Study highlights importance of physical causes in refractory illness



Identifying and treating metabolic deficiencies in patients with treatment-resistant (refractory) depression can improve symptoms and in some cases even lead to remission. These are the findings of new research from the University of Pittsburgh School of Medicine.

Speaking about the findings, Dr David Lewis, Professor at the Department of Psychiatry at the University stated: “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.”

Study leader, Dr Lisa Pan, also of the Pitt School of Medicine says that the major depressive disorder, which is also referred to simply as depression, is one of the most common mental disorders; with at least 15 percent of patients not finding relief from conventional treatments such as antidepressant medications and psychotherapy. Depression is also the cause of more than two-thirds of suicides that occur annually.

The groundwork for the current study was laid five years ago when Dr. Pan was involved in treating a teenager 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,” Dr Pan explained.

Looking for answers, Dr. Pan discussed the case with Dr Jerry Vockley, and Dr David Finegold, both of whom have backgrounds in genetics. Though a series of biochemical tests, the three discovered that the patient had a cerebrospinal fluid deficiency in biopterin, a protein involved in the synthesis of several brain signaling chemicals called neurotransmitters. CSF is the fluid which surrounds and bathes the brain within the skull.

The patient was then given an analogue of biopterin to correct the deficiency, the his depression symptoms largely disappeared, going on to be a thriving college student. This success prompted the researchers to examine other young adults with depression who were not responding to treatment.

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

In almost all of the patients, treating the underlying deficiency improved their depression symptoms, with some patients experiencing complete remission. Dr. Pan noted that the further along the patients progress in this metaboilic treatment, the better they became.

“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,” said Dr. Pan.

This blog post has been produced from original material provided by UPMC/University of Pittsburgh Schools of the Health Sciences. It has been edited for style & content and posted by staff of Peak Health Online’s Well-being Library & Information Centre. Visit us at: www.PeakHealthOnline.com

The UPMC/University of Pittsburgh Schools of the Health Sciences source material for this blog may be viewed here: http://www.upmc.com/media/NewsReleases/2016/Pages/l-pan.aspx

The full study, by Dr Lisa A Pan et al, published by the Amercian Journal of Psychiatry, may be viewed here: http://ajp.psychiatryonline.org/doi/abs/10.1176/appi.ajp.2016.15111500?journalCode=ajp