Biomarkers for conduct problems: Abnormal conditioning to punishments and rewards

描述(申请人提供)：品行障碍是儿童最常见和最重要的临床障碍之一，目前正在不断努力改进品行障碍的诊断标准和亚型。从理论上讲，包括条件反射缺陷在内的神经生物学标记物可以为诊断过程带来客观信息，并有助于区分生命过程中持续的行为障碍个体和更多的短暂性反社会儿童。这项先导性研究的长期目标是为未来对儿童和青少年行为障碍的前瞻性纵向研究奠定基础，该研究可以为这一重要发展阶段的连续性和变化提供新的见解，并对诊断和治疗具有潜在的意义。根据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点是减少了对惩罚的条件反射，增强了对奖励的条件反射，而同时存在条件反射缺陷和不利的家庭环境的儿童表现出更多的行为问题。通过追求三个具体目标来检验假设：1)确定行为问题与奖惩的条件反射之间的关系，2)确定行为问题的稳定性和变化性，以及条件反射措施对早发性持续反社会群体的特异性，以及3)确定条件性缺陷是否与心理社会逆境交互作用于行为问题的易感性。这项先导性研究计划评估纽约布鲁克林地区340名8岁男孩和女孩的行为障碍症状、自主神经调节和社会逆境，并在9岁时进行为期一年的跟踪调查。电皮肤和心血管活动将在食欲和厌恶的条件反射任务中进行评估。该研究方案的创新之处在于：(1)首次考察了儿童行为问题与欲望条件反射和厌恶条件反射之间的关系；(2)采用前瞻性纵向设计；(3)研究了条件反射缺陷与心理社会因素在行为问题易感性中的交互作用。NIH支持这一提议将为申请者提供过渡到独立调查人员所需的经验。更重要的是，识别早期生物标记物，如条件性缺陷，以及心理社会因素的作用，可能会增加对行为问题发展过程中潜在的精神病理过程的洞察。从程序上讲，这一知识对临床诊断和行为矫正治疗计划具有潜在的意义，并可能有助于针对那些最有需要的儿童进行针对性的治疗。

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.