Neurocognitive functioning, clinical course and functional outcome in first-treatment bipolar I disorder patients with and without clinical relapse: A 1-year follow-up study.

OBJECTIVES: Due to limited research on the association between recurrence of mood episodes and the longitudinal course of neurocognitive functioning in early phase bipolar I disorder (BD I), the impact of recurrence on neurocognition remains unclear. Further, a strong correlation between neurocognitive impairment and functional impairment has been demonstrated. The longitudinal relationship between neurocognitive impairment and functional outcome in relation to recurrence is, however, not established. METHODS: The current study investigated the longitudinal relationship between neurocognition, recurrence of mood episodes and functional outcome in a sample of first-treatment (FT) BD I patients (N = 42), with and without relapse, during a 1-year follow-up period. The longitudinal course of neurocognitive functioning in the patients was also compared to that of a group of healthy controls (N = 143). RESULTS: Compared to both patients with relapse and healthy controls, no-relapse patients showed neurocognitive improvements. The polarity of the relapse episodes was mostly depressive, and for the no-relapse patients, reduction of symptoms was associated with neurocognitive improvement. No-relapse patients showed better global and occupational functioning. CONCLUSIONS: The current study found different neurocognitive and functional trajectories in FT BD I patients with and without relapse, with differences at follow-up to some degree being mediated by current symptoms. The current findings highlight the importance of treatment focusing on neurocognition and symptom states with the aim of improving functional recovery.

Course of neurocognitive function in first treatment bipolar I disorder: One-year follow-up study.

Neurocognitive impairment has been found to be a marked feature in bipolar disorder (BD), also in the early phase of the illness. The longitudinal course of neurocognitive functioning, however, remains sparsely investigated. The aims of the study were to investigate the course of neurocognitive function in BD I, and to what degree neurocognitive change or stability is observed also on the individual level. Forty-two patients and 153 comparable healthy controls were assessed at baseline and one-year follow-up. Compared to the healthy control (HC) group BD I patients perform significantly poorer at both baseline and follow-up across all neurocognitive domains and on most neurocognitive subtests. Neurocognitive impairment remained stable for most patients from baseline to follow-up, both on a group level and when investigating individual trajectories, indicative of a relatively stable course of neurocognitive functioning in the early phase of BD I.

An exploration of metacognitive beliefs and thought control strategies in bipolar disorder.

BACKGROUND: Metacognitive factors influence depression, but are largely unexplored in bipolar disorders. We examined i) differences in metacognitive beliefs and thought control strategies between individuals with bipolar disorder and controls, and ii) to what extent clinical characteristics were related to levels of metacognitive beliefs and thought control strategies in bipolar disorder. METHOD: Eighty patients with bipolar disorder were assessed for age at onset of affective disorder, number of affective episodes, symptoms of mania and depression, metacognitive beliefs (MCQ-30) and thought control strategies (TCQ). Control subjects (N=166) completed MCQ-30 and TCQ. Factors impacting on metacognitive beliefs and thought control strategies were explored with multiple linear regressions. RESULTS: Patients with bipolar disorder reported higher levels of unhelpful metacognitive beliefs and thought control strategies than controls. Metacognitive beliefs were mainly influenced by depressive symptoms, and age at onset of affective illness. Thought control strategies were mainly influenced by metacognitive beliefs and age at onset of affective illness. CONCLUSION: Our findings suggest that metacognitive beliefs and control strategies are relevant in bipolar disorder. Depression and age at onset of affective disorder could contribute to metacognitive beliefs in bipolar disorder, and influence the use of thought control strategies. This indicates potential relationships that warrant further investigation for clinical relevance.

Duration of untreated illness in first-treatment bipolar I disorder in relation to clinical outcome and cannabis use.

There is little knowledge about the role of the duration of untreated bipolar (DUB) illness in first-treatment bipolar disorder I (BD I), its association with symptoms at start of first treatment, and development over the first year, and limited knowledge about factors that influence the length of DUB. Substance use has shown to delay identification of primary psychiatric disorders, and while cannabis use is common in BD the role of cannabis in relationship to DUB is unclear. The aim of the present study is to examine the associations between DUB and key clinical outcomes at baseline in BD I, and at one year follow-up, and to evaluate the influence of cannabis use. Patients with first-treatment BD I (N=62) completed comprehensive clinical evaluations, which included both DUB and the number of previous episodes. There were no significant associations between DUB and key clinical outcomes. Longer duration from first manic episode to treatment was associated with risk of starting excessive cannabis use after onset of the bipolar disorder. The main finding is the lack of significant associations between features of previous illness episodes and clinical outcomes. Long duration of untreated mania seems to increase the risk for later cannabis use.

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

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.

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.

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

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

Neurocognitive features in subgroups of bipolar disorder.

OBJECTIVE: 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. METHODS: A total of 199 patients with BD were characterized by clinical and neurocognitive features. The distribution of subgroups in this sample was: BD-I, 64% and BD-II, 36%; 60% had a history of psychosis; 57% had depression as the presenting polarity; 61% had an early onset of BD, 25% had a mid onset, and 14% had a late onset. We used multivariate regression analyses to assess relationships between neurocognitive variables and clinical subgroups. RESULTS: Both BD-I diagnosis and elevated presenting polarity were related to impairments in verbal memory, with elevated presenting polarity explaining more of the variance in this cognitive domain (22.5%). History of psychosis and BD-I diagnosis were both related to impairment in semantic fluency, with history of psychosis explaining more of the variance (11.6%). CONCLUSION: Poor performance in verbal memory appears to be associated with an elevated presenting polarity, and poor performance in semantic fluency appears to be associated with a lifetime history of psychosis.

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

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

Neurocognitive functioning in patients recently diagnosed with bipolar disorder.

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

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.

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.

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.

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.

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.

Neuropsychological and electrophysiological indices of neurocognitive dysfunction in bipolar II disorder.

OBJECTIVES: There are conflicting findings regarding the nature and degree of neurocognitive dysfunction in bipolar II disorder (BD II). The aim of this study was to describe different levels of neurocognitive functioning in BD II by combining behavior-based methods (neuropsychological testing) and event-related potentials (ERP). METHODS: Twenty-five consecutively referred outpatients fulfilling DSM-IV criteria for BD II and 28 matched controls performed a neuropsychological test battery targeting working memory/attention, executive functions, verbal and visual memory, and psychomotor speed. In addition, ERPs for measuring early and controlled stages of information processing were recorded using a duration mismatch negativity (MMN) paradigm and a three-tone auditory oddball paradigm. RESULTS: Compared to controls, BD II patients' performance was significantly impaired on all neuropsychological measures, except for phonemic verbal fluency, with moderate to strong effect sizes ranging from 0.62 to 1.34. The ERP results indicate dysfunctions in early stages of information processing, showing a significant MMN latency increase and attenuated frontal amplitudes in BD II patients. Female patients showed increased P3a latency compared to female controls, but no group differences were found for P3b latency or amplitude, the ERP component expressing controlled information processing. CONCLUSIONS: The functional significance of neuropsychological impairment is discussed. Differences regarding some aspects of executive function may be related to psychomotor speed, and not primarily to dysexecutive functioning. ERP results must be interpreted with caution, but the differences found in MMN latency and amplitudes may be related to fronto-temporal circuitry underlying pre-attentive stimulus change detection as measured by MMN, and are discussed in relation to previous research on MMN in other neuropsychiatric conditions.