title: Interplay of hippocampal volume and hypothalamus-pituitary-adrenal axis function as markers of stress vulnerability in men at ultra-high risk for psychosis.
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.
  
  
  METHODS
  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.
authors: Department of Psychiatry,Prevention and Early Intervention Program for Psychosis, DouglasMental Health University Institute,McGill University,Montréal,Québec,Canada.
authors: M
authors: M
authors: Pruessner
authors: Department of Psychiatry,Prevention and Early Intervention Program for Psychosis, DouglasMental Health University Institute,McGill University,Montréal,Québec,Canada.
authors: L
authors: L
authors: Bechard-Evans
authors: Department of Psychiatry,Prevention and Early Intervention Program for Psychosis, DouglasMental Health University Institute,McGill University,Montréal,Québec,Canada.
authors: S
authors: S
authors: Pira
authors: Department of Psychiatry,Prevention and Early Intervention Program for Psychosis, DouglasMental Health University Institute,McGill University,Montréal,Québec,Canada.
authors: R
authors: R
authors: Joober
authors: Departments of Neurology & Neurosurgery, and Biomedical Engineering,Brain Imaging Centre,Montreal Neurological Institute,McGill University,Montréal,Québec,Canada.
authors: D L
authors: DL
authors: Collins
authors: Departments of Psychiatry, and Psychology,McGill Centre for Studies in Aging,Douglas Mental Health University Institute,McGill University,Montréal,Québec,Canada.
authors: J C
authors: JC
authors: Pruessner
authors: Department of Psychiatry,Prevention and Early Intervention Program for Psychosis, DouglasMental Health University Institute,McGill University,Montréal,Québec,Canada.
authors: A K
authors: AK
authors: Malla
mesh_terms: D000328:Adult; D015415:Biomarkers; D004198:Disease Susceptibility; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D011618:Psychotic Disorders / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D012306:Risk; D013315:Stress, Psychological / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D006854:Hydrocortisone
keywords: Cortisol; hippocampus; hypothalamus-pituitary-adrenal axis; sex differences; stress; ultra-high risk for psychosis