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Antipsychotic Drugs Increase the Activity of Endogenous Retroviruses

From left: Olivia Diem and Marisa Schäffner

HELENA offers graduate students a variety of projects to choose from in interdisciplinary research teams at one of the leading centers for environmental health research. Results from Olivia Diem and Marisa Schäffner, graduate students at the Institute of Virology, have been published in PLoS ONE.

The activity of human endogenous retroviruses (HERVs) in brain cells of patients with schizophrenia or bipolar disorders may be increased by treatment with antipsychotic medication. Scientists of the Institute of Virology showed that drugs such as valproic acid may influence HERV expression likely by inducing epigenetic alterations.

Antipsychotic drug treatment of schizophrenia and bipolar disorders* may stimulate the activity of human endogenous retroviruses (HERVs)* that are natural components of the human genome. This was described by the graduate student Olivia Diem, a member of the research group of Christine Leib-Mösch. Elevated expression levels of various HERV groups have been repeatedly described in patients with schizophrenia and associated with the disease. Now for the first time, the research team at Helmholtz Zentrum München has shown that this stimulation may be caused at least partially by the patients’ medication. The researchers conclude that the medication may influence the epigenetic* state of some but not all HERV types.

“Our results show that medication should be generally tested for epigenetic effects on the target cells. Not only endogenous retroviruses, but also cellular genes may be activated or inactivated leading to severe side effects,” said Professor Leib-Mösch, explaining the background of the study.

Schizophrenia is a multifactorial neuropsychiatric disorder. Besides genetic predisposition, various environmental factors such as infections during pregnancy, but also endogenous retroviruses may play a role. The identification of some HERVs that are activated in schizophrenia independent of drug treatment could therefore help to understand the pathomechanisms of the disease. The goals of the Helmholtz Zentrum München are to understand the pathomechanisms of common human diseases and to derive new targets for diagnosis, therapy and prevention.

Background

* Neuropsychiatric disorders are often treated with drugs such as valproic acid, which can modulate the epigenetic state of cells through inhibition of histone deacetylases.

* Human endogenous retroviruses (HERVs) constitute about 9% of the genome and are remnants of germ line infections by exogenous retroviruses about 30 to 40 million years ago. Since that time HERVs have been amplified and spread throughout our genome by retrotransposition and reinfection. The expression of HERVs is normally restricted by epigenetic mechanisms of the host cell. However, HERVs can be reactivated by environmental factors such as radiation or chemicals. The group of HERV-K(HML-2) elements represents the youngest and most active HERVs in humans. Along with several other HERV groups, HERV-K(HML-2) has been repeatedly associated with schizophrenia – interestingly, the activity of these HERVs in brain cells is not influenced by valproic acid.

* Epigenetics describes characteristics of the genome that are not determined by the nucleotide sequence of the DNA but by its chemical state (e.g. methylation level) or marks of the chromatin environment (e.g. histone acetylation or methylation). Epigenetic alterations contribute to the activation or inactivation of genes. Epigenetic characteristics can be altered by environmental influences and passed on during cell division.

Publication

Diem O, Schäffner M, Seifarth W, Leib-Mösch C., Influence of Antipsychotic Drugs on Human Endogenous Retrovirus (HERV) Transcription in Brain Cells. PLoS One. 2012;7(1):e30054. Epub 2012 Jan 11 [abstract]

 

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