Cerebral White Matter Changes in Young Healthy Individuals With High Trait Anxiety: A Tract-Based Spatial Statistics Study

Background: Abnormalities in prespecified and empirical white matter tracts in young patients with anxiety-related disorders have been reported in some diffusion tensor imaging (DTI) studies. However, with few literatures examining the association between the integrity of whole brain white matter and trait anxiety levels in the non-clinical populations, whether white matter changes arise in young healthy individuals with high trait anxiety remains unknown. Methods: We examined whole brain white matter alterations in young healthy individuals with high anxiety but without history of neurological or psychiatric disorders via DTI technology. Group comparison of tract-based spatial statistics (TBSS) was performed to investigate the microstructural diffusion alterations in 38 high anxious subjects in comparison with 34 low anxious subjects matched with age, gender, and degree of education. These analyses controlled for depression to establish specificity to trait anxiety. Results: Young healthy subjects with high trait anxiety had significantly decreased fractional anisotropy (FA) values in multiple clusters, including corona radiate (CR), anterior thalamic radiation (ATR), inferior fronto-occipital fasciculus (IFOF), bilaterally, body, genu, and splenium of corpus callosum (CC) and forceps minor, compared with low trait anxious subjects. For the abnormal FA regions, the other diffusion metrics were also altered slightly. Conclusions: Non-clinical individuals with high anxiety already have white matter alterations in the thalamus-cortical circuit and some emotion-related areas that were widely reported in anxiety-related disorders. The altered white matter may be a vulnerability marker in individuals at high risk of clinical anxiety. These findings can deepen our understanding of the pathological mechanism of anxiety and further support the need for preventive interventions in high anxiety individuals.