Voxel-based Diffusion Tensor Imaging Study Of Brain White Matter In Patients With Generalized Anxiety Disorder

Object To assess the microstructure integrity of brain white matter tracts in patients with first-episode treatment-naive general anxiety disorders (GAD) using diffusion tensor imaging (DTI) technique. To explore the possible pathological mechanism of brain function in GAD from neuroimaging field.Methods Twenty two first-episode,treatment-naive and no comorbid patients with GAD,aged 18 to 44 years old (according to the diagnosis criteria of DSM-IV-TR Handbook of Differential Diagnosis, SCID-I/P) and thirty nine age-and educational level-matched healthy controls were enrolled. All subjects were assessed using Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD), Penn State Worry Questionnaire (PSWQ), and State-Trait Anxiety Inventory (STAI). HAMA scores≥18,PSQW scores≥60 and HAMD scores<12 were needed in patients, and both HAMA and HAMD scores≤7 were needed in controls.Then, all subjects accepted the MRI scans and DTI. Using software DTI-Studio and SPM2,the fractional anisotropy (FA) in brain white matter of the two groups were compared by voxel-based analysis. The areas with continous 50 voxels and above were considered be a significant different area (P<0.005).Then these areas were superimposed to the standard brain of SPM2.Using a self-develop software, the average FA in these significant different areas of each subject were calculated. Then Spearman’s correlation analysis was carried to test the association among FA and disease course and clinical scales’scores (HAMA, PSWQ, STAI).Results Twenty two patients with GAD and thirty nine healthy controls accepted MRI scan. Data could be analyzed finally including sixteen GAD patients (8 females and 8 males) and twenty six healthy controls(13 females and 13 males).The result showed that compared to healthy controls, FA significantly decreased in the left medial frontal and right insula white matter and increased in right amygdala in first-episode treatment-naive GAD patients (P<0.005).The Spearman correlation analysis showed a significant positive correlation between FA in amygdala white matter in GAD patients and the scores of PSWQ, HAMA and S-AI and T-AI (P<0.05).No significant correlation were found between FA in left medial frontal and insla white matter and scales’scores (P>0.05).Furthermore, a positive correlation existed between the average disease duration of GAD and FA in the right amygdale white matter (P> 0.05).And no significant correlation between duration of disease and scales’scores were found (P>0.05).Conclusions 1.This study found that microstructure abnormalities in right amygdala, left medial frontal and right insula brain white matter tracts in first-episode treatment-naive GAD patients, which suggests brain white matter lesion has happened at the early period of GAD.2.FA increase in amygdala in GAD patients suggests that the connectivity among amygdala and some other brain areas maybe increase, which implys the activate of amygdala-based fear conditional reflex neural circuitry were abnormal.The individuals with GAD persistently process environmental information sensitively, which leads to the clinical symptoms, persistent restlessness, increased arousal,autonomic nerve dysfunction, and so on.3.FA increased in right amygdala in GAD patients reflects lateralization of amygdala function. The right amygdala unconsciously prior processes the threatening information.4.Abnormal activation degree of right amygdala white matter tracts is dose-reponse associated with the severity and disease duration, while, the white matter abnormalities degree in left medial frontal and right insula is not related to the severity and disease duration in GAD patients.