New research suggests depression may be linked to blood levels of a substance called acetyl-L-carnitine (LAC), an amino acid that occurs naturally in the body. According to a study published in the Proceedings of the National Academy of Sciences, people with major depressive disorder (MDD) have lower levels of the substance than their healthy peers. What’s more, the study showed deficiencies in LAC reflected both the severity of the patient’s depression and the age of its onset. And patients with the lowest levels of LAC had the worst symptoms. Taken together, the findings suggest a new biological marker for depression—and, potentially, a new path for treatment.
The findings aren’t entirely unexpected. Previous research suggested a link between LAC deficiency and depression in rodents. (Well, “depression-like behavior,” since it’s tricky to diagnose depression in rats.) Given supplemental LAC, they turned around within a few days—compared to the two to four weeks typical of other treatments. That’s true of humans, too: It takes weeks to know whether depression medication is working.
To see whether depressed humans had similarly low levels of LAC, researchers recruited 20- to 70-year-old men and women in New York City who’d been admitted to local hospitals for depressive episodes. They had their blood tested and their medical histories collected; 28 of the patients had moderate depression, while 43 had severe depression. They were matched with healthy people of the same sex and similar age.
Comparing the healthy and depressed people, researchers found the latter had significantly lower LAC levels. That was true for both men and women, and the lowest levels were found among those with the worst symptoms—those most resistant to treatment, or who’d had the earliest onsets of depression. Childhood exposure to violence or a history of abuse, neglect, or poverty also correlated with lower levels of LAC.
“We’ve identified an important new biomarker of major depression disorder,” Natalie Rasgon, professor of psychiatry and behavioral sciences at Stanford and a co-author of the study, told the Stanford Medicine newsletter. Connecting LAC-deficiency to depression can increase our understanding of the biological factors for depression, as well as suggest new avenues for treatment.
“This is the first paper that says people with clinical depression have low levels of this molecule,” says James Potash, professor of psychiatry and behavioral sciences at Johns Hopkins University School of Medicine. “The question mark is: Can you use acetyl-L-carnitine as a treatment for a subset of people with depression?” Potash, who was not involved with the research, is already looking forward to what a randomized, double-blind clinical trial might show. “The hypothesis would be that a subset of people—those who’ve been measured and have a low level of acetyl-L-carnitine in their system—would be the ones who’d respond to this treatment.”
In fact, acetyl-L-carnitine is already available as a dietary supplement; it has been marketed as a nutritional supplement for a variety of cognitive ailments, including depression and Alzheimer's disease. But that means very little about its potential as a treatment. Rasgon cautioned that people shouldn’t just run out and start buying supplements.
“We have many previous examples of how nutritional supplements widely available over the counter and unregulated by the Food and Drug Administration—for example, omega-3 fatty acids or various herbal substances—are touted as panaceas for you-name-it, and then don’t pan out,” she said. In these early stages, acetyl-L-carnitine shows real potential. Only more research will show whether it lives up to it.
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