Microstructure Abnormalities of Diffusion Tensor Imaging Measures in First-Episode, Treatment-Naïve Adolescents With Major Depressive Disorder: An Integrated AFQ and TBSS Study

Abstract

Purpose: Structural changes during depressive episodes in adolescents with major depressive disorder (MDD) remains unclear due to participant heterogeneity, illness chronicity, and medication confounders. This study aimed to explore white matter (WM) microstructural changes in first-episode, treatment-naïve adolescents with MDD using an integrated diffusion tensor imaging (DTI) approach.

Method: We recruited 66 subjects, including 37 adolescents with MDD and 29 healthy controls. Two main DTI techniques, automated fiber quantification (AFQ) and tract-based spatial statistics (TBSS), were used to analyze fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) in WM tracts. DTI measures were then correlated with the depressive symptoms evaluated by Hamilton Depression Rating Scale scores (HAMD-17).

Findings: In AFQ, MDD patients showed significant segmental differences in WM tracts compared to controls, including a negative correlation between SLF AD values and depression severity. TBSS revealed reduced FA in the cingulum, forceps minor, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, SLF, and uncinate fasciculus in MDD.

Conclusion: Our integrated DTI analysis in a unique first-episode, medication-naïve cohort revealed microstructural changes in adolescent MDD not previously reported. These findings may provide imaging markers for early detection and enhance our understanding of depression pathology in youth.

Keywords: adolescents; automated fiber quantification; diffusion tensor imaging; major depressive disorder; tract‐based spatial statistics.

FIGURE 1

Automated fiber quantification (AFQ) reveals nodes in tracts with significant differences in diffusion measures between pubertal children with major depressive disorder (pcMDD) and healthy controls (HCs). In (A), nodes of the left IFO with a significant difference in FA (left panel) and RD (right panel) are shaded in yellow. In (B), nodes of the right IFO with a significant difference in FA (left panel) and RD (right panel) are shaded in yellow. In (C), nodes of the right SLF with a significant difference in FA (left panel), RD (middle panel) and AD (right panel) are shaded in yellow. In (D), nodes of the left UNC with a significant difference in FA (left panel) and MD (right panel) are shaded in yellow. The solid lines represent the mean FA, MD, RD, and AD values and are colored blue and orange for pcMDD and HCs, respectively. AD = axial diffusivity; FA = fractional anisotropy; IFO = inferior frontal‐occipital fasciculus; MD = mean diffusivity; RD = radial diffusivity; SLF = superior longitudinal fasciculus; UNC = uncinate fasciculus.

FIGURE 2

Tract‐based spatial statistics (TBSS) results comparing fractional anisotropy (FA) values in adolescents with major depressive disorder (MDD) and healthy controls (HCs). Note: The FA maps show axial, coronal, and sagittal views (from left to right). Red voxels represent the mean white matter skeleton from the entire sample, and other colored voxels represent white matter regions with lower FA in pubertal children with major depressive disorder (pcMDD) compared with HCs (p < 0.05, threshold‐free cluster enhancement [TFCE]‐corrected). (A) Right cingulum (cingulate gyrus, CinG). (B) Callosum forceps minor (CFM). (C) Bilateral inferior fronto‐occipital fasciculus (IFO). (D) Left inferior longitudinal fasciculus (ILF). (E) Right superior longitudinal fasciculus (SLF). (F) Left uncinate fasciculus (UNC).

FIGURE 3

Correlations among fractional anisotropy (FA) values in white matter (WM) regions, mean values of nodes with differences, and HAMD‐17 scores. (A): Correlations between the mean diffusion measures of nodes with differences and HAMD‐17 score. (B): Correlations between the FA values of WM regions and HAMD‐17 scores. Spearman correlation was employed, with the correlation coefficient r values denoted using the color bar; * indicates statistical significance. AD: axial diffusivity; CFM: callosum forceps minor; CinG: cingulum (cingulate gyrus); FA: fractional anisotropy; HAMD‐17: Hamilton Depression Rating Scale; IFO: inferior fronto‐occipital fasciculus; ILF: inferior longitudinal fasciculus; L: left; MD: mean diffusivity; R: right; RD: radial diffusivity; SLF: superior longitudinal fasciculus; UNC: uncinate fasciculus.