Quantitative MRI at 7-Tesla reveals novel frontocortical myeloarchitecture anomalies in major depressive disorder

Abstract Whereas meta-analytical data highlight abnormal frontocortical macrostructure (thickness/surface area/volume) in Major Depressive Disorder (MDD), the underlying microstructural processes remain uncharted, due to the use of conventional MRI scanners and acquisition techniques. We uniquely combined Ultra-High Field MRI at 7.0 Tesla with Quantitative Imaging to map intracortical myelin (proxied by longitudinal relaxation time T 1 ) and iron concentration (proxied by transverse relaxation time T 2 *), microstructural processes deemed particularly germane to cortical macrostructure. Informed by meta-analytical evidence, we focused specifically on orbitofrontal and rostral anterior cingulate cortices among adult MDD patients ( N = 48) and matched healthy controls (HC; N = 10). Analyses probed the association of MDD diagnosis and clinical profile (severity, medication use, comorbid anxiety disorders, childhood trauma) with aforementioned microstructural properties. MDD diagnosis ( p’s < 0.05, Cohen’s D = 0.55–0.66) and symptom severity ( p’s < 0.01, r = 0.271–0.267) both related to decreased intracortical myelination (higher T 1 values) within the lateral orbitofrontal cortex, a region tightly coupled to processing negative affect and feelings of sadness in MDD. No relations were found with local iron concentrations. These findings allow uniquely fine-grained insights on frontocortical microstructure in MDD, and cautiously point to intracortical demyelination as a possible driver of macroscale cortical disintegrity in MDD.