Effects of antipsychotics on cortisol, interleukin-6 and hippocampal perfusion in healthy volunteers
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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=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<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.
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An activated inflammatory system is relevant for patients with psychotic disorders, such as schizophrenia, by affecting physical health, brain structure, clinical outcome and the action of antipsychotics.
“an activated inflammatory system is also relevant for patients with psychotic disorders, such as schizophrenia, by affecting physical health, brain structure, clinical outcome and the action of antipsychotics”
From Why are depressed patients inflamed? A reflection on 20 years of research on depression, glucocorticoid resistance and inflammation (2017) · cites this paper as Handley et al., 2016
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- Authors
- Handley, R., Mondelli, V., Zelaya, F., Marques, T., Taylor, H., Reinders, A. A. T. S., Chaddock, C., McQueen, G., Hubbard, K., Papadopoulos, A., Williams, S., McGuire, P., Pariante, C., & Dazzan, P.
- Affiliations
- King's College London (GB)
- Corresponding author
- Mondelli, Valeria
- ORCID
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 174
- Issue
- 1-3
- Pages
- 99-105
- ISSN
- 0920-9964 (ISSN-L)
- OpenAlex
- W2340020194
- Cited by
- 42
- References
- 54
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 3 · 2018: 8 · 2017: 4 · 2016: 2
- FWCI
- 5.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Schizophrenia Research (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- South London and Maudsley NHS Foundation Trust
- King's College London
- Netherlands Organization for Scientific Research (451–07-009, 451-07-009)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- antipsychotic drugs, haloperidol
- MeSH terms
- Aripiprazole, Adolescent, Adult, Cerebrovascular Circulation, Double-Blind Method, Haloperidol, Hippocampus, Humans, Hydrocortisone, Male, Rest, Saliva, Spin Labels, Antipsychotic Agents, Interleukin-6, Cross-Over Studies, Young Adult
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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