# EXPOSURE TO TETRACYCLINE ANTIBIOTICS AND THE POTENTIAL PROTECTIVE EFFECT ON SCHIZOPHRENIA RISK.

> **NIH NIH R21** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $412,808

## Abstract

SUMMARY
Several lines of evidence suggest that tetracycline antibiotics, such as minocycline and doxycycline, are a
promising new avenue to explore for prevention and treatment of schizophrenia. Tetracycline presumably targets
increased synapse elimination by microglia underlying schizophrenia. This is the first strategy based on disease
mechanism that is uncovered by preclinical studies, including the largest genetic and transcriptomic studies, as
well as state-of-the-art stemcell-based technologies. It can therefore be viewed as the first pay-off of the
tremendous efforts made by the global genomics consortia to generate novel leads to understand and treat
schizophrenia. Over the last decades, multiple small clinical trials have been performed to test potential efficacy
of new drugs for prevention and treatment of schizophrenia. Most of these trials failed or could not be replicated,
perhaps because of a limited scientific premise. Here we suggest building better evidence for the potential
efficacy of tetracycline antibiotics before performing large clinical trials. We will use one of the largest datasets
in the world for which both detailed information of tetracycline exposure is available for all individuals in Denmark,
as well as information on schizophrenia spectrum disorders diagnosed in all psychiatric treatment settings. The
longitudinal nature of the data sources, and the length and extent of the follow-up of the subjects, is unique and
unprecedented: 25 years follow-up period provides the opportunity to investigate whether the exposure to
tetracycline antibiotics prevents or delays onset of a schizophrenia spectrum disorder.
First, we will analyze the risk of a schizophrenia spectrum disorder after exposure to the brain-penetrant
doxycycline. Next, we will look at the role of timing and duration of exposure to these antibiotics. Finally, we will
compare the influence of exposure to doxycycline prescribed for acne on schizophrenia risk with exposure to
other types of treatments prescribed for acne and to unexposed individuals. We will perform matched cohort
studies to compare the exposed group with an unexposed group, or with a group exposed to other types of
medication. As confounders we consider sex, socioeconomic status, family history of mental illness, and
psychiatric and somatic comorbidity. The outcome of this study will be a better understanding of the utility of
tetracycline antibiotics for prevention and treatment of schizophrenia spectrum disorders and will inform the
design of a placebo-controlled randomized clinical trial of tetracycline for schizophrenia prevention, with the
developmental period and potential dose informed by the results found here.

## Key facts

- **NIH application ID:** 10039207
- **Project number:** 1R21MH123913-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Veerle Bergink
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $412,808
- **Award type:** 1
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10039207

## Citation

> US National Institutes of Health, RePORTER application 10039207, EXPOSURE TO TETRACYCLINE ANTIBIOTICS AND THE POTENTIAL PROTECTIVE EFFECT ON SCHIZOPHRENIA RISK. (1R21MH123913-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10039207. Licensed CC0.

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