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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Historically, the insula was considered primary gustatory cortex. Now it is known to play a more comprehensive role in the processing of sensory information, including acting as primary cortex for interoceptive information, including autonomic nervous system mediated changes. As such, it is critical for emotional feeling in accord with the James-Lange theory, a role previously ascribed to the limbic system. Neuroimaged abnormal grey matter volumes or activity levels in the insula have been associated with schizophrenia, eating disorders, anxiety and mood disorders, conduct disorder, autism, addiction, and chronic pain. The significance of these abnormal activity patterns remains theoretical. Neuropsychological studies have linked dominant insula injury with various symptoms of aphasia, but its exact role in language processing remains uncertain as most cases involve lesions that extend into perisylvian language zones. Functional neuroimaging studies have found insula hyper-activations, typically in conjunction with anterior cingulate cortex, for all manner of experimental tasks including those involving perception, intentional action, and consciousness. Such neuroimaged activity is unlikely to be task-specific, but rather reflective of generic changes in autonomic activity in response to salience, homeostatic incongruence, or cognitive challenge.
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PMID:Contributions of the insula to cognition and emotion. 2444 2

Like most psychiatric disorders, autism spectrum disorders have both a genetic and an environmental component. While previous studies have clearly demonstrated the contribution of in utero (prenatal) environment on autism risk, most of them focused on transient environmental factors. Based on a recent sibling study, we hypothesized that environmental factors could also come from the maternal genome, which would result in persistent effects across siblings. In this study, the possibility of maternal genotype effects was examined by looking for common variants (single-nucleotide polymorphisms or SNPs) in the maternal genome associated with increased risk of autism in children. A case/control genome-wide association study was performed using mothers of probands as cases, and either fathers of probands or normal females as controls. Autism Genetic Resource Exchange and Illumina Genotype Control Database were used as our discovery cohort (n = 1616). The same analysis was then replicated on Simon Simplex Collection and Study of Addiction: Genetics and Environment datasets (n = 2732). We did not identify any SNP that reached genome-wide significance (P < 10(-8) ), and thus a common variant of large effect is unlikely. However, there was evidence for the possibility of a large number of alleles of effective size marginally below our power to detect.
Autism Res 2014 Apr
PMID:Investigation of maternal genotype effects in autism by genome-wide association. 2457 47

This article describes the teenage vision of the founder of the Multidisciplinary Association for Psychedelic Studies (MAPS) that humanity's future would be aided by the therapeutic and spiritual potential of psychedelic substances. The article traces the trajectory of MAPS from inception in 1986 to its present, noting future goals with respect to research, outreach, and harm reduction. MAPS was created as a non-profit psychedelic pharmaceutical company in response to the 1985 scheduling of 3,4-methylenedioxymethamphetamine (MDMA). Overcoming many hurdles, MAPS developed the first double-blind, placebo-controlled trial of MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) and plans for FDA prescription approval in 2021. MAPS' program of research expanded to include a trial of lysergic acid diethylamide (LSD)-assisted psychotherapy for anxiety when facing life-threatening illness, observational studies of ibogaine in the treatment of addiction, and studies of MDMA for social anxiety in people with autism spectrum disorders. MAPS meets the challenges of drug development through a clinical research team led by a former Novartis drug development professional experienced in the conduct, monitoring, and analysis of clinical trials. MAPS' harm-reduction efforts are intended to avoid backlash and build a post-prohibition world by assisting non-medical users to transform difficult psychedelic experiences into opportunities for growth.
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PMID:History and future of the Multidisciplinary Association for Psychedelic Studies (MAPS). 2483 Jan 83

The knowledge that diverse populations of dopaminergic neurons within the ventral tegmental area (VTA) can be distinguished in terms of their molecular, electrophysiological and functional properties, as well as their differential projections to cortical and subcortical regions has significance for key brain functions, such as the regulation of motivation, working memory and sensorimotor control. Almost without exception, this understanding has evolved from landmark studies performed in the male sex. However, converging evidence from both clinical and pre-clinical studies illustrates that the structure and functioning of the VTA dopaminergic systems are intrinsically different in males and females. This may be driven by sex differences in the hormonal environment during adulthood ('activational' effects) and development (perinatal and/or pubertal 'organizational' effects), as well as genetic factors, especially the SRY gene on the Y chromosome in males, which is expressed in a sub-population of adult midbrain dopaminergic neurons. Stress and stress hormones, especially glucocorticoids, are important factors which interact with the VTA dopaminergic systems in order to achieve behavioral adaptation and enable the individual to cope with environmental change. Here, also, there is male/female diversity not only during adulthood, but also in early life when neurobiological programing by stress or glucocorticoid exposure differentially impacts dopaminergic developmental trajectories in male and female brains. This may have enduring consequences for individual resilience or susceptibility to pathophysiological change induced by stressors in later life, with potential translational significance for sex bias commonly found in disorders involving dysfunction of the mesocorticolimbic dopaminergic systems. These findings highlight the urgent need for a better understanding of the sexual dimorphism in the VTA if we are to improve strategies for the prevention and treatment of debilitating conditions which differentially affect men and women in their prevalence and nature, including schizophrenia, attention/deficit hyperactivity disorder, autism spectrum disorders, anxiety, depression and addiction.
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PMID:Sex-dependent diversity in ventral tegmental dopaminergic neurons and developmental programing: A molecular, cellular and behavioral analysis. 2494 15

Metabotropic glutamate receptors are class C G-protein-coupled receptors which respond to the neurotransmitter glutamate. Structural studies have been restricted to the amino-terminal extracellular domain, providing little understanding of the membrane-spanning signal transduction domain. Metabotropic glutamate receptor 5 is of considerable interest as a drug target in the treatment of fragile X syndrome, autism, depression, anxiety, addiction and movement disorders. Here we report the crystal structure of the transmembrane domain of the human receptor in complex with the negative allosteric modulator, mavoglurant. The structure provides detailed insight into the architecture of the transmembrane domain of class C receptors including the precise location of the allosteric binding site within the transmembrane domain and key micro-switches which regulate receptor signalling. This structure also provides a model for all class C G-protein-coupled receptors and may aid in the design of new small-molecule drugs for the treatment of brain disorders.
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PMID:Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain. 2504 98

Although G protein-coupled receptors are primarily known for converting extracellular signals into intracellular responses, some receptors, such as the group 1 metabotropic glutamate receptor, mGlu5, are also localized on intracellular membranes where they can mediate both overlapping and unique signaling effects. Thus, besides "ligand bias," whereby a receptor's signaling modality can shift from G protein dependence to independence, canonical mGlu5 receptor signaling can also be influenced by "location bias" (i.e., the particular membrane and/or cell type from which it signals). Because mGlu5 receptors play important roles in both normal development and in disorders such as Fragile X syndrome, autism, epilepsy, addiction, anxiety, schizophrenia, pain, dyskinesias, and melanoma, a large number of drugs are being developed to allosterically target this receptor. Therefore, it is critical to understand how such drugs might be affecting mGlu5 receptor function on different membranes and in different brain regions. Further elucidation of the site(s) of action of these drugs may determine which signal pathways mediate therapeutic efficacy.
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PMID:Location-dependent signaling of the group 1 metabotropic glutamate receptor mGlu5. 2532 2

Serotonin is one of the most important neurotransmitters influencing mental health and, thus, is a potential target for pharmaco-logical treatments. Functional neuroimaging techniques, such as positron-emission tomography (PET) and single photon emission computed tomography (SPECT), could provide persuasive evidence for the association between mental disorders and serotonin. In this concise review, we focus on evidence of the links between serotonin and major depressive disorders, as well as other mood disorders, anxiety disorders, schizophrenia, addiction, attention deficit hyperactivity disorder (ADHD), and autism.
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PMID:Serotonin and mental disorders: a concise review on molecular neuroimaging evidence. 2559 22

This longitudinal study investigated the prevalence, predictors, and related factors for Internet addiction among elementary and junior high school students in Taiwan. A convenient sample of grades 3, 5, and 8 students (n = 1153) was recruited from six elementary and one junior high schools. They were assessed during the beginning and the end of the spring semester of 2013. Internet addiction was examined by the Chen Internet Addiction Scale (CIAS). Other factors were screened using the Chinese version of the Autism Spectrum Quotient (AQ) for autistic trait, the Parental Bonding Instrument (PBI) for parenting, the Family APGAR for family support, the Social Adjustment Inventory for Children and Adolescents for social function, and the Swanson, Nolan, and Pelham, version IV scale (SNAP-IV) for ADHD symptoms. The prevalence of Internet addiction decreased from 11.4% to 10.6%. Male, low family support, poor social adjustment, and high ADHD-related symptoms were related to Internet addiction. However, there was an inverse relationship between autistic traits and Internet addiction. Further, its predictivity could be accounted by poor academic performance, male, and protective parenting style. Internet addiction is not uncommon among youths in Taiwan. The predictors identified in this study could be the specific measures for the development of a prevention program for Internet addiction in the youth population.
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PMID:ADHD and autistic traits, family function, parenting style, and social adjustment for Internet addiction among children and adolescents in Taiwan: a longitudinal study. 2561 44

The presynaptic, cocaine- and amphetamine-sensitive dopamine (DA) transporter (DAT, SLC6A3) controls the intensity and duration of synaptic dopamine signals by rapid clearance of DA back into presynaptic nerve terminals. Abnormalities in DAT-mediated DA clearance have been linked to a variety of neuropsychiatric disorders, including addiction, autism, and attention deficit/hyperactivity disorder (ADHD). Membrane trafficking of DAT appears to be an important, albeit incompletely understood, post-translational regulatory mechanism; its dysregulation has been recently proposed as a potential risk determinant of these disorders. In this study, we demonstrate a link between an ADHD-associated DAT mutation (Arg615Cys, R615C) and variation on DAT transporter cell surface dynamics, a combination only previously studied with ensemble biochemical and optical approaches that featured limited spatiotemporal resolution. Here, we utilize high-affinity, DAT-specific antagonist-conjugated quantum dot (QD) probes to establish the dynamic mobility of wild-type and mutant DATs at the plasma membrane of living cells. Single DAT-QD complex trajectory analysis revealed that the DAT 615C variant exhibited increased membrane mobility relative to DAT 615R, with diffusion rates comparable to those observed after lipid raft disruption. This phenomenon was accompanied by a loss of transporter mobilization triggered by amphetamine, a common component of ADHD medications. Together, our data provides the first dynamic imaging of single DAT proteins, providing new insights into the relationship between surface dynamics and trafficking of both wild-type and disease-associated transporters. Our approach should be generalizable to future studies that explore the possibilities of perturbed surface DAT dynamics that may arise as a consequence of genetic alterations, regulatory changes, and drug use that contribute to the etiology or treatment of neuropsychiatric disorders.
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PMID:Single-quantum-dot tracking reveals altered membrane dynamics of an attention-deficit/hyperactivity-disorder-derived dopamine transporter coding variant. 2574 72

Extensive research over the past thirty years has demonstrated a vital role for metabotropic glutamate (mGlu) receptors in the major functions of the central nervous system (CNS). A wealth of preclinical studies provide evidence that pharmacological targeting of mGlu receptors can effectively attenuate the development of symptoms and progression of many CNS disorders in animal models. In this review we summarize the current knowledge on the involvement of mGlu receptors in the pathophysiology of neuropsychiatric disorders (schizophrenia, depression, anxiety and cognitive disorders, pain perception and addiction), as well as neurodegenerative (Alzheimer's, Huntington's and Parkinson's diseases) and neurodevelopmental (fragile X syndrome and autism spectrum disorders) diseases. We further emphasize the therapeutic potential of mGlu receptors' pharmacological modulators in these diseases, describe the results of clinical trials with these compounds and discuss the potential sources of translational difficulties.
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PMID:Metabotropic Glutamate Receptors in Central Nervous System Diseases. 2577 73


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