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Interplay of hippocampal volume and hypothalamus-pituitary-adrenal axis function as markers of stress vulnerability in men at ultra-high risk for psychosis

Published online by Cambridge University Press:  24 October 2016

M. Pruessner ,
L. Bechard-Evans ,
S. Pira ,
R. Joober ,
D. L. Collins ,
J. C. Pruessner  and
A. K. Malla
M. Pruessner*
Affiliation:
Department of Psychiatry, Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, McGill University, Montréal, Québec, Canada
L. Bechard-Evans
Affiliation:
Department of Psychiatry, Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, McGill University, Montréal, Québec, Canada
S. Pira
Affiliation:
Department of Psychiatry, Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, McGill University, Montréal, Québec, Canada
R. Joober
Affiliation:
Department of Psychiatry, Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, McGill University, Montréal, Québec, Canada
D. L. Collins
Affiliation:
Departments of Neurology & Neurosurgery, and Biomedical Engineering, Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montréal, Québec, Canada
J. C. Pruessner
Affiliation:
Departments of Psychiatry, and Psychology, McGill Centre for Studies in Aging, Douglas Mental Health University Institute, McGill University, Montréal, Québec, Canada
A. K. Malla
Affiliation:
Department of Psychiatry, Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, McGill University, Montréal, Québec, Canada
*
*Address for correspondence: M. Pruessner, PhD, Department of Psychiatry, Prevention and Early Intervention Program for Psychoses, Douglas Mental Health University Institute, Wilson Pavilion, 6875 Boulevard La Salle, Montréal, Québec, CanadaH4H 1R3. (Email: marita.pruessner@mcgill.ca)
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Abstract

Background

Altered hypothalamus-pituitary-adrenal (HPA) axis function and reduced hippocampal volume (HV) are established correlates of stress vulnerability. We have previously shown an attenuated cortisol awakening response (CAR) and associations with HV specifically in male first-episode psychosis patients. Findings in individuals at ultra-high risk (UHR) for psychosis regarding these neurobiological markers are inconsistent, and assessment of their interplay, accounting for sex differences, could explain incongruent results.

Method

Study participants were 42 antipsychotic-naive UHR subjects (24 men) and 46 healthy community controls (23 men). Saliva samples for the assessment of CAR were collected at 0, 30 and 60 min after awakening. HV was determined from high-resolution structural magnetic resonance imaging scans using a semi-automatic segmentation protocol.

Results

Cortisol measures and HV were not significantly different between UHR subjects and controls in total, but repeated-measures multivariate regression analyses revealed reduced cortisol levels 60 min after awakening and smaller left HV in male UHR individuals. In UHR participants only, smaller left and right HV was significantly correlated with a smaller total CAR (ρ = 0.42, p = 0.036 and ρ = 0.44, p = 0.029, respectively), corresponding to 18% and 19% of shared variance (medium effect size).

Conclusions

Our findings suggest that HV reduction in individuals at UHR for psychosis is specific to men and linked to reduced post-awakening cortisol concentrations. Abnormalities in the neuroendocrine circuitry modulating stress vulnerability specifically in male UHR subjects might explain increased psychosis risk and disadvantageous illness outcomes in men compared to women.

Keywords

Cortisolhippocampushypothalamus-pituitary-adrenal axissex differencesstressultra-high risk for psychosis
Type
Original Articles
Information
Psychological Medicine , Volume 47 , Issue 3 , February 2017 , pp. 471 - 483
Copyright
Copyright © Cambridge University Press 2016 

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