A patient has pneumonia with cough and fever. Another patient has pneumonia without a cough and fever. Are these two different "disorders"? No, you'd say. But why not? Because the symptom of cough doesn't represent a different disease.
A patient has depression with mania. Another patient has depression with mania. Are these two different "disorders". Yes, you'd say. But why? Because mania is a different set of symptoms than depression, you might say. But cough and fever are symptoms, which we said did not represent a different disease.
That's the intuition behind the concept of diagnostic validators. It's not enough to say that symptoms differ and thus we have different "disorders". You have to show that those different symptoms represent some kind of different conditions or diseases. How do you do so? Not by simply referring back to the different symptoms: that would be tautologous. You have to have some different line of evidence, separate from symptoms, that represents a different illness. In the case of pneumonia, you have access to pathology: tests can show evidence of inflammation in the lung, whether or not you have a cough and fever. So those symptoms don't represent a different disease.
In the case of psychiatry, we don't have access to pathology (usually). So what should the independent lines of evidence be?
This is where this classic article from 1970 revolutionized psychiatry. Eli Robins, the chairman at the Washington University in St Louis, had trained at Massachusetts General Hospital (MGH) in Boston. But in that era, the major US cities were dominated by psychoanalytic ideology. Robins was influenced by Emil Kraepelin, the late 19th century German psychiatrist who taught that "diagnosis is prognosis", that the course of illness tells you which symptoms represent different diseases. Robins left Boston to go to the smaller city of St Louis, and from there, he trained a series of researchers who produced the change in US psychiatry which led to the third edition of DSM (DSM-III) in 1980 - a change much needed at that time, but which, it may be questioned, has hardened into a new ideology with DSM-IV and 5.
With his colleague Samuel Guze, Robins articulated four other diagnostic validators that, along with symptoms, should be used to identify if groups of patients differ from each other enough to justify seeing them as having different diagnoses (their article focused on schizophrenia, but they later applied these principles to all diagnoses). Those validators are shown in the box to the left. The most important is course of illness, Kraepelin's key criterion. Some conditions are chronic, and symptoms are present all the time (like schizophrenia); others are episodic, with symptoms coming and going (like manic-depression). The next most important validator is genetics: if diagnoses are genetic, you'll find evidence in family members. Next are laboratory tests or biological markers (which are useful in research but not yet in clinical practice). Robins and Guze also referred to "delimitation from other disorders", which meant that symptoms were specific to one condition rather than another. This is not always the case, since many symptoms, like anxiety, can occur in many conditions. Since that classic study, instead of delimitation, the diagnostic validator of treatment effects has been used, although it should be used cautiously, since many drugs are nonspecific in effect, and some, like amphetamines, are even effective in normal individuals. Treatment effects can also be seen as a proxy for biological markers, but only if treatment effects are specific to an illness (like antidepressant-induced mania).
Unfortunately, these diagnostic validators have been suppressed by the evolution of DSM. Originally, these diagnostic validators were the basis for scientific justification for diagnoses in psychiatric research, leading to the original Research Diagnostic Criteria (RDC) that Robins' St. Louis group created. The RDC identified about two dozen scientifically valid diagnoses. DSM-III started with those diagnoses, and added about 270 others. In almost all cases, although the other diagnostic validators were used to justify diagnoses, only symptoms were used in the DSM criteria definitions (an exception is schizophrenia, where there is a course criterion of 6 months or longer for psychosis). Now we have about 400 diagnoses in DSM-5, and clinicians are used to only looking at symptoms for definitions. This leads to the perennial arguments: Is the attentional problem ADHD or bipolar disorder? Is the anxiety part of major depressive disorder or generalized anxiety disorder? Is the sexual impulsivity mania or a paraphilia or borderline personality? These debates will never end as long as they are conducted on the single dimension of symptoms.
This classic paper reminds us that symptoms only go so far: like cough and fever, we need to look elsewhere to know which symptoms matter diagnostically and which don't. We need to look to course of illness, genetics, and treatment effects.
We'll discuss these diagnostic validators repeatedly throughout clinical discussions of differential diagnosis in PL, so we encourage readers to take the time to read this classic article, and learn to use these four modified diagnostic validators in clinical practice.