These women also had similar electroencephelograms (EEG) -- recordings of brain electrical activity as unique as an individual's fingerprints -- that showed characteristics of anxious temperament, further strengthening the association of this shared genetic factor with anxiety. The study appears in the current issue of the journal Psychiatric Genetics.
"These results shed more light on the genetic origins of anxiety, which can sometimes be a warning sign for developing alcoholism," says NIAAA Director T.K. Li, M.D. "Such multidimensional studies that integrate neurogenetics, behavioral science, and the study of the brain are vital to increasing our fundamental knowledge of the genes related to complex psychiatric disorders."
Research physician Mary-Anne Enoch, M.D., and colleagues in the Laboratory of Neurogenetics in NIAAA's Division of Intramural Clinical and Biological Research in Bethesda, Maryland, conducted the study. The team investigated a gene that encodes catechol-O-methyltranferase, or COMT, a major enzyme responsible for the metabolism of certain neurotransmitters --the nervous system's chemical messengers -- including norepinephrine, which affects anxiety.
General Anxiety
People can inherit various possible forms, or polymorphisms, of the COMT gene, which in turn can affect the metabolism of their neurotransmitters. Dr. Enoch's team hypothesized that a particular genetic polymorphism identified as COMT Val158Met might be associated with anxiety as measured by a personality dimension test and EEG records."We set out to investigate the relationship of COMT gene variants with general anxiety, the normal range of anxiety experienced by people in the community every day, not the more severe clinical disorders," says Dr. Enoch. "We chose to conduct this study in two communities very different from each other."
The study participants included 92 women and 57 men, most of whom identified themselves as Caucasian, living in suburban Bethesda, Maryland, and a group of Plains American Indians in rural Oklahoma that comprised 149 women and 103 men.
The researchers had the study volunteers respond to psychological questionnaires that use harm avoidance as a measure of the dimensions of anxiety. As another measure of anxiety, they also recorded the volunteers' EEG readings, which are known to display highly inherited characteristic patterns. In addition to these tests, the study team analyzed DNA from blood samples to determine the variants of the COMT gene among the study group participants.
As expected, the women from both groups scored higher than the men on the harm avoidance measurements, indicating they experienced a higher state of general anxiety. Significantly, regardless of their ethnic background, the women from either group who shared a particular genetic makeup, or genotype, identified as COMT Met158/Met 158 were among those who tested highest for anxiety -- higher than other women who lacked that particular genotype. In addition, the women with COMT Met158/Met158 also exhibited a low-voltage alpha EEG, a specific brain-wave pattern associated with anxiety disorders and alcoholism.
Men Had Lower Scores
"Other studies have shown that women have lower COMT levels than men. In addition the COMT Met158/Met158 genotype is associated with a threefold to fourfold decrease in COMT enzyme levels," says Dr. Enoch. "Therefore our study suggests that women with this genotype may be more vulnerable to anxiety because their COMT levels fall below a minimum threshold."The men in the study who had the COMT Met158/Met 158 genotype did not rank as high on anxiety tests as the women, and their scores were similar to the test results of men with other genotypes. They also did not have the low-voltage alpha EEG. "Men naturally tend to have lower anxiety scores," says Dr. Enoch, "but it's possible that there may be a caveat here that a larger sample population may be necessary to study the association in men."
