Abnormal Brain Folding a Biomarker for Major Depressive Disorder

Summary: Researchers discovered a biomarker for major depressive disorder (MDD) in the brain’s outer layer folds, or gyri. The investigation, first of its kind, associates MDD with the local gyrification index (LGI), a measure of cortical folding derived from brain scans.

The study revealed that patients with MDD exhibit decreased cortical folding, particularly in the left pars triangularis. This breakthrough lays groundwork for a better understanding of MDD and potential treatment targets.

Key Facts:

  1. This study is the first to examine the association between major depressive disorder (MDD) and the local gyrification index (LGI) of multiple cortical regions.
  2. Researchers found that patients with MDD showed lower LGI values, indicating decreased cortical folding, particularly in the left pars triangularis.
  3. Clinical characteristics of MDD, such as the recurrence and duration of illness, were associated with increased gyrification in several occipital and temporal cortical regions.

Source: Korea University College of Medicine

In appearance, the human brain’s outermost layer, called the cortex, is a maze of tissue folds. The peaks or raised surfaces of these folds, called gyri, play an important role in the proper functioning of the brain.

Improper gyrification—or the development of gyri—has been implicated in various neurological disorders, one of them being the debilitating and widespread mental illness­, major depressive disorder (MDD).

LGI is a measurement of cortical folding that is derived from brain scans as a ratio of the curved and smoothed surfaces of the cortex in a region of interest. Credit: Neuroscience News

Although prior studies have shown that abnormal cortical folding patterns are associated with MDD, a reliable indicator has so far remained out of reach.

Now, in a positive turn of events, researchers led by Professor Byung-Joo Ham and Associate Professor Kyu-Man Han from Korea University Medicine have reported the successful identification of a neuroimaging-based biomarker for MDD in a recent study published on 8 May 2023 in Psychological Medicine.

Talking about the unique finding that sets apart their study from the previous ones, Prof. Ham explains, “Our first-of-its-kind study investigated the association of MDD with the local gyrification index or LGI of multiple cortical regions at the whole-brain level and the association of LGI with the clinical characteristics of MDD.”

But what indeed is local gyrification index (LGI)?

LGI is a measurement of cortical folding that is derived from brain scans as a ratio of the curved and smoothed surfaces of the cortex in a region of interest.

In this study, the researchers compared the LGI values from multiple cortical regions in the brain of patients with MDD with those of healthy individuals. The neuroimaging data used to compare and analyze both groups were obtained from magnetic resonance imaging scans.

Prof. Ham and his team showed that LGI values from multiple cortical regions in the brain of patients with MDD showed hypogyrification—a condition characterized by decreased cortical folding—when compared with healthy individuals.

They found that patients with MDD showed significantly lower LGI values in 7 out of the 66 cortical regions assessed (in both hemispheres of the brain), which included the prefrontal cortex, anterior cingulate cortex, insula, and several temporal and parietal regions.

Notably, the most significant hypogyrification was observed in the left pars triangularis of patients with MDD. These findings are nothing short of a breakthrough in MDD research!

When asked to share his thoughts about the study’s results, Dr. Han asserts that there is more to their findings than what meets the eye. 

“The cortical regions that we assessed in our study have been previously shown to affect emotional regulation. This means that abnormal cortical folding patterns may be associated with the dysfunction of neural circuits involved in emotional regulation, thus contributing to the pathophysiology of MDD,” he adds reflectively.  

The study’s findings firmly establish LGI as a relatively stable neuroimaging marker for MDD, when compared with previously identified biomarkers. This is because LGI values reflect the long-drawn developmental process of gyrification that is not spontaneously affected by an individuals’ state during the measurement process.

It is also worth highlighting the robustness of this study, given that it involved a larger sample size of participants, which gives it an edge over similar studies conducted previously.

Interestingly, the researchers noted that the clinical characteristics of MDD, including the recurrence and duration of illness in patients, were associated with increased gyrification in several occipital and temporal cortical regions.

However, they did not observe any significant difference in the LGI values in these regions between the patient and control groups.

With the head start given by this study, future research could explore the genetic factors that predispose individuals to abnormal cortical folding patterns, and, in turn, MDD. The study can also serve as a roadmap for the selection of cortical regions as targets for medical treatments aimed at reducing the symptoms of this condition.

Overall, by identifying a new biomarker for MDD, this study has paved the way for a deeper understanding of a serious and pervasive mental health problem, which could hopefully take the medical community one step closer to finding an effective solution in the future.

About this major depressive disorder research news

Author: Gihyun Park
Source: Korea University College of Medicine
Contact: Gihyun Park – Korea University College of Medicine
Image: The image is credited to Neuroscience News

Original Research: Open access.
Decreased Cortical Gyrification in Major Depressive Disorder” by Byung-Joo Ham et al. Psychological Medicine


Abstract

Decreased Cortical Gyrification in Major Depressive Disorder

Background

Early neurodevelopmental deviations, such as abnormal cortical folding patterns, are candidate biomarkers of major depressive disorder (MDD). We aimed to investigate the association of MDD with the local gyrification index (LGI) in each cortical region at the whole-brain level, and the association of the LGI with clinical characteristics of MDD.

Methods

We obtained T1-weighted images from 234 patients with MDD and 215 healthy controls (HCs). The LGI values from 66 cortical regions in the bilateral hemispheres were automatically calculated according to the Desikan–Killiany atlas. We compared the LGI values between the MDD and HC groups using analysis of covariance, including age, sex, and years of education as covariates. The association between the clinical characteristics and LGI values was investigated in the MDD group.

Results

Compared with HCs, patients with MDD showed significantly decreased LGI values in the cortical regions, including the bilateral ventrolateral and dorsolateral prefrontal cortices, medial and lateral orbitofrontal cortices, insula, right rostral anterior cingulate cortex, and several temporal and parietal regions, with the largest effect size in the left pars triangularis (Cohen’s f2 = 0.361; p = 1.78 × 10−13). Regarding the association of clinical characteristics with LGIs within the MDD group, recurrence and longer illness duration were associated with increased gyrification in several occipital and temporal regions, which showed no significant difference in LGIs between the MDD and HC groups.

Conclusions

These findings suggest that the LGI may be a relatively stable neuroimaging marker associated with MDD predisposition.