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Child and Adolescent Psychiatric... Oct 2019Eating disorders are severe psychiatric illnesses with a typical age of onset in adolescence. Brain research in youth and young adults may help us identify specific... (Review)
Review
Eating disorders are severe psychiatric illnesses with a typical age of onset in adolescence. Brain research in youth and young adults may help us identify specific neurobiology that contributes to onset and maintenance of those disorders. This article provides a state-of-the-art review of our current understanding of the neurobiology of anorexia nervosa and bulimia nervosa. This includes brain structure and function studies to understand food restriction, binge-eating or purging behaviors, cognitive and emotional factors, as well as interoception. Binge-eating disorder and avoidant restrictive food intake disorder are also discussed, but the literature is still very small.
Topics: Adolescent; Anorexia Nervosa; Binge-Eating Disorder; Brain; Bulimia Nervosa; Child; Feeding and Eating Disorders; Humans; Magnetic Resonance Imaging; Nerve Net; Neurobiology; Young Adult
PubMed: 31443880
DOI: 10.1016/j.chc.2019.05.007 -
The Lancet. Psychiatry Aug 2016Drug addiction represents a dramatic dysregulation of motivational circuits that is caused by a combination of exaggerated incentive salience and habit formation, reward... (Review)
Review
Drug addiction represents a dramatic dysregulation of motivational circuits that is caused by a combination of exaggerated incentive salience and habit formation, reward deficits and stress surfeits, and compromised executive function in three stages. The rewarding effects of drugs of abuse, development of incentive salience, and development of drug-seeking habits in the binge/intoxication stage involve changes in dopamine and opioid peptides in the basal ganglia. The increases in negative emotional states and dysphoric and stress-like responses in the withdrawal/negative affect stage involve decreases in the function of the dopamine component of the reward system and recruitment of brain stress neurotransmitters, such as corticotropin-releasing factor and dynorphin, in the neurocircuitry of the extended amygdala. The craving and deficits in executive function in the so-called preoccupation/anticipation stage involve the dysregulation of key afferent projections from the prefrontal cortex and insula, including glutamate, to the basal ganglia and extended amygdala. Molecular genetic studies have identified transduction and transcription factors that act in neurocircuitry associated with the development and maintenance of addiction that might mediate initial vulnerability, maintenance, and relapse associated with addiction.
Topics: Brain; Humans; Neural Pathways; Neurobiology; Substance-Related Disorders
PubMed: 27475769
DOI: 10.1016/S2215-0366(16)00104-8 -
Molecular Psychiatry Jan 2021The current opioid epidemic is one of the most severe public health crisis in US history. Responding to it has been difficult due to its rapidly changing nature and the... (Review)
Review
The current opioid epidemic is one of the most severe public health crisis in US history. Responding to it has been difficult due to its rapidly changing nature and the severity of its associated outcomes. This review examines the origin and evolution of the crisis, the pharmacological properties of opioids, the neurobiology of opioid use and opioid use disorder (OUD), medications for opioid use disorder (MOUD), and existing and promising approaches to prevention. The results of the review indicate that the opioid epidemic is a complex, evolving phenomenon that involves neurobiological vulnerabilities and social determinants of health. Successfully addressing the epidemic will require advances in basic science, development of more acceptable and effective treatments, and implementation of public health approaches, including prevention. The advances achieved in addressing the current crisis should also serve to advance the science and treatment of other substance use disorders.
Topics: Analgesics, Opioid; Humans; Neurobiology; Opioid Epidemic; Opioid-Related Disorders; Social Factors
PubMed: 32020048
DOI: 10.1038/s41380-020-0661-4 -
Cold Spring Harbor Perspectives in... Apr 2021Drug addiction is a chronic relapsing disorder, and a significant amount of research has been devoted to understand the factors that contribute to the development, loss... (Review)
Review
Drug addiction is a chronic relapsing disorder, and a significant amount of research has been devoted to understand the factors that contribute to the development, loss of control, and persistence of compulsive addictive behaviors. In this review, we provide an overview of various theories of addiction to drugs of abuse and the neurobiology involved in elements of the addiction cycle. Specific focus is devoted to the role of the mesolimbic pathway in acute drug reinforcement and occasional drug use, the role of the mesocortical pathway and associated areas (e.g., the dorsal striatum) in escalation/dependence, and the contribution of these pathways and associated circuits to conditioned responses, drug craving, and loss of behavioral control that may underlie drug relapse. By enhancing the understanding of the neurobiological factors that mediate drug addiction, continued preclinical and clinical research will aid in the development of novel therapeutic interventions that can serve as effective long-term treatment strategies for drug-dependent individuals.
Topics: Behavior, Addictive; Disease Progression; Humans; Neurobiology; Recurrence; Substance-Related Disorders
PubMed: 32205414
DOI: 10.1101/cshperspect.a039628 -
Cell Feb 2020We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical...
We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neurodevelopmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In cells from the human cortex, expression of risk genes is enriched in excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.
Topics: Autistic Disorder; Case-Control Studies; Cell Lineage; Cerebral Cortex; Cohort Studies; Exome; Female; Gene Expression Regulation, Developmental; Gene Frequency; Genetic Predisposition to Disease; Humans; Male; Mutation, Missense; Neurobiology; Neurons; Phenotype; Sex Factors; Single-Cell Analysis; Exome Sequencing
PubMed: 31981491
DOI: 10.1016/j.cell.2019.12.036 -
Current Biology : CB Jan 2022Psychedelics are compounds that alter consciousness by acting on serotonin receptors in the brain. The term 'psychedelic', from the Greek for mind manifesting, refers to... (Review)
Review
Psychedelics are compounds that alter consciousness by acting on serotonin receptors in the brain. The term 'psychedelic', from the Greek for mind manifesting, refers to the drugs' subjective effects and was first proposed by Humphry Osmond in 1956. Other terms have been used to emphasize different aspects of the psychological experiences produced by various related compounds, including hallucinogens (perceptual), entheogens (spiritual), and empathogens or entactogens (social/emotional). The diversity in terminology reflects the existence of hundreds of potential psychedelic compounds with a spectrum of behavioral and neurobiological effects. Recent data on the effectiveness of psychedelics for treating mental illnesses has led to a resurgence of interest in their neurobiological effects. The purpose of this Primer is to provide those interested in the field of psychedelics with a concise and accessible overview of the scientific data.
Topics: Brain; Consciousness; Hallucinogens; Humans; Mental Disorders; Neurobiology
PubMed: 35077687
DOI: 10.1016/j.cub.2021.12.009 -
International Journal of Environmental... Sep 2021The notion of food "addiction" often focuses on the overconsumption of sweet tasting foods or so-called sugar "addiction". In the extreme, some have suggested that sugar... (Review)
Review
The notion of food "addiction" often focuses on the overconsumption of sweet tasting foods or so-called sugar "addiction". In the extreme, some have suggested that sugar and sweet tastes elicit neural and behavioral responses analogous to those observed with drugs of abuse. These concepts are complicated by the decades long uncertainty surrounding the validity and reproducibility of functional magnetic resonance imaging (fMRI) methodologies used to characterize neurobiological pathways related to sugar and sweet taste stimuli. There are also questions of whether sweet taste or post-ingestion metabolic consequences of sugar intake would lead to addiction or excessive caloric intake. Here, we present a focused narrative review of literature related to the reward value of sweet taste which suggests that reward value can be confounded with the construct of "addictive potential". Our review seeks to clarify some key distinctions between these constructs and questions the applicability of the addiction construct to human over-eating behaviors. To adequately frame this broad discussion requires the flexibility offered by the narrative review paradigm. We present selected literature on: techniques used to link sugar and sweet tastes to addiction neurobiology and behaviors; sugar and sweet taste "addiction"; the relationship of low calorie sweetener (LCS) intake to addictive behaviors and total calorie intake. Finally, we examined the reward value of sweet tastes and contrasted that with the literature describing addiction. The lack of reproducibility of fMRI data remains problematic for attributing a common neurobiological pathway activation of drugs and foods as conclusive evidence for sugar or sweet taste "addiction". Moreover, the complicated hedonics of sweet taste and reward value are suggested by validated population-level data which demonstrate that the consumption of sweet taste in the absence of calories does not increase total caloric intake. We believe the neurobiologies of reward value and addiction to be distinct and disagree with application of the addiction model to sweet food overconsumption. Most hypotheses of sugar "addiction" attribute the hedonics of sweet foods as the equivalent of "addiction". Further, when addictive behaviors and biology are critically examined in totality, they contrast dramatically from those associated with the desire for sweet taste. Finally, the evidence is strong that responses to the palatability of sweets rather than their metabolic consequences are the salient features for reward value. Thus, given the complexity of the controls of food intake in humans, we question the usefulness of the "addiction" model in dissecting the causes and effects of sweet food over-consumption.
Topics: Behavior, Addictive; Humans; Reproducibility of Results; Reward; Sugars; Sweetening Agents; Taste
PubMed: 34574716
DOI: 10.3390/ijerph18189791 -
Nature Reviews. Neuroscience Feb 2019Narcolepsy is the most common neurological cause of chronic sleepiness. The discovery about 20 years ago that narcolepsy is caused by selective loss of the neurons... (Review)
Review
Narcolepsy is the most common neurological cause of chronic sleepiness. The discovery about 20 years ago that narcolepsy is caused by selective loss of the neurons producing orexins (also known as hypocretins) sparked great advances in the field. Here, we review the current understanding of how orexin neurons regulate sleep-wake behaviour and the consequences of the loss of orexin neurons. We also summarize the developing evidence that narcolepsy is an autoimmune disorder that may be caused by a T cell-mediated attack on the orexin neurons and explain how these new perspectives can inform better therapeutic approaches.
Topics: Animals; Autoimmune Diseases; Humans; Narcolepsy; Nervous System; Neurobiology; Orexins
PubMed: 30546103
DOI: 10.1038/s41583-018-0097-x -
Biological Psychiatry Sep 2019Stress-related neuropsychiatric disorders, such as major depressive disorder and posttraumatic stress disorder, exact enormous socioeconomic and individual consequences.... (Review)
Review
Stress-related neuropsychiatric disorders, such as major depressive disorder and posttraumatic stress disorder, exact enormous socioeconomic and individual consequences. Resilience, the process of adaptation in the face of adversity, is an important concept that is enabling the field to understand individual differences in stress responses, with the hope of harnessing this information for the development of novel therapeutics that mimic the body's natural resilience mechanisms. This review provides an update on the current state of research of the neurobiological mechanisms of stress resilience. We focus on physiological and transcriptional adaptations of specific brain circuits, the role of cellular and humoral factors of the immune system, the gut microbiota, and changes at the interface between the brain and the periphery, the blood-brain barrier. We propose viewing resilience as a process that requires the integration of multiple central and peripheral systems and that elucidating the underlying neurobiological mechanisms will ultimately lead to novel therapeutic options.
Topics: Adaptation, Psychological; Blood-Brain Barrier; Brain; Depressive Disorder, Major; Gastrointestinal Microbiome; Humans; Immune System; Neurobiology; Psychophysiology; Resilience, Psychological; Stress Disorders, Post-Traumatic; Synaptic Transmission
PubMed: 31178098
DOI: 10.1016/j.biopsych.2019.04.011 -
Journal of Visualized Experiments : JoVE Feb 2016Having appropriate in vivo and in vitro systems that provide translational models for human disease is an integral aspect of research in neurobiology and the...
Having appropriate in vivo and in vitro systems that provide translational models for human disease is an integral aspect of research in neurobiology and the neurosciences. Traditional in vitro experimental models used in neurobiology include primary neuronal cultures from rats and mice, neuroblastoma cell lines including rat B35 and mouse Neuro-2A cells, rat PC12 cells, and short-term slice cultures. While many researchers rely on these models, they lack a human component and observed experimental effects could be exclusive to the respective species and may not occur identically in humans. Additionally, although these cells are neurons, they may have unstable karyotypes, making their use problematic for studies of gene expression and reproducible studies of cell signaling. It is therefore important to develop more consistent models of human neurological disease. The following procedure describes an easy-to-follow, reproducible method to obtain homogenous and viable human neuronal cultures, by differentiating the chromosomally stable human neuroblastoma cell line, SH-SY5Y. This method integrates several previously described methods(1-4) and is based on sequential removal of serum from media. The timeline includes gradual serum-starvation, with introduction of extracellular matrix proteins and neurotrophic factors. This allows neurons to differentiate, while epithelial cells are selected against, resulting in a homogeneous neuronal culture. Representative results demonstrate the successful differentiation of SH-SY5Y neuroblastoma cells from an initial epithelial-like cell phenotype into a more expansive and branched neuronal phenotype. This protocol offers a reliable way to generate homogeneous populations of neuronal cultures that can be used for subsequent biochemical and molecular analyses, which provides researchers with a more accurate translational model of human infection and disease.
Topics: Cell Count; Cell Culture Techniques; Cell Differentiation; Cell Line, Tumor; Humans; Neurobiology; Neuroblastoma; Neurons
PubMed: 26967710
DOI: 10.3791/53193