Recently, I was asked to appear on an internet broadcast focused on the diagnosis of myocardial infarctions, which includes the role of the well-known cardiac physical stress tests.1 Did we have any comparable helpful stress tests in psychiatry?
That sounded intriguing, so I readily agreed, even if I thought the answer was no. But I had been retired from clinical practice for 5 years, so maybe I had missed a new development like this.
Stress tests for schizophrenia
Very quickly, a long-forgotten memory emerged. It must have been traumatic.
When I began my medical career some 50 years ago, we tried such a stress test. I believe I was on my clinical rotation in psychiatry at Yale Medical School and we had a patient that exhibited some sort of psychosis. Was the diagnosis schizophrenia, manic-depression, or something else? The team couldn’t seem to agree. Treatment would depend on the answer.
The argument for the recommended action was this. If you gave such a patient in question a stimulant drug like an amphetamine, it would increase the release of dopamine in the brain, thereby increasing any symptoms of schizophrenia and, voila, that would confirm the diagnosis.2 Remember that this was the time before improvements in ethically obtaining informed consent.
The theory was right and it did so in our patient, but in his and other cases, the increased symptoms of hallucinations or delusions intensified and persisted. It was as though we opened Pandora’s Box to full-blown schizophrenia, perhaps never to close again. That felt like an obvious violation of the Hippocratic Oath to do no harm. No wonder similar endeavors ceased for some time.
Nevertheless, the promise of correctly diagnosing what we thought was schizophrenia before any psychosis emerged was too important to ignore. Based on our current knowledge, we already knew correct diagnosis might take years. The longer we delayed treatment—social, psychotherapeutic, and/or medication—the worse the outcome would be.
Waiting for psychotic symptoms to emerge would be like diagnosing coronary artery disease after someone already had a myocardial infarction—helpful to some extent, but not nearly enough. What we needed was a suitable and safe stimulus with associated reliable outcome measures.
Researchers from Yale took up this challenge once again.3 After reviewing all the recent trials of biological and social stimuli that might compose a useful stress test for schizophrenia, they came up with a different proposal. They concluded that cannabis or, more specifically, the primary active component of THC, may offer unique advantages because:
. The recreational use of marijuana has been linked to transient psychosis
. Cannabis exposure in adolescence is associated with later psychosis in some vulnerable individuals
. Laboratory studies of THC (as limited as they are) show it is well-tolerated in healthy subjects, including that any detection of psychosis that usually remits after the test day
. For any rare prolongation of THC psychosis, antidotes (ie, lorazepam, extended observation) can help
1. Khera A Kathireson S. Is coronary atheroschlerosis one disease or many? Circulation. 2017:135:1005-1007.
2 Angrist BM Gershon S. The phenomenology of experimentally induced amphetamine psychosis—preliminary observations. Biol Psychiatry. 1970:2:95-107.
3. Gupta A, Ranganathan M, D’Souza DC.: The early identification of psychosis: Can lessons be learnt from Cardiac Stress Testing? Psychopharmacology. 2016;233:19-37.