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

Rowena Handley; Valeria Mondelli; Fernando Osmin Zelaya; Tiago Andre Reis Marques; Heather Taylor; Antje Annechien Talea Simone Reinders; Christopher Chaddock; Grant McQueen; Kathryn Hubbard; A Papadopoulos; Steven Charles Rees Williams; Philip McGuire; Carmine Maria Pariante; Paola Dazzan

doi:10.1016/j.schres.2016.03.039

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

Rowena Handley, Valeria Mondelli, Fernando Osmin Zelaya, Tiago Andre Reis Marques, Heather Taylor, Antje Annechien Talea Simone Reinders, Christopher Chaddock, Grant McQueen, Kathryn Hubbard, A Papadopoulos, Steven Charles Rees Williams, Philip McGuire, Carmine Maria Pariante, Paola Dazzan

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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 (3mg), aripiprazole (10mg) 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=.007), than in either placebo (p=.013; CI=0.45, 0.406) or aripiprazole (p=.037; CI= -0.520, -0.014). Interleukin-6 levels were also lower following haloperidol (F(2,22)=4.19, p=.048) in comparison with placebo (p=.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<0.0001) and left (peak voxel T=5.17, p<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.

Original language	English
Journal	Schizophrenia Research
Early online date	22 Apr 2016
DOIs	https://doi.org/10.1016/j.schres.2016.03.039
Publication status	E-pub ahead of print - 22 Apr 2016

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Handley, R., Mondelli, V., Zelaya, F. O., Reis Marques, T. A., Taylor, H., Reinders, A. A. T. S., Chaddock, C., McQueen, G., Hubbard, K., Papadopoulos, A., Williams, S. C. R., McGuire, P., Pariante, C. M., & Dazzan, P. (2016). Effects of antipsychotics on cortisol, interleukin-6 and hippocampal perfusion in healthy volunteers. Schizophrenia Research. Advance online publication. https://doi.org/10.1016/j.schres.2016.03.039

@article{8661811052e4464ca38fb33a5709cda2,

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

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 (3mg), aripiprazole (10mg) 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=.007), than in either placebo (p=.013; CI=0.45, 0.406) or aripiprazole (p=.037; CI= -0.520, -0.014). Interleukin-6 levels were also lower following haloperidol (F(2,22)=4.19, p=.048) in comparison with placebo (p=.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<0.0001) and left (peak voxel T=5.17, p<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.",

author = "Rowena Handley and Valeria Mondelli and Zelaya, {Fernando Osmin} and {Reis Marques}, {Tiago Andre} and Heather Taylor and Reinders, {Antje Annechien Talea Simone} and Christopher Chaddock and Grant McQueen and Kathryn Hubbard and A Papadopoulos and Williams, {Steven Charles Rees} and Philip McGuire and Pariante, {Carmine Maria} and Paola Dazzan",

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doi = "10.1016/j.schres.2016.03.039",

language = "English",

journal = "Schizophrenia Research",

issn = "0920-9964",

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TY - JOUR

T1 - Effects of antipsychotics on cortisol, interleukin-6 and hippocampal perfusion in healthy volunteers

AU - Handley, Rowena

AU - Mondelli, Valeria

AU - Zelaya, Fernando Osmin

AU - Reis Marques, Tiago Andre

AU - Taylor, Heather

AU - Reinders, Antje Annechien Talea Simone

AU - Chaddock, Christopher

AU - McQueen, Grant

AU - Hubbard, Kathryn

AU - Papadopoulos, A

AU - Williams, Steven Charles Rees

AU - McGuire, Philip

AU - Pariante, Carmine Maria

AU - Dazzan, Paola

PY - 2016/4/22

Y1 - 2016/4/22

N2 - 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 (3mg), aripiprazole (10mg) 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=.007), than in either placebo (p=.013; CI=0.45, 0.406) or aripiprazole (p=.037; CI= -0.520, -0.014). Interleukin-6 levels were also lower following haloperidol (F(2,22)=4.19, p=.048) in comparison with placebo (p=.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<0.0001) and left (peak voxel T=5.17, p<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.

AB - 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 (3mg), aripiprazole (10mg) 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=.007), than in either placebo (p=.013; CI=0.45, 0.406) or aripiprazole (p=.037; CI= -0.520, -0.014). Interleukin-6 levels were also lower following haloperidol (F(2,22)=4.19, p=.048) in comparison with placebo (p=.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<0.0001) and left (peak voxel T=5.17, p<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.

U2 - 10.1016/j.schres.2016.03.039

DO - 10.1016/j.schres.2016.03.039

M3 - Article

SN - 0920-9964

JO - Schizophrenia Research

JF - Schizophrenia Research

ER -

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

Abstract

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