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

The emergence of the cortisol circadian rhythm in monozygotic and dizygotic twin infants: the twin-pair synchrony

OBJECTIVE: Studies on the influence of genetic factors on the ontogeny of cortisol circadian rhythm in infants are lacking. This study evaluated the influence of twinning and the heritability on the age of emergence of salivary cortisol rhythm. DESIGN AND SUBJECTS: A longitudinal study was performed using salivary samples obtained during morning and night, at 2, 4, 8, 12, 16, 20 and 24 weeks of postnatal life in 34 infants, 10 monozygotic (MZ) and 7 dizygotic (DZ) twin pairs. Salivary cortisol was determined by radioimmunoassay (RIA). Zigosity was verified by DNA analysis of at least 13 short tandem repeat polymorphisms. Difference of the emergence of cortisol circadian rhythm, within each twin pair, the intraclass correlation coefficient and the heritability index (h(2)) were calculated. RESULTS: The mean (± SEM) age of emergence of salivary cortisol circadian rhythm was similar in MZ and DZ (7·8 ± 1·0 vs 7·4 ± 1·3 weeks). Seven pairs showed coincidence of the emergence of cortisol rhythm. Ten pairs were not coincident; among them the within-pair difference of emergence of salivary circadian rhythm was similar in both MZ and DZ groups. The intraclass correlation coefficients were rMZ = 0·60, P = 0·02; and rDZ = 0·65, P = 0·03, respectively. The heritability index (h(2)) was 0·21 (ns). CONCLUSIONS: Salivary circadian rhythm appeared at the same postnatal age in MZ and DZ twin infants. Although several physiological aspects might be involved, the heritability index, obtained in the present study, suggests less genetic than environmental impact on the age of the onset of the cortisol circadian rhythm. Our data also indicated that each twin-pair show synchrony because they probably shared prenatal and postnatal environmental synchronizers

Promise and Pitfalls of Animal Models of Schizophrenia

Animal models are indispensible tools for advancing understanding of the cause of any given disease and developing new treatments. Developing animal models for schizophrenia presents formidable challenges owing to the distinctively human nature of the symptoms that define it and the thus-far-obscured underlying biological mechanisms. Nevertheless, progress has been and continues to be made in this important field of endeavor. This article discusses the challenges facing investigators who seek to develop and use animal models for translational research in schizophrenia and the responses that have emerged to those challenges, as well as the likely pathways that will lead to future progress

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

Anti-depressant and anxiolytic like behaviors in PKCI/HINT1 knockout mice associated with elevated plasma corticosterone level

<p>Abstract</p> <p>Background</p> <p>Protein kinase C interacting protein (PKCI/HINT1) is a small protein belonging to the histidine triad (HIT) family proteins. Its brain immunoreactivity is located in neurons and neuronal processes. PKCI/HINT1 gene knockout (KO) mice display hyper-locomotion in response to D-amphetamine which is considered a positive symptom of schizophrenia in animal models. <it>Postmortem </it>studies identified PKCI/HINT1 as a candidate molecule for schizophrenia and bipolar disorder. We investigated the hypothesis that the PKCI/HINT1 gene may play an important role in regulating mood function in the CNS. We submitted PKCI/HINT1 KO mice and their wild type (WT) littermates to behavioral tests used to study anti-depressant, anxiety like behaviors, and goal-oriented behavior. Additionally, as many mood disorders coincide with modifications of hypothalamic-pituitary-adrenal (HPA) axis function, we assessed the HPA activity through measurement of plasma corticosterone levels.</p> <p>Results</p> <p>Compared to the WT controls, KO mice exhibited less immobility in the forced swim (FST) and the tail suspension (TST) tests. Activity in the TST tended to be attenuated by acute treatment with valproate at 300 mg/kg in KO mice. The PKCI/HINT1 KO mice presented less thigmotaxis in the Morris water maze and spent progressively more time in the lit compartment in the light/dark test. In a place navigation task, KO mice exhibited enhanced acquisition and retention. Furthermore, the afternoon basal plasma corticosterone level in PKCI/HINT1 KO mice was significantly higher than in the WT.</p> <p>Conclusion</p> <p>PKCI/HINT1 KO mice displayed a phenotype of behavioral and endocrine features which indicate changes of mood function, including anxiolytic-like and anti-depressant like behaviors, in conjunction with an elevated corticosterone level in plasma. These results suggest that the PKCI/HINT 1 gene could be important for the mood regulation function in the CNS.</p

Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stress

The subgranular zone of the adult hippocampal dentate gyrus contains a pool of neural stem cells that continuously divide and differentiate into functional granule cells. It has been shown that production of new hippocampal neurons is necessary for amelioration of stress-induced behavioral changes by antidepressants in animal models of depression. The survival of newly born hippocampal neurons is decreased by chronic psychosocial stress and increased by exposure to enriched environments. These observations suggest the existence of a link between hippocampal neurogenesis, stress-induced behavioral changes, and the beneficial effects of enriched environment. To show causality, we subjected transgenic mice with conditionally suppressed neurogenesis to psychosocial stress followed by environmental enrichment. First, we showed that repeated social defeat coupled with chronic exposure to an aggressor produces robust and quantifiable indices of submissive and depressive-like behaviors; second, subsequent exposure to an enriched environment led to extinction of the submissive phenotype, while animals exposed to an impoverished environment retained the submissive phenotype; and third, enrichment was not effective in reversing the submissive and depressive-like behaviors in transgenic mice lacking neurogenesis. Our data show two main findings. First, living in an enriched environment is highly effective in extinguishing submissive behavioral traits developed during chronic social stress, and second, these effects are critically dependent on adult neurogenesis, indicating that beneficial behavioral adaptations are dependent on intact adult neurogenesis