What perhaps many do not know is that the causes of the development of depression go far beyond serotonin deficiency in the brain. Through some clinical studies, it has been repeatedly concluded that the role of serotonin in depression has been "exaggerated", which may show that the chemical imbalance theory may be wrong.
The real causes of depression
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People often think they always know what causes chronic depression, but research shows that over 80% of the public actually have a chemical imbalance in their brain. The book "Listen to Prozac" spent months on the New York Times bestseller list, as the work describes the transformative value of treating depression with medications that aim to correct this imbalance.
The imbalanced brain chemical being talked about is the famous serotonin, which is an important neurotransmitter that promotes feel-good effects. It helps regulate the brain systems that control everything from sleep to sex drive, as well as body temperature and hunger. For many decades, serotonin has also been touted as a pharmaceutical MVP for combating depression.
Medicines that are widely prescribed – such as Prozac (fluoxetine) – are provided to treat the disease in its chronic “mode”, as they increase the level of serotonin in the brain.
Research points to other causes that go beyond low serotonin
Joanna Moncrieff of the University of London took 361 papers from six research areas to examine and carefully evaluated at least 17 of them. Among them, she found no convincing evidence that lower serotonin levels were the cause of depression or that it was even associated with the state in question.
People who had depression did not appear to have less serotonin activity in their brain than people without the disorder. The genetic study that was done apparently also seemed to rule out any link between the genes that affect hormone levels and the disease, even when stress was considered as a possible co-author.
After arriving at the realization that serotonin deficiency probably could not be the cause of depression, scientists began to go after what would then be the main cause.
the wrong treatment
Doctors began to focus on serotonin as the cause of depression because of a drug for tuberculosis. In the 1950s, physicians began to prescribe iproniazid, which is a compound developed to target the Mycobacterium tuberculosis bacterium residing in the lungs. The drug wasn't exactly very good for treating tuberculosis, but it ended up favoring patients in another way.
A completely unexpected and pleasant side effect surprised everyone: “The lung function and everything else was not getting much better, but mood tended to improve," said clinical psychiatrist and director of the Depression Research Program at Yale University, Gerard Sanacora.
Surprised with the results of the medicine that was initially used only for the treatment of tuberculosis, the researchers started studies to find out how iproniazid and drugs related acts in the brain of rats and rabbits, to then initiate a new treatment for depression.
They found that the drugs prevented the animals' bodies from absorbing compounds called amines and serotonin, chemicals that transmit messages between nerve cells in the brain.
By the late 1980s, the introduction of selective serotonin reuptake inhibitor (SSRI) drugs, such as Prozac, had become commonplace. The hypothesis that serotonin is still the most plausible explanation for depression is passed on to this day.