Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

Hypothalamic-Pituitary-Adrenal Axis Dysfunction and Illness Progression in Bipolar Disorder

BACKGROUND: Impaired stress resilience and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis are suggested to play key roles in the pathophysiology of illness progression in bipolar disorder (BD), but the mechanisms leading to this dysfunction have never been elucidated. This study aimed to examine HPA axis activity and underlying molecular mechanisms in patients with BD and unaffected siblings of BD patients. METHODS: Twenty-four euthymic patients with BD, 18 siblings of BD patients, and 26 healthy controls were recruited for this study. All subjects underwent a dexamethasone suppression test followed by analyses associated with the HPA axis and the glucocorticoid receptor (GR). RESULTS: Patients with BD, particularly those at a late stage of illness, presented increased salivary post-dexamethasone cortisol levels when compared to controls (p = 0.015). Accordingly, these patients presented reduced ex vivo GR responsiveness (p = 0.008) and increased basal protein levels of FK506-binding protein 51 (FKBP51, p = 0.012), a co-chaperone known to desensitize GR, in peripheral blood mononuclear cells. Moreover, BD patients presented increased methylation at the FK506-binding protein 5 (FKBP5) gene. BD siblings presented significantly lower FKBP51 protein levels than BD patients, even though no differences were found in FKBP5 basal mRNA levels. CONCLUSIONS: Our data suggest that the epigenetic modulation of the FKBP5 gene, along with increased FKBP51 levels, is associated with the GR hyporesponsiveness seen in BD patients. Our findings are consistent with the notion that unaffected first-degree relatives of BD patients share biological factors that influence the disorder, and that such changes are more pronounced in the late stages of the illness

Avaliação da vigilância de contatos de casos novos de tuberculose no Estado de Mato Grosso - Brasil Evaluation of surveillance of contacts of new tuberculosis cases in the state of Mato Grosso - Brazil

OBJETIVO: Avaliar as ações de vigilância de contatos de casos novos de tuberculose em Mato Grosso no período de 1999 a 2004. MÉTODOS: Estudo epidemiológico descritivo baseado em dados do Sistema de Informação de Agravos de Notificação-Tuberculose. O número de casos novos de tuberculose, o número de contatos (estimados, examinados e não examinados) e a taxa de incidência de tuberculose foram analisados segundo a faixa etária. Calculou-se, por ano de estudo, a média de contatos examinados para cada caso de tuberculose segundo a faixa etária. Os casos de tuberculose pulmonar com e sem contatos examinados foram analisados segundo o resultado da baciloscopia. RESULTADOS: Em 2004, Mato Grosso apresentou 41,3 casos de tuberculose por 100 mil habitantes. A mesorregião centro-sul apresentou a maior taxa de incidência (57 casos/100 mil habitantes) e uma taxa de 15% de contatos examinados. Entre os menores de 15 anos, examinaram-se 63 contatos (60,5%), enquanto entre aqueles com 15 anos ou mais, examinaram-se 389 contatos (8,9%). Em 1999, a média de contatos examinados em Mato Grosso foi de 0,02 (0,5%), e, em 2004, ela alcançou 0,42 (10,5%). O percentual de contatos examinados foi 40,0% maior entre os contatos de casos bacilíferos (OR = 1,4; IC95%: 1,08-1,83). CONCLUSÕES: O percentual de contatos examinados é muito baixo, principalmente entre os adultos. A normatização do exame de contatos de tuberculose pela Secretaria de Vigilância em Saúde do Ministério da Saúde não tem sido suficiente para garantir que esse grupo de maior risco de adoecimento seja priorizado pelos serviços de saúde de Mato Grosso.<br>OBJECTIVE: To evaluate surveillance of contacts of new tuberculosis cases in the state of Mato Grosso from 1999 to 2004. METHODS: This was a descriptive epidemiological study based on data from the Tuberculosis Case Registry Database. The number of new tuberculosis cases, the number of contacts (estimated, investigated, and uninvestigated), and the tuberculosis incidence rate were analyzed by age bracket. The mean rate of contacts investigated for each case of tuberculosis by age bracket was calculated per year of study. The cases of pulmonary tuberculosis with and without contacts investigated were analyzed by sputum smear microscopy results. RESULTS: In 2004, there were 41.3 cases of tuberculosis per 100,000 inhabitants in the state of Mato Grosso. The south-central region presented the highest incidence rate (57 cases/100,000 inhabitants) and a 15% rate of contacts investigated. Among those younger than 15 years, 63 contacts (60.5%) were investigated, whereas among those aged 15 or older, 389 (8.9%) were investigated. In 1999, the mean rate of contacts investigated statewide was 0.02 (0.5%), and, in 2004, it reached 0.42 (10.5%). The percentage of contacts investigated was 40% higher among the contacts of contagious cases (OR = 1.4; 95% CI: 1.08-1.83). CONCLUSIONS: The percentage of contacts investigated is very low, principally among adults. The adoption of the standards for investigation of tuberculosis contacts proposed by the Brazilian National Ministry of Health Department of Health Surveillance has not ensured that this group at highest risk of developing active tuberculosis be given priority at health care facilities in the state of Mato Grosso

Telomere Length, Oxidative Stress, Inflammation and BDNF Levels in Siblings of Patients with Bipolar Disorder: Implications for Accelerated Cellular Aging

Background: Growing evidence supports the existence of neurobiological trait abnormalities in individuals at genetic risk for bipolar disorder. The aim of this study was to examine potential differences in brain-derived neurotrophic factor, cytokines, oxidative stress, and telomere length markers between patients with bipolar disorder, their siblings, and healthy controls. Methods: Thirty-six patients with bipolar disorder type I, 39 siblings, and 44 healthy controls were assessed. Serum levels of brain-derived neurotrophic factor, interleukin-6, interleukin-10, tumor necrosis factor-α, C-C motif chemokine 11, C-C motif chemokine 24, and 3-nitrotyrosine were measured, as were the activities of glutathione peroxidase, glutathione reductase, and glutathione S-transferase. Telomere length (T/S ratio) was measured using quantitative polymerase chain reaction. Results: Telomere length was different between the 3 groups (P = .041) with both patients and siblings showing a shorter T/S ratio compared with healthy controls. Patients showed increased levels of interleukin-6 (P = .005) and interleukin-10 (P = .002) compared with controls as well as increased levels of interleukin-6 (p = 0.014) and CCL24 (P = .016) compared with their siblings. C-C motif chemokine 11 levels were increased in siblings compared with controls (P = .015), and a similar tendency was found in patients compared with controls (P = .045). Glutathione peroxidase activity was decreased in patients compared with controls (P = .006) and siblings (P = .025). No differences were found for the other markers. Conclusions: The present results suggest that unaffected siblings may present accelerated aging features. These neurobiological findings may be considered as endophenotypic traits. Further prospective studies are warranted