Only females show a stable association between neuroticism and microstructural asymmetry of the cingulum across childhood and adolescence: A longitudinal DTI study

Neuroticism is characterized by a tendency to experience negative and anxious emotions. This personality trait is linked to an increased risk of anxiety and mood disorders. In a cross-sectional 3T diffusion tensor imaging (DTI) study in children and adolescents, we found an association between neuroticism and a relative imbalance between left and right (i.e., asymmetry) fractional anisotropy (FA) in the cingulum and white matter underlying the ventromedial prefrontal cortex with opposite directions in females and males. Here we analyzed the longitudinal follow-up DTI data, which was acquired in 76 typically-developing 7- to 18-year-olds, including up to 11 scans per subject. Neuroticism was assessed up to four times. Our longitudinal DTI measurements substantiate robust associations between higher neuroticism scores and increased left relative to right cingulum FA in females and decreased left relative to right cingulum FA in males. In females, the association was already present in late childhood and with a stable expression across childhood and adolescence. In males, the association gradually emerged during adolescence. Future longitudinal studies should clarify which neurobiological factors (e.g., genetic variation, prenatal stress, sex hormones) contribute to the sex-specific associations in the relationship between neuroticism and interhemispheric microstructural asymmetry of the cingulum. HighlightO_LIWe analyzed a unique longitudinal DTI dataset covering late childhood and adolescence. C_LIO_LIIn the cingulum, left-right fractional anisotropy (FA) asymmetry scaled with neuroticism. C_LIO_LIFemales displayed a stable association of neuroticism with increased cingulum asymmetry. C_LIO_LIMales showed an association between neuroticism and decreased cingulum FA asymmetry. C_LIO_LIThe association in males became more accentuated during adolescence C_LI