It's an important finding because it shows -- for the first time with definitive imaging evidence -- that the depressed brain responds 'differently' to different treatments. It may also help doctors better understand why a particular treatment might work for one patient and not another.
The results are published in the January 2004 issue of the Archives of General Psychiatry. The study was led by The Rotman Research Institute at Baycrest Centre for Geriatric Care, in collaboration with the Centre for Addiction and Mental Health (CAMH), and University of Toronto.
"When treating clinical depression we know that one type of treatment doesn't fit all," says principal investigator Dr. Helen Mayberg, a senior scientist at The Rotman Research Institute at Baycrest and the Sandra A. Rotman Chair in Neuropsychiatry at the University of Toronto.
"Our imaging study shows that you can correct the depression network along a variety of pathways. Anti-depressant drugs change the chemical balance in the brain through effects at very specific target sites. Cognitive behavioral therapy also changes brain activity, it's just tapping into a different component of the same depression circuit board."
The most common treatments for clinical depression are CBT or other types of psychotherapy, drug therapy, or a combination of both. It's not unusual for treatment to go through a trial-and-error period until one is found to provide optimal results for a patient, with the least side effects.
With CBT, patients learn to evaluate emotional provocation in their environment in a new way. They are taught cognitive strategies for reducing automatic reactivity to negative thoughts.
Using positron emission tomography (PET) -- multi-colored imaging that pinpoints where maximum changes in brain metabolism occur -- Dr. Mayberg's team, led by CBT expert Zindel Segal, PhD, and graduate student Kimberly Goldapple, generated a detailed picture of what this self-correction looks like.
CBT has theoretically been considered a top-down approach because it focuses on the cortical (top) area of the brain -- associated with thinking functions -- to modulate abnormal mood states. It aims to modify attention and memory functions, affective bias and maladaptive information processing. In contrast, drug therapy is considered a bottom-up approach because it alters the chemistry in the brain stem and limbic (bottom) regions which drive more basic emotional and circadian behaviors resulting in eventual upstream changes in depressive thinking.
In this current study in Archives, 14 clinically-depressed adult patients underwent a full course of CBT. They each received 15 to 20 individualized outpatient sessions. None were on drug therapy. The patients' brains were scanned prior to beginning treatment and at the end of the full course of therapy.
Investigators found that CBT targets many of the same limbic and cortical regions affected by drug therapy, but in 'different directions'. With drug therapy, metabolism (blood flow) decreases in the limbic area and increases in the cortical area. With CBT, Mayberg and colleagues identified the reverse pattern: limbic increases (in the hippocampus, dorsal mid cingulate) and cortical decreases (in the dorsolateral, ventrolateral and medial orbital frontal; inferior temporal and parietal). Furthermore, each treatment showed changes in unique brain regions supporting the top-down, bottom-up theories.
What explains this reverse pattern? As CBT patients learn to turn off the thinking paradigm that leads them to dwell on negative thoughts and attitudes, activity in certain areas in the cortical (thinking, attention) region are decreasing as well.
"The challenge continues to be how to figure out 'how to best treat' for what the brain needs," says Dr. Mayberg. She suggests that brain scans may one day become a useful component of the treatment protocol for clinically depressed patients, helping doctors to determine in advance what treatment will be most efficacious, as well as monitor the effectiveness of a particular treatment strategy.
Dr. Mayberg's research team included Kimberly Goldapple (The Rotman Research Institute), and Drs. Zindel Segal, Sidney Kennedy, Mark Lau and Peter Bieling, and Carol Garson of the Department of Psychiatry (CAMH).
The study was funded by the Sandra A. Rotman Chair in Neuropsychiatry (Rotman Research Institute, University of Toronto), the Canadian Institutes of Health Research, and a University of Toronto Institute of Medical Science Open Fellowship Award.
Dr. Mayberg is now Professor of Psychiatry and Neurology at Emory University School of Medicine in Atlanta, and remains an associate scientist with The Rotman Research Institute at Baycrest.
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