Lifetime cocaine use is a potential predictor for conversion from major depressive disorder to bipolar disorder: A prospective study.

AIM: We aimed to identify whether lifetime cocaine use is a risk factor for conversion from major depressive disorder (MDD) to bipolar disorder (BD) in an outpatient sample of adults. METHODS: This prospective cohort study included 585 subjects aged 18 to 60 years who had been diagnosed with MDD as assessed by the Mini International Neuropsychiatric Interview (MINI-Plus) at baseline (2012-2015). Subjects were reassessed a mean of 3 years later (2017-2018) for potential conversion to BD as assessed by the MINI-Plus. Lifetime cocaine use was assessed using the Alcohol, Smoking, and Substance Involvement Screening Test. RESULTS: In the second wave, we had 117 (20%) losses, and 468 patients were reassessed. The rate of conversion from MDD to BD in 3 years was 12.4% (n = 58). A logistic regression analysis showed that the risk for conversion from MDD to BD was 3.41-fold higher (95% confidence interval, 1.11-10.43) in subjects who reported lifetime cocaine use at baseline as compared to individuals who did not report lifetime cocaine use at baseline, after adjusting for demographic and clinical confounders. CONCLUSION: These findings showed that lifetime cocaine use is a potential predictor of conversion to BD in an MDD cohort. Further studies are needed to assess the possible underlying mechanisms linking exposure to cocaine with BD conversion.

Serum level of nerve growth factor is a potential biomarker of conversion to bipolar disorder in women with major depressive disorder.

AIM: The aim of this study was to identify biomarkers associated with major depressive disorder (MDD) and conversion from MDD to bipolar disorder (BD) in an outpatient sample of women. METHODS: This was a longitudinal study including women diagnosed with MDD and aged 18 to 60 years. The follow-up was 3 years. The diagnosis was performed using the Mini International Neuropsychiatric Interview Plus. Blood collection was just performed in the first phase. Serum interleukin-6, tumor necrosis factor-α, brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and nerve growth factor (NGF) levels were measured using a commercial immunoassay kit. RESULTS: We included 156 women. The conversion rate from MDD to BD was 15.4% (n = 24). NGF serum levels were increased in patients who converted to BD compared to the remitted MDD group and current MDD group (P = 0.013). The Bonferroni post-hoc test for multiple comparisons revealed significant differences for higher NGF levels in patients who converted to BD compared to patients with current MDD (P = 0.037). Interleukin-6, tumor necrosis factor-α, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor serum levels did not differ among the groups. CONCLUSION: Our results suggest that NGF might be a useful biomarker associated with early detection of conversion to BD, helping clinicians in the clinical diagnosis.

Association between obesity and suicide in woman, but not in man: a population-based study of young adults.

The relationship between obesity and suicide risk is still unclear with controversial research results. The aim of this study is to investigate the relationship between obesity and suicide risk for men and women in a population-based study of young adults. This is a cross-sectional population-based study that identified young adults between 18 and 35 years of age. Suicide risk was investigated through the structured clinical interview Mini. Weight and height were assessed, and participants were classified as normal-weight body mass index (BMI < 30) or obese (BMI > 30). The prevalence of obesity was of 19.9% of the total sample (n = 1953). Obesity was more prevalent among women and participants between 27 and 35 years of age. Suicide risk was present in 13.0% of the sample and more prevalent among women. In our study we found an association between obesity and suicide risk for women, but not for men. Obesity was associated with a higher prevalence of suicide risk in women. Given the strength of the relationship between BMI and suicide, identifying the mechanisms associated with obesity, especially for women, can lead to new insights into the prevention of suicide risk.

The role of metabolic syndrome as a mediator in the relationship between CCL11 levels and the presence of a mood episode with mixed features in young adults with bipolar disorder.

Mixed features presentation in bipolar disorder (BD) represents the most severe form of the disease. BD may lead to cognitive and functional deterioration, a process known as neuroprogression, which appears to be exacerbated by increased serum levels of CCL11, a neuroprogression-related cytokine. Metabolic syndrome (MetS) is highly prevalent in BD, and it is known that the presence of MetS may increase inflammation, which may contribute to increased CCL11 levels, and consequently impact on the severity of the disorder. What is not known is whether the MetS mediates the association between CCL11 levels and the presence of mood episodes with mixed features in BD. Therefore, the aim of this study was to investigate the mediating effect of MetS on the relationship between CCL11 levels and the presence of mood episodes with mixed features in BD, in a population-based study. This is a cross-sectional study that included 184 young adults, 92 with BD and 92 populational controls, matched by sex and age. BD diagnosis was assessed using the Mini International Neuropsychiatric Interview - PLUS. Mood episodes with mixed features was defined according to DSM-IV and DSM-5 criteria. MetS was defined according to the National Cholesterol Education Program (NCEP/ATP III). Substance use was assessed through the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). CCL11 serum levels were analyzed using the multiplex analysis method Luminex 200™ system. The mediation model was tested using the MedMod module of the JAMOVI 2.4.8 software. Mediation analysis indicated a trend towards significance of MetS mediating the association between CCL11 and the presence of a mood episode with mixed features in BD (p = 0.065). Individuals with BD presenting with a mood episode with mixed features and MetS may have accelerated neuroprogression due to the influence of MetS on CCL11 levels, therefore, assessing for MetS occurrence in this population and implementing early interventions to prevent its development may be effective ways of delaying cognitive impairments related to this cytokine.

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.

Predictors of illicit substance abuse/dependence during young adulthood: A machine learning approach.

Prior studies have found an especially high prevalence of illicit substance use among adolescents and young adults in Brazil. The current study aimed to employ machine learning techniques to identify predictors of illicit substance abuse/dependence among a large community sample of young adults followed for 5 years. This prospective, population-based cohort study included a sample of young adults between the ages of 18-24 years from Pelotas, Brazil at baseline (T1). The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) was used to assess illicit substance abuse/dependence. A clinical interview was conducted to collect data on sociodemographic characteristics and psychopathology. Elastic net was used to generate a regularized linear model for the machine learning component of this study, which followed standard machine learning protocols. A total of 1560 young adults were assessed at T1, while 1244 were reassessed at the 5-year follow-up period (T2). The strongest predictors of illicit substance abuse/dependence at baseline (AUC of 0.83) were alcohol abuse/dependence, tobacco abuse/dependence, being in a current major depressive episode, history of a lifetime manic episode, current suicide risk, and male sex. The strongest predictors for illicit substance abuse/dependence at the 5-year follow-up (AUC: 0.79) were tobacco abuse/dependence at T1, history of a lifetime manic episode at T1, male sex, alcohol abuse/dependence at T1, and current suicide risk at T1. Our findings indicate that machine learning techniques hold the potential to predict illicit substance abuse/dependence among young adults using sociodemographic/clinical characteristics, with relatively high accuracy.

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.

Predictors of conversion from major depressive disorder to bipolar disorder.

The present study has two main aims: (1) To assess whether childhood trauma helps to differentiate Major Depressive Disorder (MDD) from Bipolar Disorder (BD) in a cross-sectional design; and (2) Describe the rate of conversion from MDD to BD, as well as the clinical and demographic predictors of conversion from MDD to BD in a prospective cohort design. We conducted a prospective cohort study in two phases, in the city of Pelotas, RS, Brazil. In the first phase, 565 subjects diagnosed with MDD, and 127 with BD according to the Mini International Neuropsychiatric Interview were included. In the second phase, only individuals with MDD were reevaluated for potential conversion to BD. The rate of conversion from MDD to BD in 3 years was 12.4%. Predictors of conversion from MDD to BD included lower educational level, use of illicit substances, younger age of the first depressive episode, and family history of BD. Childhood trauma was not a significant risk factor for conversion to BD in our prospective study. Our findings can contribute to the prevention and identification of conversion from MDD to BD, as well as to the establishment of more targeted therapeutic interventions, improving the prognosis of these individuals.

Sleep alterations in individuals recently diagnosed with bipolar disorder across different mood stages.

OBJECTIVES: To assess the differences in sleep impairments in major depressive disorder (MDD) and individuals recently diagnosed with bipolar disorder (BD) across different mood stages. METHODS: This is a cross-sectional study corresponding to the second wave of a prospective clinical cohort of a sample of outpatients. The first wave included subjects diagnosed with MDD aged 18 to 60 years. Averaging 3 years after the first phase (second wave), conversion from MDD to BD diagnosis was assessed using the Mini International Neuropsychiatric Interview. The total sample was divided into four groups: euthymic MDD, MDD in a current episode, euthymic BD, and BD in a current mood episode. The sleep alterations were assessed using the Pittsburgh Sleep Quality Index. RESULTS: The sample included 468 subjects (261 euthymic MDD, 149 MDD currently depressed, 16 euthymic BD, and 42 BDs currently in a (hypo)manic or depressive episode). Euthymic BD differed from euthymic MDD only in the domains of sleep efficiency and sleep disturbances, showing lower sleep efficiency (PR 4.91 [95%CI 1.94 - 12.42]) and higher sleep disturbances (PR 3.38 [95%CI 1.32 - 8.67]) in subjects recently diagnosed with BD during euthymia. These differences remained significant after adjusting for the potential confounding factors. CONCLUSIONS: The findings point out the relevance of regular sleep assessments in individuals recently diagnosed with BD, since the differences in sleep quality observed could provide insights regarding prognosis, treatment, and the extent to which these individuals display significant subsyndromal symptomatology, even in the absence of a mood episode.

Cognitive complaints in individuals recently diagnosed with bipolar disorder: A cross-sectional study.

AIM: To assess the differences in subjective cognitive dysfunction between major depressive disorder (MDD) and recently diagnosed Bipolar Disorder (BD) across euthymia and mood episodes. METHODS: This is a cross-sectional study corresponding to the second wave of a longitudinal study. The first wave consisted of subjects aged between 18 and 60 diagnosed with MDD. In the follow up after three years (second wave), conversion from MDD to BD diagnosis was assessed by qualified psychologists using the Mini International Neuropsychiatric Interview (MINI-Plus). Subjects were categorized in four diagnostic groups: euthymic MDD, MDD in a current mood episode, euthymic BD, and BD in a current mood episode. All subjects completed the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA), an instrument specifically designed for detecting subjective cognitive deficits in BD. RESULTS: The total sample (n = 468) included 410 subjects with MDD and 58 individuals recently diagnosed with BD. We subdivided the 2 groups based on their current mood state, and found a significant difference in COBRA total scores between euthymic BD individuals (median 17.00 [IQR: 8.75 - 20.75]) and euthymic MDD subjects (median 8.00 [IRQ: 5.00 - 14.00], p = 0.002), showing higher subjective cognitive dysfunction in individuals recently diagnosed with BD. The differences remained significant after adjusting for the presence of lifetime psychotic symptoms. We found no differences between MDD and BD during an acute mood episode. LIMITATION: The small sample size of individuals with BD. CONCLUSION: The findings suggest a higher presence of subjective cognitive complaints among individuals recently diagnosed with BD in comparison to individuals with MDD during euthymia.

Effects of depression and excess body weight on cognition and functioning in young adults: A population-based study.

OBJECTIVES: The purpose of this study is to assess the independent effects of depression and excess body weight (EBW) on cognition and functioning in a community sample of young adults. METHODS: This was a cross-sectional of 943 young adults. The diagnosis of a current depressive episode was performed using the Mini International Neuropsychiatric Interview (MINI). Cognition and functioning were assessed using the Montreal Cognitive Assessment (MoCA) and the Functional Assessment Short Test (FAST), respectively. The EBW was defined as BMI ≥ 25.0 kg/m2. The independent main effects of depression and EBW, as well as the analysis interaction were performed using two-way analysis of covariance (ANCOVA). RESULTS: The total sample comprised 943 adults, with 75 (8.0%) individuals diagnosed with a current depressive episode and 493 (52,6%) with EBW. Of the 75 subjects with depression, 40 were identified with EBW comorbidity. Subjects with depression and EBW comorbidity reported greater cognitive and functional impairment, as compared to individuals with depression without EBW. There was a significant interaction between depression and EBW on MoCA total (p<0.001) as well as FAST total (p=0.010), work (p=0.002), cognition (p=0.023), finances (p=0.032) and relationships domains (p=0.008). CONCLUSIONS: The adverse effects of depression and EBW are independent and cumulative with respect to cognition and functioning of individuals. The understanding of the complex interactions between cognition, functioning, EBW and depression are important for development of preventive and therapeutic strategies.

Childhood trauma and bipolar spectrum: a population-based sample of young adults.

Introduction Childhood trauma has been suggested to be involved in susceptibility to bipolar disorder (BP). However, it remains unclear whether the occurrence of childhood trauma is differently distributed in subthreshold bipolar disorder (SBP). Objective To assess childhood trauma in young adults with SBP, as compared to young adults with BP and population controls (PC). Method This was a cross-sectional, population-based study. The Mini International Neuropsychiatric Interview (MINI) was used to define the groups with BP (subjects with a lifetime or current manic episode or lifetime or current hypomania with a history of a depressive episode), SBP (subjects with a history of hypomanic episode without lifetime or current depressive episode), and subjects without mood disorders (PC). Childhood trauma was assessed using de Childhood Trauma Questionnaire (CTQ). We investigated differences regarding childhood trauma across the three groups (BP, SBP and PC). Result Except for sexual abuse, all subtypes of childhood trauma remained associated with the BP group as compared to PC. Additionally, when we compared SBP and BP, significant differences were found only for emotional abuse. No significant differences were found in relation to childhood trauma between the SBP and PC groups after adjusting for confounding factors. Conclusion These findings suggest that investigating childhood trauma, with a particular focus on emotional abuse, could be considered a preventive measure and potentially improve the prognosis.

Resilience as a mediator factor in the relationship between childhood trauma and mood disorder: A community sample of young adults.

BACKGROUND: Studies on the field of mood disorders has mainly focusing on the risk factors associated to develop the illness or the clinical factors associated with the clinical progression. Less attention was given to factors such as resilience that may be associated with better outcomes in the course of mood disorders. In this study, we assessed the mediation effect of resilience on the relationship between childhood trauma and mood disorders, as well as the severity of depressive symptoms in a population-based sample. METHODS: This is a cross-sectional study with a community sample of young adults with bipolar disorder (BD), major depressive disorder (MDD), and community controls without any mood disorder. The trauma experiences during childhood were assessed by Childhood Trauma Questionnaire (CTQ). The severity of depressive symptoms was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and to assess the resilience was used the Resilience Scale (RS-25). RESULTS: All subtypes of trauma were associated with both MDD and BD, however, only physical and emotional abuse differentiated BD from MDD subjects. Bootstrapping-enhanced mediation analyses indicated that resilience partly mediated the association of childhood trauma to both mood disorder and severity of depression. LIMITATION: The employed mediation analyses are cross-sectional in nature, which limits any firm conclusions regarding causality. CONCLUSIONS: The findings support the clinical assumption that resilient subjects may be partly protected against the detrimental long-term effects of childhood trauma. This study provides important information regarding the relationships among childhood trauma, resilience, and mood disorder.

Childhood trauma and increased peripheral cytokines in young adults with major depressive: Population-based study.

OBJECTIVE: The aim of this study was to evaluate the effect of childhood trauma in cytokine serum levels of individuals with MDD. METHODS: This was a cross-sectional study population-based, with people aged 18 to 35. The Mini International Neuropsychiatric Interview (M.I.N.I) measured to current major depressive disorder (MDD). To evaluate traumatic experiences during childhood, the Childhood Trauma Questionnaire (CTQ) was applied. Serum TNF- α, IL-6 and IL-10 levels were measured by ELISA using a commercial kit. RESULTS: The total sample comprised 166 young adults, of these: 40.4% were subjects with MDD and childhood trauma and 59.6% were diagnosed with MDD without childhood trauma. In relation to serum interleukin levels, subjects with childhood trauma showed a significantly higher serum IL-6 (p = 0.013) and IL-10 levels (p = 0.022) to compare no childhood trauma. Subjects with childhood trauma was observed positive correlation between serum IL-6 and physical abuse (r = 0.232, p = 0.035) and emotional abuse (r = 0.460, p ≤ 0.001). Moreover, IL-10 were positive correlation with physical abuse (r = 0.258, p = 0.013). TNF- α was not associated with childhood trauma. CONCLUSION: Childhood maltreatment may result higher inflammation dysregulation in individuals with depression than individuals that no has childhood maltreatment.

Serum GDNF levels and anxiety disorders in a population-based study of young adults.

OBJECTIVE: The aim of this study was to verify the serum GDNF levels in individuals with anxiety disorder (AD) in a population-based study. METHODS: This was a cross-sectional study population-based, with people aged 18 to 35. AD's assessment was performed using the Mini International Neuropsychiatric Interview (M.I.N.I). Serum GDNF was measured by ELISA using a commercial kit. RESULTS: The prevalence was 3.3% for post-traumatic stress disorder, 6.7% for panic disorders, 17% generalized anxiety disorder, 5.1% for obsessive- compulsive disorder and 7.5% for social phobia. Serum GDNF levels was higher in individuals with panic disorders (p = 0.013), generalized anxiety (p = 0.035), obsessive- compulsive disorder (p = 0.005) and social phobia (p = 0.004), when compared to individuals without ADs. Only post traumatic stress disorder is not associated with serum GDNF levels (p = 0.119). CONCLUSION: In this paper, we observed increased serum levels of GDNF in individuals with anxiety disorders, suggesting that this biomarker can be used as a putative marker for AD's. The knowledge of the physiological changes related to anxiety disorders can provide a better understanding of AD's pathogenesis, as well as, mechanisms involved in the progression of this condition.

Serum brain-derived neurotrophic factor levels in subjects with major depressive disorder with previous suicide attempt: A population-based study.

Major depressive disorders (MDD) and suicide are significant public health concerns. Recent studies have been demonstrated that alterations in Brain Derived Neurotrophic Factor (BDNF) can be associated with this psychiatric disorders, MDD and suicide. Thus, the aim of this study was to evaluate differences in serum levels in individuals with MDD and with or without suicide attempt (SA), from a population-based sample. This was a paired cross-sectional study nested in a population-based study. The psychopathology screen was performed with the Mini-International Neuropsychiatric Interview (MINI). The total population of the sample consisted of 147 subjects distributed in three groups: 49 healthy controls, 49 subjects with MDD and 49 subjects with MDD and SA (MDD + SA). The BDNF serum levels were significantly reduced in subjects with MDD and MDD + SA compared to the healthy controls. However, there were no significant differences between the MDD and MDD + SA groups with respect to BDNF serum levels. These results suggest that SA did not interfere in the serum levels of BDNF, indicating that this neurotrophin may be related to the diagnosis of MDD and not to suicide attempt.

Childhood trauma and bipolar spectrum: a population-based sample of young adults

Abstract Introduction Childhood trauma has been suggested to be involved in susceptibility to bipolar disorder (BP). However, it remains unclear whether the occurrence of childhood trauma is differently distributed in subthreshold bipolar disorder (SBP). Objective To assess childhood trauma in young adults with SBP, as compared to young adults with BP and population controls (PC). Method This was a cross-sectional, population-based study. The Mini International Neuropsychiatric Interview (MINI) was used to define the groups with BP (subjects with a lifetime or current manic episode or lifetime or current hypomania with a history of a depressive episode), SBP (subjects with a history of hypomanic episode without lifetime or current depressive episode), and subjects without mood disorders (PC). Childhood trauma was assessed using de Childhood Trauma Questionnaire (CTQ). We investigated differences regarding childhood trauma across the three groups (BP, SBP and PC). Result Except for sexual abuse, all subtypes of childhood trauma remained associated with the BP group as compared to PC. Additionally, when we compared SBP and BP, significant differences were found only for emotional abuse. No significant differences were found in relation to childhood trauma between the SBP and PC groups after adjusting for confounding factors. Conclusion These findings suggest that investigating childhood trauma, with a particular focus on emotional abuse, could be considered a preventive measure and potentially improve the prognosis.

Serum levels of nerve growth factor (NGF) in patients with major depression disorder and suicide risk.

Nerve growth factor (NGF) is an important member of the neurotrophins group and their involvement in the pathophysiology of major depression disorder (MDD) and suicide risk (SR) has been recently suggested. The aim of this study is to evaluate the changes in NGF serum levels in individuals with MDD and with or without risk of suicide, in subjects from a young population-based sample. This is a paired cross-sectional study nested in a population-based study. Individuals were rated for MDD and SR by a diagnostic interview--Mini International Neuropsychiatric Interview (M.I.N.I). The total population of the sample was comprised of 141 subjects distributed in three groups: 47 healthy controls, 47 subjects with current depressive episode without SR (MDD) and 47 subjects with current depressive episode and with SR (MDD + SR). NGF serum levels were significantly reduced in the MDD and MDD + SR groups when compared with controls (p ≤ 0.001). However, there were no differences in NGF levels between the MDD and MDD + SR groups (p = 1.000). These results suggest that reduced NGF serum levels can be a possible biomarker of MDD.