Psychosocial health modifies associations between HPA-axis function and brain structure in older age

Isabelle F. van der Velpen, Maud de Feijter, Rutika Raina, Fatih Özel, Marieke Perry, M. Arfan Ikram, Meike W. Vernooij, Annemarie I. Luik*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Background: Dysregulation of the negative feedback loop of the hypothalamic-pituitary-adrenal (HPA) axis may have damaging effects on the brain, potentially under influence of psychosocial health factors. We studied associations between functioning of the negative feedback loop of HPA-axis, measured with a very low-dose dexamethasone suppression test (DST), and brain structure in middle-aged and older adults, and whether these associations were modified by psychosocial health. Methods: From 2006 to 2008, 1259 participants (mean age 57.6 ± 6.4, 59.6 % female) of the population-based Rotterdam Study completed a very low-dose DST (0.25 mg) and underwent magnetic resonance imaging (MRI) of the brain. Self-reported psychosocial health (depressive symptoms, loneliness, marital status, perceived social support) were assessed in the same time period. Multivariable linear and logistic regression were used to study cross-sectional associations between cortisol response and brain volumetrics, cerebral small vessel disease markers and white matter structural integrity. To assess the effect of psychosocial health on these associations, analyses were further stratified for psychosocial health markers. Results: Cortisol response was not associated with markers of global brain structure in the overall study sample. However, in participants with clinically relevant depressive symptoms, a diminished cortisol response was associated with smaller white matter volume (mean difference: − 1.00 mL, 95 %CI = − 1.89;− 0.10) and smaller white matter hyperintensity volume (mean difference: − 0.03 mL (log), 95 %CI = − 0.05;0.00). In participants with low/moderate perceived social support compared to those with high social support, a diminished cortisol response was associated with larger gray matter volume (mean difference: 0.70 mL, 95 %CI = 0.01;1.39) and higher fractional anisotropy (standardized mean difference 0.03, 95 %CI = 0.00;0.06). Conclusion: Diminished function of the HPA-axis is differently associated with brain structure in community-dwelling middle-aged and older adults with clinically relevant depressive symptoms or suboptimal social support, but not in adults without depressive symptoms or with optimal social support.

Original languageEnglish
Article number106106
Publication statusPublished - Jul 2023

Bibliographical note

The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. This work was partly supported by the JPND project Social Health And Reserve in the Dementia patient journey (SHARED) and financed through projects funded by the Netherlands Organisation for Health Research and Development (Grant nos. 733051082 and 733050831). A.I. Luik was supported by a Sleep Research Society Foundation Early Career Development Award.

Publisher Copyright: © 2023


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