Executive functions and memory in bipolar disorders I and II: new insights from meta-analytic results.

OBJECTIVE: To perform a systematic review and meta-analysis of executive functions (EF) and episodic memory in bipolar disorder (BD). METHODS: A literature search was conducted on three electronic databases. Results were combined using random-effects meta-analysis. RESULTS: A total of 126 studies (6424 patients with BDI, 702 with BDII, and 8276 controls) were included. BDI was associated with moderate to large impairments across all cognitive functions and BDII with small-to-medium impairments. Small significant differences were identified between BDI and BDII on all cognitive functions except inhibition. The Trail Making Test (TMT) (g = 0.74, 95% CI: 0.67-0.80), Hayling Test (g = 0.58, 95% CI: 0.34-0.81), Digit Span Total (g = 0.79, 95% CI: 0.57-1.01), and Category Fluency (g = 0.59, 95% CI: 0.45-0.72) tasks were most sensitive to cognitive impairment in BDI. The TMT (g = 0.65, 95% CI: 0.50-0.80) and Category Fluency (g = 0.56, 95% CI: 0.37-0.75) were also sensitive to cognitive alterations in patients with BDII. CONCLUSION: BD type I was associated with more severe and widespread impairments than BDII, which showed smaller impairments on all functions except inhibition, where impairments were larger. Education and (hypo)manic symptoms should be further investigated in future studies due to their possible influence on the neuropsychological profile of BD. The instruments identified in this review should be considered for inclusion in cognitive assessment batteries in BD.

Dopaminergic agents in the treatment of bipolar depression: a systematic review and meta-analysis.

OBJECTIVE: To systematically examine the effects of dopaminergic agents (modafinil, armodafinil, pramipexole, methylphenidate, and amphetamines) on bipolar depression outcomes. METHODS: Meta-analysis of randomized controlled trials was performed to assess the efficacy and safety of treatment with dopaminergic agents in bipolar depression. In a secondary analysis, findings from both randomized controlled trials and high-quality observational studies were pooled by means of meta-analytic procedures to explore dopaminergic treatment-related new mania. RESULTS: Nine studies (1716 patients) were included in our meta-analysis of randomized controlled trials. Treatment with dopaminergic agents for bipolar depression was associated with an increase in both response (1671 individuals, RR 1.25, 95% CI 1.05 to 1.50) and remission rates (1671 individuals, RR 1.40, 95% CI 1.14, 1.71). There was no evidence of an increased risk of mood switch associated with this treatment (1646 individuals, RR 0.96, 95% CI 0.49, 1.89). Our secondary analysis (1231 individuals) yielded a cumulative incidence of mood switch of 3% (95% CI 1.0, 5.0) during a mean follow-up period of 7.5 months. CONCLUSIONS: Preliminary findings suggest that dopaminergic agents may represent a useful alternative for the treatment of bipolar depression, with no evidence for a related increase in the risk of mood destabilization during short-term follow-up.

A longitudinal mirror-image assessment of morbidity in bipolar disorder.

BACKGROUND: Evidence about the clinical course of bipolar disorder is inconsistent and limited. The aim of this study was to assess changes in morbidity in patients with bipolar disorder along a mean follow-up period of 80months. METHODS: Based on a mirror-image design, the follow-up period of each patient was divided into two halves. Then, three measures of morbidity - number of affective episodes, time spent ill, and cycle length - were recorded and compared between each half of the follow-up period. RESULTS: On average, there was a trend to a smaller amount of time spent with subclinical symptomatology during the second half of the follow-up period. In contrast, there were no differences in terms of number of episodes, time spent with clinical symptoms, or cycle length between the first and second half of the follow-up period. A subgroup analysis identified 21.9% of patients with consistent data of a worsening during follow-up. CONCLUSIONS: The results suggest that, on average, there is stability or slight improvement of clinical morbidity over the course of BD. Then, worsening of the clinical course may be a feature of a subgroup of patients rather than an inherent characteristic of the disorder. These subgroups or patient profiles could represent an opportunity for further studies to assess clinical, pathophysiologic, and therapeutic features associated with them.

Are major depression and bipolar disorder neuropsychologically distinct? A meta-analysis of comparative studies.

BACKGROUND: Neuropsychological deficits are present in both major depression and bipolar disorder. So far, however, reports directly comparing these mood disorders with regard to cognitive outcomes have been scant and yielded inconsistent results. This work aims to combine the findings of comparative studies of cognition in major depression and bipolar disorder in order to explore whether these neuropsychiatric conditions present with distinct cognitive features. METHODS: The main online databases were extensively searched to retrieve reports assessing neurocognitive functioning in two groups of mood disorder patients, one with major depressive disorder and another with bipolar disorder, both in the same phase of illness. Between-group effect sizes for cognitive variables were obtained from selected studies and pooled by means of meta-analytic procedures. RESULTS: During euthymia, a significant overall effect size (Hedges'g=0.64, P<0.001) favoring major depressive disorder was found for verbal memory as assessed with list learning tests, whereas no significant between-group differences were found for the remaining variables analyzed. During depressive episodes, similar cognitive outcomes were observed between groups. CONCLUSION: At present, it is not possible to postulate specific neuropsychological profiles for major depression and bipolar disorder in light of available evidence. It remains to be ascertained whether the differences found for verbal memory constitute an expression of distinct underlying mechanisms or whether they are best explained by sample characteristics or differential exposure to variables with a negative impact on cognition.

Social cognition in euthymic bipolar disorder: systematic review and meta-analytic approach.

OBJECTIVE: Deficits in social cognition have been reported in euthymic subjects with bipolar disorder (BD). However, some studies have failed to find differences favoring controls. As most investigations have been conducted with small samples, they have not had sufficient power to detect statistically significant differences. Furthermore, studies communicating positive results have scarcely attempted to estimate effect sizes for patient-control differences. The aim of this study was to summarize the findings of reports on social cognition in patients with euthymic BD and to combine their data to identify possible deficits and quantify their magnitude. METHOD: Systematic literature review and meta-analysis. RESULTS: Impairments of moderate magnitude (0.5 < d < 0.8) were noted across mentalizing skills, whereas small but significant effect sizes (d < 0.5) were observed for facial emotion recognition. No patient-control differences were found for decision-making. CONCLUSION: Meta-analytic findings provide evidence for emotion processing and theory of mind deficits in remitted bipolar patients. However, it is not yet clear whether these areas of impairment are related to neurocognitive dysfunctions or to medication effects. The results are discussed with regard to targets for future neuropsychological research on BDs.