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

Whereas meta-analytical data highlight abnormal frontocortical microstructure (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 T1) and iron concentration (proxied by transverse relaxation time T2*), microstructural processes deemed particularly germane to cortical microstructure. 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 T1 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 disintegration in MDD.

Jurjen Heij, Wietske van der Zwaag, Tomas Knapen, Matthan W. A. Caan, Birte Forstmann, Dick J. Veltman, Guido van Wingen, Moji Aghajani