Alterations of intrinsic brain activity in subthreshold depression after internet-based cognitive behavioral therapy intervention

Background Subthreshold depression (SD) is a prevalent mental health condition that is recognized as a key precursor to major depressive disorder (MDD) and has a significant negative impact on individuals' quality of life. Internet-based cognitive behavioral therapy (ICBT) is considered an efficacious psychological intervention that enhances access to psychotherapeutic services. Nevertheless, the neuromechanism underlying the effectiveness of ICBT in SD has not been explored until now. This study seeks to investigate the intrinsic alterations in brain activity in SD before and after ICBT intervention using resting-state functional MRI (rs-fMRI) analysis. Methods Twenty-five individuals with SD and 25 age- and gender-matched healthy controls (HC) were enrolled in the study. SD received ICBT intervention and underwent MRI scans within 48 hours before and after the intervention, along with clinical assessment scales. HC underwent a single MRI scan at the time of enrollment. Analyses of amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) were conducted to assess intrinsic brain activity in all participants. Two-sample t-tests were performed to compare whole-brain differences of ALFF and DC between HC and SD before ICBT intervention, and paired-sample t-tests were employed to examine changes in whole-brain ALFF and DC in SD before and after ICBT intervention. The associations among altered ALFF and DC values and the changes in clinical assessment scores in SD were evaluated by Pearson or Spearman correlation analyses. Results Compared to HC, decreased DC in the right precuneus (PCUN) and increased ALFF in the right insula (INS) were found in SD before ICBT intervention. After ICBT intervention, ALFF in the left hippocampus (HIP) was increased, and DC in the right medial and paracingulate gyri (DCG) was reduced in SD. Altered ALFF values in the left HIP showed a negative correlation with the changes in Patient Health Questionnaire-9 Items (PHQ-9) scores, and a positive correlation with the changes in Frequency of Actions and Thoughts Scale in terms of rewarding behaviours (FATS-ReB) scores. Altered DC values in the right DCG positively correlated with the changes in Competencies of Cognitive Therapy Scale-Therapist Report in terms of behavioral activation (CCTS-TR-BhA) scores. Conclusions The findings provide new insights into the altered intrinsic brain activities in SD. More importantly, this study demonstrates the potential intrinsic activity changes in brain regions associated with ICBT response to SD, further elucidating the neuropsychological mechanism underlying the efficacy of ICBT. Trial registration: This protocol was retrospectively registered at Chinese Clinical Trial Register (ChiCTR) on February 22, 2022, with Identifier: ChiCTR2200056884 (https://www.chictr.org.cn/showproj.html?proj=154448).