Young Links Gene Variant to Depression and Mental Illness
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COMOIACommunicationsNews2007 News ArchiveYoung Links Gene Variant to Depression and Mental Illness
In their study to be released March 15 in the Journal Biological Psychiatry, the researchers link inheritance of a common serotonin transporter (SERT) gene variant to enlargement of a region of the brain known as the pulvinar nucleus of the thalamus, which may be important to depression and related mental illness because it helps select attention to negative visual stimuli and fearful emotions.
About 45% of Caucasians carry at least one copy of the gene variant in question, known as the SERT short allele. When individuals inherit two copies of the short allele (approximately 20% of people with European heritage), their pulvinar is 20% larger and contains 20% more neurons than usual.
The pulvinar functions to feed information about the threat content of the environment to the brain’s limbic system, which is then responsible for creating feelings of fear and danger that act as motivation for many human actions. For instance, in one study, scientists investigated a patient with damage to the pulvinar, and found that there was a lack of normal limbic system response to threatening pictures when he pictures were presented on the side of the pulvinar damage. One of the interesting properties of this pulvinar threat detection system is that the signals are sent to the limbic system subconsciously – the limbic system can respond without an individual actually experiencing an awareness that they have seen anything.
“Since people with two SERT–short alleles have larger than normal pulvinar, we believe that they subconsciously pay more attention to potentially negative and threatening sights and sounds, and spend more time ruminating on the negative thoughts,” lead author Keith A. Young, Ph.D. from the CTVHCS and the Department of Psychiatry at Texas A&M Health Science Center says. “This increased capacity to focus attention on the negative aspects of existence may be why individuals that inherit the SERT- short-short gene combination have a higher incidence of depression.”
In other words, there may be a genetically determined type of brain anatomy that feeds inappropriately negative signals to the brain’s emotional processing system: An “…..inward cause that (melancholy men) carry with them; an object which cannot be removed, but sticks as close, and is as inseparable as a shadow to a body.”
Dr Young adds, “The idea that depression stems primarily from brain anatomy, rather than brain chemistry, is controversial, but is gaining momentum in the scientific literature”.
In addition to the present data which suggest that SERT is involved in an enlargement of the pulvinar, researchers at the Clinical Brain Disorders Branch of the NIH have linked the SERT-short genetic variation to a reduction in the volume of the frontal cortex and amygdala, part of the same limbic circuit affected by the pulvinar. By facilitating attention to negative emotional processing through enlargement of the pulvinar, and by limiting the capacity of the cortex and amygdala to appropriately respond to these stimuli, the SERT- short gene variant may predispose individuals to depression and related disorder such as anxiety and Post-Traumatic Stress Disorder (PTSD), depending on whether a person is exposed to high or low levels of chronic stress or trauma. As a result, the SERT gene is gaining a scientific reputation as one of the major determinants of both brain anatomy influence on human emotions.
To perform the research, the investigators studied brains from 49 normal and mentally ill people whose brains were donated for research. Thin sections of tissue from the pulvinar were stained so that brain nerve cells (neurons) could be counted with special computerized microscopes, and DNA was studied to determine who inherited the SERT short allele. The researchers counted over 20,000 neurons during their 1-year long study.
The Texas researchers are turning their attention to alternative procedures such as MRI, genetics and animal models to verify the effects of the SERT gene on brain anatomy. In one set of experiments, the Central Texas VA group will study 1400 soldiers at Fort Hood and 500 community volunteers to determine whether SERT and other related genes have an effect on brain anatomy and on the development of depression and PTSD in troops returning from Iraq and Afghanistan.
The research was performed with funding from the National Institute of Mental Health (MH 59145), as a collaboration between Keith A. Young, Ph.D., Vice-Chair for Psychiatry Research at the Central Texas VA and Texas A&M University Health Science Center, and Dwight C. German, Professor of Psychiatry at UTSWMC in Dallas. Paul .B Hicks, Leigh A. Holcomb, Willy L. Bonkale from the Central Texas VA and Umar Uzdani from UTSWMC also participated in the research. Additional support for the study was obtained from the Veterans Administration, the Zigenbein Memorial Fund, and the Theodore and Vada Stanley Foundation.
