Although typical mutations expected in childhood-onset polyneuropathies are seen less frequently, polyneuropathies are frequently encountered as findings of complex, multisystemic diseases.

Advances in genetics have led to an increase in the heterogeneity of hereditary polyneuropathies, causing difficulties in the use of existing classifications. Although typical mutations expected in childhood-onset polyneuropathies are seen less frequently, polyneuropathies are frequently encountered as findings of complex, multisystemic diseases.Loneliness and social isolation are common sources of chronic stress in modern society. Epidemiological studies have demonstrated that loneliness and social isolation increase mortality risk as much as smoking or alcohol consumption and more than physical inactivity or obesity. Ralimetinib clinical trial Loneliness in human is associated with higher blood pressure whereas enhanced atherosclerosis is observed in animal models of social isolation. Loneliness and social isolation lead to activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, enhanced sympathetic nerve activity, impaired parasympathetic function and a proinflammatory immune response. These mechanisms have been implicated in the development of cardiovascular disease conferred by social isolation although a causal relationship has not been established so far. There is evidence that oxidative stress is likely to be a key molecular mechanism linking chronic psychosocial stress to cardiovascular disease. NADPH oxidase-mediated oxidative stress in the hypothalamus has been shown to be required for social isolation-induced HPA axis activation in socially isolated rats. Oxidative stress in the rostral ventrolateral medulla is also a key regulator of sympathetic nerve activity. In the vasculature, oxidative stress increases vascular tone and promote atherogenesis through multiple mechanisms. Thus, preventing oxidative stress may represent a therapeutic strategy to reduce the detrimental effects of social stress on health.

Children exhibiting extreme anxious temperament (AT) are at an increased risk for developing anxiety and depression. Our previous mechanistic and neuroimaging work in young rhesus monkeys linked the central nucleus of the amygdala to AT and its underlying neural circuit.

Here, we used laser capture microscopy and RNA sequencing in 47 young rhesus monkeys to investigate AT’s molecular underpinnings by focusing on neurons from the lateral division of the central nucleus of the amygdala (CeL). RNA sequencing identified numerous AT-related CeL transcripts, and we used immunofluorescence (n= 3) and tract-tracing (n= 2) methods in a different sample of monkeys to examine the expression, distribution, and projection pattern of neurons expressing one of these transcripts.

We found 555 AT-related transcripts, 14 of which were confirmed with high statistical confidence (false discovery rate < .10), including protein kinase C delta (PKCδ), a CeL microcircuit cell marker implicated in rodent threat processing. We characterized PKCδ neurons in the rhesus CeL, compared its distribution with that of the mouse, and demonstrated that a subset of these neurons project to the laterodorsal bed nucleus of the stria terminalis.

These findings demonstrate that CeL PKCδ is associated with primate anxiety, provides evidence of a CeL to laterodorsal bed nucleus of the stria terminalis circuit that may be relevant to understanding human anxiety, and points to specific molecules within this circuit that could serve as potential treatment targets for anxiety disorders.

These findings demonstrate that CeL PKCδ is associated with primate anxiety, provides evidence of a CeL to laterodorsal bed nucleus of the stria terminalis circuit that may be relevant to understanding human anxiety, and points to specific molecules within this circuit that could serve as potential treatment targets for anxiety disorders.Posttraumatic stress disorder (PTSD) in adolescents is common and debilitating. In contrast to adult PTSD, relatively little is known about the neurobiology of adolescent PTSD, nor about how current treatments may alter adolescent neurodevelopment to allow recovery from PTSD. Improving our understanding of biological mechanisms of adolescent PTSD, taken in the context of neurodevelopment, is crucial for developing novel and personalized treatment approaches. In this review, we highlight prevailing constructs of PTSD and current findings on these domains in adolescent PTSD. Notably, little data exist in adolescent PTSD for prominent adult PTSD constructs, including threat learning and attentional threat bias. Most work to date has examined general threat processing, emotion regulation, and their neural substrates. These studies suggest that adolescent PTSD, while phenomenologically similar to adult PTSD, shows unique neurodevelopmental substrates that may impair recovery but could also be targeted in the context of adolescent neuroplasticity to improve outcomes. Both cross-sectional and longitudinal data suggest abnormal frontolimbic development compared with typically developing youths, a pattern that may differ from resilient youths. Whether current treatments such as trauma-focused psychotherapy engage these targets and restore healthy neurodevelopment remains an open question. We end our review by highlighting emerging areas and knowledge gaps that could be addressed to better characterize the biology underlying adolescent PTSD. Emerging studies in computational modeling of decision making, caregiver-related transmission of traumatic stress, and other areas may offer new targets that could harness adolescent neurobehavioral plasticity to improve resilience and recovery for some of our most vulnerable youths.Cognitive flexibility enables appropriate responses to a changing environment and is associated with positive life outcomes. Adolescence, with its increased focus on transitioning to independent living, presents particular challenges for youths with autism spectrum disorder (ASD) who often struggle to behave in a flexible way when faced with challenges. This review focuses on brain mechanisms underlying the development of flexible cognition during adolescence and how these neural systems are affected in ASD. Neuroimaging studies of task switching and set-shifting provide evidence for atypical lateral frontoparietal and midcingulo-insular network activation during cognitive flexibility task performance in individuals with ASD. Recent work also examines how intrinsic brain network dynamics support flexible cognition. These dynamic functional connectivity studies provide evidence for alterations in the number of transitions between brain states, as well as hypervariability of functional connections in adolescents with ASD.