Research On Brain Fear Circuitry In Treatment-Naive Patients With Generalized Anxiety Disorder And Patients With Panic Disorder

Objective To explore the characteristics of fear circuitry in patients with generalized anxiety disorder (GAD) and patients with panic disorder (PD), and to identify the unique biological markers for GAD and PD respectively on the basis of theory of brain networks.Methods We recruited22GAD patients,24PD patients and35educational level-and age-matched healthy controls. All subjects were screened by Structured Clinical Interview for DSM-Ⅳ-TR Axis I Disorders, Research Version, Patient Edition (SCID-I/P). Patients who met DSM-Ⅳ diagnostic criteria for GAD or PD without comorbidity aged18-44years old, treatment-naive were enrolled. All subjects were evaluated with Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD).The inclusion criteria were HAMA and HAMD scores<7points for healthy controls (HCs). Moreover, patients with GAD were assessed with the Penn State Worry Questionnaire (PSWQ), and patients with PD were assessed with Panic Disorder Severity Scale (PDSS). All of the above assessments and evaluation were implemented by two professional psychiatrists. After completion of MRI scans for all subjects, the unqualified data due to head movements and other factors were excluded.1) For ecStroop cognitive tasks-dependent fMRI study, a total of14GAD patients,14PD patients, and25HCs were enrolled. Brain activation difference between the three groups was examined by ANOVA. Post hoc tests were used to examine the difference between every two groups.2) For resting-state functional connectivity (RSFC),15GAD patients,17PD patients, and22HCs were enrolled. Region of interest (ROI)-based functional connectivity analysis were employed on the basis of seed point of amygdala. Functional connectivity difference between the three groups was examined by ANOVA. Post hoc tests were used to examine the difference of connectivity strength between every two groups.Results (1) As compared with the HCs, brain regions with increased activation by processing neutral words in GAD and PD were left amygdala, right insula, right inferior parietal lobule and left thalamus. Brain region with increased activation by processing neutral words in PD were left brainstem when comparing to GAD and HCs.As compared with the HCs, brain regions with increased activation by processing anxious words in GAD and PD were left thalamus and right insular.The activity-decreased brain area by processing anxious words in GAD group was superior frontal gyrus (BA9) as compared with PD and HCs. As compared with the HCs, the activity-decreased brain area by processing anxious words versus neutral words in GAD and PD was left amygdala. The activity-decreased brain area by processing anxious words versus neutral words in PD was right hippocampus when comparing to GAD and HCs.(2)As compared with HCs, GAD and PD showed increased functional connectivity(FC) between the left amygdala and right precuneus, GAD and PD showed decreased FC between the left amygdala and right hippocampus. Relative to patients with GAD and HCs, PD showed increased FC between the left amygdala and left brainstem, PD showed decreased FC between the left amygdala and right hippocampus.We found increased FC between the right amygdala and right brainstem, and decreased FC between the right amygdala and right hippocampus in PD and GAD when comparing to HCs, especially in PD. Interestingly, the FC between the right amygdala and left insular was increased in GAD as compared with PD and HCs.Conclusions1. The amygdale-centered fear circuitry in the brain regions of both GAD and PD patients are sensitive and easily activated which may be attributed to dysfunction of the thalamus in gating sensory information.2. The activation of fear circuitry in GAD patients may be due to "top-down" cognitive modulation deficits. 3. The activation of fear circuitry in PD patients may be due to dysregulation of the brainstem and hippocampus, resulting in "top-down" emotional modulation deficits.4. The salience network, frontoparietal network, and default mode network are involved in the modulation of fear circuitry in anxiety disorders.