Schizophrenia study finds new biomarker, drug candidate in mice | Hacker News Reader

Schizophrenia study finds new biomarker, drug candidate in mice

news.northwestern.edu

112 pointsgmays54 comments

Drug has only been tested in mice.

Of course, in this case the issue seems like it's caused by a general deficiency of single protein, maybe that's a good sign for adapting the treatment to humans.

While the protein was tested in mice, it seems that it was identified by looking at human spinal fluid.

Yes. Not a drug in the typical sense. Simply replacing the protein in which the mice are deficient (that was identified by measuring levels in human spinal fluid).

Inmiced above. Thanks!

It's been awhile since I read about this stuff...is schizophrenia a spectrum disorder like autism? If so, I wonder if there's a point on the spectrum where it's not worth treating it because of possible side effects.

I feel like our society over-pathologizes a lot of stuff and it would be a shame if we "cured" something that doesn't need a cure.

I liked how this blog[0] describes it. Schizophrenia itself isn't a spectrum, but rather you have varying levels of schizophrenia risk genes. They have positive fitness functions (creativity, cognitive flexibility, linguistic skill) until you cross the threshold to schizophrenia.

[0] https://www.psychiatrymargins.com/p/schizophrenia-is-the-pri...

> is schizophrenia a spectrum disorder like autism?

I'm a non expert but I believe some people are starting to see it that way. See: https://www.google.com/search?q=schizophrenia+spectrum+disor...

Also there's huge overlap in symptoms between bipolar I with psychosis, schizoaffective disorder, and schizophrenia. People sometimes move around between these diagnoses throughout treatment, different doctors have different opinions, patient behavior changes, etc.

I personally think these symptoms come about through many different causes and the labels are somewhat inadequate. They capture a symptom profile rather than a full understanding.

I remember reading in Courtenay Harding's (now very old) book, Recovery from Schizophrenia: Evidence, History, and Hope, that populations with a higher prevalence of bipolar tended to have a lower prevalence of schizophrenia, and vice versa. The implication was that the same thing was being expressed differently in differing contexts. I would be curious if more contemporary studies bore this out.

I believe I've heard that synaptic pruning may be implicated in both.

The overlap is not huge at all. Beside psychosis, they have no overlap, and the quality of the psychosis in the two illnesses is far removed from each other.

I'm speaking about people I've known and been close to. As an example, my brother shifted around diagnosis between bipolar I, schizoaffective, and schizophrenia often while I was growing up. He's not the only person I know like this. I've spoken to psychiatrists about the ambiguity between these diagnoses.

I also know of numerous people who have spoken publicly about receiving a schizophrenia diagnosis and having it later be revised to schizoaffective disorder.

I also came to the impression that it is common to receive a bipolar I diagnosis during a psychotic episode and have it later the diagnosed as schizophrenia or schizoaffective disorder.

Sometimes if your doctor sucks you may stay in the less accurate diagnosis, sometimes for years.

Same in someone I know, shifted between bipolar and schitzoaffective and schitzophrenia. Bipolar during manic episode, later schizoaffective. A lot of paranoia and also delusions, but also refused medication due to side effects (and probably the disorder itself).

Re: anosognosia.

You might be interested in this book: https://en.wikipedia.org/wiki/Doctoring_the_Mind

Thanks, seems right up my alley.

It is a spectrum disorder.

Among those who have had first episode psychosis, the first break, there is precisely zero point on the spectrum where it's not worth treating it.

A tragic illness that wreaks havoc on the lives of the individual, and often those around them. Employment rate in the single digits, for competitive jobs.

A part of the spectrum where research shows there is nothing to cure is schizotypy/apophenia and magical thinking, but only when paired with conscientiousness and high intelligence. The combination of these traits may be linked to creative genius. But those people don't have schizophrenia.

The other Serious Mental Illness, bipolar, is far less debilitating when medicated. Esp. Type II. And linked to creative success, esp. in the arts and when paired with high verbal intelligence.

Kanye, Churchill, Cobain, Woolf, Hemingway, Van Gogh.

John Gartner, psychologist @ Hopkins, wrote a book about 20 years ago called The Hypomanic Edge.

The thesis somewhat comical yet believable, America has tons of folks on the bipolar spectrum, experiencing low level hypomania. The idea is you have to be slightly mad to leave home and travel to a distant land with nothing. Risk taking, competitiveness, etc.

As far as curing something that doesn't need a cure. There's a conversation to be had with mild forms of bipolar, especially if it never tips into full mania. Schizophrenia, after the first psychotic break, there isn't.

And the lives of those even when medicated is often really, really hard.

To this point, some cultures see schizophrenia as friendly, not scary.

https://news.stanford.edu/stories/2014/07/voices-culture-luh...

> In the United States, the voices are harsher, and in Africa and India, more benign, said Tanya Luhrmann, a Stanford professor of anthropology and first author of the article in the British Journal of Psychiatry.

> To this point, some cultures see schizophrenia as friendly, not scary.

That should not be your conclusion from the article.

"the voices" are hardly the only symptom that people with schizophrenia suffer from. A lot of those affected don't have auditory hallucinations at all and are still suffering from one of the (if not the) most debilitating mental disorders out there.

Calling it "friendly" risks trivialising of the very real symptoms.

> The striking difference was that while many of the African and Indian subjects registered predominantly positive experiences with their voices, not one American did. Rather, the U.S. subjects were more likely to report experiences as violent and hateful – and evidence of a sick condition.

> In Accra, Ghana, where the culture accepts that disembodied spirits can talk, few subjects described voices in brain disease terms. When people talked about their voices, 10 of them called the experience predominantly positive; 16 of them reported hearing God audibly. “‘Mostly, the voices are good,’” one participant remarked.

This seems clinically useful. The existence of other symptoms doesn't really change that fact.

I don't disagree at all.

I am merely commenting on your takeaway that this somehow means that some cultures see schizophrenia as "friendly", which does absolutely does not follow from the fact that the "mostly, the voices are good".

I would also think that this is likely due to cultural differences and in many cases probably adds to the problem.

https://doi.org/10.3109/09540261.2012.711746

From the full Article:

"People suffering from psychotic illness continue to hold multi-explanatory models. The cultural, religious and social explanatory models are predominant in non-western cultures."

"Limited evidence suggests that traditional belief models affect [duration of untreated psychosis], and explanatory models based on spiritual and social causes of illness may result in delayed presentations for professional help."

This idea relocates the problem from the individual to “culture” or “society,” leaving no solutions for someone suffering from schizophrenia.

I also have a hard time believing that schizophrenia manifests as something like benign quirkiness in some other country.

> I also have a hard time believing…

Well, publish that null result in a journal!

> This idea relocates the problem from the individual to “culture” or “society”...

No, one could incorporate this information just fine on an individual level by treating it as less of a scary symptom and more of something to understand.

I'm skeptical that doing mental visualization exercises can cure cancer, or that crystals give off healing energy.

I'm generally skeptical of too-good-to-be-true factoids. My skepticism is not publication-worthy, it's pretty common, and taken too far it becomes cynicism. Every once in while my skepticism is misplaced.

I am curious though - do you have individual examples, or personal experience, of how some other culture handles schizophrenia in an understanding way? I saw the journal reference...i'm more interested in specific examples.

> I'm skeptical that doing mental visualization exercises can cure cancer, or that crystals give off healing energy.

But if a respected peer-reviewed journal published a study demonstrating evidence of it, you'd want to at least take a peek.

> I am curious though - do you have individual examples, or personal experience, of how some other culture handles schizophrenia in an understanding way? I saw the journal reference...i'm more interested in specific examples.

These are in the article and the study itself.

"Among the Indians in Chennai, more than half (11) heard voices of kin or family members commanding them to do tasks. “They talk as if elder people advising younger people,” one subject said. That contrasts to the Americans, only two of whom heard family members. Also, the Indians heard fewer threatening voices than the Americans – several heard the voices as playful, as manifesting spirits or magic, and even as entertaining. Finally, not as many of them described the voices in terms of a medical or psychiatric problem, as all of the Americans did."

I have some primary care providers in the family and I've asked them since I often have differing opinions. I've asked if some people with bipolar and schizophrenia refuse specific medical treatment and just go on with their life. I've gotten the answer that many of them have learned to recognize what is happening and ride it out well enough that they can live with it. I'm sure it's highly dependent on the severity and the person.

I've noticed something similar with people on say heavy doses if hallucinogens. Some people just ride it out knowing it's the mind playing tricks on them, others hopelessly panic or make irreversible decisions.

Depending who you believe, approximately half of them are unable to see they are ill (re: anosognosia).

I suspect this is the case with many mental health conditions / neurodiverse conditions; after all, people grow up with them and if their environment is not affected or making observations (e.g. people are told or convinced that what their brains do or tell them is abnormal), why would they doubt themselves?

But this is a narrow path to walk, because if you see something and someone tries to convince you it's not there, who is right?

This is why some mental health conditions are pretty terrifying, because doubting your own mind is terrifying.

Well, there's gotta be a line you can draw somewhere between "treating people who actually need it" and "treating people because that's what policy says and we don't care about the individual".

Sometimes, that line is whether or not the state is somehow involved through social services or the criminal justice system.

It’s more complicated than that, re: anosognosia.

Not in the same way. The degree to which the symptoms manifest can range from mild to extreme, but it's dependent on the person, and each person can have symptoms exacerbated to more or less the same degree. A psychotic break can result in you believing you're chosen by god to shovel snow off the sidewalks for your neighborhood, and for the rest of your life, you will deeply and genuinely believe that to be true, and accordingly orient your life around it. You might be very normal appearing in almost every other way, but have that one singular delusion that overwhelms your capacity to think rationally about it. You might end up confabulating that you are individually responsible for making the weather warm during spring, summer, and fall, and responsible for the lack of snow.

Other delusions, hallucinations, hearing malicious voices, hearing voices which you feel you must obey, end up with individuals who have the same relative level of schizophrenic dysfunction, in terms of the way the brain operates, but the nature of the delusion can make them dangerous - "god told me to direct traffic on the freeway" or "god told me to slay demons disguised as humans".

The particulars of the case make a huge difference in how much medicine and treatment can help them live independent, normal lives. This potential treatment would be wonderful if it restores normal brain function. It also hints at why antipsychotic and other drugs which increase inhibitory signaling were partially effective.

Heck, it even has explanatory power for the different triggers of psychotic breaks - once a threshold of activity gets passed, the brain loses its ability to discriminate between legitimate, reality grounded signals and feedback that should have been inhibited, and once those neural connections are made and "configured" to operate as part of the default mode network, that person will have permanent cognitive problems.

Very cool research, and I hope it bears fruit.

No but it is a behaviourally defined disorder like autism. Which means it can and has many different causal patterns behind it.

That is there are many different things that can cause the behaviour.

Anyway on your main point, the definition of all psychiatric disorders has requirements of subjective suffering. So if you don't have subjective suffering you don't have the disorder.

That would be an incredible cure and raises the ethical question of how to get schizophrenic people well enough to understand that they need it.

This seems to be mainly about the so called negative symptoms, not positive symptoms (like hallucinations or delusions). While it is often hard to argue with people about their positive symptoms in schizophrenia or in mania, pretty much nobody who has negative symptoms wants to have them. The fact that antipsychotics do little about the negative symptoms is probably the biggest pain of schizophrenia sufferers - and they are aware of that.

Also, and this depends on the jurisdiction, but people can be forced to take psychiatric medication against their will. Or even forced to go through a treatment like ECT, for example when presenting with strong and dangerous mania. BTW, ECT has an extremely unfair popular opinion, it's one of the best treatments in all of psychiatry. It could even be that it is impossible to get a response from the patient, for example if they are catatonic and don't budge within a reasonable time - you just inject them with benzodiazepines, as this is a serious condition if left to last a long time.

ECT just comes across as a bit barbaric. I'd welcome more research into Psilocybin to achieve system reset.

Psychedelic therapy is unlikely to ever become mainstream treatment for serious mental illness like schizophrenia or bipolar disorder. In those cases, it’s significantly more likely to cause more problems than it solves. In general these new faddish psychedelic treatments are mostly effective for bougie mental illness – mild depression, anxiety, stress – but they do not belong in a treatment regimen for serious illness. There is a reason every psychedelic treatment study excludes participants with schizophrenia and bipolar.

ECT might seem barbaric and unsexy compared to dosing some psilocybin and listening to some ambient music in a cozy room, but that doesn’t reduce its clinical value for people with serious, treatment resistant disorders.

People do try psylocybin, or ketamine, or frankly just about anything. Esketamine even has regulatory approval as a tretment. Research is sometimes posted here on HN. But nothing seems to be as effective as ECT, it truly is the king of affective disorders.

BTW, and not many people know this, it is a procedure performed under full anesthesia, including muscle blockers. From the outside it looks very calm, and from the inside the patient's experience is pretty much identical to taking a nap.

It is not risk free, precisely because of the anesthesia, so in most areas one can only get it if they try enough other treatments - like 2 or 3 or something like that, ideally from different classes of drugs. But definitely do consider this if you're suffering and nothing seems to help (enough).

My great friend, when we were 20, shot himself in the head while we were doing shrooms. This is not an uncommon occurrence. Thousands of incidents of self harm happen every year in the US alone because of these drugs.

I would advise anyone against this. Don't believe the weird hype (that mostly all comes from a few small clicks of people looking to profit off this drug) about mushrooms being some spiritual, mental catch all. If you have any sort of mental illness you probably should avoid. Don't play Russian roulette with your sanity.

People do that after getting drunk too.

Depressed people killing themselves as soon as they start to get treatment is a known phenomenon. The energy that comes from treating depression gives them just enough oomph to get to the 'finish line.' It's quite possible they were thinking about it and never told anyone and everyone thinks it's a complete surprise caused by the drug, plenty of people have suicidal ideation or depression while giving zero indication or clues to anyone close to them that would be the case.

Even outside a drug. Breakup happens this can be a result.

Maybe if guns weren’t so accessible people wouldn’t be so quick to use them on themselves in those moments. There’s a statistic out there where a gun in the home is most likely to harm you.

You just do your best and leave them alone otherwise.

"Leave them alone" is easy to type into a comment textbox but is much more difficult when it's a neighbor, or a family member, or someone else you have to interact with at a regular interval.

I highly recommend the book Hidden Valley Road for anyone curious about how difficult schizophrenia is for families and the researchers trying to find treatments.

I have two close friends who are schizophrenic and have been psychotic myself. I know what I'm talking about.

Very strange how HN elevates news about random drug candidates at very early stages of development.

There is a very active landscape of people developing/validating 'biomarkers' for neurological and psychiatric disorders and developing drugs specifically for those populations with the biomarker present; this news is far from extraordinary.

The real news is when these reach FDA approval.

Identifying a biomarker for a psychological condition, particularly one like schizophrenia which is hugely disruptive for individuals affected and has a seemingly random onset around early adulthood, is significant in its own right even if it doesn’t lead to a pharmaceutical intervention. It could help identify new risk factors, potential non-pharmaceutical interventions like life style changes, and maybe even identify people who are at risk of developing schizophrenia and preparing them for its onset before their first hallucination and avoiding a downward spiral.

Disproportionately many geeks have very strong opinions about psychiatry, probably because we have a lot of people who consider themselves neurodivergent, as well as plenty of folks who experiment with drugs.

Absolutely nothing strange about following research, and sharing and discussing has nothing to do with elevating.

What is actually weird is how often users here makes it an issue when research papers on novel drugs are shared here.

Given how debilitating schizophrenia can be, and how compromised the current treatments are - hey, you don't mind making uncontrollable strange expressions on your face forever, do you? - things like this give hope, even if it's just a little bit.

You are right: it is, thankfully, no longer extraordinary on a per-biomarker basis.

As yet another step in mapping the space of biomarkers for diseases, it is noteworthy and worth a thumbs-up somewhere in the universe.

Why is it noteworthy on HN? I think it is because HN likes optimistic stories about scientific progress on lots of dimensions.

I find this very suspect that a biomarker for schizophrenia is found before "black" gene/biomarker is found. It sounds like a setup for mass gaslighting and institutionalization by big pharma. Society is always looking for an easy way to institutionalize people it doesn't agree with. This is the big tech version.

Interesting... too bad it requires a spinal tap, not a super fun test to get.

I don't have schizophrenia so I don't speak from personal experience, but it sounds bad enough that a spinal tap is worth the diagnosis and potential relief.

Sure, but any test that requires something painful like a spinal tap requires someone to already be in a dire state. What I mean is if it could be done through a blood test prevention would be much easier to test for without needing to have a severe episode first.

Approximately half of the people with schizophrenia don’t believe they are ill, which is why they refuse treatment (see: anosognosia). It is a very strange illness.

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