Brisa Solé

Efficacy of Functional Remediation in Bipolar Disorder: A Multicenter Randomized Controlled Study

OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukeys post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.

Functional Impairment and Disability across Mood States in Bipolar Disorder

BACKGROUND Bipolar disorder (BD) represents a chronic and recurrent illness that can lead to severe disruptions in family, social, and occupational functioning. The severity of mood symptomatology has been associated with functional impairment in this population. However, the majority of studies have assessed global functioning without considering specific domains. The main objective of the current study was to assess specific life domains of functioning as well as the overall functioning in patients with BD across different mood states ([hypo] mania, depression, or euthymia) compared with healthy controls by the means of a standardized scale validated for BD. METHODS The sample included 131 subjects with BD (68 in remission, 31 hypo [manic], and 32 depressed) and 61 healthy controls. The Functioning Assessment Short Test was used to assess overall and multiple areas of functional impairment (autonomy, occupational functioning, cognitive functioning, interpersonal relationships, financial issues, and leisure time). RESULTS The results showed significant intergroup differences; depressed patients had the lowest functioning (48.03 ± 12.38) followed by (hypo) manic patients (39.81 ± 13.99). The euthymic group showed least impairment in functioning compared with the depression and (hypo) mania groups (11.76 ± 12.73) but still displayed significant impairment when compared with the healthy control group (5.93 ± 4.43). CONCLUSIONS This study indicates that depressive symptoms are associated with greater negative impact on psychosocial functioning than (hypo) manic symptoms. Further deficits in functioning seem to persist during remission. The results highlight the importance of aggressively treating depression and mania and the need to develop psychosocial interventions targeting to improve functional outcomes.

Long-term outcome of cognitive impairment in bipolar disorder.

OBJECTIVE To evaluate the longitudinal course and outcome of cognitive deficits and their clinical correlates in bipolar disorder. METHOD One hundred thirteen participants (68 patients and 45 healthy controls) were assessed by the means of a neuropsychological battery targeting attention, psychomotor speed, verbal memory, and executive functions at baseline: 68 euthymic outpatients with a DSM-IV diagnosis of bipolar disorder (53 bipolar I and 15 bipolar II) were enrolled at the Bipolar Disorder Unit of the Hospital Clinic of Barcelona. Forty-five patients completed the follow-up. The assessments started in February 1999 and finished in July 2010. The primary outcome of the study was the change in the neuropsychological performance in the patient group. RESULTS Repeated-measures analyses showed significant effects of time in 2 cognitive domains: attention and executive functions. Attention slightly improved (P = .043) but executive function worsened (P = .001). Regression analyses showed that the duration of illness and baseline subdepressive symptoms were associated with poor performance in executive function. Subdepressive symptoms at endpoint were associated with poor functioning. The best predictor of low functioning was verbal memory dysfunction at baseline. CONCLUSIONS The cognitive impairment remained stable across the follow-up period in many measures assessed except for a worsening of executive measures, which have been found to be associated with the duration of illness and subdepressive symptoms.

Neurocognitive impairment and psychosocial functioning in bipolar II disorder.

Solé B, Bonnin CM, Torrent C, Balanzá‐Martínez V, Tabarés‐Seisdedos R, Popovic D, Martínez‐Arán A, Vieta E. Neurocognitive impairment and psychosocial functioning in bipolar II disorder.

Are bipolar II patients cognitively impaired? A systematic review

BACKGROUND There is evidence that bipolar disorder (BD) is associated with significant neurocognitive deficits and this occurs in individuals with BD type I (BD I) and with BD type II (BD II). Only a few studies have focused on cognitive impairment in BD II. The aim of this study was to describe the pattern of cognitive impairment in patients with BD II, in order to identify specific cognitive deficits that distinguish BD II from BD I patients as well as from healthy subjects. METHOD We performed a systematic review of the literature of neuropsychological studies of BD II published between 1980 and July 2009. Fourteen articles fulfilled the inclusion criteria and were included in this review. RESULTS Main cognitive deficits found in BD II include working memory and some measures of executive functions (inhibitory control) and approximately half of the studies also detected verbal memory impairment. CONCLUSIONS There are subtle differences between the two subtypes regarding cognition. This may suggest neurobiological differences between the two subgroups which will be helpful in order to determine cognitive endophenotypes in BD subtypes.

Six-month functional outcome of a bipolar disorder cohort in the context of a specialized-care program

Rosa AR, Reinares M, Amann B, Popovic D, Franco C, Comes M, Torrent C, Bonnín CM, Solé B, Valentí M, Salamero M, Kapczinski F, Vieta E. Six‐month functional outcome of a bipolar disorder cohort in the context of a specialized‐care program. Bipolar Disord 2011: 13: 679–686.

Functional impairment in bipolar II disorder: Is it as disabling as bipolar I?

INTRODUCTION It is well established that patients with bipolar disorder experience functional impairment even in remission. Nevertheless, bipolar II disorder remains understudied because most investigations to date include only bipolar I patients or just a small sample of bipolar II patients, without explicitly comparing both subtypes of disorder. The main objective of the current report is to evaluate overall and multiple domains of functioning, specifically in bipolar II disorder compared to patients with bipolar I disorder and healthy subjects. METHODS 233 subjects from 3 groups were compared: bipolar I patients (n=106), bipolar II patients (n=66) and healthy controls (n=61). Bipolar patients meeting criteria of remission were recruited at the Hospital Clinic of Barcelona and at different study sites in Argentina. All participants were assessed with 17-item Hamilton Depression Rating Scale (HAM-D), Young Mania Rating Scale (YMRS) and the Functioning Assessment Short Test (FAST). Clinical and sociodemographic data were also recorded. RESULTS Both subgroups of patients, bipolar I and bipolar II, showed lower overall functioning (p<0.001) and in each domain of the FAST scale (all, p<0.001) when compared to the healthy control group. Tukey post hoc test revealed that bipolar II patients scored worse in the cognitive domain compared to bipolar I patients. However, after controlling for potential confounding variables, this difference disappeared and only older age (p<0.005) and HAM-D scores (p<0.001) remained significant. CONCLUSIONS Our results suggest that bipolar II patients are as disabled as bipolar I patients. This may be explained, in part, because bipolar II patients experience greater lifetime residual depressive symptoms than the bipolar I subgroup, which may have particular impact on cognitive domains of functioning.

Neurocognitive impairment across the bipolar spectrum.

Bipolar disorder is a severe mental illness that affects nearly 4.4% of the general population when bipolar spectrum disorders are taken into account. Neurocognitive impairment is thought to be a core deficit of this illness since it is present during euthymia. In fact, 40–60% of euthymic patients present with neurocognitive disturbances. Not only the clinical factors but also disturbances in neurocognition can influence the functional outcome of BD patients. Hence, further research is needed in order to clarify the relationship between these variables. Despite the growing body of evidence that has emerged during the last decade, no unique neurocognitive profile has been proposed yet for either BD subtype. The majority of the studies recluted heterogeneous samples (including both bipolar I and II) or focused on BD‐I patients only. The aim of this review is to give an overall picture of the main neurocognitive disturbances found in the bipolar spectrum and particularly in BD‐II, where the findings are more ambiguous. An extensive review of all the literature has been done regarding this subtype (from 1980 until July 2009). Data available until now suggest that deficits are present across the bipolar spectrum (BD‐I and BD‐II), but they seem slightly more severe in BD‐I. The extent to which either subtype share—or not—some similarities is still unknown. More studies are required but it would also be interesting to reach a consensus in the neuropsychological assessment of BD to facilitate comparisons between the different studies.

Verbal memory as a mediator in the relationship between subthreshold depressive symptoms and functional outcome in bipolar disorder.

BACKGROUND Most studies on the factors involved in the functional outcome of patients with bipolar disorder have identified subsyndromal depressive symptoms and cognitive impairment as key players. However, most studies are cross-sectional and very few have analyzed the interaction between cognition and subclinical depression. The present study aimed to identify the role of cognition, and particularly verbal memory, and subthreshold depressive symptoms in the functional outcome of patients with bipolar I and II disorder at one year follow-up. METHOD A confirmatory analysis was performed using the path analysis. A total of 111 euthymic patients were included to test the role of verbal memory as a mediator in the relationship of subthreshold depressive symptoms and functional outcome at one year follow-up. Measures of verbal memory, subthreshold depressive symptoms and functioning (at baseline, at 6 months and at one year follow-up) were gathered through the use of a neuropsychological assessment and validated clinical scales. RESULTS The hypothesized mediation model displayed a good fit to data (Chi=0.393, df=2, p=0.625; RMSEA<0.001 with CI: 0.001-0.125 and CFI=1.00). Functional outcome at one year follow-up was predicted by the functional outcome at baseline, which in turn, was related to subthreshold depressive symptoms at baseline and to the verbal composite memory scores as a mediator variable. CONCLUSION The results of this study prospectively confirm previous findings on the disabling role of subthreshold depressive symptoms and verbal memory impairment on psychosocial functioning. However, these results come from a sample with moderate to severe functional impairment; hence, as a limitation, this may hinder the generalization of these results.

Cognition as a target in major depression: New developments

Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric illness often accompanied of cognitive dysfunction which may persist even when patients achieve clinical remission. Currently, cognitive deficits emerge as a potential target because they compromise the functional outcome of depressed patients. The aim of this study was to review data for several potential pharmacological treatments targeting cognition in MDD, resulting from monotherapy or adjunctive treatment. An extensive and systematic Pubmed/Medline search of the published literature until March 2014 was conducted using a variety of search term to find relevant articles. Bibliographies of retrieved papers were further examined for publications of interest. Searches were limited to articles available in English language. We describe studies using modafinil, lisdexamfetamine, ketamine, lanicemine, memantine, galantamine, donepezil, vortioxetine, intranasal oxytocin, omega-3, s-adenosyl-methionine, scopolamine and erythropoietin. From these articles, we determined that there are a number of promising new therapies, pharmacological agents or complementary medicines, but data are just emerging. Drugs and therapies targeting cognitive dysfunction in MDD should prove effective in improving specific cognitive domains and functioning, while ruling out pseudospecificity.