Cardiovascular Risk Predicts White Matter Hyperintensities, Brain Atrophy and Treatment Resistance in Major Depressive Disorder: Role of Genetic Liability.

IF 5.3 2区 医学 Q1 PSYCHIATRY
Marco Paolini, Melania Maccario, Virginia Saredi, Anna Verri, Federico Calesella, Laura Raffaelli, Cristina Lorenzi, Sara Spadini, Raffaella Zanardi, Cristina Colombo, Sara Poletti, Francesco Benedetti
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Abstract

Introduction: Depressive disorders are a leading cause of global disease burden, particularly with the challenge of treatment-resistant depression (TRD). Research points to a complex bidirectional relationship between cardiovascular (CV) risk factors and TRD, with CV risk negatively impacting brain structure and potentially influencing antidepressant resistance. Moreover, the association between depression and the genetic vulnerability to cardiovascular disease suggests a shared pathophysiological process between the two. This study investigates the mediating role of brain structural alterations in the relationship between CV and cerebrovascular (CeV) risk and treatment resistance in depression.

Methods: We assessed 165 inpatients with Major depressive disorder. Each patient's CV risk was assessed via the QRISK 3 calculator. For a subset of patients, CV and CeV disease polygenic risk scores (PRS) were obtained. All patients underwent a 3 T MRI scan, and white matter hyperintensities estimates and indicators of brain trophic state were obtained.

Results: Both CV risk and CV disease PRSs are associated with treatment resistance status, white matter hyperintensities, and indicators of brain atrophy. Mediation analyses suggested that CV-induced brain alterations might underlie the relation between CV genetic and phenotypic risk and antidepressant treatment resistance.

Conclusion: These results underscore the need to explore cardiovascular risk management as part of treatment strategies for depression, pointing toward a shared pathophysiological process linking heart and brain health in treatment-resistant depression.

导言:抑郁症是造成全球疾病负担的主要原因之一,尤其是耐药性抑郁症(TRD)带来的挑战。研究表明,心血管(CV)风险因素与 TRD 之间存在复杂的双向关系,CV 风险会对大脑结构产生负面影响,并可能影响抗抑郁药的耐受性。此外,抑郁症与心血管疾病遗传易感性之间的关联表明两者之间存在共同的病理生理过程。本研究探讨了大脑结构改变在抑郁症患者的心血管和脑血管(CeV)风险与抗抑郁治疗之间关系中的中介作用:方法:我们对 165 名重度抑郁症住院患者进行了评估。每个患者的心血管风险都通过 QRISK 3 计算器进行了评估。对部分患者进行了CV和CeV疾病多基因风险评分(PRS)。所有患者都接受了 3 T MRI 扫描,并获得了白质高密度估计值和脑营养状态指标:结果:CV 风险和 CV 疾病 PRS 均与治疗抵抗状态、白质高密度和脑萎缩指标相关。中介分析表明,CV引起的脑部改变可能是CV遗传和表型风险与抗抑郁治疗耐受性之间关系的基础:这些结果强调了将心血管风险管理作为抑郁症治疗策略的一部分进行探索的必要性,并指出在治疗耐受性抑郁症患者中,心脏和大脑健康之间存在着共同的病理生理过程。
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来源期刊
Acta Psychiatrica Scandinavica
Acta Psychiatrica Scandinavica 医学-精神病学
CiteScore
11.20
自引率
3.00%
发文量
135
审稿时长
6-12 weeks
期刊介绍: Acta Psychiatrica Scandinavica acts as an international forum for the dissemination of information advancing the science and practice of psychiatry. In particular we focus on communicating frontline research to clinical psychiatrists and psychiatric researchers. Acta Psychiatrica Scandinavica has traditionally been and remains a journal focusing predominantly on clinical psychiatry, but translational psychiatry is a topic of growing importance to our readers. Therefore, the journal welcomes submission of manuscripts based on both clinical- and more translational (e.g. preclinical and epidemiological) research. When preparing manuscripts based on translational studies for submission to Acta Psychiatrica Scandinavica, the authors should place emphasis on the clinical significance of the research question and the findings. Manuscripts based solely on preclinical research (e.g. animal models) are normally not considered for publication in the Journal.
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