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Putamen structure and function in familial risk for depression: a multimodal imaging study

      ABSTRACT

      Background

      The putamen has been implicated in depressive disorders, but how its structure and function increase depression risk is not clearly understood. We examine how putamen volume, neuronal density, and mood-modulated functional activity relate to family history and prospective course of depression.

      Methods

      The study includes 115 2nd and 3rd generation offspring at high- or low-risk for depression based on the presence/absence of major depressive disorder (MDD) in the first generation. Offspring were followed longitudinally using semi-structured clinical interviews blind to their familial risk; putamen structure, neuronal integrity, and functional activation were indexed by structural MRI, proton magnetic resonance spectroscopy (MRS, N-acetyl aspartate/creatine ratio, NAA/Cr), 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, β-left=-0.17, β-right=-0.15, ps=0.002), NAA/Cr (β-left=-0.40, β-right=-0.37, ps<0.0001), and activation modulated by valence (β-left=-0.22, β-right=-0.27, ps<0.05). Volume differences were greater at younger, and NAA/Cr differences at older, ages. Lower putamen volume also predicted MDD episodes up to 8 years after the scan (β-left=-0.72, p=0.013; β-right=-0.83, p=0.037). MRS and task fMRI measures were modestly correlated (0.27≤r≤0.33).

      Discussion

      Findings demonstrate abnormalities in putamen structure and function in individuals at high-risk for MDD. 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.

      Keywords

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