Childhood trauma history is linked to abnormal brain metabolism of non-medicated adult patients with major depressive disorder

Abstract

Objectives: Childhood trauma is a risk factor that may lead to persistent brain metabolic abnormalities, predisposing individuals to major depressive disorder (MDD). To better elucidate the pathogenesis of MDD, we investigated the neurometabolic changes in unmedicated MDD patients who had experienced childhood trauma (CT).

Methods: In this study, 37 unmedicated MDD patients with CT, 35 unmedicated MDD patients without CT, and 30 healthy control participants underwent high-resolution proton magnetic resonance spectroscopy (¹H-MRS) examination. Bilateral metabolic ratios of N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr in the prefrontal white matter (PWM), anterior cingulate cortex (ACC), putamen, and cerebellum were obtained.

Results: MDD patients showed neurometabolic changes in the cortico-striato-cerebellar (CSC) circuit. Furthermore, MDD patients showed significantly lower NAA/Cr and higher Cho/Cr ratio in the bilateral ACC and putamen, and higher NAA/Cr and lower Cho/Cr ratio in the cerebellum. Childhood trauma reduced the Cho/Cr ratio in the left ACC, which played an important role in longer and more episodes of depression.

Conclusion: Early childhood trauma has a long-lasting impact on the metabolism of adult MDD patients, leading to abnormal choline metabolism of the left ACC. Abnormal biochemical metabolism in the CSC circuit may be an underlying pathophysiology of MDD.

Limitation: As this is a small cross-sectional study, the impact of childhood trauma on the different stages of depression has not been observed.

Keywords: Anterior cingulate cortex; Childhood trauma; Cortico-striato-cerebellar circuit; Hydrogen proton magnetic resonance spectroscopy; Major depressive disorder.