ECT-Induced Effects on Hippocampal Structure and Function and Its Differences in Schizophrenia Remission and Non-Remission Patients

Abstract

Background: Modified electroconvulsive therapy (MECT) is considered as a treatment option in drug-resistant schizophrenia (SZ). But approximately one-third of patients do not benefit from MECT in clinic. Thus it is high significance to investigate differences between MECT responders and non-responders. Accumulated evidence indicated that one of MECT action regions is the hippocampus, which also plays an important role in SZ pathophysiology. To date, no studies have investigated the differences of MECT effects to hippocampus between treatment responders and non-responders. Methods: This study recruited twenty-one SZ patients treated by four-weeks MECT (MSZ, n=21) and twenty-one SZ patients who received pharmaceutical therapy (DSZ, n=21). The MSZ was further classified to responders (MSR, n=10) or non-responders (MNR, n=11) according to treatment outcomes by the criterion of 50% PANSS total reductive ratio. Using structural and resting-state functional MRI, we measured the hippocampal volume and functional connectivity (FC) in all SZ patients (before and after treatment) and 23 healthy controls. Results: Contrast to pharmaceutical therapy, MECT induced bilateral hippocampal volume increases in MSZ. Both of MSR and MNR exhibited a hippocampus expansion after MECT, whereas a lesser baseline volume at one of hippomcapal subfield (hippocampus-amygdala transition area) was found in MNR. After MECT, increased FC between the hippocampus and brain networks associated with cognitive functions was only observed in MSR. Conclusions: MECT action mechanism in schizophrenia is complex. A combination of baseline impairment level, MECT-introduced morphological changes and post-ECT FC increases at the hippocampus may jointly contribute to the post-ECT symptom improvements in SZ. Funding Statement: This study was funded by grants from the National Nature Science Foundation of China (grant number: 81861128001, 61761166001, 81471638, 81771822, 81571759, 81660233, 81671332), the Program for Changjiang Scholars and Innovative Research Team Project (IRT0910), the ‘111’ Project (B12027) and grants from Ministry of Science and Technology of China (2016YFC1306800) and SHSMU-ION Research Center for Brain Disorders (2015NKX001). Declaration of Interests: The authors state: There is no conflict of interest. Ethics Approval Statement: The Ethics Committee of SMHC approved the study protocol. Written informed consent was obtained from all subjects prior to study participation.