MADISON – Using a technique that could point to a new way to help people with severe anxiety and other treatment-resistant psychiatric illnesses, researchers at the University of Wisconsin-Madison successfully dialed down anxious monkeys’ overactive response to a potential threat by installing a custom chemical switch in their brain cells.
About 30 percent of people with anxiety and mood disorders do not find sufficient relief in available treatments like medications and psychotherapy, leaving many to live with severe and chronic symptoms of anxiety and depression, and a significant risk of suicide. Some of them are helped by more invasive treatment options including deep brain stimulation, in which small electrodes are implanted deep into the brain.
“Treatments such as DBS are not commonly used, but when used in some cases can be very helpful,” says Ned Kalin, chair of the psychiatry department at UW-Madison and a longtime clinician and anxiety researcher. “That some patients, along with their treating physicians, make the decision to undergo such procedures as the implantation of electrodes into the brain illustrates their high level of suffering and how seriously ill they are.”
In a study published recently in the journal Molecular Therapy, Kalin and colleagues described a new method that could alter the function of specific cells in brain circuits implicated in anxiety and other types of psychiatric disorders, and lead to new, less invasive treatments.
The researchers used an established method called DREADDs, Designer Receptors Exclusively Activated by Designer Drugs. The method relies on gene therapy techniques, which make small changes to the genes in targeted cells to change the cells’ behavior. In this case, the idea is to coax brain cells called neurons to produce a unique version of a protein called a receptor on the cell membrane. Cell membrane receptors receive chemical signals that regulate the cell’s function and affect how cells communicate with one another.
Unlike other receptors in the brain that respond to naturally occurring chemical signals, the DREADDs respond only to a chemical not naturally present – the “designer” drug matched to the designer receptor – that can activate the receptor with little or no other effect in the body.
“That could be a drug you could inject or even take orally,” says Patrick Roseboom, a senior scientist in Kalin’s lab and a lead author of the new study. “When such a drug interacts with DREADDs you have the possibility of ‘fine-tuning’ the function of the brain cell that is now expressing this receptor.”