07 Nov Edinburgh Study Suggests Doxycyline May Abate Progression of Schizophrenia in Adolescents
MedicalResearch.com Interview with:
Prof. Kelleher
Ian Kelleher PhD, MB BCh BAO (Medicine)
Professor of Child and Adolescent Psychiatry
Academy of Medical Sciences Professor
Institute for Neuroscience and Cardiovascular Research
University of Edinburgh
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Schizophrenia is a severe mental illness associated with hallucinations, delusions and a marked decline in functioning. It usually begins in adulthood, in the 20s, but we know from recent research that as many as half of all individuals who develop schizophrenia had attended child and adolescent psychiatry services earlier in life for other mental health problems. That’s exciting because it suggests: maybe there’s something we could do to reduce risk of schizophrenia in adolescent psychiatry services. But, at present, we don’t have evidence that any intervention reduces schizophrenia risk in this clinical population.
Lots of researchers are interested in the antibiotic doxycycline, and the structurally similarly minocycline, because it has potential neuroprotective effects. It crosses the blood brain barrier and seems to reduce inflammation and apoptosis (or programmed cell death). We think that excessive synaptic pruning may play a key role in the development of schizophrenia. In laboratory studies, doxycycline seems to reduce the level of synaptic pruning by its effect on the immune system. Some research suggests that even low dose exposure to doxycycline may lead to long-term effects in “dampening down” activity by microglia, the brain’s resident macrophages, which are central to the process of synaptic pruning.
MedicalResearch.com: Do the results suggest a potential association between an infectious etiology and schizophrenia?
Response: That’s one possibility. It could be the case doxycycline directly treats some sort of pathogen which plays a role in the development of schizophrenia. It could also be the case that some sort of infectious agent makes microglia more active, and it’s the subsequent overactivity of microglia, for example on synaptic pruning, that plays a causal role in the development of schizophrenia. It could also be the case that doxycycline has anti-inflammatory effects that impact on schizophrenia risk without anything to do with an infectious agent. Those are all hypotheses that require further testing.
MedicalResearch.com: What should readers take away from your report?
Response: Our study implicates the immune system in the development of schizophrenia and, excitingly, identifies a potential treatment that could reduce the risk of severe mental illness in young people coming to adolescent psychiatry services. It’s important to be clear, however, that the study was observational in nature and, while we used robust statistical methods to try to deal with many of the confounds that you see in typical observational studies in order to try to get closer to identifying causal effects, we do still need to cautious about coming to causal conclusions.
Only a randomised controlled trial (RCT) could tell us for certain that doxycycline causally reduces schizophrenia risk. An RCT for this question, however, is quite unfeasible, given the huge number of participants that would be needed and the long period of time between treatment and developing the outcome. That means we really need to do our very utmost to carefully analyse observational data, like we did in this study, and triangulate data.
MedicalResearch.com: What recommendations do you have for future research as a results of this study?
Response: There are lots of more fundamental biological questions that we need to answer now in order to figure out things like: is there a key developmental window in which to administer doxycycline? How much doxycycline would be necessary? Is even a brief exposure sufficient or are longer exposures more effective? It also points to the importance of looking at other anti-inflammatory treatments in adolescent psychiatry services and the effects these may have on long-term mental health outcomes.
No disclosures, no conflicts of interest.
Citation: Lång U, Metsälä J, Ramsay H, et al. Doxycycline Use in Adolescent Psychiatric Patients and Risk of Schizophrenia: An Emulated Target Trial. American Journal of Psychiatry. 2025;0(0). doi:10.1176/appi.ajp.20240958
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The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Some links may be sponsored. Products are not warranted or endorsed.
Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.
Last Updated on November 7, 2025 by Marie Benz MD FAAD
