Abstract
IMPORTANCE: Few studies have used a large-sample, longitudinal, population-based cohort study to examine whether the COVID-19 pandemic as a global major life event is associated with structural plasticity of the adolescent hippocampus. OBJECTIVE: To examine whether Japan's first state of emergency (SoE) during the COVID-19 pandemic was associated with alterations in the macrostructures and microstructures of the hippocampus during its development. DESIGN, SETTING, AND PARTICIPANTS: The population-neuroscience Tokyo TEEN Cohort study is a prospective cohort study with 4 consecutive waves in Tokyo, Japan. Due to the SoE, data collection was suspended between March 27, 2020, and July 30, 2020. Analyzed data, comprising 1149 brain structural scans obtained from 479 participants, of whom 336 participants had undergone 2 or more scans, were collected between October 2013 and November 2021. Data were analyzed from August 2022 to December 2023. EXPOSURES: Japan's first SoE (April 7 to May 25, 2020). MAIN OUTCOMES AND MEASURES: Hippocampal volume, 12 hippocampal subfield volumes, and 7 microstructural measures of the hippocampus. RESULTS: A total of 1060 brain scans from 459 participants (214 female participants [47%]) including 246 participants from wave 1 (median [IQR] age, 11.3 [11.1-11.7] years), 358 from wave 2 (median [IQR] age, 13.8 [13.3-14.5] years), 304 from wave 3 (median [IQR] age, 15.9 [15.4-16.5] years), and 152 from wave 4 (median [IQR] age, 17.9 [17.5-18.4] years) were included in the final main analysis. The generalized additive mixed model showed a significant associations of the SoE with the mean hippocampal volume (β = 102.19; 95% CI, 0.61-203.77; P = .049). The generalized linear mixed models showed the main associations of the SoE with hippocampal subfield volume (granule cell and molecular layer of the dentate gyrus: β = 18.19; 95% CI, 2.97-33.41; uncorrected P = .02; CA4: β = 12.75; 95% CI, 0.38-25.12; uncorrected P = .04; hippocampus-amygdala transition area: β = 5.67; 95% CI, 1.18-10.17; uncorrected P = .01), and fractional anisotropy (β = 0.03; 95% CI, 0.00-0.06; uncorrected P = .04). CONCLUSIONS AND RELEVANCE: After the first SoE, a volumetric increase in the hippocampus and trend increase in 3 subfield volumes and microstructural integration of the hippocampus were observed, suggesting that the transient plasticity of the adolescent hippocampus was affected by a major life event along with the typical developmental trajectory.