Link between anxiety disorders and cellular metabolism

Anxiety disorders, ranging from social phobia to post-traumatic stress disorder, are the most common psychiatric diseases in the United States. Research in mice suggests a link between the gene that encodes Glyoxylase 1 (GLO1) and increased anxiety; however, the mechanism underlying this association has remained unclear. The normal role of GLO1 is to degrade cytotoxic byproducts of glycolysis, a function which has no obvious connection to anxiety. Margaret Distler and colleagues at the University of Chicago asked whether the primary substrate of GLO1, methylglyoxal, might have undocumented neurological effects. Using a mouse model, they demonstrated that methylglyoxal stimulates robust activity from GABAA receptors, which are neuron receptors that respond to neurotransmitters. As pharmaceuticals targeting GABAA receptors are mainstays of anxiety treatment, this study provides a definitive functional link between GLO1 activity and anxiety. The team also showed that the inhibition of GLO1 in mice reduced anxious behavior, suggesting GLO1 as a potential novel therapeutic target in humans. These findings have important clinical implications not only for anxiety disorders, but also for other central nervous system diseases having proposed associations with the gene encoding GLO1, including autism, affective disorders, and schizophrenia.