People with major depressive disorder (MDD) have low concentrations of the molecule acetyl-L-carnitine (LAC) in their blood. Severe LAC deficiency is also associated with lower responses to anti-depressant medication. The finding could pave the way for a blood test not only for the presence of depression, but for its severity too, a potentially transformative step in the fight against mental illness. The same research also indicated that childhood trauma can lower LAC levels decades later, shedding light on its relationship with adult depression.

Rats with low levels of LAC have been found to show symptoms consistent with depression. LAC changes the expression of several genes important to healthy brain function, including preventing the loss of brain cells in the hippocampus. It also helps transport fatty acids into mitochondria so deficiencies could lead to many serious implications.

Dr Carla Nasca of Rockefeller University found something similar in humans, where the diagnosis of depression is probably more accurate since patients can confirm their symptoms. In the Proceedings of the National Academy of Sciences, Nasca and colleagues report that 71 acutely depressed patients averaged 25 percent lower LAC levels than 45 non-depressed counterparts of similar age.

Moreover, Nasca found low LAC levels correlated with more severe symptoms among the most depressed segments of her sample. The relationship was particularly strong for those who hadn't responded to anti-depressant medication, known as treatment-resistant depression (TRD). Histories of childhood sexual or physical abuse were associated with low LAC levels, as was emotional neglect in women with TRD, but not in men.

LAC supplementation in rats has been found to change their behavior and lead to brain changes that indicate their depression has improved. As a bonus, supplemented rats also experienced reduced insulin resistance. Nasca's work did not test the potential of such supplementation in humans.

Even if LAC transfusions prove ineffective or unsafe, the potential for diagnosis could be world-changing. Depression is greatly underdiagnosed – by an estimated 50 percent in the United States, leaving tens of millions of people getting no treatment at all. Moreover, diagnosis achieves little if it is not accepted. Telling an employer or welfare agency “my doctor thinks I’m depressed” seldom draws the same sick leave or disability benefits applied to other conditions. An objective test could change that.

Furthermore, the symptoms of MDD can be very difficult to distinguish from type II bipolar disorder, but the treatments are very different. Recipients of the wrong medication are at a greatly increased risk of suicide. Further research will be required to see if LAC testing can distinguish the two.

Finally, research into depression treatments has been hampered by the difficulty in measuring their success, rare cases of dramatic improvement aside. This test could provide an objective scale to show whether a trial treatment is helping or not.

The association between low LAC levels and MDD easily met standards of statistical significance. Nevertheless, testing an individual's blood plasma for LAC doesn't provide a reliable test on its own. No depressed person in Nasca's sample had a LAC level much above 10 micromoles per liter (μmol/L), and only one healthy person was below 4 μmol/L. However, the majority of members of both groups fell between these values, where the test could not distinguish an individual's status.

This isn’t the first time a possible blood test for depression has been identified. However, previous work on RNA markers relied on smaller samples and has yet to be confirmed on a wider scale. Whether the two approaches can be combined into a single test that is more accurate than either on their own will require further research.