Digital Tools to Facilitate the Detection and Treatment of Bipolar Disorder: Key Developments and Future Directions.

Bipolar disorder (BD) impacts over 40 million people around the world, often manifesting in early adulthood and substantially impacting the quality of life and functioning of individuals. Although early interventions are associated with a better prognosis, the early detection of BD is challenging given the high degree of similarity with other psychiatric conditions, including major depressive disorder, which corroborates the high rates of misdiagnosis. Further, BD has a chronic, relapsing course, and the majority of patients will go on to experience mood relapses despite pharmacological treatment. Digital technologies present promising results to augment early detection of symptoms and enhance BD treatment. In this editorial, we will discuss current findings on the use of digital technologies in the field of BD, while debating the challenges associated with their implementation in clinical practice and the future directions.

Psychological resilience and mood disorders: a systematic review and meta-analysis

Abstract Objective This systematic review aims to describe the relationship between psychological resilience and mood disorders. Methods This is a systematic review and meta-analysis. The following databases were searched on November 6, 2020: PubMed, PsycINFO, and Embase. Results Twenty-three articles were included and the majority of the studies included (95.7%) showed that psychological resilience has a positive impact in mood disorders. Our meta-analysis showed that individuals with bipolar disorder presented significantly lower levels of psychological resilience compared to controls (standardized mean difference [SDM]: -0.99 [95% confidence interval {95%CI}: -1.13 to -0.85], p < 0.001). In addition, individuals with depression had significantly lower levels of psychological resilience compared to controls (SDM: -0.71 [95%CI -0.81 to -0.61], p < 0.001). Conclusion Our results showed that individuals with mood disorders are less resilient than individuals without mood disorders. Our findings reinforce the importance of investigating interventions that may help to improve psychological resilience considering its positive impact in the context of mood disorders.

COVID-19, Anxiety, and Body Mass Index Increase Leptin Levels: a Cross-sectional Multicentric Study.

Although many efforts have been made to understand the pathophysiological mechanisms of COVID-19, critical gaps remain to be explored. This study aimed to investigate potential alterations in adipokine levels (specifically adiponectin, leptin, and resistin) among individuals with COVID-19. Within this population, we further assessed the association between these markers with both, body mass index (BMI) and psychiatric symptoms. This cross-sectional study included an age- and sex-matched sample of adults with COVID-19 (cases) and without COVID-19 (controls). We evaluated the severity of psychiatric symptoms, BMI, and adipokines. Individuals with COVID-19 presented greater BMI, stress levels, and leptin levels when compared to controls. Leptin levels were greater in individuals with moderate/severe COVID-19 as compared to individuals with COVID-19 who were asymptomatic or having mild symptoms. Leptin levels were positively correlated with BMI, severity of depressive and anxiety symptoms, and stress levels in the total sample. Leptin levels were also positively correlated with BMI, severity of anxiety symptoms, and stress levels in controls. In cases, there was a positive correlation between adiponectin and the severity of depressive symptoms and stress levels and leptin/resistin with BMI. A linear regression model revealed that BMI, severity of anxiety symptoms, and the diagnosis of COVID-19 are independently associated with increased leptin levels. Thus, leptin levels seem to be impacted by the COVID-19 infection, anxiety, and BMI.

Lifestyle in bipolar disorder: A cross-sectional study.

BACKGROUND: Modifiable lifestyle behaviors are important factors for improving mental health, yet there has been a lack of research studying lifestyle as a multidimensional construct in bipolar disorder (BD). The aim of this cross-sectional study was to compare the lifestyle patterns of individuals with BD in a current mood episode with healthy controls (HCs) using the Short Multidimensional Inventory Lifestyle Evaluation (SMILE). MATERIALS AND METHODS: The sample consisted of 46 individuals with BD currently experiencing a depressive or manic episode and 50 HC, assessed using the MINI International Neuropsychiatric Interview, Montgomery-Åsberg Depression Rating Scale (MADRS), and the Young Mania Rating Scale (YMRS). The SMILE scale assesses lifestyle across seven domains: diet and nutrition, substance abuse, physical activity, stress management, restorative sleep, social support, and environmental exposures. Between-groups comparisons were performed based on the presence of a psychiatric diagnosis and the type of BD episode. RESULTS: We found significant differences in the total SMILE score (r=0.75, p<0.001) and in scores from each domain of the scale between BD and HC (p<0.05), where individuals with BD in a depressive or manic episode with or without mixed features reported worse lifestyle across all domains. Differences between individuals with BD in different mood episodes across domains on the SMILE scale were non-significant. CONCLUSION: Findings from this study highlight the presence of unhealthy lifestyle patterns in people with BD regardless of the polarity of their mood episode. Implementation of multidimensional lifestyle assessments is an essential step toward detecting the clustering of unhealthy lifestyle patterns in BD.

Predicting functional impairment in euthymic patients with mood disorder: A 5-year follow-up.

Major Depressive Disorder and Bipolar Disorder are psychiatric disorders associated with psychosocial impairment. Despite clinical improvement, functional complaints usually remain, mainly impairing occupational and cognitive performance. The aim of this study was to use machine learning techniques to predict functional impairment in patients with mood disorders. For that, analyzes were performed using a population-based cohort study. Participants diagnosed with a mood disorder at baseline and reassessed were considered (n = 282). Random forest (RF) with previous recursive feature selection and LASSO algorithms were applied to a training set with imputed data by bagged trees resulting in two main models. Following recursive feature selection, 25 variables were retained. The RF model had the best performance compared to LASSO. The most important variables in predicting functional impairment were sexual abuse, severity of depressive, anxiety, and somatic symptoms, physical neglect, emotional abuse, and physical abuse. The model demonstrated acceptable performance to predict functional impairment. However, our sample is composed of young participants and the model may not generalize to older individuals with mood disorders. More studies are needed in this direction. The presented calculator has clinical, sociodemographic, and environmental data, demonstrating that it is possible to use such information to predict functional performance.

Best Practices for Using AI Tools as an Author, Peer Reviewer, or Editor.

The ethics of generative artificial intelligence (AI) use in scientific manuscript content creation has become a serious matter of concern in the scientific publishing community. Generative AI has computationally become capable of elaborating research questions; refining programming code; generating text in scientific language; and generating images, graphics, or figures. However, this technology should be used with caution. In this editorial, we outline the current state of editorial policies on generative AI or chatbot use in authorship, peer review, and editorial processing of scientific and scholarly manuscripts. Additionally, we provide JMIR Publications' editorial policies on these issues. We further detail JMIR Publications' approach to the applications of AI in the editorial process for manuscripts in review in a JMIR Publications journal.

The comorbidity between Borderline Personality Disorder (BPD) and Generalized Anxiety Disorder (GAD): A systematic review and meta-analysis.

Borderline personality disorder (BPD) is a psychiatric condition characterized by severe instability in affect, impulse control, and interpersonal functioning. Existing literature has confirmed that BPD is highly comorbid with other psychiatric conditions, including anxiety disorders. Despite this, little research has investigated the nature of the relationship between generalized anxiety disorder (GAD) and BPD. The aim of this systematic review and meta-analysis is to synthesize the literature concerning the prevalence and clinical outcomes of BPD and GAD comorbidity in adults. The following three databases were searched on October 27, 2021: PsycINFO, PubMed, and Embase. Twenty-four studies were included (n = 21 reporting on prevalence of the comorbidity, n = 4 reporting on clinical outcomes associated with the comorbidity), 9 of which were included in a meta-analysis. The meta-analysis showed that the pooled prevalence for current GAD in individuals with BPD was 16.4% (CI 95%: 1.9%; 66.1%) in inpatient samples, and 30.6% (CI 95%: 21.9%; 41.1%) in outpatient or community samples. The pooled lifetime prevalence of GAD in individuals with BPD was 11.3% (CI 95%: 8.9%; 14.3%) in inpatient samples, and 13.7% (CI 95%: 3.4%; 41.4%) in outpatient or community samples. Comorbidity between BPD and GAD was associated with worse outcomes on measures of BPD severity, impulsivity, anger, and hopelessness. In conclusion, this systematic review and meta-analysis indicate that comorbid GAD and BPD is highly prevalent, although the pooled prevalence rates should be interpreted with caution considering the large and overlapping confidence intervals. Further, this comorbidity is associated with worse BPD symptom severity.

Lifestyle changes during the COVID-19 pandemic in Brazil: results from three consecutive cross-sectional web surveys.

OBJECTIVE: The importance of a healthy lifestyle in preventing morbidity and mortality is well-established. The COVID-19 pandemic brought about significant lifestyle changes globally, but the extent of these changes in the Brazilian population remains unclear. The objective of this study was to evaluate changes in lifestyle among the Brazilian general population during the first year of the pandemic. DESIGN: Three consecutive anonymous web surveys were carried out: survey 1 (S1)-April 2020, S2-August 2020 and S3-January 2021. SETTING: Brazil. PARTICIPANTS: The study included 19 257 (S1), 1590 (S2) and 859 (S3) participants from the general population, who were ≥18 years, of both sexes, with access to the internet, self-reporting living in Brazil and who agreed to participate after reading the informed consent. PRIMARY OUTCOME: Lifestyle changes were assessed using the Short Multidimensional Instrument for Lifestyle Evaluation-Confinement (SMILE-C). The SMILE-C assesses lifestyle across multiple domains including diet, substance use, physical activity, stress management, restorative sleep, social support and environmental exposures. We used a combination of bootstrapping and linear fixed-effect modelling to estimate pairwise mean differences of SMILE-C scores overall and by domain between surveys. RESULTS: In all the surveys, participants were mostly women and with a high education level. Mean SMILE-C scores were 186.4 (S1), 187.4 (S2) and 190.5 (S3), indicating a better lifestyle in S3 as compared with S1. The pairwise mean differences of the overall SMILE-C scores were statistically significant (p<0.001). We also observed a better lifestyle over time in all domains except for diet and social support. CONCLUSIONS: Our findings indicate that individuals from a large middle-income country, such as Brazil, struggled to restore diet and social relationships after 1 year of the pandemic. These findings have implications for monitoring the long-term consequences of the pandemic, as well as future pandemics.

ABO Blood Type and Metabolic Markers in COVID-19 Susceptibility and Severity: A Cross-Sectional Study.

Background and Aims: To evaluate the effect of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus on the function and metabolic changes, as well as the relationship of the virus with blood groups. Methods and Results: This cross-sectional study included a matched sample of adult individuals with coronavirus disease 2019 (COVID-19) (n = 114) or without (controls; n = 236). Blood samples were collected and processed for triglycerides (TGs), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and blood typing analysis. The results showed that subjects with COVID-19 had higher TG and lower HDL-C levels compared with the control group. As for blood typing, the risk of COVID-19 was higher in subjects with blood group A than in those with blood group B and in those with other blood groups. In addition, an association of COVID-19 with blood type and Rh A- was observed. When related to the severity of COVID-19 symptoms, blood type A was more protective against moderate/severe symptoms compared with blood type O. In addition, individuals with blood type O were 2.90 times more likely to have symptoms moderate/severe symptoms of COVID-19 than those with other blood groups and individuals with type A blood were less likely to have severe/moderate symptoms of COVID-19 compared with individuals without type A blood. Conclusion: The results suggest that blood type may play a role in susceptibility to SARS-CoV-2 infection and add evidence that infection with the novel coronavirus may be associated with changes in lipid metabolism.

Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy.

Cognitive decline and mood disorders increase in frequency with age. Many efforts are focused on the identification of molecules and pathways to treat these conditions. Here, we demonstrate that systemic administration of growth differentiation factor 11 (GDF11) in aged mice improves memory and alleviates senescence and depression-like symptoms in a neurogenesis-independent manner. Mechanistically, GDF11 acts directly on hippocampal neurons to enhance neuronal activity via stimulation of autophagy. Transcriptomic and biochemical analyses of these neurons reveal that GDF11 reduces the activity of mammalian target of rapamycin (mTOR), a master regulator of autophagy. Using a murine model of corticosterone-induced depression-like phenotype, we also show that GDF11 attenuates the depressive-like behavior of young mice. Analysis of sera from young adults with major depressive disorder (MDD) reveals reduced GDF11 levels. These findings identify mechanistic pathways related to GDF11 action in the brain and uncover an unknown role for GDF11 as an antidepressant candidate and biomarker.

Atypical antipsychotic-induced mania: A systematic review and meta-analysis.

BACKGROUND: The possibility of atypical antipsychotics (AA) to induce manic symptoms has been raised by several articles. The objective of this study was to describe whether exposure to AA may induce mania in mood disorders. METHODS: We performed a systematic review following the preferred reporting items for systematic reviews and meta-analysis guidelines. The systematic search encompassed all relevant studies published until April 4th, 2022. A meta-analysis testing whether treatment emergent mania (TEM) is more frequent with the use of AA compared with placebo was performed. RESULTS: A total of 52 studies were included in the systematic review. We found 24 case reports or case series describing 40 manic/hypomanic episodes allegedly induced by AA. Twenty-one placebo-controlled trials were included in a meta-analysis including 4823 individuals treated with AA and 3252 individuals receiving placebo. Our meta-analysis showed that the use of AA protects against the development of TEM (OR: 0.68 [95 % CI: 0.52-0.89], p = 0.005). LIMITATIONS: AA-induced mania/hypomania was not the primary outcome in any of the observational or interventional studies. TEM was not homogeneously defined across studies. In most case reports it was not possible to establish causality between the use of AA and the development of manic symptoms. CONCLUSIONS: TEM is more frequent with placebo than with AA, which suggests that AA exposure does not represent a relevant risk for TEM. Mania/hypomania induced by an AA seems to be rare events, since anecdotal evidence from case reports and case series were not observed in observational prospective and interventional studies.

Stress levels, psychological symptoms, and C-reactive protein levels in COVID-19: A cross-sectional study.

BACKGROUND: Although many studies have pointed out a possible relationship between COVID-19 and the presence of psychiatric disorders, the majority of the studies have significant limitations. This study investigates the influence of COVID-19 infection on mental health. METHODS: This cross-sectional study included an age- and sex-matched sample of adult individuals positive (cases) or negative (controls) for COVID-19. We evaluated the presence of psychiatric conditions and C-reactive protein (CRP). RESULTS: Findings showed greater severity of depressive symptoms, higher levels of stress, and greater CRP in cases. The severity of depressive and insomnia symptoms, as well as the CRP were more remarkable in individuals with moderate/severe COVID-19. We found a positive correlation between stress and severity of anxiety, depression, and insomnia in individuals with or without COVID-19. There was a positive correlation between CRP levels and severity of depressive symptoms in cases and controls, and a positive correlation between CRP levels and the severity of anxiety symptoms and stress levels only in individuals with COVID-19. Individuals with COVID-19 and depression had greater CRP than those with COVID-19 without current major depressive disorder. LIMITATIONS: We cannot infer causality because this is a cross-sectional study, and the majority of COVID-19 sample was asymptomatic or had mild symptoms, which may limit the generalizability of our findings for moderate/severe cases. CONCLUSIONS: Individuals with COVID-19 showed greater severity of psychological symptoms, which may impact on the development of psychiatric disorders in the future. CPR seem to be a promising biomarker for earlier detection of post-COVID depression.

Triggers for acute mood episodes in bipolar disorder: A systematic review.

OBJECTIVES: To identify triggers of acute mood episodes in bipolar disorder (BD). METHODS: We performed a systematic review in the following databases: Pubmed, Embase, and PsycInfo following the preferred reporting items for systematic reviews and meta-analysis guidelines. The systematic search encompassed all relevant studies published until May 23rd, 2022. RESULTS: A total of 108 studies (case reports/case series, interventional, prospective and retrospective studies) were included in the systematic review. While several decompensation triggers were identified, pharmacotherapy was the one with the largest body of evidence, particularly the use of antidepressants as triggers of manic/hypomanic episodes. Other identified triggers for mania were brain stimulation, energy drinks, acetyl-l-carnitine, St. John's wort, seasonal changes, hormonal changes and viral infections. There is a relative paucity of evidence concerning triggers for depressive relapses in BD, with possible triggers including fasting, decreased sleep and stressful life events. CONCLUSIONS: This is the first systematic review about triggers/precipitants of relapse in BD. Despite the importance of identification and management of potential triggers for BD decompensation, there is a lack of large observational studies addressing this topic, with most of the included studies being case reports/case series. Notwithstanding these limitations, antidepressant use is the trigger with the strongest evidence for manic relapse. More studies are needed to identify and manage triggers for relapse in BD.

Lifestyle Behaviors, Depression, and Anxiety Among Individuals Living in Canada During the COVID-19 Pandemic.

The aim of our study was to investigate the association between lifestyle behaviors and symptoms of depression and anxiety during the COVID-19 pandemic in Canada. A web survey was conducted between July 3-August 3, 2020, across Canada. The main outcomes considered were a positive screening for depression, as evaluated by the PHQ-2 and positive screening for anxiety, as evaluated by the GAD-7. Lifestyle behaviors were assessed using the Short Multidimensional Lifestyle Inventory Evaluation-Confinement (SMILE-C), an instrument adapted for lifestyle behaviors during the COVID-19 pandemic. The total sample size included 404 participants, of which 24.3% had a positive screen for depression, 20.5% for anxiety, and 15.5% for both. We found significant differences in SMILE-C scores between individuals with a positive and individuals with a negative screen for depression (P < .001). Likewise, there were significant differences in SMILE-C scores between individuals with a positive and individuals with a negative screen for anxiety (P < .001). We found an association between unhealthy lifestyle behaviors and symptoms of depression and anxiety during the COVID-19 lockdown in Canada. The findings highlight the importance of lifestyle medicine (LM) education and targeted lifestyle interventions to promote healthy behaviors and help reduce the burden of mental disorders.

The HARM models: Predicting longitudinal physical aggression in patients with schizophrenia at an individual level.

The prediction and prevention of aggression in individuals with schizophrenia remains a top priority within forensic psychiatric settings. While risk assessment methods are well rooted in forensic psychiatry, there are no available tools to predict longitudinal physical aggression in patients with schizophrenia within forensic settings at an individual level. In the present study, we used evidence-based risk and protective factors, as well as variables related to course of treatment assessed at baseline, to predict prospective incidents of physical aggression (4-month, 12-month, and 18-month follow-up) among 151 patients with schizophrenia within the forensic mental healthcare system. Across our HARM models, the balanced accuracy (sensitivity + specificity/2) of predicting physical aggressive incidents in patients with schizophrenia ranged from 59.73 to 87.33% at 4-month follow-up, 68.31-80.10% at 12-month follow-up, and 46.22-81.63% at 18-month follow-up, respectively. Additionally, we developed separate models, using clinician rated clinical judgement of short term and immediate violent risk, as a measure of comparison. Several modifiable evidence-based predictors of prospective physical aggression in schizophrenia were identified, including impulse control, substance abuse, impulsivity, treatment non-adherence, mood and psychotic symptoms, substance abuse, and poor family support. To the best of our knowledge, our HARM models are the first to predict longitudinal physical aggression at an individual level in patients with schizophrenia in forensic settings. However, it is important to caution that since these machine learning models were developed in the context of forensic settings, they may not be generalisable to individuals with schizophrenia more broadly. Moreover, a low base rate of physical aggression was observed in the testing set (6.0-11.6% across timepoints). As such, larger cohorts will be required to determine the replicability of these findings.

Biological rhythms disruption mediates the association between mother's diagnosis of bipolar disorder and offspring's emotional/behavioral problems.

OBJECTIVE: The current study assesses whether the association between diagnosis of Bipolar Disorder (BD) in mothers and emotional and behavioral problems (EBP) in their offspring is mediated by a disruption in the offspring's biological rhythms. METHODS: A probabilistic sample of 492 public school children (ages 7-8, 48 % female) were assessed for biological rhythms disruption and EBP using the Biological Rhythms Interview for Assessment in Neuropsychiatry for Kids and the Strengths and Difficulties Questionnaire, respectively. Mothers' mental health (BD = 64) was evaluated using a standardized clinical interview. A mediation analysis was conducted to assess the effect of the mother's diagnosis of BD on the EBP of their offspring in relation to the offspring's biological rhythms disruptions. RESULTS: When compared to offspring of mothers without BD, offspring of mothers with BD showed greater difficulty in maintaining biological rhythms and higher prevalence of EBP. Using the presence of EBP as the outcome, 75 % of the effect of mother's BD diagnosis was mediated by offspring's biological rhythms disruption. CONCLUSIONS: Biological rhythms disruption in children fully mediates the effect of the mother's diagnosis of BD on the child's EBP. These data encourage the development of further studies to find effective strategies to prevent and treat biological rhythms disruption in offspring of mothers with BD.

Childhood trauma, inflammatory biomarkers and the presence of a current depressive episode: Is there a relationship in subjects from a population study?

This study aims to compare the serum cytokine levels between controls, individuals with a current depressive episode (CDE) with childhood trauma and individuals with CDE without childhood trauma. This is a cross-sectional with paired sample nested in a population-based study. For the purposes of the current study, subjects who had psychotic symptoms, generalized anxiety disorder, and who refused to perform blood collection were excluded. Subsequently, only individuals who had a current depressive episode were selected (n = 76). Another 76 subjects were randomly paired by sex and age, constituting a population control group. The measurements of serum cytokine levels were performed using the multiplex analysis method. In the group with a CDE, when compared to the population control group, the following cytokines were high: IL-1ß, IL-2, IL-4, IL-6, IL-17A, IFN-γ and TNF-α (p < 0.05). On the other hand, there was a decrease in the levels of cytokines IL-10 (p = 0.027) and IL12p70 (p = 0.001). Bonferroni test demonstrates that there is no statistically significant difference in serum cytokine levels between subjects with a CDE, with and without trauma (p > 0.05). In a multivariable logistic regression, adjusting for socioeconomic status, tobacco, alcohol and illicit drugs abuse/dependence, and use of psychiatric medication, we found that cytokines serum levels remained associated with CDE even when adjusted for these potential confounders. Our findings demonstrate that monitoring cytokine levels and immune function may be beneficial in preventing the development of a CDE. However, future research is necessary to investigate the impact of trauma on the relationship between inflammation and CDE.

Theoretical procedures of the cross-cultural adaptation process of the Child Mania Rating Scale - Parent Version (CMRS-P) for the Brazilian context.

OBJECTIVES: To describe the theoretical procedures employed in the process of cross-cultural adaptation (CCA) for Brazil of the Child Mania Rating Scale - Parent Version (CMRS-P). METHODS: Seven steps were carried out: (1) translations and synthesis; (2) Committee of Judges-I; (3) grammatical review; (4) Committee of Judges-II; (5) semantic analysis (pre-test); (6) back-translation; and (7) discussion with the authors of the original instrument. Participants were two professional translators, 14 experts, a grammar proofreader, and 21 parents/guardians, representatives of the target population. The results were analyzed in terms of the percentage of agreement between evaluators and the content validity coefficient (CVC) and by analysis of comments and suggestions. RESULTS: Grammatical and cultural adjustments were made, in addition to substitution and/or inclusion of words and examples. Adequacy agreement indexes exceeding 86% were achieved and the CVC result for the total scale was excellent (0.95). The pre-test indicated good acceptance and understanding by participants. CONCLUSION: The proposed version proved to be promising for use in the Brazilian context, although further psychometric studies are still needed to prove the scale's validity and reliability.