Painting a Different Picture

Emily Stern, MD

Lab aims to change perception of mental illness

Sherbet orange and yellow, greens as bright as the fuzz on a tennis ball, blues reminiscent of a setting sky—all splattered across a soft gray maze. It’s not a Claude Monet painting. These colors exist on imaging scans produced by sophisticated machines in the Functional Neuroimaging Laboratory (FNL), directed by Emily Stern, MD, of the Department of Radiology. Stern and FNL researchers are studying images of the human brain to uncover the mysteries of depression, schizophrenia and other mental disorders.

With advanced tools that may change the medical landscape of psychiatry, one of the most poignant ambitions that the researchers have is to erase the stigma surrounding mental illness.

“Seeing a picture of brain areas lighting up abnormally on an MRI conveys that there is a biological problem with the brain in people with mental disorders,” said Stern. “We hope that when people hear that mental disorders have a biological basis they will think of these disorders differently, and not as something that a person can just snap out of. These are true disorders of the brain, just like there are disorders of the heart, kidney or lung. And we are just starting to understand the neurobiology behind this.”

Paintbrush and Palette

The researchers are using functional magnetic resonance imaging (functional MRI) to investigate what goes on in the brains of mentally ill patients in hopes of improving diagnosis and treatment. Like traditional MRI, functional MRI uses magnetic fields and radiofrequency pulses to send and receive energy signals to and from brain tissue to form images of the brain’s structure.

However, functional MRI takes it one step further by allowing researchers to also view brain activity. When a patient’s brain is stimulated—for instance by watching a series of photographs flash on a monitor—some parts of the brain work harder than others to do the specific task. The harder-working areas need more oxygen, and functional MRI detects associated levels of de-oxygenated blood in these regions. The different levels produce the array of colors on a scan and allow the researchers to view active brain areas.

“I like to think of it as a stress test for the brain,” said Stern. “For example, if we want to look at fear and stress circuitry in the brain, we may have the patient do a task that activates the amygdala [the part of the brain that processes emotions such as fear and anger] to assess whether it is functioning normally or not in a specific patient population.”

Gradually Painting the Picture

Although there is still much to learn, the researchers have already made some intriguing discoveries.

For instance, compared to healthy people, those with depression cannot activate a part of their brain called the ventral striatum, which is responsible for processing positive emotions. On a functional MRI scan this area does not light up in depressed patients, but does light up in healthy subjects in response to stimuli with positive content.

The researchers have also noticed gender-specific brain activity. Like patients with depression, women with premenstrual dysphorphic disorder (who are not depressed) are unable to activate the ventral striatum.

“This is an example of how we are seeing the same findings in the same brain area in two different disorders,” said Stern.

The researchers are also using functional MRI to study the overlap of symptoms across different disorders.

The blue arrow points to areas in the brain with decreased activity, while the yellow arrow points to areas of increased activity in patients with borderline personality disorder, compared to healthy people.Composite images of the brain courtesy of Emily Stern.

For instance, irritability and impulsivity are two premenstrual dysphorphic disorder symptoms that also exist in people with borderline personality disorder. When looking at the functional MRI scans of patients with these disorders, both groups share an abnormality in the brain’s frontal lobe—the “control tower” responsible for keeping emotions in check.

“In borderline personality disorder and premenstrual dysphorphic disorder, there are similar symptoms, including the same kind of inability to control behavior and negative emotions,” said Stern. “We are starting to paint the picture, but still filling in the spaces.”

The Work of Art

Stern and her team continue to fill in the spaces with the goal of one day completing the work of art—translating their findings and tools to the psychiatrist’s office.

Unlike other medical fields where doctors diagnose diseases based on biological evidence—a chest x-ray to diagnose pulmonary fibrosis or an echocardiogram to evaluate heart disease—mental health professionals make their diagnoses based on observing patient behavior and assessing reported symptoms using Diagnostic and Statistical Manual of Mental Disorders (DSM) guidelines.

“In addition to existing measures, we want to use imaging tools as objective biomarkers that can help in the diagnosis.” said Stern.

She also believes that these tools may guide treatment.

“This is important because, typically, it can take up to six weeks to know if a medication that is prescribed for a certain psychiatric disease is effective for that patient. If it isn’t, then the patient has been suffering for those six weeks, and you have to start over.” said Stern.

Rather, Stern illustrates the ideal patient encounter as one where doctors can confidently predict whether a treatment will work without this trial-and-error period.

“With imaging tools, we are hoping that we can do a type of functional scan to see a patient’s pattern of brain activity,” said Stern. “From that, we could determine how likely a patient is to respond to a certain medication or behavioral intervention. The goal is to get a ‘signature’ that will indicate what will be effective in individual patients.”