title: Elevation of the ACTH/cortisol ratio in female opioid dependent patients: A biomarker of aging and correlate of metabolic and immune activation.
abstract: BACKGROUND
  Whilst the hypothalamic-pituitary-adrenal (HPA) Axis is a major stress axis, and is necessarily perturbed in opioid dependency, and stress is a major contributor to aging mechanisms, the HPA axis has not been studied in opioid dependency in an age-dependent manner.
  
  
  OBJECTIVE
  Hypothesis - Differences in age dependent levels of HPA components.
  
  
  METHODS
  Cross-sectional comparison of general medical and opioid dependent patients (ODP, GMP). Setting - Primary Care. Patients - 51 GMC, 233 ODP. Ages 37.92+1.95 v. 37.12+0.62 years (P - N.S.) and 33.33% v. 71.67% male (p<0.0001). Intervention(s) - Measurement ACTH, cortisol and their ratio (ACR). Main Outcome Measure(s) - Pre-planned analysis ACR.
  
  
  RESULTS
  Impact of immune and metabolic markers.
  
  
  RESULTS
  ACTH/cortisol was a negative biomarker for age in female patients. Whilst the mean ACR were not different, the (log) ACTH/cortisol showed a positive relationship with age:sex:status (p=0.0396) and age:status (p=0.0437). The effect of addictive status was confined to hepatitis C (HCV) positive female ODP (p=0.0355), and the age:status interaction was also stronger in female HCV+ (p=0.0075) compared to HCV - (p=0.0667) patients. Multiple regression of ACR against age, status, ALT, CRP, and Globulins confirmed many significant interactions. ACTH/cortisol ratio interacted significantly from p=0.0008 in males and p=0.0079 in females, and in both sexes four terms included addictive status.
  
  
  CONCLUSIONS
  These data establish the ACTH/cortisol ratio as a negative biomarker of aging in females, and show that this decline is more pronounced in ODP an effect which is partly related to HCV seropositivity, immune and metabolic factors. Dementias are one of the most serious health and socioeconomic issues. Multi-infarct dementia (MID) and Alzheimer´s type dementia (AD) exhibit differences in cerebrovascular blood flow velocity profiles and in presence of microemboli, detected by transcranial Doppler sonography.
authors.affiliation: School of Psychiatry and Clinical Neurosciences, University of Western Australia, Australia.
authors.forename: Albert Stuart
authors.initials: AS
authors.lastname: Reece
authors.affiliation: School of Psychiatry and Clinical Neurosciences, University of Western Australia, Australia.
authors.forename: Gary Kenneth
authors.initials: GK
authors.lastname: Hulse
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D000375:Aging / Q000378:metabolism*; D000410:Alanine Transaminase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology / Q000378:metabolism; D008297:Male; D009293:Opioid-Related Disorders / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000276:immunology / Q000378:metabolism; D012737:Sex Factors
chemical_list: D015415:Biomarkers; D000324:Adrenocorticotropic Hormone; D002097:C-Reactive Protein; D000410:Alanine Transaminase; D006854:Hydrocortisone