Publication date: Jul 05, 2025
The parahippocampal cortex (PHC) is a highly interconnected region within the medial temporal lobe (MTL) and is essential in memory, emotion and cognition. According to the cognitive model of depression, dysfunctions in these processes constitute the pathophysiological foundation of major depressive disorder (MDD). Research suggests that human personality, and neuroticism in particular, plays an important role in the development and disease progression of MDD. Furthermore, extensive neuroimaging evidence indicates that neuroticism and depression share overlapping structural and functional correlates, potentially including the PHC. In a matched sample of 86 adults (43 MDD patients, 43 control participants, mean age 31. 4 years, range 18-61 years, 40 female), PHC thickness was measured using structural MRI at an ultra-high field strength of 7 T and compared to the level of neuroticism as measured by the NEO-FFI scale. MDD patients exhibited significantly lower left hemispheric PHC thickness compared to healthy controls (p = 0. 002, η = 0. 119). Additionally, linear regression analysis revealed a significant association between neuroticism and PHC thickness within both hemispheres (L: p = 0. 012, β = -0. 414; R: p = 0. 008, β = -0. 512), with highly neurotic individuals displaying reduced cortical thickness. These findings suggest that, in combination with neuroticism, PHC thickness could serve as a potential biomarker of depression. Our results underscore the importance of multimodal assessments in MDD, potentially contributing to the foundation of individualised clinical decision-making and paving the way towards precision psychiatry.