Sensory Mechanisms and Self-Injury

二十多年前，NIH估计了与自我伤害行为（SIB）相关的成本， 智力和发育残疾（IDD）超过30亿美元（美国）。几乎没有理由认为， 流行率估计已经改变，但保健费用肯定已经改变。尽管在行为方面取得了进展， 评估和治疗个别SIB病例，我们对疾病风险的科学理解仍然存在 严格限制。“等待事态发展”办法的一个后果是， 在疾病发作后很长时间才治疗，使其成为临床上困难和昂贵的（并且通常是顽固的） 问题.与我们自己的预测相反，很明显，在非常年幼的儿童中， 延迟，通常被视为SIB“风险因素”的变量（例如，语言表达能力差）可能具有预后 价值，但做得很少，以分离儿童的初始风险。同样清楚的是， 这应该在SIB风险的综合生物行为模型中考虑， 更精确地划分“高/低”风险群体。根据我们迄今为止的工作，形成了以下框架： (1)有一个亚组的非常年轻的儿童IDD与改变周围神经支配和免疫细胞 活性;（2）这可能是发展表型的生物基质的一部分，其特征在于 感觉反应的异常模式。我们假设，SIB更有可能出现在以下情况下， 都有这种早期表现型。 我们已经确定，外周神经支配，免疫细胞活性， 异常的感觉反应性可以在患有以下疾病的儿童中很早就被客观可靠地测量到： 在SIB发作之前，发育迟缓。 本申请的总体目标是应用 采用前瞻性发展方法模拟SIB风险。因此，我们假设儿童亚组 伴有（i）外周感觉神经支配改变，（ii）炎症和免疫活性增加，和（iii） 增加的感觉反应性将是SIB的最高病因风险。结果将产生临床影响 因为（a）目前评估和处理SIB的方法依赖于SIB的出现，因此可能 错过了更大的生物和行为可塑性的早期机会，以及（B）假定的风险标志物是 研究提供了合理的和新的目标，转向早期预防这种毁灭性的， 昂贵的临床条件。

Over two decades ago, NIH estimated costs associated with self-injurious behavior (SIB) associated with intellectual and developmental disabilities (IDD) exceeded $3 billion (US). There is little reason to think the prevalence estimates have changed but assuredly the costs of care have. Despite progress in the behavioral assessment and treatment of individual SIB cases, our scientific understanding of risk for the disorder remains severely limited. One consequence of the `wait till it develops' approach is that individual SIB cases tend to be treated long after the onset of the disorder making it a clinically difficult and expensive (and often intractable) problem. Contrary to our own predictions, it has become clear that in very young children with developmental delay, variables typically considered as SIB `risk factors' (e.g., poor expressive language) may have prognostic value but do little to separate children on initial risk. Equally clear is there may be individual difference markers which should be considered in an integrated bio-behavioral model of SIB risk to stratify vulnerable children with more precision into `high/low' risk groups. Based on our work to date, the following framework has emerged: (1) there is a subgroup of very young children with IDD with altered peripheral innervation and immune cell activity; (2) this may be part of the biological substrate for the development of a phenotype characterized by abnormal patterns of sensory responsiveness. We hypothesize that SIB is more likely to emerge in cases that have this early phenotype. We have already established that peripheral innervation, immune cell activity, and abnormal sensory responsiveness can be objectively and reliably measured very early in children with developmental delays, prior to the onset of SIB. The overall objective of this application is to apply a prospective developmental approach to model SIB risk. Accordingly, we hypothesize the subgroup of children with (i) altered peripheral sensory innervation, (ii) increased inflammatory and immune activity, and (iii) increased sensory reactivity will be at the highest etiological risk for SIB. The outcomes will have clinical impact because (a) current methods of assessment and treatment of SIB rely on the emergence of SIB and thus likely miss early opportunities for greater biological and behavioral plasticity, and (b) the putative risk markers being investigated provide plausible and novel targets in a shift towards early prevention of this devastating and costly clinical condition.