Only connect

Depression is bad for the brain, and attempts to treat it often fail. But Yale researchers and a Belgian company have come up with a technique that can examine nerve cells in the brains of living people. It offers many possibilities—including a way to develop novel kinds of antidepressants.

Yale neuropsychologist Irina Esterlis and her colleagues used the new technique to show that depression correlates with lower numbers of synapses in the brain. (Synapses are the tiny gaps between nerve endings that allow two nerve cells to communicate.) They injected participants with a tracer that attaches to a protein found on every nerve ending. The tracer tagged each synaptic connection in a way that made it visible to a positron emission tomography (PET) scanner.

Until now, it was impossible to determine synaptic density in the brains of living people. But Esterlis’s team confirmed that low synaptic density is bad news. In people with major depressive disorder or post-traumatic stress disorder (PTSD), they found, synapses between neurons in parts of the brain involved with mood and cognition are sparser than in healthy people. (The findings appeared in the April issue of Nature Communications.)

Consider ketamine: for patients with severe treatment-resistant depression, it can work like magic. It does this by synaptogenesis, or regrowing synapses in the brain; the effect on symptoms can last for up to ten days. The PET imaging technique, Esterlis says, will help researchers measure the effects of new medicines—comparing synaptogenic drugs, working out the complexities of dosing, seeking longer-lasting effects.