What is the Connection Between Serotonin and Depression?

The relationship between serotonin and depression is a complex one. In the simplest explanation, low levels of this neurotransmitter, which circulates through the gut and the central nervous system, can directly lead to a depressed mood and anxiety conditions. This explanation leaves out the fact that there are several other identifiable neurotransmitters that affect mood chemistry, such as norepinephrine and GABA. In some cases, low levels of serotonin don’t principally cause depression and it might result from other depleted neurotransmitters or factors that science hasn’t yet identified.

The simple story of serotonin and depression is a useful metaphor when explaining to medical laypeople the interrelationship between the two, particularly if medication is advocated for treatment. It’s true that many people may have cessation of depression if they take medicines called selective serotonin reuptake inhibitors (SSRIs). These prevent receptors in the brain from performing reuptake: in other words, grabbing the free serotonin that circulates the brain and leaving less to keep the mood balanced. When an SSRI prevents this activity, theoretically, more serotonin exists to combat depression or anxiety. People with this rudimentary definition of the relationship between serotonin and depression may feel more comfortable trying an SSRI and understanding depression as medically induced.

Unfortunately, serotonin and depression aren’t always directly correlated. SSRIs don’t alleviate depression in all people with the condition. They may need to be replaced with medications that act on different neurotransmitters, like the selective serotonin and norepinephrine reuptake inhibitors (SNRIs) or drugs like atypical antipsychotics which are increasingly being advocated for treatment resistant depression. Notably, some clinicians do not favor the term "treatment resistant," since it seems to reflect unfavorably on the patient. The condition seems to be resistant only if low serotonin is viewed as the singular possible cause of depression, and most professionals would not make this mistake.

Another important piece to understanding serotonin and depression is that balance is highly important. Adding greater amounts of serotonin to the body may result in a deadly illness called serotonin syndrome. Amounts need to be increased slightly and people must be careful not to take more than one medication that can elevate serotonin levels to dangerous highs.

On a similar note, there are some types of depression which are unlikely to respond well to inhibition of serotonin reuptake. Patients with bipolar or mood disorders may have intensely negative reactions to SSRIs. This most occurs if they are mistakenly diagnosed with unipolar depression and treated as such. In the bipolar brain, extra free serotonin frequently results in mania or hypomania.

Recent discussion about SSRI use has led to concern that SSRIs may occasionally cause or precipitate bipolar disorder in those people who don’t yet have the disease, but might be vulnerable to it. This is all the more reason to understand the intricacies and delicate balance of neurotransmitters and how they may act on the brain. As yet, full comprehension of that relationship eludes even the most learned in the psychiatric and neurological fields.