Indicated prevention of mental disorders in subjects with initial panic symptomatology: effectiveness and underlying mechanisms of action

精神障碍是常见的，并与相当大的个人和社会负担。因此，增加研究工作是必要的，不仅治疗，而且预防精神病理学。先前的研究已经证明，患有惊恐发作（PA）及其较温和形式的恐惧发作（FS）的受试者患上几种类型的精神病理学的风险增加，包括惊恐和其他精神障碍（例如，焦虑、抑郁、物质使用）。其他研究结果表明，FS/PA可能构成与恐惧/焦虑（特别是过度的威胁反应）相关的脑回路中潜在功能障碍的表型指标，因此可能是有用的预防研究的目标点。然而，尽管对PA或阈下/轻度惊恐障碍受试者的早期干预已被证明可有效降低惊恐严重程度和相关逆境，但目前尚不清楚在惊恐（FS/PA）初始体征时进行干预是否可以防止症状进一步进展为惊恐障碍和各种其他类型的精神病理学。这项随机对照试验在具有初始恐慌症状（FS/PA）但没有全阈值精神障碍的高危受试者中进行，旨在测试基于CBT的短暂恐慌相关预防性干预是否可以有效减少当前的精神病理症状（干预功效）并前瞻性预防全阈值精神障碍的发生（预防功效）。为了确定中枢作用机制，将应用实验范式（条件反射、NPU威胁测试和威胁隐现测试），检查干预和预防功效是否由对急性威胁和潜在伤害的防御反应性的有利变化介导。

Mental disorders are common and associated with considerable individual and societal burden. Thus, increased research efforts are necessary to not only treat but also prevent psychopathology. Previous research has demonstrated that subjects with panic attacks (PA) and their milder forms, fearful spells (FS), are at increased risk for several types of psychopathology including panic but also other mental disorders (e.g., anxiety, depression, substance use). Additional findings suggest that FS/PA may constitute phenotypical indicators of underlying dysfunctions in brain circuits associated with fear/ anxiety (especially excessive threat responsivity) and may thus be useful as target points in prevention research. However, although early intervention in subjects with PA or subthreshold/ mild panic disorder has been shown to effectively reduce panic severity and associated adversity, it is unclear so far whether intervening at initial signs of panic (FS/PA) can prevent a further symptom progression towards panic disorder and various other types of psychopathology. This randomized controlled trial in high-risk subjects with initial panic symptomatology (FS/PA) but no full-threshold mental disorder aims to test whether a brief CBT-based panic-related preventive intervention can effectively reduce current psychopathological symptoms (intervention efficacy) and prospectively prevent the onset of full-threshold mental disorders (prevention efficacy). To identify central mechanisms of action, experimental paradigms (conditioning, NPU threat test and threat-looming test) will be applied examining whether intervention and prevention efficacy are mediated by favorable changes in defensive responsivity to acute threat and potential harm.