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Reduced neurite orientation in the neostriatum mediates the association between childhood trauma and cognitive impairment in major depressive disorder
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DOI：10.1038/s41398-026-04323-9.png)
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Abstract
En 中文
Cognitive impairment in patients with major depressive disorder (MDD) and a history of childhood trauma (CT) may be associated with microstructural abnormalities in the neostriatum, including the caudate and putamen. However, the nature of these alterations and their role in cognitive dysfunction remain unclear. This study aimed to characterise neostriatal microstructural alterations and examine whether they mediate the association between CT and cognitive impairment in MDD. Multi-shell diffusion MRI data from 148 patients with MDD and 47 healthy controls (HCs) were analysed using free-water diffusion tensor imaging (FWDTI) and neurite orientation dispersion and density imaging (NODDI). CT and cognition were assessed using the Childhood Trauma Questionnaire and the MATRICS Consensus Cognitive Battery, respectively. Compared with HCs, MDD patients showed significantly higher tissue-corrected fractional anisotropy (FAt) in the bilateral caudate. CT severity was significantly positively correlated with FAt and intracellular volume fraction, while significantly negatively correlated with neurite orientation dispersion (OD) in the neostriatum. Mediation analysis further showed that OD and FAt in the right putamen partially mediated the association between CT and cognitive impairment. These findings suggest that the neostriatum may represent a key neurobiological substrate linking CT to cognitive dysfunction in MDD and support the utility of advanced diffusion MRI metrics for characterising trauma-related microstructural alterations.
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