September 20, 2018

Anxiety disorders affect some 40 million Americans; more than 16 million Americans suffer from depression, according to the Anxiety and Depression Association of America. Researchers at the University of Wisconsin–Madison and the Wisconsin National Primate Research Center (WiNPRC) have discovered brain pathways in juvenile monkeys that may lead to the development of anxiety and depression later in life.

Extreme early life anxiety is a significant risk factor for anxiety disorders and depression in humans, and discovering a connection between two areas of the brain that are connected to anxious temperament in pre-adolescent rhesus macaques could be a significant breakthrough.

“We are continuing to discover the brain circuits that underlie human anxiety, especially the alterations in circuit function that underlie the early childhood risk to develop anxiety and depressive disorders,’’ said Ned Kalin, MD, chair of the psychiatry department at UW–Madison.

“In data from a species closely related to humans, these findings strongly point to alterations in human brain function that contribute to the level of an individual’s anxiety. Most importantly these findings are highly relevant to children with pathological anxiety and hold the promise to guide the development of new treatment approaches.”

The study used functional magnetic resonance imaging (fMRI) to study the connections between two regions of the brain. It builds on the group’s earlier study that used positron emission tomography (PET) scans to study metabolism in the same circuitry; fMRI detects oxygenation changes in blood while PET measures neuronal metabolic activity. Taken together, said Jonathan Oler, PhD, the study’s co-lead author, the new findings demonstrate that the degree of synchronization between these brain regions is correlated with anxious temperament.

“When we began this research, we knew so little about the brain regions involved, especially in primate species,’’ Oler says. “This study speaks to how important it is to study animals that are related to humans as they allow us to learn about the causes of human anxiety and by so doing we can potentially develop better treatment and hopefully prevention strategies.”

Oler and Kalin say their analysis suggests that the same genes that underlie the connectivity of this circuit also underlie anxious temperament. Studies underway in the Kalin laboratory are aimed at identifying gene alterations in the anxiety-related brain regions, and have the potential to lead to new treatments that are directed at the cause of anxiety rather than just the symptoms.

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