Biobehavioral correlates of an fMRI index of striatal tissue iron in depressed patients

Abstract

Dopaminergic function is a critical transdiagnostic neurophysiological dimension with broad relevance in psychiatry. Normalized T2*-weighted (nT2*w) imaging has been previously investigated as a method to quantify biological properties of tissue in the striatum (e.g., tissue iron), providing a widely available, in vivo marker with potential relevance to dopaminergic function; but no prior study to our knowledge has examined this neuroimaging marker in clinical depression. In a treatment-seeking, clinically depressed sample ( n \u2009=\u2009110), we quantified tissue iron (nT2*w) in striatal regions. We assessed test-retest reliability and correlated values with dimensional features across levels of analysis, including demographic/biological (sex, age, Body Mass Index), neuroanatomical (hippocampal atrophy, which was quantified using a recently validated machine-learning algorithm), and performance-based (Affective Go/NoGo task performance) indices with relevance to depressive neurocognition. Across patients, decreased tissue iron concentration (as indexed by higher nT2*w) in striatal regions correlated with indices of decreased cognitive-affective function on the Affective Go/NoGo task. Greater caudate nT2*w also correlated with greater hippocampal atrophy. Striatal tissue iron concentrations were robustly lower in female patients than males but gender differences did not explain relations with other neurocognitive variables. A widely available fMRI index of striatal tissue properties, which exhibited strong psychometric properties and can be readily quantified from most fMRI datasets irrespective of study-specific features such as task design, showed relevance to multiple biobehavioral markers of pathophysiology in the context of moderate-to-severe, treatment-resistant depression. Striatal tissue iron may play a role in dimensional and subgroup-specific features of depression, with implications for future research on depression heterogeneity.