Exploring protective factors in a high-risk subsample: the pivotal role of paternal support in preventing depression in a cohort of young adults.

BACKGROUND: Major depressive disorder (MDD) is a global concern due to its widespread prevalence and morbidity. Identifying protective factors in high-risk individuals, including those with a familial predisposition, maltreatment history, and socio-economic vulnerabilities, is crucial. METHODS: We assessed a high-risk subsample within a young adult population cohort (n = 791; mean age = 31.94 [SD = 2.18]) across three waves. Using multiple regression models to analyse higher education, feeling supported, spirituality, psychotherapy access, higher socioeconomic status, involvement in activities, cohabitation, and family unity in Waves 1 and 2, and their association with MDD resilience at Wave 3. RESULTS: In the high-risk group, MDD incidence was 13.7% (n=24). Paternal support had a protective effect on MDD incidence (OR = 0.366; 95% CI [0.137 to 0.955], p = 0.040) and suicidal attempt risk (OR = 0.380; 95% CI [0.150 to 0.956], p = 0.038). Higher resilience scores were also protective (OR = 0.975; 95% CI [0.953 to 0.997], p = 0.030), correlating with reduced BDI (r = 0.0484; B = -0.2202; 95% CI [-0.3572 to -0.0738]; p = 0.003) and MADRS scores (r = 0.0485; B = -0.2204; 95% CI [-0.3574 to -0.0741]; p = 0.003). CONCLUSIONS: Our paper emphasizes reorienting the MDD approach, focusing on positive prevention strategies. It highlights fathers' crucial role in family-based interventions and promoting resilience in high-risk populations.

Validating the efficacy and value proposition of mental fitness vocal biomarkers in a psychiatric population: prospective cohort study.

Background: The utility of vocal biomarkers for mental health assessment has gained increasing attention. This study aims to further this line of research by introducing a novel vocal scoring system designed to provide mental fitness tracking insights to users in real-world settings. Methods: A prospective cohort study with 104 outpatient psychiatric participants was conducted to validate the "Mental Fitness Vocal Biomarker" (MFVB) score. The MFVB score was derived from eight vocal features, selected based on literature review. Participants' mental health symptom severity was assessed using the M3 Checklist, which serves as a transdiagnostic tool for measuring depression, anxiety, post-traumatic stress disorder, and bipolar symptoms. Results: The MFVB demonstrated an ability to stratify individuals by their risk of elevated mental health symptom severity. Continuous observation enhanced the MFVB's efficacy, with risk ratios improving from 1.53 (1.09-2.14, p=0.0138) for single 30-second voice samples to 2.00 (1.21-3.30, p=0.0068) for data aggregated over two weeks. A higher risk ratio of 8.50 (2.31-31.25, p=0.0013) was observed in participants who used the MFVB 5-6 times per week, underscoring the utility of frequent and continuous observation. Participant feedback confirmed the user-friendliness of the application and its perceived benefits. Conclusions: The MFVB is a promising tool for objective mental health tracking in real-world conditions, with potential to be a cost-effective, scalable, and privacy-preserving adjunct to traditional psychiatric assessments. User feedback suggests that vocal biomarkers can offer personalized insights and support clinical therapy and other beneficial activities that are associated with improved mental health risks and outcomes.

Drug Repurposing and Personalized Treatment Strategies for Bipolar Disorder Using Transcriptomic.

OBJECTIVE: The present study combined transcriptomic data and computational techniques based on gene expression signatures to identify novel bioactive compounds or FDA-approved drugs for the management of Bipolar Disorder (BD). METHODS: Five transcriptomic datasets, comprising a total of 165 blood samples from BD case-control, were selected from the Gene Expression Omnibus repository (GEO). The number of subjects varied from 6 to 60, with a mean age ranging from 35 to 48, with a gender variation between them. Most of the patients were on pharmacological treatment. Master Regulator Analysis (MRA) and Gene Set Enrichment Analysis (GSEA) were performed to identify statistically significant genes between BD and HC and their association with the mood states of BD. Additionally, existing molecules with the potential to reverse the transcriptomic profiles of disease-altered regulons in BD were identified using the LINCS and cMap databases. RESULTS: MRA identified 59 potential MRs candidates modulating the regulatory units enriched with genes altered in BD, while the GSEA identified 134 enriched genes, and a total of 982 regulons had their activation state determined. Both analyses showed genes exclusively associated with mania, depression, or euthymia, and some genes were common between the three mood states. We identified bioactive compounds and licensed drug candidates, including antihypertensives and antineoplastics, as promising candidates for treating BD. Nevertheless, experimental validation is essential to authenticate these findings in subsequent studies. CONCLUSION: Although preliminary, our data provides some insights regarding the biological patterns of BD into distinct mood states and potential therapeutic targets. The combined transcriptomic and bioinformatics strategy offers a route to advance drug discovery and personalized medicine by tapping into gene expression information.

Perinatal factors as risk factors of bipolar disorder onset in young adulthood: a 22-year birth cohort.

BACKGROUND: Bipolar disorder (BD) is a leading cause of disability-adjusted life years in young adults. Complications during prenatal periods have been associated with BD previously. The study aims to examine the association between perinatal factors and BD in order to prevent the risk of developing BD. METHODS: 3,794 subjects from the 1993 Pelotas population-based birth cohort study were included. We assessed 27 initial variables at birth and modelled BD onset at 18 and 22 years. We performed bivariate analysis, using binomial logistic regression models. The variables with p-value smaller than 0.05 were included into a multiple regression with confounding variables. RESULTS: Maternal smoking was associated with a 1.42-fold increased risk of BD at 18 or 22 years old (95% CI: 1.091-1.841), and maternal passive exposure to tobacco with a 1.43-fold increased risk (95% CI: 1.086-1.875). No association was found between other perinatal factors and BD after controlling for confounding factors. CONCLUSION: The results of this cohort corroborate with previous findings in the literature that already indicate the negative outcomes of maternal smoking during pregnancy. They may now be linked to other studies to target these factors for preventing the development of BD.

Factors associated with suicide risk in young women with premenstrual dysphoric disorder: A population-based study.

PURPOSE: Women with premenstrual dysphoric disorder (PMDD) are more likely to report suicide ideation and behavior when compared to women without PMDD. However, there is a lack of studies investigating the risk factors for suicide risk in women with PMDD. Thus, the aim of this study is to assess the factors associated with suicide risk in young women with PMDD. METHODS: This is a cross-sectional study including 128 young women with PMDD who were recruited from the community. PMDD and suicide risk were assessed by trained psychologists using the Mini International Neuropsychiatric Interview (MINI-PLUS). Suicide risk evaluation includes six questions that assess suicidal intention, planning and previous attempts. Subjects who answer yes to any of the six questions are classified as having current suicide risk. RESULTS: The prevalence of current suicide risk in women with PMDD was 28.1%. The factors associated with suicide risk in this population were: presenting current panic disorder (OR: 18.71 [95% CI: 1.02 - 343.27], p=0.048), a non-white skin color (OR: 4.18 [CI 95%: 1.28 - 13.61], p=0.018), greater severity of depressive symptoms (OR: 1.22 [95% CI: 1.12 - 1.32], < 0.001), and history of childhood trauma (OR: 1.04 [95% CI: 1.01 - 1.08], 0.010). CONCLUSION: Our findings indicate that there are key sociodemographic and clinical factors associated with suicide risk in young women with PMDD, enabling clinicians to identify at-risk individuals who could benefit from further screening and interventions.

Early exposure to cannabis and bipolar disorder incidence: Findings from a 22-year birth cohort study in Brazil.

BACKGROUND AND OBJECTIVES: Bipolar disorder is a chronic condition affecting millions of people worldwide. Currently, there is some evidence to suggest that cannabis use during adolescence may be an environmental risk factor for its onset, however inconsistencies have been observed across the literature. Considering this, we aimed to assess whether early lifetime cannabis is associated with subsequent bipolar disorder in young adults between 18 and 22 years of age. METHODS: Using data from the 1993 Pelotas (Brazil) birth cohort (n = 5249), cannabis exposure was examined at age 18 by self-report, and bipolar disorder diagnosis was measured at age 22 using the Mini International Neuropsychiatric Interview (MINI). In order to control the analysis, we considered socioeconomic status index, sex, skin color, physical abuse by parents and lifetime cocaine use. RESULTS: A total of 3781 individuals were evaluated in 2015 aged 22 years, of whom 87 were diagnosed with the bipolar disorder onset after the age of 18. Lifetime cannabis use predicted bipolar disorder onset at 22 years old (OR 1.82, 95% CI [1.10, 2.93]), and the effect remained after adjusting for socioeconomic status, sex, skin color, and physical abuse by parents (OR 2.00, 95% CI [1.20, 3.25]). However, this association was attenuated to statistically non-significant after further adjustment for all available covariates, including lifetime cocaine use (OR 1.79, 95% CI [0.95, 3.19]). We also found similar results for early cocaine use, where the association with bipolar disorder onset did not maintain significance in the multivariate model (OR 1.35, 95% CI [0.62, 2.86]). Otherwise, when we considered cannabis or cocaine lifetime use as a unique feature, our findings showed that the adolescent exposure to cannabis or cocaine increased the odds by 1.95 times of developing bipolar disorder at 22 years age, even when controlling for all other study variables (OR 2.14, 95% CI [1.30, 3.47]). Finally, our models suggest that cocaine use may potentially exert a major influence on the effect of lifetime cannabis use on bipolar disorder onset, and that physical abuse by parents and sex may modify the effect of cannabis use for later bipolar disorder onset. CONCLUSION: Based on our findings, early cannabis exposure predicted bipolar disorder onset in young adults, but this association was confounded by cocaine use. Contrary to schizophrenia, cannabis as a sole exposure was not associated with bipolar disorder onset after adjusting for control variables.

Changes on risky drinking after the COVID-19 outbreak in Brazil: results from three consecutive web surveys.

INTRODUCTION: Risky drinking (RD) is associated with an increased risk of chronic and infectious diseases, injuries, and violence. This study aimed to assess changes in risky drinking (RD) in Brazil after COVID-19 outbreak, both overall and among individuals with self-reported chronic diseases and mental health disorders. METHODS: We conducted three independent, anonymous web surveys in Brazil including adult participants: S1 (April/2020, n=19,257), S2 (August/2020, n=1,590), and S3 (January/2021, n=859). Participants were recruited through adapted snowball sampling and sponsored social network advertisements. RD was assessed using the Alcohol Use Disorder Identification Test-Concise, designed to identify individuals at risk of alcohol-related problems. Logistic regression analyses with bootstrapping (B=2,000) were performed, with stratification by sex, age, education, employment, household size, and the presence of chronic and mental health conditions, as well as lifestyle factors, to address sample imbalances. RESULTS: The estimated prevalence of RD was 45.8% [95%CI 45.5, 46.1] in S1, 35.3% [95%CI 34.9, 35.6] in S2, and 33.7% [95%CI 33.3, 34.0] in S3. Participants with chronic diseases consistently presented lower RD prevalence across all three surveys, compared to those without such conditions. Conversely, individuals with mental health disorders presented higher RD prevalence than those without such diagnoses in S1 and S2, but not in S3. DISCUSSION: Despite the decrease in RD prevalence, monitoring of alcohol consumption trends remains essential for shaping effective public health policies. Additionally, the observed variations among individuals reporting chronic and mental health disorders highlight the need for targeted interventions in future crises.

Premorbid intelligence quotient and school failure as risk markers for bipolar disorder and major depressive disorder.

Mood disorders significantly impact global health, with MDD ranking as the second leading cause of disability in the United States and BD ranking 18th. Despite their prevalence and impact, the relationship between premorbid intelligence and the subsequent development of BD and MDD remains inconclusive. This study investigates the potential of premorbid Intelligence Quotient (IQ) and school failure frequency as risk factors for Bipolar Disorder (BD) and Major Depressive Disorder (MDD) in a birth cohort setting. We analyze data from the Pelotas population-based birth cohort study, comprising 3580 participants aged 22, who had no prior mood disorder diagnoses. Utilizing regression models and accounting for potential confounders, we assess the impact of IQ and school failure, measured at age 18, on the emergence of BD and MDD diagnoses at age 22, using individuals without mood disorders as comparators. Results reveal that lower IQ (below 70) at 18 is associated with an increased risk of BD (Adjusted Odds Ratio [AOR] 1.75, 95%CI: 1.00-3.09, p < 0.05), while higher IQ (above 120) is linked to MDD (AOR 2.16, 95%CI: 1.24-3.75, p < 0.001). Moreover, an elevated number of school failures is associated with increased BD risk (AOR 1.23, 95%CI: 1.11-1.41, p < 0.001), particularly for BD type 1 (AOR 1.36, 95% CI: 1.17-1.58, p < 0.001). These findings offer insights into the distinct premorbid intellectual characteristics of BD and MDD and contribute to a deeper understanding of their developmental trajectories, potentially informing the development of risk assessment tools for mood disorders.

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.

Cannabidiol as an Adjunctive Treatment for Acute Bipolar Depression: A Pilot Study: Le cannabidiol comme traitement d'appoint de la dépression bipolaire aiguë : une étude pilote.

OBJECTIVE: The treatment of bipolar depression remains challenging due to the limited effective and safe therapeutic options available; thus, developing newer treatments that are effective and well tolerable is an urgent unmet need. The objective of the present trial was to test 150 to 300 mg/day of cannabidiol as an adjunctive treatment for bipolar depression. METHOD: A randomized, double-blind, placebo-controlled pilot study to assess the efficacy of adjunctive cannabidiol in bipolar depression was used. Efficacy parameters were changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 8. Secondary outcomes included response and remission rates, changes in anxiety and psychotic symptoms, and changes in functioning. Patients continued double-blind treatment until week 12 to monitor for adverse effects, laboratory analysis, and manic symptoms. Study registry: NCT03310593. RESULTS: A total of 35 participants were included. MADRS scores significantly decreased from baseline to the endpoint (placebo, -14.56; cannabidiol, -15.38), but there was no significant difference between the groups. Similarly, there were no other significant effects on the secondary outcomes. However, an exploratory analysis showed a significant effect of cannabidiol 300 mg/day in reducing MADRS scores from week 2 to week 8 (placebo, -6.64; cannabidiol, -13.72). There were no significant differences in the development of manic symptoms or any other adverse effects. CONCLUSION: Cannabidiol did not show significantly higher adverse effects than placebo. Despite the negative finding on the primary outcome, an exploratory analysis suggested that cannabidiol should be further studied in bipolar depression in higher doses of at least 300 mg/day and under research designs that could better control for high placebo response.

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.

Does the intensity of dissociation predict antidepressant effects 24 hours after infusion of racemic ketamine and esketamine in treatment-resistant depression? A secondary analysis from a randomized controlled trial.

BACKGROUND: Ketamine and esketamine have both shown significant antidepressant effects in treatment-resistant depression (TRD), and conflicting evidence suggests that induced dissociation by these drugs can be a clinical predictor of esketamine/ketamine's efficacy. METHODS: This study is a secondary analysis from a bi-center, randomized, controlled trial. Participants were randomly assigned 1:1 to receive an IV infusion of esketamine (.25 mg/kg) or racemic ketamine (.50 mg/kg) over 40 minutes. Dissociative symptoms were assessed using the Clinician-Administered Dissociative State Scale (CADSS) 40 minutes following the beginning of the infusion. The variation in depression scores was measured with the Montgomery-Asberg Depression Rating Scale (MADRS), which was administered before the intervention as a baseline measure and 24 hrs, 72 hrs, and 7 days following infusion. RESULTS: Sixty-one patients were included in the analysis. Examining CADSS scores of 15 or below, for every 1-point increment in the CADSS score, there was a mean change of -0.5 (SD = 0.25; p-value 0.04) of predicted MADRS score from baseline to 24 hrs. The results for 72 hrs and 7 days following infusion were not significant. Limitations: This study was not designed to assess the relationship between ketamine or esketamine-induced dissociation and antidepressant effects as the main outcome, therefore confounding variables for this relationship were not controlled. CONCLUSION: We suggest a positive relationship between dissociation intensity, measured by CADSS, and antidepressant effect 24 hours after ketamine and esketamine infusion for a CADSS score of up to 15 points.

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.

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.

Genetics of cannabis use in opioid use disorder: A genome-wide association and polygenic risk score study.

BACKGROUND: Individuals with an Opioid Use Disorder (OUD) have increased rates of cannabis use in comparison to the general population. Research on the short- and long-term impacts of cannabis use in OUD patients has been inconclusive. A genetic component may contribute to cannabis cravings. AIMS: Identify genetic variants associated with cannabis use through Genome-wide Association Study (GWAS) methods and investigate a Polygenic Risk Score (PRS). In addition, we aim to identify any sex differences in effect size for genetic variants reaching or nearing genome-wide significance in the GWAS. METHODS: The study outcomes of interest were: regular cannabis use (yes/no) (n = 2616), heaviness of cannabis use (n = 1293) and cannabis cravings (n = 836). Logistic and linear regressions were preformed, respectively, to test the association between genetic variants and each outcome, regular cannabis use and heaviness of cannabis use. GWAS summary statistics from a recent large meta-GWAS investigating cannabis use disorder were used to conduct PRS's. Findings are limited to a European ancestry sample. RESULTS: No genome-wide significant associations were found. Rs1813412 (chromosome 17) for regular cannabis use and rs62378502 (chromosome 5) for heaviness of cannabis use were approaching genome-wide significance. Both these SNPs were nominally significant (p<0.05) within males and females, however sex did not modify the association. The PRS identified statistically significant association with cannabis cravings. The variance explained by all PRSs were less than 1.02x10-2. CONCLUSION: This study provides promising results in understanding the genetic contribution to cannabis use in individuals living with OUD.

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.