Campbell Claire E, Gauderman W James, Herting Megan M
Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
Neuroscience Graduate Program, University of Southern California, Los Angeles, California, USA 90089-2520.
medRxiv. 2025 May 18:2025.05.16.25327790. doi: 10.1101/2025.05.16.25327790.
The World Health Organization (WHO) ranks depression as the number one non-fatal contributor to the global burden of disease. Previous work finds that early intervention prior to onset leads to preferred outcomes. To examine depression prior to onset, risks are assessed in relation to depressive prodromal behavior and brain biomarkers. Research shows environmental and genetic risks both separately influence depression onset, but little research has examined their interaction. Thus, we examined whether the socioeconomic predictor of family income-to-needs ratio (INR) may have independent and/or interactive effects with an individual's depression polygenic risk score (D-PRS) on youth behavior and brain structure and function. We leveraged the U.S. based ABCD Study - an existing longitudinal dataset; this work examined ~8,000 subjects, 9-10 year-of-age at baseline to 11-12 year-of-age at 2-year follow-up. Historically, genetic analysis was conducted in European-like samples. Therefore, our work first assesses effects in youth with European-like genetic ancestry. Next, to improve generalizability, the same analyses were conducted in youths who are not European-like. Overall, D-PRS was associated with behavior and brain within the European-like youths, but less so in the not European-like sample. A potential moderating effect of INR on D-PRS was also seen for brain network connectivity, with further main effects of INR in youths from lower socioeconomic statuses. The findings from this project suggests behavior-brain biomarkers associated with socioeconomic status and depression risk vary by genetic ancestry, further highlighting the importance of precision-based medicine research in hopes of improving early detection and treatment of depression.
世界卫生组织（WHO）将抑郁症列为全球疾病负担的首要非致命因素。先前的研究发现，在发病前进行早期干预会带来更好的结果。为了在发病前检查抑郁症，需要根据抑郁前驱行为和脑生物标志物来评估风险。研究表明，环境风险和遗传风险都会分别影响抑郁症的发作，但很少有研究探讨它们之间的相互作用。因此，我们研究了家庭收入需求比（INR）这一社会经济预测指标是否可能与个体的抑郁症多基因风险评分（D-PRS）在青少年行为以及脑结构和功能方面存在独立和/或交互作用。我们利用了基于美国的青少年大脑认知发展（ABCD）研究——一个现有的纵向数据集；这项研究调查了约8000名受试者，基线时年龄为9至10岁，在2年随访时年龄为11至12岁。从历史上看，基因分析是在具有欧洲血统的样本中进行的。因此，我们的研究首先评估具有欧洲血统的青少年的影响。接下来，为了提高普遍性，我们在非欧洲血统的青少年中进行了相同的分析。总体而言，D-PRS与具有欧洲血统的青少年的行为和大脑有关，但在非欧洲血统的样本中相关性较小。对于脑网络连接性，还发现了INR对D-PRS的潜在调节作用，并且INR对社会经济地位较低的青少年有进一步的主要影响。该项目的研究结果表明，与社会经济地位和抑郁症风险相关的行为-脑生物标志物因基因血统而异，这进一步凸显了精准医学研究对于改善抑郁症早期检测和治疗的重要性。
