Putamen Structure and Function in Familial Risk for Depression: A Multimodal Imaging Study
Ardesheer Talati1,2, Milenna T. van Dijk1,2, Lifang Pan1,2, Xuejun Hao1,2, Zhishun Wang1,3, Marc Gameroff1,2, Zhengchao Dong1,4, Jürgen Kayser1,2, Stewart Shankman7, Priya J. Wickramaratne1,2,5, Jonathan Posner8, Myrna M. Weissman1,2,6
1Department of Psychiatry, Columbia University Irving Medical Center and Vagelos College of Physicians and Surgeons, Columbia University, New York, New York; 2Division of Translational Epidemiology, New York State Psychiatric Institute, New York, New York; 3Division of Translational Imaging, New York State Psychiatric Institute, New York, New York; 4Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York; 5Department of Biostatistics, Columbia University Mailman School of Public Health, New York, New York; 6Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York; 7Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, Illinois; 8Department of Psychiatry, Duke University, Durham, North Carolina
Received 11 January 2022; revised 14 June 2022; accepted 16 June 2022; published online 16 July 2022.
Abstract
Background: The putamen has been implicated in depressive disorders, but how its structure and function increase depression risk is not clearly understood. Here, we examined how putamen volume, neuronal density, and mood-modulated functional activity relate to family history and prospective course of depression. Methods: The study includes 115 second- and third-generation offspring at high or low risk for depression based on the presence or absence of major depressive disorder in the first generation. Offspring were followed longitudinally using semistructured clinical interviews blinded to their familial risk; putamen structure, neuronal integrity, and functional activation were indexed by structural magnetic resonance imaging (MRI), proton magnetic resonance spectroscopy (N-acetylaspartate/creatine ratio), and functional MRI activity modulated by valence and arousal components of a mood induction task, respectively. Results: After adjusting for covariates, the high-risk individuals had lower putamen volume (standardized betas, Ã-left = -0.17, Ã-right = -0.15, ps = .002), N-acetylaspartate/creatine ratio (Ã-left= -0.40, Ã-right= -0.37, ps < .0001), and activation modulated by valence (Ã-left = -0.22, Ã-right = -0.27, ps < .05) than low-risk individuals. Volume differences were greater at younger ages, and N-acetylaspartate/creatine ratio differences were greater at older ages. Lower putamen volume also predicted major depressive disorder episodes up to 8 years after the scan (Ã-left = -0.72, p = .013; Ã-right = -0.83, p = .037). Magnetic resonance spectroscopy and task functional MRI measures were modestly correlated (0.27 = r = 0.33). Conclusions: Findings demonstrate abnormalities in putamen structure and function in individuals at high risk for major depressive disorder. Future studies should focus on this region as a potential biomarker for depressive illness, noting meanwhile that differences attributable to family history may peak at different ages based on which MRI modality is being used to assay them.
Key Words: High-risk; Magnetic resonance imaging (MRI); Magnetic resonance spectroscopy (MRS); Major depressive disorder (MDD); Multimodal imaging; Putamen; Research Domain Criteria (RDoC)