Revealing complexity: Segmentation of hippocampal subfields in adolescents with major depressive disorder reveals specific links to cognitive dysfunctions

Abstract

BackgroundHippocampal disruptions represent potential neuropathological biomarkers in depressed adolescents with cognitive dysfunctions. Given heterogeneous outcomes of whole-hippocampus analyses, we investigated subregional abnormalities in depressed adolescents, and their associations with symptom severity and cognitive dysfunctions. MethodsSeventy-nine first-episode depressive patients (age = 15.54±1.83) and seventy-one healthy controls (age = 16.18±2.85) were included. All participants underwent T1 and T2 weighted imaging, completed depressive severity assessments and performed cognitive assessments on memory, emotional recognition, cognitive control, and attention abilities. Freesurfer v6.0 was used to segment each hippocampus into 12 subfields. Multivariable analyses of variance were performed to identify overall and disease severity related abnormalities in patients. LASSO regression was also conducted to explore the associations between hippocampal subfields and cognitive abilities in patients. ResultsDepressed adolescents showed decreases in the dentate gyrus, CA1, CA2/3, CA4, fimbria, tail, and molecular layer. Analyses of overall symptom severity, duration, selfharm behaviour and suicidality suggested that severity-related decreases mainly manifested in CA regions and involved surrounding subfields with disease severity increases. LASSO regression indicated that hippocampal subfields abnormalities had strongest associations with memory impairments, with CA regions and dentate gyrus showing highest weights. ConclusionsHippocampal abnormalities are widespread in depressed adolescents and such abnormalities may spread from CA regions to surrounding areas with the disease progresses. Abnormalities in CA regions and dentate gyrus among these subfields primarily link with memory impairments in patients. These results demonstrate that hippocampal subsections may serve as useful biomarkers of depression progression in adolescents, offering new directions for early clinical intervention.