Mood regulation in euthymic patients with a history of antidepressant-induced mania.

INTRODUCTION: The use of antidepressants in bipolar disorder (BD) remains contentious, in part due to the risk of antidepressant-induced mania (AIM). However, there is no information on the architecture of mood regulation in patients who have experienced AIM. We compared the architecture of mood regulation in euthymic patients with and without a history of AIM. METHODS: Eighty-four euthymic participants were included. Participants rated their mood, anxiety and energy levels daily using an electronic (e-) visual analog scale, for a mean (SD) of 280.8(151.4) days. We analyzed their multivariate time series by computing each variable's auto-correlation, inter-variable cross-correlation, and composite multiscale entropy of mood, anxiety, and energy. Then, we compared the data features of participants with a history of AIM and those without AIM, using analysis of covariance, controlling for age, sex, and current treatment. RESULTS: Based on 18,103 daily observations, participants with AIM showed significantly stronger day-to-day auto-correlation and cross-correlation for mood, anxiety, and energy than those without AIM. The highest cross-correlation in participants with AIM was between mood and energy within the same day (median (IQR), 0.58 (0.27)). The strongest negative cross-correlation in participants with AIM was between mood and anxiety series within the same day (median (IQR), -0.52 (0.34)). CONCLUSION: Patients with a history of AIM have a different underlying mood architecture compared to those without AIM. Their mood, anxiety and energy stay the same from day-to-day; and their anxiety is negatively correlated with their mood.

The Role of Online Well-Being Therapy in Overcoming Allostatic Overload in Medical Workers: A Pilot Randomized Controlled Study.

INTRODUCTION: Stress may lead to allostatic overload. Well-being therapy (WBT) might mitigate it by enhancing psychological well-being and protecting from psychological symptoms. Since no reports are available on the use of WBT in allostatic overload, we evaluated online WBT effects in reducing allostatic overload in medical workers during the coronavirus pandemic. METHODS: Sixty-six participants with allostatic overload were enrolled and randomly assigned to eight sessions of online WBT (n = 32) or eight sessions of an online psychoeducation program on healthy lifestyle (CON) (n = 34). The primary outcome was the prevalence rate of allostatic overload in the two groups at session 8 (T2). Secondary analyses were performed on changes in the PsychoSocial Index (PSI) and Psychological Well-Being (PWB) scales scores at the same time points. Generalized estimating equation models were employed. RESULTS: The WBT group showed a significantly lower rate of allostatic overload at T2 than the CON group (28.13% vs. 70.59%, p < 0.001); similar results were found at T1, T3, and T4 (p < 0.001). Compared to CON, WBT produced a significant decrease in psychological distress (p < 0.001) and abnormal illness behavior (p = 0.031), as well as a significant improvement in PWB autonomy, environmental mastery, personal growth, positive relations with others, purpose in life, and self-acceptance (p < 0.001). CONCLUSION: Online WBT may be an effective non-pharmacological therapeutic strategy for individuals with allostatic overload. These findings need to be further validated in different clinical populations.

Neurocognition across bipolar disorder phases compared to healthy subjects.

INTRODUCTION: Bipolar disorder (BD) is associated with cognitive abnormalities that may persist during euthymia and are linked to poor occupational performance. The cognitive differences between phases of BD are not well known. Therefore, a cross-sectional study with a relatively large population was conducted to evaluate the differences among BD phases in a wide range of neurocognitive parameters. METHODS: Neuropsychological profile of 169 patients with a diagnosis of BD in manic, depressive, mixed, and euthymic phases between the ages of 18 and 70 years were compared to 45 healthy individuals' between ages of 24 and 69 years. The working memory (digit-span backward test), face recognition, executive functions (verbal fluency and Stroop test), face recognition, and visual and verbal memory (immediate and delayed recall) were evaluated. For BD subgroup analyses, we used the Kruskal-Wallis (KW) test. Then, for the comparison of BD versus healthy individuals, we used the Mann-Whitney U (MWU) test. RESULTS: Analyses based on non-parametric tests showed impairments in BD for all tests. There were no significant differences between phases. CONCLUSION: Cognitive performance in patients with BD appears to be mostly unrelated to the phase of the disorder, implying that cognitive dysfunction in BD is present even during remission.

Factors associated with sexual dysfunction in patients with bipolar disorder.

OBJECTIVES: The aims of our study were to assess the sexual function in men with bipolar disorder type 1 in remission and to determine the various sociodemographic, clinical and therapeutic factors associated with sexual dysfunction. METHODS: We conducted a cross-sectional study over an 18-month period (January 2020-June 2021) in which we included men followed up for bipolar disorder type 1 in the euthymic phase strictly defined by a score <8 on the Young Mania Rating Scale and a score ≤7 on the Hamilton Depression Rating Scale. Sexual function was assessed using the Arizona Sexual Experiences Scale (Asex) in its Arabic-validated version. RESULTS: Sixty patients were included in the study. The mean age was 42.5 (SD=11.1) years. Among the patients, 68% had sexual dysfunction according to the total score of the Asex scale. According to univariate analysis, several factors were significantly associated with sexual dysfunction in patients with bipolar disorder type 1: age (P=0.001), total number of hospitalizations for thymic relapse (P=0.015), total number of depressive episodes (P=0.006) and depressive dominant polarity (P=0.046). The factors identified as modifying sexuality according to the total score of the Asex scale by multivariate analysis were age at first antipsychotic prescription: P=0.01; ORa=1.109; 95% CI [1.021-1.206] and number of hospitalizations for thymic relapse: P=0.015; ORa=1.259; 95% CI [1.046-1.546]. CONCLUSION: Studies assessing factors associated with sexual dysfunction in patients with bipolar disorder type 1 in euthymia were mostly concerned with the effects of psychotropic drugs on sexual function, with factors inherent in bipolar illness itself not widely addressed in the literature. According to the results of our study, sexual dysfunction in patients with bipolar disorder in the euthymic phase is frequent and significantly associated with clinical factors inherent in the bipolar illness itself and its course.

Evaluating a Comprehensive Model of Euthymia.

INTRODUCTION: In research and treatment of mood disorders, "euthymia" traditionally denotes the absence of clinically significant mood disturbance. A newer, expanded definition of euthymia also includes positive affect and psychological well-being. OBJECTIVE: We aimed to test this comprehensive model of euthymia and estimate the coherence and predictive power of each factor in the model. METHODS: Community-dwelling adults (N = 601), including both mental health outpatients and non-patients at high risk for personality pathology, completed a battery of interviews and questionnaires at time 1. Most (n = 497) were reassessed on average 8 months later (time 2). We modeled euthymia using standard mood, personality, and psychosocial functioning assessments rather than measures designed specifically for euthymia. RESULTS: The hypothesized model of euthymia was supported by confirmatory factor analysis: specific measures loaded on three lower order factors (mood disturbance, positive affect, and psychological well-being) that reflected general euthymia at time 1. Each factor (general euthymia plus lower order factors) demonstrated moderately strong concurrent (time 1) and predictive (time 1-2) correlations with outcomes, including employment status, income, mental health treatment consumption, and disability. Compared to positive affect and psychological well-being, mood disturbance had stronger incremental (i.e., nonoverlapping) relations with these outcomes. CONCLUSIONS: Support for a comprehensive model of euthymia reinforces efforts to improve assessment and treatment of mood and other disorders. Beyond dampening of psychological distress, euthymia-informed treatment goals encompass full recovery, including enjoyment and meaning in life.

Psychiatric comorbidity in individuals with bipolar disorder: relation with clinical outcomes and functioning.

The aim was to assess the lifetime prevalence of psychiatric comorbidity (PC) in Brazilian euthymic individuals with bipolar disorder type I, and investigate its effects on clinical outcomes and functioning. A group of 179 outpatients with BD-I in the recuperation phase were assessed, of whom 75 (41.9%) had PC and 104 (58.1%) had not. Both groups were compared using sociodemographic/clinical questionnaire, Structured Clinical Interview for DSM-IV axis I and II, Sheehan Disability and Barratt Impulsiveness Scales. Patients with PC presented less religious affiliation, more history of lifetime psychotic symptoms, rapid cycling, suicide attempts, worse scores of functioning, and higher prevalence of personality disorders. Ordinal logistic regression indicated that PC was associated with increased odds of worse levels of disability. Therefore, it could be observed that patients with BD evaluated only in euthymia presented a high mental disorders comorbidity. Considering their burdensome impact, appropriate management is a challenging reality and a crucial factor in reducing morbidity and mortality associated with BD. Further longitudinal studies on their relationship may broaden interventions to reduce patient's suffering.

Social support among individuals with bipolar disorder during euthymic phase: A systematic review.

INTRODUCTION: In spite of the recent increase in scientific publications showing an expressive interest in studies about social support, there are still scarce publications regarding this thematic and bipolar disorder, mostly when evaluating the individuals in the state of euthymia. Euthymia referred a state that a bipolar patient does not have signs/symptoms of (hipo)mania or depression, thus assessing individuals in this state may reduce response bias. OBJECTIVE: The objective of this study is to identify the impact of social support on bipolar disorder in patients in the euthymic phase. METHODS: A systematic search of observational studies on PubMed/Medline, PsycINFO, EMBASE, Scopus and Web of Science databases was performed from February 2021 to August 2022. RESULTS: In total, seven studies fulfilled the eligibility criteria. According to three studies, bipolar disorder patients had lower social support than healthy controls. Contrastingly, one study showed bipolar patients did not have different social support compared to healthy controls. CONCLUSIONS: Even though few papers with low or middle risk of bias were included in this review, we found that not only does social support could act as a protective factor for bipolar patients but also that clinical manifestations of the disorder seem to affect social support. This systematic review suggests the narrowed evidence field with different measures and type of evaluation from studies on social support and bipolar disorder, which highlights the need for further investigations on this theme.

The Clinical Science of Euthymia: A Conceptual Map.

Euthymia is a trans-diagnostic construct characterized by lack of mood disturbances; presence of positive affect; balance of psychological well-being dimensions, flexibility, consistency, and resistance to stress. The aim of this critical review is to draw a conceptual map of euthymia. Relationships with other constructs, continuum between euthymia and dysthymia with discomfort as an intermediate area, associations with lifestyle, clinimetric assessment, role of psychotherapeutic interventions, establishment of therapeutic targets, and neurobiological mechanisms are discussed. The model is based on the bipolar nature of well-being dimensions. Euthymia means using allostasis optimally and maintaining a healthy balance that promotes positive aspects of brain and body health through health-promoting behaviors. It may provide a framework for a renewed definition of recovery, for measuring treatment outcome and for targeting interventions, including the sequential administration of therapeutic components. Clinical assessment requires a clinimetric approach encompassing a broad range of aspects, such as allostatic load and lifestyle behaviors, all interacting with each other and contributing to the euthymia/dysthymia balance. Clinimetric indices for assessing euthymia (the Clinical Interview for Euthymia and the Euthymia Scale) and related constructs (the Clinical Interview for Dysthymia and the Semi-Structured Interview for the Diagnostic Criteria for Psychosomatic Research) are presented here. Well-Being Therapy, a psychotherapeutic strategy specifically aimed at pursuing euthymia, relies on self-observation of well-being episodes using a structured diary as a distinct therapeutic ingredient. The clinical science of euthymia may unravel innovative approaches to assessment and treatment of psychiatric and medical disorders, according to a unitary conceptual framework.

Decreased acylated and total ghrelin levels in bipolar disorder patients recovering from a manic episode.

BACKGROUND: To date, only few studies have investigated ghrelin levels in bipolar disorders, and all have exclusively measured acylated ghrelin, with none investigating total ghrelin (acylated and des-acylated). We aimed to investigate peripheral levels of acylated and total ghrelin in subjects experiencing a manic episode of bipolar disorder. METHODS: Peripheral levels of acylated and total ghrelin were measured in hospitalised medicated individuals recovering from a manic episode. Enzyme-linked immunosorbent assays (ELISA) were used to measure ghrelin levels in patients and compared with healthy controls. The relationship between ghrelin levels in bipolar disorder, self-reported hunger measures, demographic and clinical parameters was investigated with correlational analyses. RESULTS: Twenty-four subjects (15 males, 9 females) recovering from mania and 27 matched healthy controls (13 males, 14 females) were recruited for the study. Mean values of both acylated (187 vs.520 pg/mL) and total ghrelin (396 vs. 648 pg/mL) were significantly reduced in bipolar disorder (p = 0.001). Ghrelin levels correlated positively with markers of illness severity and negatively with prescribed mood stabilizers, second-generation antipsychotics, weight and body mass index. CONCLUSION: Peripheral measurements of acylated and total ghrelin were both reduced in bipolar disorder patients compared to healthy controls. Whilst illness severity promotes higher ghrelin levels, pharmacological treatment and weight gain exercise the opposite effect.

Clinimetric properties of the Chinese version of the Euthymia Scale.

The present study was conducted to primarily evaluate the clinimetric sensitivity of the Chinese version of the Euthymia Scale (ES), testing whether this measure discriminated between different groups of patients. Concurrent validity, a clinimetric property that refers to the assessment of the extent to which the rating scale under examination correlates with another related, previously validated, assessment instrument, was also tested investigating whether the ES significantly and negatively correlated with measures of depression and anxiety. A cross-sectional study was conducted. A total of 295 inpatients were recruited from different medical settings and included in this study. In addition to the ES, participants completed the PHQ-9 for the assessment of depression and the GAD-7 for the evaluation of symptoms of generalized anxiety. The clinimetric sensitivity of the ES was evaluated using the Mann-Whitney test and the Kruskal-Wallis analysis of variance, whereas the concurrent validity was tested via Spearman's correlation coefficients. The ES total score and its subscales of psychological flexibility and well-being discriminated between different groups of inpatients and sensitively differentiated depressed from non-depressed patients. Negative and statistically significant correlations between the ES and measures of depression and anxiety were found. Findings of the present study indicate that the Chinese version of the ES is a valid and sensitive clinimetric index that can be used not only to differentiate depressed from non-depressed patients but also as a screening measure to detect vulnerability to depression in a wide range of medical patients.

Sensitivity and concurrent validity of the Japanese version of the Euthymia scale: a clinimetric analysis.

BACKGROUND: Euthymia is characterized by the lack of mood disorders, the presence of positive affects, psychological flexibility and well-being, a unifying outlook on life, and resistance to stress. The Euthymia Scale (ES) is a 10-item self-rating clinimetric index assessing euthymia. OBJECTIVES: The present study was conducted to examine the clinimetric sensitivity and concurrent validity of the Japanese version of the Euthymia Scale (ES-J). METHODS: A cross-sectional online survey was conducted. The Mini-International Neuropsychiatric Interview was used to determine the presence of past or current major depressive episodes (MDE). The clinimetric sensitivity was evaluated using the Analysis of Variance (ANOVA). Pearson's correlation coefficients were performed to examine the concurrent validity of the ES-J. RESULTS: A total of 1030 eligible participants completed the survey. The ES-J differentiated healthy subjects from complete remission (i.e., those with a past history of MDE without current MDE) (p < 0.001), from those with past or current history of MDE (p < 0.001), subjects with current MDE from those with sub-threshold symptoms of depression (p < 0.001), and healthy participants from subjects with moderate to severe symptoms of psychological distress (p < 0.001). The associations between the ES-J and measures of psychological well-being, resilience, life satisfaction, and social support were significantly positive (0.353 < r < 0.666, p < 0.001). A negative relationship between the ES-J and measures of psychological distress was also found (r = - 0.595, p < 0.001). CONCLUSIONS: The findings of the present study indicated that the ES-J is a valid and highly sensitive clinimetric index, which can be used as a screening measure in the clinical process of assessment of recovery, particularly when symptoms are expected to be mild and/or when dealing with subclinical symptoms of psychological distress and depression. The findings of this study also support the use of the ES-J to detect vulnerability to depression and to identify subjects at higher risk of relapse.

• The ES-J was a highly sensitive clinimetric index.• The ES-J distinguished healthy subjects from those with past or current major depression.• The ES-J was highly sensitive to sub-threshold symptoms of depression.• The ES-J was a valid screening measure.• The ES-J can be used to detect a kind of vulnerability and risk of relapse.

The effect of concomitant benzodiazepine use on neurocognition in stable, long-term patients with bipolar disorder.

OBJECTIVE: Neurocognitive dysfunction is a common feature of bipolar disorder even in euthymia, and psychopharmacological treatment could have an effect on cognition. Long-term prescription of benzodiazepines in bipolar disorder is a common practice, and their effect on neurocognition has not been well studied in this population. The aim of this study was to evaluate the impact of concomitant benzodiazepine long-term use on neurocognitive function in stable euthymic bipolar disorder patients. METHODS: Seventy-three euthymic bipolar disorder outpatients and 40 healthy individuals were assessed using a neurocognitive battery. Patients were classified in two groups according to the presence of benzodiazepines in their treatment: the benzodiazepine group (n = 34) and the non- benzodiazepine group (n = 39). Neurocognitive performance was compared between the groups using a multivariate analysis of covariance, considering age, number of depressive episodes, adjuvant antipsychotic drugs, Young Mania Rating Scale score and Hamilton Depression Rating Scale score as covariates. RESULTS: Both bipolar disorder groups (benzodiazepine and non-benzodiazepine) showed an impairment in memory domains (Immediate Visual Memory [p = 0.013], Working Memory [p < 0.001], and Letter-Number Sequence [p < 0.001] from the Wechsler Memory Scale-Revised-III) and slower processing speed functions (Stroop Colour [p < 0.001]) relative to the control group. Nevertheless, the benzodiazepine group showed a greater impairment in executive functions (Conceptual Level Responses [p = 0.024] from the Wisconsin Card Sorting Test and Frontal Assessment Battery [p = 0.042]). CONCLUSION: Although memory and processing speed impairments were found in bipolar disorder, regardless of their benzodiazepine treatment, benzodiazepine users presented additional neurocognitive impairments in terms of executive functioning. These findings support restricted prescription of benzodiazepines in individuals with bipolar disorder.

Medication adherence in bipolar disorder: Exploring the role of predominant polarity.

OBJECTIVES: Medication non-adherence is one important reason behind sub-optimal outcome from treatment of bipolar affective disorder (BPAD). Though various reasons behind medication non-adherence have been identified, little is known about the medication adherence patterns across various predominant polarities (PP) in BPAD. METHODS: 100 euthymic patients of BPAD were purposively recruited and the PP were determined. Subsequently, Morisky Medication adherence scale (MMAS); Global Assessment of Functioning (GAF); Oslo Social Support Scale and World Health Organization Quality of Life scale- Brief version (WHOQOL-Bref) were administered. Analysis of covariance (ANCOVA) was done to estimate the difference of scores of MMAS after adjusting for any potential confounders. RESULTS: Overall, 44 patients with manic PP (MPP), 17 with depressive PP (DPP) and 39 with indeterminate PP (IPP) were recruited. It was found that patients who presented with DPP showed significantly higher medication adherence as compared to MPP. CONCLUSION: Knowledge of PP of a patient of BPAD can be useful in anticipating medication adherence and treatment outcome. The major limitations included non-probability sampling, cross-sectional design and limited generalizability of the results.

The cherry effect or the issue behind well-being.

Humans define well-being on predefined assumptions, based on inner and outer criteria as references. As illustrated, these criteria are subject to constant change, even in a situation when one is acting freely and is in control of all possible external influences. Even in scenarios that seemingly allow autonomy with one variable to analyse, underlying "irrationality" affects our ability to define and operationalize any desirable trait or state, such as well-being, euthymia or health. Before eating a bowl full of cherries, one creates an idea of how much cherries he/she will eat. However, as one starts eating, perception and following assumptions change. As cherries labeled as most desirable disappear, other cherries start to appear more alluring. The cherry effect could be of relevance in defining the terms such as well-being, euthymia and basically any other term encompassing a complex category of the human condition dependent on our perceived reality.

Assessment of cognitive performances in major depressed patients: a 6-month follow-up study.

OBJECTIVE: Our study aimed to assess the longitudinal change of cognitive functions in depressed patients after a 6-month interval free of mood symptoms. METHODS: In a longitudinal study, 65 patients diagnosed with recurrent major depressive disorder were evaluated twice with neurocognitive tests, during an acute depressed episode and after 6 months of euthymia. The cognitive dimension was assessed with neuropsychological tests of attention and processing speed, memory, verbal fluency, psychomotor speed and executive functions. The severity of depression was evaluated through Hamilton Depression Rating Scale - 17 items. All the results were compared with the outcomes of 35 healthy controls, both in depression and euthymia. RESULTS: Depressed patients compared to controls displayed significant statistical differences for most cognitive tests applied, verbal and working memory being the most severely impaired. They were still impaired at the second evaluation. Significant differences were noted between the euthymic and control group, too. Between the depression phase and euthymia, patients obtained significant improvement for attention and processing speed, verbal fluency, motor speed and executive functions. CONCLUSIONS: Results from the current study indicate that cognitive impairment is more severe for depressed patients, decreases for euthymic subjects, and lasts longer after depressive symptoms remit.

Psychiatry's pursuit of euthymia: another wild goose chase or an opportunity for principle-based facilitation?

The authors are encouraged that the field of psychiatry is moving towards including euthymia and its components (e.g., well-being, flourishing and resilience) as well as dysfunction (i.e., psychopathology and its symptoms) in its assessment and treatment. We are concerned, however, that to guide its pursuit of euthymia, psychiatry appears to be adopting the same 'outside-in' paradigm as positive psychology; that the positive must be 'put into' people via assisting them to adopt new positive beliefs and persistently practice psychotherapeutic techniques. We fear that if psychiatry continues to view the positive through this 'outside-in' lens, its pursuit of euthymia will bear small fruit. In this editorial, we posit that mental health and psychopathology can be viewed from the same basis because both are created in the same way; from the 'inside-out' via people's use of three psycho-spiritual Principles-Universal Mind, Consciousness and Thought. We posit that people can use these Principles in a way that either creates distressing symptoms or releases innate euthymia. We further posit that via awareness and sufficient insight-based understanding of how these Principles manifest within everyone, psychiatry can achieve a deeper understanding of the source of all psychological experience that will facilitate its pursuit of euthymia.

Laughter therapy in diabetes.

Gelotology, or the science of laughter, is developing as a complementary field of medicine. Laughter therapy has been shown to have multifaceted physiological and endocrine benefits, and is being used to help manage various chronic diseases. This communication describes some aspects of laughter therapy, and reviews evidence related to its therapeutic potential in diabetes care.

TNF-α and its soluble receptors mediate the relationship between prior severe mood episodes and cognitive dysfunction in euthymic bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is one of the most disabling mental health conditions in the world. Symptoms of cognitive impairment in BD contribute directly to occupational and social deficiencies and are very difficult to treat. Converging evidence suggests that BD patients have increased peripheral markers of inflammation. The hypothesis of neuroprogression in BD postulates that cognitive deficits develop over the course of the illness and are influenced by prior severe mood episodes, leading to wear-and-tear on the brain- however, there exists a paucity of data statistically testing a mediating role of immune molecules in cognitive dysfunction in BD. METHODS: This is a cross-sectional study. We measured serum levels of tumor necrosis factor alpha (TNF-α), and soluble (s) TNF receptors one and two (sTNF-R1 and sTNF-R2) in 219 euthymic BD patients and 52 Healthy Controls (HCs). Structural equation modeling (SEM) was used for the primary purpose of assessing whether TNF markers (measured by the multiple indicators TNF-α, sTNF-R1 and sTNF-R2) mediate the effect or number of prior severe mood episodes (number of prior psychiatric hospitalizations) on cognitive performance. RESULTS: BD and HC groups did not differ on circulating levels of TNF molecules in the present study. However, we found higher sTNF-R1 concentration in 'late-stage' BD illness (>1 prior psychiatric hospitalization) compared to those in early stage illness. In the subsequent SEM, we found that the model fits the data acceptably (Chi-square = 49.2, p = 0.3), and had a 'close fit' (RMSEA = 0.02, PCLOSE = 0.9). Holding covariates constant (age, sex, premorbid IQ, education, and race), we found that the standardized indirect effect was significant, p = 0.015, 90%CI [-0.07, -0.01], indicating that the estimated model was consistent with peripheral TNF markers partially mediating a causal effect of severe mood episodes on executive function. CONCLUSIONS: Our results indicate that circulating levels of TNF molecules partially mediate the relationship between prior severe mood episodes and executive function in BD. These results may implicate TNF variables in the neuroprogressive course of BD and could point to novel interventions for cognition.

Functioning in euthymic patients with bipolar disorder: A systematic review and meta-analysis using the Functioning Assessment Short Test.

OBJECTIVES: Systematically review the prevalence of functional impairment (FI) in euthymic patients with bipolar disorder (BD), as assessed only with the Functioning Assessment Short Test (FAST), explore the prevalence of this impairment among all the domains, identify the most compromised of them and the clinical variables associated with low functioning in this population. METHODS: Meta-analyses were performed, searching for relevant papers published from 2007 to 2019 in Medline, Embase, Cochrane, PsycINFO databases and via hand-searching, without language restrictions. 1128 studies were initially identified, 13 of which were ultimately chosen based on the eligibility criteria. A two-step meta-analysis was performed using the mean difference with a 95% confidence interval for continuous variables and proportion estimation with a fixed-effects model for categorical variables. RESULTS: In the first step, all FAST domains showed worse FI in patients than in healthy controls, with significant differences between groups. In the second step, the prevalence of FI domains were as follows: global, 58.6%; occupational, 65.6%; cognitive, 49.2%; autonomy, 42.6%; interpersonal relationships, 42.1%; leisure, 29.2%; and financial issues, 28.8%. Residual depressive symptoms were the most frequently cited variable associated with FI. CONCLUSIONS: This study reinforces the relevant functional impact of BD in this population and suggests that the occupational domain may be the most impaired. Greater efforts should be directed toward targeting functioning in patient care, as it constitutes the most meaningful endpoint of response to treatment, especially with occupational and cognitive rehabilitation, thus allowing patients to overcome the course of illness and carry fulfilling lives.

Impaired social cognition in bipolar disorder: A meta-analysis of Theory of Mind in euthymic patients.

OBJECTIVE: To conduct a meta-analysis of Theory of Mind studies exclusively in euthymic patients with bipolar disorder. METHOD: After the exclusion of studies evaluating symptomatic patients during acute episodes, we performed a meta-analysis including a total of 30 studies, comparing 1294 euthymic bipolar disorder patients and 1116 healthy controls. RESULTS: Patients with bipolar disorder presented a significant impairment in Theory of Mind performance when compared to controls (Hedge's g = -0.589, 95% confidence interval: -0.764 to -0.414, Z = -6.594, p < 0.001). When compared to controls, Theory of Mind was impaired in patients with both bipolar disorder I (Hedge's g = -0.663, 95% confidence interval: -0.954 to -0.372, Z = -4.462, p < 0.001) and bipolar disorder II (Hedge's g = -1.165, 95% confidence interval: -1.915 to -0.415, Z = -3.044, p = 0.002). Theory of Mind impairments were also significantly more severe in verbal tasks (Hedge's g = -1.077, 95% confidence interval: -1.610 to -0.544, Z = -3.961 p < 0.001) than visual tasks (Hedge's g =-0.614, 95% confidence interval: -0.844 to -0.384, Z = -5.231, p < 0.001) when compared to controls. CONCLUSION: The results obtained confirm that Theory of Mind is impaired in remitted bipolar disorder patients, being a potential endophenotype for bipolar disorder. Moreover, we found higher deficits in verbal Theory of Mind, compared with visual Theory of Mind. Since most studies were cross-sectional, there is a need for longitudinal studies to evaluate whether the deficits detected in Theory of Mind are progressive over the course of the illness.