Reduced Hippocampal Volume and Its Relationship With Verbal Memory and Negative Symptoms in Treatment-Naive First-Episode Adolescent-Onset Schizophrenia

Accumulating neuroimaging evidence has shown remarkable volume reductions in the hippocampi of patients with schizophrenia. However, the relationship among hippocampal morphometry, clinical symptoms, and cognitive impairments in schizophrenia is still unclear. In this study, high-resolution structural magnetic resonance imaging data were acquired in 36 patients with adolescent-onset schizophrenia (AOS, age range: 13-18 years) and 30 age-, gender-, and education-matched typically developing controls (TDCs). Hippocampal volume was assessed automatically through volumetric segmentation and measurement. After adjusting for total intracranial volume, we found reduced hippocampal volume in individuals with AOS compared with TDCs, and the hippocampal volume was positively correlated with verbal memory and negatively correlated with negative symptoms in AOS. In addition, mediation analysis revealed the indirect effect of hippocampal volume on negative symptoms via verbal memory impairment. When the negative symptoms were represented by 2 dimensions of deficits in emotional expression (EXP) and deficits in motivation and pleasure (MAP), the indirect effect was significant for EXP but not for MAP. Our findings provide further evidence of hippocampal volume reduction in AOS and highlight verbal memory impairment as a mediator to influence the relationship between hippocampal morphometry and negative symptoms, especially the EXP dimension of negative symptoms, in individuals with AOS.