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. Highlight ### Competing Interest Statement Hartwig R. Siebner has received honoraria as speaker from Sanofi Genzyme, Denmark and Novartis, Denmark, as consultant from Sanofi Genzyme, Denmark, Lophora, Denmark, and Lundbeck AS, Denmark, and as editor-in-chief (Neuroimage Clinical) and senior editor (NeuroImage) from Elsevier Publishers, Amsterdam, The Netherlands. He has received royalties as book editor from Springer Publishers, Stuttgart, Germany and from Gyldendal Publishers, Copenhagen, Denmark. The authors declare no potential conflict of interest. * DWI : diffusion weighted imaging DT : diffusion tensor DTI : diffusion tensor imaging ROI : region-of-interest FA : fractional anisotropy AD : axial diffusivity MD : mean diffusivity RD : radial diffusivity vmPFC : ventromedial prefrontal cortex vmPFCWM : ventromedial prefrontal cortex white matter UF : uncinate fasciculus WM : white matter