Brain Network Controllability and Its Regional Gene Expression Profile Associated With Suicidal Tendencies in Major...

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Suicidality is a severe symptom of major depressive disorder (MDD).
• Understanding the brain's structural dynamics and gene expression in MDD patients with suicidality is crucial but remains unclear.
• Previous research has not fully elucidated the network-wide alterations associated with suicidal ideation and behavior in MDD.

Purpose of the Study:

• To investigate network-wide structural dynamics and transcriptional patterns in MDD patients with varying levels of suicidality.
• To compare brain network controllability (ANC) and gene expression profiles between MDD patients with suicidal ideation (MDDSI), suicidal behavior (MDDSB), and without suicidal ideation (MDDNSI), alongside healthy controls (HCs).
• To identify specific gene functions and cell types implicated in the neural circuits of suicidality within MDD.

Main Methods:

• Recruited 124 participants: 31 MDDNSI, 34 MDDSI, 22 MDDSB, and 37 HCs.
• Utilized diffusion tensor imaging (DTI) and network-based statistics (NBS) to analyze structural connectivity.
• Measured average network controllability (ANC) and performed weighted gene coexpression network analysis (WGCNA) for gene expression patterns.

Main Results:

• MDDSI patients showed decreased ANC in the suicidal ideation (SI) circuit compared to MDDNSI patients, with altered gene expression.
• MDDSB patients exhibited reduced ANC in the suicidal behavior (SB) circuit compared to MDDNSB patients, alongside distinct gene expression changes.
• Genes within both SI and SB circuits were enriched in gamma-aminobutyric acid (GABA) neurons, suggesting their involvement.

Conclusions:

• Differential ANC in SI and SB networks distinctly influences brain state trajectories in MDD patients.
• Specific transcriptional patterns and cell types, including GABA neurons, are associated with brain regions related to suicidal ideation and behavior in depression.
• This study provides novel insights into the neurobiological underpinnings of suicidality in MDD.