Cingulate atrophy as a shared structural basis for cognitive and functional brain impairments in GAD, PD, and OCD: Links to shared gene expression and treatment implications.

Journal: Journal of affective disorders
Published Date: Oct 14, 2025

Abstract

BACKGROUND: Structural brain deficits associated with generalized anxiety disorder (GAD), panic disorder (PD), and obsessive-compulsive disorder (OCD) have been documented, but their integration within a unified framework remains unexplored. This study investigates, in anxiety and anxiety-related disorders, whether they share neurophysiological bases, whether structural changes (SCs) are linked to common genes, whether shared SCs co-occur with similar functional brain impairments, and whether brain morphometry can serve as biomarkers for diagnosis and treatment prediction. METHODS: Participants included 100 individuals with GAD, 58 with PD, 45 with OCD, and 85 healthy controls, all drug-free. Structural and resting-state functional magnetic resonance imaging scans and clinical assessments were conducted before and after 4 weeks of paroxetine monotherapy. Analyses included voxel-based and surface-based morphometry; functional connectivity (FC) and Granger causality analysis (GCA) with shared SCs as regions of interest; associations between clinical assessments and neuroimaging metrics; associations between gene expression profiles and SCs; and machine learning. RESULTS: Cingulate atrophy (CA) emerged as a common SC, with disorder-specific atrophy in gray matter volume (GMV) and cortical surface. Transcriptome-neuroimaging correlations identified shared genetic associations with GMV alterations, with negatively correlated genes enriched in neurodevelopment and cellular growth regulation (ND-CGR). Cingulate GMV was positively correlated with cognitive performance in GAD and PD patients. FC and GCA showed CA disrupted networks governing emotional regulation and cognitive control, characterized by overactive top-down influence and reduced bottom-up feedback. Machine learning demonstrated strong performance in classification and treatment response prediction, with cingulate morphometry contributing significantly. CONCLUSIONS: CA is a shared neural substrate in GAD, PD, and OCD, linked to genetic disruptions in ND-CGR, cognitive impairments, and functional brain deficits. Cingulate morphometry holds promise as a biomarker for diagnosis and treatment response in these conditions.

Authors

  • Haohao Yan
    Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China.
  • Yiding Han
    Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
  • Xiaoxiao Shan
    Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
  • Huabing Li
    Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, China.
  • Feng Liu
    Department of Vascular and Endovascular Surgery, The First Medical Center of Chinese PLA General Hospital, 100853 Beijing, China.
  • Ping Li
    Department of Gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
  • Yonggui Yuan
    Department of Psychosomatic and Psychiatry, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
  • Jingping Zhao
    Department of Psychiatry of the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center on Mental Disorders, Changsha, Hunan, China; National Technology Institute on Mental Disorders, Changsha, Hunan, China; Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China. Electronic address: [email protected].
  • Wenbin Guo
    Department of Psychiatry of the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center on Mental Disorders, Changsha, Hunan, China; National Technology Institute on Mental Disorders, Changsha, Hunan, China; Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China. Electronic address: [email protected].

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