Effect of basal ganglia injury on central dopamine activity in Gulf War syndrome: Correlation of proton magnetic resonance spectroscopy and plasma homovanillic acid levels

Background: Many complaints of Gulf War veterans are compatible with a neurologic illness involving the basal ganglia. Methods: In 12 veterans with Haley Gulf War syndrome 2 and in 15 healthy control veterans of similar age, sex, and educational level, we assessed functioning neuronal mass in both basal ganglia by measuring the ratio of N-acetyl-aspartate to creatine with proton magnetic resonance spectroscopy. Central dopamine activity was assessed by measuring the ratio of plasma homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenlyglycol (MHPG). Results: The logarithm of the age-standardized HVA/ MHPG ratio was inversely associated with functioning neuronal mass in the left basal ganglia (R²=0.56; F_1,27=33.82; P<.001) but not with that in the right (R²= 0.04; F_1,26= 1.09; P =.30). Controlling for age, renal clearances of creatinine and weak organic anions, handedness, and smoking did not substantially alter the associations. Conclusions: The reduction in functioning neuronal mass in the left basal ganglia of these veterans with Gulf War syndrome seems to have altered central dopamine production in a lateralized pattern. This finding supports the theory that Gulf War syndrome is a neurologic illness, in part related to injury to dopaminergic neurons in the basal ganglia.