Biomarkers for conduct problems: Abnormal conditioning to punishments and rewards

描述（由申请人提供）：品行障碍是儿童中最常见和最重要的临床障碍之一，并且正在不断努力改进品行障碍的诊断标准和分型。从理论上讲，包括条件反射缺陷在内的神经生物学标记可以为诊断过程提供客观信息，并有助于区分终身持续的行为障碍个体亚型和更短暂的反社会儿童。本初步研究的长期目标是为未来儿童和青少年品行障碍的前瞻性纵向研究奠定基础，从而为这一重要发展时期的连续性和变化提供新的见解，并为诊断和治疗提供潜在的指导。基于先前的文献和申请人最近的发现，中心假设是8岁和9岁有行为问题的儿童的特征是对惩罚的条件反射减少，对奖励的条件反射增强，条件反射缺陷和不良家庭环境的儿童表现出更多的行为问题。假设将通过追求三个具体目标进行测试：1)确定行为问题与奖惩条件反射之间的关系；2)确定行为问题的稳定性和变化以及对早发持续性反社会群体的条件反射措施的特异性；3)确定条件反射缺陷是否与社会心理逆境相互作用，以诱发行为问题。这项试点研究计划在纽约布鲁克林地区的340名38岁男孩和女孩的社区样本中评估行为障碍症状、自主调节和社会逆境，并在9岁时进行为期一年的随访。在食欲和厌恶条件反射任务期间，将评估皮肤电和心血管活动。这项研究的创新之处在于：(1)首次研究了儿童行为问题与食欲条件反射和厌恶条件反射平衡之间的关系，(2)采用了前瞻性纵向设计，(3)研究了条件反射缺陷和心理社会因素在行为问题易发性中的相互作用。NIH对该提案的支持将为申请人提供过渡到独立研究者所需的经验。更重要的是，识别早期生物标志物，如条件反射缺陷，以及社会心理因素的作用，可能会增加对行为问题发展中涉及的潜在精神病理过程的了解。从程序上讲，这些知识对临床诊断和行为矫正治疗方案具有潜在的意义，并可能有助于针对那些最需要的儿童进行治疗。

DESCRIPTION (provided by applicant): Conduct disorder is one of the most common and important clinical disorders in children, and continuing efforts are being made to improve diagnostic criteria for and subtyping of conduct disorder. Neurobiological markers, including conditioning deficits, could in theory bring objective information to the diagnostic process and help differentiate the life-course persistent subtype of conduct disordered individuals from more transitory antisocial children. The long term goal of this pilot study is to lay the foundations fo a future prospective longitudinal study of conduct disorder in childhood and adolescence which can provide new insight into continuity and change throughout this important developmental period, with potential implications for diagnosis and treatment. The central hypotheses, based on both the prior literature and the applicant's recent findings, are that children with conduct problems at both ages 8 and 9 are characterized by reduced conditioning to punishments and enhanced conditioning to rewards, and that children with both conditioning deficits and adverse home environments show more conduct problems. Hypotheses will be tested by pursuing three specific aims: 1) to determine the relationships between conduct problems and conditioning to both rewards and punishments, 2) to determine the stability and change in conduct problems and the specificity of conditioning measures to the early-onset persistently antisocial group, and 3) to determine whether conditioning deficits interact with psychosocial adversity in predisposing to conduct problems. This pilot study plans to assess conduct disorder symptoms, autonomic conditioning, and social adversity in a community sample of 340 8-year-old boys and girls in the area of Brooklyn, New York, and also in a one-year follow-up at age 9 years. Electrodermal and cardiovascular activity will be assessed during appetitive and aversive conditioning tasks. The research proposal is innovative because: (1) for the first time it examines associations between conduct problems and the balance of appetitive conditioning and aversive conditioning in children, (2) it uses a prospective longitudinal design, and (3) it investigates the interaction between conditioning deficits and psychosocial factors in predisposing to conduct problems. NIH support of this proposal will provide the applicant with the experience necessary to transition into an independent investigator. More importantly, identification of early biomarkers such as conditioning deficits, along with the role of psychosocial factors, may increase insight into the underlying psychopathological processes involved in the development of conduct problems. Programmatically this knowledge has potential implications for clinical diagnosis and behavioral modification treatment programs, and may help to target treatment efforts on those children in most need.