Abstract

Background: The presence of subthreshold depression significantly increases the likelihood of developing major depressive disorder and is linked to a higher burden of illness and suicide risk. Although the neural mechanism of bright light therapy (BLT) remains unclear, it is considered as an effective intervention for subthreshold depression. The amygdala has been shown to play a critical role in depression. And light has been associated with the serotoninergic system. The objective of this clinical trial was to evaluate the relationship between BLT and the functional connectivity (FC) alterations of the amygdala, as well as the serotoninergic distribution in subthreshold depression. Methods: Subthreshold depression subjects were randomly divided into two groups: the BLT group (N = 47) and the placebo group (N = 42). The Hamilton Depression Rating Scale (HDRS) was the main measure of outcome, while the Centre for Epidemiologic Studies Depression Scale (CESD) and Beck Depression Inventory (BDI) served as secondary measures, which were evaluated before and after 8 weeks. The participants also underwent resting-state functional magnetic resonance imaging before and after 8 weeks. Seed-based whole-brain static FC (sFC) and dynamic FC (dFC) analyses of the bilateral amygdala and their subfields were conducted. Besides, a multivariate regression model was utilized to predict HDRS, CESD and BDI scores alterations after BLT. In addition, the JuSpace toolbox was employed to compute the correlations between sFC/dFC of the amygdala subfields and the serotoninergic system activity both in the BLT and the placebo group. Results: BLT group showed decreased CESD score and HDRS score from pre-treatment to post-treatment compared to the placebo group. Also, compared to baseline, BLT group showed increased sFC of right basolateral amygdala (BLA)/superficial amygdala (SFA)-right middle temporal gyrus (MTG) and dFC of right centralmedial amygdala (CMA) and right inferior orbital frontal gyrus, and decreased sFC of right amygdalostriatal transition (AStr)/CMA- left thalamus and dFC of right SFA- right medial prefrontal cortex after intervention. Changes in sFC of the right BLA-right MTG showed positive correlation with changes in BDI score before and after BLT. Moreover, combining the baseline sFC and dFC of the amygdala could predict HDRS, CESD and BDI changes after BLT intervention. Additionally, compared to baseline, sFC of the right BLA alterations after BLT were significantly associated with spatial distribution of 5HT1a and 5-HT2a receptors, while dFC of the right CMA alterations after BLT were significantly associated with spatial distribution of 5HT1a receptor. Conclusions: These findings indicated that BLT could relieve depressive symptoms and alter FC of the amygdala in subthreshold depression. Combining baseline sFC and dFC of the amygdala may have the potential to assess the effectiveness of BLT in treating subthreshold depression. Moreover, FC changes of the amygdala with the serotoninergic system after BLT may underline the antidepressant mechanisms of BLT.

Acknowledgements

The study was supported by grants from the National Natural Science Foundation of China (81671670, 81971597, and 82172530); National Key Research and Development Project (2020YFC2005700); Key-Area Research and Development Program of Guangdong Province (2020B1111100001). The funding organizations play no further role in study design, data collection, analysis and interpretation and paper writing.

References

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