image: This is Dilip V. Jeste, M.D. view more
Credit: UC San Diego School of Medicine
Researchers at the Stein Institute for Research on Aging at the University of California, San Diego have received a $4 million grant from the National Institute of Mental Health (NIMH), part of the National Institutes of Health, to study accelerated biological aging in schizophrenia.
"Schizophrenia is one of the most serious, challenging, and disabling mental illnesses," said principal investigator Dilip V. Jeste, MD, Estelle and Edgar Levi Chair in Aging, Distinguished Professor of Psychiatry and Neurosciences at UC San Diego School of Medicine, and director of the Stein Institute.
Characterized by symptoms such as delusions, loss of touch with reality and social withdrawal, this chronic condition has become one of the leading causes of disability and premature mortality in the world. In the United States alone, the overall annual cost of schizophrenia is estimated to be more than $60 billion.
Scientists have long observed that schizophrenia is more than a brain disease, as it also affects a wide range of physical functions and entails more rapid biological aging. A number of studies have suggested that physiological changes seen throughout the body occur at an earlier age in people with schizophrenia. For example, young adults suffering from this mental condition are prone to diseases associated with growing older, such as diabetes and cardiovascular problems.
"Even though schizophrenia has been associated with a higher risk for suicide, two-thirds of the excess deaths in patients suffering from this mental illness are from other causes," said Jeste. "The lifespan of patients with schizophrenia is usually 20 to 25 years shorter than those of unaffected individuals."
The new study will directly examine biological aging in schizophrenia by using a battery of psychiatric and medical interviews, as well as several state-of-the-art laboratory techniques. Over the course of five years, the team will annually follow more than 250 subjects, aged 26 to 65 years.
Root causes of a decrease in average lifespan in people with schizophrenia have long remained a mystery. Although some studies have suggested that it could be explained by poorer access to treatment, many scientists have suspected that there may be other, more fundamental factors involved.
However, previous attempts to decipher these factors failed to provide a conclusive answer. "Often studies lacked the longitudinal approach that involves repeated observations over long periods of time," said Jeste. "In addition, there was an insufficient understanding of the biology and neuroscience underlying the condition at the time of these studies."
To unravel biological mechanisms underlying faster aging, Jeste and colleagues will measure and analyze a panel of biomarkers associated with insulin dysregulation, inflammation, oxidative stress, and cell aging. The last study involves measuring the length of telomeres – regions of DNA that protect the ends of chromosomes from deterioration and have been linked to longevity. In addition, researchers will investigate the effects of factors related to chronicity of schizophrenia, such as cumulative effects of medication.
"Up to one percent of adults are affected by schizophrenia. By providing new insights into the mechanisms of the disease, our study might open pathways to novel therapies and interventions to improve the health and quality of life of schizophrenia patients," said Jeste.
The investigative team includes Dilip V. Jeste, MD; Gregory Light, PhD, associate professor of psychiatry; Nicole Lanouette, MD, assistant clinical professor of psychiatry; Paul Mills, PhD, professor of psychiatry and Director of UC San Diego Clinical Translational Research Institute (CTRI) Research Tools Program; Wesley Thompson, PhD, assistant professor of psychiatry; all at UC San Diego School of Medicine; and Owen Walkowitz, MD, Professor-in-Residence, Department of Psychiatry, UC San Francisco.
This study is funded by NIMH grant # R1 MH094151.