Brain scan study connects parahippocampal cortex thinning with depression and neuroticism

A neuroimaging study from Germany found that people with major depressive disorder tend to show significantly reduced thickness of the parahippocampal cortex in the left hemisphere of the brain compared to healthy individuals. Participants with higher levels of neuroticism also tended to have reduced thickness of this brain region in both hemispheres. The paper was published in Translational Psychiatry.

The parahippocampal cortex, located in the medial temporal lobe next to the hippocampus, is part of the limbic system and plays an important role in memory and spatial navigation. It acts as a major input and output hub for the hippocampus, helping process information that later becomes stored as long-term memory.

One of its best-studied roles is contextual processing, which allows the brain to understand where and when events occur. The parahippocampal cortex is also deeply involved in scene recognition, helping people identify and remember places. Brain imaging studies show it becomes active when individuals view landscapes, rooms, or buildings, providing contextual cues that link memories to specific environments.

Damage to this region can impair the ability to recall locations or navigate familiar areas. The parahippocampal cortex works closely with the entorhinal cortex and hippocampus to create spatial maps. Beyond navigation, it contributes to episodic memory — the long-term recollection of specific events — by encoding the “background” information surrounding those events.

Study author Dominik Nießen and colleagues note that the parahippocampal cortex is involved in several cognitive processes that tend to be disrupted in major depressive disorder, including episodic, associative, and source memory, contextual processing, scene perception, and emotional regulation. They aimed to determine whether these disruptions are linked to structural changes in this brain area, specifically its cortical thickness.

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The study included 43 patients diagnosed with major depressive disorder and 43 healthy individuals as controls. Participants’ average age was about 31 years. Patients were recruited from the Department of Psychiatry at RWTH Aachen University Hospital in Aachen, Germany, and met established diagnostic criteria for depression. Some also had other conditions: eight had personality disorders, three had posttraumatic stress disorder, two had alcohol use disorder, and several had other psychiatric diagnoses.

All participants completed an assessment of neuroticism using the NEO Five-Factor Inventory and underwent magnetic resonance imaging. Neuroticism is a personality trait characterized by a tendency to experience frequent negative emotions, such as anxiety, sadness, and irritability, along with emotional instability.

As expected, patients with major depressive disorder had higher neuroticism scores than the healthy participants. They also showed reduced thickness of the parahippocampal cortex in the left hemisphere. Across the entire sample, higher neuroticism scores were associated with lower thickness of the parahippocampal cortex in both hemispheres.

“These findings suggest that, in combination with neuroticism, parahippocampal thickness could serve as a potential biomarker of depression. Our results underscore the importance of multimodal assessments in MDD [major depressive disorder], potentially contributing to the foundation of individualized clinical decision-making and paving the way towards precision psychiatry,” the study authors concluded.

The study shows that thickness of the parahippocampal cortex can potentially serve as a biomarker of depression. However, it should be noted that the design of the study does not allow any causal inferences to be derived from the results. While it is possible that major depressive disorder leads to changes in the parahippocampal cortex, it is also possible that individuals in which this cortex is thinner are more prone to depression. Other options also remain open.

The paper, “7-Tesla ultra-high field MRI of the parahippocampal cortex reveals evidence of common neurobiological mechanisms of major depressive disorder and neurotic personality traits,” was authored by Dominik Nießen, Ravichandran Rajkumar, Dilsa Cemre Akkoc Altinok, Gereon Johannes Schnellbächer, Shukti Ramkiran, Jana Hagen, Nadim Jon Shah, Tanja Veselinović, and Irene Neuner.