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BACKGROUND: Major Depressive Disorder (MDD) and obesity are bidirectionally related, but the amount of weight-gain secondary to MDD is unknown. We aimed to estimate the adjusted effect of MDD on weight-change in prospective studies compared to individuals without MDD. METHODS: Scopus/MEDLINE, PsycInfo, Web of Science and Cochrane were systematically searched for prospective observational studies of participants with a diagnosis of MDD. We included studies that conducted regression analyses on weight-variables. We searched for weight-variables reported at baseline, follow-up, and regression analyses. A meta-analysis of the odds ratios reported in logistic regression models was performed using the generic inverse weight variance method. RESULTS: Eight studies were included with a total of 60,443 subjects; 56.8 % with MDD. Weight-variables included weight, BMI, waist circumference, fat mass, and obesity incidence. In three follow-up reports, weight-variables increased more in participants with MDD and its subphenotypes than in control subjects, except for one MDD subphenotype. Meta-analysis of three eligible studies (n = 21,935) showed a significantly greater likelihood of incident obesity in participants with MDD (OR:1.48, 95%CI 1.03-2.13). MDD subphenotype reports might suggest a greater risk for atypical MDD. LIMITATIONS: Heterogeneity in weight related variables, follow-ups, and regression models; scarcity of follow-up data; and limited studies eligible for meta-analysis. CONCLUSIONS: Despite previous associations between MDD and obesity, current prospective evidence on MDD related weight-change is scarce and heterogeneous. Our findings suggest a need to standardize weight-change assessment in MDD trials. Moreover, careful weight tracking and management should be incorporated in clinical settings. PROSPERO registration CRD42020214427.
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Transtorno Depressivo Maior , Adulto , Humanos , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/diagnóstico , Estudos Prospectivos , Obesidade/epidemiologia , Aumento de Peso , Estudos Observacionais como AssuntoRESUMO
BACKGROUND: Treatment in bipolar disorder (BD) is commonly applied as a multimodal therapy based on decision algorithms that lack an integrative understanding of molecular mechanisms or a biomarker associated clinical outcome measure. Pharmacogenetics/genomics study the individual genetic variation associated with drug response. This selective review of pharmacogenomics and pharmacogenomic testing (PGT) in BD will focus on candidate genes and genome wide association studies of pharmacokinetic drug metabolism and pharmacodynamic drug response/adverse event, and the potential role of decision support tools that incorporate multiple genotype/phenotype drug recommendations. MAIN BODY: We searched PubMed from January 2013 to May 2019, to identify studies reporting on BD and pharmacogenetics, pharmacogenomics and PGT. Studies were selected considering their contribution to the field. We summarize our findings in: targeted candidate genes of pharmacokinetic and pharmacodynamic pathways, genome-wide association studies and, PGT platforms, related to BD treatment. This field has grown from studies of metabolizing enzymes (i.e., pharmacokinetics) and drug transporters (i.e., pharmacodynamics), to untargeted investigations across the entire genome with the potential to merge genomic data with additional biological information. CONCLUSIONS: The complexity of BD genetics and, the heterogeneity in BD drug-related phenotypes, are important considerations for the design and interpretation of BD PGT. The clinical applicability of PGT in psychiatry is in its infancy and is far from reaching the robust impact it has in other medical disciplines. Nonetheless, promising findings are discovered with increasing frequency with remarkable relevance in neuroscience, pharmacology and biology.
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BACKGROUND: Major depressive disorder (MDD) is highly prevalent among medical students (MS). Abuse experiences, as well as stress, are among the factors associated with MDD. However, their association with MDD in MS has been scarcely addressed. METHODS: A cross-sectional study design was used to evaluate the association between MDD and possible risk factors, focusing on current and past abuse experiences inside and outside the academic setting in a large representative MS sample (nâ¯=â¯1,068) using self-report instruments to assess MDD (PHQ-9) and perceived academic stress levels during exam season. RESULTS: Depressive symptom severity directly correlates with levels of perceived academic stress. The prevalence of MDD was 16.2%. A history of emotional abuse during childhood or adolescence, as well as most types of current abuse were associated with MDD. Multiple logistic regression analysis showed that current emotional abuse outside school had the strongest association with MDD in MS, followed by a personal history of depression and suicide attempt, a family history of depression, and perceived academic stress levels. LIMITATIONS: Cross-sectional design, participants represent a specific population, and other variables that could be associated with MDD: comorbid psychiatric disorders, current antidepressant treatment and protective factors (resilience and health-promoting coping strategies) were not evaluated. CONCLUSIONS: MDD is strongly associated with several risk factors that include most types of current and past abuse experiences. Timely identification of individuals at-risk will be critical to establish preventive strategies to limit the impact of MDD in MS and offer prompt therapeutic alternatives when needed.
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Maus-Tratos Infantis/psicologia , Transtorno Depressivo Maior/psicologia , Estudantes de Medicina/psicologia , Adolescente , Adulto , Criança , Estudos Transversais , Transtorno Depressivo Maior/epidemiologia , Família , Feminino , Humanos , Masculino , Transtornos Mentais/psicologia , México/epidemiologia , Fatores de Risco , Fatores Socioeconômicos , Estresse Psicológico/psicologia , Tentativa de Suicídio , Adulto JovemRESUMO
OBJECTIVES: The prevalence of obesity has dramatically increased in many countries and it is particularly high in patients with bipolar disorder (BD). A region in the first intron of the fat mass- and obesity-associated (FTO) gene, encompassing markers rs9939973, rs8050136, and rs9939609, has been consistently associated with obesity and body mass index (BMI) in different populations. We sought to determine whether FTO is associated with BMI and/or obesity in patients with BD. METHODS: The sample included 129 Mexican Mestizo patients with bipolar I or bipolar II disorder. After obtaining informed consent, participants were evaluated with the Structured Clinical Interview for DSM-IV Axis I Disorders and weight, height, and body measurements were recorded. DNA was extracted from a 5-mL blood sample and real-time polymerase chain reaction was performed. The results were analyzed with Haploview v4.2 and SPSS v21. RESULTS: Differences in mean BMI were explained by rs8050136 and rs9939609 genotypes, especially by comparing non-carriers and carriers of two copies of the risk allele (Tukey's p ≤ 0.019), with a mean difference in BMI as high as 7.81 kg/m(2) . Differences in BMI were also explained by the interaction of the genotype (rs8050136 and/or rs9939609), the use of second-generation antipsychotics, and the use of mood stabilizers (p ≤ 0.41). Obesity was also associated with these two markers when patients with and without obesity were compared. CONCLUSIONS: In patients with BD, differences in BMI may be affected by the presence of FTO risk alleles, especially in homozygous individuals for these variants. Besides evaluating the possible metabolic effects of certain antipsychotics or mood stabilizers, it is important to evaluate the role of other factors such as FTO risk alleles.
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Antipsicóticos/farmacologia , Transtorno Bipolar , Índice de Massa Corporal , Obesidade , Proteínas/genética , Alelos , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/genética , Transtorno Bipolar/fisiopatologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Genótipo , Humanos , Masculino , México , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/genética , Obesidade/psicologiaRESUMO
INTRODUCTION: AFECTS is a novel psychometric instrument that provides an integrated framework based on affective temperamental traits and their trait dimensions. It has the potential to be used in clinical and research fields to study psychopathology and mental health. It is now necessary to field-test this instrument with diverse populations and psychopathological entities. OBJECTIVE: The primary aim was to test the construct validity and the internal consistency of the Spanish Version of the AFECTS instrument on Mexican subjects. AFECTS characteristics were then compared between general population and stable psychiatric patients. METHODS: A cross-sectional design involving 350 subjects from the general population in México City and 91 stable patients with a bipolar disorder (BPD, n=20), major depressive disorder (MDD, n=35), or with a schizophrenia (n=36) diagnosis. RESULTS: A six-factor structure in trait dimensions, explaining 61.4% of the variance, with a Cronbach׳s alpha of 0.93 was found. Euthymic (23%) and hyperthymic (12%) affective temperaments were the most frequent, while dysphoric (3%) and apathetic (3%) were the least. Trait dimension differences were found in Volition, Sensitivity, and the Instability Index between the groups, particularly those with a bipolar disorder. LIMITATIONS: Use of a self report instrument, and a small sample not representative of the Mexican population or patients with psychiatric conditions. CONCLUSIONS: The Spanish Version of the AFECTS instrument has adequate psychometric properties. This version of AFECTS will allow the use of this instrument among Spanish speaking populations and contribute to the continued research efforts on integrative models such as AFECT.
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Transtorno Bipolar/psicologia , Transtorno Depressivo Maior/psicologia , Personalidade , Inquéritos e Questionários/normas , Temperamento , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , PsicometriaRESUMO
OBJECTIVE: Second-generation antipsychotics (SGAs) are among the first-line treatments for bipolar disorder and schizophrenia, but have a tendency to generate metabolic disturbances. These features resemble a metabolic syndrome for which a central autonomic imbalance has been proposed that may originate from the hypothalamic suprachiasmatic nuclei. In a clinical trial, we hypothesized that melatonin, a hormone that regulates the suprachiasmatic nucleus, could attenuate SGA-induced adverse metabolic effects. METHODS: In an eight-week, double-blind, randomized, placebo-controlled, parallel-group clinical trial, we evaluated the metabolic effect of melatonin in SGA-treated patients in terms of weight, blood pressure, lipid, glucose, body composition, and anthropometric measures. A total of 44 patients treated with SGAs, 20 with bipolar disorder and 24 with schizophrenia, randomly received placebo (n = 24) or melatonin 5 mg (n = 20). RESULTS: The melatonin group showed a decrease in diastolic blood pressure (5.1 versus 1.1 mmHg for placebo, p = 0.003) and attenuated weight gain (1.5 versus 2.2 kg for placebo, F = 4.512, p = 0.040) compared to the placebo group. The strong beneficial metabolic effects of melatonin in comparison to placebo on fat mass (0.2 versus 2.7 kg, respectively, p = 0.032) and diastolic blood pressure (5.7 versus 5.5 mmHg, respectively, p = 0.001) were observed in the bipolar disorder and not in the schizophrenia group. No adverse events were reported. CONCLUSIONS: Our results show that melatonin is effective in attenuating SGAs' adverse metabolic effects, particularly in bipolar disorder. The clinical findings allow us to propose that SGAs may disturb a centrally mediated metabolic balance that causes adverse metabolic effects and that nightly administration of melatonin helps to restore. Melatonin could become a safe and cost-effective therapeutic option to attenuate or prevent SGA metabolic effects.
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Antioxidantes/uso terapêutico , Melatonina/uso terapêutico , Transtornos Mentais/complicações , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/etiologia , Adulto , Análise de Variância , Antropometria , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Transtornos Mentais/tratamento farmacológico , Estudos Retrospectivos , Adulto JovemRESUMO
The prevalence of depression in Medical Students (MS) is higher than in the general population and changes with time. It is not known whether the prevalence of depression is higher and the associated factors different between students that initiate the last and first academic years in Medical School. Objective To compare the prevalence of depression and the associated factors in MS that start their academic courses in the first and the last academic years. Methods This is a cross sectional, observational and analytical study. A total of 1871 MS participated: 1240 were in the initiation of the first academic year, and 631 in the initiation of the last academic year. Participants answered a written survey conformed by a questionnaire about risk factors for depression and assessed for current depression with the Patients Health Questionnaire-9 (PHQ-9). Results The prevalence of depression (PHQ-9>10) was significantly higher in last year MS compared to first year MS (5.7 vs. 3.5%). The percentage of MS with a personal history of depression was higher in last year compared to first year MS (12.1% vs. 7.1%), as was the mean for previous depressive episodes (3.2 vs. 1.6). The age of onset for depressive episodes was higher in the last year group. Conclussions The prevalence of depression in MS that initiated the academic year is higher in the last year than at the beginning of the first year of the career, and could be attributed, among other factors, to a cumulative phenomenon resulting from the allostatic load that this academic process currently generates. A personal history of depression and other situational factors are associated to the presence of depression in a differential manner according to the academic year and should be considered in future studies.
La prevalencia de depresión en estudiantes de la Facultad de Medicina (EM) es mayor que en la población general y cambia a lo largo del tiempo. No se conoce si la prevalencia de depresión es mayor y los factores asociados son diferentes en estudiantes que inician el último y el primer año académico de la carrera de Medicina. Objetivo Comparar la prevalencia de Depresión y los factores asociados en EM que inician el año académico en primer año y aquellos que realizan el año de internado. Método Este es un estudio observacional, transversal y analítico. Participaron un total de 1871 EM: 1240 que iniciaban el primer año de la carrera y 631 que iniciaban el año de internado. Los alumnos contestaron una encuesta en papel compuesta por el Cuestionario sobre Factores de riesgo para Depresión y el Cuestionario sobre la Salud del Paciente (PHQ-9, por sus siglas en inglés) para evaluar la presencia actual de depresión. Resultados La prevalencia de Depresión (PHQ-9>10) resultó significativamente mayor en los estudiantes de internado comparados con los de primer año (5.7 vs. 3.5%). El porcentaje de alumnos con antecedente personal de depresión fue mayor en los alumnos de internado con respecto a los de primer año (12.1% vs. 7.1%), como lo fue el promedio de episodios depresivos previos (3.2 vs. 1.6). La edad de inicio del primer episodio depresivo fue significativamente mayor para los del quinto año. Conclusiones La prevalencia de Depresión en EM que inician el año académico es mayor en la etapa final de la carrera y puede ser atribuible, entre otros factores, a un fenómeno acumulativo de carga alostática que actualmente genera este proceso educativo. Los antecedentes personales para depresión y los factores situacionales se asocian a la presencia de depresión de una forma diferente de acuerdo al año académico y deben de ser considerados en futuros estudios.