Biological psychiatry
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Opioid use disorder (OUD) is a chronic, relapsing condition, often associated with legal, interpersonal, and employment problems. Medications demonstrated to be effective for OUD are methadone (a full opioid agonist), buprenorphine (a partial agonist), and naltrexone (an opioid antagonist). Methadone and buprenorphine act by suppressing opioid withdrawal symptoms and attenuating the effects of other opioids. ⋯ Naloxone is an opioid antagonist used to reverse opioid overdose, and take-home naloxone programs aim to prevent fatal overdose. All medication-assisted treatment is limited by lack of access and by stigma. In seeking to stem the rising toll from OUD, expanding access to approved treatment such as methadone, for which there remains the best evidence of efficacy, may be the most useful approach.
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Biological psychiatry · Feb 2018
ReviewHarnessing Gut Microbes for Mental Health: Getting From Here to There.
There has been an explosion of interest in the study of microorganisms inhabiting the gastrointestinal tract (gut microbiota) and their impact on host health and physiology. Accumulating data suggest that altered communication between gut microbiota and host systems could participate in disorders such as obesity, diabetes mellitus, and autoimmune disorders as well as neuropsychiatric disorders, including autism, anxiety, and major depressive disorders. The conceptual development of the microbiome-gut-brain axis has facilitated understanding of the complex and bidirectional networks between gastrointestinal microbiota and their host, highlighting potential mechanisms through which this environment influences central nervous system physiology. ⋯ However, uncertainty remains regarding the generalizability of controlled animal studies to the more multifaceted pattern of human pathophysiology, especially with regard to the therapeutic potential for neuropsychiatric health. This narrative review summarizes current understanding of gut microbial influence over physiological function, with an emphasis on neurobehavioral and neurological impairment based on growing understanding of the gut-brain axis. Experimental and clinical data regarding means of therapeutic manipulation of gut microbiota as a novel treatment option for mental health are described, and important knowledge gaps are identified and discussed.
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Biological psychiatry · Mar 2017
ReviewMaternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates.
A subset of women who are exposed to infection during pregnancy have an increased risk of giving birth to a child who will later be diagnosed with a neurodevelopmental or neuropsychiatric disorder. Although epidemiology studies have primarily focused on the association between maternal infection and an increased risk of offspring schizophrenia, mounting evidence indicates that maternal infection may also increase the risk of autism spectrum disorder. A number of factors, including genetic susceptibility, the intensity and timing of the infection, and exposure to additional aversive postnatal events, may influence the extent to which maternal infection alters fetal brain development and which disease phenotype (autism spectrum disorder, schizophrenia, other neurodevelopmental disorders) is expressed. ⋯ Maternal immune activation models in mice, rats, and nonhuman primates suggest that the maternal immune response is the critical link between exposure to infection during pregnancy and subsequent changes in brain and behavioral development of offspring. However, differences in the type, severity, and timing of prenatal immune challenge paired with inconsistencies in behavioral phenotyping approaches have hindered the translation of preclinical results to human studies. Here we highlight the promises and limitations of the maternal immune activation model as a preclinical tool to study prenatal risk factors for autism spectrum disorder, and suggest specific changes to improve reproducibility and maximize translational potential.
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Biological psychiatry · Mar 2017
ReviewEmerging Roles for the Gut Microbiome in Autism Spectrum Disorder.
Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder that affects one in 45 children in the United States, with a similarly striking prevalence in countries around the world. However, mechanisms underlying its etiology and manifestations remain poorly understood. Although ASD is diagnosed based on the presence and severity of impaired social communication and repetitive behavior, immune dysregulation and gastrointestinal issues are common comorbidities. ⋯ We further discuss potential effects of the microbiota on ASD-associated symptoms, drawing on signaling mechanisms for reciprocal interactions among the microbiota, immunity, gut function, and behavior. In addition, we discuss recent findings supporting a role for the microbiome as an interface between environmental and genetic risk factors that are associated with ASD. These studies highlight the integration of pathways across multiple body systems that together can impact brain and behavior and suggest that changes in the microbiome may contribute to symptoms of neurodevelopmental disease.
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Brain disorders remain one of the defining challenges of modern medicine and among the most poorly served with new therapeutics. Advances in human neurogenetics have begun to shed light on the genomic architecture of complex diseases of mood, cognition, brain development, and neurodegeneration. ⋯ However, the path from genetics to new medicines is far from clear and can take decades, even for the most well-understood genetic disorders. In this review, we define three challenges for the field of neurogenetics that we believe must be addressed to translate human genetics efficiently into new therapeutics for brain disorders.