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Brain scans reveal parahippocampal cortex thinning in those with depression and neuroticism
https://medicalxpress.com/news/2025-07-brain-scans-reveal-parahippocampal-cortex.html [medicalxpress.com]
Depression is a mental health disorder characterized by a recurrent or persistent sadness and a loss of interest in activities that were previously deemed pleasurable, sometimes accompanied by changes in sleep, appetite and perceived energy levels. One of the most debilitating types of depression is major depressive disorder (MDD), which entails a pervasive low mood for a prolonged time, which in turn adversely impacts people's ability to engage in daily activities.
As depression is estimated to be experienced by approximately 3.5% of people worldwide, understanding its neurophysiological underpinnings and its characteristic brain signatures is of utmost importance. Past studies have linked depression, particularly MDD, to structural changes in a brain region known as the medial temporal lobe, which has been implicated in the formation and retrieval of memories, as well as in emotional processing and decision-making.
Researchers at Aachen University and Forschungszentrum Jülich GmbH recently carried out a study aimed at exploring the link between the structure of a specific part of the MTL, namely the parahippocampal cortex (PHC), and MDD. Their paper, published in Translational Psychiatry, suggests that the thickness of the PHC is an indicator of both MDD and neuroticism, a psychological trait marked by a pronounced tendency to feel negative emotions (e.g., anxiety, guilt, anger, etc.).
"The PHC is a highly interconnected region within the medial temporal lobe (MTL) and is essential in memory, emotion and cognition," wrote Dominik Nießen, Ravichandran Rajkumar and their colleagues in their paper. "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, play an important role in the development and disease progression of MDD."
Interestingly, recent neuroscience studies found that the brains of people diagnosed with depression and those scoring higher on recognized tests of neuroticism often share some similarities, some of which relate to the PHC. The PHC is a part of the MTL found to support various cognitive functions, including spatial processing, as well as the encoding and retrieval of emotional memories.
The key objective of the recent study by Nießen, Rajkumar and their colleagues was to further investigate how the overall structure of the PHC varies in individuals diagnosed with MDD or exhibiting higher levels of neuroticism. To do this, they scanned the brains of several individuals, some of whom were diagnosed with MDD, using a neuroimaging technique known as structural magnetic resonance imaging (MRI).
"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," explained Nießen, Rajkumar and their colleagues.
The researchers subsequently analyzed the brain scans collected from the study participants in conjunction with their mental health information and ratings on neuroticism tests. Overall, their findings suggest the PHC of people diagnosed with MDD and rating higher on neuroticism scales is thinner than that of individuals with low neuroticism ratings and no reported mental health conditions.
"MDD patients exhibited significantly lower left hemispheric PHC thickness compared to healthy controls (pfdr = 0.002, η2 = 0.119)," wrote the authors. "Additionally, linear regression analysis revealed a significant association between neuroticism and PHC thickness within both hemispheres (L: pfdr = 0.012, β = −0.414; R: pfdr = 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."
This recent work by Nießen, Rajkumar and their colleagues identifies a new potential biomarker that could contribute to the diagnosis and understanding of persistent cases of depression. In the future, this team's findings could inspire other medical researchers and neuroscientists to closely examine the possible role of the PHC in depression and neuroticism.
"Our results underscore the importance of multimodal assessments in MDD, potentially contributing to the foundation of individualized clinical decision-making and paving the way towards precision psychiatry," wrote the authors.
More information: Dominik Nießen et al, 7-Tesla ultra-high field MRI of the parahippocampal cortex reveals evidence of common neurobiological mechanisms of major depressive disorder and neurotic personality traits, Translational Psychiatry (2025). DOI: 10.1038/s41398-025-03435-y [doi.org]
