Lili Zhang,1– 3 Yunshu Zhang,2,3 Wentao Guo,2,3 Qi Ma,1,4 Feng Zhang,2,3 Keqing Li,2,3 Qizhong Yi1,4 

1The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2Hebei Provincial Mental Health Center, Baoding, Hebei Province, People’s Republic of China; 3Hebei Key Laboratory of Major Mental and Behavioural Disorders, Baoding, Hebei Province, People’s Republic of China; 4Xinjiang Clinical Research Center for Mental (Psychological) Disorder, Urumqi, People’s Republic of China

Correspondence: Qizhong Yi, The First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushan Road, Urumqi, 830054, People’s Republic of China, Tel +86 13079911689, Email qizhongyi@126.com Keqing Li, Hebei Provincial Mental Health Center, No. 572, Dongfeng East Road, Baoding City, Hebei Province, 071000, People’s Republic of China, Tel +86 13703288007, Email like2125@sina.com

Purpose: Depressive disorder is a mental health disorder with complicated etiopathogenesis. Environmental stress and neurodevelopment combined with other factors contribute to the occurrence of depression. Especially for the depressive disorder with chronic negative stress, it has characteristics of recurrence and poor curative effect because of unclear mechanism. Here, we investigated the hippocampal structures and functional connectivity (FC) according to resting-state functional magnetic resonance imaging in patients with depression who underwent chronic negative stress.
Patients and Methods: A total of 65 patients with depression (34 underwent chronic negative stress and 31 non-underwent chronic negative stress) and 30 healthy controls who did not undergo chronic negative stress were included in the study. The volumes of hippocampal subfields, seed-based FCs between hippocampus and the whole brain voxels, and ROI-wise-based FC between hippocampal subfields were compared among the three groups.
Results: In the patients with depression who underwent chronic negative stress, the volumes of right_GC-ML-DG-head, right_CA4-head and right_CA3-head increased, FCs between Temporal_Mid_R, Precuneus_R, Frontal_Sup_R, Temporal_Sup_R, Angular_L, Frontal_Inf_Tri_R, Supp_Motor_Area_R, Precentral_L and hippocampus increased, and FCs between parasubiculum and CA3, and presubiculum and CA1 decreased. When compared to the patients who did not undergo chronic negative stress, the patients who underwent chronic negative stress had larger volumes of right_GC-ML-DG-head and right_CA3-head, higher FCs between Frontal_Sup_R, Frontal_Inf_Tri_R and hippocampus, and lower FCs between presubiculum and CA1.
Conclusion: The depression underwent chronic negative stress may experience disrupted hippocampal structures and functional connectivity. It may be one of potential depressive disorder subtypes.

Keywords: depressive disorder, chronic stress, hippocampus, functional connectivity