Resting-state functional magnetic resonance imaging and tryptophan hydroxylase-2 methylation interaction in major depressive disorder

Jul 17, 2025Brain research bulletin

How brain activity at rest and gene changes in serotonin production relate in major depression

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Abstract

The right superior temporal gyrus has abnormal activity in individuals with major depressive disorder (MDD).

In a study of 98 patients with MDD and 63 controls, significant differences were found in brain activity between the two groups.
The amplitude of low-frequency fluctuation (ALFF) in the right superior temporal gyrus was notably different in MDD patients (p < 0.05).
Regional homogeneity (ReHo) in the right middle temporal gyrus and left middle occipital gyrus also showed significant differences (p < 0.05).
Functional connectivity (FC) between the right superior temporal gyrus and right superior frontal gyrus, as well as between right middle temporal gyrus and right middle occipital gyrus, differed significantly between MDD patients and controls (p < 0.05).
The interaction between ALFF activity in the right superior temporal gyrus and TPH2 methylation may be linked to the occurrence of MDD (β=-2.108, p = 0.004).
ReHo activity in the right middle temporal gyrus and TPH2 methylation could also be associated with MDD (β=-1.720, p = 0.018).

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BACKGROUND: Functional abnormalities in different brain regions are related to major depressive disorder (MDD). In our previous study, we demonstrated that DNA methylation of Tryptophan Hydroxylase-2 (TPH2) is related to the occurrence of MDD. The present study aimed to identify the interaction of the functional activities of brain regions identified as regions of interest (RoI) in MDD with TPH2 gene methylation to explore their relationship.

METHODS: Data from 98 patients with MDD and 63 controls were utilized. The amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and fractional ALFF (fALFF), were used to identify ROIs regions in the RESTPlus Software of MATLAB. General linear regression (GLM) was performed to analyze the association between functional connectivity (FC) found in rs-fMRI and the effect of TPH2 DNA methylation in patients with MDD and controls.

RESULTS: In the rs-fMRI analysis, the ALFF of right superior generalized gyrus (STG) was significantly different between the MDD and HCs groups (p < 0.05). The ReHo of right Middle temporal gyrus (MTG) and left middle occipital gyrus (MOG) were significantly different between the two groups (p < 0.05). These ROIs were used to further analyze the FC differences between MDD and HCs, and it was found that the FC of right STG and right superior frontal gyrus (SFG) and the FC of right MTG and right MOG were significantly different between the two groups (p < 0.05). It was further found that the interaction between ALFF activity of the right STG and TPH2-5-203 methylation (β=-2.108, p = 0.004), ReHo activity level of the right MTG, and TPH2-5-203 methylation were correlated with the occurrence of MDD (β=-1.720, p = 0.018).

CONCLUSION: This study found that the functional activities of the temporal lobe, middle occipital gyrus, and superior frontal gyrus were abnormal in patients with MDD compared to HCs. Furthermore, the interaction of functional activities of the right superior temporal gyrus /middle temporal gyrus and TPH2 methylation were associated with the occurrence of MDD, suggesting that the combination of functional activities and DNA methylation was helpful for diagnosis of MDD.

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