For functional studies, be they fluorodeoxyglucose positron emission tomography (FDG PET), rs-fMRI, task-based fMRI, diffusion tensor imaging (DTI) or MEG there generally is hypoactivation and disconnection between brain regions. …
Histologically this gray matter reduction is accompanied by dendritic and synaptic density decreases which likely signals a lack of communication (disconnection theory) across selected neural networks…
According to Orliac et al. (2013), patients with schizophrenia have reduced functional connectivity in the default mode network and salience network. Furthermore, decreased connectivity in the paracingulate cortex is associated with difficulties with abstract thought, whereas decreased connectivity in the left striatum is associated with delusions and depression. Longer memory response time for face recognition was also associated with functional connectivity abnormalities in early-schizophrenia, centered in the anterior cingulate...
This is in line with the frontotemporoparietal network disruption theory in schizophrenia that is well-known (Friston and Frith, 1995). …
In a study that conducted by Lottman et al., patients with schizophrenia showed an increased connectivity between auditory and subcortical networks …
Both increased and decreased functional connectivity has been observed in patients with schizophrenia vs. controls, in resting state and during various tasks
Mondino et al. (2016) found that transcranial direct current stimulation can decrease negative symptoms course and the severity of auditory verbal hallucination in patients with schizophrenia. This improvement was associated with reduction in functional connectivity between the left anterior insula and left temporoparietal junction (middle and superior temporal gyri and Wernicke’s area)
Overall I think it’s pretty complicated. I imagine that when you wrote explaining “everything” was tongue in cheek, but I think there are a lot of things that need to be explained about schizophrenia beyond the seven that you wrote about. I hope you keep doing some research in this area and continue to refine your theory.
I imagine that when you wrote explaining “everything” was tongue in cheek
Sorta. I kinda feel like my hypothesis (or something very close to it) really is an elegant explanation for everything about schizophrenia. Of course, I don’t know that—among other things, I don’t know everything about schizophrenia (obviously). I was writing this partly in the hopes that you or other commenters would tell me about aspects of schizophrenia that my hypothesis can’t explain, or contradicts, if such aspects exist. And then I can drop that hypothesis and find something better to believe. :)
Do you think that anything in your excerpt contradicts my hypothesis? Seems to be almost entirely decreases in connectivity, right?
That said, I don’t put much stock in functional connectivity comparisons anyway—e.g. you don’t really know if those regions are talking directly to each other vs correlated for some other reason, and even leaving that aside, you can’t disentangle what control-vs-SCZ difference is caused by direct physical connectivity differences versus “when schizophrenics are hanging out in the fMRI machine their wandering minds tend to be thinking about different things than when the control group people are hanging out in the fMRI machine”, or whatever.
[I very generally find it quite hard to learn anything useful from neuroimaging data, compared to most other types of neuroscience data / evidence. But maybe that’s just me. You do you. :-) ]
A lot of the quotes do find decreased connectivity, but some of them find increased connectivity between certain regions. It makes me think that there’s a probability there might be something more complicated than just “increased or decreased”, but rather specific types of connections. But that’s just a guess, and I think an explanation across all cortical connections is more parsimonious and therefore more likely a priori.
Of your criteria of “things to explain”, here are some thoughts:
4.1 The onset of schizophrenia is typically in the late-teens-to-twenties, 4.2 Positive symptoms—auditory hallucinations (hearing voices), “distortions of self-experience”, etc. 4.3 Negative symptoms—yes these are all critical to explain.
4.4 Creativity—hm, this is tricky and probably needs to be contextualized. Some people disagree that schizophrenia is associated with increased creativity in relatives, although I personally agree with it. I don’t think it’s a core aspect.
4.5 Anticorrelation with autism—I don’t think this is a core aspect. I’m not even sure it’s true.
4.6 Relation to myelination—I think this is likely true, but I think it’s too low level to call a core aspect of the disease per se. I agree with your point about two terms always yielding search results, this is true of Alzheimer’s disease as well.
4.7 Schizophrenia and blindness—I don’t think this is a core aspect, I agree with you it’s probably not true.
Other core aspects I think should be explained:
1. Specific types of gene pathways that are altered in people with schizophrenia being related to the development/function of whatever the physiologic thing being hypothesized is. Genetics are causal, so this is usually pretty helpful, albeit quite complex.
2. Cognitive deficits: These include impairments in executive function, working memory, and other cognitive domains. These are usually considered distinct from negative symptoms (anhedonia, blunted affect, etc), and usually involve a decline from functioning premorbid/earlier in life.
3. Why nicotine is helpful.
4. Why antipsychotics/neuroleptics seem to be helpful (at least in certain circumstances).
5. Why there is so much variability in the disorder? Why do some people end up with predominantly delusions, hallucinations, or negative symptoms as the core part of their experience with schizophrenia?
Just some thoughts. As I said, I’m glad you’re focused on this!
LOL I’m not focused on this at all. I think I’ve spent a whopping four days of my life thinking hard about schizophrenia—one day in 2021 that didn’t go anywhere, one day last summer where I read a bunch of papers and thought of this hypothesis and felt pretty good about it and then moved on to other things, then one more day like a week later to research and write the blindness + schizophrenia post, and yesterday to write this post. Schizophrenia not a significant personal or professional interest of mine. I am very impressed with myself for fooling you. Or maybe you’re just being polite. :)
(Understanding schizophrenia is plausibly indirectly helpful for my professional interests, for various reasons. Also, I have a rule-of-thumb that if I can write a decent blog post in four hours, I should just do it, often it leads to unexpected good things!)
Yeah the “things to explain” could have been more accurately titled “aspects of schizophrenia that I can easily think of right now, from either off the top of my head or skimming the wikipedia article”. :-P
I think the cognitive deficits are very straightforwardly and naturally predicted by my hypothesis.
I wrote something about nicotine but a different commenter said that what I wrote was flagrantly wrong. (I put a warning in the OP.) Guess I need to think about that more. Honestly, I don’t have a great understanding of what nicotine does to the brain in the first place. Something something acetylcholine :-P
I haven’t looked into antipsychotics / neuroleptics, and agree that doing so would be an obvious next step, and indeed maybe I should have done it before posting this. Sorry. I’ll put it on my to-do list.
Interesting, thanks. All makes sense and no need to apologize. I just like it when people write/think about schizophrenia and want to encourage it, even as a side project. IMO, it’s a very important thing for our society to think about.
Interesting theory and very important topic.
I think the best data source here is probably neuroimaging. Here’s a recent review: https://www.frontiersin.org/articles/10.3389/fnins.2022.1042814/full. Here are some quotes from that:
Overall I think it’s pretty complicated. I imagine that when you wrote explaining “everything” was tongue in cheek, but I think there are a lot of things that need to be explained about schizophrenia beyond the seven that you wrote about. I hope you keep doing some research in this area and continue to refine your theory.
Thanks!
Sorta. I kinda feel like my hypothesis (or something very close to it) really is an elegant explanation for everything about schizophrenia. Of course, I don’t know that—among other things, I don’t know everything about schizophrenia (obviously). I was writing this partly in the hopes that you or other commenters would tell me about aspects of schizophrenia that my hypothesis can’t explain, or contradicts, if such aspects exist. And then I can drop that hypothesis and find something better to believe. :)
Do you think that anything in your excerpt contradicts my hypothesis? Seems to be almost entirely decreases in connectivity, right?
That said, I don’t put much stock in functional connectivity comparisons anyway—e.g. you don’t really know if those regions are talking directly to each other vs correlated for some other reason, and even leaving that aside, you can’t disentangle what control-vs-SCZ difference is caused by direct physical connectivity differences versus “when schizophrenics are hanging out in the fMRI machine their wandering minds tend to be thinking about different things than when the control group people are hanging out in the fMRI machine”, or whatever.
[I very generally find it quite hard to learn anything useful from neuroimaging data, compared to most other types of neuroscience data / evidence. But maybe that’s just me. You do you. :-) ]
A lot of the quotes do find decreased connectivity, but some of them find increased connectivity between certain regions. It makes me think that there’s a probability there might be something more complicated than just “increased or decreased”, but rather specific types of connections. But that’s just a guess, and I think an explanation across all cortical connections is more parsimonious and therefore more likely a priori.
Of your criteria of “things to explain”, here are some thoughts:
4.1 The onset of schizophrenia is typically in the late-teens-to-twenties, 4.2 Positive symptoms—auditory hallucinations (hearing voices), “distortions of self-experience”, etc. 4.3 Negative symptoms—yes these are all critical to explain.
4.4 Creativity—hm, this is tricky and probably needs to be contextualized. Some people disagree that schizophrenia is associated with increased creativity in relatives, although I personally agree with it. I don’t think it’s a core aspect.
4.5 Anticorrelation with autism—I don’t think this is a core aspect. I’m not even sure it’s true.
4.6 Relation to myelination—I think this is likely true, but I think it’s too low level to call a core aspect of the disease per se. I agree with your point about two terms always yielding search results, this is true of Alzheimer’s disease as well.
4.7 Schizophrenia and blindness—I don’t think this is a core aspect, I agree with you it’s probably not true.
Other core aspects I think should be explained:
1. Specific types of gene pathways that are altered in people with schizophrenia being related to the development/function of whatever the physiologic thing being hypothesized is. Genetics are causal, so this is usually pretty helpful, albeit quite complex.
2. Cognitive deficits: These include impairments in executive function, working memory, and other cognitive domains. These are usually considered distinct from negative symptoms (anhedonia, blunted affect, etc), and usually involve a decline from functioning premorbid/earlier in life.
3. Why nicotine is helpful.
4. Why antipsychotics/neuroleptics seem to be helpful (at least in certain circumstances).
5. Why there is so much variability in the disorder? Why do some people end up with predominantly delusions, hallucinations, or negative symptoms as the core part of their experience with schizophrenia?
Just some thoughts. As I said, I’m glad you’re focused on this!
Update: there’s some discussion of antipsychotics in my follow-up post: Model of psychosis, take 2 :)
LOL I’m not focused on this at all. I think I’ve spent a whopping four days of my life thinking hard about schizophrenia—one day in 2021 that didn’t go anywhere, one day last summer where I read a bunch of papers and thought of this hypothesis and felt pretty good about it and then moved on to other things, then one more day like a week later to research and write the blindness + schizophrenia post, and yesterday to write this post. Schizophrenia not a significant personal or professional interest of mine. I am very impressed with myself for fooling you. Or maybe you’re just being polite. :)
(Understanding schizophrenia is plausibly indirectly helpful for my professional interests, for various reasons. Also, I have a rule-of-thumb that if I can write a decent blog post in four hours, I should just do it, often it leads to unexpected good things!)
Yeah the “things to explain” could have been more accurately titled “aspects of schizophrenia that I can easily think of right now, from either off the top of my head or skimming the wikipedia article”. :-P
I think the cognitive deficits are very straightforwardly and naturally predicted by my hypothesis.
I wrote something about nicotine but a different commenter said that what I wrote was flagrantly wrong. (I put a warning in the OP.) Guess I need to think about that more. Honestly, I don’t have a great understanding of what nicotine does to the brain in the first place. Something something acetylcholine :-P
I haven’t looked into antipsychotics / neuroleptics, and agree that doing so would be an obvious next step, and indeed maybe I should have done it before posting this. Sorry. I’ll put it on my to-do list.
Interesting, thanks. All makes sense and no need to apologize. I just like it when people write/think about schizophrenia and want to encourage it, even as a side project. IMO, it’s a very important thing for our society to think about.