If you are unfortunate enough to develop acute chest pain this winter, you will probably be assessed by a clinician who will order a battery of tests to determine if your symptoms result from pneumonia, bronchitis, heart disease or something else. These tests can not only yield a precise diagnosis, they ensure you will receive the appropriate treatment for your specific illness.
If, however, you are unfortunate enough to have a psychotic episode this winter, the process of arriving at a diagnosis will be quite different. In fact, there are not many choices available to you.
Most people with a psychotic disorder are labeled as having either schizophrenia or bipolar disorder. The distinction has been in textbooks for a century: schizophrenia (originally dementia praecox) is associated with delusions, hallucinations, an absence of affect and a chronic course—meaning that it can become an unyielding condition. Bipolar disorder (originally manic depression) can also involve delusions and hallucinations and, typically, dramatic swings in mood. It has a fluctuating course, which means that it may be more episodic. But outside of textbooks, in the real world of the emergency room or clinic, these distinctions are less clear because many patients do not neatly fit the formal descriptions. Sadly, there are no blood tests or scans to distinguish schizophrenia from bipolar disorder.
While clinicians have become very skilled at assessing symptoms and signs, the absence of such tests poses a serious problem in psychiatry. Do all people with a label of schizophrenia have the same disorder? What about the large number of people who appear to have aspects of both schizophrenia and bipolar? Are these disorders, diagnosed exclusively by signs and symptoms, identifying distinct biological entities, or could there be many different illnesses with a continuum of psychotic signs and symptoms? These questions are not merely academic. As with chest pain, getting a precise diagnosis is key to selecting the best treatment.
Moving psychiatry into a new era of biologically based diagnosis has been a long-sought goal—and a priority at the National Institute of Mental Health, where I served as director for 13 years. The challenges are many, but a new study published online in December 2015 in the American Journal of Psychiatry raises fresh hope.
The study led by neuroscientist Brett Clementz of the University of Georgia, psychiatrist Carol Tamminga of the University of Texas Southwestern Medical Center in Dallas, and their colleagues at Yale University and Harvard University found distinct “biotypes” of psychosis that can be identified with quantitative biomarkers. In this study, from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium, 711 people with a diagnosis of schizophrenia, bipolar disorder or schizoaffective disorder (a hybrid of schizophrenia and bipolar disorder) were given a variety of tests assessing brain functions that have been associated with psychosis. These included a battery of cognitive tests, a measure of auditory processing, an assessment of cognitive control, as well as EEGs and studies of eye movements. In addition, each subject had an MRI scan of his or her brain.
Ignoring the clinical diagnosis, researchers pooled the data and analyzed them with unbiased, criterion-free statistical methods to look for biotypes. Perhaps it is not surprising that the computer analysis from a large population with three diagnostic categories would find three clusters or biotypes. But the three biotypes have very little relation to the three traditional diagnostic categories. In fact, people with schizophrenia, bipolar and schizoaffective disorders were distributed across the three biotypes. And the biotypes did not differ simply by symptom severity or the presence of mania-related symptoms.
Is there any reason to think that these biotypes are more valid than a clinical diagnosis based on symptoms? A few observations suggest that the B-SNIP investigators may be on to something.
First, some of the biotype differences were also found in first-degree family members, for whom data were also collected, suggesting a genetic basis for the new categories. Second, biotypes differed in social functioning—with people in biotype 1 showing more serious functional impairment relative to the other biotypes. Third, the brain-imaging studies, which were not used in defining the biotypes, showed clear differences in regional gray matter, especially in the frontal, cingulate, temporal and parietal cortices.
Although none of these observations proves that the biotypes are more valid than clinical diagnosis, these findings together encourage a novel approach to the diagnosis of psychotic disorders. Going forward it will be important to know whether genomic variation, functional brain measures or other behavioral measures can refine or further validate these biotypes.
More Precise Treatment
Precision medicine has become a buzzword to describe the diagnostic revolution in cancer and other diseases. The concept is simply that the tools of modern biology, including genetics and imaging, can deconstruct current diagnostic categories to yield more precise disease groups—sometimes at the level of a specific genetic variation—that can be matched to more personalized treatments.
For mental disorders, where laboratory tests have not been used in the clinic, precision medicine could be a disruptive innovation, revealing that many of the current diagnostic categories are imprecise and biologically heterogeneous. We are seeing evidence of this in autism and attention-deficit/hyperactivity disorder, as well as depression and anxiety disorders. Autism, for example, is almost certainly a large, loose diagnostic label covering a variety of conditions that are genetically diverse, albeit superficially similar.
The NIMH has proposed a new approach to the diagnosis of mental disorders that calls for the incorporation of biological, cognitive, behavioral and social data, in addition to observed symptoms and signs. Known as the Research Domain Criteria, or RDoC, it has been controversial both because it represents a major break with traditional psychiatry and because some doubt that it is viable. The data from the B-SNIP study provide early evidence for the RDoC approach.
Of course, the real test of the B-SNIP biotypes—or any new method of diagnosis—is whether they will be useful in targeting treatments and predicting outcomes. That will require studies of treatment response. Usually in the U.S., people with schizophrenia receive antipsychotic medication and psychosocial supports such as counseling, vocational training and other forms of help. Physicians treat bipolar disorder with mood stabilizers, antipsychotic drugs, and sometimes antidepressants and psychosocial supports. Treatment remains empirical, with few guides to know which person will respond to a given therapy.
One of the hopes of precision medicine for psychiatry is that the use of biomarkers will provide more predictability so that patients and clinicians can make more informed and precise treatment decisions. Psychotic disorders are among the most disabling conditions in all of medicine—with enormous costs in dollars and suffering for patients and their families. New approaches to diagnosis and treatment are long overdue.
Editor's note: This article was adapted from a post on the MIND Guest Blog.