Gill Hartej, Badulescu Sebastian, Di Vincenzo Joshua D, Tabassum Aniqa, McKenzie Andrea, Shah Hiya, Amin Mahrus, Llach Cristian-Daniel, Rosenblat Joshua D, McIntyre Roger S, Mansur Rodrigo B
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
J Affect Disord. 2025 Mar 15;373:88-93. doi: 10.1016/j.jad.2024.12.090. Epub 2024 Dec 26.
Abnormalities in effort-based decision-making have been consistently reported in major depressive disorder (MDD). Evidence indicates that metabolic factors, such as insulin resistance and dyslipidemia, which are highly prevalent in MDD, are independently associated with reward disturbances. Herein, we investigate the moderating effect of metabolic factors on effort-based decision-making in individuals with MDD.
Forty-nine adults with MDD completed the Effort Expenditure for Rewards Task (EEfRT). Anthropometric and laboratorial parameters were assessed in all participants. We conducted a factor analysis to identify combinations of correlated metabolic variables, and reduce the number of comparisons.
Proxy markers of elevated insulin resistance (OR: 0.816, p < 0.001) and hyperglycemia (OR: 0.898, p = 0.021) were associated with a lower willingness to exert physical effort for rewards in the EEfRT. In contrast, elevated HDL (OR: 1.165, p = 0.004), and elevated non-HDL cholesterol and triglycerides (OR: 1.184, p < 0.001) were associated with increased frequency of hard task choices. These associations were independent of age, sex, depressive symptoms severity and medication use. Computational modeling revealed that the insulin resistance (β = 0.275, p = 0.035) and cholesterol factors (β = 0.565, p < 0.001) were independently associated with increased effort discounting.
Post-hoc analysis using a relatively small sample of convenience.
Metabolic factors significantly and independently modulated effort-based decision-making in patients with MDD. These results have implications for our understanding of reward disturbances in MDD, and offer insights for further mechanistic investigations.
在重度抑郁症（MDD）中，基于努力的决策异常现象一直被报道。有证据表明，MDD中高度普遍存在的代谢因素，如胰岛素抵抗和血脂异常，与奖赏障碍独立相关。在此，我们研究代谢因素对MDD患者基于努力的决策的调节作用。
49名成年MDD患者完成了奖赏任务的努力支出（EEfRT）。对所有参与者进行了人体测量和实验室参数评估。我们进行了因子分析，以识别相关代谢变量的组合，并减少比较次数。
胰岛素抵抗升高（OR：0.816，p < 0.001）和高血糖（OR：0.898，p = 0.021）的替代指标与在EEfRT中为获得奖赏而付出体力努力的意愿较低相关。相比之下，高密度脂蛋白升高（OR：1.165，p = 0.004），以及非高密度脂蛋白胆固醇和甘油三酯升高（OR：1.184，p < 0.001）与选择困难任务的频率增加相关。这些关联独立于年龄、性别、抑郁症状严重程度和药物使用情况。计算模型显示，胰岛素抵抗（β = 0.275，p = 0.035）和胆固醇因素（β = 0.565，p < 0.001）与努力折扣增加独立相关。
使用相对较小的便利样本进行事后分析。
代谢因素显著且独立地调节了MDD患者基于努力的决策。这些结果对我们理解MDD中的奖赏障碍具有启示意义，并为进一步的机制研究提供了见解。
