Infants and small children who over-respond to sound, sight, or touch are thought to have above-average risk for developing an anxiety disorder. A new study adds to the accumulating body of research supporting this concept and may point to potential biomarkers and targets for future strategies designed to reduce the risk.

A team led by Chad M. Sylvester, M.D., Ph.D., of the University of Washington, St. Louis, used fMRI to study the brain responses of 45 newborns to a set of auditory stimuli delivered while they were asleep. The results were correlated with an assessment of anxiety in their mothers. The results were reported in the American Journal of Psychiatry.

The team also included three BBRF Scientific Council members: Joan Luby, M.D., BBRF 2020 Ruane Prize winner, 2004 Klerman Prize winner, 2008 and 2004 BBRF Independent Investigator and 1999 Young Investigator; Daniel Pine, M.D., 2011 BBRF Ruane Prize winner and 2000 BBRF Independent Investigator; and Deanna Barch, Ph.D., 2013 BBRF Distinguished Investigator, 2006 Independent Investigator and 2000 and 1995 Young Investigator.

The infants in the study ranged in age from 3 to 40 days. Each received an fMRI scan that lasted 6 to 7 minutes, during which time loud white-noise bursts lasting four tenths of a second were delivered at irregular intervals. Such unpatterned sensory stimuli are termed "deviant" by scientists, meaning that to those who hear them, they are unexpected.

The response of various brain systems to unexpected stimuli provides insights into processes in the brain that have evolved to enable individuals to respond to "salient" (i.e., relevant or important) information entering the brain from the senses, and just as important, to suppress responses to stimuli that are not relevant or helpful in a given context.

In older children and adults with anxiety disorder, researchers have noted weakened inhibitory responses, which can translate into an individual's overresponse to unexpected but trivial stimuli such as the blaring of a car horn or drone of a lawnmower engine. Overresponse to sensory information can also lead individuals to become overly vigilant, to the point where "being on the lookout" for unexpected (but trivial) inputs can impair function. Both overresponse and hypervigilance are among the symptoms of anxiety disorders.

Dr. Sylvester and colleagues found that the infants manifested a robust and widespread neural response to irregular stimuli, similar to patterns found previously in adults. In adults, the affected brain regions include three neural networks that respond to salient stimuli: the salience network, the cingulo-opercular network, and the ventral attention network.

The potential importance of these observations was seen when network activity levels in the newborns were correlated with their mothers' scores on a standard measure of anxiety, derived from a survey the mothers completed within weeks following childbirth. All the mothers participating in the study were within the "normal" range of "trait anxiety" scores, and were ranked in relative terms from higher to lower.

In infants born to mothers with higher anxiety scores, activity was higher in a subset of brain regions when they (the infants) were exposed to deviant stimuli. In other brain regions, activity following deviant stimuli was lower in infants born to mothers with higher anxiety scores.

These may be valuable biomarkers, the researchers say. "Our results suggest that neural stimulus-response properties near birth signal risk" for processes in the brain "that generate later-life anxiety."

Examining brain function in neonates may illuminate risk markers, they say, "that could be obscured" in older individuals whose brains may have a chance to compensate for deficiencies at the beginning of life. "Measuring brain activity differences during infancy may uncover 'core' deficits that occur before" such subsequent changes.

The researchers note that children with anxiety disorders "face elevated risks in adulthood of many other disorders, including depression, substance-use disorders, eating disorders, and bipolar disorder. Thus, uncovering early risk profiles could inform attempts to identify mechanism-based targets that reduce the burden from many mental disorders."