Journal of psychiatry and brain science最新文献

Endogenous neuropeptide Oxytocin (OXT) plays a crucial role in modulating pro-social behavior and the neural response to social/emotional stimuli. Intranasal administration is the most common method of delivering OXT. Intranasal OXT has been implemented in clinical studies of various psychiatric disorders with mixed results, mainly related to lack of solid pharmacodynamics and pharmacokinetics model. Due to intranasal OXT's mechanism of reducing the activation of neural areas implicated in emotional responding and emotion regulation, a psychopathology with this target mechanism could be potentially excellent candidate for future clinical trial. In this regard, irritability in youth may be a very promising target for clinical studies of intranasal OXT. Here we provide a mini-review of fifteen randomized controlled trials in pediatric patients with diagnoses of autism spectrum disorder (ASD), Prader-Willi syndrome (PWS), or Phelan-McDermid syndrome (PMS). Most studies had small sample sizes and varying dosages, with changes in irritability, mainly as adverse events (AEs). Neuroimaging results showed modulation of the reward processing system and the neural areas implicated in social-emotional information processing by intranasal OXT administration. Further research is needed to determine the most effective dose and duration of OXT treatment, carefully select target psychopathologies, verify target engagement, and measure adverse event profiles.

Depression is the most common mental illness in the U.S. affecting nearly 40 million adults age 18 years and older. Depression has both genetic and environmental influences. In addition, women are more likely to be affected by depression than men. However, the relationship between genes and depression is complex and may be influenced by sex. Understanding the genetic basis of sex-specific differences for depression has the potential to lead to new biological understanding of the etiology of depression in females compared to males and to promote the development of novel and more effective pharmacotherapies. This review examines the role of sex in genetic associations with depression for both genome-wide association and candidate gene studies. While the genetic association signals of depression differ by sex, the role of sex in the heritability of depression is complex and warrants further investigation.

Affective reactions to acute stressors often evoke exacerbations of psychotic symptoms and sometimes de novo psychotic symptoms and initial psychotic episodes. Across the lifespan, affective reactions to acute stressors are enhanced by successive adverse childhood experiences (ACEs), in a process called "behavioral sensitization". The net effects of behavioral sensitization of acute stress responses are to alter responsivity to positive and negative feedback and to unexpected events, regardless of valence, leading to the maladaptive assignment of salience to stimuli and events. The assignment of "aberrant" salience to stimuli and events has profound consequences for learning and decision-making, which can influence both the positive and negative symptoms of psychosis. In this review, we discuss some of the psychological and neural mechanisms by which affective reactivity to acute stress, and its sensitization through the experience of stress and trauma across the lifespan, impact both the positive and negative symptoms of psychosis. We recount how the reward and salience networks of the brain, together with inputs from the dopamine and serotonin neurotransmitter systems, are implicated in both affective reactivity to stress and the symptoms of psychosis, likely mediate the effects of stress and trauma on the symptoms of psychosis and could serve as targets for interventions.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by early-onset repetitive behaviors, restricted interests, sensory and motor difficulties, and impaired social interactions. Converging evidence from neuroimaging, lesion and postmortem studies, and rodent models suggests cerebellar involvement in ASD and points to promising targets for therapeutic interventions for the disorder. This review elucidates understanding of cerebellar mechanisms in ASD by integrating and contextualizing recent structural and functional cerebellar research.

Autism spectrum disorders are common neurodevelopmental disorders that are defined by core behavioral symptoms but have diverse genetic and environmental risk factors. Despite its etiological heterogeneity, several unifying theories of autism have been proposed, including a central role for cerebellar dysfunction. The cerebellum follows a protracted course of development that culminates in an exquisitely crafted brain structure containing over half of the neurons in the entire brain densely packed into a highly organized structure. Through its complex network of connections with cortical and subcortical brain regions, the cerebellum acts as a sensorimotor regulator and affects changes in executive and limbic processing. In this review, we summarize the structural, functional, and genetic contributions of the cerebellum to autism.

Bipolar disorder (BD) is a common mood disorder that can have severe consequences during later life, including suffering and impairment due to mood and cognitive symptoms, elevated risk for dementia and an especially high risk for suicide. Greater understanding of the brain circuitry differences involved in older adults with BD (OABD) in later life and their relationship to aging processes is required to improve outcomes of OABD. The current literature on gray and white matter findings, from high resolution structural and diffusion-weighted magnetic resonance imaging (MRI) studies, has shown that BD in younger age groups is associated with gray matter reductions within cortical and subcortical brain regions that subserve emotion processing and regulation, as well as reduced structural integrity of white matter tracts connecting these brain regions. While fewer neuroimaging studies have focused on OABD, it does appear that many of the structural brain differences found in younger samples are present in OABD. There is also initial suggestion that there are additional brain differences, for at least a subset of OABD, that may result from more pronounced gray and white matter declines with age that may contribute to adverse outcomes. Preclinical and clinical data supporting neuro-plastic and -protective effects of mood-stabilizing medications, suggest that treatments may reverse and/or prevent the progression of brain changes thereby reducing symptoms. Future neuroimaging research implementing longitudinal designs, and large-scale, multi-site initiatives with detailed clinical and treatment data, holds promise for reducing suffering, cognitive dysfunction and suicide in OABD.

Loneliness, or the subjective feeling of social isolation, is an important social determinant of health. Loneliness is associated with poor physical health, including higher rates of cardiovascular disease and dementia, faster cognitive decline, and increased risk of mortality, as well as disruptions in mental health, including higher levels of depression, anxiety, and negative affect. Theoretical accounts suggest loneliness is a complex cognitive and emotional state characterized by increased levels of inflammation and affective disruptions. This review examines affective neuroscience research on social isolation in animals and loneliness in humans to better understand the relationship between perceptions of social isolation and the brain. Loneliness associated increases in inflammation and neural changes consistent with increased sensitivity to social threat and disrupted emotion regulation suggest interventions targeting maladaptive social cognitions may be especially effective. Work in animal models suggests the neural changes associated with social isolation may be reversible. Therefore, ameliorating loneliness may be an actionable social determinant of health target. However, more research is needed to understand how loneliness impacts healthy aging, explore the role of inflammation as a potential mechanism in humans, and determine the best time to deliver interventions to improve physical health, mental health, and well-being across a diverse array of populations.