Fanelli Giuseppe, Bralten Janita, Franke Barbara, Roth Mota Nina, Atti Anna Rita, De Ronchi Diana, Monteleone Alessio Maria, Grassi Luigi, Serretti Alessandro, Fabbri Chiara
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
Br J Psychiatry. 2025 Jun 23:1-10. doi: 10.1192/bjp.2025.82.
Major depressive disorder (MDD) and insulin resistance-related conditions are major contributors to global disability. Their co-occurrence complicates clinical outcomes, increasing mortality and symptom severity.
In this study, we investigated the association of insulin resistance-related conditions and related polygenic scores (PGSs) with MDD clinical profile and treatment outcomes, using primary care records from UK Biobank.
We identified MDD cases and insulin resistance-related conditions, as well as measures of depression treatment outcomes (e.g. resistance) from the records. Clinical-demographic variables were derived from self-reports, and insulin resistance-related PGSs were calculated using PRS-CS. Univariable analyses were conducted to compare sociodemographic and clinical variables of MDD cases with (IR+) and without (IR-) lifetime insulin resistance-related conditions. Multiple regressions were performed to identify factors, including insulin resistance-related PGSs, potentially associated with treatment outcomes, adjusting for confounders.
Among 30 919 MDD cases, 51.95% were IR+. These had more antidepressant prescriptions and classes utilisation and longer treatment duration than patients without insulin resistance-related conditions ( < 0.001). IR+ participants showed distinctive depressive profiles, characterised by concentration issues, loneliness and inadequacy feelings, which varied according to the timing of MDD diagnosis relative to insulin resistance-related conditions. After adjusting for confounders, insulin resistance-related conditions (i.e. cardiovascular diseases, hypertension, non-alcoholic fatty liver disease, obesity/overweight, prediabetes and type 2 diabetes mellitus) were associated with antidepressant non-response/resistance and longer treatment duration, particularly when MDD preceded insulin resistance-related conditions. No significant PGS associations were found with antidepressant treatment outcomes.
Our findings support an integrated treatment approach, prioritising both psychiatric and metabolic health, and public health strategies aimed at early intervention and prevention of insulin resistance in MDD.
重度抑郁症（MDD）和胰岛素抵抗相关疾病是导致全球残疾的主要因素。它们的共同出现使临床结果复杂化，增加了死亡率和症状严重程度。
在本研究中，我们使用英国生物银行的初级保健记录，调查了胰岛素抵抗相关疾病和相关多基因评分（PGS）与MDD临床特征和治疗结果之间的关联。
我们从记录中识别出MDD病例和胰岛素抵抗相关疾病，以及抑郁症治疗结果的测量指标（如抵抗）。临床人口统计学变量来自自我报告，胰岛素抵抗相关PGS使用PRS-CS计算。进行单变量分析以比较有（IR+）和无（IR-）终生胰岛素抵抗相关疾病的MDD病例的社会人口统计学和临床变量。进行多元回归以确定包括胰岛素抵抗相关PGS在内的可能与治疗结果相关的因素，并对混杂因素进行调整。
在30919例MDD病例中，51.95%为IR+。与无胰岛素抵抗相关疾病的患者相比，这些患者有更多的抗抑郁药处方和药物类别使用，治疗持续时间更长（<0.001）。IR+参与者表现出独特的抑郁特征，其特征为注意力不集中、孤独和不足感，这根据MDD诊断相对于胰岛素抵抗相关疾病的时间而有所不同。在调整混杂因素后，胰岛素抵抗相关疾病（即心血管疾病、高血压、非酒精性脂肪性肝病、肥胖/超重、糖尿病前期和2型糖尿病）与抗抑郁药无反应/抵抗和更长的治疗持续时间相关，特别是当MDD先于胰岛素抵抗相关疾病出现时。未发现PGS与抗抑郁药治疗结果有显著关联。
我们的研究结果支持一种综合治疗方法，优先考虑精神和代谢健康，以及旨在早期干预和预防MDD患者胰岛素抵抗的公共卫生策略。
