Researchers question link between depression and serotonin

According to the Centers for Disease Control and Prevention’s most recent polling data, 13.6 percent of American adults take an antidepressant. Most antidepressant medications work by increasing levels of serotonin, the so-called “happy chemical” thought to play a role in mood regulation.

But a recent umbrella review, meaning a review of reviews, suggests there’s little evidence depression is associated with low serotonin levels. These findings contradict the “chemical imbalance” theory of depression, first proposed in the 1960s and made widely popular in the late 1980s due to the insurgence of selective serotonin reuptake inhibitors (SSRIs).

Many psychiatrists already acknowledge the chemical imbalance theory is an oversimplification. And while Christian psychiatrists are skeptical that medication alone can cure depression, they also caution against writing off antidepressants altogether.

Published July 20 in Molecular Psychology by researchers at University College London, the review assessed 17 large-scale studies that collectively included tens of thousands of participants. The authors claim it is the first comprehensive review to evaluate all relevant evidence for the serotonin theory of depression.

The studies selected for analysis covered six major areas of research on the relationship between serotonin and depression, including evaluation of serotonin concentrations and gene expression.

Compiling the data from each of these reviews, the researchers concluded there is no consistent evidence of an association between serotonin and depression. Specifically, they found no evidence that depressed people have lower levels of serotonin than do non-depressed people. Even studies in which serotonin availability was intentionally reduced showed no effect on participants’ mood. Genetic studies showed no differences in the serotonin transporter gene between depressed and healthy groups.

“This research is important because many people take antidepressants because they have been told they have a chemical imbalance. It may be difficult news, but people deserve to know there is no evidence to support this idea,” tweeted lead study author Joanna Moncrieff. But Moncrieff also warned on her website against suddenly stopping an antidepressant treatment, as this could cause severe withdrawal symptoms. She instead recommends working with a medical professional to stop treatment gradually.

Dr. Warren Kinghorn, a psychiatrist at Durham VA Medical Center and joint professor of psychiatry and theology at Duke University’s Medical Center and Divinity School, is not surprised by the study’s findings. He pointed out that depression’s broad clinical definition makes it hard to pinpoint what causes it. “When we talk about depression, [what] we’re talking about is probably a lot of different things that are all bundled into one category,” he said.

Dr. Karl Benzio, a Christian psychiatrist and founder of Lighthouse Network, which provides a helpline and case management for those who need addiction and mental health treatment, described the chemical imbalance theory as reductionist: multiple neurotransmitters likely play a role in depression, not just serotonin.

Kinghorn did not want to downplay the possibility of a biological mechanism contributing to depression. He noted the study excluded certain subtypes of depression from its analysis, including bipolar and postpartum, which could later be proven to have a biological foundation.

He also said the study doesn’t show that antidepressants are ineffective. In fact, other studies show that antidepressants can be beneficial, even if we don’t fully understand how they work. Benzio explained antidepressant medication can be like a bandage that corrects misfiring in the brain.

In his practice, Kinghorn rarely prescribes antidepressants to his patients without also offering a broader set of treatment options. These include therapy and social connection. “I’ll never frame [antidepressants] as ‘this is all you need’,” he said. For milder cases of depression, he believes choosing to pursue therapy without medication can be appropriate.

Benzio has been prescribing antidepressants to patients for 33 years. He said many patients struggling with depression are in a dark fog that prevents them from thinking clearly. Medication can help ease the fog, allowing them to take steps towards improving the quality of their lives, such as exercising and eating well.

But Benzio has never witnessed a patient’s depression being cured by medication. Instead, he recommends an approach that incorporates body, mind, and spirit. While medication attends to the body and can help with better decision-making, psychotherapy (talk therapy) can help enforce better decision-making.

With time, Benzio said better decision-making improves brain chemistry naturally. “It is all about skills, skills, skills,” he said. “In all areas of life, but especially psychological and spiritual skills.” He lamented that because our society prioritizes academic ability and extracurriculars over life skills, most people lack the hard knocks toolkit needed to be resilient amidst trials.

Kinghorn encourages Christians to respond to depression within the framework of who we are as God’s creatures. “We are wayfarers on a journey to God, and we live as … living, breathing beings who love and seek connection with each other,” he said. While medication is often an important component of treatment, to view it as the only component diminishes our humanity.