Institut National de la Santé et de la Recherche Médicale (INSERM) U1084-LNEC Experimental and Clinical Neurosciences Laboratory, Poitiers, France; Team Psychobiology of Compulsive Disorders, University of Poitiers, Poitiers, France; Service de Neurologie de l'Hôpital de Poitiers, Poitiers, France.
Institut National de la Santé et de la Recherche Médicale (INSERM) U1084-LNEC Experimental and Clinical Neurosciences Laboratory, Poitiers, France; Team Psychobiology of Compulsive Disorders, University of Poitiers, Poitiers, France; INSERM European Associated Laboratory Psychobiology of Compulsive Habits, Cambridge, United Kingdom; INSERM CIC-0802, Poitiers, France.
Biol Psychiatry. 2014 May 15;75(10):825-32. doi: 10.1016/j.biopsych.2013.09.031. Epub 2013 Oct 11.
The factors contributing to the development and severity of obsessive-compulsive spectrum disorders such as obsessive-compulsive disorder, Tourette's syndrome, pathological gambling, and addictions remain poorly understood, limiting the development of therapeutic and preventive strategies. Recent evidence indicates that impulse-control deficits may contribute to the severity of compulsivity in several of these disorders. This suggests that impulsivity may be a transnosological endophenotype of vulnerability to compulsivity. However, the precise nature of the link between impulsivity and compulsivity in anxiety-related compulsive disorders remains unknown.
We investigated the relationship between impulsivity and the development of a compulsive behavior in rats, which captures the hallmarks of compulsivity as defined in the DSM-IV--namely, that it is maladaptive, excessive, repetitive, and anxiolytic.
We demonstrate that a high-impulsivity trait, as measured in the five-choice serial reaction time task, predicts an increased propensity to develop compulsivity as measured in a schedule-induced polydipsia procedure. Trait impulsivity and compulsivity were nonlinearly related. This impulsivity-compulsivity relationship was lost after the development of compulsivity or under chronic treatment with atomoxetine, a noradrenergic reuptake inhibitor used to treat attention-deficit/hyperactivity disorder. Atomoxetine treatment both decreased impulsivity and prevented the development of compulsivity in high-impulsive animals.
These observations provide insight into the reciprocal influence of impulsivity and compulsivity in compulsive disorders and suggest that atomoxetine may be a useful treatment for patients suffering from obsessive-compulsive spectrum disorders with high impulsivity.
导致强迫症谱系障碍（如强迫症、妥瑞氏症、病态赌博和成瘾）发展和严重程度的因素仍知之甚少，这限制了治疗和预防策略的发展。最近的证据表明，冲动控制缺陷可能导致这些疾病中的几种强迫症的严重程度。这表明冲动性可能是强迫症易感性的跨疾病内表型。然而，焦虑相关强迫症中冲动性和强迫性之间的确切联系性质仍不清楚。
我们研究了冲动性与大鼠强迫行为发展之间的关系，这种行为捕捉了 DSM-IV 中定义的强迫症的特征，即它是适应不良、过度、重复和缓解焦虑的。
我们证明，在五选择序列反应时间任务中测量的高冲动特质，预测了在计划诱导的多饮程序中测量的强迫性增加倾向。特质冲动性和强迫性呈非线性关系。这种冲动-强迫关系在强迫性发展后或在去甲肾上腺素再摄取抑制剂阿托西汀（用于治疗注意缺陷/多动障碍）的慢性治疗下丧失。阿托西汀治疗既能降低冲动性，又能防止高冲动性动物发生强迫性。
这些观察结果提供了对强迫性障碍中冲动性和强迫性相互影响的深入了解，并表明阿托西汀可能是治疗具有高冲动性的强迫症谱系障碍患者的有用药物。
