State institute pioneers depression findings with PET scan research

Groundbreaking research conducted by the New York State Psychiatric Institute focuses on the root causes of depression, a disease that affects 14.8 million American adults in a given year.

Located in Washington Heights at 1051 Riverside Dr., the NYSPI is affiliated with New York Presbyterian Hospital as well as Columbia’s Department of Psychiatry and the University Medical Center. Research findings at the Department of Psychiatry are implemented into clinical care at the Medical Center.

Positron emission tomography imaging—the injection of small amounts of radioactive material into the body, which then give off gamma rays that are detected by a special gamma camera—produces images that illuminate the structure and function of internal organs. Using evidence from PET scans, NYSPI researchers are building a new body of knowledge surrounding depression, while dispelling common misconceptions of the disease’s cause.

“For years people have said that depression or mood disorders are a chemical imbalance in the brain,” NYSPI Chief of the Department of Neuroscience John Mann, M.D., said. “Now we have a large imaging center here on the medical campus and we’re actually able to image brain neurotransmitter systems in patients. Now we’ve shown unequivocal evidence of neurotransmitter abnormalities in bipolar disorder and in major depression, and we’ve shown how these abnormalities can have an impact on the probability of patients responding to different types of treatment.”

Currently, there is no scientific system of assigning anti-depressants to patients, Mann explained. Doctors choose anti-depressants for patients based on each drug’s potential side effects and patients’ lifestyles, as well as relying on familiar medication. Once a patient begins taking an anti-depressant, it takes four to six weeks for the doctor to discern whether the patient is benefiting from the drug.

“That’s a long time,” Mann said, “An hour feeling depressed feels like a day. Choosing the best medication for that patient up front can make a big difference to how long they stay depressed.”

Kaleigh, BC ’09, whose last name is being withheld because she does not want her comments to affect her job prospects, recalls the difficulty in finding the best medication to treat her bipolar disorder.

“One of the things that I struggled with for the longest time was that I was actually originally misdiagnosed as having unipolar depression, and I really was bipolar,” Kaleigh said. “So I tried out a couple of anti-depressants, which actually made things worse and made me very agitated and very hypomanic—it was bad. It would have been really fantastic if someone had been able to see what was actually going on and could’ve actually figured out what medication worked for me. Eventually that happened, and my doctor figured it out, but it was more of a trial and error type thing where my psychiatrist was like ‘Okay, we’ll try this.’”

Current NYSPI research may be able to prevent future cases like Kaleigh’s, according to Mann. “We have funding from the National Institute of Health to do more precise studies to try to understand where the specific types of anti-depressants with different modes of action can have their therapeutic outcome predicted by these [PET] scans,” Mann said. “That will change the treatment approach in the sense that patients would come in, see a physician, have a scan, and depending on results of the scan, the doctor can see which treatment they will be started out on.”

Another area of current mental health research focuses on how genetic factors and negative childhood experiences can cause depression.

“We’ve known clinically for a while now that there are genetic factors and an impact of adverse childhood experience that may influence the probability of developing a mood disorder in adulthood or even childhood/adolescence, but the pathway whereby that happens, we’ve known very little about it,” Mann said. “Now with devices like these brain scans, we can see neurotransmitter consequences of gene variance, adverse childhood experiences, and we can see how the brain abnormalities that are characteristic of depression may be caused. That’s another big thing, because that raises the potential for early screening and prevention.”

The possibility of early screening and prevention inspired hope in Kaleigh, who hopes to start a family one day.

“One thing that I worry about a lot, I mean I’m probably thinking way ahead of myself, I do want to have children someday, but at the same time I worry about how my own genetics might negatively impact a child and anything that would support early detection or prediction of mental disorder symptoms I would be very interested to see that actually developed into something,” Kaleigh said.

In addition to improving clinical care, this research will also have a tremendous impact on patient-doctor dialogue, Mann said.

“The brain has been molded by a combination of genetics and childhood experiences into a neurochemical profile that looks the same as that of people who already have depression, so we have evidence that people are at risk with the scanner images,” Dr. Mann said.

“It’s one thing saying we believe you have a biochemical abnormality compared to actually seeing the biochemical abnormality. Patients usually have difficulty with the notion that their illness is more than a by-product of stress. So they think, why would you treat it with medicine? Plus, when people get better from depression they can’t imagine getting sick again, so the motivation to go on taking it [medicine] is not great, a lot of people stop taking it too soon. Seeing the abnormality on a brain scan makes the idea that depression is a real illness much more convincing and motivates the patient to stick with the treatment.”

Depressive disorder often co-occurs with substance abuse. Appropriately, new research at NYPSI also deals with disorders of brain reward circuitry, which lead to substance abuse.
“There are areas in the brain that when you stimulate them in animal experiments, they’re very re-enforcing in terms of the behavior that leads to the stimulation,” Mann explained. “If a rodent, say, presses a lever and some sugary water comes out of the bottle, they press it again, and they keep pressing and there’s more and more pressing, but if it’s regular water coming out, their presses are fewer.”

In humans, a similar response to rewarding activity can be seen. “The reward experience involves certain neurotransmitters in the brain. Many things are rewarding, it might be eating chocolate, it might be video games, it might be sex, it might be getting terrific grades, it might be doing well in sports,” Mann continued. “These experiences favor repeating the behavior because they feel good. But you can achieve similar effects by taking drugs of abuse—amphetamines, cocaine, cannabis, etcetera—all these experiences and the drugs of abuse have been found to have certain common properties. In the brain they activate very specific pathways that lead to dopamine release.”

Disordered brain reward circuitry explains why some people develop debilitating addictions.

“Some people end up being alcoholics, some people end up playing video games all hours of the night and can’t stop. Internet sex is another example. All these things are interrelated, connected to the same reward pathways of the brain,” Mann said. “Now we can study what’s wrong with the circuitry, why people are more genetically predisposed to become drug addicts. That also means we can identify and begin to think about novel treatments to help addictions and prevent addictions.”

When asked when these findings will be applied in clinical care, Mann replied, “These are constantly moving fields and we’re already working on different ideas that come out of this research in the clinic, so it’s starting to happen now.”

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