Cortical surface area alterations shaped by genetic load for neuroticism

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Neuroticism is a significant risk factor for major depressive disorder (MDD).
• Previous research identified biological correlates of neuroticism, including cortical alterations in brain regions relevant to affective disorders.

Purpose of the Study:

• To investigate the influence of a polygenic score for neuroticism (PGS) on cortical brain structure.
• To examine associations between neurotic phenotype and cortical measures in healthy controls (HC) and MDD patients.

Main Methods:

• Utilized a discovery sample (n=1014) and a replication sample (n=604) comprising HC and MDD patients.
• Assessed the association between PGS for neuroticism and cortical surface area and thickness.
• Conducted subgroup analyses stratified by case-control status.

Main Results:

• PGS for neuroticism was significantly associated with decreased cortical surface area in the inferior parietal cortex, precuneus, rostral cingulate cortex, and inferior frontal gyrus.
• Replication confirmed associations between PGS and surface area in the inferior parietal cortex and precuneus.
• Neurotic phenotype correlated negatively with surface area in similar cortical regions, particularly the inferior parietal cortex and precuneus.

Conclusions:

• Genetically influenced alterations in cortical surface area, especially in regions involved in internally focused cognition, may play a role in the development of neuroticism.
• No significant associations were found between PGS and cortical thickness.