The Song of the Cell: An Exploration of Medicine and the New Human

by Siddhartha Mukherjee

discovered a “slow” pathway, instigated by serotonin, that might be responsible for depression. Serotonin, Greengard and other researchers had found, doesn’t only act as a “fast” neurotransmitter, and depression isn’t just a malfunctioning neuronal circuit that can be reset by increasing serotonin in the synapse. Rather, serotonin sets off a “slow” signal in neurons—biochemical signals that come on cat’s feet—including altering the activity and function of several intracellular proteins that Greengard’s lab had identified. Paul believes that these proteins, which modify neuronal activity, are crucial to the slow signaling in neurons that regulate mood and emotional homeostasis. In his earlier work, he had shown that one such factor, called DARPP-32, is critically responsible to the way a neuron responds to another transmitter, called dopamine, which is involved in many other neurological functions, including our mind’s response to reward and addiction. “It’s not just the level of serotonin,” Paul said emphatically, jabbing his fingers in the air. The New York air was clear and bitingly cold, and his breath left a drifting trail of mist behind him. “That’s way too simple. It’s what serotonin does to the neuron. The way it changes the neuron’s chemistry, and its metabolism,” he said. “And that might vary from one individual to the next.” He turned to face me. “In your case, there might be inputs, or genetic reasons, that makes the response more difficult to sustain or restore.”