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Background The efficacy of adjunctive group psychoeducation in bipolar disorder has been proven although treatment response differ among individuals. The aim of this study was to characterize responders and non-responders to group psychoeducation in order to identify baseline variables that could predict treatment response. Methods The sample was composed of 103 medicated euthymic patients with bipolar disorder referred to 21 sessions of group psychoeducation (6 months). Sociodemographic and clinical variables, temperament, circadian rhythms, BDNF, cognitive and psychosocial functioning were collected. At the 18-month endpoint, the patients were split in two groups on the basis of having suffered any recurrence. Significant group differences were included in a logistic regression analysis. Results Ninety patients out of 103 engaged in group psychoeducation, 47 of whom (52.2%) responded to psychoeducation and 43 (47.8%) did not. Recurrences occurred more often in the follow-up, the most common being depression. Responders and non-responders differed in gender, age at diagnosis, latency of diagnosis, temperament, attention composite score and BDNF. Lower age at diagnosis of bipolar disorder, lower cyclothimic temperament scores and being male -which was associated with bipolar type I and a trend to more previous manic episodes- were significantly related to a better response to psychoeducation in the regression analysis. Limitations No control group. Conclusions This study identifies age at diagnosis as a significant modifiable risk factor of treatment response, highlighting the need for early identification of bipolar disorder. Existing programs should be adjusted to the characteristics of specific subpopulations in the framework of a personalized approach.

Introduction Bipolar disorder is related to a high level of personal, familial, social and economic burden. There is a need for feasible adjunctive psychological interventions easy to implement in clinical practice in order to enhance aspects that medication alone cannot achieve. This study aims to evaluate the impact of a 12-session adjunctive integrative program designed for patients with bipolar disorder. Methods This is a single-blind prospective, randomized controlled trial involving a total of 132 outpatients with bipolar disorder who will be recruited from the Hospital Clinic of Barcelona. All participants will be randomly assigned to two arms. All the patients will receive treatment as usual (TAU) but in addition the experimental group will receive an integrative approach consisting of 12-sessions of 90 min each in which contents of psychoeducation for patients have been combined with a session for family members, and complemented with aspects related to health promotion, mindfulness training, and strategies for cognitive and functional enhancement. The whole sample will be assessed at baseline, after completion (3-months) and at 12 months from baseline regarding demographic and clinical variables, psychosocial and cognitive functioning, wellbeing and quality of life. The primary outcome measure will be improvement in psychosocial functioning. Conclusions If the integrative approach is effective, it would allow clinicians to cover different areas that may be affected by bipolar disorder, by means of a brief intervention that can therefore be easily generalized to clinical practice. Trial registration NCT04031560 . Date registered July 24, 2019.

BackgroundImproving 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.MethodsA 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.ResultsThe 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.ConclusionsResults 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.

Objective: This study was aimed at identifying differences in the prodromal symptoms and their duration, risk factors and markers of vulnerability in patients presenting a first episode mania (FEM) or psychosis (FEP) with onset in late adolescence or adulthood in order to guide tailored treatment strategies. Methods: Patients with a FEM or FEP underwent a clinical assessment. Prodromes were evaluated with the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R). Chi-squared tests were conducted to assess specific prodromal symptoms, risk factors or markers of vulnerability between groups. Significant prodromal symptoms were entered in a stepwise forward logistic regression model. The probabilities of a gradual versus rapid onset pattern of the prodromes were computed with logistic regression models. Results: The total sample included 108 patients (FEM = 72, FEP = 36). Social isolation was associated with the prodromal stage of a FEP whilst Increased energy or goal-directed activity with the prodrome to a FEM. Physically slowed down presented the most gradual onset whilst Increased energy presented the most rapid. The presence of obstetric complications and difficulties in writing and reading during childhood were risk factors for FEP. As for markers of vulnerability, impairment in premorbid adjustment was characteristic of FEP patients. No specific risk factor or marker of vulnerability was identified for FEM. Conclusion: Early characteristics differentiating FEP from FEM were identified. These findings might help shape early identification and preventive intervention programmes.

Obstetric complications (OCs) may contribute to the heterogeneity that characterizes psychiatric illness, particularly the phenotypic presentation of first episode psychoses (FEP). Our aim was to examine the relationship between OCs and socio-demographic, clinical, functioning and neuropsychological characteristics in affective and non-affective FEP. We performed a cross-sectional,study where we recruited participants with FEP between 2011 and 2021, and retrospectively assessed OCs using the Lewis-Murray scale. OCs were used as a dichotomous variable and further stratified into three subtypes: complications of pregnancy, abnormal fetal growth and development, and difficulties in delivery. We performed a logistic stepwise forward regression analysis to examine variables associated with the presence of OCs. Of the 104 participants (67 affective FEP and 37 non-affective FEP), 31.7% (n = 33) had experienced OCs. Subjects with OCs showed a more gradual emergence of prodromal symptoms as well as higher negative and total Positive and Negative Syndrome Scale (PANSS) scores. In the multivariate analysis, the presence of OCs was independently associated with a younger age at first episode of any type (OR = 0.904, p = 0.003) and slower emergence of prodromal symptoms (OR = 0.274, p = 0.011). When considering specific types of OCs, those related with fetal growth were associated with worse neuropsychological performance, while OCs at delivery were related to earlier onset of illness and more severe symptoms. In conclusion, OCs signaled a specific FEP phenotype characterized by earlier and more protracted onset of illness as well as more burdensome symptoms, independently of FEP type (i.e., affective vs non-affective). These results indicate a potential target of early intervention in FEP.

Background: The evolution of cognitive performance throughout the lifespan in bipolar disorder (BD) is understudied. This cross-sectional study aims to describe the cognitive performance across age groups. Methods: A sample of 654 participants was recruited for this study (BD = 432 and healthy controls -HC- =222). Three subgroups, divided according to age range (18 to 35, 36 to 49, and >= 50 years old) were analyzed after administering a comprehensive neuropsychological battery including six cognitive domains. Demographic, clinical, and psychosocial functioning data were also analyzed. Generalized linear models (GLM) with age, diagnostic group, and age x group as main effects were carried out to examine their potential association on cognitive domains. Subsequently, a GLM in the BD sample was conducted to analyze interactions of several clinical variables by age on each cognitive domain.Results: Main effects of diagnostic group and age were found in all cognitive domains. Significant group x age effect interaction was found for attention domain (p = 0.02) demonstrating a worse cognitive evolution across age in BD, driven by older age, but not in HC. Significant interaction effects of higher number of manic episodes and older age were also found in attention and verbal memory. Older age was also associated with a longer duration of illness, higher number of episodes, more somatic comorbidities, and poorer psychosocial functioning.Conclusions: These results suggest that older age was associated with a selective cognitive decline in BD in the attentional domain. These findings highlight the importance of developing interventions targeting cognitive dysfunction throughout the BD adulthood lifespan.

The main aim of this study is to evaluate the impact of functional remediation (FR) in serum brain derived neurotrophic factor (BDNF) levels in euthymic adult patients with Bipolar Disorder (BD). A total of 128 participants were recruited at the Hospital Clinic of Barcelona. They were assessed at baseline and at the end of follow-up by the means of Hamilton Depression Scale (HAM-D), Young Mania Rating Scale (YMRS) and Functioning Assessment Short Test (FAST), as well as a clinical structured interview to collect clinical and demographic variables of interest. Blood samples were also collected to assess BDNF levels. After baseline assessment, patients received FR, Psychoeducation or treatment as usual (TAU). One hundred and two out of 126 participants finished the study distributed as follows: FR group (n = 39); Psychoeducation group (n = 47) and TAU group (n = 16). Longitudinal repeated-measures analyses addressing the treatment effect on BDNF levels showed non-significant differences between the three groups (Pillai's trace = 0.06; F(2,97)= 0.28; p = 0.75), suggesting no interaction between treatment allocation and time on BDNF levels. The results of this study suggest that FR has no effect on peripheral BDNF levels in euthymic patients with BD, despite the improvement in psychosocial functioning.

Background The Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego (TEMPS-A) is a self-administered questionnaire intended to assess five affective temperaments: depressive, cyclothymic, hyperthymic, irritable and anxious. Our objective was to examine the psychometric properties of the TEMPS-A using a sample comprised by patients with bipolar disorder (BD) and healthy controls (HC) and to determine cut-off scores for each temperament. Methods Five hundred and ninety-eight individuals (327 BD and 271 HC) completed the TEMPS-A. Cronbach's alpha was used to examine internal consistency reliability. Test-retest reliability and association between different temperamental scales were assessed using Spearman correlation. To confirm factor structure a confirmatory factor analysis (CFA) was carried out. Cut-off scores indicating the presence of dominant temperament were also calculated. Results Internal consistency was optimal for all temperament subscales (α: 0.682- 0.893). The questionnaire demonstrated good test-retest reliability (ρ: 0.594–0.754). The strongest positive associations were found between cyclothymic and anxious and between depressive and anxious temperaments. Hyperthymic and depressive as well as hyperthymic and anxious temperaments showed a strong negative correlation. Limitations The HC sample was not matched with the BD group. There were some sociodemographic and clinical differences between groups that may impact on the obtained results. A portion of patients with BD was recruited from tertiary centers. Conclusions The Spanish version of the Barcelona TEMPS-A questionnaire presents a good internal consistency and their results are stable in clinical population. The performance of the Barcelona TEMPS-A is as good as the original scale.

Evidence has shown heterogeneity of cognitive function among patients with bipolar disorder (BD). Our study aims to replicate recent findings of cognitive subgroups, as well as we assessed subjective cognitive difficulties and functioning in each cluster.Hierarchical cluster analysis was conducted to examine whether there were distinct neurocognitive subgroups based on neurocognitive battery. Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) and Functioning Assessment Short Test (FAST) were used to assess subjective cognitive difficulties and functional impairment.We found three distinct subgroups: a first cluster with intact cognition (n = 30, 43.5%), a second cluster with selective cognitive impairment (n = 23, 33.3%), and a third cluster with globally cognitive impairment (n = 16, 23.3%). The intact group had more years of education (p .001) and higher estimated IQ (p .001) than globally and selectively impaired subgroups. Additionally, they were younger (p = .011), had an earlier age at bipolar diagnosis (p .037) and earlier age of first hospitalization (p .035) compared to individuals with globally cognitive impairment.This is a cross-sectional design with a small sample including only patients from a tertiary hospital.Our results give support to the existence of a continuum of severity from patients without impairment to those with poor cognitive functioning. Patients in the intact group seem to have higher cognitive reserve than other two groups. However, they also experienced cognitive complaints and some degree of functional impairment. These findings suggest the importance of using a combo of instruments (e.g., objective and subjective cognitive measures plus functioning instruments) for a complete assessment of patients with BD.

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.

Background Smartphone apps are becoming increasingly used by service users in mental health care and research for diverse aims. However, it is well-known the high prevalence of cognitive impairment in some people suffering from severe mental illnesses such as bipolar disorder (BD), which impacts on their psychosocial functioning and quality of life. In this context, the main aim of this paper is to investigate through exploratory analyses the role of specific cognitive deficits in the retention, engagement, and usability of a psychoeducational smartphone app in a group of patients with BD. Methods 51 remitted BD patients were asked to use the app for 3 months. Baseline and 3-months follow-up clinical and usability assessments were conducted. Twenty-seven independent results from a comprehensive neurocognitive test of the same participants were retrieved separately of the 2 years before or after the use of the app. Post-hoc exploratory analyses were carried out using Spearman correlations to identify significant cognitive deficits domains influencing the usability and retention with the app. Results There were no statistically significant cognitive variables associated with the use, reported usability or retention with the app. Some variables associated with executive functions, verbal and visual memory correlated significantly with previous use of smartphones. Limitations Post-hoc analysis with a limited sample size. Conclusion These preliminary results suggests that patients with BD and mild cognitive deficits do not present any limitation in using mental health apps. In our case, the adoption of a user-centred design in the development process of the app could have mitigated the participants' difficulties when using the app.

Background Despite the potential importance of understanding violent criminal behavior (VCB) in individuals suffering from bipolar disorder (BD), previous findings are conflicting. The aims of the present study are to clarify the association of VCB and BD in comparison to general population and other psychiatric conditions. Methods A systematic review of literature from January 1st, 1980 through January 16th, 2017 from 3 electronic databases (MEDLINE/PubMed, EMBASE and PsycInfo), following the PRISMA and the MOOSE statements. Original peer-reviewed studies reporting data on VCB in BD were included. A random-effects meta-analysis was performed. Potential sources of heterogeneity were examined through subgroup and meta-regression analyses. The protocol was registered in PROSPERO, CRD42017054070. Results Twelve studies providing data from 58,475 BD participants. The prevalence of VCB in BD was 7.1% (95%CI = 3.0‒16.5%; k = 4). The association of BD and VCB compared to general population was not significant (OR = 2.784; 95% CI, 0.687‒11.287, P = .152). The association was significant only in cross-sectional studies, in studies in which VCB was assessed through self-reported measures, and in studies conducted in the USA. BD was more likely to be associated with VCB when BD patients were compared to controls with depressive disorders, whilst it was found to be less associated with VCB when BD was compared to psychotic disorders. Limitations 1. the methodological heterogeneity across the included studies. 2. causal inferences were precluded by the inclusion of cross-sectional studies. Conclusions These findings might provide a more balance portrait of the association between BD and VCB to clinicians, law enforcement and general public.

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.

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.

BACKGROUND: Biological rhythms (BR) disturbance has been suggested as a potential mediator of mood episodes in Bipolar Disorder (BD). The Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) was designed as an assessment tool to evaluate BR domains comprehensively. In the context of a trial evaluating a smartphone application delivering personalized psychoeducational contents for BD (SIMPLe 1.0), the main aim of this study is to evaluate the potential impact of SIMPLe 1.0 in BR regulation using the BRIAN scale.METHODS: 51 remitted BD patients were asked to use the application for 3 months. Paired t-test analyses were employed to compare baseline and follow-up BRIAN´s total and domains scores. The sample was divided into completers and non-completers of the study to evaluate differences between groups regarding BRIAN scores using ANCOVA analyses.RESULTS: The BRIAN's mean total score of the whole sample significantly decreased from baseline to post-intervention (35.89 (SD 6.64) vs. 31.18 (SD 6.33), t = 4.29, p = 0.001). At post-intervention, there was a significant difference between groups regarding the total BRIAN mean score (29.47 (SD 6.21) completers vs. 35.92 (SD 3.90) non-completers, t = 2.50, p = 0.02). This difference was maintained after conducting a one-way ANCOVA controlling for pre-intervention BRIAN scores, F (1, 46) = 10.545, p=0.002.LIMITATIONS: A limited sample, pre-post measures, and a short study timeframe could have affected the results. Additional factors affecting BR, such as medication, could not be ruled out.CONCLUSION: Our results suggest that there are potential positive effects of a psychoeducational smartphone application as an adjunctive to treatment as usual on BD patients' BR.

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 1.5 SDs above/below the normative group mean, as follows: a low performance (LP) 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.

Over the last decade, there has been a growing appreciation of the importance of identifying and treating cognitive impairment associated with bipolar disorder, since it persists in remission periods. Evidence indicates that neurocognitive dysfunction may significantly influence patients’ psychosocial outcomes. An ever-increasing body of research seeks to achieve a better understanding of potential moderators contributing to cognitive impairment in bipolar disorder in order to develop prevention strategies and effective treatments. This review provides an overview of the available data from studies examining treatments for cognitive dysfunction in bipolar disorder as well as potential novel treatments, from both pharmacological and psychological perspectives. All these data encourage the development of further studies to find effective strategies to prevent and treat cognitive impairment associated with bipolar disorder. These efforts may ultimately lead to an improvement of psychosocial functioning in these patients.

(1) Background: bipolar disorder (BD) is a chronic disease that often leads to functional impairment. The objective of this study is to elucidate which variables are associated with better functional outcomes in a sample of euthymic patients with BD. (2) Methods: patients were recruited at the Hospital Clinic of Barcelona and they underwent a clinical interview, a functional assessment, and a comprehensive neuropsychological evaluation. After that, patients were divided into two groups according to the Functioning Assessment Short Test total score: functionally remitted vs. functionally impaired. Following this, a multivariate logistic regression was run in order to identify clinical, demographic and cognitive factors associated with functional remission. (3) Results: a total of 420 euthymic patients with BD were assessed for this study, distributed as follows: functionally remitted (n = 221) and functionally impaired (n = 199). Finally, the multivariate logistic regression revealed that only five variables significantly contributed to the model, including: lifetime history of psychotic symptoms (the variable that contributed the most to the model), followed by the Hamilton Depression total score, and cognitive performance (executive functions and verbal memory). (4) Conclusions: treatments to ensure a good functional outcome in BD should specially prevent psychosis, target subthreshold depressive symptoms and enhance cognition, more specifically executive functions and verbal memory.

(1) Background: The cognitive reserve (CR) concept has not been precisely defined in severe mental disorders and has been estimated using heterogeneous methods. This study aims to investigate and develop the psychometric properties of the Cognitive Reserve Assessment Scale in Health (CRASH), an instrument designed to measure CR in people with severe mental illness; (2) Methods: 100 patients with severe mental illness (non-affective psychoses and affective disorders) and 66 healthy controls were included. The internal consistency and convergent validity of CRASH were assessed. Spearman’s correlations coefficients were also performed to examine the relationship between CRASH and neuropsychological tests, psychosocial functioning, and clinical course; (3) Results: The internal consistency was high (Cronbach’s alpha coefficient = 0.903). The CRASH global score had a large positive correlation with the Cognitive reserve questionnaire total score (r = 0.838, p < 0.001), demonstrating good convergent validity. The correlation coefficients between the CRASH total scores and clinical, functional, and neuropsychological performance were different between groups. In order to provide clinical interpretation, severity classification based on diagnosis (non-affective psychotic disorders, affective disorders, and healthy controls) have been created; (4) Conclusions: CRASH is the first CR measure developed specifically for patients with severe mental illness, facilitating reliable and valid measurement of this construct. The scale may aid in the stratification of patients and the implementation of personalized interventions.

Background The working alliance plays an essential role in the treatment of patients with different diseases. However, this variable has received little attention in patients with bipolar disorder. Therefore, this systematic review aimed to examine the working alliance's influence on these patients’ treatment outcomes, analyze its role in the adherence to pharmacotherapy, and identify the variables that are related to a good working alliance. Methods PubMed, PsycINFO, and Web of Science databases were searched until January 5, 2018 using a predetermined search strategy. Then, a formal process of study selection and data extraction was conducted. Results Seven articles fulfilled the inclusion criteria and they included a total of 3,985 patients with bipolar disorder type I and II. Although the working alliance's ability to predict the duration and presence of manic and depressive symptoms is unclear, a good working alliance facilitates the adherence to pharmacological treatment. In addition, good social support for patients is associated with a strong working alliance. Limitations The selected studies used different definitions and measures of the working alliance and adherence, and most used self-reports to assess the working alliance. Furthermore, the relationships found among the variables were correlational. Conclusions The working alliance can play an important role in adjunctive psychological therapies and in pharmacological and somatic treatments for patients with bipolar disorder. However, the number of studies on working alliance in bipolar disorder is rather limited and there is methodological heterogeneity between the studies.

People with bipolar disorder frequently experience persistent residual symptoms, problems in psychosocial functioning, cognitive impairment, and poor quality of life. In the last decade, the treatment target in clinical and research settings has focused not only on clinical remission, but also on functional recovery and, more lately, in personal recovery, taking into account patients’ well-being and quality of life. Hence, the trend in psychiatry and psychology is to treat bipolar disorder in an integrative and holistic manner. This literature review offers an overview regarding psychosocial functioning in bipolar disorder. First, a brief summary is provided regarding the definition of psychosocial functioning and the tools to measure it. Then, the most reported variables influencing the functional outcome in patients with bipolar disorder are listed. Thereafter, we include a section discussing therapies with proven efficacy at enhancing functional outcomes. Other possible therapies that could be useful to prevent functional decline and improve functioning are presented in another section. Finally, in the last part of this review, different interventions directed to improve patients’ well-being, quality of life, and personal recovery are briefly described.

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

Functional improvement has become one of the aims of the treatment of bipolar disorder. However, scant attention has been given to family functioning, even though it has a role in the illness outcome and is affected by the disorder. The aims of this study were to compare family functioning reported by euthymic patients with bipolar disorder and healthy controls; explore the level of congruence in the perception of family environment between patients with bipolar disorder and their relatives; and analyse the relationship between clinical variables and family functioning. The sample comprised 82 adult euthymic subjects with bipolar disorder, 82 family caregivers of these patients and 47 healthy controls. Participants completed the Family Environment Scale. Results showed moderate correlations and a mean pattern almost identical between relatives' and patients' reported scores in family functioning subscales. There were significant differences between patients and controls, favourable for the latter, in the subscales cohesion (p

Background During the last fifteen years, the possibility of delivering psychoeducation programs through Internet-based platforms have been explored. Studies evaluating those programs have shown good to acceptable retention rates. In this context, we developed a smartphone application (SIMPLe) collecting information about mood symptoms and offering personalized psychoeducation messages. The main aims of this study were to evaluate the feasibility, acceptability and satisfaction of the smartphone application. Methods The study was conducted from March to August 2015. Participation in the study was proposed to a consecutive sample of adult patients attending an outpatient mental health clinic. Sociodemographic data, clinical and functional assessments alongside smartphone ownership and uses were collected at baseline and at 3 months' follow-up. A 5 item Likert-scale satisfaction questionnaire was also employed. Results 51 participants were initially enrolled in the study, 36 (74%) remained actively using the application after 3 months. The whole sample interacted with the application a mean of 77 days (SD=26.2). During these days they completed 88% of the daily tests. Over 86% of the participants agreed that the experience using the application was satisfactory. Limitations The diversity of smartphones operating systems led to a moderate, although representative, sample number. Additionally, the subjective data reporting, narrow time frame of use and stability of the patients could have affected the results. Conclusions The results confirm that this particular intervention is feasible and represent a satisfactory and acceptable instrument for the self-management of bipolar disorder as an add-on to the usual treatment but future clinical trials must still probe its efficacy.

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 Clinic 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 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.

The chronic, long-term evolution of bipolar disorder (BD) requires a careful clinical characterization with prognostic implications in terms of symptom and functional control. The OPTHYMUM multicenter study was conducted in France with the objective of evaluating residual symptoms on overall functioning of BD patients during inter-episodic period. The aims of the present study were to identify the potentially modifiable (e.g., treatable) and non-modifiable variables associated with functional impairment during the inter-episodic periods of BD. Sample was divided into two groups according to level of functioning (adequate vs. impaired), based on the FAST scale total score. FAST cut-off for functional impairment is a score >11. The two subgroups were compared as per sociodemographic and clinical variables with standard univariate analyses, and a logistic regression model was created. The model as a whole contained independent non-modifiable factors (age, gender, BD type, illness duration) and modifiable factors (illness severity, predominant polarity, depressive and manic residual symptoms, comorbidities). The final model was statistically significant (χ 2 = 53.89, df = 5, p

Objective This study aimed to assess (1) whether there were clinical, neuropsychological and functional differences between and within affective and non-affective psychoses at baseline and two years-follow-up and (2) to explore clinical and neuropsychological predictors of psychosocial functioning in the whole sample. Method This is a subanalysis from a multicentre, naturalistic, longitudinal prospective study (‘Phenotype-genotype and environmental interaction. Application of a predictive model in first psychotic episodes’). The sample consisted of 192 patients with a first psychotic episode (FEP): 142 with non-affective psychoses and 50 with affective psychoses. Student t-tests, paired t-tests, Pearson correlations, ANOVAs and regression analyses were performed. Results At baseline, the groups differed in perseverative errors (WCST), Premorbid Adjustment Scale (PAS), family history of psychiatric disorder, negative (PANSS) and manic symptoms (YMRS). At two years follow-up, the groups differed in all the PANSS subscales and in depressive symptoms assessed by the MADRS. When the whole sample was considered, the regression model which best explained the estimated variance in functioning at follow-up (41%) was composed by PANSS total score and verbal fluency assessed by the FAS (COWAT). Conclusions We found clinical and neurocognitive differences at baseline which decreased in the follow-up. Reduced performances at baseline in executive functions in combination with symptom severity (PANSS) were predictors of FEP patients’ poor functional outcome.

Background: In the last decade, there has been an increasing advent of innovative concepts in psychological interventions aimed at empowering bipolar patients by means of technological advancements and taking advantage of the proliferation of the Internet. Since the adoption of these technologies for behavioral monitoring and intervention is not trivial in clinical practice, the main objective of this review is to provide an overview and to discuss the several initiatives published so far in the literature related to the Internet-based technologies aimed to deliver evidence-based psychological interventions for bipolar disorder patients. Methods: We conducted a comprehensive systematic review of the literature from multiple technological, psychiatric and psychological domains. The search was conducted by applying the Boolean algorithm “BIPOLAR AND DISORDER AND (treatment OR intervention) AND (online OR Internet OR webbased OR smartphone OR mobile)” at MEDLINE, SCOPUS, EMBASE, ClinicalTrials, ISI Web of Science and Google Scholar. Results: We identified over 251 potential entries matching the search criteria and after a thorough manual review, 29 publications pertaining to 12 different projects, specifically focusing on psychological interventions for bipolar patients through diverse Internet-based methods, were selected. Limitations: Taking into consideration the diversity of the initiatives and the inconclusive main outcome results of the studies, there is still limited evidence available to draw firm conclusions about the efficacy of interventions using Internet-based technologies for bipolar disorder. Conclusions: However, considering the high rates of retention and compliance reported, they represent a potential highly feasible and acceptable method of delivering this kind of interventions to bipolar patients.

Introduction Bipolar disorder is a relapsing-remitting condition affecting approximately 1–2% of the population. Even when the treatments available are effective, relapses are still very frequent. Therefore, the burden and cost associated to every new episode of the disorder have relevant implications in public health. The main objective of this study was to estimate the associated health resource consumption and direct costs of manic episodes in a real world clinical setting, taking into consideration clinical variables. Methods Bipolar I disorder patients who recently presented an acute manic episode based on DSM-IV criteria were consecutively included. Sociodemographic variables were retrospectively collected and during the 6 following months clinical variables were prospectively assessed (YMRS,HDRS-17,FAST and CGI-BP-M). The health resource consumption and associate cost were estimated based on hospitalization days, pharmacological treatment, emergency department and outpatient consultations. Results One hundred and sixty-nine patients from 4 different university hospitals in Catalonia (Spain) were included. The mean direct cost of the manic episodes was €4771. 77% (€3651) was attributable to hospitalization costs while 14% (€684) was related to pharmacological treatment, 8% (€386) to outpatient visits and only 1% (€50) to emergency room visits. The hospitalization days were the main cost driver. An initial FAST score >41 significantly predicted a higher direct cost. Conclusions Our results show the high cost and burden associated with BD and the need to design more cost-efficient strategies in the prevention and management of manic relapses in order to avoid hospital admissions. Poor baseline functioning predicted high costs, indicating the importance of functional assessment in bipolar disorder.

Resumen Introduccion El Trastorno Bipolar (TB) es una enfermedad con frecuentes recaidas y remisiones que afecta a aproximadamente el 1 al 2% de la poblacion mundial. Aun con la eficacia de los tratamientos disponibles actualmente, las recaidas son frecuentes. Por tanto, el costo y consumo de recursos asociados a cada nuevo episodio tienen un impacto importante en el sistema sanitario. El principal objetivo de este estudio fue el de estimar los costos directos y recursos sanitarios empleados durante el tratamiento de episodios maniacos en la practica clinica diaria, teniendo en cuenta ademas variables clinicas. Metodos Fueron incluidos de manera consecutiva pacientes quienes hayan presentado recientemente un episodio maniaco agudo segun los criterios del DSM-IV. Se recogieron de manera retrospectiva variables sociodemograficas y durante los siguientes 6 meses se realizaron evaluaciones clinicas sistematicas que incluian YMRS,HDRS-17,FAST and CGI-BP-M. El consumo de recursos sanitarios y los costos asociados fueron estimados a partir de los dias de hospitalizacion, el tratamiento farmacologico, las visitas a urgencias y ambulatorias. Resultados Se incluyeron 169 pacientes de 4 hospitales universitarios de Cataluna, Espana. El costo directo medio de cada episodio maniaco fue de €4771. De estos, 77% (€3651) correspondia a los costos de hospitalizacion, 14% (€684) al tratamiento farmacologico, 8% (€386) a las visitas ambulatorias y solo 1% (€50) a visitas en urgencias. Los dias de hospitalizacion fueron el mayor componente del costo total. Un puntaje inicial de FAST >41 predijo de forma significativa un mayor costo directo. Conclusiones Nuestros resultados demuestran el elevado costo y consumo de recursos sanitarios asociados al TB y reflejan la necesidad de disenar mas y mejores estrategias costo-efectivas en el manejo y prevencion de episodios maniacos a fin de evitar ingresos hospitalarios. Un peor estado funcional basal es predictivo de mayores costos, indicando la importancia de realizar una evaluacion funcional en el TB de manera sistematica.

The concept of well-being which focuses on positive emotions has received increased research attention. However, a consensus definition of this term is lacking. The Well-Being Index scale (WHO-5) is a generic, self-report scale that contains five Likert-type items to evaluate psychological well-being. This construct may provide a relevant outcome in bipolar disorder (BD) research and care beyond the rating of mood symptoms. Thus, in the current study, the psychometric properties of the WHO-5 Spanish version were assessed in a sample of euthymic patients with BD.Patients with BD- I and BD-II and healthy controls completed the Well-Being Index (WHO-5) together with an assessment of depressive (Hamilton Depression Rating Scale-17; HAM-D) and manic symptoms (Young Mania Rating Scale; YMRS); and a measure of psychosocial functioning (Functioning Assessment Short Test; FAST). Internal consistency reliability was measured through Cronbach's alpha. Test-retest reliability was calculated comparing the WHO-5 total score at baseline and after 10 days of the first administration. To assess the structure of the scale, a principal component analysis (PCA) was carried out. Correlations between the WHO-5, HAM-D, YMRS and FAST were calculated. Finally, a t-test for independent samples was applied to compare the WHO-5 total score in the patient and control groups.A total of 104 patients with BD and 40 healthy controls were included in this study. A Chronbach's alpha of 0.83 indicated acceptable internal consistency. A paired sample t-test revealed no significant differences between WHO-5 total score at baseline and at follow-up (tn = - 0.72; df = 15; p = 0.48). The PCA provided a single factor solution that accounted for 59.74% of the variation in WHO-5. Test-retest reliability was high (r = 0.83; p0.001). Moderate negative correlations were observed between the WHO-5 total score, the FAST (r = - 0.46.; p0.001) and the HAM-D (r = - 0.68; p0.001), but not with the YMRS (r = - 0.07; p = 0.42). Finally, significant differences were found when comparing the WHO-5 total score between patient and healthy controls (t = 5.1; df = 147; p0.001).some limitations include the lack of a comparator scale to test for validity construct and the small sample size in the test-retest reliability CONCLUSIONS: The WHO-5 shows an acceptable reliability index and measures a unitary construct in a Spanish population of euthymic patients with BD.

Data describing bipolar disorder in older adults people are scarce, particularly with regard to functional status. This observational, comparative study assessed psychosocial functioning in 33 euthymic older adults with bipolar disorder compared with 30 healthy controls. In addition, we evaluated the association between clinical variables and poor functioning in the patient group. The mean age of the group was 68.70 years. Patients with bipolar disorder experienced poorer psychosocial functioning (19.15 ± 11.36) than healthy controls (5.17 ± 3.72; p = 0.0001), as assessed using the Functioning Assessment Short Test. Significant differences between the groups were found for specific domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, and interpersonal relationships (p = 0.0001, respectively). The largest variation was observed in overall functioning (Cohen's d = 0.63). The number of previous hospitalizations was strongly associated with poor overall functioning (F = 7.217, p = 0.002). Older patients with bipolar disorder had a greater functional impairment than the healthy control group. Implementation of novel rehabilitation models is critical to help patients manage their illness.

Altres ajuts: Plan Nacional 2013-2016 with a Miguel Servet Research Contract (MS14/00041). We acknowledge also the generous support by the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain. Up to 60% of patients with bipolar disorder (BD) have a history of traumatic events, which is associated with greater episode severity, higher risk of comorbidity and higher relapse rates. Trauma-focused treatment strategies for BD are thus necessary but studies are currently scarce. The aim of this study is to examine whether Eye Movement Desensitization and Reprocessing (EMDR) therapy focusing on adherence, insight, de-idealisation of manic symptoms, prodromal symptoms and mood stabilization can reduce episode severity and relapse rates and increase cognitive performance and functioning in patients with BD. This is a single-blind, randomized controlled, multicentre trial in which 82 patients with BD and a history of traumatic events will be recruited and randomly allocated to one of two treatment arms: EMDR therapy or supportive therapy. Patients in both groups will receive 20 psychotherapeutic sessions, 60 min each, during 6 months. The primary outcome is a reduction of affective episodes after 12 and 24 months in favour of the EMDR group. As secondary outcome we postulate a greater reduction in affective symptoms in the EMDR group (as measured by the Bipolar Depression Rating Scale, the Young Mania Rating Scale and the Clinical Global Impression Scale modified for BD), and a better performance in cognitive state, social cognition and functioning (as measured by the Screen for Cognitive Impairment in Psychiatry, The Mayer-Salovey-Caruso Emotional Intelligence Test and the Functioning Assessment Short Test, respectively). Traumatic events will be evaluated by The Holmes-Rahe Life Stress Inventory, the Clinician-administered PTSD Scale and the Impact of Event Scale. The results of this study will provide evidence whether a specific EMDR protocol for patients with BD is effective in reducing affective episodes, affective symptoms and functional, cognitive and trauma symptoms. The trial is registered at ClinicalTrials.gov, identifier: . Registered on 3 December 2015. The online version of this article (doi:10.1186/s13063-017-1910-y) contains supplementary material, which is available to authorized users.

International audience; Background: Many patients with bipolar disorder (BD) experience residual symptoms during their inter-episodic periods. The study aimed to analyse the relationship between residual depressive symptoms, sleep disturbances and self-reported cognitive impairment as determinants of psychosocial functioning in a large sample of euthymic BD patients. Methods: This was a cross-sectional study of 468 euthymic BD outpatients. We evaluated the residual depressive symptoms with the Bipolar Depression Rating Scale, the sleep disturbances with the Pittsburgh Sleep Quality Index, the perceived cognitive performance using visual analogic scales and functioning with the Functioning Assessment Short Test. Structural equation modelling (SEM) was used to describe the relationships among the residual depressive symptoms, sleep disturbances, perceived cognitive performance and functioning. Results: SEM showed good fit with normed chi square=2.46, comparative fit index=0.94, root mean square error of approximation=0.05 and standardized root mean square residuals=0.06. This model revealed that residual depressive symptoms (path coefficient =0.37) and perceived cognitive performance (path coeffi-cient=0.27) were the most important features significantly related to psychosocial functioning. Sleep disturbances were indirectly associated with functioning via residual depressive symptoms and perceived cognitive performance (path coefficient=0.23). Conclusions: This study contributes to a better understanding of the determinants of psychosocial functioning during the inter-episodic periods of BD patients. These findings should facilitate decision-making in therapeutics to improve the functional outcomes of BD during this period.

The recurrent nature of bipolar disorder (BD), and the high morbidity and mortality associated with the illness advocate for an integrative treatment in which medication is complemented with psychological approaches. This chapter explores the role of adjunctive psychotherapy in BD. The most commonly tested psychological treatments have been cognitive-behavioural therapy, psychoeducation, interpersonal and social rhythm therapy, and family intervention. Functional remediation represents a new option for patients with functional impairment. Most findings indicate the benefits of adjunctive psychological treatments to improve the outcomes of BD. Controversial results have also been found, highlighting the need for a better identification of treatment moderators and mediators to design interventions tailored to the target population. Recently, cognitive remediation, mindfulness-based cognitive therapy, dialectical behaviour therapy, and eye movement desensitization and reprocessing have begun to be tested, as well as Internet-based psychological interventions, but it is too early to draw conclusions about their efficacy.

Background: Although several adjunctive psychological interventions are effective in the maintenance of bipolar disorders (BD), no attempt has been made to classify them according to their ability to prevent manic versus depressive episodes. Our study aims to rank the adjunctive psychotherapies for the prophylaxis of BD by means of their polarity index (PI). Methods: Randomized controlled trials comparing the efficacy of a psychological intervention with a comparator in BD maintenance treatment in patients aged over 18 were systematically reviewed. Exclusion criteria were a small sample size, a study sample not exclusively composed of bipolar patients and the absence of a control group. PI is a novel metric indicating the relative antimanic versus antidepressive preventive efficacy of treatments. PI was retrieved by calculating the ratio of the number needed to treat (NNT) for prevention of depression and the NNT for prevention of mania. PI >1.0 indicates a relatively higher antimanic prophylactic efficacy and PI Results: A total of 9 studies were included. PI was 0.33, 0.63 and 0.89 for cognitive-behavioral therapy, 0.42 for family-focused therapy, 0.73 and 0.78 for psychoeducation, 1 for enhanced relapse prevention, 1.78 for caregiver group psychoeducation and 3.36 for brief technique-driven interventions. With regard to the PI for 1 cognitive-behavioral study, enhanced relapse prevention and brief technique-driven interventions may not be reliable since those trials were negative. Conclusions: The PI provides a measure of how much depression-preventive or (hypo) mania-preventive an intervention is and may guide the choice of adjunctive psychotherapy in the context of individualized long-term treatment of BD.

BACKGROUND: The functional outcome of Bipolar Disorder (BD) is highly variable. This variability has been attributed to multiple demographic, clinical and cognitive factors. The critical next step is to identify combinations of predictors that can be used to specify prognostic subtypes, thus providing a basis for a staging classification in BD. METHODS: Latent Class Analysis was applied to multiple predictors of functional outcome in a sample of 106 remitted adults with BD. RESULTS: We identified two subtypes of patients presenting "good" (n=50; 47.6%) and "poor" (n=56; 52.4%) outcome. Episode density, level of residual depressive symptoms, estimated verbal intelligence and inhibitory control emerged as the most significant predictors of subtype membership at the p

IntroductionMost studies selected euthymic patients with bipolar disorder in inter-episodic phase according to clinical remission criteria at least between 1 and 6 months. However, possible differences can exist in the course of clinical symptoms in bipolar patients related to the duration of clinical remission.ObjectivesThe main aim of this study was to evaluate the clinical status of bipolar patients after 6 months of clinical remission.MethodsWe performed a cross-sectional study of bipolar outpatients in clinical remission for at least 6 months. Bipolar Depression Rating Scale (BDRS), Young Mania Rating scale, Pittsburgh Sleep Quality Index (PSQI) scale, Visual Analogic Scales (VAS) evaluated cognitive impairment were used to assess residual symptomatology of patients. Multivariate analysis (MANCOVA) was conducted for analysing possible differences between 3 groups of patients according to their duration of clinical remission (< 6 months–1 year, < 1 year–3 years, < 3 years–5 years).ResultsA total of 525 patients were included into the study. The multivariate analysis indicated a significant effect of the duration of clinical remission on the different residual symptoms (Pillai's trace: F 4.48, P < 0.001). The duration of clinical remission was associated with the significant improvement of the BDRS total score (P = 0.013), the PSQI total score (P < 0.001) and the cognitive VAS total score (P < 0.001)ConclusionThese results support a possible improvement of residual symptoms according to the duration of clinical remission in bipolar patients. Any definition of euthymia should specify the duration criteria.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Objective Although many studies showed the negative impact of residual symptoms on the course of bipolar disorder (BD), there is a need to examine potential differences in residual symptoms according to the duration of euthymia in remitted BD patients. Method This was a large cross-sectional study of 525 euthymic BD out-patients. A multivariate analysis of covariance was conducted to compare depressive and manic residual symptoms, sleep disturbances and cognitive complaints among three patient groups on the basis of duration of euthymia (A. 6 months to

Despite the high morbidity and mortality associated with bipolar depression, the optimal treatment for this phase is still a matter of debate. The aim of the current review was to provide updated evidence about the efficacy and tolerability of anticonvulsants in the treatment of acute bipolar depression. A comprehensive review of randomized controlled trials (RCTs) evaluating the use of anticonvulsants for the treatment of acute bipolar depression up to June 2011 was conducted by means of the PubMed-Medline database. Eligibility criteria included active comparator-controlled or placebo-controlled randomized studies involving monotherapy or combination therapy. A total of 18 RCTs fulfilled the inclusion criteria. Studies supported the efficacy of divalproex as monotherapy in acute bipolar depression but small sample size was a common methodological limitation. Findings were inconclusive for lamotrigine and carbamazepine although overall lamotrigine may have a beneficial but modest effect. Negative results were found for levetiracetam and gabapentin but the evidence base on these agents is scant. All anticonvulsants were generally well tolerated. No double-blind RCTs were found for the use of other anticonvulsants such as oxcarbazepine, licarbazepine, zonisamide, retigabine, pregabalin, tiagabine, felbamate and vigabatrine in the acute treatment of bipolar depression. To sum up, taking into consideration the efficacy and tolerability profiles of anticonvulsants, current evidence supports the use of divalproex and lamotrigine in the treatment of acute bipolar depression. However, available data for most other anticonvulsants are inconclusive and further RCTs with larger sample sizes are needed before drawing firm conclusions.

Objective To provide empirical evidence of the effect of subthreshold symptomatology (both depressive and manic) on psychosocial functioning, neurocognition and quality of life in bipolar disorder. Methods A total of 133 participants were enrolled for this study (bipolar patients, n = 103; healthy controls, n = 30). Patients were divided into two groups according to their levels of subthreshold symptomatology: the subsyndromic group was constituted by those patients with upper levels of subthreshold symptomatology (HDRS ≥ 4 and YMRS ≥ 3) and the asymptomatic group represented the patients with lower scores (HDRS ≤ 3 and YMRS ≤ 2). All participants were administered a comprehensive neuropsychological battery. Moreover the patients answered the SF-36 (Quality of Life, QoL) and were interviewed with the WHODAS-2 (Psychosocial functioning and disability). One-way ANOVA were used in order to compare the differences between the three groups. Results The analyses revealed that both patients groups, albeit free of acute symptoms of mania or depression, differed in terms of functioning and disability assessed with the WHODAS-2. Specifically, the total global score of disability was higher for the subsyndromic group indicating more impairment (p = 0.008). The same pattern of impairment was found for three of its domains: “understanding and communicating” (p = 0.013); “self-care” (p = 0.035) and “getting along with others” (p = 0.024). The subsyndromic group also scored lower when compared to their counterparts in the Mental Component of QoL of the SF-36 (p = 0.045). Finally, in the neuropsychological performance verbal learning and memory was found to be impaired regardless the levels of subthreshold symptomatology, suggesting that this variable is a robust indicator of neuropsychological impairment in BD patients. Conclusions This report presents empirical data suggesting a moderate impact of subthreshold symptoms on functioning/disability and QoL and a discrete impact on neuropsychological impairment.