Progressive grey matter atrophy in adolescents with major depressive disorder revealed by causal structural covariance network

TL;DR

This study shows how brain structure changes over time in adolescents with depression, revealing causal connections between key brain regions.

Contribution

The study identifies causal structural covariance networks and progressive gray matter atrophy in adolescent depression.

Findings

Adolescents with depression show gray matter atrophy in regions like the vmPFC, dACC, MCC, and insula.

The atrophy progresses to subgenual ACC and networks like default mode and frontoparietal with longer illness duration.

Key brain regions exert positive causal effects on networks involved in cognitive control, reward, and self-referential processing.

Abstract

Adolescence is a period marked by highest vulnerability to the onset of depression, with profound implications for adult health. Neuroimaging studies have revealed considerable atrophy in brain structure in these patients with depression. Of particular importance are regions responsible for cognitive control, reward, and self-referential processing. However, the causal structural networks underpinning brain region atrophies in adolescents with depression remain unclear.

This study aimed to investigate the temporal course and causal relationships of gray matter atrophy within the brains of adolescents with depression.

We analyzed T1-weighted structural images using voxel-based morphometry in first-episode adolescent patients with depression (n=80, 22 males; age = 15.57±1.78) and age, gender matched healthy controls (n=82, 25 males; age = 16.11±2.76) to identify the disease stage-specific gray matter abnormalities. Then, with granger causality analysis, we arranged the patients’ illness duration chronologically to construct the causal structural covariance networks that investigated the causal relationships of those atypical structures.

Compared to controls, smaller volumes in ventral medial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), middle cingulate cortex (MCC) and insula areas were identified in patients with less than 1 year illness duration, and further progressed to the subgenual ACC, regions of default, frontoparietal networks in longer duration. Causal network results revealed that dACC, vmPFC, MCC and insula were prominent nodes projecting exerted positive causal effects to regions of the default mode and frontoparietal networks. The dACC, vmPFC and insula also had positive projections to the reward network, which included mainly the thalamus, caudate and putamen, while MCC also exerted a positive causal effect on the insula and thalamus.

These findings revealed the progression of structural atrophy in adolescent patients with depression and demonstrated the causal relationships between regions involving cognitive control, reward and self-referential processes.

None Declared