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Janak P.H.,University of California at San Francisco | Bowers M.S.,Virginia Institute for Psychiatric and Behavioral Genetics | Corbit L.H.,University of California at San Francisco | Corbit L.H.,University of Sydney
Neuropsychopharmacology | Year: 2012

Drug abstinence is frequently compromised when addicted individuals are re-exposed to environmental stimuli previously associated with drug use. Research with human addicts and in animal models has demonstrated that extinction learning (non-reinforced cue-exposure) can reduce the capacity of such stimuli to induce relapse, yet extinction therapies have limited long-term success under real-world conditions (Bouton, 2002; OBrien, 2008). We hypothesized that enhancing extinction would reduce the later ability of drug-predictive cues to precipitate drug-seeking behavior. We, therefore, tested whether compound stimulus presentation and pharmacological treatments that augment noradrenergic activity (atomoxetine; norepinephrine reuptake inhibitor) during extinction training would facilitate the extinction of drug-seeking behaviors, thus reducing relapse. Rats were trained that the presentation of a discrete cue signaled that a lever press response would result in cocaine reinforcement. Rats were subsequently extinguished and spontaneous recovery of drug-seeking behavior following presentation of previously drug-predictive cues was tested 4 weeks later. We find that compound stimulus presentations or pharmacologically increasing noradrenergic activity during extinction training results in less future recovery of responding, whereas propranolol treatment reduced the benefit seen with compound stimulus presentation. These data may have important implications for understanding the biological basis of extinction learning, as well as for improving the outcome of extinction-based therapies. © 2012 American College of Neuropsychopharmacology. All rights reserved. Source

Chou L.-N.,National Taiwan University | Kuo P.-H.,National Cheng Kung University | Kuo P.-H.,Virginia Institute for Psychiatric and Behavioral Genetics | Lin C.C.H.,Eli Lilly and Company | And 3 more authors.
Behavior Genetics | Year: 2010

This study aimed to estimate the relative contributions from genetic and environmental factors to the Wisconsin Card Sorting Test (WCST) performance, a widely used measurement for assessing frontal lobe function. Participants included 350 pairs of twins (257 MZ and 93 DZ) and 47 same-sex sib-pairs, aged 12-16 years, systematically recruited from junior high schools in Taipei. A computerized version of the WCST was administered for each participant and its nine indexes were used for subsequent analysis. Univariate analysis in structural equation modeling was performed for each WCST index using Mx program. The ACE model for each WCST index indicated no significant genetic influence, whereas the shared environmental influence ranged from 30 to 38% for four indexes (Perseverative Errors, Perseverative Responses, Categories Achieved, and Conceptual Level Responses). We concluded that WCST performance might be an indicator more for environmental insult than for genetic influences on frontal lobe function. © 2009 Springer Science+Business Media, LLC. Source

Chartier K.G.,Virginia Commonwealth University | Chartier K.G.,Virginia Institute for Psychiatric and Behavioral Genetics | Vaeth P.A.C.,Pacific Institute for Research and Evaluation | Caetano R.,University of Texas at Dallas
Alcohol Research: Current Reviews | Year: 2013

Alcohol consumption is differentially associated with social and health harms across U.S. ethnic groups. Native Americans, Hispanics, and Blacks are disadvantaged by alcohol-attributed harms compared with Whites and Asians. Ethnicities with higher rates of risky drinking experience higher rates of drinking harms. Other factors that could contribute to the different effects of alcohol by ethnicity are social disadvantage, acculturation, drink preferences, and alcohol metabolism. This article examines the relationship of ethnicity and drinking to (1) unintentional injuries, (2) intentional injuries, (3) fetal alcohol syndrome (FAS), (4) gastrointestinal diseases, (5) cardiovascular diseases, (6) cancers, (7) diabetes, and (8) infectious diseases. Reviewed evidence shows that Native Americans have a disproportionate risk for alcohol-related motor vehicle fatalities, suicides and violence, FAS, and liver disease mortality. Hispanics are at increased risk for alcohol-related motor vehicle fatalities, suicide, liver disease, and cirrhosis mortality; and Blacks have increased risk for alcohol-related relationship violence, FAS, heart disease, and some cancers. However, the scientific evidence is incomplete for each of these harms. More research is needed on the relationship of alcohol consumption to cancers, diabetes, and HIV/AIDS across ethnic groups. Studies also are needed to delineate the mechanisms that give rise to and sustain these disparities in order to inform prevention strategies. Source

Barclay N.L.,Northumbria University | Gehrman P.R.,University of Pennsylvania | Gregory A.M.,Goldsmiths, University of London | Eaves L.J.,Virginia Institute for Psychiatric and Behavioral Genetics | Silberg J.L.,Virginia Commonwealth University
Sleep | Year: 2015

Study Objectives: To determine prevalence and heritability of insomnia during middle/late childhood and adolescence; examine longitudinal associations in insomnia over time; and assess the extent to which genetic and environmental factors on insomnia remain stable, or whether new factors come into play, across this developmental period.Design: Longitudinal twin study.Setting: Academic medical center.Patients or Participants: There were 739 complete monozygotic twin pairs (52%) and 672 complete dizygotic twin pairs (48%) initially enrolled and were followed up at three additional time points (waves). Mode ages at each wave were 8, 10, 14, and 15 y (ages ranged from 8-18 y).Interventions: None.Measurements and Results: Clinical ratings of insomnia symptoms were assessed using the Child and Adolescent Psychiatric Assessment (CAPA) by trained clinicians, and rated according to Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition-Revised criteria for presence of "clinically significant insomnia," over four sequential waves. Insomnia symptoms were prevalent but significantly decreased across the four waves (ranging from 16.6% to 31.2%). "Clinically significant insomnia" was moderately heritable at all waves (h2 range = 14% to 38%), and the remaining source of variance was the nonshared environment. Multivariate models indicated that genetic influences at wave 1 contributed to insomnia at all subsequent waves, and that new genetic influences came into play at wave 2, which further contributed to stability of symptoms. Nonshared environmental influences were time-specific.Conclusion: Insomnia is prevalent in childhood and adolescence, and is moderately heritable. The progression of insomnia across this developmental time period is influenced by stable as well as new genetic factors that come into play at wave 2 (modal age 10 y). Molecular genetic studies should now identify genes related to insomnia progression during childhood and adolescence. Source

Bowers M.S.,Virginia Institute for Psychiatric and Behavioral Genetics | Bowers M.S.,Institute for Drug and Alcohol Studies | Chen B.T.,University of California at San Francisco | Bonci A.,University of California at San Francisco | Bonci A.,Wheeler Center for the Neurobiology of Addiction
Neuron | Year: 2010

Experience-dependent plasticity at excitatory synapses of the mesocorticolimbic system is a fundamental brain mechanism that enables adaptation to an ever-changing environment. These synaptic responses are critical for the planning and execution of adaptive behaviors that maximize survival. The mesocorticolimbic system mediates procurement of positive reinforcers such as food and sex; however, drugs of abuse resculpt this crucial circuitry to promote compulsive drug-seeking behavior. This review will discuss the long-term changes in glutamatergic neurotransmission that occur within the mesolimbic system following cocaine exposure. In addition, we will examine how these long-lasting neuroadaptations may drive the pathology of psychostimulant addiction. Finally, we review clinical trials that highlight antagonists at excitatory AMPA receptors as promising targets against cocaine abuse. © 2010 Elsevier Inc. Source

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