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，目前正在不断努力改进品行障碍的诊断标准和亚型。神经生物学标志物，包括条件反射缺陷，理论上可以为诊断过程提供客观信息，并有助于区分行为障碍个体的生命过程持续亚型和更短暂的反社会儿童。这项试点研究的长期目标是为未来的前瞻性纵向研究奠定基础，在儿童和青少年的行为障碍，可以提供新的见解的连续性和变化，在整个重要的发展时期，诊断和治疗的潜在影响。基于先前的文献和申请人最近的发现，中心假设是，在8岁和9岁时都有行为问题的儿童的特征在于减少对惩罚的调节和增强对奖励的调节，并且具有调节缺陷和不利的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）确定行为问题和条件反射之间的关系，以奖励和惩罚，2）确定的稳定性和变化的行为问题和条件反射措施的特异性早发性持续反社会群体，和3）确定条件反射缺陷是否与心理社会逆境在诱发行为问题。这项试点研究计划在社区样本的340名8岁的男孩和女孩在布鲁克林区，纽约，并在为期一年的后续行动，在9岁的行为障碍症状，自主调节和社会逆境进行评估。将在食欲和厌恶条件反射任务期间评估皮电和心血管活动。本研究的创新之处在于：（1）首次探讨了行为问题与儿童食欲条件反射和厌恶条件反射的平衡之间的关系;（2）采用了前瞻性纵向设计;（3）研究了条件反射缺陷与心理社会因素之间的相互作用。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，沿着心理社会因素的作用，可能会增加对行为问题发展所涉及的潜在精神病理过程的洞察力。从程序上讲，这种知识对临床诊断和行为矫正治疗方案有潜在的影响，并可能有助于将治疗工作集中在最需要的儿童身上。

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.