According to the most recent estimates from the National Institutes of Health (NIH), over 16 million American adults had at least one major depressive episode in 2016.
The disorder severely interfered with the daily lives of 10 million of these people.
New research suggests that this form of treatment-resistant depression may be down to a deficiency of a molecule called acetyl-L-carnitine (LAC), and that measuring the blood levels of this molecule may prove to be an effective way of diagnosing the disorder.
The new study was carried out by neuroendocrinology professor Bruce McEwen and research associate Carla Nasca — both affiliated with the Rockefeller University in New York, in collaboration with Natalie Rasgon, a professor of psychiatry at the Stanford University School of Medicine in California.
LAC, the brain, and depression
In a healthy body, LAC is responsible for a number of key brain processes. The molecule plays a crucial role in intermediary metabolism and drives the expression of certain genes.
Some studies have shown that dietary supplementation with LAC has a neuroprotective and antidepressant role, as well as being a promising avenue for anti-aging therapies that may slow down cognitive decline.
Furthermore, previous work led by Nasca and Prof. McEwen has shown that supplementing LAC improves depressive symptoms in mice. This is because LAC regulates a gene that, in turn, controls the levels of a substance called glutamate.
Glutamate is an important neurotransmitter that facilitates the communication between nerve cells, sending signals between neurons and enabling the brain to learn and form new memories.
Too much glutamate, however, can damage the neurons. Additionally, some studies have found that women with depression and suicidal tendencies have overactive glutamate receptors.
In their previous work, Nasca and Prof. McEwen showed that treating rodents with LAC ameliorates brain dysfunction in an area called the medial amygdala — a brain region with key roles in emotional behavior and social interactions.
LAC deficiency and treatment resistance
In the current study, the researchers assessed the LAC blood levels of people who had received a diagnosis of major depressive disorder and compared them with people who did not have the disorder.
The scientists found that LAC levels were significantly lower in people with depression compared with age-matched controls.
Furthermore, the researchers found that individuals with extremely low levels of LAC had more severe forms of depression and were more likely to develop the disorder early on.
Also, low levels of LAC correlated with a history of childhood trauma and with treatment-resistant depression. The association was particularly strong in women.
Carla Nasca explains: "In patients with depression, something is causing a problem in the mechanisms related to the biology of LAC."
"And, surprisingly, the deficiency in LAC is even stronger in patients that don't respond to standard antidepressants," she adds.
Prof. McEwen also comments on the findings, saying that they "should motivate research into the action of LAC on glutamate function and behavioral states."
"Additional research into other novel biomarkers to more precisely pinpoint [major depressive disorder] diagnosis could ultimately lead to a different way of thinking about treatments."
Prof. Bruce McEwen