RESUMO
OBJECTIVE: We have previously reported higher brain serotonin 1A (5-HT1A ) autoreceptor binding in antidepressant-naïve patients with Major Depressive Disorder (MDD) compared with healthy volunteers, and a decrease in binding in MDD after selective serotonin reuptake inhibitor (SSRI) treatment. This SSRI effect is also present in rodents administered SSRIs chronically. We therefore sought to determine the duration of antidepressant medication effects on 5-HT1A receptor binding after medication discontinuation. METHODS: Positron emission tomography (PET) imaging with the 5-HT1A receptor radioligand [11 C]WAY-100635 was performed in 66 individuals with current DSM-IV MDD to examine relationships between 5-HT1A binding and time since most recent antidepressant treatment. All subjects were medication-free for at least 2 weeks prior to scanning. Thirty-two additional MDD comparison subjects were antidepressant naïve. RESULTS: No differences in [11 C]WAY-100635 binding were observed between antidepressant naïve and antidepressant exposed MDD groups in 13 a priori cortical and subcortical regions of interest, including raphe autoreceptors, assessed simultaneously in linear mixed effects models. Furthermore, [11 C]WAY-100635 binding did not correlate with time off antidepressants in the antidepressant exposed patients considering these ROIs. The same results were observed when effects of treatment discontinuation of any psychotropic medication used to treat their depression was examined. CONCLUSION: These results indicate that any antidepressant-associated downregulation of 5-HT1A autoreceptor binding reverses within 2 weeks of medication discontinuation. Since this effect is hypothesized to mediate the antidepressant action of SSRIs, and perhaps other antidepressants, it suggests that patients who need ongoing treatment may relapse rapidly when medication is discontinued. Moreover, 2 weeks appears to be a sufficiently long washout of antidepressant medications for a reliable measure of illness-related binding levels.
Assuntos
Antidepressivos/administração & dosagem , Transtorno Depressivo Maior/metabolismo , Piperazinas/farmacocinética , Piridinas/farmacocinética , Receptor 5-HT1A de Serotonina/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Antagonistas do Receptor 5-HT1 de Serotonina/farmacocinética , Adulto , Antidepressivos/uso terapêutico , Radioisótopos de Carbono , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/tratamento farmacológico , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Ligação Proteica , Compostos Radiofarmacêuticos/farmacocinética , Inibidores Seletivos de Recaptação de Serotonina/uso terapêuticoRESUMO
BACKGROUND: Comorbid anxiety disorders have been considered a risk factor for suicidal behavior in patients with mood disorders, although results are controversial. The aim of this two-year prospective study was to determine if lifetime and current comorbid anxiety disorders at baseline were risk factors for suicide attempts during the two-year follow-up. METHODS: We evaluated 667 patients with mood disorders (504 with major depression and 167 with bipolar disorder) divided in two groups: those with lifetime comorbid anxiety disorders (n=229) and those without (n=438). Assessments were performed at baseline and at 3, 12, and 24 months. Kaplan-Meier survival analysis and log-rank test were used to evaluate the relationship between anxiety disorders and suicide attempts. Cox proportional hazard regression was performed to investigate clinical and demographic variables that were associated with suicide attempts during follow-up. RESULTS: Of the initial sample of 667 patients, 480 had all three follow-up interviews. During the follow-up, 63 patients (13.1%) attempted suicide at least once. There was no significant difference in survival curves for patients with and without comorbid anxiety disorders (log-rank test=0.269; P=0.604). Female gender (HR=3.66, P=0.001), previous suicide attempts (HR=3.27, P=0.001) and higher scores in the Buss-Durkee Hostility Inventory (HR=1.05, P≤0.001) were associated with future suicide attempts. CONCLUSIONS: Our results suggest that comorbid anxiety disorders were not risk factors for suicide attempts. Further studies were needed to determine the role of anxiety disorders as risk factors for suicide attempts.
Assuntos
Transtornos de Ansiedade/epidemiologia , Transtornos do Humor/epidemiologia , Ideação Suicida , Tentativa de Suicídio/psicologia , Tentativa de Suicídio/estatística & dados numéricos , Adulto , Transtornos de Ansiedade/psicologia , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/psicologia , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologia , Feminino , Hostilidade , Humanos , Masculino , Transtornos do Humor/psicologia , Estudos Prospectivos , Fatores de Risco , Fatores de TempoRESUMO
Tuberculosis (TB) and depression act synergistically via social, behavioral, and biological mechanisms to magnify the burden of disease. Clinical depression is a common, under-recognized, yet treatable condition that, if comorbid with TB, is associated with increased morbidity, mortality, community TB transmission, and drug resistance. Depression may increase risk of TB reactivation, contribute to disease progression, and/or inhibit the physiological response to anti-tuberculosis treatment because of poverty, undernutrition, immunosuppression, and/or negative coping behaviors, including substance abuse. Tuberculous infection and/or disease reactivation may precipitate depression as a result of the inflammatory response and/or dysregulation of the hypothalamic-pituitary-adrenal axis. Clinical depression may also be triggered by TB-related stigma, exacerbating other underlying social vulnerabilities, and/or may be attributed to the side effects of anti-tuberculosis treatment. Depression may negatively impact health behaviors such as diet, health care seeking, medication adherence, and/or treatment completion, posing a significant challenge for global TB elimination. As several of the core symptoms of TB and depression overlap, depression often goes unrecognized in individuals with active TB, or is dismissed as a normative reaction to situational stress. We used evidence to reframe TB and depression comorbidity as the 'TB-depression syndemic', and identified critical research gaps to further elucidate the underlying mechanisms. The World Health Organization's Global End TB Strategy calls for integrated patient-centered care and prevention linked to social protection and innovative research. It will require multidisciplinary approaches that consider conditions such as TB and depression together, rather than as separate problems and diseases, to end the global TB epidemic.
Assuntos
Antituberculosos/uso terapêutico , Depressão/epidemiologia , Tuberculose/psicologia , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Efeitos Psicossociais da Doença , Depressão/complicações , Progressão da Doença , Farmacorresistência Bacteriana , Comportamentos Relacionados com a Saúde , Humanos , Adesão à Medicação/psicologia , Assistência Centrada no Paciente/organização & administração , Estigma Social , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologiaRESUMO
Suicidal behavior is often conceptualized as a response to overwhelming stress. Our model posits that given a propensity for acting on suicidal urges, stressors such as life events or major depressive episodes (MDEs) determine the timing of suicidal acts. Depressed patients (n=415) were assessed prospectively for suicide attempts and suicide, life events and MDE over 2 years. Longitudinal data were divided into 1-month intervals characterized by MDE (yes/no), suicidal behavior (yes/no) and life event scores. Marginal logistic regression models were fit, with suicidal behavior as the response variable and MDE and life event score in either the same or previous month, respectively, as time-varying covariates. Among 7843 person-months, 33% had MDE and 73% had life events. MDE increased the risk for suicidal behavior (odds ratio (OR)=4.83, P⩽0.0001). Life event scores were unrelated to the timing of suicidal behavior (OR=1.06 per 100 point increase, P=0.32), even during a MDE (OR=1.12, P=0.15). However, among those without borderline personality disorder (BPD), both health- and work-related life events were key precipitants, as was recurrent MDE, with a 13-fold effect. The relationship of life events to suicidal behavior among those with BPD was more complex. Recurrent MDE was a robust precipitant for suicidal behavior, regardless of BPD comorbidity. The specific nature of life events is key to understanding the timing of suicidal behavior. Given unanticipated results regarding the role of BPD and study limitations, these findings require replication. Of note, that MDE, a treatable risk factor, strongly predicts suicidal behaviors is cause for hope.
Assuntos
Transtorno da Personalidade Borderline/psicologia , Transtorno Depressivo Maior/psicologia , Acontecimentos que Mudam a Vida , Tentativa de Suicídio/psicologia , Adulto , Transtorno da Personalidade Borderline/complicações , Transtorno Depressivo Maior/complicações , Feminino , Humanos , Estudos Longitudinais , Masculino , Razão de Chances , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
Brain-derived neurotrophic factor (BDNF) has been implicated in the mechanism of age-related regional brain volumetric changes. Healthy volunteers with the valine to methionine polymorphism at codon 66 of the BDNF gene (val66met) exhibit decreased volume of a number of brain structures, including hippocampus, temporal and occipital lobar gray matter volumes, and a negative correlation between age and the volume of bilateral dorsolateral prefrontal cortices. We sought to characterize the relationship between age, BDNF and amygdala volumes among healthy volunteers. We measured amygdala volumes in 55 healthy, right-handed volunteers who underwent structural magnetic resonance imaging (MRI) and were also characterized demographically and genotyped with respect to BDNF. Using an ANCOVA model, we found that amygdala volumes were inversely correlated with age in BDNF val66met carriers but not in non-carriers. This is the first report of age-related BDNF val66met polymorphism effects on amygdala volume.