Associations of altered leukocyte DDR1 promoter methylation and childhood trauma with bipolar disorder and suicidal behavior in euthymic patients.

Altered DNA methylation (DNAm) patterns of discoidin domain receptor 1 (DDR1) have been found in the blood and brain of patients with schizophrenia (SCZ) and the brain of patients with bipolar disorder (BD). Childhood trauma (CT) is associated with changes in DNAm that in turn are related to suicidal behavior (SB) in patients with several psychiatric disorders. Here, using MassARRAY® technology, we studied 128 patients diagnosed with BD in remission and 141 healthy controls (HCs) to compare leukocyte DDR1 promoter DNAm patterns between patients and HCs and between patients with and without SB. Additionally, we investigated whether CT was associated with DDR1 DNAm and mediated SB. We found hypermethylation at DDR1 cg19215110 and cg23953820 sites and hypomethylation at cg14279856 and cg03270204 sites in patients with BD compared to HCs. Logistic regression models showed that hypermethylation of DDR1 cg23953820 but not cg19215110 and CT were risk factors for BD, while cg14279856 and cg03270204 hypomethylation were protective factors. In patients, CT was a risk factor for SB, but DDR1 DNAm, although associated with CT, did not mediate the association of CT with SB. This is the first study demonstrating altered leukocyte DDR1 promoter DNAm in euthymic patients with BD. We conclude that altered DDR1 DNAm may be related to immune and inflammatory mechanisms and could be a potential blood biomarker for the diagnosis and stratification of psychiatric patients.

Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force.

BACKGROUND: Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD. METHODS: We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials. RESULTS: Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias. CONCLUSIONS: Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers.

Emotional intelligence: a comparison between patients after first episode mania and those suffering from chronic bipolar disorder type I.

BACKGROUND: Deficits in emotional intelligence (EI) were detected in patients with bipolar disorder (BD), but little is known about whether these deficits are already present in patients after presenting a first episode mania (FEM). We sought (i) to compare EI in patients after a FEM, chronic BD and healthy controls (HC); (ii) to examine the effect exerted on EI by socio-demographic, clinical and neurocognitive variables in FEM patients. METHODS: The Emotional Intelligence Quotient (EIQ) was calculated with the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Performance on MSCEIT was compared among the three groups using generalized linear models. In patients after a FEM, the influence of socio-demographic, clinical and neurocognitive variables on the EIQ was examined using a linear regression model. RESULTS: In total, 184 subjects were included (FEM n = 48, euthymic chronic BD type I n = 75, HC n = 61). BD patients performed significantly worse than HC on the EIQ [mean difference (MD) = 10.09, standard error (s.e.) = 3.14, p = 0.004] and on the understanding emotions branch (MD = 7.46, s.e. = 2.53, p = 0.010). FEM patients did not differ from HC and BD on other measures of MSCEIT. In patients after a FEM, EIQ was positively associated with female sex (ß = -0.293, p = 0.034) and verbal memory performance (ß = 0.374, p = 0.008). FEM patients performed worse than HC but better than BD on few neurocognitive domains. CONCLUSIONS: Patients after a FEM showed preserved EI, while patients in later stages of BD presented lower EIQ, suggesting that impairments in EI might result from the burden of disease and neurocognitive decline, associated with the chronicity of the illness.

Can magnetic resonance imaging enhance the assessment of potential new treatments for cognitive impairment in mood disorders? A systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force.

BACKGROUND: Developing treatments for cognitive impairment is key to improving the functioning of people with mood disorders. Neuroimaging may assist in identifying brain-based efficacy markers. This systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force examines the evidence from neuroimaging studies of pro-cognitive interventions. METHODS: We included magnetic resonance imaging (MRI) studies of candidate interventions in people with mood disorders or healthy individuals, following the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE, Cochrane Library, and Clinicaltrials.gov from inception to 30th April 2021. Two independent authors reviewed the studies using the National Heart, Lung, Blood Institutes of Health Quality Assessment Tool for Controlled Intervention Studies and the quality of neuroimaging methodology assessment checklist. RESULTS: We identified 26 studies (N = 702). Six investigated cognitive remediation or pharmacological treatments in mood disorders (N = 190). In healthy individuals, 14 studies investigated pharmacological interventions (N = 319), 2 cognitive training (N = 73) and 4 neuromodulatory treatments (N = 120). Methodologies were mostly rated as 'fair'. 77% of studies investigated effects with task-based fMRI. Findings varied but most consistently involved treatment-associated cognitive control network (CCN) activity increases with cognitive improvements, or CCN activity decreases with no cognitive change, and increased functional connectivity. In mood disorders, treatment-related default mode network suppression occurred. CONCLUSIONS: Modulation of CCN and DMN activity is a putative efficacy biomarker. Methodological recommendations are to pre-declare intended analyses and use task-based fMRI, paradigms probing the CCN, longitudinal assessments, mock scanning, and out-of-scanner tests.

Virtual Ontogeny of Cortical Growth Preceding Mental Illness.

BACKGROUND: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. METHODS: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. RESULTS: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. CONCLUSIONS: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.

Sex differences in neurocognitive and psychosocial functioning in bipolar disorder.

BACKGROUND: Sex differences influence the clinical characteristics and course of illness of bipolar disorder (BD). OBJECTIVE: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: Lack of assessment of visuo-spatial working memory. CONCLUSIONS: 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.

Identifying neurocognitive heterogeneity in Older Adults with Bipolar Disorder: a cluster analysis.

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.

Longitudinal Structural Brain Changes in Bipolar Disorder: A Multicenter Neuroimaging Study of 1232 Individuals by the ENIGMA Bipolar Disorder Working Group.

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

Self-reported neurocognitive symptoms during COVID-19 lockdown and its associated factors in a sample of psychiatric patients. Results from the BRIS-MHC study.

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.

Does cognitive impairment in bipolar disorder impact on a SIMPLe app use?

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.

Predictors of Bipolar Disorder Versus Schizophrenia Diagnosis in a Multicenter First Psychotic Episode Cohort: Baseline Characterization and a 12-Month Follow-Up Analysis.

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.

Validity of the Shahin Mixed Depression Scale: A Self-Rated Instrument Designed to Measure the Non-DSM Mixed Features in Depression.

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.

Using structural MRI to identify bipolar disorders - 13 site machine learning study in 3020 individuals from the ENIGMA Bipolar Disorders Working Group.

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.

Improving Functioning, Quality of Life, and Well-being in Patients With Bipolar Disorder.

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.

Cognitive Reserve Assessment Scale in Health (CRASH): Its Validity and Reliability.

(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.

Testing the efficacy of INtegral Cognitive REMediation (INCREM) in major depressive disorder: study protocol for a randomized clinical trial.

BACKGROUND: 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. METHODS: 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. DISCUSSION: 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. TRIAL REGISTRATION: Clinical Trials NCT03624621 . Date registered 10th of August 2018 and last updated 24th August 2018.

Functional remediation improves bipolar disorder functioning with no effects on brain-derived neurotrophic factor levels.

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.

Spanish validation of the Barcelona TEMPS-A questionnaire in patients with bipolar disorder and general population.

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.

Cognitive Remediation Interventions in Schizoaffective Disorder: A Systematic Review.

Background: Patients with schizoaffective disorder (SAD) suffer from cognitive impairment, which negatively influences their functionality. Cognitive remediation (CR) interventions have been shown to be effective in patients with schizophrenia (SZ) and bipolar disorder (BD), but evidence in SAD is limited so far. The aim of this study is to systematically review the published data on CR interventions, either in neurocognition or social cognition, in patients with SAD. Methods: We conducted a comprehensive, computerized literature search using terms related to CR interventions in psychotic and affective disorders, and particularly in SAD. Pubmed, Embase, and Web of Knowledge databases were used up to February 28th, 2018 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search returned 2672 articles of which four were finally selected meeting the inclusion criteria. Results: Cognitive Enhancement Therapy, computerized Cognitive Remediation Therapy and Cognitive Training showed positive results in subsamples of patients with SAD regarding neurocognition and functioning in comparable terms to patients with schizophrenia as well as in a greater extent in quality of life. Benefits in social cognition were also described when Social Cognition Interaction Training was considered in patients with SAD. Conclusions: CR interventions seem to improve neurocognition and social cognition in patients with SAD as well as functioning and quality of life. However, further randomized controlled trials on CR interventions with an optimized design focusing on selected sample of patients with SAD are imperative.