A Major Transformation in Psychiatry?

Jeffrey A. Lieberman, MD


May 03, 2012

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Hello, this is Dr. Jeffrey Lieberman of Columbia University, speaking to you today for Medscape. For some time now, I have said that the one thing that would have the biggest impact on changing the way the public looks at mental illness is the development of a diagnostic test. As you know, in the specialty of psychiatry, all of our clinical diagnoses are made by evaluating the signs and symptoms objectively reported by an individual or their informants, taking a history and observing the patient's behavior while conducting a mental status exam. We don't have a laboratory basis for diagnoses yet. In almost every other area of medicine, laboratory diagnoses are confirmatory or at least inform the diagnostic process. There are some exceptions -- for example, migraine headaches -- but for the vast majority of medical conditions, some laboratory tests, x-rays, or electrophysiologic assessments are used to confirm or at least significantly inform the diagnosis.

Psychiatric diagnoses have long had certain issues with validity in the minds of the public and other healthcare professionals. The Diagnostic and Statistical Manual of Mental Disorders (DSM), third and fourth editions -- and soon to be fifth edition -- were great steps in establishing consistency and reliability across diagnoses, but they have not been able to establish validity in the way a diagnosis is typically verified by pathologic evidence, and we don't have the confirmatory laboratory-based tests. For this reason, stigma, skepticism, and questions about mental health diagnoses have continued.

A recent series of developments signals the beginning of a change in that situation. The US Food and Drug Administration just approved the use of Amyvid™ [florbetapir F 18 injection; Eli Lilly], a radial ligand for an agent used in PET imaging. It has affinity for the beta-amyloid protein, and it can be used in the diagnosis of Alzheimer's disease. This augments nuclear medicine-based approaches to the assessment of patients with suspected Alzheimer's disease. Previously we used fluorodeoxyglucose to assess the level of metabolism and blood flow in patients suspected of having Alzheimer's disease.

A number of blood-based tests have been marketed that are based on proteomic or metabolomic analysis of serum or plasma. These tests claim to have diagnostic specificity for disorders such as schizophrenia and depression. These tests have not yet been fully validated, and they are not reimbursed by third-party payers for the most part up until now, but they signal efforts to use blood-based analytic tests focusing on proteomics and metabolomics to determine the signature of individuals with specific psychiatric disorders.

A variety of different imaging assessments have been developed at an experimental level, which holds significant promise for being applied clinically in the diagnosis of mental illnesses, particular mood disorders, depression, bipolar disorder, suicide risk, and psychotic disorders such as schizophrenia. Among these are the use of PET techniques that examine the uptake and synthesis of dopamine as measured by floradopa, or displacement from D2 receptors by stimulated release of dopamine using a D2 ligand such as citalopram raclopride. In MRI, functional MRI techniques have been developed that use paramagnetic contrast agents such as gadolinium to measure blood flow or metabolism, or the use of bold deoxygenated hemoglobin measures to interrogate specific green regions and define the anatomical basis for a mood disorder.

These developments herald the beginning of a period when diagnostic testing will come into clinical use in the discipline of psychiatry for the purposes of evaluating and establishing diagnosis of mental disorders. The proof will be when the evidence is compelling enough that this is included in the various diagnostic criteria (eg, DSM numerates for diagnoses) and, perhaps most important, when third-party payers begin reimbursing for these tests. This is the beginning of an exciting and potentially transformative time for our profession. Thank you for listening. This is Dr. Jeffrey Lieberman of Columbia University, speaking to you today for Medscape.


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