Sneezes and tics

Histamine is best known for its association with runny noses, itchy eyes, and sneezing—not tics. But a rare mutation causing histamine deficiency in the brain has given researchers a better idea of what goes awry in Tourette syndrome (TS).

For several years, associate professor of psychiatry Christopher Pittenger ’94, ’94MS, has studied a family of eight siblings and their father, all of whom have or have had some degree of TS, a disorder that provokes repetitive, semi-involuntary movements. All nine have a mutated histidine decarboxylase gene (Hdc), leaving them with faulty copies of the enzyme that makes histamine.

This family is exceptional. Most TS cases arise from different causes, poorly understood, and most TS patients have normal Hdc genes. But lab mice with an Hdc mutation are prone to ticlike behavior, sniffing the same spot again and again—confirming that the mutation causes TS in these rare cases.

Pittenger’s team found that injecting histamine into the basal ganglia of mice reduced levels of dopamine, which is known to be involved in TS. Excessive dopamine can lead to abnormal movements.

Giving the mice histamine eliminated their ticlike sniffing, showing that histamine can regulate dopamine levels. (The results appeared in the January 8 Neuron.)

A clearer picture of TS mechanics and histamine’s role could one day lead to better TS drugs—even for TS patients without the mutation. “Understanding the details,” Pittenger says, “will hopefully lead us to new ways to tweak the system, to try to get it back into balance.”