Gyrification patterns in first-episode, drug-naïve major depression: Associations with plasma levels of brain-derived neurotrophic factor and psychiatric symptoms

Tomoya Natsuyama; Naomichi Okamoto; Keita Watanabe; Enkhmurun Chibaatar; Hirofumi Tesen; Gaku Hayasaki; Atsuko Ikenouchi; Shingo Kakeda; Reiji Yoshimura

doi:10.3389/fpsyt.2022.1031386

Gyrification patterns in first-episode, drug-naïve major depression: Associations with plasma levels of brain-derived neurotrophic factor and psychiatric symptoms

Front Psychiatry. 2023 Jan 6:13:1031386. doi: 10.3389/fpsyt.2022.1031386. eCollection 2022.

Authors

Tomoya Natsuyama¹, Naomichi Okamoto¹, Keita Watanabe², Enkhmurun Chibaatar¹, Hirofumi Tesen¹, Gaku Hayasaki¹, Atsuko Ikenouchi^{1

3}, Shingo Kakeda⁴, Reiji Yoshimura¹

Affiliations

¹ Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan.
² Open Innovation Institute, Kyoto University, Kyoto, Japan.
³ Medical Center for Dementia, Hospital of University of Occupational and Environmental Health, Kitakyushu, Japan.
⁴ Department of Radiology, Graduate School of Medicine, Hirosaki University, Hirosaki, Japan.

Abstract

Background and objectives: Cortical structural changes in major depressive disorder (MDD) are usually studied using a voxel-based morphometry approach to delineate the cortical gray matter volume. Among cortical structures, gyrification patterns are considered a relatively stable indicator. In this study, we investigated differences in gyrification patterns between MDD patients and healthy controls (HCs) and explored the association of gyrification patterns with plasma brain-derived neurotrophic factor (BDNF) levels and depressive symptoms in MDD patients.

Methods: We evaluated 79 MDD patients and 94 HCs and assessed depression severity in the patients using the 17-item Hamilton Depression Rating Scale (HAM-D). Blood samples of both groups were collected to measure plasma BDNF levels. Magnetic resonance imaging (MRI) data were obtained using three-dimensional fast-spoiled gradient-recalled acquisition. Differences in plasma BDNF levels between groups were examined using the Mann-Whitney U test. Principal component analysis and orthogonal partial least squares discriminant analysis (OPLS-DA) were conducted to investigate the gyrification patterns which were significantly different between the groups, i.e., those with variable importance in projection (VIP) scores of >1.5 and p-value < 0.05 in multiple regression analyses adjusted for age and sex. Finally, multiple regression analysis was performed on the selected gyrification patterns to examine their association with BDNF levels in the two groups and HAM-D in the patients.

Results: There were no significant differences in plasma BDNF levels between the groups. We found that 108 (71.0%) of 152 total local gyrification indices were MDD < HC. We identified 10 disease-differentiating factors based on critical gyrification features (VIP > 1.5 and p-value adjusted for age and sex < 0.05). However, we found no significant correlations between the 10 gyrification patterns and plasma BDNF levels and no interaction with group. Moreover, no significant correlations were observed between the local gyrification indices and HAM-D total scores.

Conclusion: These results suggest that abnormal early cortical neurodevelopment may mediate vulnerability to MDD, independent of plasma BDNF levels and depressive symptoms.

Keywords: brain-derived neurotrophic factor; cerebral cortex; gray matter; gyrification; major depression.