Volume of the Dentate Gyrus/CA4 Hippocampal subfield mediates the interplay between sleep quality and depressive symptoms

Abstract Emerging evidence increasingly suggests that poor sleep quality is associated with depressive symptoms. The hippocampus plays a crucial role in the interplay between sleep disturbance and depressive symptomatology e.g., accelerated hippocampal atrophy is typically seen in both insomnia disorder and depression. Hence, it is critical to examine the pivotal role of hippocampal volumes in modulating the interplay between poor sleep quality and depressive symptoms in large-scale healthy populations. To cover this research gap, the present study investigated the association between self-reported sleep quality, depressive symptoms, and hippocampal total and subfields’ volumes. Furthermore, we assessed the mediatory role of hippocampal volumes on the link between sleep quality and depressive symptoms in a large sample (N=1603) of young adults using mediation analysis. Sleep quality was correlated with self-report depressive symptoms. Moreover, sleep quality was found to be negatively associated with the volume of three hippocampal subfields, including dentate gyrus (DG), cornu ammonis fields (CA-3 and CA-4), but not correlated with total hippocampal volume. Interestingly, the volume of hippocampal DG and CA4 mediated the influence of poor sleep quality on depressive symptoms. Our findings improved our current understanding of the relationship between sleep disturbance, depressive symptomatology, and hippocampal subfields in the healthy populations. Considering the crucial role of DG in hippocampal neurogenesis, our results suggest that poor sleep quality may contribute to depression through a reduction of DG volume leading to impaired neurogenesis which is crucial for the regulation of mood.