The quest for biological markers of mental illness has turned up few good candidates. But emerging evidence suggests that the erosion of telomeres at the ends of chromosomes might be linked to brain function.

Telomeres, the repetitive DNA sequences that cap chromosomes, protect the vulnerable ends of replicating chromosomes in a process similar to how the plastic wrapping at the ends of shoelaces protects them from fraying. In 1990, researchers discovered that telomere length in somatic cells is inversely correlated with age (Nature 346, 866–868; 1990). A newborn child, for example, has between 6,000 and 15,000 repeating telomeric base pairs. But, with each cell replication, the telomeres shorten by a few base pairs. On average, human telomeres disappear at a rate of 40–60 base pairs per year. This progressively occurs until the telomeres reach a critically short length, impairing the cells from efficiently replicating, eventually leading them to become cancerous, become dormant or die.

Since the 1990s, evidence has accumulated tentatively linking telomere erosion to a suite of clinical disorders. Telomeres seem to erode more rapidly in disorders such as diabetes, obesity, hypertension, cardiovascular disease and chronic stress (Atherosclerosis 195, 83–89; 2007; Obesity, doi:10.1038/oby.2008.413; 2008; Intern. Med. 42, 150–153; 2003).

In 2000, Thomas von Zglinicki's group at Newcastle University's Institute for Ageing and Health in Britain reported that increased telomere erosion is also found in dementia, the first such report in a neurological disorder (Lab. Invest. 80, 1739–1747; 2000). “When I first saw the results, my first impression was that this is nonsense,” says von Zglinicki, whose group has since confirmed that telomere length provides a personal history of cell replication, oxidative stress and inflammation, much like the way growth rings divulge information of a tree's chronological age.

But von Zglinicki is still skeptical that information based solely on telomere length can be used to diagnose disorders. “Telomere length depends on many factors, with genetics probably playing the strongest role,” says von Zglinicki, who is now conducting research that hopes to use telomere length alongside an arsenal of other measurements (including degree of oxidative stress, DNA damage and inflammation) to form a diagnosis.

In 2003, an analysis of immune cells taken from people with Alzheimer's disease suggested that telomeres erode more rapidly in those with the disorder than their healthy counterparts (Neurobiol. Aging 24, 77–84; 2003).

Some scientists have speculated that schizophrenia is actually a syndrome of accelerated aging (Schizophr. Bull., doi:10.1093/schbul/sbm140; 2007). And in February and May of this year, two reports were published hinting that people with schizophrenia have telomere erosion rates almost twice those of normal people (J. Psychiatry Neurosci. 33, 244–247; 2008; Mol. Psychiatry 13, 118–119; 2008). “This is significant because it is something that can actually be measured in psychiatric disorders,” says Hung-Teh Kao, an author of one of the studies and an associate professor of psychiatry at Brown University.

“Normally, all the diagnostic evidence we gather is from patient interviews, as there is no laboratory test for schizophrenia,” says Kao. His study, which looked at the DNA of white blood cells, suggests that, on average, people with schizophrenia in their late 30s have telomere lengths about 1,700 base pairs shorter than normal people of their age.

Although the exact role of telomere erosion in disease and in the brain remains a mystery, it does provide a glimmer of hope to areas of psychiatry research, such as schizophrenia, where the unsuccessful quest for a pathophysiological explanation has been elusive. “Telomere length may not be the end result,” says Kao, “but having something measurable is a first and important step.”