Tone Hellvin

Neurocognitive functioning in patients recently diagnosed with bipolar disorder

Hellvin T, Sundet K, Simonsen C, Aminoff SR, Lagerberg TV, Andreassen OA, Melle I. Neurocognitive functioning in patients recently diagnosed with bipolar disorder. Bipolar Disord 2012: 14: 227–238.

BDNF val66met modulates the association between childhood trauma, cognitive and brain abnormalities in psychoses

OBJECTIVE Brain derived neurotrophic factor (BDNF) is important for brain development and plasticity, and here we tested if the functional BDNF val66met variant modulates the association between high levels of childhood abuse, cognitive function, and brain abnormalities in psychoses. METHOD 249 patients with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder were consecutively recruited to the TOP research study (mean±age: 30.7±10.9; gender: 49% males). History of childhood trauma was obtained using the Childhood Trauma Questionnaire. Cognitive function was assessed through a standardized neuropsychological test battery. BDNF val66met was genotyped using standardized procedures. A sub-sample of n=106 Caucasians with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder (mean±age: 32.67±10.85; 49% males) had data on sMRI. RESULTS Carriers of the Methionine (met) allele exposed to high level of childhood abuse demonstrated significantly poorer cognitive functioning compared to homozygotic Valine (val/val) carriers. Taking in consideration multiple testing, using a more conservative p value, this was still shown for physical abuse and emotional abuse, as well as a trend level for sexual abuse. Further, met carriers exposed to high level of childhood sexual abuse showed reduced right hippocampal volume (r(2)=0.43; p=0.008), and larger right and left lateral ventricles (r(2)=0.37; p=0.002, and r(2)=0.27; p=0.009, respectively). Our findings were independent of age, gender, diagnosis and intracranial volume. CONCLUSION Our data demonstrate that in patients with psychoses, met carriers of the BDNF val66met with high level of childhood abuse have more cognitive and brain abnormalities than all other groups.

Psychosocial function in schizophrenia and bipolar disorder: Relationship to neurocognition and clinical symptoms

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.

Sex differences in neuropsychological performance and social functioning in schizophrenia and bipolar disorder.

OBJECTIVE 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. METHOD 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. RESULTS 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. CONCLUSIONS 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.

Neurocognitive features in subgroups of bipolar disorder

To examine which subgroups of DSM‐IV bipolar disorder (BD) [BD type I (BD‐I) or BD type II (BD‐II), and subgroups based on history of psychosis, presenting polarity, and age at onset] differentiate best regarding neurocognitive measures.

Validation of the Norwegian version of the Social Functioning Scale (SFS) for schizophrenia and bipolar disorder

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.

An association between affective lability and executive functioning in bipolar disorder

Studies suggest altered affect regulation manifested by affective lability in manic/mixed and euthymic states in patients with bipolar disorder (BD). Altered affect regulation may arise from disturbances in interactions between the cognitive and the emotional brain networks. However, the relationship between affective lability and executive function has not previously been studied. Our aim was to investigate affective lability, as measured with the Affective Lability Scale (ALS) in patients with BD (N=32) compared to healthy controls (HC) (N=60), and its relationship to executive functioning. We found significantly higher ALS scores in the BD than in the HC group, indicating a higher degree of affective lability in patients with BD. Sub-sample analysis revealed a significant positive relationship between affective lability and semantic set shifting abilities in BD only. These findings suggest that higher levels of affective lability compared with controls are a trait as well as state dependent in BD, and that disturbed affective lability may arise from an aberrant interaction between cognitive and emotional brain networks.

History of psychosis and previous episodes as potential explanatory factors for neurocognitive impairment in first-treatment bipolar I disorder.

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.

Treatment Delay and Excessive Substance Use in Bipolar Disorder

The aim of the present study was to investigate the relationship between treatment delay and excessive substance use. A total of 151 bipolar disorder (BD) I and II patients were consecutively recruited from in- and outpatient psychiatric units, and categorized as primary or secondary BD (without or with antecedent excessive substance use). Predictors of treatment delay among all patients, and predictors of subsequent excessive substance use among primary BD patients, were investigated with logistic regression analyses. The median treatment delay was 2.0 years (IQR 14.0). The risk of long treatment delays was increased in patients with BD II disorder, no lifetime psychosis, a higher age at first contact with specialized psychiatric services, primary BD, and excessive substance use. In primary BD, the risk for developing excessive substance use was increased in males, in patients with shorter education and longer treatment delays. Patients with antecedent excessive substance use had reduced risk of long treatment delays. The risk of developing excessive substance use after BD onset increased with longer treatment delays.

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

Bipolar disorder (BD), over the long term, can manifest a variety of outcomes depending on a number of different conditions. There is a need for further knowledge regarding preventive factors as well as predictors of the disabling course of the disorder. Studies regarding the impact on functional outcome of premorbid and current general intellectual function [intelligence quotient (IQ)] and premorbid functioning in BD patients are sparse. The present study addressed the role of premorbid functioning [assessed with the Premorbid Adjustment Scale (PAS)], intelligence, course of illness, and sociodemographics on occupational outcome in BD.