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.

Examining associations, moderators and mediators between childhood maltreatment, social functioning, and social cognition in psychotic disorders: a systematic review and meta-analysis.

Childhood maltreatment (CM) has been related to social functioning and social cognition impairment in people with psychotic disorders (PD); however, evidence across different CM subtypes and social domains remains less clear. We conducted a systematic review and meta-analysis to quantify associations between CM, overall and its different subtypes (physical/emotional/sexual abuse, physical/emotional neglect), and domains of social functioning and social cognition in adults with PD. We also examined moderators and mediators of these associations. A PRISMA-compliant systematic search was performed on 24 November 2022 (PROSPERO CRD42020175244). Fifty-three studies (N = 13 635 individuals with PD) were included in qualitative synthesis, of which 51 studies (N = 13 260) with 125 effects sizes were pooled in meta-analyses. We found that CM was negatively associated with global social functioning and interpersonal relations, and positively associated with aggressive behaviour, but unrelated to independent living or occupational functioning. There was no meta-analytic evidence of associations between CM and social cognition. Meta-regression analyses did not identify any consistent moderation pattern. Narrative synthesis identified sex and timing of CM as potential moderators, and depressive symptoms and maladaptive personality traits as possible mediators between CM and social outcomes. Associations were of small magnitude and limited number of studies assessing CM subtypes and social cognition are available. Nevertheless, adults with PD are at risk of social functioning problems after CM exposure, an effect observed across multiple CM subtypes, social domains, diagnoses and illness stages. Maltreated adults with PD may thus benefit from trauma-related and psychosocial interventions targeting social relationships and functioning.

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.

Functioning in older adults with bipolar disorder: A report on recommendations by the International Society of bipolar disorder (ISBD) older adults with bipolar disorder (OABD) task force.

OBJECTIVES: Despite the importance of psychosocial functioning impairment in Bipolar Disorder (BD), its role among Older Adults with BD (OABD) is not well known. The development of guidelines for the assessment of psychosocial functioning helps to facilitate a better understanding of OABD and can lead to better tailored interventions to improve the clinical outcomes of this population. METHODS: Through a series of virtual meetings, experts from eight countries in the International Society of Bipolar Disorder (ISBD) on OABD task force developed recommendations for the assessment of psychosocial functioning. RESULTS: We present (1) a conceptualization of functioning in OABD and differences compared with younger patients; (2) factors related to functioning in OABD; (3) current measures of functioning in OABD and their strengths and limitations; and, (4) other potential sources of information to assess functioning. CONCLUSIONS: The task force created recommendations for assessing functioning in OABD. Current instruments are limited, so measures specifically designed for OABD, such as the validated FAST-O scale, should be more widely adopted. Following the proposed recommendations for assessment can improve research and clinical care in OABD and potentially lead to better treatment outcomes.

Association between childhood maltreatment and social functioning in individuals with affective disorders: A systematic review and meta-analysis.

OBJECTIVE: Childhood maltreatment has been linked to impairments in social functioning and social cognition in adults with affective disorders. However, conclusions have been limited by inconsistent findings across different maltreatment subtypes and social domains. We conducted a systematic review and meta-analysis to quantify associations between childhood maltreatment (overall and subtypes - physical, emotional and/or sexual abuse, and/or physical and/or emotional neglect) and different domains of social functioning and social cognition in adults with affective disorders (bipolar disorder or major depressive disorder). We also examined effect moderators and mediators of these associations. METHODS: A systematic search was performed on 12.12.2022 which identified 29 studies included in qualitative synthesis (n = 3022 individuals with affective disorders), of which 27 (n = 2957) were pooled in meta-analyses. Across studies, five social functioning and five social cognition domains were examined, of which four domains of social functioning and two domains of social cognition had sufficient data for meta-analysis (PROSPERO CRD42022288976). RESULTS: Social functioning: childhood maltreatment was associated with lower global social functioning (r = -0.11 to -0.20), poorer interpersonal relations (r = -0.18 to -0.33), and with aggressive behaviour (r = 0.20-0.29) but was unrelated to vocational functioning. Emotional abuse and emotional neglect showed the largest magnitudes of effect. Social cognition: there was no meta-analytic evidence of associations between maltreatment and social cognition domains. Exploratory moderation analyses did not identify any consistent moderators. Narrative synthesis identified attachment style as possible moderator, and sensory patterns, anxiety, and depressive symptoms as possible mediators between childhood maltreatment and social outcomes. Overall, the available evidence was limited, particularly in relation to social cognition. CONCLUSIONS: Adults with affective disorders are at risk of social functioning difficulties after childhood maltreatment exposure, an effect observed across multiple maltreatment subtypes, social functioning domains, and diagnoses. Addressing social functioning problems may benefit maltreated adults with both bipolar disorder and major depressive disorder.

Obstetric complications and genetic risk for schizophrenia: Differential role of antenatal and perinatal events in first episode psychosis.

BACKGROUND: Obstetric complications (OCs) are key contributors to psychosis risk. However, it is unclear whether they increase psychosis vulnerability independently of genetic risk, in interaction with it, or are a manifestation of psychosis proneness. We examined the role of distinct types of OCs in terms of psychosis risk and tested whether they interact differently with genetic vulnerability, whilst accounting for other known environmental risk factors. STUDY DESIGN: 405 participants (219 first episode psychosis patients and 186 healthy volunteers) underwent a comprehensive assessment of OCs, measured using the Lewis-Murray scale and divided into complications of pregnancy, abnormalities of foetal growth and development, and complications of delivery. Participants were compared in terms of history of OCs, polygenic risk score for schizophrenia (PRS-SZ) and interactions between these. RESULTS: Both complications of pregnancy and abnormalities of foetal growth were significantly associated with case-control status (p = 0.02 and 0.03, respectively), whereas complications of delivery were not. PRS-SZ showed a significant association with psychosis (p = 0.04), but there were no significant interactions between genetic risk for schizophrenia and OCs, either when these were considered globally or separated based on their timeframe. CONCLUSIONS: We observed no significant interaction between genetic and obstetric vulnerability, yet distinct types of OCs may have a different impact on psychosis risk, based on their nature and timeframe. Examining their differential role might clarify their relative contributions to this risk.

Vickybot, a Chatbot for Anxiety-Depressive Symptoms and Work-Related Burnout in Primary Care and Health Care Professionals: Development, Feasibility, and Potential Effectiveness Studies.

BACKGROUND: Many people attending primary care (PC) have anxiety-depressive symptoms and work-related burnout compounded by a lack of resources to meet their needs. The COVID-19 pandemic has exacerbated this problem, and digital tools have been proposed as a solution. OBJECTIVE: We aimed to present the development, feasibility, and potential effectiveness of Vickybot, a chatbot aimed at screening, monitoring, and reducing anxiety-depressive symptoms and work-related burnout, and detecting suicide risk in patients from PC and health care workers. METHODS: Healthy controls (HCs) tested Vickybot for reliability. For the simulation study, HCs used Vickybot for 2 weeks to simulate different clinical situations. For feasibility and effectiveness study, people consulting PC or health care workers with mental health problems used Vickybot for 1 month. Self-assessments for anxiety (Generalized Anxiety Disorder 7-item) and depression (Patient Health Questionnaire-9) symptoms and work-related burnout (based on the Maslach Burnout Inventory) were administered at baseline and every 2 weeks. Feasibility was determined from both subjective and objective user-engagement indicators (UEIs). Potential effectiveness was measured using paired 2-tailed t tests or Wilcoxon signed-rank test for changes in self-assessment scores. RESULTS: Overall, 40 HCs tested Vickybot simultaneously, and the data were reliably transmitted and registered. For simulation, 17 HCs (n=13, 76% female; mean age 36.5, SD 9.7 years) received 98.8% of the expected modules. Suicidal alerts were received correctly. For the feasibility and potential effectiveness study, 34 patients (15 from PC and 19 health care workers; 76% [26/34] female; mean age 35.3, SD 10.1 years) completed the first self-assessments, with 100% (34/34) presenting anxiety symptoms, 94% (32/34) depressive symptoms, and 65% (22/34) work-related burnout. In addition, 27% (9/34) of patients completed the second self-assessment after 2 weeks of use. No significant differences were found between the first and second self-assessments for anxiety (t8=1.000; P=.34) or depressive (t8=0.40; P=.70) symptoms. However, work-related burnout scores were moderately reduced (z=-2.07, P=.04, r=0.32). There was a nonsignificant trend toward a greater reduction in anxiety-depressive symptoms and work-related burnout with greater use of the chatbot. Furthermore, 9% (3/34) of patients activated the suicide alert, and the research team promptly intervened with successful outcomes. Vickybot showed high subjective UEI (acceptability, usability, and satisfaction), but low objective UEI (completion, adherence, compliance, and engagement). Vickybot was moderately feasible. CONCLUSIONS: The chatbot was useful in screening for the presence and severity of anxiety and depressive symptoms, and for detecting suicidal risk. Potential effectiveness was shown to reduce work-related burnout but not anxiety or depressive symptoms. Subjective perceptions of use contrasted with low objective-use metrics. Our results are promising but suggest the need to adapt and enhance the smartphone-based solution to improve engagement. A consensus on how to report UEIs and validate digital solutions, particularly for chatbots, is required.

Data-driven cognitive phenotypes in subjects with bipolar disorder and their clinical markers of severity.

BACKGROUND: Subjects with bipolar disorder (BD) show heterogeneous cognitive profile and that not necessarily the disease will lead to unfavorable clinical outcomes. We aimed to identify clinical markers of severity among cognitive clusters in individuals with BD through data-driven methods. METHODS: We recruited 167 outpatients with BD and 100 unaffected volunteers from Brazil and Spain that underwent a neuropsychological assessment. Cognitive functions assessed were inhibitory control, processing speed, cognitive flexibility, verbal fluency, working memory, short- and long-term verbal memory. We performed hierarchical cluster analysis and discriminant function analysis to determine and confirm cognitive clusters, respectively. Then, we used classification and regression tree (CART) algorithm to determine clinical and sociodemographic variables of the previously defined cognitive clusters. RESULTS: We identified three neuropsychological subgroups in individuals with BD: intact (35.3%), selectively impaired (34.7%), and severely impaired individuals (29.9%). The most important predictors of cognitive subgroups were years of education, the number of hospitalizations, and age, respectively. The model with CART algorithm showed sensitivity 45.8%, specificity 78.4%, balanced accuracy 62.1%, and the area under the ROC curve was 0.61. Of 10 attributes included in the model, only three variables were able to separate cognitive clusters in BD individuals: years of education, number of hospitalizations, and age. CONCLUSION: These results corroborate with recent findings of neuropsychological heterogeneity in BD, and suggest an overlapping between premorbid and morbid aspects that influence distinct cognitive courses of the disease.

Cognition in older adults with bipolar disorder: An ISBD task force systematic review and meta-analysis based on a comprehensive neuropsychological assessment.

OBJECTIVES: We aim to characterize the cognitive performance in euthymic older adults with bipolar disorder (OABD) through a comprehensive neuropsychological assessment to obtain a detailed neuropsychological profile. METHODS: We conducted a systematic search in MEDLINE/Pubmed, Cochrane, and PsycInfo databases. Original studies assessing cognitive function in OABD (age ≥50 years ) containing, at a minimum, the domains of attention/processing speed, memory, and executive functions were included. A random-effects meta-analysis was conducted to summarize differences between patients and matched controls in each cognitive domain. We also conducted meta-regressions to estimate the impact of clinical and socio-demographic variables on these differences. RESULTS: Eight articles, providing data for 328 euthymic OABD patients and 302 healthy controls, were included in the meta-analysis. OABD showed worse performance in comparison with healthy controls, with large significant effect sizes (Hedge's g from -0.77 to -0.89; p < 0.001) in verbal learning and verbal and visual delayed memory. They also displayed statistically significant deficits, with moderate effect size, in processing speed, working memory, immediate memory, cognitive flexibility, verbal fluency, psychomotor function, executive functions, attention, inhibition, and recognition (Hedge's g from -0.52 to -0.76; p < 0.001), but not in language and visuoconstruction domains. None of the examined variables were associated with these deficits. CONCLUSIONS: Cognitive dysfunction is present in OABD, with important deficits in almost all cognitive domains, especially in the memory domain. Our results highlight the importance of including a routine complete neuropsychological assessment in OABD and also considering therapeutic strategies in OABD.

Randomised controlled cognition trials in remitted patients with mood disorders published between 2015 and 2021: A systematic review by the International Society for Bipolar Disorders Targeting Cognition Task Force.

BACKGROUND: Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence-based pro-cognitive treatments indicated for patients in remission. With this systematic review of randomised controlled trials (RCTs), the International Society for Bipolar Disorders (ISBD) Targeting Cognition Task force provides an update of the most promising treatments and methodological recommendations. METHODS: The review included RCTs of candidate pro-cognitive interventions in fully or partially remitted patients with major depressive disorder or bipolar disorder. We followed the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE and Cochrane Library from January 2015, when two prior systematic reviews were conducted, until February 2021. Two independent authors reviewed the studies with the Revised Cochrane Collaboration's Risk of Bias tool for Randomised trials. RESULTS: We identified 16 RCTs (N = 859) investigating cognitive remediation (CR; k = 6; N = 311), direct current or repetitive magnetic stimulation (k = 3; N = 127), or pharmacological interventions (k = 7; N = 421). CR showed most consistent cognitive benefits, with two trials showing improvements on primary outcomes. Neuromodulatory interventions revealed no clear efficacy. Among pharmacological interventions, modafinil and lurasidone showed early positive results. Sources of bias included small samples, lack of pre-screening for objective cognitive impairment, no primary outcome and no information on allocation sequence masking. CONCLUSIONS: Evidence for pro-cognitive treatments in mood disorders is emerging. Recommendations are to increase sample sizes, pre-screen for impairment in targeted domain(s), select one primary outcome, aid transfer to real-world functioning, investigate multimodal interventions and include neuroimaging.

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.

Predictors of functional impairment in bipolar disorder: Results from 13 cohorts from seven countries by the global bipolar cohort collaborative.

OBJECTIVES: Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well-characterized samples of individuals with BD. METHODS: Thirteen cohorts from 7 countries included n = 5882 individuals with BD across multiple sites. The statistical approach consisted of a systematic uniform application of analyses across sites. Each site performed a logistic regression analysis with empirically derived "higher versus lower function" as the dependent variable and selected clinical and demographic variables as predictors. RESULTS: We found high rates of functional impairment, ranging from 41 to 75%. Lower community functioning was associated with depressive symptoms in 10 of 12 of the cohorts that included this variable in the analysis. Lower levels of education, a greater number of prior mood episodes, the presence of a comorbid substance use disorder, and a greater total number of psychotropic medications were also associated with low functioning. CONCLUSIONS: The bipolar clinical research community is poised to work together to characterize the multi-dimensional contributors to impairment and address the barriers that impede patients' complete recovery. We must also identify the core features which enable many to thrive and live successfully with BD. A large-scale, worldwide, prospective longitudinal study focused squarely on BD and its heterogeneous presentations will serve as a platform for discovery and promote major advances toward optimizing outcomes for every individual with this illness.

Prodromal phase: Differences in prodromal symptoms, risk factors and markers of vulnerability in first episode mania versus first episode psychosis with onset in late adolescence or adulthood.

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

Efficacy of an integrative approach for bipolar disorder: preliminary results from a randomized controlled trial.

BACKGROUND: Bipolar disorder (BD) represents one of the most therapeutically complex psychiatric disorders. The development of a feasible comprehensive psychological approach to complement pharmacotherapy to improve its clinical management is required. The main objective of the present randomized controlled trial (RCT) was to test the efficacy of a novel adjunctive treatment entitled integrative approach in patients with BD, including: psychoeducation, mindfulness training, and functional remediation. METHODS: This is a parallel two-armed, rater-blind RCT of an integrative approach plus treatment as usual (TAU), v. TAU alone. Participants were recruited at the Hospital Clinic of Barcelona and randomized to one of the two conditions. They were assessed at baseline and after finishing the intervention. The main outcome variable included changes in psychosocial functioning assessed through the Functioning Assessment Short Test (FAST). RESULTS: After finishing the treatment, the repeated-measures analyses revealed a significant group × time interaction in favor of the patients who received the integrative approach (n = 28) compared to the TAU group (n = 37) (Pillai's trace = 0.10; F(1,57) = 6.9; p = 0.01), improving the functional outcome. Significant effects were also found in two out of the six domains of the FAST, including the cognitive domain (Pillai's trace = 0.25; F(1,57) = 19.1; p < 0.001) and leisure time (Pillai's trace = 0.11; F(1,57) = 7.15; p = 0.01). Regarding the secondary outcomes, a significant group × time interaction in Hamilton Depression Rating Scale changes was detected (Pillai's trace = 0.08; F(1,62) = 5.6; p = 0.02). CONCLUSION: This preliminary study suggests that the integrative approach represents a promising cost-effective therapy to improve psychosocial functioning and residual depressive symptoms in patients suffering from BD.

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.

Affective cognition in bipolar disorder: A systematic review by the ISBD targeting cognition task force.

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.

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.

Cognitive Impairment in Bipolar Disorder: Treatment and Prevention Strategies.

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.

Are patients with bipolar disorder and comorbid attention-deficit hyperactivity disorder more neurocognitively impaired?

OBJECTIVE: Research on neurocognitive impairment in adult patients with comorbid bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD) is very scarce. This study assessed the neurocognitive profile of a comorbid group (BD+ADHD) compared with that of pure BD (pBD) group, pure ADHD (pADHD) group and healthy controls (HCs). METHODS: This was a three-site study comprising 229 subjects: 70 patients with pBD, 23 with BD+ADHD, 50 with pADHD, and 86 HCs. All patients with BD had been euthymic for at least 6 months. Neuropsychological performance was assessed using a comprehensive neurocognitive battery. RESULTS: Our results showed that all the clinical groups had poorer performance than the HCs in all the neurocognitive domains except for executive functions. No significant differences were observed between the pBD and BD+ADHD groups in any of the cognitive domains, with these two groups showing greater impairment than the pADHD group in executive functions and visual memory. CONCLUSIONS: Our results, although preliminary, suggest that the BD+ADHD group showed the same neurocognitive profile as pBD patients, most likely reflecting the same neurobiological basis. On the other hand, the pADHD group showed a more selective moderate impairment in attention.

Impact of childhood trauma on cognitive profile in bipolar disorder.

OBJECTIVES: Bipolar Disorder (BD) is associated with cognitive impairment even during remission periods. Nonetheless, this impairment seems to adjust to different profiles of severity. Our aim was to examine the potential impact of childhood trauma (CT) on cognitive performance and, more specifically, on neurocognitive profile membership. METHODS: Using a data-driven strategy, 113 euthymic bipolar patients were grouped according to their cognitive performance using a hierarchical clustering technique. Patients from the three resulting clusters, the so-called "low", "average", and "high performance" groups, were then compared in terms of main sociodemographic, clinical and functioning variables, including CT measures. One-way ANOVA, a chi-square test and partial correlations were used for this purpose, as appropriate. A multinomial logistic regression model was used to determine which variables contributed to neurocognitive clustering membership. RESULTS: Patients from the three neurocognitive clusters differed in terms of sociodemographic, clinical, functioning and CT variables. Scores on the Childhood Trauma Questionnaire (CTQ), especially on the physical negligence subscale, were also associated with a poor cognitive performance. The multinomial regression model indicated that CTQ total scores and the estimated intelligence quotient (IQ) significantly contributed to differentiation among the three neurocognitive groups. CONCLUSIONS: Our results confirmed that CT significantly impacts on cognitive performance during adulthood in BD. The data obtained suggest that a history of CT could act as a liability marker for cognitive impairment. A higher estimated IQ may act as a protective factor against cognitive decline in this group of patients.