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Serotonin & depression: what’s the link?

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Low serotonin levels can lead to depression, but it is not the only neurotransmitter that affects mood. Selective serotonin reuptake inhibitors (SSRIs) can help some people, but not all, and too much serotonin can be dangerous. Bipolar patients may have negative reactions to SSRIs, and there is concern that they may cause or precipitate bipolar disorder. The relationship between neurotransmitters and mood is complex and not fully understood.

The relationship between serotonin and depression is complex. In the simplest explanation, low levels of this neurotransmitter, which circulates through the gut and central nervous system, can directly lead to depressed moods and anxiety. This explanation rules out the fact that there are several other identifiable neurotransmitters that influence mood chemistry, such as norepinephrine and GABA. In some cases, low serotonin levels do not primarily cause depression and could result from other depleted neurotransmitters or factors that science has not yet identified.

The simple story of serotonin and depression is a useful metaphor when explaining to the layman the interrelationship between the two, particularly if drugs are required for treatment. It is true that many people can have their depression lift if they take medicines called selective serotonin reuptake inhibitors (SSRIs). These prevent receptors in the brain from carrying out the reuptake: in other words, grabbing the free serotonin circulating in the brain and leaving less to keep the mood balanced. When an SSRI prevents this activity, theoretically, more serotonin exists to fight 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 related. SSRIs do not relieve depression in all people with the condition. They may need to be replaced with drugs that target different neurotransmitters, such as selective serotonin and norepinephrine reuptake inhibitors (SNRIs), or drugs such as atypical antipsychotics that are increasingly being recommended for treatment-resistant depression. In particular, some clinicians do not favor the term “treatment resistant,” as it seems to reflect unfavorably on the patient. The condition appears to be resistant only if low serotonin is viewed as the single possible cause of depression, and most professionals would not make this mistake.

Another important piece to understanding serotonin and depression is that balance is very important. Adding larger amounts of serotonin to the body can lead to a life-threatening disease called serotonin syndrome. Amounts need to be increased slightly, and people need to be careful not to take more than one drug that can elevate serotonin levels to dangerous levels.

On a similar note, there are some types of depression that hardly respond well to serotonin reuptake inhibition. Patients with bipolar or mood disorders can have intensely negative reactions to SSRIs. This occurs especially if unipolar depression is misdiagnosed and treated as such. In the bipolar brain, the extra free serotonin often causes mania or hypomania.

Recent discussion of SSRI use has led to concern that SSRIs may occasionally cause or precipitate bipolar disorder in those people who do not yet have the illness, but may be vulnerable to it. This is all the more reason to understand the complexity and delicate balance of neurotransmitters and how they can affect the brain. So far, full understanding of that relationship eludes even the most learned in psychiatry and neurology.

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