Department of Psychiatry, Columbia University Irving Medical Center, New York, New York10032, USA.
Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, New York10032, USA.
Eur Psychiatry. 2023 Jan 24;66(1):e17. doi: 10.1192/j.eurpsy.2023.4.
Reported childhood adversity (CA) is associated with development of depression in adulthood and predicts a more severe course of illness. Although elevated serotonin 1A receptor (5-HTR) binding potential, especially in the raphe nuclei, has been shown to be a trait associated with major depression, we did not replicate this finding in an independent sample using the partial agonist positron emission tomography tracer [C]CUMI-101. Evidence suggests that CA can induce long-lasting changes in expression of 5-HTR, and thus, a history of CA may explain the disparate findings.
Following up on our initial report, 28 unmedicated participants in a current depressive episode (bipolar = 16, unipolar = 12) and 19 non-depressed healthy volunteers (HVs) underwent [C]CUMI-101 imaging to quantify 5-HTR binding potential. Participants in a depressive episode were stratified into mild/moderate and severe CA groups via the Childhood Trauma Questionnaire. We hypothesized higher hippocampal and raphe nuclei 5-HTR with severe CA compared with mild/moderate CA and HVs.
There was a group-by-region effect ( = 0.011) when considering HV, depressive episode mild/moderate CA, and depressive episode severe CA groups, driven by significantly higher hippocampal 5-HTR binding potential in participants in a depressive episode with severe CA relative to HVs ( = 0.019). Contrary to our hypothesis, no significant binding potential differences were detected in the raphe nuclei ( > 0.05).
With replication in larger samples, elevated hippocampal 5-HTR binding potential may serve as a promising biomarker through which to investigate the neurobiological link between CA and depression.
报告的儿童逆境(CA)与成年期抑郁症的发展有关,并预测疾病的病程更为严重。尽管已经证明升高的血清素 1A 受体(5-HTR)结合潜能,特别是在中缝核中,与重度抑郁症有关,但我们在使用部分激动剂正电子发射断层扫描示踪剂 [C]CUMI-101 的独立样本中并未复制此发现。有证据表明,CA 可以诱导 5-HTR 表达的持久变化,因此,CA 病史可能可以解释这种差异。
在我们的初步报告之后,28 名未经治疗的当前抑郁发作患者(双相 16 例,单相 12 例)和 19 名未患抑郁症的健康志愿者(HV)接受了 [C]CUMI-101 成像以定量 5-HTR 结合潜能。通过童年创伤问卷将处于抑郁发作的患者分为轻度/中度 CA 和重度 CA 组。我们假设与轻度/中度 CA 和 HV 相比,重度 CA 的海马和中缝核 5-HTR 更高。
当考虑 HV、抑郁发作轻度/中度 CA 和抑郁发作重度 CA 组时,存在组-区域效应( = 0.011),这是由重度 CA 的抑郁发作患者的海马体 5-HTR 结合潜能明显高于 HV 驱动的( = 0.019)。与我们的假设相反,在中缝核中未检测到明显的结合潜能差异(> 0.05)。
在更大的样本中进行复制后,升高的海马体 5-HTR 结合潜能可能成为一种有前途的生物标志物,可用于研究 CA 与抑郁症之间的神经生物学联系。