“Genetic studies also seemed to rule out any connection between genes affecting serotonin levels and depression, even when the researchers tried to consider stress as a possible cofactor.”
Joanna Thompson in Quanta: People often think they know what causes chronic depression. Surveys indicate that more than 80% of the public blames a “chemical imbalance” in the brain. That idea is widespread in pop psychology and cited in research papers and medical textbooks. Listening to Prozac, a book that describes the life-changing value of treating depression with medications that aim to correct this imbalance, spent months on the New York Times bestseller list.
The unbalanced brain chemical in question is serotonin, an important neurotransmitter with fabled “feel-good” effects. Serotonin helps regulate systems in the brain that control everything from body temperature and sleep to sex drive and hunger. For decades, it has also been touted as the pharmaceutical MVP for fighting depression. Widely prescribed medications like Prozac (fluoxetine) are designed to treat chronic depression by raising serotonin levels. Yet the causes of depression go far beyond serotonin deficiency. Clinical studies have repeatedly concluded that the role of serotonin in depression has been overstated. Indeed, the entire premise of the chemical-imbalance theory may be wrong, despite the relief that Prozac seems to bring to many patients.
A literature review that appeared in Molecular Psychiatry in July was the latest and perhaps loudest death knell for the serotonin hypothesis, at least in its simplest form. An international team of scientists led by Joanna Moncrieff of University College London screened 361 papers from six areas of research and carefully evaluated 17 of them. They found no convincing evidence that lower levels of serotonin caused or were even associated with depression. People with depression didn’t reliably seem to have less serotonin activity than people without the disorder. Experiments in which researchers artificially lowered the serotonin levels of volunteers didn’t consistently cause depression. Genetic studies also seemed to rule out any connection between genes affecting serotonin levels and depression, even when the researchers tried to consider stress as a possible cofactor. “If you were still of the opinion that it was simply a chemical imbalance of serotonin, then yeah, it’s pretty damning,” said Taylor Braund, a clinical neuroscientist and postdoctoral research fellow at the Black Dog Institute in Australia who was not involved in the new study. (“The black dog” was Winston Churchill’s term for his own dark moods, which some historians speculate were depression.)
The realization that serotonin deficits by themselves probably don’t cause depression has left scientists wondering what does. The evidence suggests that there may not be a simple answer. In fact, it’s leading neuropsychiatric researchers to rethink what depression might be. More here.