Decreased Neuroautonomic Complexity in Men during an Acute Major Depressive Episode: Analysis of Heart Rate Dynamics

Major depression affects multiple physiologic systems. Therefore, analysis of signals that reflect integrated function may be useful in probing dynamical changes in this syndrome. Increasing evidence supports the conceptual framework that complex variability is a marker of healthy, adaptive control mechanisms and that dynamical complexity decreases with aging and disease. We tested the hypothesis that heart rate (HR) dynamics in non-medicated, young to middle-aged males during an acute major depressive episode would exhibit lower complexity compared with healthy counterparts. We analyzed HR time series, a neuroautonomically regulated signal, during sleep, using the multiscale entropy method. Our results show that the complexity of the HR dynamics is significantly lower for depressed than for non-depressed subjects for the entire night (P<0.02) and combined sleep stages 1 and 2 (P<0.02). These findings raise the possibility of using the complexity of physiologic signals as the basis of novel dynamical biomarkers of depression

Comparison of two peptide radiotracers for prostate carcinoma targeting

OBJECTIVES: Scintigraphy is generally not the first choice treatment for prostate cancer, although successful studies using bombesin analog radiopeptides have been performed. Recently, a novel peptide obtained using a phage display library demonstrated an affinity for prostate tumor cells. The aim of this study was to compare the use of a bombesin analog to that of a phage display library peptide (DUP-1) radiolabeled with technetium-99m for the treatment of prostate carcinoma. The peptides were first conjugated to S-acetyl-MAG3 with a 6-carbon spacer, namely aminohexanoic acid. METHODS: The technetium-99m labeling required a sodium tartrate buffer. Radiochemical evaluation was performed using ITLC and was confirmed by high-performance liquid chromatography. The coefficient partition was determined, and in vitro studies were performed using human prostate tumor cells. Biodistribution was evaluated in healthy animals at various time points and also in mice bearing tumors. RESULTS: The radiochemical purity of both radiotracers was greater than 95%. The DUP-1 tracer was more hydrophilic (log P = -2.41) than the bombesin tracer (log P = -0.39). The biodistribution evaluation confirmed this hydrophilicity by revealing the greater kidney uptake of DUP-1. The bombesin concentration in the pancreas was greater than that of DUP-1 due to specific gastrin-releasing peptide receptors. Bombesin internalization occurred for 78.32% of the total binding in tumor cells. The DUP-1 tracer showed very low binding to tumor cells during the in vitro evaluation, although tumor uptake for both tracers was similar. The tumors were primarily blocked by DUP1 and the bombesin radiotracer primarily targeted the pancreas. CONCLUSION: Further studies with the radiolabeled DUP-1 peptide are recommended. With further structural changes, this molecule could become an efficient alternative tracer for prostate tumor diagnosis

Stress-induced c-Fos expression is differentially modulated by dexamethasone, diazepam and imipramine

Immobilization stress upregulates c-Fos expression in several CNS areas. Repeated stress or the use of drugs can modulate stress-induced c-Fos expression. Here, we investigated in 40 different areas of the rat brain the effects of dexamethasone (SDX, a synthetic glucocorticoid), diazepam (SBDZ, a benzodiazepine), and imipramine (IMI, an antidepressant) on the c-Fos expression induced by restraint stress. Wistar rats were divided into four groups and submitted to 20 days of daily injection of saline (three first groups) or imipramine, 15 mg/kg, i.p. On day 21, animals were submitted to injections of saline (somatosensory, SS), SDX (1 mg/kg, i.p.), SBDZ (5 mg/kg, i.p.), or IMI (15 mg/kg, i.p.) before being submitted to restraint. Immediately after stress, the animals were perfused and their brains processed with immunohistochemistry for c-Fos (Ab-5 Oncogene Science). Dexamethasone reduced stress- induced c-Fos expression in SS cortex, hippocampus, paraventricular nucleus of the hypothalamus (PVH), and locus coeruleus (LC), whereas diazepam reduced c-Fos staining in the SS cortex, hippocampus, bed nucleus of stria terminalis, septal area, and hypothalamus (preoptic area and supramammillary nucleus). Chronic administration of imipramine decreased staining in the hippocampus, PVH, and LC, while increasing it in the nucleus raphe pallidus. We conclude that dexamethasone, diazepam and imipramine differentially modulate stress-induced Fos expression. the present study provides an important comparative background that may help in the further understanding of the effects of these compounds and on the brain activation as well as on the behavioral, neuroendocrine, and autonomic responses to stress.UFRRJ, Dept Physiol Sci, BR-23890000 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilWeb of Scienc

A transdisciplinary perspective of chronic stress in relation to psychopathology throughout life span development

The allostatic load (AL) model represents an interdisciplinary approach to comprehensively conceptualize and quantify chronic stress in relation to pathologies throughout the life cycle. This article first reviews the AL model, followed by interactions among early adversity, genetics, environmental toxins, as well as distinctions among sex, gender, and sex hormones as integral antecedents of AL. We next explore perspectives on severe mental illness, dementia, and caregiving as unique human models of AL that merit future investigations in the field of developmental psychopathology. A complimenting transdisciplinary perspective is applied throughout, whereby we argue that the AL model goes beyond traditional stress–disease theories toward the advancement of person-centered research and practice that promote not only physical health but also mental healt

Preliminary spatiotemporal analysis of the association between socio-environmental factors and suicide

<p>Abstract</p> <p>Background</p> <p>The seasonality of suicide has long been recognised. However, little is known about the relative importance of socio-environmental factors in the occurrence of suicide in different geographical areas. This study examined the association of climate, socioeconomic and demographic factors with suicide in Queensland, Australia, using a spatiotemporal approach.</p> <p>Methods</p> <p>Seasonal data on suicide, demographic variables and socioeconomic indexes for areas in each Local Government Area (LGA) between 1999 and 2003 were acquired from the Australian Bureau of Statistics. Climate data were supplied by the Australian Bureau of Meteorology. A multivariable generalized estimating equation model was used to examine the impact of socio-environmental factors on suicide.</p> <p>Results</p> <p>The preliminary data analyses show that far north Queensland had the highest suicide incidence (e.g., Cook and Mornington Shires), while the south-western areas had the lowest incidence (e.g., Barcoo and Bauhinia Shires) in all the seasons. Maximum temperature, unemployment rate, the proportion of Indigenous population and the proportion of population with low individual income were statistically significantly and positively associated with suicide. There were weaker but not significant associations for other variables.</p> <p>Conclusion</p> <p>Maximum temperature, the proportion of Indigenous population and unemployment rate appeared to be major determinants of suicide at a LGA level in Queensland.</p

The sleep EEG spectrum is a sexually dimorphic marker of general intelligence

The shape of the EEG spectrum in sleep relies on genetic and anatomical factors and forms an individual “EEG fingerprint”. Spectral components of EEG were shown to be connected to mental ability both in sleep and wakefulness. EEG sleep spindle correlates of intelligence, however, exhibit a sexual dimorphism, with a more pronounced association to intelligence in females than males. In a sample of 151 healthy individuals, we investigated how intelligence is related to spectral components of full-night sleep EEG, while controlling for the effects of age. A positive linear association between intelligence and REM anterior beta power was found in females but not males. Transient, spindle-like “REM beta tufts” are described in the EEG of healthy subjects, which may reflect the functioning of a recently described cingular-prefrontal emotion and motor regulation network. REM sleep frontal high delta power was a negative correlate of intelligence. NREM alpha and sigma spectral power correlations with intelligence did not unequivocally remain significant after multiple comparisons correction, but exhibited a similar sexual dimorphism. These results suggest that the neural oscillatory correlates of intelligence in sleep are sexually dimorphic, and they are not restricted to either sleep spindles or NREM sleep