Depression affects a relatively large portion of Americans. It is normal to feel depressed on occasion, but severe negative moods and lack of interest in what was once considered a pleasurable activity, for a prolonged length of time (everyday for 2 weeks), may reflect major depressive disorder. Approximately 16% of Americans will experience major depressive order at some point in their lives (Kessler and Wang 2008). Major depressive disorder varies in severity and can persist anywhere from months to years. For some people it becomes debilitating and can contribute to other health problems. Depression is the leading risk factor for suicide, and is among the top three causes of death for people between ages 15 and 35 (Gazzaniga 2018). Depression may not only alter the life of those who experience it, but also the lives of those close to the sufferer. If you have ever been close with someone suffering major depression you have probably witnessed the life disruption it entails.
Much research has focused on uncovering causes of depression. Depression involves numerous variables and cannot be explained by what is often referred to as a “chemical imbalance,” or shortage of a specific neurotransmitter called serotonin. Neurotransmitters transmit signals from one neuron (a type of brain cell) to another. Mental processes and behavior are influenced by varying degrees of neurotransmitter activity. There are two general categories of neurotransmitters: mediating and modulatory. Mediating neurotransmitters act directly on target cells; modulatory neurotransmitters adjust and fine-tune actions of mediating neurotransmitters. Serotonin is a modulatory neurotransmitter.
When I discuss depression with students in psychology courses the topic almost always involves talking about the chemical imbalance myth. Students often say things like “But I thought depression was due to a chemical imbalance” or “I have always heard that depression is because of low serotonin.” Many people suffering depression say they can’t help that they have depression, as “it is due to a chemical imbalance.” This leads them to often accept that they must take medication, and taking medication is the only thing they can do the deal with their condition. According to the drug company Pfizer the antidepressant drug Zoloft works by correcting a chemical imbalance in the brain. Forest Pharmaceuticals state on their website that research indicates the cause of depression is a chemical imbalance, most notably serotonin imbalance. In addition, they assert Lexapro (an antidepressant) is thought to work by restoring the brain’s chemical balance (Jarrett 2015). They never indicate what exactly that “balance” is. Is the balance different for different brain areas? Is a different balance required when different neurotransmitters are interacting?
Neuroscientist Christian Jarrett asserts that the imbalance myth can be traced to the 1950s and early 1960s. Psychiatric researchers discovered drugs that alter neurotransmitter levels in the brain sometimes change people’s mood. As an example, when some people were given the blood pressure drug Raudixin, which decreases serotonin levels, their moods became negative. Similar observations led researchers to conclude emotional states are associated with neurotransmitter levels. However, these researchers didn’t claim that mood was solely dependent on chemical levels. They pointed out that anxiety and depression involve many biochemical, physiological and psychological factors.
Studies do not consistently show that serotonin levels are lower in people with depression than without depression. Studies do not consistently show that L-tryptophan, which boosts serotonin levels, enhance the mood of depressed people (Shaw et al. 2002). Artificially reducing people’s level of serotonin doesn’t reliably produce a depressing effect (Delgado et al. 1994). These inconsistencies are often ignored by those promoting the “chemical imbalance” explanation of depression. They often point to the effectiveness of drugs called SSRIs (selective serotonin reuptake inhibitors), which boost serotonin levels. Findings regarding benefits of SSRIs are highly variable; sometimes they are effective, and sometimes they aren’t. Often the difference between those receiving the drug and those receiving placebo are not statistically significant. The U.S. National Institute of Mental Health Laboratory of Clinical Science has stated that “the efficacy of selective serotonin reuptake inhibitors…cannot be used as primary evidence for serotonergic dysfunction in the pathophysiology of any mental disorder” (Lacasse and Leo 2005).
If low levels of serotonin are the cause of depression it is puzzling why drugs that have the opposite effect of SSRIs have been shown to decrease levels of depression. Tianeptine, which involves decreasing levels of serotonin, has been show to be an effective treatment for those suffering depression (Jarrett 2015). Nickel and colleagues (2003) conducted a double blind, randomized controlled study comparing the effects of receiving tianeptine (selective serotonin reuptake enhancer) and paroxetine (selective serotonin reuptake inhibitor). The participants in the study were 44 depressed inpatients. Participants improved in all measures, with no statistically significant differences between those receving tianeptine and paroxetine. The researchers concluded both drugs are clinically effective; however, their opposite mechanisms challenge the claim that low levels of serotonin are the cause of depression. Drugs targeting different mechanisms and varying neurotransmitters have been shown to be successful for the treatment of depression. As an example, Ketamine, a veterinary anesthetic, has been shown to improve depressive symptoms (Kandel 2018). Ketamine doesn’t target serotonin but instead the primary excitatory neurotransmitter glutamate.
Most antidepressants promote the growth of new cells and new brain connections; it may be that the primary mechanisms underpinning successful drug treatment involve these factors. Jarrett suggests that the most important action of antidepressants (beyond placebo effects) might be to increase the growth of new brain cells.
Depression is Complex
Brain chemistry is important for mental processes, all of which involve electro-chemical signaling. An excess or shortage of neurotransmitters can lead to negative outcomes. Excessive glutamate can cause abnormally high brain activity producing seizures can lead to brain cell death and destroy brain connections. Low levels of the primary inhibitory neurotransmitter GABA (gamma-aminobutyric acid) can cause seizures. In the case of depression a simple explanation involving a chemical imbalance isn’t enough: Depression is complex and involves many variables and interactions.
Genetic factors, as well as situational and cognitive factors, should also be investigated when determining the foundations of depression. Situational factors such as the loss of a loved one or divorce may lead to depression. Depression risk is increased when one experiences multiple negative events. Individuals that demonstrate negative thinking regarding themselves, their situations and the future are at risk for depression.
It is likely that one of the reasons the chemical imbalance myth has persisted is in the hope that it will reduce stigma. If one has a chemical imbalance they can’t control, they can’t be blamed for what is sometimes viewed as a mental weakness. Unfortunately a strictly biological explanation for depression doesn’t seem to take away the stigma. A meta-analysis was conducted by Schomerus and colleagues (2012) examining people’s perceptions of mental illness. They found an increased awareness of biological explanations over time, but they didn’t find this awareness decreased the stigma of mental illness: “[A] better biological understanding of mental illness has not translated into greater social acceptance of mentally ill persons” (Schomerus et al. 2012, 449).
Delgado, P.L. et al. 1994. Serotonin and the neurobiology of depression: Effects of tryptophan depletion is drug-free depressed patients. Archives of General Psychiatry, 51(11), 865.
Gazzaniga, M. 2018. Psychological Science 6th edition. New York, NY: Norton.
Jarrett, C. 2015. Great Myths of the Brain. Malden, MA: Wiley Blackwell.
Kandel, E. 2018. The Disordered Mind: What Unusual Brains Tell Us About Ourselves. New York, NY: Farrar, Straus and Giroux.
Kessler, R.C, and Wang, P.S. 2008. The descriptive epidemiology of commonly occurring mental disorders in the Untited States. Annual Review of Public Health, 29, 115-129.
Lacasse, J.R., and Leo, J. 2005. Serotonin and depression: A disconnect between the advertisements and the scientific literature. PLos Medicine, 2(12), e392.
Nickel, T. et al. 2003. Clinical and neurobiological effects of tianeptine and paroxetine in major depression. Journal of Clincal Psychopharmacology, 23, 153-168.
Schomerus, G. et al. 2012. Evolution of public attitudes about mental illness: A systematic review and meta-analysis. Acta Psychiatrica Scandinavica, 125(6), 440-452. Shaw, K. 2002. Tryptophan and 5- hydroxytryptophan for depression. Cochrane Database System Review, 1.