Distinct therapeutics of depression work on a common brain network
Poster No:
658
Submission Type:
Abstract Submission
Authors:
Wenqiang Xu1, Gong-Jun Ji2, Kai Wang2, Yinian Yang2
Institutions:
1Anhui Medical University, Hefei, Anhui, 2Anhui Medical University, Hefei, Anhui Province
First Author:
Co-Author(s):
Introduction:
Understanding the neural mechanisms underlying depression remission is crucial for developing effective treatments. Here we tested whether brain regions longitudinally changed with antidepressive therapies were neuroanatomically heterogeneous but are part of a specific depression remission network.
Methods:
We systematically searched the longitudinal studies of antidepressive therapies to identify brain regions of treatment-induced GMV increases in depression patients. Utilizing the study-derived coordinates, a novel remission network mapping (RNM) approach, incorporating sensitivity, specificity and conjunction analyses, was employed to delineate the depression remission network (DRN). This approach was conducted using the normative connectome data of 652 Asian participants (validated in a data of 1000 Western participants). Multiple datasets were used to validate this DRN, and show its clinical implication.
Group- and individual-level validation datasets. We systematically searched longitudinal studies reporting cortical thickness (CT) increases after treatment. The reported coordinates were collected as group-level validation data. Individual-level validation was performed on two independent longitudinal datasets of depression patients treated by ECT (including USTC and AHMU cohorts) and one control group (patients with Parkinson's disease treated with rTMS).
To further validate our DRN in the context of clinical therapies, we tested whether the DRN is spatially overlapped with common targets of deep brain stimulation (DBS) (11 sites in Burke, M.J., et al., 2022, Molecular Psychiatry) and target atlas of repetitive transcranial magnetic stimulation (rTMS) (Siddiqi, S.H., et al., 2020, The American Journal of Psychiatry) for depression. The statistical significance of was tested by permutation tests.
Finally, the DRN was used to explain the outcome variability of rTMS treatment for depression patients (n=24). Specifically, the DRN was binarized to identify positive regions as a seedmap. We test whether the average changes of functional connectivity strength within seedmap mask were correlated to the Hamilton Depression Scale-17 (HAMD-17) improvement rates using partial Pearson correlation, controlling for age, gender, education, HAMA, HAMD-17, and disease duration
Group- and individual-level validation datasets. We systematically searched longitudinal studies reporting cortical thickness (CT) increases after treatment. The reported coordinates were collected as group-level validation data. Individual-level validation was performed on two independent longitudinal datasets of depression patients treated by ECT (including USTC and AHMU cohorts) and one control group (patients with Parkinson's disease treated with rTMS).
To further validate our DRN in the context of clinical therapies, we tested whether the DRN is spatially overlapped with common targets of deep brain stimulation (DBS) (11 sites in Burke, M.J., et al., 2022, Molecular Psychiatry) and target atlas of repetitive transcranial magnetic stimulation (rTMS) (Siddiqi, S.H., et al., 2020, The American Journal of Psychiatry) for depression. The statistical significance of was tested by permutation tests.
Finally, the DRN was used to explain the outcome variability of rTMS treatment for depression patients (n=24). Specifically, the DRN was binarized to identify positive regions as a seedmap. We test whether the average changes of functional connectivity strength within seedmap mask were correlated to the Hamilton Depression Scale-17 (HAMD-17) improvement rates using partial Pearson correlation, controlling for age, gender, education, HAMA, HAMD-17, and disease duration
Results:
Total of 17 depression experiments including 581 participants were included in this study. The included treatment modalities comprise pharmacotherapy, electroconvulsive therapy (ECT), psychotherapy, and magnetic seizure therapy.The RNM analysis identified bilateral amygdala and parahippocampal gyrus as hub regions of the DRN (Figure 1).
The group-level validation analysis indicated the DRN showing stronger functional connectivity to brain regions with CT changes in depression than non-depressed patients (P=0.0073; figure 2A). The individual-level validation analysis indicated the DRN showing stronger spatial correlation with remission networks of individual depression patient (USTC cohort P<0.0001; AHMU cohort P=0.0006; figure 2B) than controls.
The real DBS targets of depression showed greater functional connectivity to the DRN than random targets (P=0.0015, 10,000 permutation tests; figure 2C). The DRN is similar to the TMS targeting atlas previously reported (spatial similarity r=0.721, permutation test P=0.004, 10,000 permutation tests; figure 2D) uisng Neuromaps toolbox.
Finally, we demonstrated that the amelioration of depression symptom is positively associated with the functional connectivity increase within the DRN (r=0.603, P=0.008; figure 2E). No significant correlation was found for non-depression symptoms.
The group-level validation analysis indicated the DRN showing stronger functional connectivity to brain regions with CT changes in depression than non-depressed patients (P=0.0073; figure 2A). The individual-level validation analysis indicated the DRN showing stronger spatial correlation with remission networks of individual depression patient (USTC cohort P<0.0001; AHMU cohort P=0.0006; figure 2B) than controls.
The real DBS targets of depression showed greater functional connectivity to the DRN than random targets (P=0.0015, 10,000 permutation tests; figure 2C). The DRN is similar to the TMS targeting atlas previously reported (spatial similarity r=0.721, permutation test P=0.004, 10,000 permutation tests; figure 2D) uisng Neuromaps toolbox.
Finally, we demonstrated that the amelioration of depression symptom is positively associated with the functional connectivity increase within the DRN (r=0.603, P=0.008; figure 2E). No significant correlation was found for non-depression symptoms.
·Figure 1. Remission network mapping (RNM) approach
·Figure 2.Validation and clinical implication of depression remission network
Conclusions:
Distinct clinical therapies may work on a common brain network that underlying the remission of depression patients.
Brain Stimulation:
TMS
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural)
Novel Imaging Acquisition Methods:
Multi-Modal Imaging 2
Keywords:
Other - Depression/Remission network mapping /Connectivity/Neuroimaging/Neuromodulation
1|2Indicates the priority used for review
Provide references using author date format
Siddiqi, S.H. (2020), 'Distinct Symptom-Specific Treatment Targets for Circuit-Based Neuromodulation', The American Journal of Psychiatry