Mood disorders and suicidal behavior have moderate heritability and are associated with altered corticolimbic serotonin 1A receptor (5-HT_1A) brain binding. However, it is unclear whether this reflects genetic effects or epigenetic effects of childhood adversity, compensatory mechanisms, or illness stress-related changes. We sought to separate such effects on 5-HT_1A binding by examining high familial risk individuals (HR) who have passed through the age of greatest risk for psychopathology onset with and without developing mood disorder or suicidal behavior. PET imaging quantified 5-HT_1A binding potential BP_ND using [¹¹C]CUMI-101 in healthy volunteers (HV, N = 23) and three groups with one or more relatives manifesting early-onset mood disorder and suicide attempt: 1. unaffected HR (N = 23); 2. HR with lifetime mood disorder and no suicide attempt (HR-MOOD, N = 26); and 3. HR-MOOD with previous suicide attempt (HR-MOOD + SA, N = 20). Findings were tested in an independent cohort not selected for family history (HV, MOOD, and MOOD + SA, total N = 185). We tested for regional BP_ND differences and whether brain-wide patterns distinguished between groups. Low ventral prefrontal 5-HT_1A BP_ND was associated with lifetime mood disorder diagnosis and suicide attempt, but only in subjects with a family history of mood disorder and suicide attempt. Brain-wide 5-HT_1A BP_ND patterns including low ventral prefrontal and mesiotemporal cortical binding distinguished HR-MOOD + SA from HV. A biological endophenotype associated with resilience was not observed. Low ventral prefrontal 5-HT_1A BP_ND may reflect familial mood disorder and suicide-related pathology. Further studies are needed to determine if higher ventral prefrontal 5-HT_1A BP_ND confers resilience, reducing risk of suicidal behavior in the context of familial risk, and thereby offer a potential prevention target.

情绪障碍和自杀行为具有中度遗传性，并且与改变的皮质边缘血清素 1A 受体 (5-HT _1A ) 脑结合有关。然而，尚不清楚这是否反映了童年逆境、补偿机制或疾病应激相关变化的遗传效应或表观遗传效应。我们试图通过检查高家族风险个体 (HR) 来区分这些对5-HT _{1A结合的影响，这些个体已经过了精神病理学发作的最大风险年龄，有或没有发展为情绪障碍或自杀行为。}PET 成像_使用[ 11 ^C ]CUMI-101 在健康志愿者（HV _、N = 23）和三组有一个或多个亲属表现出早发性情绪障碍和自杀未遂：1. 未受影响的 HR（N  = 23）；2. 有终生情绪障碍且无自杀企图的 HR (HR-MOOD, N  = 26)；和 3. HR-MOOD 与之前的自杀未遂（HR-MOOD + SA，N  = 20）。结果在一个未选择家族史的独立队列中进行测试（HV、MOOD 和 MOOD + SA，总N  = 185）。我们测试了区域性 BP _ND差异以及全脑模式是否在各组之间有所区分。低腹侧前额叶 5-HT _1A BP _ND与终生情绪障碍诊断和自杀未遂有关，但仅限于有情绪障碍和自杀未遂家族史的受试者。全脑 5-HT _1A BP _ND模式，包括低腹侧前额叶和近颞叶皮层结合，将 HR-MOOD + SA 与 HV 区分开来。没有观察到与弹性相关的生物内表型。低腹侧前额叶 5-HT _1A BP _ND可能反映家族性情绪障碍和自杀相关病理。需要进一步的研究来确定较高的腹侧前额叶 5-HT _1A BP _ND是否赋予弹性，在家族风险的背景下降低自杀行为的风险，从而提供潜在的预防目标。