title: Reduced hippocampal volume and hypothalamus-pituitary-adrenal axis function in first episode psychosis: evidence for sex differences.
abstract: BACKGROUND
  Hippocampal volume (HV) decline is an important marker of psychosis and has been associated with hypothalamus-pituitary-adrenal (HPA) axis dysregulation in various disorders. Given recent findings of sex differences in HPA axis function in psychosis, the current study investigated differences in HV in male and female first episode psychosis (FEP) patients and controls and the interaction of HV with the cortisol awakening response (CAR) and symptoms.
  
  
  METHODS
  Fifty-eight patients with a diagnosis of FEP (39 men, 19 women) and 27 healthy community controls (15 men, 12 women) underwent structural magnetic resonance imaging (MRI) on a 1.5 T scanner. Hippocampal volume was determined using previously established segmentation protocols. Saliva samples for cortisol assessment were collected at 0, 30 and 60 min after awakening. Psychotic symptoms were assessed with the Scale for Assessment of Positive Symptoms (SAPS), the Scale for Assessment of Negative Symptoms (SANS) and the Global Assessment of Functioning (GAF) scale.
  
  
  RESULTS
  Male patients had significantly smaller left and right HVs compared to male controls, which appeared to be secondary to global brain volume differences. However, even when controlling for overall brain size, male patients showed smaller HV compared to female patients. The CAR was significantly lower in male patients compared to male controls and female patients. Only in male patients, smaller left HV was significantly associated with a blunted CAR, and smaller HV bilaterally was related to positive psychotic symptoms and lower levels of functioning.
  
  
  CONCLUSIONS
  We propose that reduced hippocampal volume and an attenuated cortisol awakening response are related markers of increased stress vulnerability in male psychosis patients and that both contribute to the unfavorable clinical picture in men.
authors.affiliation: Department of Psychiatry, Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Marita
authors.initials: M
authors.lastname: Pruessner
authors.affiliation: Department of Psychiatry, Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Lepage
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: D Louis
authors.initials: DL
authors.lastname: Collins
authors.affiliation: Department of Psychiatry, McGill Centre for Studies in Aging, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Pruessner
authors.affiliation: Department of Psychiatry, Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Ridha
authors.initials: R
authors.lastname: Joober
authors.affiliation: Department of Psychiatry, Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Malla
mesh_terms: D000328:Adult; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011618:Psychotic Disorders / Q000473:pathology* / Q000503:physiopathology*; D012463:Saliva / Q000737:chemistry; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D006854:Hydrocortisone
keywords: Cortisol awakening response; First episode psychosis; Hippocampus; Hypothalamus–pituitary–adrenal axis; Sex differences