George Aghajanian, MD, professor emeritus of psychiatry, whose work in the area of neuropharmacology has advanced the understanding of and treatments for mental illness, has been chosen to receive a Pioneer Award from The International College of Neuropsychopharmacology (CINP).
The award will be presented to Aghajanian at the 30th CINP World Congress in July in Seoul, Korea.
According to a letter from CINP President Shigeto Yamawaki, the award is reserved for researchers whose discoveries have “transformed our knowledge concerning neurochemical actions into a greater understanding of brain health and disease.”
Aghajanian has made numerous contributions to the field of mental health during his more than 50-year association with the Yale Department of Psychiatry.
In the 1960s, he was the first to record the single cell activity of the newly discovered monoaminergic (serotonergic, noradrenergic, and dopaminergic) neurons in the brain.
“From there, we were able to study their intrinsic electrophysiological properties as well as the effects of neurotransmitters and drugs on their function,” he said. “In essence this work established that monoaminergic neurons were regulated in a negative feedback fashion via somatodendritic autoreceptors (receptors to their own transmitter). Over succeeding decades it was shown that psychotropic drugs produced their effects acting upon presynaptic autoreceptors as well as postsynaptic receptors. This led to clinical applications such as the use of clonidine for opiate withdrawal.”
More recently, in an equal collaboration with Ronald Duman, PhD, Elizabeth Means and House Jameson Professor of Psychiatry and Professor of Neuroscience, Aghajanian worked to show that the rapid and prolonged antidepressant effects of ketamine result from the ability of just a single dose of the drug to rapidly increase synaptic connectivity.
“Essentially, ketamine is able to rapidly activate biochemical pathways that promote synaptogenesis, which surprisingly change brain structure within 24 hours,” he said. “This structural change can explain how just a single dose of ketamine can produce rapid clinical changes that far outlast the presence of the drug in the body.”
He said this mechanism is relevant to the pathophysiology of depression since it has been shown that depression is associated with a marked loss of structural synaptic connections.
“This mechanism contrasts with conventional antidepressants, which take weeks to act, do not restore synaptic connectivity, and are limited in effectiveness in almost half of treated patients during the course of their illness,” he said. “On a broader level, the ketamine studies establish that synapses can be restored, a concept we now find also applies to other major psychiatric disorders such as schizophrenia where there is also a loss of synaptic connectivity.”