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Serotonin Map of the Brain To Optimize Antidepressant Development

While many people find antidepressants helpful for managing major depression, others are unable to find them therapeutic. It has long been thought that the neurotransmitter serotonin is responsible for contributing to cases of depression. Researchers and pharmaceutical companies alike have long believed that serotonin is the primary underlying factor associated with poor mood and other psychological disorders.

Despite the fact that I strongly disagree with this assumption, it doesn’t mean that serotonin plays no role in contributing to depression. Recently, researchers began further investigating serotonergic processes in a way that’s never been done before.  Their ultimate goal is to to create a “serotonin map of the brain” to determine specific areas of the serotonin system that would be beneficial to target with medications, and others that may be better to avoid targeting.  In other words, scientists are trying actually get a more sufficient understanding of how serotonin works in the brain… it’s about time.

Developing a Serotonin Map of the Brain

Researchers working at the Johns Hopkins Brain Science Institute are currently in the process of creating a “serotonin map of the brain.” The project is being lead by Dr. Jeremiah Cohen who suggests that pharmaceutical developments in psychiatry are limited by a general lack of knowledge of neurotransmitters like serotonin. Cohen was quoted as saying, “We are working with a blunt system and we need to refine it.”

In the past, scientists didn’t appear to have the necessary technological tools to carry out the mapping of neurotransmitters. Just to give you a zeitgeist comparison, a lead researcher from this project stated that this research in neuroscience is at a similar stage of development to where physics was back with Galileo and Newton.  In other words, researchers are finally starting to just figure out some of the basics of brain functioning.

Researchers are attempting to figure out how groups of cells in the serotonin system connect to produce emotional behavior. A majority of antidepressants elicit broad effects throughout the entire serotonin system, thus their effects are untargeted. With this “serotonin map of the brain” researchers hope to target components of the serotonin system that specifically apply to a particular disorder. They believe that selective targeting within the system will allow for more favorable psychotropic treatment outcomes with less side effects.

Serotonin Brain Map: Preliminary Research (2015)

Preliminary research: The research will begin by examining serotonin neurons within the brains of mice during a “reward task” vs. during a “punishment task.” Researchers will observe the mouse behavior during the reward task vs. the punishment task and create a map of neurons that are involved in behavioral responses.  They will then determine the behavioral responses that share commonalities with human responses during these same tasks.

Purpose: To better understand the biological mechanisms of mood and to determine how groups of neurons connect and act to produce various emotional behaviors. Researchers ultimately would like to create this map to help companies create psychotropic medications that selectively target certain areas of the brain or neurons that are relevant to a specific mental disorder. This would result in new batches of drug developments for nearly every mental illness that’s influenced by serotonergic maladaptations.

For example, if you were diagnosed with “depression” and the exact functions of serotonin were mapped, companies may be able to develop a medication that targets the serotonergic processes that influence depressed emotional behavior. Other drugs may be modified to specifically target an illness like social anxiety. The potential breakthrough associated with the serotonin brain map would likely lead to a marked improvement in the quest to develop better treatments for mental illnesses and would also likely improve psychiatric treatment outcomes.

The newer drugs would be more like a “smart bomb” as opposed to an “atomic bomb.” A smart bomb hones in on a specific area and delivers the drug response, whereas an atomic bomb is untargeted and hits everything.

Benefits of Serotonin Map of the Brain

A majority of antidepressants function by inhibiting the reuptake of serotonin throughout the brain. This raises extracellular levels of serotonin, leading to an antidepressant effect in many people. The problem is that these drugs influence serotonin levels in every region of the brain; they are untargeted. Researchers working on the serotonin map believe that if treatments were more targeted to specific regions responsible for improving mood, they could eliminate some side effects and increase antidepressant efficacy.

  • Antidepressant development: They hope that much of this information can be used in the development of new antidepressants. Specifically they want to give pharmaceutical companies a blueprint which allows them to better understand how serotonin affects certain brain regions. This will allow them to create more targeted drugs that will likely carry less side effects.
  • Brain regions: For a variety of reasons, researchers want to know the brain regions that interact with serotonin to produce an improved mood. They know that current antidepressants are untargeted in that they raise serotonin levels throughout the brain. Unfortunately certain brain regions may be detrimentally affected by these elevations – leading to adverse reactions or poor efficacy.
  • Mood elevation: Researchers want to determine how serotonin actually works to improve mood. In other words, what brain regions are involved and/or neuronal regions to produce an antidepressant effect. The current understanding is that raising serotonin levels can improve mood, but the specific brain regions involved are unknown.
  • Neuroscience: We are in the earliest stages of neuroscientific developments and things like mapping various neurotransmitters is necessary to get a better understanding of each system within the brain.  By gaining insight into the interworkings of the serotonin system, we will be able to better understand mental illness from a neurotransmitter perspective.
  • Serotonin: It is important to get a better understanding of how this neurotransmitter affects our functioning. When we feel happy, is it elevated in a certain region? When we feel sad does it decrease in a certain region? As of now, we only know that inhibiting the reuptake of it with certain drugs can help. However why does one SSRI work for Person A and not Person B, yet a different SSRI works for Person B? This research may provide some insight regarding this phenomenon.
  • Side effects: One of the goals of these researchers is to understand interactions between serotonin and certain regions of the brain. They want to determine various interactions between brain regions and serotonergic antidepressant that cause side effects. Ultimately they would like to figure out what can be done to mitigate and eliminate side effects from serotonin-based drugs.
  • Targeted treatments: Another specific goal is to come up with targeted, serotonergic treatments for depression. In other words, directly stimulate the particular regions of the brain that give the majority of the antidepressant effect, while eliminating stimulation upon those that don’t and/or could result in problematic side effects.

Problems with Serotonin Map of the Brain

There are no inherent problems with mapping serotonin in the brain. Having an enhanced understanding of serotonergic processes provides researchers with information that could lead to development of improved, targeted treatments. However, it is important to realize that not everyone is actually affected by serotonin when they are depressed. Although raising serotonin is beneficial to some individuals, it doesn’t mean that targeting the serotonin system in everyone is going to be beneficial.

Saying that low serotonin is the root cause of a person’s depression isn’t very scientific. This would be comparable to saying that low opioid production is the root cause of a person’s depression. Why? Because for many, taking Suboxone for depression works better than any antidepressant. Just because a particular drug treats depression, doesn’t mean that whatever it is targeting is the cause of a person’s depression. (Recommended reading: Dopamine vs. Serotonin, Low Norepinephrine, etc. – there is no definitive neurotransmitter implicated in all cases of depression).

From the perspective of treating a specific mental illness like depression, this news shouldn’t be all that exciting, especially if your depression won’t benefit from serotonergic changes.  From broad scientific perspective, this however will be a considerable scientific advancement – assuming the map is fully accurate. That said, it should also be mentioned that regardless of the findings in this “brain map,” from a patient perspective, targeted treatments do not account for individual differences in things like metabolism.

Other genetic factors and individual physiological factors are best accounted for with tools like GeneSight which provide individualized genetic testing. Additionally even with newer, more targeted serotonergic medications, it is important to understand that drug tolerance is inevitable. Finding ways to prevent tolerance among those receiving benefit from these drugs will be crucial for those that require lifelong psychotropic treatment.

Suggestion: All major neurotransmitters should be “mapped”

There aren’t any major problems with the serotonin map of the brain, it is a very beneficial project and highly important. Mapping serotonin will provide insight into activity within the brain and give us a better idea of what is really happening with serotonergic functioning in cases of depression.  In time, researchers should map every major neurotransmitter within the brain to simply get a better understanding of how other neurotransmitters influence behavior, interact, and overlap in terms of function.

  • Acetylcholine
  • Dopamine
  • GABA
  • Glutamate
  • Norepinephrine

To better treat other conditions such as ADHD, dementia, etc. mapping all neurotransmitters should be considered essential science. This team of researchers could theoretically take the time to map out each neurotransmitter (when they finish serotonin) or another research group could take it upon themselves to map out a neurotransmitter like dopamine.

Future Proposal: Neurotransmitter Templates & Individualized Targeting

It would be interesting if the individuals were able to come up with an optimal performance template. In other words, some sort of template that showed optimal serotonergic functioning in the human brain for emotional behavior. The reason a template would likely be beneficial is due to the fact that there are often individual differences. Two individuals with depression may not necessarily have the same serotonergic imbalances.

Therefore coming up with an optimal serotonergic template would be beneficial in that it would allow researchers to pinpoint specific serotonergic maladaptations that may be contributing to a person’s illness. However, it would also (likely) show researchers that some individuals may already have a perfectly functioning serotonergic system, and may need to target other neurotransmitters like dopamine, glutamate, norepinephrine, etc.

Additionally it would seem ideal if a person could visit a professional for a serotonin or neurotransmitter analysis, determine imbalances, and they may be able to get a drug customized and tailored to fit their individual biology. This targeted form of treatment would be beneficial, but still imperfect in that a person would likely eventually develop a tolerance.

Verdict: Serotonin Map of the Brain is Important

This is highly important research that needs to be conducted, but it could be argued that it is highly important for other neurotransmitters to be mapped.  Serotonin is a good neurotransmitter to start with simply because it is often the most talked about in depression and anxiety.  It will give us a better understanding of how serotonin regulates mood and the specific regions that are involved in producing an “antidepressant response.” Ultimately this map should help refine existing serotonergic antidepressant treatments.

That said, it is still clear that artificial elevations and targeting of serotonin don’t always improve a person’s depression. Therefore, there is a clear need to continuously think outside the box and develop new treatments with alternative pharmacological mechanisms. It would also be highly beneficial to map out other common neurotransmitters in a hierarchical manner, starting with the ones that are speculated to be most involved in mental illness (e.g. serotonin, dopamine, norepinephrine).

Most would agree that this “serotonin brain map” should’ve been conducted years ago. However, according to researchers conducting the map, no scientist had the technology to complete such a study.  Now they finally have the technology and work is getting done.  Fortunately, someone is finally doing the hard work that will give us a better understanding of serotonin in the brain.

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