Cross-species RNAi therapy via AAV delivery alleviates neuropathic pain by targeting GCH1.

Tetrahydrobiopterin (BH4) expression is normally strictly controlled; however, its intracellular levels increase considerably following nerve damage. GTP cyclohydrolase I (GCH1) plays a crucial role in regulating BH4 concentration, with an upregulation observed in the dorsal root ganglion in cases of neuropathic pain. In this study, we aimed to develop and evaluate the clinical potential of an RNA interference-based adeno-associated virus (AAV) targeting GCH1 across various species to decrease BH4 levels and, consequently, alleviate neuropathic pain symptoms.

Sex-Specific Effects of Anxiety on Cognition and Activity-Dependent Neural Networks: Insights From (Female) Mice and (Wo)men.

Background: Neuropsychiatric symptoms, such as depression and anxiety, are observed in 90% of patients with Alzheimer's disease (AD), two-thirds of whom are women. Neuropsychiatric symptoms usually manifest long before AD onset creating a therapeutic opportunity. Here, we examined the impact of anxiety on AD progression and the underlying brainwide neuronal mechanisms.

GluN2B on Adult-Born Granule Cells Modulates (R,S)-Ketamine's Rapid-Acting Effects in Mice.

Background: Standard antidepressant treatments often take weeks to reach efficacy and are ineffective for many patients. (R,S)-ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to be a rapid-acting antidepressant and to decrease depressive symptoms within hours of administration. While previous studies have shown the importance of the GluN2B subunit of the NMDA receptor on interneurons in the medial prefrontal cortex, no study to our knowledge has investigated the influence of GluN2B-expressing adult-born granule cells.

Provider Factors Likely to Impact Access and Uptake of Long-Acting Injectable Cabotegravir for Transgender Women in the United States: Results of a Qualitative Study.

Long-acting injectable cabotegravir (CAB-LA) was US Food and Drug Administration-approved in 2021. However, little is known about providers' CAB-LA knowledge, attitudes, challenges, and prescribing preferences for transgender women patients. Understanding this is critical to developing new pre-exposure prophylaxis (PrEP) interventions tailored to transgender women.

A SMARTR workflow for multi-ensemble atlas mapping and brain-wide network analysis.

In the last decade, activity-dependent strategies for labelling multiple immediate early gene (IEG) ensembles in mice have generated unprecedented insight into the mechanisms of memory encoding, storage, and retrieval. However, few strategies exist for brain-wide mapping of multiple ensembles, including their overlapping population, and none incorporate capabilities for downstream network analysis. Here, we introduce a scalable workflow to analyze traditionally coronally-sectioned datasets produced by activity-dependent tagging systems.

TAAR1 agonists improve glycemic control, reduce body weight and modulate neurocircuits governing energy balance and feeding.

Objective: Metabolic Syndrome, which can be induced or exacerbated by current antipsychotic drugs (APDs), is highly prevalent in schizophrenia patients. Recent preclinical and clinical evidence suggest that agonists at trace amine-associated receptor 1 (TAAR1) have potential as a new treatment option for schizophrenia. Intriguingly, preclinical tudies have also identified TAAR1 as a novel regulator of metabolic control.

Hallucination-Proneness is Associated With a Decrease in Robust Averaging of Perceptual Evidence.

Background And Hypothesis: Hallucinations are characterized by disturbances in perceptual decision-making about environmental stimuli. When integrating across multiple stimuli to form a perceptual decision, typical observers engage in "robust averaging" by down-weighting extreme perceptual evidence, akin to a statistician excluding outlying data. Furthermore, observers adapt to contexts with more unreliable evidence by increasing this down-weighting strategy.

Sex-Specific Effects of Anxiety on Cognition and Activity-Dependent Neural Networks: Insights from (Female) Mice and (Wo)Men.

Introduction: Neuropsychiatric symptoms (NPS), such as depression and anxiety, are observed in 90% of Alzheimer's disease (AD) patients, two-thirds of whom are women. NPS usually manifest long before AD onset creating a therapeutic opportunity. Here, we examined the impact of anxiety on AD progression and the underlying brain-wide neuronal mechanisms.

The functional heterogeneity of PACAP: Stress, learning, and pathology.

Pituitary adenylate cyclase-activating peptide (PACAP) is a highly conserved and widely expressed neuropeptide that has emerged as a key regulator of multiple neural and behavioral processes. PACAP systems, including the various PACAP receptor subtypes, have been implicated in neural circuits of learning and memory, stress, emotion, feeding, and pain. Dysregulation within these PACAP systems may play key roles in the etiology of pathological states associated with these circuits, and PACAP function has been implicated in stress-related psychopathology, feeding and metabolic disorders, and migraine.

Perspective on equitable translational studies and clinical support for an unbiased inclusion of the LGBTQIA2S+community.

Research regarding the mental health of the Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual, 2 Spirit (LGBTQIA2S+) community has been historically biased by individual and structural homophobia, biphobia, and transphobia, resulting in research that does not represent the best quality science. Furthermore, much of this research does not serve the best interests or priorities of LGBTQIA2S + communities, despite significant mental health disparities and great need for quality mental health research and treatments in these populations. Here, we will highlight how bias has resulted in missed opportunities for advancing understanding of mental health within LGBTQIA2S + communities.

Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.

Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan's unimodality dip test).

The effects of base rate neglect on sequential belief updating and real-world beliefs.

Base-rate neglect is a pervasive bias in judgment that is conceptualized as underweighting of prior information and can have serious consequences in real-world scenarios. This bias is thought to reflect variability in inferential processes but empirical support for a cohesive theory of base-rate neglect with sufficient explanatory power to account for longer-term and real-world beliefs is lacking. A Bayesian formalization of base-rate neglect in the context of sequential belief updating predicts that belief trajectories should exhibit dynamic patterns of dependence on the order in which evidence is presented and its consistency with prior beliefs.

Weapons of stress reduction: (R,S)-ketamine and its metabolites as prophylactics for the prevention of stress-induced psychiatric disorders.

Exposure to stress is one of the greatest contributing factors to developing a psychiatric disorder, particularly in susceptible populations. Enhancing resilience to stress could be a powerful intervention to reduce the incidence of psychiatric disease and reveal insight into the pathophysiology of psychiatric disorders. (R,S)-ketamine and its metabolites have recently been shown to exert protective effects when administered before or after a variety of stressors and may be effective, tractable prophylactic compounds against psychiatric disease.

Early Course of Symptom Development in Anorexia Nervosa.

Purpose: Anorexia nervosa (AN) commonly begins in adolescence; however, detailed knowledge of symptom trajectories, including their temporal sequence, is less well elucidated. The purpose of the present study is to describe the onset and duration of disordered eating behaviors prior to a diagnosis of AN, examine concordance between child and parent report, and examine the relationships between timing of symptom onset and illness severity.

Methods: Seventy-one adolescents (ages 12-18 years) and their parents were interviewed about dieting, restriction, loss of control/binge eating, purging, excessive/compulsive exercise, weight history, and amenorrhea.

Early life adversity shapes neural circuit function during sensitive postnatal developmental periods.

Early life adversity (ELA) is a major risk factor for mental illness, but the neurobiological mechanisms by which ELA increases the risk for future psychopathology are still poorly understood. Brain development is particularly malleable during prenatal and early postnatal life, when complex neural circuits are being formed and refined through an interplay of excitatory and inhibitory neural input, synaptogenesis, synaptic pruning, myelination, and neurogenesis. Adversity that influences these processes during sensitive periods of development can thus have long-lasting and pervasive effects on neural circuit maturation.

Propranolol Administration Modulates Neural Activity in the Hippocampal Hilus During Fear Retrieval.

Altered fear learning is a strong behavioral component of anxiety disorders such as post-traumatic stress disorder (PTSD). Recent efforts have attempted to combine exposure therapies with drugs that target fear memory retrieval and memory reconsolidation, in order to improve treatment efficacy. The noradrenergic (NA) signaling system is of particular interest, due to its role in regulating the stress response and its involvement in fear and learning processes.

Sustained Negative Mental Health Outcomes Among Healthcare Workers Over the First Year of the COVID-19 Pandemic: A Prospective Cohort Study.

To characterize the evolution of healthcare workers' mental health status over the 1-year period following the initial COVID-19 pandemic outbreak and to examine baseline characteristics associated with resolution or persistence of mental health problems over time. We conducted an 8-month follow-up cohort study. Eligible participants were healthcare workers working in Spain.

A Review of Clinical Practice Guidelines in the Diagnosis and Treatment of Attention-Deficit/Hyperactivity Disorder.

Clinical practice guidelines (CPGs) are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances. CPGs have evolved during the last 2 decades from general consensus statements by prominent practitioners in the field to highly structured instruments. The Institute of Medicine has laid out specific standards for selecting the experts who develop a CPG and the process by which CPGs are developed.

Acute ()-Ketamine Administration Induces Sex-Specific Behavioral Effects in Adolescent but Not Aged Mice.

(,)-ketamine is an -methyl-D-aspartate (NMDA) receptor antagonist that was originally developed as an anesthetic. Most recently, (,)-ketamine has been used as a rapid-acting antidepressant, and we have reported that (,)-ketamine can also be a prophylactic against stress in adult mice. However, most pre-clinical studies have been performed in adult mice.

Differential Effects of Human P301L Tau Expression in Young versus Aged Mice.

The greatest risk factor for developing Alzheimer's disease (AD) is increasing age. Understanding the changes that occur in aging that make an aged brain more susceptible to developing AD could result in novel therapeutic targets. In order to better understand these changes, the current study utilized mice harboring a regulatable mutant P301L human transgene (rTg(TauP301L)4510), in which P301L tau expression can be turned off or on by the addition or removal of doxycycline in the drinking water.

Reviving through human hippocampal newborn neurons.

Recent contradictory data has renewed discussion regarding the existence of adult hippocampal neurogenesis (AHN) in humans, i.e., the continued production of new neurons in the brain after birth.