Effects of antipsychotics on cortisol, interleukin-6 and hippocampal perfusion in healthy volunteers

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Title: Effects of antipsychotics on cortisol, interleukin-6 and hippocampal perfusion in healthy volunteers
Author(s): Handley, R
Mondelli, V
Zelaya, F
Marques, T
Taylor, H
Reinders, AATS
Chaddock, C
McQueen, G
Hubbard, K
Papadopoulos, A
Williams, S
McGuire, P
Pariante, C
Dazzan, P
Item Type: Journal Article
Abstract: This randomized within-subject, double blind study aimed to compare the effects of a single dose of two different antipsychotics (haloperidol and aripiprazole) on cortisol, interleukin (IL)-6 and hippocampal regional Cerebral Blood Flow (rCBF) in the same 17 healthy male individuals. Subjects received a single dose of haloperidol (3 mg), aripiprazole (10 mg) and placebo, in a randomized order on three study appointments.We measured salivary cortisol levels at multiple time points, IL-6 levels from plasma samples, and resting cerebral blood flow (rCBF), using a pulsed continuous arterial spin labeling (pCASL) sequence (1.5T). We found significantly lower cortisol levels in the haloperidol condition (F(2,32) = 5.78, p = 0.007), than in either placebo (p = 0.013; CI = 0.45, 0.406) or aripiprazole (p = 0.037; CI = −0.520, −0.014). Interleukin-6 levels were also lower following haloperidol (F(2,22) = 4.19, p = 0.048) in comparison with placebo (p = 0.02; CI = 0.14, 1.8), but not with aripiprazole. Finally, we found a greater rCBF in the right (peak voxel: T = 6.47, p b 0.0001) and left (peak voxel T = 5.17, p b 0.01) hippocampus following haloperidol compared with placebo, and at trend level also in the left hippocampus following aripiprazole compared with placebo (T = 4.07, p = 0.057). These differences in hippocampal rCBF after both antipsychotics were no longer evident (haloperidol) or present at trend level (aripiprazole), after controlling for cortisol and IL-6 levels. Our findings suggest that haloperidol can directly regulate the hypothalamic-pituitary-adrenal (HPA) axis and immune system through a pharmacological action via D2 receptor antagonism. Finally, our data suggest that the increased hippocampal rCBF is a manifestation of the reduction in IL-6 and cortisol which follows the administration of haloperidol.
Publication Date: 22-Apr-2016
Date of Acceptance: 31-Mar-2016
URI: http://hdl.handle.net/10044/1/54565
DOI: https://dx.doi.org/10.1016/j.schres.2016.03.039
ISSN: 0920-9964
Publisher: Elsevier
Start Page: 99
End Page: 105
Journal / Book Title: Schizophrenia Research
Volume: 174
Issue: 1-3
Copyright Statement: © 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Keywords: Science & Technology
Life Sciences & Biomedicine
Psychiatry
Cortisol
Inflammation
Antipsychotic
Cerebral blood flow
Hippocampus
Dopamine
CEREBRAL-BLOOD-FLOW
1ST EPISODE PSYCHOSIS
STRIATAL DOPAMINE RELEASE
ATYPICAL ANTIPSYCHOTICS
1ST-EPISODE PSYCHOSIS
RAT HIPPOCAMPUS
GREY-MATTER
SCHIZOPHRENIA
STRESS
ASSOCIATION
Antipsychotic
Cerebral blood flow
Cortisol
Dopamine
Hippocampus
Inflammation
Science & Technology
Life Sciences & Biomedicine
Psychiatry
Cortisol
Inflammation
Antipsychotic
Cerebral blood flow
Hippocampus
Dopamine
CEREBRAL-BLOOD-FLOW
1ST EPISODE PSYCHOSIS
STRIATAL DOPAMINE RELEASE
ATYPICAL ANTIPSYCHOTICS
1ST-EPISODE PSYCHOSIS
RAT HIPPOCAMPUS
GREY-MATTER
SCHIZOPHRENIA
STRESS
ASSOCIATION
11 Medical And Health Sciences
17 Psychology And Cognitive Sciences
Psychiatry
Publication Status: Published
Appears in Collections:Clinical Sciences
Imaging Sciences
Faculty of Medicine



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