Depression may involve both too much, too little serotonin
Selective serotonin reuptake inhibitors, or SSRIs, are the most commonly prescribed medications for depression. SSRIs increase serotonin levels by preventing the neurotransmitter from being removed from the synaptic cleft. Because many people with depression experience a reduction of symptoms when taking SSRIs, scientists had concluded that depression is caused by an overall decrease in serotonin in the brain. Despite this well-regarded hypothesis, however, unmedicated patients with depression often demonstrate normal levels of serotonin metabolites in their cerebrospinal fluid.
A recent study published in Frontiers in Behavioral Neuroscience suggests that people with depression may have serotonin over-expressed in some places and under-expressed in others. Specifically, they proposed that serotonin levels are abnormally high in the dorsal raphe nuclei, the cluster of neurons responsible for serotonin production, yet they are sparse in other areas of the brain. These other areas include regions that have been implicated in mood disorders, such as the hippocampus. Researchers theorized that high levels of serotonin at the dorsal raphe nuclei and low levels elsewhere would result in normal levels of serotonin metabolites at the lumbar region of the spinal cord, the place where doctors typically retrieve the cerebrospinal fluid. This would explain why people with depression appear to have normal serotonin levels despite symptoms that suggest the opposite.
The researchers tested their theory that depression is characterized by simultaneously low and high serotonin levels by investigating serotonin levels in non-human primates. Researchers exposed macaques to early life stress, a behavioral condition believed to result in the development of mood disorders. Once the young, early-stressed monkeys were fully grown, the scientists examined the level of serotonin metabolites in their cerebrospinal fluid. Rather than collect the cerebrospinal fluid from the lumbar region of the spinal cord as with humans, the researchers collected samples from the cistern magna, an area in close proximity to the dorsal raphe nuclei. If depression causes an increase of serotonin at the raphe nucleus, they should find greater levels of serotonin metabolites in the stressed monkeys compared to their peers. Sure enough, they found that monkeys with early life stress had increased levels of the serotonin metabolite near the dorsal raphe nuclei. They also found that this increase in serotonin was associated with lower volume of the left hippocampus, one of the areas associated with depression. This reduced hippocampal volume could very well be the result of decreased levels of serotonin. These two results supported their claim that depression is characterized by high levels of serotonin in some brains areas, yet reduced serotonin in others.
If researchers find concrete proof that serotonin levels have a predictable distribution in not only depressed monkeys but people as well, the entire way in which doctors medicate depression will be overturned. Currently, roughly half of patients suffering from depression do not experience relief from their symptoms after two rounds of SSRIs; this could be due to SSRIs increasing serotonin in the dorsal raphe nucleus without influencing mood regions elsewhere. The researchers suggested conquering these treatment resistant cases of depression with multiple kinds of medication. This is a process known as “stacking” that is often utilized in other health conditions such as diabetes and hypertension with the idea that more medications increase the chance that one will work. Before effective medication for depression can really hit its stride, however, scientists need to understand the mechanisms that trigger the disease in the first place. It is not enough to hope that one medication will “just happen to work.” In order to truly increase the quality of life for people with depression, doctors need to be able to provide both reliable and scientifically fueled treatment.
Sovereign Health Group considers all possible treatment options for patients who are suffering from mental health and substance abuse disorders. This is why Sovereign leads the way in dual-diagnosis treatment. For further questions, please contact 866-544-5504.
Written by Courtney Lopresti, Sovereign Health Group writer