F. Perry Wilson, MD
@fperrywilson.bsky.social
Director, Clinical and Translational Research Accelerator @Yale. Columnist @medscape.
How Medicine Works and When It Doesn't in bookstores now!
How Medicine Works and When It Doesn't in bookstores now!
For more detail and discussion, please check out my column @medscape: buff.ly/zF3G3bd
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November 6, 2025 at 6:42 PM
For more detail and discussion, please check out my column @medscape: buff.ly/zF3G3bd
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/🧵
What we need: replication studies and, ideally, a real randomized trial.
Until then, I'm hopeful but dubious. Which, honestly, is probably the right stance for most observational research.
Until then, I'm hopeful but dubious. Which, honestly, is probably the right stance for most observational research.
November 6, 2025 at 6:42 PM
What we need: replication studies and, ideally, a real randomized trial.
Until then, I'm hopeful but dubious. Which, honestly, is probably the right stance for most observational research.
Until then, I'm hopeful but dubious. Which, honestly, is probably the right stance for most observational research.
So where does this leave us?
I started out thinking "this can't be right." I'm still pretty skeptical. But sometimes important discoveries are hiding in plain sight.
Given the stakes with schizophrenia, this deserves more investigation.
I started out thinking "this can't be right." I'm still pretty skeptical. But sometimes important discoveries are hiding in plain sight.
Given the stakes with schizophrenia, this deserves more investigation.
November 6, 2025 at 6:42 PM
So where does this leave us?
I started out thinking "this can't be right." I'm still pretty skeptical. But sometimes important discoveries are hiding in plain sight.
Given the stakes with schizophrenia, this deserves more investigation.
I started out thinking "this can't be right." I'm still pretty skeptical. But sometimes important discoveries are hiding in plain sight.
Given the stakes with schizophrenia, this deserves more investigation.
Result? The doxycycline group looks great by comparison, even if the drug does nothing for schizophrenia.
The authors could easily check this by only including kids who got antibiotics AFTER starting psychiatric care. But that analysis isn't reported.
The authors could easily check this by only including kids who got antibiotics AFTER starting psychiatric care. But that analysis isn't reported.
November 6, 2025 at 6:42 PM
Result? The doxycycline group looks great by comparison, even if the drug does nothing for schizophrenia.
The authors could easily check this by only including kids who got antibiotics AFTER starting psychiatric care. But that analysis isn't reported.
The authors could easily check this by only including kids who got antibiotics AFTER starting psychiatric care. But that analysis isn't reported.
Here's how that would mess things up:
Some kids who wouldn't normally need psychiatric care get pushed over that edge by doxycycline. Now they're in the study group, but they're actually the HEALTHIEST kids in that group.
Some kids who wouldn't normally need psychiatric care get pushed over that edge by doxycycline. Now they're in the study group, but they're actually the HEALTHIEST kids in that group.
November 6, 2025 at 6:42 PM
Here's how that would mess things up:
Some kids who wouldn't normally need psychiatric care get pushed over that edge by doxycycline. Now they're in the study group, but they're actually the HEALTHIEST kids in that group.
Some kids who wouldn't normally need psychiatric care get pushed over that edge by doxycycline. Now they're in the study group, but they're actually the HEALTHIEST kids in that group.
Second, and this is the big one: collider bias.
They only looked at kids who had psychiatric services. What if doxycycline slightly increases the need for psychiatric care (maybe mild depression in some kids)?
They only looked at kids who had psychiatric services. What if doxycycline slightly increases the need for psychiatric care (maybe mild depression in some kids)?
November 6, 2025 at 6:41 PM
Second, and this is the big one: collider bias.
They only looked at kids who had psychiatric services. What if doxycycline slightly increases the need for psychiatric care (maybe mild depression in some kids)?
They only looked at kids who had psychiatric services. What if doxycycline slightly increases the need for psychiatric care (maybe mild depression in some kids)?
But I have doubts.
First, there's no clear dose-response effect. Higher doses should show stronger effects if this is causal. The medium dose looks best here, which is... odd.
First, there's no clear dose-response effect. Higher doses should show stronger effects if this is causal. The medium dose looks best here, which is... odd.
November 6, 2025 at 6:41 PM
But I have doubts.
First, there's no clear dose-response effect. Higher doses should show stronger effects if this is causal. The medium dose looks best here, which is... odd.
First, there's no clear dose-response effect. Higher doses should show stronger effects if this is causal. The medium dose looks best here, which is... odd.
They also did a negative control analysis. Did doxycycline prevent anorexia nervosa? Nope. This suggests the doxycycline group isn't just healthier overall.
So far so good.
So far so good.
November 6, 2025 at 6:41 PM
They also did a negative control analysis. Did doxycycline prevent anorexia nervosa? Nope. This suggests the doxycycline group isn't just healthier overall.
So far so good.
So far so good.
The researchers did good work ruling out some obvious confounders. The main one? Acne. That's probably why these teens got doxycycline.
But when they looked at non-tetracycline acne drugs, no protective effect. So it's not just treating acne that helps.
But when they looked at non-tetracycline acne drugs, no protective effect. So it's not just treating acne that helps.
November 6, 2025 at 6:41 PM
The researchers did good work ruling out some obvious confounders. The main one? Acne. That's probably why these teens got doxycycline.
But when they looked at non-tetracycline acne drugs, no protective effect. So it's not just treating acne that helps.
But when they looked at non-tetracycline acne drugs, no protective effect. So it's not just treating acne that helps.
The results over 15 years:
- No doxycycline: 2.74% developed schizophrenia
- Low exposure: 2.22%
- Medium exposure: 1.42%
- High exposure: 2.0%
That's a 20-50% reduction. If real, this would be the first preventative treatment for schizophrenia.
- No doxycycline: 2.74% developed schizophrenia
- Low exposure: 2.22%
- Medium exposure: 1.42%
- High exposure: 2.0%
That's a 20-50% reduction. If real, this would be the first preventative treatment for schizophrenia.
November 6, 2025 at 6:41 PM
The results over 15 years:
- No doxycycline: 2.74% developed schizophrenia
- Low exposure: 2.22%
- Medium exposure: 1.42%
- High exposure: 2.0%
That's a 20-50% reduction. If real, this would be the first preventative treatment for schizophrenia.
- No doxycycline: 2.74% developed schizophrenia
- Low exposure: 2.22%
- Medium exposure: 1.42%
- High exposure: 2.0%
That's a 20-50% reduction. If real, this would be the first preventative treatment for schizophrenia.
The design choice here is smart. Comparing doxycycline users to ALL non-users would be messy. Maybe they just have better access to care or something. Using other antibiotics as the comparison group controls for that. Other differences were adjusted statistically.
November 6, 2025 at 6:41 PM
The design choice here is smart. Comparing doxycycline users to ALL non-users would be messy. Maybe they just have better access to care or something. Using other antibiotics as the comparison group controls for that. Other differences were adjusted statistically.
The new study uses Finland's national health database. They looked at 52,786 adolescents who had at least one psychiatric visit and received antibiotics.
About a third got doxycycline, the rest got other antibiotics.
Link: buff.ly/l9UUhQS
About a third got doxycycline, the rest got other antibiotics.
Link: buff.ly/l9UUhQS
November 6, 2025 at 6:41 PM
The new study uses Finland's national health database. They looked at 52,786 adolescents who had at least one psychiatric visit and received antibiotics.
About a third got doxycycline, the rest got other antibiotics.
Link: buff.ly/l9UUhQS
About a third got doxycycline, the rest got other antibiotics.
Link: buff.ly/l9UUhQS
Maybe schizophrenia is caused by an infection? This was actually a popular theory in the early 1900s. The bug most linked to schizophrenia (still weakly) is Toxoplasma.
But here's the problem: doxycycline doesn't work against Toxoplasma. So we need another explanation.
But here's the problem: doxycycline doesn't work against Toxoplasma. So we need another explanation.
November 6, 2025 at 6:41 PM
Maybe schizophrenia is caused by an infection? This was actually a popular theory in the early 1900s. The bug most linked to schizophrenia (still weakly) is Toxoplasma.
But here's the problem: doxycycline doesn't work against Toxoplasma. So we need another explanation.
But here's the problem: doxycycline doesn't work against Toxoplasma. So we need another explanation.
First, is it even plausible that an antibiotic could affect the brain?
Actually, yes. The brain is super complex, and doxycycline can cross the blood-brain barrier just fine. But that doesn't mean it does anything once it gets there.
Actually, yes. The brain is super complex, and doxycycline can cross the blood-brain barrier just fine. But that doesn't mean it does anything once it gets there.
November 6, 2025 at 6:41 PM
First, is it even plausible that an antibiotic could affect the brain?
Actually, yes. The brain is super complex, and doxycycline can cross the blood-brain barrier just fine. But that doesn't mean it does anything once it gets there.
Actually, yes. The brain is super complex, and doxycycline can cross the blood-brain barrier just fine. But that doesn't mean it does anything once it gets there.
For more detail and discussion, please check out my column @medscape: buff.ly/zF3G3bd
/🧵
/🧵
November 6, 2025 at 6:39 PM
For more detail and discussion, please check out my column @medscape: buff.ly/zF3G3bd
/🧵
/🧵
What we need: replication studies and, ideally, a real randomized trial.
Until then, I'm hopeful but dubious. Which, honestly, is probably the right stance for most observational research.
Until then, I'm hopeful but dubious. Which, honestly, is probably the right stance for most observational research.
November 6, 2025 at 6:39 PM
What we need: replication studies and, ideally, a real randomized trial.
Until then, I'm hopeful but dubious. Which, honestly, is probably the right stance for most observational research.
Until then, I'm hopeful but dubious. Which, honestly, is probably the right stance for most observational research.
So where does this leave us?
I started out thinking "this can't be right." I'm still pretty skeptical. But sometimes important discoveries are hiding in plain sight.
Given the stakes with schizophrenia, this deserves more investigation.
I started out thinking "this can't be right." I'm still pretty skeptical. But sometimes important discoveries are hiding in plain sight.
Given the stakes with schizophrenia, this deserves more investigation.
November 6, 2025 at 6:39 PM
So where does this leave us?
I started out thinking "this can't be right." I'm still pretty skeptical. But sometimes important discoveries are hiding in plain sight.
Given the stakes with schizophrenia, this deserves more investigation.
I started out thinking "this can't be right." I'm still pretty skeptical. But sometimes important discoveries are hiding in plain sight.
Given the stakes with schizophrenia, this deserves more investigation.
Result? The doxycycline group looks great by comparison, even if the drug does nothing for schizophrenia.
The authors could easily check this by only including kids who got antibiotics AFTER starting psychiatric care. But that analysis isn't reported.
The authors could easily check this by only including kids who got antibiotics AFTER starting psychiatric care. But that analysis isn't reported.
November 6, 2025 at 6:39 PM
Result? The doxycycline group looks great by comparison, even if the drug does nothing for schizophrenia.
The authors could easily check this by only including kids who got antibiotics AFTER starting psychiatric care. But that analysis isn't reported.
The authors could easily check this by only including kids who got antibiotics AFTER starting psychiatric care. But that analysis isn't reported.
Here's how that would mess things up:
Some kids who wouldn't normally need psychiatric care get pushed over that edge by doxycycline. Now they're in the study group, but they're actually the HEALTHIEST kids in that group.
Some kids who wouldn't normally need psychiatric care get pushed over that edge by doxycycline. Now they're in the study group, but they're actually the HEALTHIEST kids in that group.
November 6, 2025 at 6:39 PM
Here's how that would mess things up:
Some kids who wouldn't normally need psychiatric care get pushed over that edge by doxycycline. Now they're in the study group, but they're actually the HEALTHIEST kids in that group.
Some kids who wouldn't normally need psychiatric care get pushed over that edge by doxycycline. Now they're in the study group, but they're actually the HEALTHIEST kids in that group.
Second, and this is the big one: collider bias.
They only looked at kids who had psychiatric services. What if doxycycline slightly increases the need for psychiatric care (maybe mild depression in some kids)?
They only looked at kids who had psychiatric services. What if doxycycline slightly increases the need for psychiatric care (maybe mild depression in some kids)?
November 6, 2025 at 6:39 PM
Second, and this is the big one: collider bias.
They only looked at kids who had psychiatric services. What if doxycycline slightly increases the need for psychiatric care (maybe mild depression in some kids)?
They only looked at kids who had psychiatric services. What if doxycycline slightly increases the need for psychiatric care (maybe mild depression in some kids)?
But I have doubts.
First, there's no clear dose-response effect. Higher doses should show stronger effects if this is causal. The medium dose looks best here, which is... odd.
First, there's no clear dose-response effect. Higher doses should show stronger effects if this is causal. The medium dose looks best here, which is... odd.
November 6, 2025 at 6:39 PM
But I have doubts.
First, there's no clear dose-response effect. Higher doses should show stronger effects if this is causal. The medium dose looks best here, which is... odd.
First, there's no clear dose-response effect. Higher doses should show stronger effects if this is causal. The medium dose looks best here, which is... odd.
They also did a negative control analysis. Did doxycycline prevent anorexia nervosa? Nope. This suggests the doxycycline group isn't just healthier overall.
So far so good.
So far so good.
November 6, 2025 at 6:39 PM
They also did a negative control analysis. Did doxycycline prevent anorexia nervosa? Nope. This suggests the doxycycline group isn't just healthier overall.
So far so good.
So far so good.
The researchers did good work ruling out some obvious confounders. The main one? Acne. That's probably why these teens got doxycycline.
But when they looked at non-tetracycline acne drugs, no protective effect. So it's not just treating acne that helps.
But when they looked at non-tetracycline acne drugs, no protective effect. So it's not just treating acne that helps.
November 6, 2025 at 6:39 PM
The researchers did good work ruling out some obvious confounders. The main one? Acne. That's probably why these teens got doxycycline.
But when they looked at non-tetracycline acne drugs, no protective effect. So it's not just treating acne that helps.
But when they looked at non-tetracycline acne drugs, no protective effect. So it's not just treating acne that helps.
The results over 15 years:
- No doxycycline: 2.74% developed schizophrenia
- Low exposure: 2.22%
- Medium exposure: 1.42%
- High exposure: 2.0%
That's a 20-50% reduction. If real, this would be the first preventative treatment for schizophrenia.
- No doxycycline: 2.74% developed schizophrenia
- Low exposure: 2.22%
- Medium exposure: 1.42%
- High exposure: 2.0%
That's a 20-50% reduction. If real, this would be the first preventative treatment for schizophrenia.
November 6, 2025 at 6:39 PM
The results over 15 years:
- No doxycycline: 2.74% developed schizophrenia
- Low exposure: 2.22%
- Medium exposure: 1.42%
- High exposure: 2.0%
That's a 20-50% reduction. If real, this would be the first preventative treatment for schizophrenia.
- No doxycycline: 2.74% developed schizophrenia
- Low exposure: 2.22%
- Medium exposure: 1.42%
- High exposure: 2.0%
That's a 20-50% reduction. If real, this would be the first preventative treatment for schizophrenia.