Hippocampal Structures Among Japanese Adolescents Before and After the COVID-19 Pandemic

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.

Figure 1.. COVID-19 Cases and Mobility of Citizens in Tokyo From November 2019 to October 2020

The period of Japan’s first state of emergency (April 7 to May 25, 2020) is indicated by the blue shaded areas. Daily number of newly reported cases of COVID-19 is plotted for all ages (A) and individuals aged 10 to 20 years in Tokyo (C), using data from the Ministry of Health, Labour and Welfare in Japan. Daily time spent at home per month is plotted for citizens in Tokyo using Google COVID-19 Community Mobility Reports (B). The weekly number of days at school (D), weekly extracurricular activity days (E), and psychological distress (F) per month are plotted for general adolescents from pn-TTC subsamples. B, Reference month was February 2020. D to F, Reference month was November 2019. Relevant statistical methods and results are provided in eMethods 1 and eAppendix 1 in Supplement 1. ^aP < .001. ^bP < .01. ^cP < .05.

Figure 2.. Transformations of Magnetic Resonance Imaging (MRI) Scan Date

Relative to July 29, 2020, the dates of MRI scans taken from July 29, 2020, to July 29, 2021, were converted to relative values using the log (A), linear (B), and binary transformations (C) (ie, RV.log, RV.linear, and RV.binary), which are indicated by dots with color gradation from dark purple to light purple. In addition, based on our calculation method, MRI scans taken outside this year interval (both before and after) were set to 0, which are indicated by gray dots. The shaded area indicates the period of Japan's first state of emergency (April 7 to May 25, 2020).

Figure 3.. Longitudinal Sample and Developmental Trajectory of the Hippocampus During Adolescence

Ages of participants at magnetic resonance imaging (MRI) scan (A), mean hippocampal volume (B), mean granule cell and molecular layer of the dentate gyrus (GC-ML-DG) volume (C), and mean hippocampal fractional anisotropy (FA) (D). ID indicates identifier.

Figure 4.. Association of the COVID-19 State of Emergency (SoE) With Mean Hippocampal Volume Along With Adolescent Developmental Trajectory

Purple gradation indicates the magnitude of RV.log from 141 magnetic resonance imaging (MRI) scans for boys (A) and girls (C). The scans from the previous wave for the participants are shown in gray. The corresponding 146 MRI scans were scanned at the age of 16 years or older for boys (B) and girls (D).