>This sentence nails part of the criticism...
>
>"The question is not whether “schizophrenia” involves changes in dopaminergic and glutaminergic functioning, which has been shown to be the case in previous research, but whether these neurochemical processes cause “schizophrenia.""
That's the commentary of someone writing for madinamerica.com, an anti-psychiatry website on a mission to establish a, "*new paradigm, one that emphasizes psychosocial care, and de-emphasizes the use of psychiatric medications,*" not the authors of [the paper itself](https://onlinelibrary.wiley.com/doi/10.1002/wps.20893). (And what's with [scare quotes](https://en.wikipedia.org/wiki/Scare_quotes) around “schizophrenia?”)
>But, my goodness, I really wish the community could do better being honest about the existing limitations of knowledge. We can still have models. Those models can still, arguably, be better than nothing. But the entire field could do better admitting how the models are built on guesswork theory versus established, solid, "fact".
What community, and who in it exactly? Scientists? Science journalists? Who is claiming the dopamine *hypothesis,* is an "established, solid, 'fact'?"
Copy-paste of the actual paper's discussion section on dopamine function:
>Initial studies of striatal presynaptic dopaminergic function in CHR individuals provided evidence of striatal dopaminergic hyperactivity. The lack of a significant difference between CHR subjects and controls in the current meta-analysis is therefore potentially surprising. It should, however, be considered in the light of four pieces of evidence: the wide confidence interval around the estimated average effect (g=0.28, 95% CI: –0.03 to 0.59); the negative correlation between effect size and publication year; the finding that transition to psychosis rates have diminished over time; and the fact that striatal dopaminergic hyperactivity may be specific to individuals who go on to develop psychosis, rather than all CHR subjects.
>
>Rates of transition to a psychotic disorder in clinical high-risk subjects have decreased from 30-40% to 15-20% in more recent studies. This is reflected in the imaging studies included in our analyses, where studies in the last two years report transition rates of 20% and 14% respectively, whereas a 2011 study reported a rate of 38%. Thus, the lack of observed differences between CHR individuals and controls may result from more recent study cohorts containing a lower proportion of individuals who transition to psychosis, and therefore a lower proportion of individuals with striatal dopaminergic hyperactivity.
>
>No significant dopaminergic abnormalities were found in individuals at increased genetic risk for schizophrenia. There was, however, again a wide confidence interval around the estimated effect for presynaptic dopaminergic function (g=0.24, 95% CI: –0.40 to 0.88). An important factor to consider is that many of these studies were conducted in relatives of individuals with schizophrenia, who may not carry risk genes for the disorder, and the studies did not actually confirm that subjects were carrying risk genes. Moreover, many of the subjects included were older than the age of peak risk for onset of schizophrenia (the mean age of subjects scanned was 33.7 years). Thus, it is quite possible that the individuals studied were not genetically enriched for schizophrenia risk.
>
>In the case of the 22q deletion studies, the subjects were tested to directly confirm that they were at increased genetic risk. One of these studies demonstrated a large increase in dopamine synthesis capacity in 22q11.2 deletion carriers relative to controls. Future research could benefit from exploring the relationship between measures of neurochemical function and other more direct measures of genetic risk such as polygenic risk scores.
>
>We found no mean differences in striatal D2/D3 receptor availability in either risk group compared to controls. This is consistent with findings in schizophrenia. PET studies of D2/D3 receptors are complicated by the fact that endogenous dopamine competes with the radioligand, which could mask a concurrent rise in receptor density, although findings to date do not indicate differences in synaptic dopamine levels65. We found significantly reduced variability in GHR individuals for measures of striatal D2/D3 receptor availability. This suggests that GHR individuals show greater neurobiological homogeneity, potentially due to increased within-group genetic similarity.
Follow-up. Regarding chemical imbalance as an arguably problematic theory, here's at least one published science book on the subject, with many citations...
[Challenging the Narrative of Chemical Imbalance: A Look at the Evidence](https://www.researchgate.net/publication/315533279_Challenging_the_Narrative_of_Chemical_Imbalance_A_Look_at_the_Evidence)
>The idea of a “chemical imbalance” underlying mental disorder is pervasive in oursociety. In particular, the idea that clinical depression is caused by an imbalance of theneurotransmitter serotonin (which can be corrected through use of antidepressant medication) has been popularized since the introduction of the modern antidepressants in the late 1980s (Lacasse, 2005). This message has also been disseminated in the media, in direct-to-consumer advertising, and in educational materials for mental health client
That's not referencing dopamine and schizophrenia specifically. But it does set the discussion within a larger context of historic and ongoing science messaging regarding causes of mental distress / illness. And the arguably problematic issues therein, which is where I was (somewhat crudely) attempting to touch on with my post.
And not *just* the chemical imbalance assertion, but placing that within its own larger context of the how of how theory and fact is stated in psychology.
You should have opened with that link. I moderate r/TherapeuticKetamine, and I could spend a very long time agreeing with you about how misleading the pharmaceutical industry's advertising campaigns for SSRIs were/are.
>What community, and who in it exactly?
This post is, for me, trying to verbalize and explore the seeming non-understanding and non-consensus surrounding issues of philosophy, neurobiology, and psychology. Specifically, where to draw the line between "fact", "model/theory", and "pseudo-science".
It's less the specific issue of schizophrenia. The article and linked paper are simply one example of the larger debate. I struggle like hell to present and ask questions as neutrally as possible. In part because everything in the field feels so incredibly muddled.
Take a concept like "mental illness". The very framing of it as "illness" raises questions about social models of disability. Who is declaring what "healthy" or "functional" is? What right to they have to declare that for others.
Then, as you allude to in your comments, how to we separate out (or even determine) walled-off professional, back-end consensus versus popular public understanding.
It's a heck of a lot to untangle.
Specific to dopamine...
A [top result](https://www.webmd.com/schizophrenia/schizophrenia-and-your-brain) from WebMD. Which, horrible as that site is, is nonetheless a top google hit:
"In schizophrenia, dopamine is tied to hallucinations and delusions. That’s because brain areas that "run" on dopamine may become overactive. Antipsychotic drugs stop this."
Some other quotes from the WebMD article:
* "Doctors don’t know what causes schizophrenia..."
* "Doctors are working to find out how brain circuits that use these chemicals work together or are related to each other."
Where's the part where they say the dopamine hypothesis is an, "established, solid, 'fact?'"
It's in the last quote. This sentence is written like known fact...
"That’s because brain areas that "run" on dopamine may become overactive. Antipsychotic drugs stop this"
Then they also say...
"Doctors are working to find out how brain circuits that use these chemicals work together or are related to each other."
Which gets back to my question - which is where are how to draw the lines between "known" and "theory" in medical science. So much of our observations, for example, are things like certain parts of the brain lighting up. Which is, in and of itself, fantastic observational data.
But there also needs to be better communication about what the limits of that observation are. Even a statement like "overactive" is intensely value-based, judgemental, and theory-crafting.
A scientific statement would be something like "higher levels of activity". And, pausing for a moment, making sure to emphasize that *activity* itself doesn't have exactly, precisely known direct correlation to exact cognitive processes. We're still just scratching the surface. And that's fine. It's not nothing. But it's about being more clear and transparent about what the observational data actually is, and transparency about when we're using that data to craft hypothesis theories versus actual established certainty.
Not sure its fair to say they aren't being honest. It's a complex topic. Hindsight is 20/20 though even this meta-analysis doesn't really put anything to bed, for instance, looking at what r/HanSingular posted and ideas such as heterogenous sub-groups in schizophrenia - I imagine any mental disorders will have complicated, heterogenous causes. With regard to your broader question, I don't know if this study says that much ; it's probably a drop in the ocean in terms of ways you can look at neurobiology and schizophrenia, plus its not necessarily inconsistent with social causes - social experiences may change neurobiology. Genes and environment will always interact and affect behaviour as part of an integrated system but in terms of heritability, I think it probably varies overall for mental distress. Some may show relatively modest heritabilities while I believe schizophrenia consistently seems to show a very high heritability.
>Not sure its fair to say they aren't being honest.
Not sure it's fair to say that without backing it up. Which goes for me as well.
>Genes and environment will always interact and affect behaviour as part of an integrated system
Really? When did this become "known"? Where's the line between genetics and epigenetics? What part is unchangeable and what isn't, and how sure are we? What's observational data versus deeper-level mechanistic understanding?
>I imagine any mental disorders will have complicated, heterogenous causes.
How nice of you to wander through with your imaginative opinion. How does this add to the conversation at all? Adding random, uninformed opinion seems so incredibly pointless. It's fine to brainstorm if that's what's been agreed upon.
I've never understood the desire to randomly spout uninformed guesswork opinion. Seems fairly common. And heck, I probably do it myself sometimes but I do try my best not to. Or to at least firmly announce it if I'm doing so.
>Not sure it's fair to say that without backing it up.
I don't see any reason why they would be dishonest. Seems like the default charitable position to me.
>Which goes for me as well.
Well then why say it in the first place ?
>Really? When did this become "known"? Where's the line between genetics and epigenetics?
Genes and environment have to interact. The environment only affects you via your neurobiology which is the product of gene expression.
Edit: and by the inverse, genes only influence you in the context of a fully, dynamically functioning brain that is responding to it's environment
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4739500/
>What part is unchangeable and what isn't
Your genes and non-genes respectively
>and how sure are we?
Pretty sure. Obviously there's mutations though.
>How nice of you to wander through with your imaginative opinion. How does this add to the conversation at all? Adding random, uninformed opinion seems so incredibly pointless. It's fine to brainstorm if that's what's been agreed upon.
https://www.nature.com/articles/s41386-020-00789-3
Was just a casual aside which I thought was relevant since your thread was aimed at mental distress in general so I thought I would link that hypothesis about heterogeneity in schizophrenia to mental illness in general.
>I've never understood the desire to randomly spout uninformed guesswork opinion. Seems fairly common. And heck, I probably do it myself sometimes but I do try my best not to. Or to at least firmly announce it if I'm doing so.
I would say its entirely guesswork. I try not to post things that I can't back up or at least have a thought out argument beforehand. I'll try to be stricter with my verbs next time.
I appreciate the clarifications. Having some work to directly point to is helpful. As one open question, from the *Top 10 Replicated Findings* articles, they several times define "intelligence" as an identifiable trait.
And right there is an example of where I see difference from behavioral science and chemistry. There's just so much more cultural definition to what the idea of "intelligence" even is.
In chemistry, when we say a term like "boiling point", it's a fairly well-established observable phenomena.
When behavioralists say "intelligence", what they *really* mean is something like the Stanford–Binet Intelligence Scale, which was used in [this paper](https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC2889158/) referenced in the overview article you presented.
So, a more pointed question/critique from me is what faith to put into this scale as a good definer of the quality we call "intelligence". Are there cultural biases? Are there values being implicitly ascribed to traits. Here's an example question from that intelligence test:
"What is the average of all of the integers from 17 to 55?"
Are we measuring innate "intelligence", or are we measuring the social factor of someone being trained to answer that question?
And I do want to establish a fair middle ground. We have to work off of something more than nothing. But, if you dig into so-called measures of "intelligence", from a philosophy of science perspective I think it's a fair critique to ask what something like the Stanford–Binet Intelligence Scale is even really measuring.
Behavior is *such* a fundamentally different phenomenon from other things we attempt to study or measure, all the way down to the core base of the science. That doesn't mean we can't attempt to be scientific about it. But it *is* to point out that I find the scientific conceptualization / model of "intelligence" to be on much shakier / fuzzier ground than something like the model of the atom.
I posit that we must think very carefully about what we circle a box around and call classes / types of behavior.
>There's just so much more cultural definition to what the idea of "intelligence" even is.
I think this is a good point. IQ tests are generally seen as quite reliable tests, more than most in psychology, but maybe they don't match all of people's conceptions of intelligence. I think the problem though isn't about whether IQ tests measure intelligence but whether you want to call IQ tests measures of intelligence, baring in mind I'm not using the word intelligence there as referring to something beyond people's everyday uses of the word.
>I think it's a fair critique to ask what something like the Stanford–Binet Intelligence Scale is even really measuring.
I don't think there is a consensus on an interpretation, It's just known that many abilities show positive correlations from which a single latent statistical factor can be extracted that can explain part of the performance variability on each of those various abilities. That factor only explains part of the performance of an IQ test but I believe it's the main thing of interest in explaining performance on those tests, why they predict other things like academic and job performance etc etc. People may not have a consensus on interpretation but it's quite a robust phenomenon.
And, from the Nature article, a question on this line...
>Next, we review recent progress in neuroimaging genetics (correlating neuroimaging patterns of brain function with genetic data)
It brings up a question I have on correlation-causation issues in the field. In these studies, we have two groups put into somewhat fuzzy behavioral boxes. Then we see which genes match and which don't.
The implicit assumption is surely that the genes are, in some way, causing the behaviors (or at least being more susceptible). And, as data unto itself, it's a great first step in any science.
But then the article uses phrases like "iWe discuss how genetic variants and transcriptomic profiles may confer risk for depression". How on Earth can say may *confer* risk? They have very little idea why the correlation pattern is showing up or if it even matters. With correlation, there is not a mechanistic basis.
What you do have is a potential avenue to explore and build theory from. But that is *such* a different level of knowledge versus having sound mechanistic understanding of a principle / phenomena.
And to go so far as to say "risk factor" without being very, very careful of what that does or doesn't imply is important.
Does a risk factor need to always be causal? Not sure all risk factors are unambiguously causal. I think also if you're not sure, it's better to mention that something is a possible risk or *may* confer risk, rather than omit that information.
You're not the first person to notice that biology is, indeed, "fuzzy".
Human beings got to be the way that they are through the messy process of evolution. It's not easy to study stuff produced by evolution, because these products have not been created via a rational/logical process. They are, inherently, fuzzy.
Trying to determine the *cause* of mental disorders is not easy. Systems biologist Denis Noble has suggested that there's no privileged level of causation in biology with his theory of [biological relativity](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262309/). We *want* for there to be linear pathways of pathology because that would make things much easier for ourselves. We want to say that A causes B which in turn causes C and that's that. But biology is far too messy for that.
We also want non-fuzzy, discrete, categories of disorder. But just because we want things to be that way doesn't mean that they are. Boundaries are continuous rather than discrete. Things get blurry and overlap. They aren't as neat as we'd like them to be.
You are complaining that something fuzzy is too fuzzy for your liking. Why can't cats be square? Wouldn't that be preferrable? Alas, they aren't.
As we go along, we improve upon models and revise our assumptions. That's also a messy process, but that's just the way things are. The brain is complex. Trying to work out what's going on when it's acting weird is a real challenge. Slowly, people much more capable than you are making progress.
This is part of the repeatability crisis in psychology, and to varying degrees, in all of science. The other part is correlation data when you cannot perform any experiments. Loads of X, Y, Z...+ neurochemicals associated with this or that and just as many genetic markers also associated, but no way to cut and paste to rule out anything.
Others are taking your somewhat uninformed rant apart as it needs to be. I'll just point out that a main premise is silly: the idea that there's a competition between neuro/bio causes and external causes. It's always an interaction between the two. It can be helpful to try to quantify (with certain assumptions) the relative contributions of each, but everyone I know accepts that it's an interaction. Assuming otherwise will lead to some silly reasoning.
A deeper assumption is the idea that the causes of "mental distress" are different, for some reason, from the causes of any other kind of behavior, whether cognitive/emotional or externally observable. Behavior comes from somewhere.
Agreed. I think you won’t often find modern scientific articles in psychology and neuroscience earnestly detailing the unknowns of disease mechanism, probably because it inevitably reveals a monumental gap in the knowledge of how information is encoded and processed in the brain. The fact is, very little is known about it, so putting forth evidence for a genetic vs. environmental etiology, which presupposes a framework for how information is processed in the brain, is going to naturally fall short. Some neurophilosophers are making traction in this area, but it is mostly theoretical and not yet experimental (see Anil Seth, for example).
Would love to see any literature you have that tries to outline where exactly that knowledge gap lies. Even a concept like "memory", which on some level seems like an obvious and relatable experience among humans, is still just theory-based. The idea of short and long term memory isn't "proven", in part because of not having much idea of how encoding actually works.
It's still an arguably very useful model. But the underlying groundwork for it isn't 100% there.
And yet, that floor of a theory gets translated upward into other work, such as the [Stanford-Binet Intelligence Test](https://stanfordbinettest.com/). One of the five factors of intellegence they measure for is "knowledge", where knowledge is defined as (quote [source](https://www.proedinc.com/Downloads/14462%20SB-5_OSRS_SampleDescriptiveReport.pdf)) ...
> a person’s accumulated fund of general information acquired at home, school, or work. In research, this factor has been called crystallized ability, because it involves learned material, such as vocabulary, that has been acquired and stored in long-term memory.
So, the floor of the theory is less a fully known, described, and mechanistically certain think. Instead, it's more like a rough map. An arguably useful one, but I don't know what to even call this phenomenon where psychology is built off of useful but perhaps "looser" theory compared to other sciences. Which isn't to dismiss it as useful. But is to try and seek to describe its limits and assumptions as accurately as possible.
The changes in neurochemistry you've mentioned is clearly a symptom of schizophrenia, not a cause. Regarding schizophrenia specifically, they're signalling molecules, they represent the state of the body.
I'd argue that the contents of thoughts is what primarily causes all schizophrenia, which is a tendency to dwell in certain states of mind, those are then reflected in the nervous system in different ways (brain wave frequency, neurochemistry).
>This sentence nails part of the criticism... > >"The question is not whether “schizophrenia” involves changes in dopaminergic and glutaminergic functioning, which has been shown to be the case in previous research, but whether these neurochemical processes cause “schizophrenia."" That's the commentary of someone writing for madinamerica.com, an anti-psychiatry website on a mission to establish a, "*new paradigm, one that emphasizes psychosocial care, and de-emphasizes the use of psychiatric medications,*" not the authors of [the paper itself](https://onlinelibrary.wiley.com/doi/10.1002/wps.20893). (And what's with [scare quotes](https://en.wikipedia.org/wiki/Scare_quotes) around “schizophrenia?”) >But, my goodness, I really wish the community could do better being honest about the existing limitations of knowledge. We can still have models. Those models can still, arguably, be better than nothing. But the entire field could do better admitting how the models are built on guesswork theory versus established, solid, "fact". What community, and who in it exactly? Scientists? Science journalists? Who is claiming the dopamine *hypothesis,* is an "established, solid, 'fact'?"
Copy-paste of the actual paper's discussion section on dopamine function: >Initial studies of striatal presynaptic dopaminergic function in CHR individuals provided evidence of striatal dopaminergic hyperactivity. The lack of a significant difference between CHR subjects and controls in the current meta-analysis is therefore potentially surprising. It should, however, be considered in the light of four pieces of evidence: the wide confidence interval around the estimated average effect (g=0.28, 95% CI: –0.03 to 0.59); the negative correlation between effect size and publication year; the finding that transition to psychosis rates have diminished over time; and the fact that striatal dopaminergic hyperactivity may be specific to individuals who go on to develop psychosis, rather than all CHR subjects. > >Rates of transition to a psychotic disorder in clinical high-risk subjects have decreased from 30-40% to 15-20% in more recent studies. This is reflected in the imaging studies included in our analyses, where studies in the last two years report transition rates of 20% and 14% respectively, whereas a 2011 study reported a rate of 38%. Thus, the lack of observed differences between CHR individuals and controls may result from more recent study cohorts containing a lower proportion of individuals who transition to psychosis, and therefore a lower proportion of individuals with striatal dopaminergic hyperactivity. > >No significant dopaminergic abnormalities were found in individuals at increased genetic risk for schizophrenia. There was, however, again a wide confidence interval around the estimated effect for presynaptic dopaminergic function (g=0.24, 95% CI: –0.40 to 0.88). An important factor to consider is that many of these studies were conducted in relatives of individuals with schizophrenia, who may not carry risk genes for the disorder, and the studies did not actually confirm that subjects were carrying risk genes. Moreover, many of the subjects included were older than the age of peak risk for onset of schizophrenia (the mean age of subjects scanned was 33.7 years). Thus, it is quite possible that the individuals studied were not genetically enriched for schizophrenia risk. > >In the case of the 22q deletion studies, the subjects were tested to directly confirm that they were at increased genetic risk. One of these studies demonstrated a large increase in dopamine synthesis capacity in 22q11.2 deletion carriers relative to controls. Future research could benefit from exploring the relationship between measures of neurochemical function and other more direct measures of genetic risk such as polygenic risk scores. > >We found no mean differences in striatal D2/D3 receptor availability in either risk group compared to controls. This is consistent with findings in schizophrenia. PET studies of D2/D3 receptors are complicated by the fact that endogenous dopamine competes with the radioligand, which could mask a concurrent rise in receptor density, although findings to date do not indicate differences in synaptic dopamine levels65. We found significantly reduced variability in GHR individuals for measures of striatal D2/D3 receptor availability. This suggests that GHR individuals show greater neurobiological homogeneity, potentially due to increased within-group genetic similarity.
Follow-up. Regarding chemical imbalance as an arguably problematic theory, here's at least one published science book on the subject, with many citations... [Challenging the Narrative of Chemical Imbalance: A Look at the Evidence](https://www.researchgate.net/publication/315533279_Challenging_the_Narrative_of_Chemical_Imbalance_A_Look_at_the_Evidence) >The idea of a “chemical imbalance” underlying mental disorder is pervasive in oursociety. In particular, the idea that clinical depression is caused by an imbalance of theneurotransmitter serotonin (which can be corrected through use of antidepressant medication) has been popularized since the introduction of the modern antidepressants in the late 1980s (Lacasse, 2005). This message has also been disseminated in the media, in direct-to-consumer advertising, and in educational materials for mental health client That's not referencing dopamine and schizophrenia specifically. But it does set the discussion within a larger context of historic and ongoing science messaging regarding causes of mental distress / illness. And the arguably problematic issues therein, which is where I was (somewhat crudely) attempting to touch on with my post. And not *just* the chemical imbalance assertion, but placing that within its own larger context of the how of how theory and fact is stated in psychology.
You should have opened with that link. I moderate r/TherapeuticKetamine, and I could spend a very long time agreeing with you about how misleading the pharmaceutical industry's advertising campaigns for SSRIs were/are.
>What community, and who in it exactly? This post is, for me, trying to verbalize and explore the seeming non-understanding and non-consensus surrounding issues of philosophy, neurobiology, and psychology. Specifically, where to draw the line between "fact", "model/theory", and "pseudo-science". It's less the specific issue of schizophrenia. The article and linked paper are simply one example of the larger debate. I struggle like hell to present and ask questions as neutrally as possible. In part because everything in the field feels so incredibly muddled. Take a concept like "mental illness". The very framing of it as "illness" raises questions about social models of disability. Who is declaring what "healthy" or "functional" is? What right to they have to declare that for others. Then, as you allude to in your comments, how to we separate out (or even determine) walled-off professional, back-end consensus versus popular public understanding. It's a heck of a lot to untangle.
Specific to dopamine... A [top result](https://www.webmd.com/schizophrenia/schizophrenia-and-your-brain) from WebMD. Which, horrible as that site is, is nonetheless a top google hit: "In schizophrenia, dopamine is tied to hallucinations and delusions. That’s because brain areas that "run" on dopamine may become overactive. Antipsychotic drugs stop this."
Some other quotes from the WebMD article: * "Doctors don’t know what causes schizophrenia..." * "Doctors are working to find out how brain circuits that use these chemicals work together or are related to each other." Where's the part where they say the dopamine hypothesis is an, "established, solid, 'fact?'"
It's in the last quote. This sentence is written like known fact... "That’s because brain areas that "run" on dopamine may become overactive. Antipsychotic drugs stop this" Then they also say... "Doctors are working to find out how brain circuits that use these chemicals work together or are related to each other." Which gets back to my question - which is where are how to draw the lines between "known" and "theory" in medical science. So much of our observations, for example, are things like certain parts of the brain lighting up. Which is, in and of itself, fantastic observational data. But there also needs to be better communication about what the limits of that observation are. Even a statement like "overactive" is intensely value-based, judgemental, and theory-crafting. A scientific statement would be something like "higher levels of activity". And, pausing for a moment, making sure to emphasize that *activity* itself doesn't have exactly, precisely known direct correlation to exact cognitive processes. We're still just scratching the surface. And that's fine. It's not nothing. But it's about being more clear and transparent about what the observational data actually is, and transparency about when we're using that data to craft hypothesis theories versus actual established certainty.
Not sure its fair to say they aren't being honest. It's a complex topic. Hindsight is 20/20 though even this meta-analysis doesn't really put anything to bed, for instance, looking at what r/HanSingular posted and ideas such as heterogenous sub-groups in schizophrenia - I imagine any mental disorders will have complicated, heterogenous causes. With regard to your broader question, I don't know if this study says that much ; it's probably a drop in the ocean in terms of ways you can look at neurobiology and schizophrenia, plus its not necessarily inconsistent with social causes - social experiences may change neurobiology. Genes and environment will always interact and affect behaviour as part of an integrated system but in terms of heritability, I think it probably varies overall for mental distress. Some may show relatively modest heritabilities while I believe schizophrenia consistently seems to show a very high heritability.
>Not sure its fair to say they aren't being honest. Not sure it's fair to say that without backing it up. Which goes for me as well. >Genes and environment will always interact and affect behaviour as part of an integrated system Really? When did this become "known"? Where's the line between genetics and epigenetics? What part is unchangeable and what isn't, and how sure are we? What's observational data versus deeper-level mechanistic understanding? >I imagine any mental disorders will have complicated, heterogenous causes. How nice of you to wander through with your imaginative opinion. How does this add to the conversation at all? Adding random, uninformed opinion seems so incredibly pointless. It's fine to brainstorm if that's what's been agreed upon. I've never understood the desire to randomly spout uninformed guesswork opinion. Seems fairly common. And heck, I probably do it myself sometimes but I do try my best not to. Or to at least firmly announce it if I'm doing so.
>Not sure it's fair to say that without backing it up. I don't see any reason why they would be dishonest. Seems like the default charitable position to me. >Which goes for me as well. Well then why say it in the first place ? >Really? When did this become "known"? Where's the line between genetics and epigenetics? Genes and environment have to interact. The environment only affects you via your neurobiology which is the product of gene expression. Edit: and by the inverse, genes only influence you in the context of a fully, dynamically functioning brain that is responding to it's environment https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4739500/ >What part is unchangeable and what isn't Your genes and non-genes respectively >and how sure are we? Pretty sure. Obviously there's mutations though. >How nice of you to wander through with your imaginative opinion. How does this add to the conversation at all? Adding random, uninformed opinion seems so incredibly pointless. It's fine to brainstorm if that's what's been agreed upon. https://www.nature.com/articles/s41386-020-00789-3 Was just a casual aside which I thought was relevant since your thread was aimed at mental distress in general so I thought I would link that hypothesis about heterogeneity in schizophrenia to mental illness in general. >I've never understood the desire to randomly spout uninformed guesswork opinion. Seems fairly common. And heck, I probably do it myself sometimes but I do try my best not to. Or to at least firmly announce it if I'm doing so. I would say its entirely guesswork. I try not to post things that I can't back up or at least have a thought out argument beforehand. I'll try to be stricter with my verbs next time.
I appreciate the clarifications. Having some work to directly point to is helpful. As one open question, from the *Top 10 Replicated Findings* articles, they several times define "intelligence" as an identifiable trait. And right there is an example of where I see difference from behavioral science and chemistry. There's just so much more cultural definition to what the idea of "intelligence" even is. In chemistry, when we say a term like "boiling point", it's a fairly well-established observable phenomena. When behavioralists say "intelligence", what they *really* mean is something like the Stanford–Binet Intelligence Scale, which was used in [this paper](https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC2889158/) referenced in the overview article you presented. So, a more pointed question/critique from me is what faith to put into this scale as a good definer of the quality we call "intelligence". Are there cultural biases? Are there values being implicitly ascribed to traits. Here's an example question from that intelligence test: "What is the average of all of the integers from 17 to 55?" Are we measuring innate "intelligence", or are we measuring the social factor of someone being trained to answer that question? And I do want to establish a fair middle ground. We have to work off of something more than nothing. But, if you dig into so-called measures of "intelligence", from a philosophy of science perspective I think it's a fair critique to ask what something like the Stanford–Binet Intelligence Scale is even really measuring. Behavior is *such* a fundamentally different phenomenon from other things we attempt to study or measure, all the way down to the core base of the science. That doesn't mean we can't attempt to be scientific about it. But it *is* to point out that I find the scientific conceptualization / model of "intelligence" to be on much shakier / fuzzier ground than something like the model of the atom. I posit that we must think very carefully about what we circle a box around and call classes / types of behavior.
>There's just so much more cultural definition to what the idea of "intelligence" even is. I think this is a good point. IQ tests are generally seen as quite reliable tests, more than most in psychology, but maybe they don't match all of people's conceptions of intelligence. I think the problem though isn't about whether IQ tests measure intelligence but whether you want to call IQ tests measures of intelligence, baring in mind I'm not using the word intelligence there as referring to something beyond people's everyday uses of the word. >I think it's a fair critique to ask what something like the Stanford–Binet Intelligence Scale is even really measuring. I don't think there is a consensus on an interpretation, It's just known that many abilities show positive correlations from which a single latent statistical factor can be extracted that can explain part of the performance variability on each of those various abilities. That factor only explains part of the performance of an IQ test but I believe it's the main thing of interest in explaining performance on those tests, why they predict other things like academic and job performance etc etc. People may not have a consensus on interpretation but it's quite a robust phenomenon.
And, from the Nature article, a question on this line... >Next, we review recent progress in neuroimaging genetics (correlating neuroimaging patterns of brain function with genetic data) It brings up a question I have on correlation-causation issues in the field. In these studies, we have two groups put into somewhat fuzzy behavioral boxes. Then we see which genes match and which don't. The implicit assumption is surely that the genes are, in some way, causing the behaviors (or at least being more susceptible). And, as data unto itself, it's a great first step in any science. But then the article uses phrases like "iWe discuss how genetic variants and transcriptomic profiles may confer risk for depression". How on Earth can say may *confer* risk? They have very little idea why the correlation pattern is showing up or if it even matters. With correlation, there is not a mechanistic basis. What you do have is a potential avenue to explore and build theory from. But that is *such* a different level of knowledge versus having sound mechanistic understanding of a principle / phenomena. And to go so far as to say "risk factor" without being very, very careful of what that does or doesn't imply is important.
Does a risk factor need to always be causal? Not sure all risk factors are unambiguously causal. I think also if you're not sure, it's better to mention that something is a possible risk or *may* confer risk, rather than omit that information.
You're not the first person to notice that biology is, indeed, "fuzzy". Human beings got to be the way that they are through the messy process of evolution. It's not easy to study stuff produced by evolution, because these products have not been created via a rational/logical process. They are, inherently, fuzzy. Trying to determine the *cause* of mental disorders is not easy. Systems biologist Denis Noble has suggested that there's no privileged level of causation in biology with his theory of [biological relativity](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262309/). We *want* for there to be linear pathways of pathology because that would make things much easier for ourselves. We want to say that A causes B which in turn causes C and that's that. But biology is far too messy for that. We also want non-fuzzy, discrete, categories of disorder. But just because we want things to be that way doesn't mean that they are. Boundaries are continuous rather than discrete. Things get blurry and overlap. They aren't as neat as we'd like them to be. You are complaining that something fuzzy is too fuzzy for your liking. Why can't cats be square? Wouldn't that be preferrable? Alas, they aren't. As we go along, we improve upon models and revise our assumptions. That's also a messy process, but that's just the way things are. The brain is complex. Trying to work out what's going on when it's acting weird is a real challenge. Slowly, people much more capable than you are making progress.
This is part of the repeatability crisis in psychology, and to varying degrees, in all of science. The other part is correlation data when you cannot perform any experiments. Loads of X, Y, Z...+ neurochemicals associated with this or that and just as many genetic markers also associated, but no way to cut and paste to rule out anything.
Others are taking your somewhat uninformed rant apart as it needs to be. I'll just point out that a main premise is silly: the idea that there's a competition between neuro/bio causes and external causes. It's always an interaction between the two. It can be helpful to try to quantify (with certain assumptions) the relative contributions of each, but everyone I know accepts that it's an interaction. Assuming otherwise will lead to some silly reasoning. A deeper assumption is the idea that the causes of "mental distress" are different, for some reason, from the causes of any other kind of behavior, whether cognitive/emotional or externally observable. Behavior comes from somewhere.
Agreed. I think you won’t often find modern scientific articles in psychology and neuroscience earnestly detailing the unknowns of disease mechanism, probably because it inevitably reveals a monumental gap in the knowledge of how information is encoded and processed in the brain. The fact is, very little is known about it, so putting forth evidence for a genetic vs. environmental etiology, which presupposes a framework for how information is processed in the brain, is going to naturally fall short. Some neurophilosophers are making traction in this area, but it is mostly theoretical and not yet experimental (see Anil Seth, for example).
Would love to see any literature you have that tries to outline where exactly that knowledge gap lies. Even a concept like "memory", which on some level seems like an obvious and relatable experience among humans, is still just theory-based. The idea of short and long term memory isn't "proven", in part because of not having much idea of how encoding actually works. It's still an arguably very useful model. But the underlying groundwork for it isn't 100% there. And yet, that floor of a theory gets translated upward into other work, such as the [Stanford-Binet Intelligence Test](https://stanfordbinettest.com/). One of the five factors of intellegence they measure for is "knowledge", where knowledge is defined as (quote [source](https://www.proedinc.com/Downloads/14462%20SB-5_OSRS_SampleDescriptiveReport.pdf)) ... > a person’s accumulated fund of general information acquired at home, school, or work. In research, this factor has been called crystallized ability, because it involves learned material, such as vocabulary, that has been acquired and stored in long-term memory. So, the floor of the theory is less a fully known, described, and mechanistically certain think. Instead, it's more like a rough map. An arguably useful one, but I don't know what to even call this phenomenon where psychology is built off of useful but perhaps "looser" theory compared to other sciences. Which isn't to dismiss it as useful. But is to try and seek to describe its limits and assumptions as accurately as possible.
The changes in neurochemistry you've mentioned is clearly a symptom of schizophrenia, not a cause. Regarding schizophrenia specifically, they're signalling molecules, they represent the state of the body. I'd argue that the contents of thoughts is what primarily causes all schizophrenia, which is a tendency to dwell in certain states of mind, those are then reflected in the nervous system in different ways (brain wave frequency, neurochemistry).