Long-term outcome predictors after functional remediation in patients with bipolar disorder.

BACKGROUND: Improving functioning in patients with bipolar disorder (BD) is one of the main objectives in clinical practice. Of the few psychosocial interventions that have been specifically developed to enhance the psychosocial outcome in BD, functional remediation (FR) is one which has demonstrated efficacy. The aim of this study was to examine which variables could predict improved functional outcome following the FR intervention in a sample of euthymic or subsyndromal patients with BD. METHODS: A total of 92 euthymic outpatients were included in this longitudinal study, with 62 completers. Partial correlations controlling for the functional outcome at baseline were calculated between demographic, clinical and neurocognitive variables, and functional outcome at endpoint was assessed by means of the Functioning Assessment Short Test scale. Next, a multiple regression analysis was run in order to identify potential predictors of functional outcome at 2-year follow-up, using the variables found to be statistically significant in the correlation analysis and other variables related to functioning as identified in the previous scientific literature. RESULTS: The regression model revealed that only two independent variables significantly contributed to the model (F(6,53): 4.003; p = 0.002), namely verbal memory and inhibitory control. The model accounted for 31.2% of the variance. No other demographic or clinical variable contributed to the model. CONCLUSIONS: Results suggest that patients with better cognitive performance at baseline, especially in terms of verbal memory and executive functions, may present better functional outcomes at long term follow-up after receiving functional remediation.

Identifying social cognition subgroups in euthymic patients with bipolar disorder: a cluster analytical approach.

BACKGROUND: Bipolar disorder (BD) is associated with social cognition (SC) impairments even during remission periods although a large heterogeneity has been described. Our aim was to explore the existence of different profiles on SC in euthymic patients with BD, and further explore the potential impact of distinct variables on SC. METHODS: Hierarchical cluster analysis was conducted using three SC domains [Theory of Mind (ToM), Emotional Intelligence (EI) and Attributional Bias (AB)]. The sample comprised of 131 individuals, 71 patients with BD and 60 healthy control subjects who were compared in terms of SC performance, demographic, clinical, and neurocognitive variables. A logistic regression model was used to estimate the effect of SC-associated risk factors. RESULTS: A two-cluster solution was identified with an adjusted-performance group (N = 48, 67.6%) and a low-performance group (N = 23, 32.4%) with mild deficits in ToM and AB domains and with moderate difficulties in EI. Patients with low SC performance were mostly males, showed lower estimated IQ, higher subthreshold depressive symptoms, longer illness duration, and poorer visual memory and attention. Low estimated IQ (OR 0.920, 95% CI 0.863-0.981), male gender (OR 5.661, 95% CI 1.473-21.762), and longer illness duration (OR 1.085, 95% CI 1.006-1.171) contributed the most to the patients clustering. The model explained up to 35% of the variance in SC performance. CONCLUSIONS: Our results confirmed the existence of two discrete profiles of SC among BD. Nearly two-thirds of patients exhibited adjusted social cognitive abilities. Longer illness duration, male gender, and lower estimated IQ were associated with low SC performance.

Social cognition in bipolar disorder: the role of sociodemographic, clinical, and neurocognitive variables in emotional intelligence.

OBJECTIVE: The main aims of this study were to examine the differences in the Emotional Intelligence (EI), the emotional domain of social cognition (SC), between euthymic patients with bipolar disorder (BD) and healthy controls (HC) and to evaluate the contribution of sociodemographic, clinical, and neuropsychological variables to EI. METHODS: We recruited 202 patients with BD and 50 HC. EI was evaluated using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). The sociodemographic, clinical, and neurocognitive variables that showed a significant association with EI were entered into hierarchical multiple regression analysis. RESULTS: BD patients obtained significantly lower scores compared to HC in the Emotional Intelligence Quotient (EIQ) and in the Understanding Emotions branch score. The best fitting model for the variables associated with EI in the patients group was a linear combination of gender, estimated IQ, family history of affective diagnosis, and executive function. The model, including these previous variables, explained up to 27.6% of the observed variance (R2  = 0.276, F = 16.406, P < 0.001). CONCLUSIONS: The identification of variables associated with deficit in EI, such as male gender, lower estimated IQ, family history of affective diagnosis. and lower executive function performance, may help in selecting treatment targets to improve SC, and especially EI, in patients with BD.

Heterogeneity of functional outcomes in patients with bipolar disorder: a cluster-analytic approach.

OBJECTIVE: The aim was to examine the heterogeneity of psychosocial outcomes in euthymic bipolar disorder (BD) patients and analyse the potential influence of distinct variables on functioning. METHOD: Using a hierarchical cluster exploratory analysis, 143 euthymic patients with diagnosis of BD were grouped according to their functional performance based on domains scores of the Functioning Assessment Short Test (FAST). The resulting groups were compared on sociodemographic, clinical and neurocognitive variables to find factors associated with each functional cluster. RESULTS: Patients were grouped in three functional profiles: patients with good functioning in all the FAST areas, patients with an intermediate profile showing great difficulties in the occupational domain and milder difficulties in most of the rest domains, and a third group with serious difficulties in almost all functional areas. Both functionally impaired groups were characterized by higher subthreshold symptoms (depressive and manic) and higher unemployment rates. The most functionally impaired group also showed lower scores on some measures of processing speed. CONCLUSION: Two of three functional profiles showed some kind of impairment which was associated with subsyndromal symptoms and cognitive performance. These patterns should be taken into consideration to develop more individualized interventions to restore, or improve, psychosocial outcomes.

Factors associated with poor functional outcome in bipolar disorder: sociodemographic, clinical, and neurocognitive variables.

OBJECTIVE: The current investigation aimed at studying the sociodemographic, clinical, and neuropsychological variables related to functional outcome in a sample of euthymic patients with bipolar disorder(BD) presenting moderate-severe levels of functional impairment. METHODS: Two-hundred and thirty-nine participants with BD disorders and with Functioning Assessment Short Test(FAST) scores equal or above 18 were administered a clinical and diagnostic interview, and the administration of mood measure scales and a comprehensive neuropsychological battery. Analyses involved preliminary Pearson bivariate correlations to identify sociodemographic and clinical variables associated with the FAST total score. Regarding neuropsychological variables, a principal component analysis (PCA) was performed to group the variables in orthogonal factors. Finally, a hierarchical multiple regression was run. RESULTS: The best fitting model for the variables associated with functioning was a linear combination of gender, age, estimated IQ, Hamilton Depression Rating Scale (HAM-D), number of previous manic episodes, Factor 1 and Factor 2 extracted from the PCA. The model, including all these previous variables, explained up to 29.4% of the observed variance. CONCLUSIONS: Male gender, older age, lower premorbid IQ, subdepressive symptoms, higher number of manic episodes, and lower performance in verbal memory, working memory, verbal fluency, and processing speed were associated with lower functioning in patients with BD.

Functional remediation in bipolar disorder: 1-year follow-up of neurocognitive and functional outcome.

BACKGROUND: Few randomised clinical trials have examined the efficacy of an intervention aimed at improving psychosocial functioning in bipolar disorder. AIMS: To examine changes in psychosocial functioning in a group that has been enrolled in a functional remediation programme 1 year after baseline. METHOD: This was a multicentre, randomised, rater-masked clinical trial comparing three patient groups: functional remediation, psychoeducation and treatment as usual over 1-year follow-up. The primary outcome was change in psychosocial functioning measured by means of the Functioning Assessment Short Test (FAST). Group×time effects for overall psychosocial functioning were examined using repeated-measures ANOVA (trial registration NCT01370668). RESULTS: There was a significant group×time interaction for overall psychosocial functioning, favouring patients in the functional remediation group (F = 3.071, d.f. = 2, P = 0.049). CONCLUSIONS: Improvement in psychosocial functioning is maintained after 1-year follow-up in patients with bipolar disorder receiving functional remediation.

Effects of functional remediation on neurocognitively impaired bipolar patients: enhancement of verbal memory.

BACKGROUND: Functional remediation is a novel intervention with demonstrated efficacy at improving functional outcome in euthymic bipolar patients. However, in a previous trial no significant changes in neurocognitive measures were detected. The objective of the present analysis was to test the efficacy of this therapy in the enhancement of neuropsychological functions in a subgroup of neurocognitively impaired bipolar patients. METHOD: A total of 188 out of 239 DSM-IV euthymic bipolar patients performing below two standard deviations from the mean of normative data in any neurocognitive test were included in this subanalysis. Repeated-measures analyses of variance were conducted to assess the impact of the treatment arms [functional remediation, psychoeducation, or treatment as usual (TAU)] on participants' neurocognitive and functional outcomes in the subgroup of neurocognitively impaired patients. RESULTS: Patients receiving functional remediation (n = 56) showed an improvement on delayed free recall when compared with the TAU (n = 63) and psychoeducation (n = 69) groups as shown by the group × time interaction at 6-month follow-up [F 2,158 = 3.37, degrees of freedom (df) = 2, p = 0.037]. However, Tukey post-hoc analyses revealed that functional remediation was only superior when compared with TAU (p = 0.04), but not with psychoeducation (p = 0.10). Finally, the patients in the functional remediation group also benefited from the treatment in terms of functional outcome (F 2,158 = 4.26, df = 2, p = 0.016). CONCLUSIONS: Functional remediation is effective at improving verbal memory and psychosocial functioning in a sample of neurocognitively impaired bipolar patients at 6-month follow-up. Neurocognitive enhancement may be one of the active ingredients of this novel intervention, and, specifically, verbal memory appears to be the most sensitive function that improves with functional remediation.

The impact of repeated manic episodes and executive dysfunction on work adjustment in bipolar disorder.

The aim of this study was to study the clinical and neurocognitive variables that best explain poor work adjustment in a sample of bipolar I euthymic patients. Eighty-five euthymic patients at the Hospital Clinic of Barcelona were assessed for this study by means of a comprehensive neuropsychological battery and a work-focused interview to determine work adjustment. Clinical and sociodemographic variables were also collected. Direct logistic regression was performed to assess the impact of demographic, clinical and neuropsychological variables on the likelihood of presenting poor work adjustment. The model that best fitted contained five variables (Hamilton Depression Rating scores, number of manic episodes, number of perseverative errors in the Wisconsin Card Sorting Test (WCST), number of depressive episodes and Trail Making Test-part B). However, only two out of these variables made a unique statistically significant contribution to the model, which were number of manic episodes (OR 1.401; CI 1.05-1.86; p = 0.021) and number of perseverative errors in the WCST (OR 1.062; CI 1.00-1.12; p = 0.044). The model explained up to 36 % of the variance in work adjustment. This study highlights the role of manic relapses and neurocognitive impairment, specifically the role of executive function, in work adjustment.

Factors associated with the discrepancy between objective and subjective cognitive impairment in bipolar disorder.

OBJECTIVE: The aim of this study is to evaluate the discrepancy between objective cognitive measures and cognitive subjective complaints in a sample of euthymic patients with bipolar disorder (BD). METHODS: One hundred and sixteen participants (83 euthymic patients with BD and 33 healthy controls) were enrolled for this study. Patients were assessed with a comprehensive neuropsychological battery and they also reported their subjective cognitive complaints with the Cognitive Complaints in Bipolar Disorder Rating Scale (COBRA). The discrepancy between objective and subjective data was calculated using a novel methodology proposed in a previous study (Miskowiak, 2016). Statistical analyses included Pearson correlations and multiple linear regression. RESULTS: Higher number of previous depressive episodes was identified as one variable associated with the global sensitivity composite score (Beta = 0.25; t = 2.1; p = 0.04) and with the verbal learning and memory sensitivity score (Beta = 0.26; t = 2.16; p = 0.03). That is, patients with more previous depressive episodes tend to over-report cognitive complaints. In contrast, higher number of previous hospitalizations was associated with stoicism in the global total score (Beta = -0.27; t = -2.24: p = 0.029) and in the domain of attention/processing speed (Beta = -0.34; t = -2.52; p = 0.016), indicating patients with more hospitalizations tend to report less cognitive complaints. DISCUSSION: Our study identified some factors that might help to explain the discrepancy between objective and subjective cognitive measures in BD, including number of previous depressive episodes and number of previous hospitalizations. This highlights the need of the combined use of both types of cognitive measures to make an accurate assessment of cognitive dysfunctions and their effective treatment.

Increased grey matter volumes in the temporal lobe and its relationship with cognitive functioning in euthymic patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is characterized by episodic mood dysregulation, although a significant portion of patients suffer persistent cognitive impairment during euthymia. Previous magnetic resonance imaging (MRI) research suggests BD patients may have accelerated brain aging, observed as lower grey matter volumes. How these neurostructural alterations are related to the cognitive profile of BD is unclear. METHODS: We aim to explore this relationship in euthymic BD patients with multimodal structural neuroimaging. A sample of 27 euthymic BD patients and 24 healthy controls (HC) underwent structural grey matter MRI and diffusion-weighted imaging (DWI). BD patient's cognition was also assessed. FreeSurfer algorithms were used to obtain estimations of regional grey matter volumes. White matter pathways were reconstructed using TRACULA, and four diffusion metrics were extracted. ANCOVA models were performed to compare BD patients and HC values of regional grey matter volume and diffusion metrics. Global brain measures were also compared. Bivariate Pearson correlations were explored between significant brain results and five cognitive domains. RESULTS: Euthymic BD patients showed higher ventricular volume (F(1, 46) = 6.04; p = 0.018) and regional grey matter volumes in the left fusiform (F(1, 46) = 15.03; pFDR = 0.015) and bilateral parahippocampal gyri compared to HC (L: F(1, 46) = 12.79, pFDR = 0.025/ R: F(1, 46) = 15.25, pFDR = 0.015). Higher grey matter volumes were correlated with greater executive function (r = 0.53, p = 0.008). LIMITATIONS: We evaluated a modest sample size with concurrent pharmacological treatment. CONCLUSIONS: Higher medial temporal volumes in euthymic BD patients may be a potential signature of brain resilience and cognitive adaptation to a putative illness neuroprogression. This knowledge should be integrated into further efforts to implement imaging into BD clinical management.

Disrupted network switching in euthymic bipolar disorder: Working memory and self-referential paradigms.

BACKGROUND: Patients with bipolar disorder (BD) frequently suffer from neurocognitive deficits that can persist during periods of clinical stability. Specifically, impairments in executive functioning such as working memory and in self-processing have been identified as the main components of the neurocognitive profile observed in euthymic BD patients. The study of the neurobiological correlates of these state-independent alterations may be a prerequisite to develop reliable biomarkers in BD. METHODS: A sample of 27 euthymic BD patients and 25 healthy participants (HC) completed working memory and self-referential functional Magnetic Resonance Imaging (fMRI) tasks. Activation maps obtained for each group and contrast images (i.e., 2-back > 1-back/self > control) were used for comparisons between patients and HC. RESULTS: Euthymic BD patients, in comparison to HC, showed a higher ventromedial prefrontal cortex activation during working memory, a result driven by the lack of deactivation in BD patients. In addition, euthymic BD patients displayed a greater dorsomedial and dorsolateral prefrontal cortex activation during self-reference processing. LIMITATIONS: Pharmacotherapy was described but not included as a confounder in our models. Sample size was modest. CONCLUSION: Our findings revealed a lack of deactivation in the anterior default mode network (aDMN) during a working memory task, a finding consistent with prior research in BD patients, but also a higher activation in frontal regions within the central executive network (CEN) during self-processing. These results suggest that an imbalance of neural network dynamics underlying external/internal oriented cognition (the CEN and the aDMN, respectively) may be one of the first reliable biomarkers in euthymic bipolar patients.

Neurocognitive impairment and psychosocial functioning in bipolar II disorder.

OBJECTIVE: There is a growing body of evidence on neurocognitive impairment in euthymic bipolar patients, but this issue has been studied mostly in bipolar I disorder, data on bipolar II (BD-II) are scant and discrepant. The two aims of this study were to ascertain whether strictly defined euthymic BD-II patients would present neurocognitive disturbances and to evaluate their impact on functional outcome. METHOD: Forty-three BD-II patients and 42 demographically and educationally matched healthy subjects were assessed with a comprehensive neuropsychological test battery and with the Social and Occupational Functioning Assessment Scale (SOFAS). The euthymia criteria were reduced (Hamilton Rating Scale for Depression score ≤6 and a Young Mania Rating Scale score ≤6) to minimize the influence of subdepressive symptomatology on cognition and functioning. RESULTS: BD-II patients showed a significantly lower performance on several measures of attention, learning and verbal memory, and executive function compared with healthy controls. The presence of subthreshold depressive symptomatology and one measure related to executive function (Trail Making Test, part B) was the variables that best predicted psychosocial functioning measured with the SOFAS. CONCLUSION: This report provides further evidence that euthymic BD-II patients present cognitive impairment which may impact psychosocial functioning.

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.

Behavioral addictions in bipolar disorders: A systematic review.

Clinical and epidemiological research suggests that behavioral addictions (BA) are associated with a wide range of psychiatric disorders. However, the relationship between BA and bipolar disorders (BD) has not been thoroughly explored. The aim of this systematic review was to critically summarize and evaluate the current available evidence regarding a possible association between BA and BD. A systematic review of major electronic databases according to PRISMA guidelines was conducted from inception to 31st December 2017. We sought quantitative studies data concerning prevalence of comorbidity, features and treatment related to BA-BD comorbidity. Data were narratively synthesized. Of the 1250 studies returned from the search, a total of 28 articles were included in this review. BA may be overrepresented in BD samples, and the other way around. Pathological gambling and kleptomania were the most prevalent conditions followed by compulsive buying, compulsive sexual behavior and internet addiction. BA was also associated with other mood disorders, anxiety disorders and substance use disorder. BD-BA comorbidity was related with more severe course of illness. Studies on treatment strategies for BD-BA comorbidity are rather limited; only one randomized controlled trial that fulfilled inclusion criteria was identified. Methodological heterogeneity in terms of design and results among studies was found. BD-BA commonly co-occurs although there is a need for rigorous studies. Routine screening and adequate assessment may be helpful in BD patients to identify individuals at risk for BA and to effectively manage the complex consequences associated with BA-BD comorbidity.

Thresholds for severity, remission and recovery using the functioning assessment short test (FAST) in bipolar disorder.

BACKGROUND: Despite its importance, no distinction between none, mild, moderate and severe functional impairment is available. Categorization of functional impairment could help to better assess randomized controlled trials (RCT) and to study the correlates of functional impairment according to severity. The Functional Assessment Short Test (FAST) is one of the most widely used measures of functional impairment in bipolar disorder and related conditions, but to date no severity cut-offs have been determined for their use in clinical research and practice. METHOD: FAST and Global Functioning Assessment (GAF) ratings from 65 euthymic outpatients with bipolar disorder at the Hospital Clínic in Barcelona were analyzed. A linear regression was computed using the FAST as the independent variable and the GAF as the dependent variable. Cut-offs scores for the FAST were estimated taking into account the GAF scores as a reference. RESULTS: Linear regression analysis with GAF scores as the dependent variable yielded the following equation: GAF score = 91,41-1,031 * FAST score. The cut-off scores for the FAST scale derived from this equation were as follows: scores from 0 to 11 included patients with no impairment. Scores from 12 to 20, represented the category of mild impairment. Moderate impairment comprised scores from 21 to 40. Finally, scores above 40 represent severe functional impairment. Further, the 4 × 4 cross-tabulation resulted in a significant association of FAST and GAF severity gradation: (Chi2 = 95,095; df = 9; p < 0,001). Chance-corrected agreement was κ = 0,65 (p < 0.001). LIMITATIONS: In the absence of a better alternative, the GAF, a broad clinical measure, was used as gold standard for establishing FAST categories according to severity. CONCLUSION: The categorization of functional impairment in four categories based on empirical data shows that 12, 20 and 40 represent clinically meaningful cut-offs of the FAST for mild, moderate, and severe functional impairment and for functional recovery, remission, and improvement. The proposed categories are suitable to be further implemented in clinical studies and RCTs.

Characterizing decision-making and reward processing in bipolar disorder: A cluster analysis.

The presence of abnormalities in emotional decision-making and reward processing among bipolar patients (BP) has been well rehearsed. These disturbances are not limited to acute phases and are common even during remission. In recent years, the existence of discrete cognitive profiles in this psychiatric population has been replicated. However, emotional decision making and reward processing domains have barely been studied. Therefore, our aim was to explore the existence of different profiles on the aforementioned cognitive dimensions in BP. The sample consisted of 126 euthymic BP. Main sociodemographic, clinical, functioning, and neurocognitive variables were gathered. A hierarchical-clustering technique was used to identify discrete neurocognitive profiles based on the performance in the Iowa Gambling Task. Afterward, the resulting clusters were compared using ANOVA or Chi-squared Test, as appropriate. Evidence for the existence of three different profiles was provided. Cluster 1 was mainly characterized by poor decision ability. Cluster 2 presented the lowest sensitivity to punishment. Finally, cluster 3 presented the best decision-making ability and the highest levels of punishment sensitivity. Comparison between the three clusters indicated that cluster 2 was the most functionally impaired group. The poorest outcomes in attention, executive function domains, and social cognition were also observed within the same group. In conclusion, similarly to that observed in "cold cognitive" domains, our results suggest the existence of three discrete cognitive profiles concerning emotional decision making and reward processing. Amongst all the indexes explored, low punishment sensitivity emerge as a potential correlate of poorer cognitive and functional outcomes in bipolar disorder.

Social cognition in bipolar disorder: Focus on emotional intelligence.

BACKGROUND: The present study aims to characterize emotional intelligence (EI) variability in a sample of euthymic bipolar disorder (BD) patients through the Mayer- Salovey-Caruso Emotional Intelligence Test (MSCEIT). METHOD: A total of 134 euthymic BD outpatients were recruited and divided into three groups according to the total Emotional Intelligence Quotient (EIQ) score of the MSCEIT, following a statistical criterion of scores 1.5SDs above/below the normative group mean, as follows: a low performance (LP) group (EIQ <85), a normal performance (NP) group (85≤EIQ≤115), and a high performance (HP) group (EIQ >115). Afterwards, main sociodemographic, clinical, functional and neurocognitive variables were compared between the groups. RESULTS: Three groups were identified: 1) LP group (n=16, 12%), 2) NP group (n=93, 69%) and 3) HP group (n=25, 19%). There were significant differences between the groups in premorbid intelligence quotient (IQ) (p=0.010), axis II comorbidity (p=0.008), subthreshold depressive symptoms (p=0.027), general functioning (p=0.013) and in four specific functional domains: autonomy, occupation, interpersonal relations and leisure time. Significant differences in neurocognitive performance were found between groups with the LP group showing the lowest attainments. LIMITATIONS: The cross-sectional design of the study. CONCLUSION: Our results suggest that EI variability among BD patients, assessed through MSCEIT, is lower than expected. EI could be associated with premorbid IQ, subthreshold depressive symptoms, neurocognitive performance and general functioning. The identification of different profiles of SC may help guide specific interventions for distinct patient subgroups aimed at improving social cognition, neurocognitive performance and psychosocial functioning.