Scientists are starting to re-think the serotonin connection as the major driver behind depressive disorders

It has been simple for so long: attempt to treat many depressive disorders by increasing serotonin levels with a variety of pharmaceuticals.

However, as helpful as many people might find their anti-depression drugs to be, they are learning that serotonin is not as all-encompassing as they once thought it was:

For the last half-century, the dominant explanation for depression has centered on serotonin. The basic idea: low levels of brain serotonin or serotonin activity leads to symptoms of depression. This theory, which is known as the “serotonin hypothesis,” is based on several data points, including animal research and the effects of antidepressants that are supposed to work by increasing brain serotonin levels. But, in the last several decades, a number of researchers have challenged the idea that serotonin plays a principal or even major role in depression.

In recent days, the serotonin hypothesis of depression has been explicitly challenged by a number of scientific publications. Most notable (at the time of this writing), a paper published in Nature Molecular Psychiatry reviewed several lines of evidence on the subject of the serotonin-depression connection and concluded that “the main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations.”

Datapoints like this recent study point to a major question: if serotonin isn’t driving depression, what does explain the brain state of the hundreds of millions of people living with it? While there are many potential explanations, here are four major systems that may prove more important to the brains of people with depression, and some ways we may be able to target them.

Those areas to study more include:

  1. Brain Rewiring (Neuroplasticity)

Supporting factors for the neuroplasticity-depression connection include imaging findings, cell study research, and measurements connected to the rewiring process. The basic idea is that in depression, there may be issues with the quality, number, and type of connections our neurons make, and this may help explain depression symptoms. Importantly, research is showing that we may be able to positively affect neuroplasticity through lifestyle factors like exercise, learning new things, and, potentially, certain dietary modifications. There is also data showing that conventional antidepressants, as well as psychedelics, may positively influence neuroplasticity.

  1. Inflammation

When excess or chronic inflammation is present in the brain, it appears to influence a number of pathways involved in depression. First, it may impair the healthy function of neurons by physically damaging them. Inflammation also may block healthy neuroplasticity, while leading to the generation of toxic breakdown molecules like quinolinic acid that could further damage neuron health and contribute to depressive pathology. Within the brain, research shows that unique immune cells called microglia may be key to sustaining inflammation. So how is our inflammatory status regulated? It appears to be sensitive to the quality of our diet, sleep, exercise, stress-lowering interventions, and potentially even nature exposure.

  1. The Gut-Brain Connection

One of the most impressive aspects of our gut is the quantity and diversity of microbes that call it home. These bacteria make up the gut microbiome. Alterations in the bacteria that live in the gut microbiome have been linked to depression. It’s thought that these bacteria may influence brain function through their effects on the vagus nerve (which runs from the gut to the brain), their impact on the immune system (e.g., by affecting levels of inflammation), and through tiny molecules they create (e.g., short-chain fatty acids) which may reach the brain by way of the bloodstream.

  1. Endocrine (Hormonal) Changes

When it comes to the regulation of brain function, a wide range of hormone pathways are thought to play important roles. This research extends to depression. And while certain hormonal changes can be hard to reverse, there’s also much we can do to help improve aspects of our endocrine signaling pathways.

Author Austin Perlmutter, MD, goes on to add insulin and estrogen levels as important possible links to depression for some people.

You can read the rest of his article in Psychology Today at this link.

Writing from personal experience, the simple act of getting some cardiovascular exercise 3-4 times a week allowed me to stop my blood pressure medications and my anti-depressants. I also stopped any substance use whatsoever. (As long as I’m on the subject of drugs, some researchers are seeing pretty amazing results in people with depression and/or PTSD through the use of psychedelics. Good article here.)

Having noted my experience, always remember that one person’s experience is an anecdote and nothing more. You should consult a board-certified mental health professional to find out what’s right for you.

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