What Do White-Matter Changes Have to Do With Anxiety?

The scientists then used a relatively new neuroimaging method called diffusion tensor imaging (DTI) on the subjects. DTI makes it possible to map the organization and strength of white matter—that is, its integrity—in the human brain. Finally they assessed whether there were any significant differences in white-matter integrity between subjects who scored high on anxiety and those who did not, while taking possibly confounding factors—age, gender, years of education, alcohol consumption, IQ, and Mini-Mental State Examination results—into consideration.

The researchers found that subjects who scored high on anxiety had decreased white-matter integrity in precisely those brain areas anticipated—the amygdala, hippocampus, thalamus, subgenual cingulate, and orbitofrontal cortices—as well as in the areas connecting them.

Whether decreased white-matter integrity actually contributes to anxiety and depressive disorders remains to be seen. But if it does, there might be clinical implications for such a finding.

"I doubt that a drug targeting the mechanisms for the decreased white-matter integrity observed in our study alone would suffice to treat symptoms of anxiety and depression, but it could perhaps be used successfully in conjunction with psychological therapeutic interventions and other pharmacological substances," Westlye told Psychiatric News. "I am not aware of any scientists looking for such a drug, but since decreased white-matter integrity has been found in many neurodegenerative and psychiatric disorders, including Alzheimer's disease and schizophrenia, I would not be surprised if this is an active area of research in the pharmaceutical industry."

Westlye also pointed out that while the specific gene variants coding for the harm-avoidance personality trait have not yet been identified, "it is very likely that some of these variants have their impact on harm avoidance via defects in the brain's white matter." Indeed, he and his team are collecting genetic data from their subjects in this study to see whether they can "detect gene variants involved in both anxiety-related personality traits and white-matter integrity."

"This study has been thoughtfully designed and has dealt with most of my criticisms about much research into personality characteristics such as harm avoidance," Anne Farmer, M.D., a professor of psychiatric nosology at the Institute of Psychiatry in London, England, told Psychiatric News. Farmer published a study on a related subject—the personality trait of harm avoidance as a predisposing factor to major depression—in the May 2003 Archives of General Psychiatry. "The results … point to disruption in the architecture of [nerve axons], which certainly makes sense in terms of current theories about the etiology of depression and anxiety."

The study was funded by the Research Council of Norway and the University of Oslo.