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Early Stress, PTSD, and the Neurobiology of Addiction

早期压力、创伤后应激障碍和成瘾的神经生物学

基本信息

批准号：
7232734
负责人：
MARTIN H TEICHER
金额：
$ 49.11万
依托单位：
MCLEAN HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-06-15 至 2009-05-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7232734
关键词：
Addictive Behavior Adolescence Adolescent Adverse effects Affect Alcohol abuse Alcohol consumption Alcohol or Other Drugs use Alcohols Amygdaloid structure Animal Model Animals Ants Ataxia Attention Attention deficit hyperactivity disorder Attenuated Barbiturates Behavior Behavioral Biological Blood Pressure Blood flow Body of uterus Brain Brain region Caring Cerebellar vermis structure Cerebellum Child Child Abuse Child Abuse and Neglect Child Sexual Abuse Child Traumatic Stress Childhood Chronic Chronic stress Cocaine Cocaine Abuse Cognitive Communities Complex Corpus striatum structure Corticosterone Corticotropin Corticotropin-Releasing Hormone Crime Daily Dependence Development Diagnostic Dopamine Dopamine-beta-monooxygenase Dose Drug Addiction Drug Exposure Drug abuse Drug usage Electroencephalography Enzymes Ethanol Event Exposure to Female Forcible intercourse Functional Magnetic Resonance Imaging Genes Genetic Genetic Polymorphism Genital system Genotype Glucocorticoid Receptor Glucocorticoids Grooming Growth Heroin Hippocampus (Brain)Homovanillic Acid Hormones Hospitalized Child Human Hydrocortisone Hydroxyindoleacetic Acid Ibogaine Incidence Individual Individual Differences Injection of therapeutic agent Intake Invasive Lead Left Link Magnetic Resonance Imaging Maintenance Major Depressive Disorder Measures Mediating Mediator of activation protein Mental Depression Messenger RNA Methylphenidate Molecular Monoamine Oxidase A Morphology Mus Neocortex Neurobiology Neurons Norepinephrine Nucleus Accumbens Numbers Oxytocin Pathway interactions Peripheral Pharmaceutical Preparations Plasma Post-Traumatic Stress Disorders Predisposition Prevalence Principal Investigator Procedures Property Protons Rate Rattus Recording of previous events Recovery Recurrence Relapse Relative (related person)Reporting Research Research Personnel Risk Risk Factors Sampling Scanning Self Administration Serotonin Sexual abuse Stereotyping Stress Structure Substance abuse problem Survivors Symptoms Synapses System Testing Time Trauma Trier Social Stress Test Validation Vasopressins Ventral Tegmental Area Weaning Woman addiction anti social barbituric acid salt base biological adaptation to stress caudate nucleus craving density design dopamine system dopamine transporter drug addict drug development drug of abuse drug withdrawal dual diagnosis dysphoria ecstasy emotional abuse experience hemodynamics hypothalamic-pituitary-adrenal axis insight interest locus ceruleus structure male maltreated children maltreatment maternal separation men mesolimbic system neural circuit neuroadaptation noradrenergic novel pediatric trauma peer physical abuse postnatal preclinical study programs promoter psychological stressor psychostimulant recurrent depression resilience response sexual assault size spectroscopic imaging stem stress management stressor substance abuser young adult

项目摘要

Exposure to repeated stress and trauma during childhood produces a cascade of molecular and cellular events that has the potential to exert enduring effects on brain development. These changes may be responsible for the development of depression, posttraumatic stress disorder (PTSD) and increased vulnerability to substance use and addiction. Study 1 will test the hypotheses that both PTSD and recurrent major depression mediate the association between childhood traumatic stress and increased risk for substance abuse. This study will also test the hypothesis that a functional polymorphism in the MAO-A promoter, which produces low levels of MAO-A activity will be associated with increased vulnerability to the adverse effects of childhood traumatic stress on drug use. These hypotheses will be tested in a sample of 20-25 year olds (n=500) who either have no history of exposure to childhood abuse or who have had a history of exposure to childhood abuse that fulfills the A(1) A(2) criteria for PTSD. Study 2 will test the hypotheses that exposure to chronic childhood traumatic stress effects the morphology, neuronal integrity and paramagnetic properties of the cerebellar vermis, and that cerebellar vermal abnormalities will be associated with enhanced risk for substance abuse. Three groups of subjects (30 per group) will be identified from the first study. Subjects will either have: (1) had no history of exposure to child abuse trauma; (2) childhood traumatic stress, and PTSD; or (3) childhood traumatic stress and recurrent major depression. Subjects in the three groups will be matched for degree of substance use. Morphometric MRI, T2-relaxometry and proton-echo-planar-spectroscopic imaging will be used to test these hypotheses. These subjects will also receive a probe dose of methylphenidate and a repeat T2-RT scan to test the hypothesis that exposure to childhood traumatic stress enhances hemodynamic response to stimulant drugs in the striatum and cerebellar vermis. Study 3 will test the hypotheses that exposure to childhood traumatic stress produces an increased and more enduring corticotropic, noradrenergic and vasopressin response, (and decreased or delayed oxytocin response) to stress in the Trier Social Stress Test. Overall, these studies will provide new insight into the neurobiological effects of chronic childhood traumatic stress and new understanding of the potential for PTSD and depression to mediate, and MAO-A levels to moderate, the association between early stress and drug abuse. These studies will also pursue the novel hypotheses that stress induced alterations in the cerebellar vermis and in oxytocin release are related to risk for substance abuse in survivors of chronic childhood traumatic stress.

童年时期遭受反复的压力和创伤会产生一系列分子和细胞事件，这些事件有可能对大脑发育产生持久的影响。这些变化可能导致抑郁症、创伤后应激障碍（PTSD）的发展，以及对物质使用和成瘾的脆弱性增加。研究1将检验创伤后应激障碍和复发性重度抑郁症在儿童创伤应激和药物滥用风险增加之间的关联中起中介作用的假设。这项研究也将测试