Distinction in the function and microstructure of white matter between major depressive disorder and generalized anxiety disorder

Yue Yu; Ting Zhang; Qianqian Li; Mengyu Song; Li Qi; Jinmei Sun; Gongjun Ji; Yanghua Tian; Kai Wang

doi:10.1016/j.jad.2025.01.018

Distinction in the function and microstructure of white matter between major depressive disorder and generalized anxiety disorder

J Affect Disord. 2025 Jan 8:S0165-0327(25)00020-5. doi: 10.1016/j.jad.2025.01.018. Online ahead of print.

Authors

Yue Yu¹, Ting Zhang², Qianqian Li³, Mengyu Song¹, Li Qi¹, Jinmei Sun¹, Gongjun Ji⁴, Yanghua Tian⁵, Kai Wang⁴

Affiliations

¹ Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
² Department of Psychology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
³ Department of Psychology and Sleep Medicine, The Second Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei 230601, China.
⁴ Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei 230032, China; School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei 230032, China; Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Hefei 230032, China; Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei 230088, China.
⁵ Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Department of Psychology and Sleep Medicine, The Second Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei 230601, China; School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei 230032, China. Electronic address: [email protected].

PMID: 39793621
DOI: 10.1016/j.jad.2025.01.018

Abstract

Background: Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are two of the leading causes of impairment to human mental health. These two psychiatric disorders overlap in many symptoms and neurobiological features thus difficult to distinguish in some cases.

Methods: We enrolled 102 participants, comprising 40 patients with MDD, 32 patients with GAD and 30 matched healthy controls (HCs), to undergo multimodal magnetic resonance imaging (MRI) scans. We identified 18 major white matter (WM) tracts with automated fiber quantification (AFQ) method, to evaluated microstructure with fractional anisotropy (FA) and function with amplitude of low-frequency fluctuation (ALFF). An analysis of variance (ANOVA) was employed to identify differences among groups. We further explored the correlations of FA and ALFF features with clinical symptoms.

Results: We identified the white matter microstructure and function of 89 participants. ANOVA and post-hoc analysis revealed that GAD group exhibited significantly higher FA of right anterior thalamic radiation (ATR) than in MDD and HC groups. Additionally, MDD group exhibited significantly decreased ALFF in forceps major (FMA), forceps minor (FMI), bilateral corticospinal tracts (CST) and left inferior fronto-occipital fasciculus (IFOF) compared to both GAD and HC group. ALFF of right CST was significantly negatively correlated to HAMA and a moderate effect size and marginal significance was found between FA of the right ATR and HAMA in GAD group.

Limitations: This study used cross-sectional data and sample size was small.

Conclusion: Tracking microstructure and function of WM with AFQ method has the potential to distinguish different psychiatric diseases.

Keywords: Amplitude of low-frequency fluctuation; Automated fiber quantification; Fractional anisotropy; Generalized anxiety disorder; Major depressive disorder.