Demantrafferty2811

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Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.Neuregulin-1 (NRG1) represents an important factor for multiple processes including neurodevelopment, brain functioning or cognitive functions. learn more Evidence from animal research suggests an effect of NRG1 on the excitation-inhibition (E/I) balance in cortical circuits. However, direct evidence for the importance of NRG1 in E/I balance in humans is still lacking. In this work, we demonstrate the application of computational, biophysical network models to advance our understanding of the interaction between cortical activity observed in neuroimaging and the underlying neurobiology. We employed a biophysical neuronal model to simulate large-scale brain dynamics and to investigate the role of polymorphisms in the NRG1 gene (rs35753505, rs3924999) in n = 96 healthy adults. Our results show that G/G-carriers (rs3924999) exhibit a significant difference in global coupling (P = 0.048) and multiple parameters determining E/I-balance such as excitatory synaptic coupling (P = 0.047), local excitatory recurrence (P = 0.032) and inhibitory synaptic coupling (P = 0.028). This indicates that NRG1 may be related to excitatory recurrence or excitatory synaptic coupling potentially resulting in altered E/I-balance. Moreover, we suggest that computational modeling is a suitable tool to investigate specific biological mechanisms in health and disease.Major depression is a prevalent illness that increases the risk of several neurological conditions. These include stroke, cardiovascular disease, and dementia including Alzheimer's disease. In this review we ask whether certain types of depression and associated loneliness may be a harbinger of cognitive decline and possibly even dementia. We propose that chronic stress and inflammation combine to compromise vascular and brain function. The resulting increases in proinflammatory cytokines and microglial activation drive brain pathology leading to depression and mild cognitive impairment, which may progress to dementia. We present evidence that by treating the inflammatory changes, depression can be reversed in many cases. Importantly, there is evidence that anti-inflammatory and antidepressant treatments may reduce or prevent dementia in people with depression. Thus, we propose a model in which chronic stress and inflammation combine to increase brain permeability and cytokine production. This leads to microglial activation, white matter damage, neuronal and glial cell loss. This is first manifest as depression and mild cognitive impairment, but can eventually evolve into dementia. Further research may identify clinical subgroups with inflammatory depression at risk for dementia. It would then be possible to address in clinical trials whether effective treatment of the depression can delay the onset of dementia.Developmental encephalopathies, including intellectual disability and autistic spectrum disorder, are frequently associated with infant epilepsy. Epileptic encephalopathy is used to describe an assumed causal relationship between epilepsy and developmental delay. Developmental encephalopathies pathogenesis more independent from epilepsy is supported by the identification of several gene variants associated with both developmental encephalopathies and epilepsy, the possibility for gene-associated developmental encephalopathies without epilepsy, and the continued development of developmental encephalopathies even when seizures are controlled. Hence, 'developmental and epileptic encephalopathy' may be a more appropriate term than epileptic encephalopathy. This update considers the best studied 'developmental and epileptic encephalopathy' gene variants for illustrative support for 'developmental and epileptic encephalopathy' over epileptic encephalopathy. Moreover, the interaction between epilepsy and developmental encephalopathies is considered with respect to influence on treatment decisions. Continued research in genetic testing will increase access to clinical tests, earlier diagnosis, better application of current treatments, and potentially provide new molecular-investigated treatments.Cortisol profiles are known to vary across phases of alcohol use disorder (AUD; e.g. chronic use, withdrawal and early/sustained recovery). These patterns have largely been established through between-subjects contrasts. Using a segmental hair cortisol concentrations (HCC) approach, retrospective longitudinal analyses are feasible. Here, we examine monthly cortisol secretion in treatment-seekers with AUD from alcohol use to abstinence. At ~6 weeks of recovery we collected hair samples from individuals with moderate-to-severe AUD. We examined HCC from three consecutive segments; proximal to the scalp representing the most recent month (sustained abstinence from alcohol), the midsegment representing the previous month in which abstinence was attained, and the distal segment representing 2 months prior during active drinking. Analyses examined main and interactive effects of segment and sex, controlling for monthly alcohol consumption. Best fit by a quadratic shape, within-subject change was significant (F1,15 = 5.27, P = 0.04, ηpartial2 = 0.26). The distal and midsegments did not differ from one another (P = 0.51). The proximal segment was significantly lower than both the distal (M∆ = 0.200, P = 0.004) and mid (M∆ = 0.175, P less then 0.001) segments. An effect of sex approached significance suggesting women had modestly higher HCC than men (MWOMEN = 1.37 vs. MMEN = 1.02, P = 0.10). Consistent with previous cross-sectional reports, these data confirm nonlinear patterns of cortisol accumulation with elevations apparent during periods of alcohol consumption and a decrease in abstinence. Capturing these within-subject patterns via HCC trajectories may serve as a valuable resource in identifying profiles associated with increased risk and post-treatment outcomes.