Lack of a Single Molecule May Indicate Severe and Treatment Resistant Depression
Depression is not a single disease. The term refers to a cluster of feelings and behaviors, brought on by a variety of underlying causes. And, unfortunately, it is often difficult to determine which type of depression a person has: a physician cannot take a mouth swab or a blood sample to diagnose the nature and severity of a patient’s psychiatric condition–at least not yet.
According to a new multi-institutional study, published in PNAS, doctors may one day be able gain insight into an individual’s depression by analyzing his or her blood. Rockefeller scientists Bruce McEwen and Carla Nasca, in collaboration with Natalie Rasgon, psychiatry professor at the Stanford University School of Medicine, show that patients with a particular type of depression have decreased blood levels of the molecule acetyl-L-carnitine (LAC)–a finding that may lead to improved diagnosis and treatment of major depressive disorder (MDD).
When LAC is Lacking
Naturally produced by the body, LAC performs a number of crucial tasks in the brain. For example, the molecule regulates energy metabolism and interacts with DNA to promote the expression of important genes. Specifically, it acts on a gene that controls levels of the neurotransmitter glutamate–a chemical implicated in almost everything that the brain does.
McEwen, the Alfred E. Mirsky Professor, and Nasca, a postdoctoral fellow of the American Foundation for Suicide Prevention, have studied the link between LAC and mood disorders using animal models. In one study, they showed that LAC supplements ameliorate depressive symptoms in mice by reversing brain-cell impairment caused by an excess of glutamate. In a separate rodent study, they observed that LAC treatment reduces depressive behavior and stress-associated neural dysfunction in the medial amygdala, a brain region involved in social interactions. These findings strongly suggest that LAC deficits contribute to a depression-like state in mice, leading the scientists to wonder whether the molecule plays a similar role in humans.