title: Antipsychotic use is associated with a blunted cortisol stress response: a study in euthymic bipolar disorder patients and their unaffected siblings.
abstract: There is ample evidence that the acute stress response is altered in schizophrenia and bipolar disorder. However, it is not clear whether such changes are related to the illness, a genetic vulnerability, or is the result of medication that is used in the majority of these patients. Therefore, we investigated determinants of the acute endocrine and autonomic stress response in healthy controls (n=48), euthymic BD1 patients (n=49) and unaffected siblings of BD1 patients (n=27). All participants completed a validated psychosocial stress task, the Trier Social Stress Test for Groups (TSST-G). Saliva levels of alpha-amylase and cortisol were measured before, during, and after exposure to stress. Compared to controls, we found a significantly blunted cortisol stress response in BD1 patients. Conversely, BD1 patients displayed exaggerated alpha-amylase levels in response to stress. Antipsychotic use was a significant contributing factor to the blunted cortisol stress response in BD1 patients. Unaffected BD1 siblings displayed similar stress-induced cortisol and alpha-amylase levels as controls, suggesting that familial risk for BD1 did not have a large effect on the functionality of the stress system. In conclusion, this study shows that euthymic BD1 patients have a substantially blunted endocrine stress response but an exaggerated autonomic stress response and that the endocrine stress response differences can be largely contributed to antipsychotic use rather than constitute a specific BD1 phenotype or vulnerability.
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands. Electronic address: L.Houtepen@umcutrecht.nl.
authors.forename: L C
authors.initials: LC
authors.lastname: Houtepen
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: M P M
authors.initials: MP
authors.lastname: Boks
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: R S
authors.initials: RS
authors.lastname: Kahn
authors.affiliation: Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Joëls
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: C H
authors.initials: CH
authors.lastname: Vinkers
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012463:Saliva / Q000187:drug effects / Q000378:metabolism; D035781:Siblings / Q000523:psychology*; D013315:Stress, Psychological / Q000150:complications*; D011795:Surveys and Questionnaires; D013997:Time Factors; D055815:Young Adult; D000516:alpha-Amylases / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D000516:alpha-Amylases; D006854:Hydrocortisone
keywords: Antipsychotic; Bipolar disorder; Medication; Siblings; Stress; TSST