Molecular phenotypes associated with antipsychotic drugs in the human caudate nucleus.

Autor: Perzel Mandell KA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA.; Department of Genetic Medicine, Johns Hopkins University School of Medicine (JHSOM), Baltimore, MD, 21205, USA., Eagles NJ; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA., Deep-Soboslay A; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA., Tao R; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA., Han S; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA.; Department of Psychiatry and Behavioral Sciences, JHSOM, Baltimore, MD, USA., Wilton R; Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD, USA., Szalay AS; Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD, USA.; Department of Computer Science, JHSOM, Baltimore, MD, USA., Hyde TM; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA.; Department of Psychiatry and Behavioral Sciences, JHSOM, Baltimore, MD, USA.; Department of Neurology, JHSOM, Baltimore, MD, USA., Kleinman JE; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA.; Department of Psychiatry and Behavioral Sciences, JHSOM, Baltimore, MD, USA., Jaffe AE; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA.; Department of Genetic Medicine, Johns Hopkins University School of Medicine (JHSOM), Baltimore, MD, 21205, USA.; Department of Psychiatry and Behavioral Sciences, JHSOM, Baltimore, MD, USA.; Department of Neuroscience, JHSOM, Baltimore, MD, USA.; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health (JHBSPH), Baltimore, MD, 21205, USA.; Department of Biostatistics, JHBSPH, Baltimore, MD, USA., Weinberger DR; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA. drweinberger@libd.org.; Department of Genetic Medicine, Johns Hopkins University School of Medicine (JHSOM), Baltimore, MD, 21205, USA. drweinberger@libd.org.; Department of Psychiatry and Behavioral Sciences, JHSOM, Baltimore, MD, USA. drweinberger@libd.org.; Department of Neurology, JHSOM, Baltimore, MD, USA. drweinberger@libd.org.; Department of Neuroscience, JHSOM, Baltimore, MD, USA. drweinberger@libd.org.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2022 Apr; Vol. 27 (4), pp. 2061-2067. Date of Electronic Publication: 2022 Mar 02.
DOI: 10.1038/s41380-022-01453-6
Abstrakt: Antipsychotic drugs are the current first-line of treatment for schizophrenia and other psychotic conditions. However, their molecular effects on the human brain are poorly studied, due to difficulty of tissue access and confounders associated with disease status. Here we examine differences in gene expression and DNA methylation associated with positive antipsychotic drug toxicology status in the human caudate nucleus. We find no genome-wide significant differences in DNA methylation, but abundant differences in gene expression. These gene expression differences are overall quite similar to gene expression differences between schizophrenia cases and controls. Interestingly, gene expression differences based on antipsychotic toxicology are different between brain regions, potentially due to affected cell type differences. We finally assess similarities with effects in a mouse model, which finds some overlapping effects but many differences as well. As a first look at the molecular effects of antipsychotics in the human brain, the lack of epigenetic effects is unexpected, possibly because long term treatment effects may be relatively stable for extended periods.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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