Why you should care
One in four American adults suffers from a mental disorder each year. What if a simple lab test could get them treated better, faster?
How can we tell if someone is mentally ill? It used to be that the answer required interviews and analyses by a psychiatrist. But clinicians may soon look for biological signals, or biomarkers, of mental illness in lab tests instead of deciphering questionnaire responses. Their offices could one day be furnished with not only a couch and armchair but also diagnostic devices similar to those found in a medical examining room.
They search for evidence of mental illness in blood and spinal fluid proteins, brain-imaging patterns and even in tones of voice.
Scientists are working to develop clinical lab tests for mental illness by identifying biomarkers for psychiatric disorders, which could transform their diagnosis and treatment. They’re searching for evidence of mental illness in blood and spinal fluid proteins, brain-imaging patterns and even in tones of voice. Biomarker tests may even predict whether someone will commit suicide. But skeptics worry that we still don’t understand mental illness enough to design objective, clear-cut tests — although that hasn’t stopped people from trying. In fact, the first biologically based diagnostic test for mental illness could make its way to the clinic in about 18 months.
Clinicians typically screen patients for psychiatric disorders with standardized questionnaires, relying as well on the Diagnostic and Statistic Manual of Mental Disorders, or DSM, which lists common symptoms of different psychiatric disorders, such as low mood, insomnia and hallucinations. The problem is that making a diagnosis rests primarily on the patient’s subjective answers to interview questions and the clinician’s subjective interpretation of them.
Without a clear-cut screening tool, psychiatric disorders can go undetected — a major possibility given the stigma of mental illness.
Without a clear-cut screening tool, psychiatric disorders can go undetected — a major possibility given the stigma of mental illness, which can make people reluctant to talk about their symptoms. It also means clinicians are prone to misdiagnosing patients, leading them to recommend ineffective or even harmful treatments. In many cases, they try different treatments before settling on the best one.
In contrast, most branches of medicine have identified biomarkers that can reveal whether someone has a particular disease or injury or if they might develop an illness in the future. For example, doctors can confirm that someone’s had a heart attack if his or her blood contains enzymes released by damaged heart tissue. “Cardiology, cancer and infectious disease — those are all 50 years ahead of us,” said Charles Marmar, chairman of the psychiatry department at NYU Langone Medical Center.
One reason for the lag is that DSM categories are broadly defined. Many of the same symptoms are present in multiple disorders — an inability to feel pleasure is found in depressed and schizophrenic patients, for example — which makes finding biomarkers unique to specific disorders extremely challenging. The brain is also more complex than other organs, and brain biopsies can be difficult and risky. But recent advances in imaging technology and molecular biology are allowing researchers to noninvasively examine brain functioning.
In February, Marmar and other scientists launched a five-year program to find biomarkers for post-traumatic stress disorder and traumatic brain injury (TBI). The PTSD Research Program at NYU is working to recruit 1,500 Iraqi war veterans who will undergo a battery of physical tests. Researchers will then identify candidate biomarkers by comparing the results of those who have PTSD and/or TBI to healthy subjects.
Some researchers in the program are using brain imaging to examine the brain activity of those with and without PTSD. A preliminary study published in June revealed that vets with PTSD had increased activity in key regions of the brain’s fear circuitry and decreased activity in areas involved in processing memories, possibly contributing to the flashback episodes that are a hallmark of the disorder.
Other researchers will even search for biomarkers in audio recordings of the soldiers’ voices, since earlier studies have found that PTSD can hinder speech and language processing. The researchers will run the recordings through software that extracts information on what the subjects said and how they said it, such as the pitch and timbre of their voices. They’ll then compare these characteristics in people with and without PTSD.
Across the pond, scientists at biotech company Psynova Neurotech have detected proteins in the blood serum of schizophrenia patients that point to an impaired ability to metabolize glucose, the brain’s primary source of fuel. Without glucose to sustain them, the brain’s tissues become damaged, activating injury-fighting immune cells whose proteins can also serve as biomarkers. Psynova is working with Utah-based Myriad Genetics on three blood tests based on these biomarkers to diagnose schizophrenia, bipolar disorder and depression. They hope to launch their first test in the U.S. within the next year and half.
Clinical lab tests could also help doctors decide on the best treatment for patients. In a recent depression study, Emory University scientists gave depressed subjects either antidepressant medication or cognitive behavioral therapy — a type of “talk therapy” that helps people change distorted thinking patterns. They then imaged their brain activity. Participants who began with below-average baseline activity in the region involved in depression benefited from cognitive behavioral therapy but not the antidepressant. People with above-average activity showed the opposite result.
A blood test may predict whether someone will commit suicide, making it easier for clinicians to intervene before it’s too late.
Lab tests may even reveal whether someone will develop a psychiatric disorder. Indiana University scientists are designing a blood test to predict whether someone will commit suicide, making it easier for clinicians to intervene before it’s too late. The researchers had men with bipolar disorder periodically give blood samples and answer questions about their psychiatric state, including a question on suicidal thoughts. They then compared blood samples drawn when suicidal thoughts were low to when they were high. The top biomarker candidate was a molecule that indicated the activity of the gene SAT1, which rose with suicide risk.
Researchers are also developing an algorithm that incorporates known risk factors, such as family history and previous suicide attempts, to be used together with the blood test and clinical questions. “People could have high levels of biomarkers and no clinical risk factors,” explains Alexander Niculescu, an associate professor of psychiatry and neuroscience at Indiana University who led the study. “We don’t want to hospitalize people based just on biomarkers.”
Niculescu’s group is developing a smartphone app that would allow people to regularly answer questions and send them to a clinician. They hope to beta test the app and publish their algorithm in 2014. If all goes well, clinicians could begin using the full screening package in about five years.
Marmar believes lab tests will emerge first for Alzheimer’s disease, where studies have already identified many proteins as biomarkers. Research will then “hit a tipping point, and [lab tests for other psychiatric disorders] will be very quickly incorporated in routine clinical practice,” he said. “I’m encouraged we can do it within the decade.” Primary care physicians may eventually screen for mental illness using blood tests taken during routine check-ups, he added.
But some experts aren’t so sure. Some cases of mental illness might not even have a biological basis, Wakefield said. If we imagine our minds as computers, a mental illness could be due to social or environmental factors causing a “software” bug that distorts our interpretation of the world, rather than a biological “hardware” glitch. Even if a robust lab test does emerge, clinicians will still need to conduct interviews to account for these external influences, experts say.
But scientists are discovering that even these can “leave a biological footprint,” Marmar said. The emerging field of epigenetics, for example, examines how environmental factors, including traumatic experiences, can change the way genes behave.
In the meantime, scientists still need to show they can reproduce their findings, said Steven Zalcman, chief of the National Institute of Mental Health’s neuroscience research branch. But as far as getting a psychiatric diagnosis from a simple lab test, the question is no longer if, but when.
“We are on the threshold of a major leap forward in the understanding of the brain. Our mantra should be to use objective, quantitative measures for everything,” Niculescu said. “Homo sapiens, quantify thyself!”
Statistics on the number of Americans with mental health disorders come from the National Institute of Mental Health, NIMH: 26.2 percent of adults over 18, or approximately 57.7 million people.