THE FUNCTIONAL CONNECTIVITY CHANGES OF THE RIGHT AMYGDALA ASSOCIATED WITH ANXIETY IN SCHIZOPHRENIA AND THE PRODROMAL PHASE
Authors: Tseng *Tzuhan , Ma Wei-Fen , Lane Hsien-Yuan , Tu Cheng-Hao 
Published: February 2025

Abstract

Background
Clinically, schizophrenia has a strong association with imbalances in emotional control. Previous study indicated that the emotional deficits in schizophrenia stems from disturbances in the amygdala networks, which may serve as a pivotal etiological factor in schizophrenia.1 Furthermore, it has been observed that different levels of anxiety were correlated with distinct patterns of functional connectivity (FC) strength between the amygdala and the dorsomedial prefrontal cortex2. Thus, we hypothesized that patients with schizophrenia(S) and prodromal(P) participants may have abnormal resting-state FC in the right amygdala networks when compared with healthy controls (HC), and this dysfunctional connectivity may be associated with different levels of anxiety.

Aim & Objectives
The study aims to explore aberrant resting-state FC in the right amygdala networks of schizophrenia patients and prodromal participants with different anxiety levels.

Method
86 participants (26 schizophrenia patients, 25 prodromal subjects, and 35 HCs) were included in this study. The anxiety levels of the participants were assessed by The STAI Scale in Chinese Mandarin. Participants with trait scores exceeding 60 was considered as high anxiety level. Each participant underwent a whole-brain anatomical scan and 200 continuous whole-brain resting-state fMRI scans. The images were preprocessed using DPARSF. The seed region of right amygdala was placed at MNI coordinates x=22, y=-6, and z=-18 as a 3mm radius spheres. The average time-activity series were extracted from the seed region, and FC maps (r-to-z value converted) of seed region were generated. The statistical analyses for standardized FC maps were conducted using SPM12. The flexible factorial design was utilized with group and anxiety factor as between-subject factors. The changes were deemed as significant if the family-wise error rate corrected cluster p &lt;0.05 (the cluster forming threshold is in uncorrected voxel p &lt;0.005).

Results
For the group effect, a significant increased FC between the amygdala and the middle frontal gyrus (MFG) has been found in the S group compared to HC, whereas the P group revealed FC values between them. For the anxiety effect, a significantly increased FC has been found in ventrolateral prefrontal cortex (vlPFC) between subjects with high and low anxiety, in both P and HC groups. The high anxiety subjects in P and HC groups revealed positive FC in vlPFC, while low anxiety subjects revealed negative FC in vlPFC. Moreover, high anxiety subjects exhibited a positive FC between amygdala and precuneus in the S group, whereas negative FC in precuneus were observed in both P and HC groups. Notably, the P group revealed FC value between S and HC groups.

Discussion & Conclusion
We found altered FCs in MFG and precuneus in both S and P groups, which may be associated with the progress from normal to illness onset. Moreover, altered FC has been also found in the vlPFC between different anxiety levels in P and HC groups. Considering the precuneus and vlPFC were involved in emotional control, the FC changes between the right amygdala and these emotion-modulating regions highlight the intricate relationship between anxiety and pathophysiological changes in schizophrenia and prodrome. Future researches are needed to include longitudinal studies to track FC changes in amygdala of high anxiety individuals transitioning from the prodrome to diagnosed schizophrenia.

References
1.Friston, K. J. (1998). 'The disconnection hypothesis.' Schizophrenia Research, 30(2), pp.115–125. Available at: https://doi-org.autorpa.cmu.edu.tw:8443/10.1016/s0920-9964(97)00140-0
2.Kim, M. J., Gee, D. G., Loucks, R. A., Davis, F. C., &Whalen, P. J. (2011). 'Anxiety dissociates dorsal and ventral medial prefrontal cortex functional connectivity with the amygdala at rest.' Cerebral Cortex, 21(7), pp. 1667-1673. Available at: https://doi.org/10.1093/cercor/bhq237