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First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d= -0.42,p= 3 x 10(-5)), with weak evidence of IQ reductions among BD-FDRs (d= -0.23,p= .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. in contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment., Australian National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [1037196, 1063960, 1066177, 510135, 1176716]; Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR) [103703, 106469, 142255]; Departament de Salut de la Generalitat de CatalunyaGeneralitat de Catalunya [SLT002/16/00331]; Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [1617]; Development Service Merit Review Award [I01CX000227]; Dokuz Eylul University Department of Scientific Research [2012.KB.SAG.062]; e:Med program [O1ZX1314B, O1ZX1314G]; Ege University School of Medicine Research Foundation [2009-D-00017]; Fundacio Marato TV3 [091630]; Netherlands Organisation for Health Research and DevelopmentNetherlands Organization for Health Research and Development [10-000-1002]; Generalitat de CatalunyaGeneralitat de Catalunya [2017SGR01271]; German Federal Ministry for Education and ResearchFederal Ministry of Education & Research (BMBF); Medical Research CouncilMedical Research Council UK (MRC) [G0901310]; Ministerstvo Zdravotnictvi Ceske Republiky [NR8786, NT13891]; National Alliance for Research on Schizophrenia and DepressionNARSAD [17319, 20244, 26731]; Swiss National Centre of Competence in Research Robotics [51NF40-185897]; National Institute of Mental HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [1S10OD017974-01, P30 NS076408, R01 MH052857, R01 MH080912, R01 MH113619, U01 MH108150, R01 MH085667]; National Institute on AgingUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [T32AG058507]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P41 EB015922, R01 MH111671, R01 MH116147, R01 MH117601, R01MH121246, R03 MH105808, U54EB020403]; Research Council of NorwayResearch Council of Norway [223273]; Spanish Ministry of Economy and Competitiveness/Instituto de Salud Carlos III [CPII19/00009, PI070066, PI1100683, PI1500467, PI18/00976]; Stanley Medical Research Institute; Swedish Research CouncilSwedish Research Council [K2007-62X-15077-04-1, K2008-62P-20597-01-3, K2010-62X-15078-07-2, K2012-61X-15078-09-3]; Swiss National Science FoundationSwiss National Science Foundation (SNSF) [32003B_156914]; VIDINetherlands Organization for Scientific Research (NWO) [452-11-014, 917-46-370]; Wellcome TrustWellcome Trust [085475/B/08/Z, 085475/Z/08/Z, 064971]; ZonMwNetherlands Organization for Health Research and Development [908-02-123], Australian National Health and Medical Research Council Grants, Grant/Award Numbers: 1037196, 1063960, 1066177, 510135, 1176716; Canadian Institutes of Health Research, Grant/Award Numbers: 103703, 106469, 142255; Departament de Salut de la Generalitat de Catalunya, Grant/Award Number: SLT002/16/00331; Deutsche Forschungsgemeinschaft, Grant/Award Number: 1617; Development Service Merit Review Award, Grant/Award Number: I01CX000227; Dokuz Eylul University Department of Scientific Research Projects Funding, Grant/Award Number: 2012.KB.SAG.062; e:Med program, Grant/Award Numbers: O1ZX1314B, O1ZX1314G; Ege University School of Medicine Research Foundation, Grant/Award Number: 2009-D-00017; Fundacio Marato TV3, Grant/Award Number: 091630; Geestkracht program of the Netherlands Organisation for Health Research and Development, Grant/Award Number: 10-000-1002; Generalitat de Catalunya, Grant/Award Number: 2017SGR01271; German Federal Ministry for Education and Research; Medical Research Council, Grant/Award Number: G0901310; Ministerstvo Zdravotnictvi Ceske Republiky, Grant/Award Numbers: NR8786, NT13891; National Alliance for Research on Schizophrenia and Depression, Grant/Award Numbers: 17319, 20244, 26731; Swiss National Centre of Competence in Research Robotics, Grant/Award Number: 51NF40-185897; National Institute of Mental Health, Grant/Award Numbers: 1S10OD017974-01, P30 NS076408, R01 MH052857, R01 MH080912, R01 MH113619, U01 MH108150, R01 MH085667; National Institute on Aging, Grant/Award Number: T32AG058507; National Institutes of Health, Grant/Award Numbers: P41 EB015922, R01 MH111671, R01 MH116147, R01 MH117601, R01MH121246, R03 MH105808, U54EB020403; Research Council of Norway, Grant/Award Number: 223273; Spanish Ministry of Economy and Competitiveness/Instituto de Salud Carlos III, Grant/Award Numbers: CPII19/00009, PI070066, PI1100683, PI1500467, PI18/00976; Stanley Medical Research Institute; Swedish Research Council, Grant/Award Numbers: K2007-62X-15077-04-1, K2008-62P-20597-01-3, K2010-62X-15078-07-2, K2012-61X-15078-09-3; Swiss National Science Foundation, Grant/Award Number: 32003B_156914; VIDI, Grant/Award Numbers: 452-11-014, 917-46-370; Wellcome Trust, Grant/Award Numbers: 085475/B/08/Z, 085475/Z/08/Z; Wellcome Trust Research Training Fellowship, Grant/Award Number: 064971; ZonMw, Grant/Award Number: 908-02-123

Sex differences influence the clinical characteristics and course of illness of bipolar disorder (BD).Therefore, the aim of the present study was to examine the role of sex differences in neurocognitive performance and psychosocial functioning in a large sample of euthymic patients suffering from BD.The sample included 462 individuals, 347 patients with BD (148 males and 199 females) and 115 healthy controls (HC) (45 males and 70 females). Performance on a comprehensive neuropsychological battery assessing six cognitive domains and psychosocial functioning was compared between groups using linear mixed models, with sex and group as main effects, group by sex interactions and center as a random effect.Males performed better than females in working memory (p 0.001), whereas females outperformed males in the verbal learning (p = 0.03) and memory recognition (p = 0.03) tasks. No significant group by sex interactions were detected in cognitive performance. There were no overall sex differences or group by sex interactions in psychosocial functioning.Lack of assessment of visuo-spatial working memory.There were no overall sex differences in neurocognition and psychosocial functioning. However, small sex differences in some measures of working memory and verbal memory were found. Individual differences of each patient, including sex perspective, should be considered in order to perform a tailored intervention plan adjusted to specific needs in the context of personalized treatment.

MRI‐derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta‐Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis‐driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large‐scale meta‐ and mega‐analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large‐scale, collaborative studies of mental illness., This review discusses the major challenges facing neuroimaging research of bipolar disorder and highlights the major accomplishments, ongoing challenges and future goals of the ENIGMA Bipolar Disorder Working Group.

Lockdown caused by COVID-19 pandemic has a negative impact on mental health. The aim was to assess self-reported neurocognitive symptoms during the lockdown and identify associated vulnerable and protective factors in a sample of psychiatric patients in a Spanish population. These results are part of the Barcelona ResIlience Survey for Mental Health COVID-19 (BRIS-MHC) project. Neurocognitive symptoms were assessed through an online survey considering the five items that represented self-reported neurocognitive complaints. We split the sample into two groups based on the severity of the self-reported neurocognitive complaints: intact cognitive function/mild cognitive impairment (CI-) and moderate/severe cognitive impairment (CI+). Univariate analyses were used to compare both groups in terms of sociodemographic and clinical variables. Multiple logistic regression models were carried out to identify clinical variables and coping strategies associated with neurocognitive symptoms. 198 patients with different psychiatric diagnoses were included in this study. One hundred seventeen patients were classified in the CI- group and 81 in the CI+ group. Depressive symptoms and negative psychotic-like symptoms were vulnerable factors for neurocognitive impairment. Coping strategies of performing physical activity, carrying out relaxing activities and maintaining a routine were protective factors against cognitive impairment. Lockdown situation negatively impact on neurocognitive function. Psychopathological symptoms and coping strategies were associated with neurocognitive symptoms during lockdown in subjects with psychiatric illness. The early treatment of psychopathological symptoms in psychiatric patients and promoting coping strategies during lockdown should be considered an intervention strategy against cognitive impairment.

Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.

BackgroundMajor depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in MDD patients, and whether this process is associated with clinical characteristics in a large multi-center international dataset.MethodsWe performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 29 samples worldwide. Normative brain aging was estimated by predicting chronological age (10-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 1,147 male and 1,386 female controls from the ENIGMA MDD working group. The learned model parameters were applied to 1,089 male controls and 1,167 depressed males, and 1,326 female controls and 2,044 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain predicted age difference (brain-PAD).FindingsOn average, MDD patients showed a higher brain-PAD of +0.90 (SE 0.21) years (Cohen’s d=0.12, 95% CI 0.06-0.17) compared to controls. Relative to controls, first-episode and currently depressed patients showed higher brain-PAD (+1.2 [0.3] years), and the largest effect was observed in those with late-onset depression (+1.7 [0.7] years). In addition, higher brain-PAD was associated with higher self-reported depressive symptomatology (b=0.05, p=0.004).InterpretationThis highly powered collaborative effort showed subtle patterns of abnormal structural brain aging in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the predictive value of these brain-PAD estimates.FundingThis work was supported, in part, by NIH grants U54 EB020403 and R01 MH116147.

Background The DSM5-defined mixed features in depression do not include psychomotor agitation, irritability or distractibility because they are considered overlapping symptoms. A growing number of modern psychiatrists have expressed dissatisfaction with this and proposed alternative sets of mixed symptoms that are much more common and clinically relevant. Among such alternative criteria were those proposed by Koukopoulos. He utilized the research diagnostic criteria of agitated depression (RDC-A) as a mixed depression subtype, and validated another form of mixed depression, the Koukopoulos criteria for mixed depression (K-DMX). Purpose This study provides psychometric validation for the first self-rated scale designed to measure the most common mixed symptoms in depression as proposed by Koukopoulos. Patients and Methods We conducted a multicenter cross-sectional study of 170 patients with unipolar depression. They completed the Shahin Mixed Depression Scale (SMDS) and underwent expert interviews as a gold standard reference. SMDS' psychometric properties were assessed, including Cronbach's alpha, factor analysis, sensitivity, specificity, predictive value and accuracy. Results We found significant association and agreement between mixity according to SMDS and the gold standard (K-DMX and RDC-A according to expert interview) with good internal consistency (Cronbach's alpha=0.87), high sensitivity (=91.4%), specificity (=98.0%), positive predictive value (=96.9%), negative predictive value (= 94.2%) and accuracy (=95.2%). Factor analysis identified one factor for psychomotor agitation and another for mixity without psychomotor agitation. Conclusion SMDS was a reliable and valid instrument for assessing the frequently encountered and clinically relevant mixed features in depression.

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.

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.

Background: Bipolar disorder (BD) is associated with cortical and subcortical structural brain abnormalities. It is unclear whether such alterations progressively change over time, and how this is related to the number of mood episodes. To address this question, we analyzed a large and diverse international sample with longitudinal magnetic resonance imaging (MRI) and clinical data to examine structural brain changes over time in BD. Methods: Longitudinal structural MRI and clinical data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) BD Working Group, including 307 patients with BD and 925 healthy control subjects, were collected from 14 sites worldwide. Male and female participants, aged 40 ± 17 years, underwent MRI at 2 time points. Cortical thickness, surface area, and subcortical volumes were estimated using FreeSurfer. Annualized change rates for each imaging phenotype were compared between patients with BD and healthy control subjects. Within patients, we related brain change rates to the number of mood episodes between time points and tested for effects of demographic and clinical variables. Results: Compared with healthy control subjects, patients with BD showed faster enlargement of ventricular volumes and slower thinning of the fusiform and parahippocampal cortex (0.18 < d < 0.22). More (hypo)manic episodes were associated with faster cortical thinning, primarily in the prefrontal cortex. Conclusions: In the hitherto largest longitudinal MRI study on BD, we did not detect accelerated cortical thinning but noted faster ventricular enlargements in BD. However, abnormal frontocortical thinning was observed in association with frequent manic episodes. Our study yields insights into disease progression in BD and highlights the importance of mania prevention in BD treatment.

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 hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta‐Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1‐weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed‐effects models and mega‐analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = −0.20), cornu ammonis (CA)1 (d = −0.18), CA2/3 (d = −0.11), CA4 (d = −0.19), molecular layer (d = −0.21), granule cell layer of dentate gyrus (d = −0.21), hippocampal tail (d = −0.10), subiculum (d = −0.15), presubiculum (d = −0.18), and hippocampal amygdala transition area (d = −0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non‐users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD., The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder.In the largest study of hippocampal subfields in bipolar disorder to date, from 23 sites worldwide, we report widespread reductions in nine of 12 subfields.The lack of differences between lithium users and healthy controls supports a possible protective role of lithium in bipolar disorder.

Background: Cognitive profiles of BD patients show a demonstrated heterogeneity among young and middle-aged patients, but this issue has not yet deeply explored in Older Adults with bipolar disorder (OABD). The aim of the present study was to analyze cognitive variability in a sample of OABD. Methods: A total of 138 OABD patients and 73 healthy controls were included in this study. A comprehensive neuropsychological assessment was administered. We performed a k-means cluster analysis method based on the neurocognitive performance to detect heterogeneous subgroups. Demographic, clinical, cognitive and functional variables were compared. Finally, univariate logistic regressions were conducted to detect variables associated with the severity of the cognitive impairment. Results: We identified three distinct clusters based on the severity of cognitive impairment: (1) a preserved group (n = 58; 42%) with similar cognitive performance to HC, (2) a group showing mild cognitive deficits in all cognitive domains (n = 64; 46%) and, finally, (3) a group exhibiting severe cognitive impairment (n = 16; 12%). Older age, late onset, higher number of psychiatric admissions and lower psychosocial functioning were associated with the greatest cognitive impairment. Lower age, more years of education and higher estimated IQ were associated with a preserve cognitive functioning. Limitations: The small sample size of the severely impaired group. Conclusions: Cognitive heterogeneity remains at late-life bipolar disorder. Demographic and specific illness factors are related to cognitive dysfunction. Detecting distinct cognitive subgroups may have significant clinical implications for tailoring specific intervention strategies adapted to the level of the impairment and also to prevent cognitive decline.

Bipolar disorders (BDs) are among the leading causes of morbidity and disability. Objective biological markers, such as those based on brain imaging, could aid in clinical management of BD. Machine learning (ML) brings neuroimaging analyses to individual subject level and may potentially allow for their diagnostic use. However, fair and optimal application of ML requires large, multi-site datasets. We applied ML (support vector machines) to MRI data (regional cortical thickness, surface area, subcortical volumes) from 853 BD and 2167 control participants from 13 cohorts in the ENIGMA consortium. We attempted to differentiate BD from control participants, investigated different data handling strategies and studied the neuroimaging/clinical features most important for classification. Individual site accuracies ranged from 45.23% to 81.07%. Aggregate subject-level analyses yielded the highest accuracy (65.23%, 95% CI = 63.47–67.00, ROC-AUC = 71.49%, 95% CI = 69.39–73.59), followed by leave-one-site-out cross-validation (accuracy = 58.67%, 95% CI = 56.70–60.63). Meta-analysis of individual site accuracies did not provide above chance results. There was substantial agreement between the regions that contributed to identification of BD participants in the best performing site and in the aggregate dataset (Cohen’s Kappa = 0.83, 95% CI = 0.829–0.831). Treatment with anticonvulsants and age were associated with greater odds of correct classification. Although short of the 80% clinically relevant accuracy threshold, the results are promising and provide a fair and realistic estimate of classification performance, which can be achieved in a large, ecologically valid, multi-site sample of BD participants based on regional neurostructural measures. Furthermore, the significant classification in different samples was based on plausible and similar neuroanatomical features. Future multi-site studies should move towards sharing of raw/voxelwise neuroimaging data.

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.

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.

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.

It is well established that patients with either bipolar disorder (BD) or attention-deficit/hyperactivity disorder (ADHD) present functional impairment even when in remission. Nevertheless, research on functional impairment with adult patients with bipolar disorder comorbid to ADHD (BD+ADHD) is very scarce. The main objective of the current report was to evaluate the overall and specific domains of functioning, in patients with BD+ADHD compared to patients with pure bipolar disorder (pBD) and healthy controls (HCs).162 subjects from 3 groups were compared: 63 pBD, 23 BD+ADHD and 76 HCs. All the patients with BD had been euthymic for at least 6 months and they were recruited at the Hospital Clinic of Barcelona. All the participants were assessed with the 17-item Hamilton Depression Rating Scale (HAM-D), the Young Mania Rating Scale (YMRS) and the Functioning Assessment Short Test (FAST). Clinical, and sociodemographic data were also recorded.Clinical groups, pBD and BD+ADHD, showed lower overall functioning (p0.001) in each domain of the FAST scale compared to the HCs. Moreover, the Tukey post hoc test revealed that the BD+ADHD group showed a worse score than pBD in the cognitive domain of the FAST. However, after controlling for potential confounding variables, only the HDRS scores (p0.026) remained significant for the cognitive domain of the FAST.The small sample size of the comorbid BD+ADHD group.Adult patients with BD+ADHD showed the worst scores in functioning compared with the HCs, but did not show more severe functional impairment than the pBD group except for the cognitive domain. Therefore our findings suggest that depressive symptoms in adults with BD+ADHD may negatively influence cognitive functioning. Further studies are needed to confirm our findings for the management of BD+ADHD.

Objectives Cognition is a new treatment target to aid functional recovery and enhance quality of life for patients with bipolar disorder. The International Society for Bipolar Disorders (ISBD) Targeting Cognition Task Force aimed to develop consensus-based clinical recommendations on whether, when and how to assess and address cognitive impairment. Methods The task force, consisting of 19 international experts from nine countries, discussed the challenges and recommendations in a face-to-face meeting, telephone conference call and email exchanges. Consensus-based recommendations were achieved through these exchanges with no need for formal consensus methods. Results The identified questions were: (I) Should cognitive screening assessments be routinely conducted in clinical settings? (II) What are the most feasible screening tools? (III) What are the implications if cognitive impairment is detected? (IV) What are the treatment perspectives? Key recommendations are that clinicians: (I) formally screen cognition in partially or fully remitted patients whenever possible, (II) use brief, easy-to-administer tools such as the Screen for Cognitive Impairment in Psychiatry and Cognitive Complaints in Bipolar Disorder Rating Assessment, and (III) evaluate the impact of medication and comorbidity, refer patients for comprehensive neuropsychological evaluation when clinically indicated, and encourage patients to build cognitive reserve. Regarding question (IV), there is limited evidence for current evidence-based treatments but intense research efforts are underway to identify new pharmacological and/or psychological cognition treatments. Conclusions This task force paper provides the first consensus-based recommendations for clinicians on whether, when, and how to assess and address cognition, which may aid patients' functional recovery and improve their quality of life.

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.

We analyzed the efficacy of functional remediation, in a sample of patients with bipolar disorder who presented with subsyndromal symptoms. From a total sample of 239 patients with bipolar I and II disorder, according to DSM-IV-TR diagnostic criteria, entering a randomized clinical trial, those patients who presented with subsyndromal symptoms were selected based on a method already described by Berk and colleagues was applied. It consists of using the Clinical Global Impression-Bipolar version (CGI-BP) to establish the scores of the Hamilton Depression Rating Scale (HAM-D) and of the Young Mania Rating Scale (YMRS) that correspond with 1 in the CGI-BP. Functional outcome and mood symptoms were assessed at 6 and at 12-month follow-up. A total of 99 patients were selected for this post-hoc analysis, allocated as follows: functional remediation (n=33); psychoeducation (n=37) and treatment as usual (TAU,n=29). The repeated-measures analyses at 12-month follow-up revealed a significant group x time interaction in favour of the patients who received functional remediation when compared to psychoeducation and TAU (F=2.93; p=0.02) at improving psychosocial functioning. Finally, mood symptoms did not significantly change in any of the three groups at any time of follow-up, as shown by the non-significant group x time interaction effect in HAM-D scores (F=1.57; p=0.18) and YMRS scores (F=1.51; p=0.20). Bipolar patients with subsyndromal symptoms improve their functional outcome when exposed to functional remediation regardless of the persistence of mood symptomatology.

Most methods for conducting meta-analysis of voxel-based neuroimaging studies do not assess whether effects are not null, but whether there is a convergence of peaks of statistical significance, and reduce the assessment of the evidence to a binary classification exclusively based on p-values (i.e., voxels can only be "statistically significant" or "non-statistically significant"). Here, we detail how to conduct a meta-analysis using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI), a novel method that uses a standard permutation test to assess whether effects are not null. We also show how to grade the strength of the evidence according to a set of criteria that considers a range of statistical significance levels (from more liberal to more conservative), the amount of data or the detection of potential biases (e.g., small-study effect and excess of significance). To exemplify the procedure, we detail the conduction of a meta-analysis of voxel-based morphometry studies in obsessive-compulsive disorder, and we provide all the data already extracted from the manuscripts to allow the reader to replicate the meta-analysis easily. SDM-PSI can also be used for meta-analyses of functional magnetic resonance imaging, diffusion tensor imaging, position emission tomography and surface-based morphometry studies.

Background: Impairments in affective cognition are part of the neurocognitive profile and possible treatment targets in bipolar disorder (BD), but the findings are heterogeneous. The International Society of Bipolar Disorder (ISBD) Targeting Cognition Task Force conducted a systematic review to (i) identify the most consistent findings in affective cognition in BD, and (ii) provide suggestions for affective cognitive domains for future study and meta‐analyses.Methods: The review included original studies reporting behavioral measures of affective cognition in BD patients vs controls following the procedures of the Preferred Reporting Items for Systematic reviews and Meta‐Analysis (PRISMA) statement. Searches were conducted on PubMed/MEDLINE, EMBASE, and PsychInfo from inception until November 2018.Results: A total of 106 articles were included (of which nine included data for several affective domains); 41 studies assessed emotional face processing; 23 studies investigated reactivity to emotional words and images; 3 investigated explicit emotion regulation; 17 assessed implicit emotion regulation; 31 assessed reward processing and affective decision making. In general, findings were inconsistent. The most consistent findings were trait‐related difficulties in facial emotion recognition and implicit emotion regulation, and impairments in reward processing and affective decision making during mood episodes. Studies using eye‐tracking and facial emotion analysis revealed subtle trait‐related abnormalities in emotional reactivity.Conclusion: The ISBD Task Force recommends facial expression recognition, implicit emotion regulation, and reward processing as domains for future research and meta‐analyses. An important step to aid comparability between studies in the field would be to reach consensus on an affective cognition test battery for BD.

(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.

OBJECTIVE The aim of this study was to identify predisposing factors and clinical features at baseline that might help predict diagnosis of bipolar disorder vs schizophrenia in a first-episode psychosis (FEP) cohort. METHODS In this prospective, naturalistic study, we evaluated a cohort of 335 subjects with FEP recruited from April 2009 to April 2012. Baseline features were compared between subjects with a final DSM-IV diagnosis of bipolar disorder and schizophrenia at 12-month follow-up. A binary logistic regression model was used to assess predictors of diagnosis of bipolar disorder at follow-up. RESULTS At 12-month follow-up, 47 of the 335 subjects included in the study received the diagnosis of bipolar disorder and 105, of schizophrenia. Subjects with a final diagnosis of bipolar disorder had a higher prevalence of family history of mood disorders (38.2% vs 18.0%, P = .02), better baseline premorbid adjustment (Premorbid Adjustment Scale [PAS]: 38.4 vs 50.6, P < .01) and psychosocial functioning (Functional Assessment Short Test [FAST]: 23.6 vs 33.7, P = .001), better cognitive flexibility (number of perseverative errors on the Wisconsin Card Sorting Test [WCST]: 14.2 vs 19.7, P = .01), more manic symptoms (Young Mania Rating Scale [YMRS]: 14.1 vs 7.3, P < .01), lesser negative symptoms (Positive and Negative Syndrome Scale negative scale [PANSS-N]: 15.0 vs 22.3, P < .001), and shorter duration of untreated psychosis (144.2 vs 194.7 days, P < .01) than subjects with a schizophrenia diagnosis. Binary logistic regression model revealed that lower FAST scores (odds ratio [OR] = 0.956; P = .015), lower PANSS-N scores (OR = 0.93; P = .048), and lower number of perseverative errors on the WCST (OR = 0.946; P = .035) were significantly related to diagnosis of bipolar disorder at follow-up. CONCLUSIONS In our FEP cohort, better psychosocial functioning, lesser negative symptoms, and better cognitive flexibility were related to diagnosis of bipolar disorder at 12-month follow-up.

Given the limitation of pharmacological treatments to treat cognitive symptoms in patients with Major Depressive Disorder (MDD), cognitive remediation programs has been proposed as a possible procognitive intervention but findings are not conclusive. This study investigates the efficacy of an INtegral Cognitive REMediation (INCREM) that includes a combination of a Functional Remediation (FR) strategy plus a Computerized Cognitive Training (CCT) in order to improve not only cognitive performance but also the psychosocial functioning and the quality of life. A single blind randomized controlled clinical trial in 81 patients with a diagnosis of MDD in clinical remission or in partial remission. Participants will be randomized to one of three conditions: INCREM (FR + CCT), Psychoeducation plus online games and Treatment As Usual (TAU). Intervention will consist in 12 group sessions, of approximately 110 min once a week. The primary outcome measure will be % of change in psychosocial functioning after treatment measured by the Functional Assessment Short Test (FAST); additionally, number of sick leaves and daily activities will also be recorded as pragmatic outcomes. To our knowledge, this is the first randomized controlled clinical trial using a combination of two different approaches (FR + CCT) to treat the present cognitive deficits and to promote their improvements into a better psychosocial functioning. Clinical Trials NCT03624621 . Date registered 10th of August 2018 and last updated 24th August 2018.

(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.

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.

Background: Brain structural and functional changes in bipolar disorder (BD) are well-established findings, but it is uncertain whether these changes are already present in first episode mania (FEM).Methods: We compared 31 FEM subjects, with 31 healthy individuals matched for age, sex, and premorbid IQ. Whole-brain voxel-wise morphometry, functional magnetic resonance imaging during the n-back task, and a functional connectivity analysis were performed.Results: There were no volumetric differences between the 2 groups. During the 2-back task, FEM patients did not perform differently from controls and activated similar regions, but they showed less deactivation in the ventromedial prefrontal cortex (vmPFC), the anterior hub of the default mode network (DMN). They showed preserved functional connectivity between the vmPFC and other regions of the DMN, but increased connectivity with the superior frontal gyrus.Conclusions: The absence of volumetric changes in FEM patients suggests that these changes could be related to progression of the illness. On the other hand, the failure of deactivation of the anterior hub of the DMN is present from the onset of the illness and may represent a core pathophysiological feature of BD.

The concept of cognitive reserve (CR) suggests that the premorbid intelligence quotient (IQ), years of education and leisure activities provide more efficient cognitive networks and therefore allow a better management of some conditions associated to cognitive impairment. Fifty-two DSM-IV diagnosed FEP subjects were matched with 41 healthy controls by age, gender and parental socio-economic status. All subjects were assessed clinically, neuropsychologically and functionally at baseline and after a two-year follow-up. To assess CR at baseline, three proxies have been integrated: premorbid IQ, years of education-occupation and leisure activities. Higher CR was associated with better cognitive, functional and clinical outcomes at baseline. The CR proxy was able to predict working memory, attention, executive functioning, verbal memory and global composite cognitive score accounting for 48.9%, 19.1%, 16.9%, 10.8% and 14.9% respectively of the variance at two-year follow-up. CR was also significantly predictive of PANSS negative scale score (12.5%), FAST global score (13.4%) and GAF (13%) at two-year follow-up. In addition, CR behaved as a mediator of working memory (B=4.123) and executive function (B=3.298) at baseline and of working memory (B=5.034) at 2-year follow-up. An additional analysis was performed, in order to test whether this mediation could be attributed mainly to the premorbid IQ. We obtained that this measure was not enough by itself to explain this mediation. CR may contribute to neuropsychological and functional outcome. Specific programs addressed to improve cognition and functioning conducted at the early stages of the illness may be helpful in order to prevent cognitive and functional decline.

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.

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

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.

BackgroundFew randomised clinical trials have examined the efficacy of an intervention aimed at improving psychosocial functioning in bipolar disorder.AimsTo examine changes in psychosocial functioning in a group that has been enrolled in a functional remediation programme 1 year after baseline.MethodThis 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).ResultsThere 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).ConclusionsImprovement in psychosocial functioning is maintained after 1-year follow-up in patients with bipolar disorder receiving functional remediation.

Amann BL, Canales-Rodriguez EJ, Madre M, Radua J, Monte G,Alonso-Lana S, Landin-Romero R, Moreno-Alcazar A,Bonnin CM, Sarro S, Ortiz-Gil J, Gomar JJ, Moro N,Fernandez-Corcuera P, Goikolea JM, Blanch J, Salvador R, Vieta E,McKenna PJ, Pomarol-Clotet E. Brain structural changes inschizoaffective disorder compared to schizophrenia and bipolar disorder.Objective: Brain structural changes in schizoaffective disorder, and howfar they resemble those seen in schizophrenia and bipolar disorder, haveonly been studied to a limited extent.Method: Forty-five patients meeting DSM-IV and RDC criteria forschizoaffective disorder, groups of patients with 45 matchedschizophrenia and bipolar disorder, and 45 matched healthy controlswere examined using voxel-based morphometry (VBM).Results: Analyses comparing each patient group with the healthycontrol subjects found that the patients with schizoaffective disorderand the patients with schizophrenia showed widespread andoverlapping areas of significant volume reduction, but the patients withbipolar disorder did not. A subsequent analysis compared the combinedgroup of patients with the controls followed by extraction of clusters. Inregions where the patients differed significantly from the controls, nosignificant differences in mean volume between patients withschizoaffective disorder and patients with schizophrenia in any of fiveregions of volume reduction were found, but mean volumes in thepatients with bipolar disorder were significantly smaller in three of five.Conclusion: The findings provide evidence that, in terms of structuralgray matter brain abnormality, schizoaffective disorder resemblesschizophrenia more than bipolar disorder.

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.

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.

Background and objectives Bipolar type II (BDII) is a frequent disorder with high morbidity and mortality, characterized by depressive and hypomanic episodes. Early diagnosis can be effective in improving long-term prognosis. However, diagnosing BDII is challenging due to the difficulty in detecting past hypomanic episodes. The HCL-32 is a widely used and reliable screening instrument for the detection of past hypomanic episodes. Making this tool available to more patients could help diagnose and treat undetected cases of BDII earlier. New technologies such as the Internet have been previously used for this purpose with favorable outcomes. Accordingly, the objective of this study is to evaluate the acceptability, validity, reliability and equivalence of an online version of this questionnaire. Methods From May 2012 to March 2013, 52 participants attending an outpatient mental health clinic completed a paper version of the HCL-32 (HCL-32) and its online version (e-HCL-32) within two weeks. After its completion, they were asked to answer a brief satisfaction survey. Results No differences were found (HCL-32 mean total score = 17.73 (SD = 7.37), e-HCL-32 mean total score = 18.28 (SD = 7.09). T = −1.720, p = 0.092, 95% CI = −1.21 to 0.09) between the results of the paper and pencil HCL-32 compared to its online version (e-HCL-32). The psychometric properties of the online version of the hypomania checklist (e-HCL-32) were good and comparable to the paper and pencil version. 80% of participants found online questionnaires to be easier to answer and more user-friendly. Conclusion The results of this study support the use of an online screening tool for the detection of previous hypomanic episodes (necessary for BDII diagnosis) as it showed to have a similar validity and reliability to the traditional paper and pencil method.

OBJECTIVES: To aid the development of treatment for cognitive impairment in bipolar disorder, the International Society for Bipolar Disorders (ISBD) convened a task force to create a consensus-based guidance paper for the methodology and design of cognition trials in bipolar disorder.METHODS: The task force was launched in September 2016, consisting of 18 international experts from nine countries. A series of methodological issues were identified based on literature review and expert opinion. The issues were discussed and expanded upon in an initial face-to-face meeting, telephone conference call and email exchanges. Based upon these exchanges, recommendations were achieved.RESULTS: Key methodological challenges are: lack of consensus on how to screen for entry into cognitive treatment trials, define cognitive impairment, track efficacy, assess functional implications, and manage mood symptoms and concomitant medication. Task force recommendations are to: (i) enrich trials with objectively measured cognitively impaired patients; (ii) generally select a broad cognitive composite score as the primary outcome and a functional measure as a key secondary outcome; and (iii) include remitted or partly remitted patients. It is strongly encouraged that trials exclude patients with current substance or alcohol use disorders, neurological disease or unstable medical illness, and keep non-study medications stable. Additional methodological considerations include neuroimaging assessments, targeting of treatments to illness stage and using a multimodal approach.CONCLUSIONS: This ISBD task force guidance paper provides the first consensus-based recommendations for cognition trials in bipolar disorder. Adherence to these recommendations will likely improve the sensitivity in detecting treatment efficacy in future trials and increase comparability between studies.

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.