How Metabolic Deficiencies Play A Role In Depression

At least 15 percent of people with depression don’t get relief from conventional treatments such as antidepressant medications and psychotherapy.

In a recent trial, researchers studying a small group of people with difficult-to-treat depression saw an improvement in symptoms and even full remission when they treated certain metabolic deficiencies.

“It’s really exciting that we now have another avenue to pursue for patients for whom our currently available treatments have failed.”

“What’s really promising about these new findings is that they indicate that there may be physiological mechanisms underlying depression that we can use to improve the quality of life in patients with this disabling illness,” says Professor David Lewis, chair of the psychiatry department at the University of Pittsburgh School of Medicine.

The study grew out of efforts by psychiatry professors Lisa Pan and David Brent to treat a teenager with with a history of suicide attempts and long-standing depression. “Over a period of years, we tried every treatment available to help this patient, and yet he still found no relief from his depression symptoms,” Pan says.


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Searching for answers, Pan contacted genetics experts Jerry Vockley and David Finegold. Through a series of biochemical tests, the three discovered the patient had a cerebrospinal fluid deficiency in biopterin, a protein involved in the synthesis of several brain signaling chemicals called neurotransmitters.

After receiving an analogue of biopterin to correct the deficiency, the patient’s depression symptoms largely disappeared.

The success prompted the researchers to examine other young adults with depression who were not responding to treatment, says Pan.

Neurotransmitter metabolism

In a recent trial published in the American Journal of Psychiatry, the researchers looked for metabolic abnormalities in 33 adolescents and young adults with treatment-resistant depression and 16 controls. Although the specific metabolites affected differed among patients, the researchers found that 64 percent of the patients had a deficiency in neurotransmitter metabolism, compared with none of the controls.

In almost all of these patients, treating the underlying deficiency improved their depression symptoms, and some patients even experienced complete remission. In addition, the further along the patients progress in the treatment, the better they are getting, says Pan.

“It’s really exciting that we now have another avenue to pursue for patients for whom our currently available treatments have failed. This is a potentially transformative finding for certain groups of people with depression,” she adds.

The team included additional researchers from the University of Pittsburgh; the University of California, San Diego; MNG Laboratories in Atlanta, Georgia; and University Medical Center Gottingen in Germany. The American Foundation for Suicide Prevention and others supported the research.

Source: University of Pittsburgh

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