of the Norwegian version of the Social Functioning Scale (SFS) and to examine social functioning in bipolar disorder (BD) compared to schizophrenia (SZ) and healthy controls (HC). SFS, a 76 item questionnaire divided into seven subscales measuring various aspects of daily life functioning, was administered to samples diagnosed with BD (n = 100) or SZ (n = 100) and to HC (n = 100), recruited from the ongoing Tematic Organized Psychosis (TOP) study. Reliability analyses prove adequate psychometric properties both for the composite full scale score (α: 0.81) as well as for the seven subscale scores (α: 0.60–0.88). Principal component analysis of the subscales confirms a one-component structure, explaining 59% of the variance. Although significantly correlated with the Global Assessment of Functioning, our results indicate that the SFS measures different aspects of social functioning, is less influenced by demographic and clinical characteristics, but differentiates at the same time significantly BD from SZ. Thus, SFS adds valuable information as a supplement to standard clinician-rated assessment tools of social functioning, suited both for research and clinical work.

In line with a dimensional approach to psychopathology, we examined whether psychosocial function and its relationship to neurocognition and clinical symptoms differ across schizophrenia and bipolar disorder subgroups with and without a history of affective or psychotic episodes. From the TOP study, a heterogeneous sample of individuals with schizophrenia spectrum disorders without (n = 60) and with a history of affective episodes (n = 54); individuals with bipolar spectrum disorders with (n = 64) and without a history of psychosis (n = 56) and healthy controls (n = 268) participated. Psychosocial functioning was measured with the Social Functioning Scale (self-rated) and the Global Assessment of Functioning Scale (clinician-rated), neurocognition with a comprehensive neuropsychological test battery, and symptoms with Inventory of Depressive Symptomatology, Young Mania Rating Scale, and Positive and Negative Syndrome Scale. Clinician-rated functioning was poorer in schizophrenia groups than in bipolar groups, but self-rated functioning was similar across all clinical groups and poorer than in controls. Neurocognition and current clinical symptoms were associated with psychosocial function in bivariate analyses, but current symptoms had a greater independent contribution to functioning than neurocognition across clinical groups in multivariate analyses. Despite differences in neurocognition and psychosocial function, groups showed the same pattern in prediction of functioning irrespective of DSM-IV or clinical definition. (JINS, 2010, 16, 771–783.)

Objectives: Neurocognitive dysfunction is milder in bipolar disorders than in schizophrenia spectrum disorders, supporting a dimensional approach to severe mental disorders. The aim of this study was to investigate the role of lifetime history of psychosis for neurocognitive functioning across these disorders. We asked whether neurocognitive dysfunction in bipolar and schizophrenia spectrum disorders depends more on history of psychosis than diagnostic category or subtype. Methods: A sample of individuals with schizophrenia (n = 102), schizoaffective disorder (n = 27), and bipolar disorder (I or II) with history of psychosis (n = 75) and without history of psychosis (n = 61) and healthy controls (n = 280), from a large ongoing study on severe mental disorder, were included. Neurocognitive function was measured with a comprehensive neuropsychological test battery. Results: Compared with controls, all 3 groups with a history of psychosis performed poorer across neurocognitive measures, while the bipolar group without a history of psychosis was only impaired on a measure of processing speed. The groups with a history of psychosis did not differ from each other but performed poorer than the group without a history of psychosis on a number of neurocognitive measures. These neurocognitive group differences were of a magnitude expected to have clinical significance. In the bipolar sample, history of psychosis explained more of the neurocognitive variance than bipolar diagnostic subtype. Conclusions: Our findings suggest that neurocognitive dysfunction in bipolar and schizophrenia spectrum disorders is determined more by history of psychosis than by Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnostic category or subtype, supporting a more dimensional approach in future diagnostic systems.

The purpose of the study was to investigate the relationship between the symptoms delusions and hallucinations measured by the Positive and Negative Syndrome Scale and cognitive insight as assessed with the Beck Cognitive Insight Scale (BCIS) in patients with schizophrenia. The BCIS is based on 2 subscales, self-reflectiveness and self-certainty, measuring objectivity, reflectiveness and openness to feedback, and mental flexibility. Overall cognitive insight was defined as the difference between self-reflectiveness and self-certainty. This cross-sectional study of 143 patients showed that the occurrence of delusions is associated with low self-reflectiveness and high self-certainty, reflecting low cognitive insight. Hallucinations in the absence of delusions were associated with high self-reflectiveness and low self-certainty, possibly reflecting more open-mindedness and higher cognitive insight. The present findings suggest that delusions are associated with low cognitive insight, whereas solitary hallucinations may be associated with high cognitive insight.

Objective: Impaired emotion perception is documented for schizophrenia, but findings have been mixed for bipolar disorder. In healthy samples females perform better than males. This study compared emotion perception in schizophrenia and bipolar disorder and investigated the effects of gender. Method: Visual (facial pictures) and auditory (sentences) emotional stimuli were presented for identification and discrimination in groups of participants with schizophrenia, bipolar disorder and healthy controls. Results: Visual emotion perception was unimpaired in both clinical groups, but the schizophrenia sample showed reduced auditory emotion perception. Healthy males and male schizophrenia subjects performed worse than their female counterparts, whereas there were no gender differences within the bipolar group. Conclusion: A disease-specific auditory emotion processing deficit was confirmed in schizophrenia, especially for males. Participants with bipolar disorder performed unimpaired.

Cognitive impairment is a core feature of psychosis spectrum disorders. Antipsychotics have at best small positive effects on cognitive performance. There is a lack of knowledge regarding the effects of antidepressants on cognitive functioning in these disorders. In the present study cognitive performance was investigated in relation to serum levels of antidepressants in persons with bipolar disorder and schizophrenia. Serum concentrations of escitalopram, citalopram and venlafaxine plus O-desmethylvenlafaxine were measured in a total of 187 participants with bipolar disorder (N=74) or schizophrenia spectrum disorders (N=113), and analyzed in relation to neuropsychological tests performance of verbal learning, verbal memory, attention, working memory, executive functioning and processing speed. Analyses were performed using linear regression adjusting for a range of confounders. There was a significant positive association between the serum level of venlafaxine plus O-desmethylvenlafaxine and verbal memory (immediate recall: Logical Memory Test immediate recall [p=0.015], and long term delayed recall: Logical Memory Test delayed recall [p=0.011]). No significant associations were seen between citalopram or escitalopram and verbal memory. There were no significant associations between the tested antidepressants and verbal learning, attention, working memory, executive functioning, or processing speed. Venlafaxine seem to be associated with better verbal memory in bipolar disorder and schizophrenia. This suggests a possible beneficial role of certain antidepressants on cognitive dysfunction, which may have clinical implications and provide insight into underlying pathophysiology. However, the current findings should be replicated in independent samples.

Objectives Explanatory factors for the observed neurocognitive impairment in early-stage bipolar I disorder (BD-I) have received little attention. The current study investigated neurocognitive functioning in first-treatment (FT) BD-I compared to FT schizophrenia (SCZ), and healthy controls (HCs), and the effect of history of psychosis and previous episodes in the two clinical groups. Methods A total of 202 FT patients with BD-I (n = 101) and SCZ spectrum disorder (n = 101), in addition to HCs (n = 101), were included. A comprehensive neurocognitive test battery was used to assess verbal learning and memory, executive functioning, processing speed, and attention and working memory. Neurocognitive functioning and the effect of history of psychosis and number of previous episodes were analyzed using separate multivariate analyses of variance and correlation analysis. Results FT patients with BD-I performed intermediately between FT SCZ spectrum patients and HCs on all measures. Compared to HCs, FT BD-I showed impaired functioning across all neurocognitive domains. No differences in neurocognitive functioning were observed in psychotic versus nonpsychotic FT patients with BD-I. With the exception of an association between number of manic episodes and two measures of executive function in FT BD-I, no associations were found between number of episodes and neurocognitive performance. Conclusions Neurocognitive impairments were present in FT BD-I, and were not explained by history of psychosis or number of previous psychotic or depressive episodes. There were indications that executive function could be associated with number of previous manic episodes.

Background Evidence of associations between neurocognitive function and cannabis use in schizophrenia is inconclusive. However, direct measures of cannabis intake and premorbid function are rarely explored in this context. We investigated the relation between cannabis use, determined by its presence in urine, and neurocognitive functioning in schizophrenia controlling for the potential bias of premorbid functioning. Methods Naturalistic study of 364 patients with schizophrenia spectrum disorder from catchment areas in Oslo, Norway. Hierarchical multiple regression analyses were used to assess the relationship between cannabis in urine and measures of neurocognitive functioning, with adjustment for confounders, including premorbid functioning. Results Cannabis was detected in the urine of 21 patients, who had significant dysfunction in several neurocognitive domains independent of a current diagnosis of cannabis abuse. However, level of premorbid functioning explained the associations for all measures. Conclusion Differences in premorbid functioning may explain apparent differences in neurocognitive function between schizophrenia spectrum patients using cannabis or not. The findings suggest that illness-related traits present early in life can affect both later cannabis use and neurocognition, probably by complex mechanisms.

Objective The aim of this study was to investigate whether suicide attempters had higher IQ, better executive functioning, or were more impulsive as measured by neuropsychological tests than non-attempters in a group of patients with schizophrenia spectrum disorders. Method One hundred seventy-four patients with schizophrenia spectrum disorders were assessed with a clinical interview for diagnosis, suicidality, symptoms and function, and underwent an extensive neurocognitive test battery. Results There were no statistically significant differences in any neurocognitive domains between lifetime suicide attempters and non-attempters, or between patients with different rates of suicide attempts. Currently suicidal patients were significantly more impulsive (had poorer inhibitory control) than currently non-suicidal patients, but this difference was mediated by positive psychotic symptoms. Conclusion The findings indicate that among patients with schizophrenia spectrum disorders, there are no significant differences in IQ or neurocognitive functioning between suicide attempters and non-attempters.

Learning potential, a dynamic multi-administration approach to assessment, is claimed to predict functional outcome in schizophrenia better than traditional single-administration neuropsychological tests.This study investigates the relation between learning potential and clinical and demographic variables, social functioning and neuropsychological abilities in a sample of 30 participants with schizophrenia with a mean IQ score within the normal range (mean Wechsler Abbreviated Scale of Intelligence (WASI) IQ=106).Two Wisconsin Card Sorting Test (WCST) based methods for assessing learning potential are compared.The dimensional approach (calculation of gain scores following training) identified one aspect of executive functioning (set shifting) to be related to learning potential. Associations with other neuropsychological tests and social functioning were however limited. The categorical approach (separating high-achievers from learners and non-learners) was not sensitive within this normal IQ sample.Although there seems to be a relation between learning potential and some aspects of executive functioning, the two existing WCST methods should be used with caution when assessing learning potential in individuals with schizophrenia who have IQ scores within the normal range.

Background The underlying nature of negative symptoms in psychosis is poorly understood. Investigation of the relationship between the different negative subsymptoms and neurocognition is one approach to understand more of the underlying nature. Apathy, one of the subsymptoms, is also a common symptom in other brain disorders. Its association with neurocognition, in particular executive functioning, is well documented in other brain disorders, but only studied in one former study of chronic patients with schizophrenia. This study investigates the association between apathy and neurocognitive functioning in patients with first episode psychosis (FEP), with the hypothesis that apathy is more associated with tests representing executive function than tests representing other neurocognitive domains. Methods Seventy-one FEP patients were assessed with an extensive neuropsychological test battery. Level of apathy was assessed with the abridged Apathy Evaluation Scale (AES-C-Apathy). Results AES-C-Apathy was only significantly associated with tests from the executive domain [Semantic fluency (r =.37, p

This study examined the potential of using the regular administration of a common neuropsychological test, the CVLT-II, to assess learning potential in schizophrenia. Based on List A trial 1 performance and the learning slope, a schizophrenia sample was divided into three learning potential groups (non-learners, learners and high-achievers) that differed in the use of learning strategies. High-achievers utilized more semantic clustering than learners and non-learners, and non-learners were less consistent in words recalled than the other two groups. This standard administration approach is a promising, time-saving alternative to the modified tests of learning potential used so far.

Social cognition and learning potential have been proposed as mediating variables between neurocognition and functional outcome in schizophrenia. The present study examined this relation in a schizophrenia group (N = 26) with normal IQ. Neurocognition was measured with a composite score from tests of verbal learning, psychomotor speed, and executive functioning. Functional outcome was defined as social problem-solving skills and assessed with a role-play test. Social cognition was indexed by tests of visual and auditory emotion perception; and learning potential by estimating a gain score using a triple administration of the WCST. Neurocognition was confirmed to be a strong predictor of social problem-solving, and emotion perception was related to both neurocognition and social problem-solving. When controlling for emotion perception, the association between neurocognition and social problem-solving was weakened, implying a mediating role of emotion perception. Learning potential was not significantly related to neurocognition or social problem-solving, and thus not found to mediate the studied relation. In conclusion, our study indicates that emotion perception is a mediator between neurocognition and functional outcome as assessed with a social problem-solving task and thus a key factor in understanding functional outcome of schizophrenia.

OBJECTIVE: In schizophrenia, increased rates of somatic mortality have been shown to correspond with a high prevalence of cardiovascular risk factors, including smoking and the metabolic syndrome. In bipolar disorder, the amount of cardiovascular risk is still largely unknown. This study compares the prevalence of smoking and metabolic disturbances in bipolar disorder and schizophrenia in a representative sample of patients under naturalistic conditions. It also compares the prevalence of risk factors in each diagnostic group with the general population. METHOD: Longitudinal data on clinical groups from October 2002 through December 2005 were from the Oslo TOP Study (DSM-IV bipolar disorder [N = 110] and schizophrenia [N = 163]). Reference data were from the 2000 to 2001 Oslo Health Study (18,770 individuals of the same area). Background variables, prevalence of smoking, and age-adjusted levels of metabolic risk factors were compared between diagnostic groups. Risk factors in both groups were then compared with the general population. RESULTS: Patients with bipolar disorder had higher levels of education, better social functioning, fewer psychiatric symptoms, and less use of medication than patients with schizophrenia. There was no significant difference between diagnostic groups in the prevalence of smoking, obesity, metabolic syndrome, or diabetes. The mean level of high density lipoprotein cholesterol was lower in schizophrenia (p < .001), and systolic blood pressure was higher in bipolar disorder (p < .05). Both diagnostic groups had a prevalence of cardiovascular risk factors about twice that of the general population. CONCLUSION: The prevalence of cardiovascular risk factors was alarmingly high for bipolar disorder and schizophrenia patients compared with the general population, and the prevalence was approximately the same in both diagnostic groups.

Background First-episode psychosis (FEP) patients show structural brain abnormalities. Whether the changes are progressive or not remain under debate, and the results from longitudinal magnetic resonance imaging (MRI) studies are mixed. We investigated if FEP patients showed a different pattern of regional brain structural change over a one-year period compared to healthy controls, and if putative changes correlated with clinical characteristics and outcome. Methods MRIs of 79 FEP (SCID-I verified diagnoses: schizophrenia, psychotic bipolar disorder, or other psychoses, mean age 27.6 (SD 7.7), 66% male) and 82 healthy controls (age 29.3 (SD 7.2) 66% male) were acquired from the same 1.5T scanner at baseline and one-year follow up as part of the TOP study, Oslo, Norway. Scans were automatically processed with the longitudinal stream in FreeSurfer. General linear models were used to analyze longitudinal change in a wide range of subcortical volumes and detailed thickness and surface area estimates across the entire cortex, and associations to clinical characteristics. Results FEP and controls did not differ significantly in annual percentage change in cortical thickness or area in any cortical region, or in any of the subcortical structures after adjustment for multiple comparisons. Within the FEP group, duration of untreated psychosis, age at illness onset, antipsychotic medication use, and remission at follow-up were not related to longitudinal brain change. Conclusion We found no longitudinal brain changes over a one-year period in FEP compared to controls. Our results do not support early progressive brain changes in psychotic disorders.

BackgroundCannabis use is associated with altered neurocognitive functioning in severe mental disorders, but data are still inconclusive and there are no studies of bipolar disorder. The aim of this study was to investigate the association between cannabis use and neurocognition in bipolar disorder compared with schizophrenia in a naturalistic setting.MethodA total of 133 patients with bipolar disorder and 140 patients with schizophrenia underwent neuropsychological assessments and clinical characterization including measures of substance use. Relationships between cannabis users and neurocognitive function were explored in the two diagnostic groups. Possible interactions between diagnosis and cannabis use were investigated, and findings were controlled for possible confounders.ResultsIn bipolar disorder subjects, cannabis use was associated with better neurocognitive function, but the opposite was the case for the schizophrenia subjects. There was a statistically significant interaction effect of diagnosis and cannabis use on focused attention (p=0.019), executive functioning (verbal fluency – set shifting) (p=0.009), logical memory-learning (p=0.007) and on logical memory-recall (p=0.004). These differences in neurocognitive function could not be explained by putative confounders.ConclusionsThe findings suggest that cannabis use may be related to improved neurocognition in bipolar disorder and compromised neurocognition in schizophrenia. The results need to be replicated in independent samples, and may suggest different underlying disease mechanisms in the two disorders.

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd., Objective: An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and previous meta-analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view. Method: Individual patient and control data were obtained from original authors for 11 measures from four common neuropsychological tests: California or Rey Verbal Learning Task (VLT), Trail Making Test (TMT), Digit Span and/or Wisconsin Card Sorting Task. Results: Impairments were found for all 11 test-measures in the bipolar group after controlling for age, IQ and gender (Ps 0.001, E.S. = 0.26–0.63). Residual mood symptoms confound this result but cannot account for the effect sizes found. Impairments also seem unrelated to drug treatment. Some test-measures were weakly correlated with illness severity measures suggesting that some impairments may track illness progression. Conclusion: This reanalysis supports VLT, Digit Span and TMT as robust measures of cognitive impairments in bipolar disorder patients. The heterogeneity of some test results explains previous differences in meta-analyses. Better controlling for confounds suggests deficits may be smaller than previously reported but should be tracked longitudinally across illness progression and treatment., This paper was partially supported by a Seventh Framework Programme grant from the European Union to the European Network of Bipolar Research Expert Centres (ENBREC), Grant No. Health‐F2‐2009‐223102.