Chemical mapping of anxiety in the brain of healthy humans: An in vivo H-1-MRS study on the effects of sex, age, and brain region

We recently presented results in an in vivo study of human brain chemistry in 'physiologic' anxiety, i.e., the anxiety of normal everyday life. Normal subjects with high anxiety demonstrated increased concentration of chemica ls in orbital frontal cortex (OFC) as compared to lower anxiety. In a separ ate study of aging we demonstrated a decrease of total chemical concentrati on in OFC of middle-aged subjects, as compared with younger age. This brain region also showed gender dependence; men demonstrating decreased chemical concentration compared to women. We hypothesized that these sex- and age-d ependent differences in OFC chemistry changes are a result of anxiety effec ts on this brain region. In the present study we examined these sex- and ag e-differential regional brain chemistry changes (as identified by localized in vivo proton magnetic resonance spectroscopy [H-1-MRS]) in relation to t he state-trait-anxiety (as measured by the State-Trait Anxiety Inventory) i n 35 healthy subjects. The concentrations for all nine chemicals of H-1-MRS spectra were measured relative to creatine across multiple brain regions, including OFC in the left hemisphere. Analysis of variance showed anxiety-s pecific effects on chemical concentration changes in OFC, which were differ ent for both sexes and age groups. Male subjects showed larger effect of an xiety on OFC chemistry as compared to females when the same sex high-anxiet y subjects were compared to lower anxiety. Similarly, middle-aged subjects showed larger effect of anxiety on OFC chemistry as compared to younger age when the same age subjects with high anxiety were compared to lower anxiet y. Largest effect of anxiety on OFC chemistry was due to changes of N-Acety l aspartate. The results indicate that the state-trait anxiety has sex- and age-differential patterns on OFC chemistry in healthy humans, providing ne w information about the neurobiological roots of anxiety. Hum. Brain Mappin g 11:261-272, 2000. (C) 2000 Wiley-Liss, Inc.