COVID-19 lockdown effects on adolescent brain structure suggest accelerated maturation that is more pronounced in females than in males

Abstract

Adolescence is a period of substantial social-emotional development, accompanied by dramatic changes to brain structure and function. Social isolation due to lockdowns that were imposed because of the COVID-19 pandemic had a detrimental impact on adolescent mental health, with the mental health of females more affected than males. We assessed the impact of the COVID-19 pandemic lockdowns on adolescent brain structure with a focus on sex differences. We collected MRI structural data longitudinally from adolescents prior to and after the pandemic lockdowns. The pre-COVID data were used to create a normative model of cortical thickness change with age during typical adolescent development. Cortical thickness values in the post-COVID data were compared to this normative model. The analysis revealed accelerated cortical thinning in the post-COVID brain, which was more widespread throughout the brain and greater in magnitude in females than in males. When measured in terms of equivalent years of development, the mean acceleration was found to be 4.2 y in females and 1.4 y in males. Accelerated brain maturation as a result of chronic stress or adversity during development has been well documented. These findings suggest that the lifestyle disruptions associated with the COVID-19 pandemic lockdowns caused changes in brain biology and had a more severe impact on the female than the male brain.

Keywords: accelerated brain maturation; adolescent cortical thinning; normative modeling.

Fig. 1.

A comparison of the pre- and post-COVID-19 pandemic lockdown data for the right hemisphere fusiform gyrus region. (A) Bayesian linear regression was used to fit a normative model (blue and red lines) to cortical thickness data in the pre-COVID-19 train sample (each data point represents a subject) for both males (blue) and females (red). The model characterizes changes in cortical thickness as a function of age and sex during typical adolescent development. (B) The same normative model (blue and red lines from Panel A) is shown superimposed on cortical thickness data for a separate sample of pre-COVID-19 data (validation sample). (C) The normative model (blue and red lines from Panel A) is shown superimposed on cortical thickness data for the post-COVID-19 lockdown (test) sample.

Fig. 2.

Z-score distributions for example brain regions in which statistically significant deviations from the normative mean in the post-COVID-19 lockdown data were observed. Normative mean cortical thickness is indicated by a vertical dashed line. (A) Histograms for six regions where females but not males showed significant deviation. (B) Histograms for the two regions where both females and males showed significant deviation.

Fig. 3.

Regions with significantly accelerated cortical thinning in the post-COVID-19 lockdown adolescent brain. Regions with accelerated thinning in the female brain (A) and male brain (B) are shown in color. These data are superimposed on the FreeSurfer adult sample brain (gray). Regional boundaries are from the Desikan–Killiany parcellation scheme.

Fig. 4.

Effect size by brain region for males and females.

Fig. 5.

Mean age acceleration by sex with 95% CI.