Douglas Kondo, M.D.: Helping Kids Beat Depression, University of Utah Brain Institute

Between 15-25% of American teens will experience depression within their lifetime, their symptoms ranging from low-level depression to suicidality. "If the same number of kids had cancer, there would be panic in the streets," said Douglas Kondo, M.D., Brain Institute and USTAR investigator, and assistant professor of psychiatry at the University of Utah.

by Julie Kiefer

"The difference with mental illness is you can’t see it."
Stigma is part of the reason why research on depression has not received the attention it deserves. As a result, diagnosis is still based on patient questioning, not an unbiased blood test or scan. Another shortcoming, common antidepressants were found to be only marginally more effective than placebo in well-conducted studies. "Diagnosis and treatment are where psychiatry lags behind the rest of medicine," said Kondo.

Giving mood a boost

Creatine – a nutritional supplement frequently taken by athletes to improve muscle performance – may provide answers to these problems. Produced naturally by the body, creatine fuels a metabolic pathway that generates energy within muscle and brain cells. The extra boost provided by creatine may help brain cells to better perform basic neurological functions involved in mood regulation.

On this basis, Kondo is investigating whether creatine can help alleviate major depressive disorder (MDD), a condition that adversely impacts an individual’s work or school, health, and family. In part because women are disproportionately affected by depression, he is assessing the effectiveness of creatine treatment in adolescent girls who fail to respond to approved antidepressant treatments.

Under the auspices of a 5-year, $3.4 million initiative funded by the Veteran Administration (VA) Mental Illness Research, Education and Clinical Center (MIRECC), Kondo is also conducting creatine studies in veterans, whose depression can be complicated by post traumatic stress disorder (PTSD) and other factors.

Building on a strong foundation

"I am not necessarily a proponent of alternative medicine," said Kondo. "I am a proponent of evidence-based medicine (EBM) that is hypothesis driven."

Kondo’s research follows up on work by his colleague and mentor, Brain Institute and USTAR investigator Perry Renshaw, M.D., Ph.D., M.B.A., professor of psychiatry at the U. Using a non-invasive technique called magnetic resonance spectroscopy imaging (MRSI), Renshaw found that the brains of depressed adults who respond well to prescription antidepressants have higher levels of phosphocreatine (PCr) – a form of cellular creatine – than non-responders. What’s more, when non-responders took creatine, their PCr levels rose significantly. Preliminary evidence suggests their depression improves, too. 

"Think of a water tower," explained Kondo. "If the reservoir is full, you can turn on the faucet in your house. But if it’s too low, there is no pressure in the system and you’re out of luck." Kondo’s work will determine whether creatine works in depressed adolescents as it does in adults.

In similar studies, Kondo is pursuing whether supplements of another naturally produced molecule, uridine, will help treat the depressive phase of bipolar disorder – also called bipolar depression – in adolescents. Renshaw’s MRSI studies in healthy adults demonstrated that uridine supplements increase production of a fundamental building block of brain cells, membrane phospholipid precursors. Similar to creatine, uridine may also enhance energy metabolism and other basic cellular functions that impact mood.

Kondo hopes to exploit the MRSI results to circumvent the current, roundabout means of diagnosing depression. He is partnering with Ridge Diagnostics, a biotechnology company based in San Diego, to develop a blood test to screen for biochemical differences – or "biomarkers" – found in adolescents with MDD. 

"The ‘Holy Grail’ would be to reliably distinguish MDD from bipolar depression," said Kondo. "A test capable of that would cause a paradigm shift in psychiatry, and would undoubtedly save lives."

A desire to help

Kondo’s arrival to the U of U’s Department of Psychiatry in 2007 was a sort of homecoming. As a medical student at the U fifteen years ago, he admired the work of his advisor, William McMahon, M.D., now chair of psychiatry, and followed in his footsteps to become a child psychiatry researcher. After graduating, he completed adult psychiatry training at the Menninger Clinic in Kansas, and a child psychiatry fellowship at Duke University Medical Center.

As a post-doctoral research fellow at the Duke Clinical Research Institute, Kondo was introduced to the devastating effects that depression has on children, and was swept by the urge to help them. "Nearly 11% of American high school children make a suicide plan each year, and 6% will say they’ve actually attempted suicide," Kondo said, then paused. "We have a long way to go."

For many reasons, Kondo believes Utah is the best place to pursue his research interests. Among them is the opportunity to learn from Renshaw, a world-renowned scientist, and to work with his previous mentor, McMahon, to expand the child psychiatry research program at the U. The cherry on top is a USTAR-funded $3.5 million state-of-the-art Brain Imaging Suite slated to open this fall within the University Neuropsychiatric Institute (UNI), a full-service psychiatric hospital.

Despite advances in diagnosing and treating depression, there will always be the need to make in-person, clinical assessments. "The clinical aspect of clinical research will always be the thing that drives me," Kondo said. His office brims with tokens of appreciation from his patients: thank-you cards; artwork; and a "Certificate of Achievement" signed by graduates from a program for troubled youth. "The most exciting thing about my job is seeing kids get better."

About USTAR:

The Utah Science Technology and Research initiative (USTAR) is a long-term, state-funded investment to strengthen Utah’s "knowledge economy" and generate high-paying jobs. Funded in March 2006 by the State Legislature, USTAR is based on three program areas. The first area involves funding for strategic investments at the University of Utah and Utah State University to recruit world-class researchers. The second area is to build state-of-the-art interdisciplinary facilities at these institutions for the innovation teams. The third program area involves teams that work with companies and entrepreneurs across the State to promote science, innovation, and commercialization activities. For more information, go to http://www.innovationutah.com or follow http://twitter.com/Innovationutah.