Relations of Lifetime Perceived Stress and Basal Cortisol With Hippocampal Volume Among Healthy Adolescents and Those at Clinical High Risk for Psychosis: A Structural Equation Modeling Approach

Katrina Aberizk; Jean M Addington; Carrie E Bearden; Kristin S Cadenhead; Tyrone D Cannon; Barbara A Cornblatt; Matcheri Keshavan; Daniel H Mathalon; Diana O Perkins; William S Stone; Ming T Tsuang; Scott W Woods; Elaine F Walker; Benson S Ku

doi:10.1016/j.biopsych.2023.11.027

Relations of Lifetime Perceived Stress and Basal Cortisol With Hippocampal Volume Among Healthy Adolescents and Those at Clinical High Risk for Psychosis: A Structural Equation Modeling Approach

Biol Psychiatry. 2023 Dec 12:S0006-3223(23)01759-6. doi: 10.1016/j.biopsych.2023.11.027. Online ahead of print.

Authors

Affiliations

¹ Department of Psychology, Emory University, Atlanta, Georgia. Electronic address: kaberiz@emory.edu.
² Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada.
³ Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, University of California, Los Angeles, California.
⁴ Department of Psychiatry, University of California, San Diego, California.
⁵ Departments of Psychology and Psychiatry, Yale University, New Haven, Connecticut.
⁶ Department of Psychiatry, Zucker Hillside Hospital, New York, New York.
⁷ Department of Psychiatry, Harvard Medical School, Harvard University, Cambridge, Massachusetts.
⁸ Department of Psychiatry, University of California, San Francisco, California.
⁹ Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
¹⁰ Department of Psychology, Emory University, Atlanta, Georgia.
¹¹ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.

PMID: 38092185
DOI: 10.1016/j.biopsych.2023.11.027

Abstract

Background: Hippocampal volume (HV) is sensitive to environmental influences. Under normative conditions in humans, HV increases linearly into childhood and asymptotes in early adulthood. Studies of humans and nonhuman animals have provided evidence of inverse relationships between several measures of stress and HV.

Methods: Using structural equation modeling, this study aimed to characterize the relationships of age, basal cortisol, biological sex, and lifetime perceived stress with bilateral HV in a sample of healthy adolescents and adolescents at clinical high risk for psychosis (CHR-P) (N = 571, 43% female; age range = 12-19.9 years). This sample included 469 individuals at CHR-P and 102 healthy comparison participants from the combined baseline cohorts of the second and third NAPLS (North American Prodrome Longitudinal Study).

Results: A structural model that constrained the individual effects of basal cortisol and perceived stress to single path coefficients, and freely estimated the effects of age and biological sex in group models, optimized model fit and parsimony relative to other candidate models. Significant inverse relationships between basal cortisol and bilateral HV were observed in adolescents at CHR-P and healthy comparison participants. Significant sex differences in bilateral HV were also observed, with females demonstrating smaller HV than males in both groups.

Conclusions: Multigroup structural equation modeling revealed heterogeneity in the relationships of age and biological sex with basal cortisol, lifetime perceived stress, and bilateral HV in individuals at CHR-P and healthy comparison participants. Moreover, the findings support previous literature indicating that elevated basal cortisol is a nonspecific risk factor for reduced HV.

Keywords: Adolescence; Hippocampus; Imaging; Prodrome; Risk; Structure.