The mediating effect of neuroticism on the association between brain signal variability in the prefrontal cortex and depression among healthy individuals

Abstract

The personality trait of neuroticism has been recognized as a risk factor for depression. Research into the interplay between brain activity, neuroticism, and subclinical depressive symptoms could potentially uncover biomarkers capable of predicting the onset of depression. Brain intrinsic signal variability, a measure of system flexibility, is related to lifespan development, cognitive performance, and mental health disorders. Despite its importance, the link between signal variability and both neuroticism and depression has not been previously explored. This study, therefore, sought to investigate the correlation between brain signal variability, neuroticism, and depressive symptoms in individuals without clinical depression. The resting-state functional magnetic resonance imaging data were collected from 103 healthy right-handed individuals (63 males, 40 females; mean age 24.73 ± 8.34 years). Neuroticism and subclinical depressive symptoms were assessed by Eysenck Personality Questionnaire and Zung Self-Rating Depression Scale, respectively. To quantify brain signal variability, voxel-wise mean-squared successive difference (MSSD) was calculated. A mediation analysis was subsequently performed to explore the interrelationships among signal variability, neuroticism, and depressive symptoms. Neuroticism showed a significant negative correlation with MSSD in several brain regions, including the medial prefrontal cortex (MPFC), dorsolateral prefrontal cortex (dlPFC), precentral gyrus, angular gyrus, and middle temporal gyrus. Additionally, MSSD in the MPFC and dlPFC were negatively associated with depressive symptoms, with neuroticism mediating this relationship. In sum, neuroticism and depressive symptoms were associated with reduced signal variability in the PFC regions. These effects suggested that dysfunctional activity within the PFC regions is linked to the etiology of depression, mediated by individual differences in neuroticism.