Early Stress and the Neurobiology of Susceptibility and Resilience to Substance Use Disorders

早期压力以及对药物使用障碍的易感性和恢复力的神经生物学

基本信息

批准号：
10642751
负责人：
MARTIN H TEICHER
金额：
$ 73.53万
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 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10642751
关键词：
Accounting Affect Age of Onset Amygdaloid structure Anger Attention deficit hyperactivity disorder Award Basal Ganglia Behavior Blood Blood flow Brain Brain region Brain-Derived Neurotrophic Factor Cerebellar vermis structure Characteristics Child Abuse and Neglect Chronic Chronology Clinical Cocaine Data Development Disease Drug Addiction Drug usage Epigenetic Process Exposure to Functional disorder Glucocorticoids Goals Heterogeneity Hippocampus Hostility Household Impulsivity Individual Inflammation Insula of Reil Intervention Knowledge Measures Mediating Mediator Mental Depression Methamphetamine Molecular Morphology Neurobiology Opioid Participant Pathway interactions Pharmaceutical Preparations Phase Polysomnography Population Attributable Risks Predisposition Prefrontal Cortex Prevention Prevention strategy Procedures Psychopathology Recording of previous events Recovery Regulation Relapse Research Risk Risk Factors Severities Sleep Stages Sleep disturbances Stress Structure Substance Use Disorder Symptoms Testing Variant Youth adverse childhood events associated symptom biological adaptation to stress brain morphology design disorder subtype drug of abuse early life stress emerging adult executive function experience gender difference high risk inflammatory marker longitudinal, prospective study maltreatment morphometry network architecture novel portability prevent programs prospective research study resilience response risk prediction substance use substance user symptomatology therapeutic target tool treatment effect treatment strategy

项目摘要

Summary' Childhood maltreatment is the most important risk factor for substance use, with maltreatment and household dysfunction accounting for about two thirds of the population attributable risk for drug dependence and iv drug use. Hence, there is a substantial subset of individuals with substance use disorders who experienced maltreatment and a substantial subset who did not. Those with maltreatment tend to have an earlier age of onset, more severe course, more comorbid symptoms, higher rates of relapse following treatments, and are more likely to have abnormalities in brain morphology. A critical question is whether the maltreated ecophenotypic variant is a distinctly different disorder or simply a more severe manifestation of the same underlying disorder. Our previous efforts during the first ten years of this award resulted in important new discoveries regarding type and timing of maltreatment, gender differences, predisposing symptoms and specific brain changes that were prospectively predictive of risk for developing substance use problems in maltreated youths. Our goal during this phase of the award is to compare maltreated and non-maltreated individuals with histories of “hard drug” substance use disorders, with opioids as primary drug of abuse, as well as unexposed non-substance using controls, to provide the first comprehensive test of the ecophenotype hypothesis that there are unique maltreated and non-maltreated substance use disorder subtypes with distinctly different molecular and neurobiological signatures. We further propose that neurobiological alterations associated with attention deficit hyperactivity disorder serve as the primary risk factor in the non-maltreated subtype rather than brain changes associated with early life stress and maltreatment. Verifying that there are two distinctly different pathways to substance use disorders would have critically important implications for prevention, treatment and design of future research studies, as each pathway may require distinctly different strategies for prevention, treatment and discovery. The second aim of the award will be to determine how exposure to maltreatment during sensitive periods becomes biologically embedded and to specifically determine how much inflammation and sleep stage disruption mediate the effects of maltreatment on brain morphometry, brain network architecture and symptoms predisposing to substance use. The purpose of this aim is to identify the most important mediators as potential therapeutic targets to prevent the emergence of substance use disorders in high-risk maltreated youth. Further, ongoing effects of inflammation and sleep disruption on neurobiology and behavior may serve as a barrier to recovery and targeting these mediators in maltreated individuals with opioid and other substance use disorders may facilitate recovery. Hence, one aim of this award is to markedly advance our understanding of substance use by testing the hypothesis that maltreatment and ADHD are not just risk factors for substance use disorder but distinctly different pathways, while the second aim is to discover potential therapeutic targets to prevent emergence of substance use and to facilitate recovery.

概括' 儿童虐待是使用虐待和家庭的最重要的危险因素功能障碍占药物依赖和IV药物的人口风险的三分之二约三分之二使用。因此，有大量的患有物质使用障碍的人经历了虐待和一个没有的大量子集。那些虐待的人倾向于发病较早，更严重的病程，更多合并症的症状，治疗后的继电器率较高，并且更有可能在脑形态上有异常。一个关键的问题是虐待的生态表型变体是否是一种截然不同的疾病，或者只是同一潜在疾病的更严重的表现。我们的在该奖项的前十年中，以前的努力导致有关类型和类型的重要新发现虐待，性别差异，易感性症状和特定大脑变化的时机前瞻性预测患有虐待年轻人的药物使用问题的风险。我们在此期间的目标该奖项的阶段是将虐待和未虐待的个体与“硬药”史进行比较药物使用障碍，阿片类药物是主要的滥用药物，以及意外的非实质性药物控制措施，提供对生态表型假设的首次综合测试，即有独特的虐待和非熟食药物使用障碍亚型具有明显不同的分子和神经生物学签名。我们进一步提出，与注意力缺陷多动症相关的神经生物学改变疾病是非癌亚型的主要危险因素，而不是与大脑变化相关的危险因素与早期生活压力和虐待。验证底物有两种截然不同的途径使用障碍对预防，治疗和未来的设计至关重要研究，因为每种途径可能需要明显不同的预防，治疗和发现。该奖项的第二个目的是确定敏感期间如何暴露于虐待时期成为生物学上的嵌入，并专门确定注射量和睡眠阶段中断介导虐待对脑形态计量学，大脑网络结构和症状易于使用。此目的的目的是确定最重要的调解人潜在的治疗靶标，以防止高风险虐待青年出现毒品的出现。此外，感染和睡眠破坏对神经生物学和行为的持续影响可能是恢复和瞄准这些介体的障碍虐待患者和其他药物使用的障碍疾病可能有助于康复。因此，该奖项的目的之一是明显提高我们对通过测试虐待和多动症的假设，不仅是毒品使用的危险因素混乱但途径截然不同，而第二个目的是发现潜在的治疗靶点防止出现药物使用并促进恢复。

项目成果

期刊论文数量（37）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Hurtful words: association of exposure to peer verbal abuse with elevated psychiatric symptom scores and corpus callosum abnormalities.

DOI：
10.1176/appi.ajp.2010.10010030
发表时间：
2010-12
期刊：
The American journal of psychiatry
影响因子：
0
作者：
Teicher MH;Samson JA;Sheu YS;Polcari A;McGreenery CE
通讯作者：
McGreenery CE

Determination of hemispheric emotional valence in individual subjects: a new approach with research and therapeutic implications.

确定个体受试者的半球情绪效价：一种具有研究和治疗意义的新方法。

DOI：
10.1186/1744-9081-3-13
发表时间：
2007
期刊：
Behavioral and brain functions : BBF
影响因子：
0
作者：
Schiffer,Fredric;Teicher,MartinH;Anderson,Carl;Tomoda,Akemi;Polcari,Ann;Navalta,CarrylP;Andersen,SusanL
通讯作者：
Andersen,SusanL

Association of Prepubertal and Postpubertal Exposure to Childhood Maltreatment With Adult Amygdala Function.

DOI：
10.1001/jamapsychiatry.2019.0931
发表时间：
2019-08
期刊：
JAMA psychiatry
影响因子：
25.8
作者：
Jianjun Zhu;S. Lowen;C. Anderson;K. Ohashi;Alaptigin Khan;Martin H. Teicher
通讯作者：
Jianjun Zhu;S. Lowen;C. Anderson;K. Ohashi;Alaptigin Khan;Martin H. Teicher

Type and timing of childhood maltreatment and severity of shutdown dissociation in patients with schizophrenia spectrum disorder.