He briefly reviews two common arguments about whether
psychiatric disorders are brain diseases.
The first Cartesian dualism that a mind emerges from the brain
and is not the same as a brain. Since a brain is necessary for all mental
phenomenon there is no specific answer to the question about whether the
phenomenon observed with psychiatric disorders are diseases. The second common argument is that grossly
detectable brain diseases (lesions at autopsy and sophisticated
imaging) eventually became the purview
of neurology. To complement Kendler’s commentary,
I would add that this has never been strictly true since both overt lesions and
physiological brain dysfunction has always been studied by psychiatrists. It has been a common antipsychiatry argument
advanced by Szasz and others based on 19th century concepts. Ron Pies (2) has recently commented that it involved
a misunderstanding of Virchow’s work on pathophysiology.
An indirect way this problem has been handled is to suggest that
it has to do with the vague definitions of disease (3). Without a clear definition, anyone can use
their own to declare that psychiatric disorders are not diseases. That has been
a common tactic used to declare that not only that mental illnesses are not diseases
– because of the lack of clear gross pathology they do not exist. Dealing with the problem at this rhetorical
level has not been very successful largely due to the lack of interest in rhetoric
on the part of medical professionals and constant repetition by the rhetoricians.
More practical philosophical attempts at disease definition like loss of function models seem to not have much traction. Munson and Resnick (4) proposed one of these models and also suggested that the loss of function is related to programming errors in biological processes.
Kendler suggests a clear path that has appeal to anyone who
has studied pathophysiology and treated illnesses without clear lesions or with
lesions that had to be the end product of some unknown pathophysiology. That group of people would be anyone who has
done an internship or residency in any medical field. Anyone with that experience has seen a wide array
of medical conditions that are polygenic in nature and have either an unknown
or highly speculative pathophysiology.
The suggested path is genetics-> pathophysiology or more
broadly “genetics -> brain -> schizophrenia.” Rather than bemoaning all of the failed GWAS
studies and Decade of the Brain, Kendler cites “the most robust empirical
findings in all of psychiatry—that genetic risk factors impact causally and
substantially on liability to all major psychiatric disorders.” More specifically he cites a 2022 report that
shows that gene expression (as mRNA levels) of risk variants for schizophrenia were
noted in the brain and no other tissue. That
brings the brain expression in his causal link into clear focus.
At that point he hedges and suggests that this may not be
robust enough to suggest that a brain disease is occurring. For me it is plenty. He goes on to suggest that there are 5 advantages
of this approach including data driven rather than metaphysical, bypasses the
19th century need for gross lesions, fits with pluralism or multiple
possible etiologies, can potentially provide information about other diseases
affecting the brain, and avoids a hard line of demarcation between normal and
disease at the physiological level. The
last point has been elaborated in the more recent past as quantitative versus
qualitative diseases and the associated variants.
On the limitation side – a genetics only approach is the main
consideration. The antipsychiatrists
that he has alluded to may be realizing that they need to finally modify their
19th century rhetoric and I have seen the equally absurd claims that
there are no genetic effects for psychiatric disorders. The difference is that Kendler is an expert
in the area – so only the most dedicated post modernists will claim that they
did their own research and came to a different conclusion. He does see the innovation of being able to
detect tissue levels effects of genetic variants as a good starting point. The goal is to elaborate the functional networks
affected by these variants, describe mechanisms at the molecular level, and how
those mechanisms are affected by variants (5).
This is really an inspiring commentary at a time when it is
getting more fashionable to attack basic science research in psychiatry. I saw
a comment just last week about how biological psychiatry was a drain on mental
health research. And there are frequent comments
about how there should be more psychosocial research, even though there is no
clear evidence that is necessary.
As a clinical psychiatrist and a physician first, my observations
have been that most people go to medical school to gain knowledge about the
human body and how to treat, prevent and where possible cure diseases. Speculative
pathophysiology and mechanisms are all part of that starting in the first two
years of basic science course and extending to clinical rounds at bedside during residency. Philosophy and endless arguments about the
nature of disease or psyche is not. Psychiatry
has lost its way many times due to an inability to recognize and respond to rhetoric.
Kendler’s solution to the question of whether mental disorders are brain diseases
is an elegant one and it is consistent with the way physicians are trained. It also establishes a boundary that some
questions in psychiatry are not answerable by philosophy.
Finally, what is still lacking? I think that ultimately, we want medicine and
psychiatry to be part of a comprehensive view of human biology. We need more comprehensive
theories about human biology and how things really work at the physiological
and molecular level. That knowledge is
currently spotty across all specialties. Biology theory rather than biological
psychiatry is really the goal here and we can use more input from theoretical
biologists of all specialties.
George Dawson, MD, DFAPA
References:
1: Kendler KS. Are
Psychiatric Disorders Brain Diseases?-A New Look at an Old Question. JAMA
Psychiatry. 2024 Feb 28. doi: 10.1001/jamapsychiatry.2024.0036. Epub ahead of
print.
2: Pies R. Did Szasz Misunderstand Virchow’s Concept of
disease? Psychiatric Times. Feb 21, 2024.
https://www.psychiatrictimes.com/view/did-szasz-misunderstand-virchow-s-concept-of-disease
3: Pies RW, Dawson G. Epistemic Humility in Psychiatry: Why We Need
More Montaigne and Less Savonarola.
Psychiatric Times. Oct 19,
2023. https://www.psychiatrictimes.com/view/epistemic-humility-in-psychiatry
4: Albert DA, Munson R, Resnik MD. Reasoning in Medicine: An Introduction to Clinical Inference. Baltimore, Maryland: The Johns Hopkins University Press, 1988: 150-180.
5: van Dongen J, Slagboom PE, Draisma HH, Martin NG, Boomsma DI. The continuing value of twin studies in the omics era. Nat Rev Genet. 2012 Sep;13(9):640-53. https://doi:10.1038/nrg3243
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