There was an opinion piece about categorical diagnosis in
psychiatry and diagnostic heterogeneity that was published in Psychiatric
Research weeks ago (1), that generated a lot of controversy. The controversy started when an online
publication characterized the article as showing that Psychiatric Diagnoses
Found to Be "Scientifically Meaningless". The author of that article
subsequently posted that the article was written by science undergraduates
re-purposed as science writers. If this
was supposed to be investigative journalism it failed at several levels not the least of which is the apparent conflict of interest by the
authors. Instead the internet article basically quotes the authors as factual
and scientific rather than a rhetorical opinion piece. What follows is my take on the Psychiatric Research Article.
The first sign of bias that a
reader may encounter in the original article is right in the abstract. The
concluding sentence reads:
“A pragmatic approach to psychiatric
assessment, allowing for recognition of individual experience, may therefore be
a more effective way of understanding distress than maintaining commitment to a
disingenuous categorical system.” (my emphasis added).
When I read this sentence, it
was difficult for me to believe that peer reviewers for a psychiatric journal
could allow it to pass. In one sentence the authors are allowed to distort and
discredit psychiatric clinical methods and diagnostic methods that have been carefully developed for over a century. I won’t belabor the definition of
“disingenuous” but it is safe to say that the expenditures in terms of brainpower
and money as well as the transparency of the process make the production of the
DSM 5 one of the more rigorous approaches to a diagnostic system in medicine.
The people sitting on the DSM 5 committees for each section were acknowledged
experts in their fields with decades of experience and published research. Production of the DSM-5 was also a multiyear
process that took 14 years to develop prior to its publication in 2015 (2). During that time there was a multiyear grant
that sponsored 13 international conferences on specific diagnostic issues. Guiding principles and conceptual issues were
examined. Public input was solicited.
Hundreds of clinicians and researchers were involved. There was transparency about potential
conflicts of interest. It was not just an intense effort – it was a unique
diagnostic effort in terms of overall vigor and resource utilization. Describing
the output of all of this work as “disingenuous” and getting that in print lead
me to question the peer review and editorial process. Are the editors and reviewers ignorant of the
effort that went into the diagnostic categories or don’t they care? It is clear
that the authors of this article don’t.
The second red flag in the paper
to anyone familiar with typical antipsychiatry arguments is the mention of
Foucault and the suggestion that psychiatric classification occurs within wider
sociocultural developments and that these roots have resulted in diagnostic
heterogeneity. In fact, Foucault’s
observations of psychiatry were inaccurate at the time and have not held up at
all over the course of time. The authors seem to ignore the actual reasons for
categorical diagnosis in the first place and list none of those
references. Practically all modern DSM
work can be traced back to the reference generally referred to as the Feighner criteria (3). Reading
those papers, clearly describes categorical diagnosis as a work in progress and
the importance of diagnosis. The authors also describe five phases for the
validation of psychiatric diagnoses. They have this comment on diagnostic heterogeneity:
“In the absence of known
etiology or pathogenesis, which is true of the more common psychiatric
disorders, marked differences in outcome, such as between complete recovery and
chronic illness, suggests that the group is not homogeneous. This latter point
is not as compelling in suggesting diagnostic heterogeneity as is the finding
of a change in diagnosis. The same illness may have variable prognosis, but until we
know more about the fundamental nature of common psychiatric illnesses, marked
differences in outcome should be regarded as a challenge to the validity of the
original diagnosis.” p 57.
These authors suggested 5 phases
to establish the diagnostic validity of psychiatric illness including the
clinical description, laboratory studies, delimitation from other disorders,
follow-up studies, and family studies. There are entire texts dedicated to some of
these markers on epidemiology and family studies. One of the mandates of the DSM-5 committees
was to review all of this data and compile it into the most clinically useful
form. In the interim they happened to
pare the total number of diagnoses from a maximum of 297 in DSM-IV to 157 in DSM-5
(see reference 2, p xxiii). This is the
basis of categorical diagnosis – not the narrative of a philosopher.
Contrary to the idea that the
current authors and the like-minded authors they have referenced have
discovered diagnostic heterogeneity it has been widely acknowledged from the
outset and by all current psychiatrists. There are no surprises here
especially for people trained as physicians. Practically every complex
biological illness is heterogeneous with heterogeneous outcomes as well as
polygenic etiologies. Their Foucauldian
criticism also ignores the fact that the Washington University group was based
on empirical research as opposed to the psychoanalytic process of the day.
The example of the empirical
approach is illustrated by tracing the development of Major Depression criteria
from 1950 to 1980. In fact, many in that group were highly skeptical of
psychoanalysis as a possible diagnostic process at all. As they started to
publish research article, one of their original articles was highly edited by a
psychoanalyst/editor to remove any reference to the term diagnosis.
The second acknowledged aspect
of psychiatric diagnosis and treatment that is given short shrift by the
authors is the issue the value of both diagnosis and formulation or as Kendler,
et al discuss:
“However, neither we nor, we
think, the developers of the criteria would claim that assessing
operationalized diagnostic criteria is all there is to a good psychiatric
evaluation. While critical, a diagnosis does not reflect everything we want to
know about a patient. Our diagnostic criteria, however detailed, never contain
all the important features of psychiatric illness that we should care about.” (see
reference 4 p. 141.)
The authors’ research method is
an exercise in subjectivity. They
basically read five chapters in the DSM 5 (schizophrenia spectrum and other
psychotic disorders, anxiety disorders, bipolar and related disorders, trauma
and stressor related disorders, and anxiety disorders) and use a technique
called “thematic analysis” “to code themes or patterns of meaning across
diagnostic categories being analyzed, with a particular focus on the
heterogeneity or differences across types of diagnostic criteria.” You don’t need an advanced research seminar
to figure out what is wrong with that picture. Here is a group of psychologists
several of whom make a career out of criticizing psychiatry and who are
building a case that psychiatric diagnoses are inferior to their own vague
diagnostic system using a qualitative technique that even their reference (5)
refers to as having “no particular kudos as an analytic method – this, we
argue, stems from the very fact that it is poorly demarcated and claimed, yet widely
used”. What outcome would any objective
observer expect?
The combinatorics
argument:
The authors make it seem like large
combinations of diagnostic features mean categorical diagnoses are problematic. Although they don’t say it explicitly -
referring to more diagnoses greater than the number of stars in the solar
system - suggests improbability. But do
large combinations of number preclude reasonable human use? A chess board for example has an 8 x 8 square
configuration and by some estimates - 10137 moves are possible. And yet players at all levels seem to be able
to negotiate a chess board and determine win, lose or draw. Master players can develop strategies that
make them more likely to win. Is there
similar evidence that diagnoses with large combinations can be managed the same
way? What follows is a mixed table of a
psychiatric diagnosis (PTSD) that yields a large number of combinations of diagnostic
criteria on the left, a dimensional scale for depression (DEP) from a standard psychological
test (MMPI), two different criteria for systemic lupus erythematosus (SLE), and
criteria for asthma. Qualifiers for each column are listed at the bottom.
Disorder
|
PTSD (1)
|
MMPI-DEP (2)
|
SLE (ACR) (3)
|
SLE (SLICC) (4)
|
Asthma (5)
|
Criteria
|
Presence of 1 (or more) of the following
symptoms:
1.
2.
3.
4.
5.
|
One or both of the following symptoms:
1.
2.
|
Two (or more) of the following:
1.
2.
3.
4.
5.
6.
7.
|
Two (or more) of the following:
1.
2.
3.
4.
5.
6.
|
|
15/26 items
|
4 of 11 criteria:
1.
2.
3.
4.
5.
6.
7.
A or B
8.
A or B
9.
A or B
10. A or B or C or
D
11. A or B or C or D or E
|
4 of 17 criteria including at least 1
clinical criterion and 1 immunologic criterion; or biopsy proven lupus
nephritis:
1.
A or B
2.
A or B
3.
4.
A or B
5.
A or B
6.
A or B
7.
A or B
8.
A or B
9.
10. A or B
11.
12.
13.
14.
15.
16. A or B
17.
|
1.
A or B or C or D
2.
A1 or A2 or A3
or B or C
|
Minimal Combinations
|
3,150
|
7.726160e6
|
330
|
2,380
|
36
|
Total Possible Combinations
|
636,120
|
7.726160e6
+ 5.311735e6 +
3.124550e6 +
1.562275e6 +
657800 + 230230 + 65780 + 14950 + 2600
+ 325
|
12,555
|
321,489
|
46
|
Footnotes:
1.
This column is from the reference: Galatzer-Levy, I.R., Bryant, R.A.,
2013. 636,120 Ways to have posttraumatic stress disorder. Perspect. Psychol.
Sci. 8, 651–662.
2.
I have several opinions from different psychologists on the current use
of this MMPI scale and the raw cut-off scores. I understand that there are
different raw scores for men and women. I can recalculate this scale based on any
numbers that may be deemed more reliable. Just email them to me along with the
evidence.
3.
American College of Rheumatology (ACR) classification criteria for Systemic Lupus Erythematosus
4.
Systemic Lupus International Collaborating Clinics (SLICC) proposed
revised classification criteria for Systemic Lupus Erythematosus
5.
There are numerous endophenotyping classifications for asthma. It is clear at this point there is no comprehensive
system of clinical classification.
What can be observed from this
table?
Apart from waxing poetically
they seem to not recognize that common psychological approaches scale to an
even larger extent – much greater than 1018. I have also
demonstrated that the way diagnostic criteria are worded makes a big difference
in counting word combinations. Just
using the DSM phrasing “or more” greatly increases the number of
combinations. Criteria designed like the
SLE criteria as a series of “A or B” choices that greatly reduce the number of
possible combinations. On the other hand
dimensional criteria like a single scale from a popular psychological test –
greatly increases the number of possible combinations because that scale is a
many n and many k. Using a
15/26 item scale results in 107 combinations. Using that as a ball park estimate for the
other clinical scales results in numbers far larger than used by the authors to
criticize categorical diagnosis. The
other aspect of this table is that less combinations is not necessarily better.
With asthma for example, these numbers are based on very basic diagnostic criteria. There are at least 2 other 6
item endophenotype systems and an additional cough variant
asthma, but currently experts in the
field have not developed a way to incorporate that level of clinical complexity
into diagnostic criteria that would be useful to clinicians. Low number of
combinations of diagnoses criteria are not necessarily better than higher
numbers – especially when the disease complexity is not captured.
The second issue with
combinatorics is that they are not predictive of anything. Great strides in
treating post-traumatic stress disorder have occurred in the past 30 years
using criteria with a high number of combinations. That obviously does not preclude patient
selection or monitoring in clinical trials of either psychotherapy or
pharmacotherapy. It does not prevent the successful diagnosis and treatment of
patients in clinical settings in many cases where severe and potentially fatal
psychiatric illness exists. As an
example, delirious mania had a fatality rate of 75% in 1849 in the United States
(7). That number has fallen to zero with psychiatric treatment based on
categorial diagnosis and the clinical training of psychiatrists to recognize
severe illness. Many of those improvements have occurred in the past 30-50
years.
In the authors selection
strategy, large sections of the DSM 5 that clearly disprove the author’s
contentions are omitted. The elimination of Neurocognitive Disorders, Sleep-Wake
Disorders, and Substance Related and Addictive Disorders for example also eliminates
biological markers and autopsy validation of criteria of diagnoses. Table 1 (p. 482 of DSM-5) contains 127
discrete categorical diagnoses across 10 categories of substances.
But the larger misunderstanding
here is that what the authors disparage as heterogeneity is an expected part of
medicine. Every physician knows that no two patients with asthma, benign
prostatic hypertrophy, or gout are the same. There are a collection of illness
features with some overlap but no truly homogeneous categories – even in
clinical trials that attempt to minimize it. Biological systems especially the
brain are designed to scale in various ways including based on combinatorics of
various biological elements. The author’s
use of the term quadrillion, happens to be the estimated number of synapses in
the brain but that is just a starting point of how systems in the human brain
can scale. The endothelial system in the
human body has more cells than the brain and massive heterogeneity that allows
for regulation of the vascular beds the human body. The hematopoietic and immune
systems have similar levels of scaling that could also result in very large
number of combinations. In none of these cases do the number of combinations of
cell types, connections, tissue behavior, or descriptions preclude diagnoses,
research or treatment. A very small
sample of this heterogeneity is suggested by the table below.
Heterogeneity In
Normal Functioning And Disease States In Human Biology (very partial list)
Endothelial cells
|
Diabetic nephropathy
|
Hematopoietic Stem Cells
|
Hepatitis C virus
|
Neuroendocrine Neoplasms
|
Ischemic Stroke
|
Leukemia - Clonal and Intraclonal cell types
|
Prostate Cancer
|
Aphasia syndromes
|
Mitochondrial Myopathies
|
Atrial Fibrillation Syndromes
|
Asthma
|
Immunodeficiency syndromes
|
Coriticobasal Degeneration
|
Diabetes Mellitus Type I and II
|
Viral Syndromes
|
Congestive Heart Failure
|
Cryptospridium genus and species
|
The authors ignore clinical heterogeneity that physicians have to address in their patients
every day. Very few physicians see
clinical trials subjects as patients requesting assistance. That means comorbid
physical illnesses, variations in patient tolerance of medical and psychological
interventions, pharmacokinetic and pharmacodynamic factors, heart disease,
liver disease, renal disease, substance use disorders, traumatic brain injuries, old age, pediatric age, suicide risk, aggression
risk, impaired functional capacity, and even pregnancy have to be addressed in
patients being seen every day by psychiatrists and adjustments have to be made.
Only physicians schooled in heterogeneity would be able to treat those people. Only physicians schooled in heterogeneity would
realize that the people in clinical trials are rarely the people being seen in
the office.
In conclusion, the authors have
a poor understanding of diagnostic heterogeneity and why it is a central part
of medicine. Some of their arguments are
similar to arguments offered up by the critics of Kraepelin in the early 20th
century. Other arguments - like the
combinatorial ones reflect a poor understanding of biological systems and how
they scale as well as a lack of understanding of medicine. Physicians know for example that diagnostic models are not completely explanatory, that over time - the explanations change, but that science exists at some level of that explanation or treatment. That is the nature of biological as opposed to physical systems. Anyone interested in
these issues can find a rich literature out there that describes these problems
and even the involved philosophy. Unfortunately, only one of the authors
referenced (out of 28) is written by anyone authoritative in that area.
The only disappointment greater
than an article like this being published is the fact that it was published in
the journal Psychiatric
Research. It has little to do with psychiatry or
research and it is shocking that the obvious problems with article were
overlooked. On the other hand, this journal was never at the top of my reading
list and this may be why.
George Dawson, MD, DFAPA
References:
1: Allsopp K, Read J, Corcoran
R, Kinderman P. Heterogeneity in psychiatric diagnostic classification.
Psychiatry Res. 2019 Sep;279:15-22. doi: 10.1016/j.psychres.2019.07.005. Epub
2019 Jul 2. PubMed PMID: 31279246.
2: Black DW, Grant JE. DSM-5 Guidebook. American Psychiatric
Publishing, Arlington, VA: pp 543.
3: Feighner JP, Robins E, Guze
SB, Woodruff RA Jr, Winokur G, Munoz R. Diagnostic criteria for use in
psychiatric research. Arch Gen Psychiatry. 1972 Jan;26(1):57-63. PubMed PMID:
5009428.
4: Kendler KS, Muñoz RA, Murphy
G. The development of the Feighner criteria: a historical perspective. Am J
Psychiatry. 2010 Feb;167(2):134-42. doi: 10.1176/appi.ajp.2009.09081155. Epub
2009 Dec 15. PubMed PMID: 20008944.
6: Kendler KS, Engstrom EJ.
Criticisms of Kraepelin's Psychiatric Nosology: 1896-1927. Am J Psychiatry.
2018 Apr 1;175(4):316-326. doi: 10.1176/appi.ajp.2017.17070730. Epub 2017 Dec
15. PubMed PMID: 29241358.
7: Bell, L., 1849. On a form of
disease resembling some advanced stage of mania and fever. Am. J. Insanity 6,
97–127.