Lifetime prevalence of psychiatric comorbidities in patients with bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: Bipolar disorder (BD) is a severe psychiatric disease and part of its burden is related to the high rates of lifetime psychiatric comorbidity (PC), with diagnostic, therapeutic, and prognostic implications. METHODS: Registered in PROSPERO (CRD42021282356). Meta-analyses were performed, searching for relevant papers published from 1993 to 2022 in Medline/PubMed (including E-Pub Ahead of Print), Embase, Cochrane Library (Central), PsycINFO, Scopus, Web of Science and via hand-searching, without language restrictions. 12.698 studies were initially identified, 114 of which were ultimately chosen based on the eligibility criteria. We performed two meta-analyses (prevalence and risk ratio) of mental health conditions among subjects with BD and then conducted a comprehensive examination of moderator effects using multivariable meta-regression models for moderators identified as significant in the univariable analysis. FINDINGS: Overall PC prevalence of at least one disorder was 38.91 % (95 % CI 35.24-42.70) and the most frequent disorders were: anxiety (40.4 % [34.97-46.06]), SUD (30.7 % [23.73-38.73]), ADHD (18.6 % [10.66-30.33]) and Disruptive, impulse-control and conduct disorder (15 % [6.21-31.84). The moderators with higher association with individual prevalences were UN's Human Development Index (HDI), female gender, age, suicide attempt, and age at onset (AAO). INTERPRETATION: It becomes evident that the prevalence of PC among individuals with BD is notably high, surpassing rates observed in the general population. This heightened prevalence persists despite significant heterogeneity across studies. Consequently, it is imperative to redirect clinical focus towards comprehensive mental health assessments, emphasizing personalized and routine screening. Additionally, there is a pressing need for the enhancement of public policies to create a supportive environment for individuals with BD, ensuring better therapeutic conditions and sustained assistance. By addressing these aspects, we can collectively strive towards fostering improved mental health outcomes for individuals with BD.

Arketamine for bipolar depression: Open-label, dose-escalation, pilot study.

There are significantly fewer options for the treatment of bipolar depression than major depressive disorder, with an urgent need for alternative therapies. In this pilot study, we treated six subjects with bipolar disorder types I and II (according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria) who had been in a current depressive episode for at least four weeks. Four subjects were female (66.66%), and the mean age was 45.33 (±12.32). Subjects received adjunct treatment with two arketamine intravenous infusions one week apart-0.5 mg/kg first and then 1 mg/kg. The mean baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total score was 36.66, which decreased to 27.83 24h after the first infusion of 0.5 mg/kg of arketamine (p = 0.036). In respect of the 1 mg/kg dose, the mean MADRS total score before the second infusion was 32.0, which dropped to 17.66 after 24h (p < 0.001). Arketamine appears to have rapid-acting antidepressant properties, consistent with previous animal studies on major depression. All individuals tolerated both doses, exhibiting nearly absent dissociation, and no manic symptoms. To the best of our knowledge, this pilot trial is the first to test the feasibility and safety of the (R)-enantiomer of ketamine (arketamine) for bipolar depression.

Psychopathological symptoms in parents and siblings of people on the autism spectrum: A systematic review and meta-analysis.

Parents and siblings of children on the autism spectrum experience significant distress, and for this reason, it is essential to understand the most prevalent psychopathological symptoms among this population. This work aims to establish the prevalence of psychopathological symptoms in parents and siblings of individuals on the autism spectrum, following the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P) criteria. Searches were carried out using the PubMed/Medline, Embase, PsycINFO, SciELO, and Biblioteca Virtual em Saúde (BVS) databases. Twenty-three articles were included in this review. Depressive symptoms were the most frequently reported conditions, with a higher prevalence in mothers of children on the autism spectrum. In the meta-analysis, mothers of children on the autism spectrum scored higher by 0.42 standard deviations on the symptom scales (SMD 0.42; CI 0.25-0.59), with low statistical heterogeneity (I2 0%, p = 0.5) when compared with mothers of children with atypical development. The psychopathological symptoms of relatives should be investigated as part of the follow-up procedures for the child on the autism spectrum to facilitate their treatment.

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.

Suicide attempt, impulsivity, and exposure to trauma in college students

Objectives: Past suicide attempt (SA) is one of the most important risk factors for suicide death. An ideation-to-action framework posits that impulsivity, potentially traumatic events, and mental disorders also play a role in increasing suicide risk. This study aimed to assess the association between trait impulsivity, lifetime exposure to trauma, and post-traumatic stress disorder (PTSD) with SA in a sample of Brazilian college students. Methods: A total of 2,137 participants filled self-reported questionnaires consisting of a sociodemographic and clinical questionnaire, Trauma History Questionnaire, Post-Traumatic Stress Disorder Checklist - Civilian version, and Barratt Impulsiveness Scale. Results: Our findings suggest that trait impulsivity may be interpreted as exerting a distal effect on SA, even in the presence of other variables - such as trauma history, psychological neglect, and PTSD - which also increase the odds of SA. High and medium levels of impulsivity, history of trauma, and PTSD increased the likelihood of SA. Conclusions: Intervention strategies to prevent SA may target trait impulsivity and exposure to traumatic experiences.

Metabolomics of Major Depressive Disorder: A Systematic Review of Clinical Studies.

Although the understanding of the pathophysiology of major depressive disorder (MDD) has advanced greatly, this has not been translated into improved outcomes. To date, no biomarkers have been identified for the diagnosis, prognosis, and therapeutic management of MDD. Thus, we aim to review the biomarkers that are differentially expressed in MDD. A systematic review was conducted in January 2022 in the PubMed/MEDLINE, Scopus, Embase, PsycINFO, and Gale Academic OneFile databases for clinical studies published from January 2001 onward using the following terms: "Depression" OR "Depressive disorder" AND "Metabolomic." Multiple metabolites were found at altered levels in MDD, demonstrating the involvement of cellular signaling metabolites, components of the cell membrane, neurotransmitters, inflammatory and immunological mediators, hormone activators and precursors, and sleep controllers. Kynurenine and acylcarnitine were identified as consistent with depression and response to treatment. The most consistent evidence found was regarding kynurenine and acylcarnitine. Although the data obtained allow us to identify how metabolic pathways are affected in MDD, there is still not enough evidence to propose changes to current diagnostic and therapeutic actions. Some limitations are the heterogeneity of studies on metabolites, methods for detection, analyzed body fluids, and treatments used. The experiments contemplated in the review identified increased or reduced levels of metabolites, but not necessarily increased or reduced the activity of the associated pathways. The information acquired through metabolomic analyses does not specify whether the changes identified in the metabolites are a cause or a consequence of the pathology.

Suicide attempt, impulsivity, and exposure to trauma in college students.

OBJECTIVES: Past suicide attempt (SA) is one of the most important risk factors for suicide death. An ideation-to-action framework posits that impulsivity, potentially traumatic events, and mental disorders also play a role in increasing suicide risk. This study aimed to assess the association between trait impulsivity, lifetime exposure to trauma, and post-traumatic stress disorder (PTSD) with SA in a sample of Brazilian college students. METHODS: A total of 2,137 participants filled self-reported questionnaires consisting of a sociodemographic and clinical questionnaire, Trauma History Questionnaire, Post-Traumatic Stress Disorder Checklist - Civilian version, and Barratt Impulsiveness Scale. RESULTS: Our findings suggest that trait impulsivity may be interpreted as exerting a distal effect on SA, even in the presence of other variables - such as trauma history, psychological neglect, and PTSD - which also increase the odds of SA. High and medium levels of impulsivity, history of trauma, and PTSD increased the likelihood of SA. CONCLUSIONS: Intervention strategies to prevent SA may target trait impulsivity and exposure to traumatic experiences.

Social support in patients with bipolar disorder and differing ages at onset.

OBJECTIVE: The main purpose of this study was to evaluate the association between age at onset and social support in outpatients with bipolar disorder who were in the recovery phase. We also investigated the association between age at onset and disability. METHODS: A total of 180 bipolar disorder I outpatients, of whom 50 had early onset with age at onset ≤18 years old, 108 had middle onset with age at onset between 19 and 39 years old, and 22 had late onset with age at onset ≥40 years old, were assessed with the Medical Outcomes Study Social Support Scale and Sheehan Disability Scale. RESULTS: The early onset group had lower tangible social support, longer length of illness, more childless participants, lower income and more suicide attempters than the late onset group. CONCLUSIONS: Early onset seems to have inferior outcomes in tangible social support than late onset, but this trend should be considered as a starting point for future studies.

Burnout syndrome and resilience in medical students from a Brazilian public college in Salvador, Brazil.

INTRODUCTION: Burnout syndrome is highly prevalent among medical students. Whereas burnout syndrome has been associated with negative outcomes, like suicidal ideation, protective factors are still unknown. OBJECTIVE: To evaluate if there is an association between burnout syndrome and resilience in medical students, assessing covariates such as depressive symptoms, suicidal ideation, and religiosity. METHOD: This cross-sectional study was carried out with a sample of 209 students from a medical school in Brazil. Burnout syndrome was assessed using the Maslach Burnout Inventory - Student Survey. Potential protective factors and aggravators to burnout syndrome were investigated using appropriate scales. RESULTS: Fifty-nine students (28.2%) presented burnout. Multivariate analysis showed that resilience was a protective factor (p < 0.001), along with being older, married or having better academic performance. Depressive symptoms were positively associated with burnout. Religiosity was not a protective factor and suicidal ideation was not associated with burnout when adjusted for depressive symptoms. CONCLUSION: Burnout is frequent among medical students, impacting mental health and academic performance. Resilience seems to be a protective factor, and the relationship between burnout and suicidal ideation is possibly mediated by depressive symptoms. Prospective studies are needed to further investigate the associations found in this study.

Burnout syndrome and resilience in medical students from a Brazilian public college in Salvador, Brazil

Abstract Introduction Burnout syndrome is highly prevalent among medical students. Whereas burnout syndrome has been associated with negative outcomes, like suicidal ideation, protective factors are still unknown. Objective To evaluate if there is an association between burnout syndrome and resilience in medical students, assessing covariates such as depressive symptoms, suicidal ideation, and religiosity. Method This cross-sectional study was carried out with a sample of 209 students from a medical school in Brazil. Burnout syndrome was assessed using the Maslach Burnout Inventory - Student Survey. Potential protective factors and aggravators to burnout syndrome were investigated using appropriate scales. Results Fifty-nine students (28.2%) presented burnout. Multivariate analysis showed that resilience was a protective factor (p < 0.001), along with being older, married or having better academic performance. Depressive symptoms were positively associated with burnout. Religiosity was not a protective factor and suicidal ideation was not associated with burnout when adjusted for depressive symptoms. Conclusion Burnout is frequent among medical students, impacting mental health and academic performance. Resilience seems to be a protective factor, and the relationship between burnout and suicidal ideation is possibly mediated by depressive symptoms. Prospective studies are needed to further investigate the associations found in this study.

Association between exposure to toxoplasmosis and major psychiatric disorders: a systematic review.

OBJECTIVE: To assess the association between exposure to toxoplasmosis and major psychiatric disorders through a systematic review of the literature. METHODS: The literature review was performed in the MEDLINE, SciELO, and PsycINFO databases. To evaluate the quality of the studies included in the review, the Newcastle-Ottawa Scale was used. RESULTS: Thirty-one studies were included, and the majority found an association between exposure to toxoplasmosis and schizophrenia or bipolar disorder (58.3 and 54.5% of the included papers, respectively), but not major depressive disorder. We found no significant difference in mean quality scores between studies that corroborated and contradicted the association hypothesis for either schizophrenia or bipolar disorder. All included papers were considered at least satisfactory according to the Newcastle-Ottawa Scale (total scores ≥ 6 out of 9). CONCLUSION: Although there was no association between exposure to toxoplasmosis and major depressive disorder, the results indicate an association with both bipolar disorder and schizophrenia, despite their heterogeneity. Further studies should be performed with more specific variables so that the nature of these relationships can be elucidated.

History of suicide attempts in patients with bipolar disorder type I: socio-demographic and clinical factors, quality of life and functioning.

INTRODUCTION: This study aims to evaluate sociodemographic and clinical factors, quality of life (QoL) and functioning associated with history of suicide attempts (SA) in a sample of bipolar disorder (BD) type I patients. METHODS: A total of 417 BD type I patients, with and without history of SA were recruited from two Brazilian specialized Mood Disorder Centers. They were assessed with a sociodemographic and clinical questionnaire, the Young Mania Rating Scale, the Hamilton Depression Rating Scale, the Structured Clinical Interviews for DSM-IV Axis I Disorders, the World Health Organization Quality of Life-BREF, and the Sheehan Disability Scale. RESULTS: One hundred and seventy-nine (42.9%) patients had a history of SA. There were no statistically significant sociodemographic differences between BD patients with and without a history of SA. Logistic regression found that lifetime hospitalization, comorbid anxiety disorders, depressive polarity in the first episode, current intensity of depressive symptoms, history of rapid cycling, family history of suicide and age at onset were significantly associated with SA in BD. Multiple linear regression showed that SA had no effect on QoL and functioning, which were affected mainly by comorbid anxiety disorders and current intensity of depressive symptoms, even in patients considered euthymic. CONCLUSION: Suicidal behavior in patients with BD is a complex phenomenon and reflects a more severe course of illness. Patients with history of SA may have worse QoL and functional impairment not because of its direct effect, but because of the greater association with clinical factors related to poor prognosis.

Prefrontal gray matter volume in adults bipolar I outpatients is associated with history of suicide attempts?

ABSTRACT Background: Patients with Bipolar Disorder (BD) have the highest lifetime risk for suicidal behavior (SB) compared to other psychiatric disorders. Neuroimaging research provides evidence of some structural and functional abnormalities in the brain of BD suicide attempters (SA), but interpretation of these findings may represent a number of features. Objective: The purpose of this study was to evaluate the volume of the prefrontal cortex in euthymic BD type I outpatients, with and without history of SA. Methods: 36 euthymic BD I outpatients (18 with and 18 without suicide attempt history) were underwent structural MRI and total and regional gray matter volumes were assessed and compared with 22 healthy controls (HC). Results: We did not found any differences in all areas between suicidal and non-suicidal BD I patients and BD patients as a group compared to HC as well. Discussion: our findings suggest that can be a different subgroups of patients in relation to prefrontal cortex volumes according to some clinical and socio-demographic caractheristics, such as number of previous episodes and continuous use of medical psychotropic drugs that may induce neuroplasticity phenomena, which restore cerebral volume and possibly can lead to long-term euthymia state.

Suicidal behavior in individuals with amyotrophic lateral sclerosis: A systematic review.

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) leads to a drastic reduction in quality of life, generating intense psychological distress and predisposing those affected to mental illness and, in more severe cases, suicidal behavior. OBJECTIVE: This is a systematic review aiming to estimate the frequency of wish to die, suicide ideation and suicide in individuals with ALS using the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). METHODS: The following databases were used: Pubmed/MEDLINE, PsycINFO, Embase, SciELO, Biblioteca Virtual de Saúde (BVS), and Cochrane Library. The choice of appropriate descriptors, or their equivalents, to define the search terms was based on the technical and scientific vocabulary of each database. RESULTS: 13 articles were included in the present systematic review, of which three were cross-sectional studies, nine were cohort-type and there was one case-control study. The studies show that individuals with ALS have a higher risk of suicide in relation to the general population, and there is evidence that this risk is even higher in the early stages of the disease. Major Depressive Disorder was the most prevalent mental disorder in the studies included. This mental health concern is often undertreated, leading to the increased susceptibility of this population to suicide. LIMITATIONS: In general, the study samples represent a highly heterogeneous population while many instruments used in the data collection were not uniform. CONCLUSIONS: The high degree of psychological vulnerability of this population, associated with a greater predisposition to suicidal behavior, should be minimized through public health measures.

Neurocognitive Impairment in Bipolar Disorder and Associated Factors: Using Population-based Norms and a Strict Criterion for Impairment Definition.

BACKGROUND: Cognitive impairment is often identified in individuals with bipolar disorder and is associated with their functional impairment. However, there is controversy surrounding potential classification methods for impairment in cognitive measures. OBJECTIVE: To examine the proportion of cognitive measures indicating impairment of attention, processing speed, memory, visuoconstructional abilities, and executive functions in individuals with bipolar disorder type I (euthymic) and healthy controls, using a strict criterion for defining impairment. METHODS: We gave 43 individuals with bipolar disorder type I and 17 healthy controls a comprehensive clinical and neuropsychological assessment. All scores were standardized using means and standard deviations according to age. Impaired performance in all cognitive measures was determined using a distribution-based threshold of z=±1645. The effects of the sociodemographic and clinical variables on cognitive performance were examined using multiple stepwise backward regression analyses. RESULTS: Clinically significant cognitive impairment was observed more frequently in the bipolar disorder group, compared to controls, on all measures. From participant factors, we found that level of education and number of manic episodes predicted variation in more cognitive measure scores. DISCUSSION: The use of population-based norms to standardize cognitive measures, and a strict criterion to define cognitive impairment, in individuals with bipolar disorder type 1 and healthy controls resulted in a prevalence of impairment in cognitive domains' frequencies of deficits that fell within the ranges previously reported in meta-analyses. CONCLUSIONS: Clinically introducing population norms and a stringent cognitive impairment criterion can facilitate more accurate measures of cognitive impairment in individuals with bipolar disorder.

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.

Self-injurious behavior and related mortality in children under 10 years of age: a retrospective health record study in Brazil

Objective: To describe and analyze data on self-injurious behavior (SIB) and related mortality in children under 10 years old in Brazil. Methods: A descriptive study was performed using secondary public health care data extracted from the Hospital Information System (Sistema de Informações Hospitalares, SIH) and Mortality Information System (Sistema de Informações sobre Mortalidade, SIM) in Brazil. The databases are available for online access at http://datasus.saude.gov.br/. Results: In Brazil, according to SIH data, 11,312 hospitalizations of patients under 10 years of age were recorded from 1998 to 2018 as resulting from SIB (ICD-10 X60-X84 codes). Of these, 65 resulted in death. According to the SIM, from 1996 to 2016, 91 deaths related to SIB were recorded, 81 (89%) in children aged 5 to 9 years, nine (9.9%) in children aged 1 to 4 years, and one (1.1%) in a child below 1 year of age. Conclusion: These results highlight the relevance of creating measures to better understand SIB and related mortality in this age group. They also reveal the vulnerability of children in Brazil and warrant further studies to address these issues.