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Rating Neurotransmitters by (Personal Preference?)

April 19, 2024

What is a neurotransmitter? 

Neurotransmitters are the chemical messengers used for communication between neurons. They are released into the synapse (gap between neurons) by the neuron referred to as the presynaptic neuron and then cause some sort of response (generally excitatory, inhibitory, or modulatory) on the postsynaptic neuron (Hook et al, 2019). 

Some traditionally recognized neurotransmitters include serotonin, dopamine, and adrenaline.

However, the scope of what a neurotransmitter is has been expanding to include a broader range of signaling chemicals. Now, substances like Nitric Oxide (NO) and ATP (yes, adenosine triphosphate, the one made in the powerhouse of the cell) are beginning to be included as well. 

Now let’s make a tier list…

For the purposes of this list, we will be focusing on some of the more traditional neurotransmitters.

Serotonin

To start off, we’ll go with one that is pretty well known: serotonin. This monoamine is involved in the signaling for a huge variety of systems including regulation of mood, sleep, digestion, and more. It is commonly associated with depression and a common treatment for depression for decades has been SSRIs (Selective Serotonin Reuptake Inhibitors) which essentially stop processes that clear serotonin from the synaptic cleft (Preskron, 1997). So serotonin is pretty cool, pretty popular, and I guess with it being linked to our ability to be well, not depressed, it should be pretty high up. 

But to put it in the S tier feels too basic. And recent advances in depression treatments support a new theory of depression involving a different neurotransmitter (more on this coming soon). So I say serotonin gets a solid A. 

Acetylcholine

Acetylcholine is one of my personal favorites. It’s most commonly known for being used by pre synaptic neurons at the neuromuscular junction which is where nerve meets muscle. This means the release of acetylcholine is essential for movement. My favorite acetylcholine fact is that botulinum toxin can be used to inhibit its release at these junctions which is actually what botox does (Nigam, 2010). Can’t wrinkle if those muscles can’t move. I’m giving acetylcholine an A!

GABA

Ah, the primary inhibitory neurotransmitter in the central nervous system. Inhibition is so important and honestly quite underrated. Without GABA, there would be too much activity which  could lead to a whole host of consequences. Low GABA levels are linked to diseases like epilepsy, motor disorders like stiff person syndrome, and even schizophrenia (Levy & Degnan, 2013). And of course, this inhibition is also crucial for sleep which is a personal favorite activity of mine. So, for the essentialness of inhibition, I think we have our first S tier neurotransmitter.

 

Epinephrine 

I may or may not be wearing my epinephrine (aka adrenaline) necklace as I write this; however, I can not say I am a huge fan of this molecule, at least, not as a neurotransmitter. It’s associated with sympathetic nervous system activity which is the part of our autonomic nervous system that responds unconsciously to stressful situations, often referred to as the fight or flight response (C.C medical). When epinephrine is released in my body, I generally want to get out of whatever situation I am in. I almost want to put this guy in D tier, but I guess the responses in my body due to epinephrine helps me get out of that situation so I’ll cut it some slack and put it in C. 

Norepinephrine 

Norepinephrine (Noradrenaline) is also involved in that fight or flight response and is generally important for arousal and alertness (Tank, 2015). I’m going to go ahead and put this one near its very chemically similar friend epinephrine in the B row. 

Glutamate 

Now we have our primary excitatory neurotransmitter (the anti-GABA). Glutamate is essential for learning and is believed to be essential in neuroplasticity (aka our brains ability to change which is very cool). Recently, glutamate has been theorized to have a role in depression and ketamine is being utilized as a way to treat treatment resistant depression (Pal, 2021). The results are very impressive and cause long term positive impacts from small doses. I like learning and I like treating depression, so S tier! 

Dopamine

Ok, I admit, I have a favorite. Dopamine is extremely important and one of the key processes it is involved in is motivation (Olguín et al, 2016). Its role in reward makes it an important molecule in guiding our behaviors as the presence of dopamine is associated with pleasurable feelings. It is also involved in movement; Parkinson’s disease, a movement disorder, is actually attributed to a decrease in dopamine production in a region called the substantia nigra.

In my eyes, dopamine is a great example of the complexities of the nervous system because it has involvement in multiple systems and its dysregulation can have a huge range of impacts. Its association with pleasurable feelings displays how in moderate amounts dopamine offers positive feelings but in excess we see how it can become harmful like in the case of addictions. So with that I say, S+ tier!!! 

To sum it up…

While creating this list, I thought long and hard about how to compare these neurotransmitters and found myself using the approach of, ‘which one could be removed’. The answer: none of them. Each of these neurotransmitters is involved in multiple systems and some dis-regulation of them can cause widespread consequences. So to completely remove any neurotransmitter would be detrimental. This demonstrates how fine tuned our brains are to function in a way where the production and use of neurotransmitters is precise and modulated. All this to say the rankings of these neurotransmitters was quite arbitrary and are based essentially on just my own opinions, but I hope you learned a little bit about the epic chemicals that allow neurons to communicate along the way! 

 

References

C. medical. (n.d.). Epinephrine (adrenaline): What it is, function, deficiency & side effects. Cleveland Clinic. https://my.clevelandclinic.org/health/articles/22611-epinephrine-adrenaline 

Hook, V., Kind, T., Podvin, S., Palazoglu, M., Tran, C., Toneff, T., Samra, S., Lietz, C., & Fiehn, O.. (2019). Metabolomics Analyses of 14 Classical Neurotransmitters by GC-TOF with LC-MS Illustrates Secretion of 9 Cell–Cell Signaling Molecules from Sympathoadrenal Chromaffin Cells in the Presence of Lithium. ACS Chemical Neuroscience, 10(3), 1369–1379. https://doi.org/10.1021/acschemneuro.8b00432

Juárez Olguín H, Calderón Guzmán D, Hernández García E, Barragán Mejía G. The Role of Dopamine and Its Dysfunction as a Consequence of Oxidative Stress. Oxid Med Cell Longev. 2016;2016:9730467. doi: 10.1155/2016/9730467. Epub 2015 Dec 6. PMID: 26770661; PMCID: PMC4684895.

Levy, L. M., & Degnan, A. J.. (2013). GABA-Based Evaluation of Neurologic Conditions: MR Spectroscopy. American Journal of Neuroradiology, 34(2), 259–265. https://doi.org/10.3174/ajnr.a2902

Nigam, P. K., & Nigam, A. (2010). Botulinum toxin. Indian journal of dermatology, 55(1), 8–14. https://doi.org/10.4103/0019-5154.60343

Pal M. M. (2021). Glutamate: The Master Neurotransmitter and Its Implications in Chronic Stress and Mood Disorders. Frontiers in human neuroscience, 15, 722323. https://doi.org/10.3389/fnhum.2021.722323

Preskorn S. H. (1997). Clinically relevant pharmacology of selective serotonin reuptake inhibitors. An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clinical pharmacokinetics, 32 Suppl 1, 1–21. https://doi.org/10.2165/00003088-199700321-00003

Tank, A. W., & Lee Wong, D. (2015). Peripheral and central effects of circulating catecholamines. Comprehensive Physiology, 5(1), 1–15. https://doi.org/10.1002/cphy.c140007

 

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  Timothy Durham was convicted of rape when a test showed his DNA genotype matched the DNA recovered from the crime scene. Eye witnesses testified that Durham was in a different state at the time of the incident, but he wasn’t exonerated from his 3000 year sentence until follow up DNA analysis showed that the preliminary forensic analysis used in the trial was misinterpreted (Thomas et al.). DNA testing serves an invaluable part in our criminal justice system, but it comes with complications and bias that can lead to wrongful convictions and misinformed juries.  

Background:

Forensic genetics aims to identify the origin of a biological sample. It can be traced back to Karl Landsteiner who discovered human ABO blood groups. With blood groups, suspects could be eliminated based on their blood type. For example, if a suspect had type A blood and there was type B blood left at the scene by the perpetrator, the investigators could rule out the suspect. Unfortunately, the reverse didn’t work. If the suspect and perpetrator both had the same blood type, it can’t be concluded that the suspect was guilty. Blood identifiers evolved into 8 distinct categories which improved the ability to eliminate suspects, but could only conclude that (if the system matched) it might be the perpetrator or this person might be related to the perpetrator (Jobling and Gill). The field evolved in the 1980s with the discovery of Minisatellites, lines of repetitive DNA that don’t encode proteins. Minisatellite patterns in DNA create what we know today as the DNA fingerprint, and it has a much higher accuracy rate than previous methods (Augustyn et al.). Around the same time, a breakthrough for victims of sexual assault was discovered. In the case of assault, bodily fluids of both the victim and the assaulter can get mixed. A process called differential lysis was created which could selectively increase the concentration of sperm in a fluid sample thereby allowing for accurate DNA testing (Jobling and Gill). Forensics evolved to use single-locus probe testing after several years because of its ease of interpretation. It looked at specific minisatellites that had high variability between subjects. This was the first DNA-based method to be used in a criminal investigation. Two murder homicides from several years apart were connected using DNA evidence. The evidence was then used to exonerate an innocent man, and the guilty party was found when he tried to evade mandatory DNA testing for all men in the small town. His guilt was then reinforced when the DNA profiles matched, and he gave a confession (Jobling and Gill). Finding DNA at a crime scene doesn’t guarantee that you’ll find a murderer. There are issues with non-pure samples and limited samples that make DNA work difficult, and accreditation of facilities and new techniques and take time (Jobling and Gill).  

Subjectivity of DNA Interpretation:

In a 2009 publication, the National Academy of Science discusses the possibility for subjective influence in lab based forensics. The interpretation bias happens in complex cases where, for example, there could be a mixture of DNA. A study published in 2011 looked specifically at this issue. A gang rape happened in Georgia, and the mixture in DNA from the case was used to prosecute one suspect after another suspect took a plea bargain to testify against him. With DNA mixtures, there are three possible conclusions: suspect excluded, suspect cannot be excluded, and inconclusive. If the suspect is excluded, it means that there’s little to no possibility that his DNA is part of the sample. If the suspect cannot be excluded, it means that there’s a possibility that his DNA is part of the sample. In the trial, the DNA examiners who knew the context of the case concluded that the suspect being prosecuted could not be excluded. The 2011 study gave the DNA evidence from this case and the DNA profiles of the suspects to 17 forensic examiners. These examiners had no context of the case, and they all worked independently. Of the 17, only 1 came to the same conclusion (suspect cannot be excluded) as the examiners who knew the context of the case. Twelve of the 17 concluded that the suspect who was prosecuted and convicted had no relation to the DNA found in the sample. Not only does this show that subjectivity occurs due to the context of the case, but the 17 examiners came up with different findings based on their past experiences meaning that not all DNA analysis is objective. Some organizations like the Scientific Working Group on DNA Analysis Methods say that quantitative statistical evidence should be presented with every categorical conclusion, but the US doesn’t require this (Dror and Hampikian).

False Positives:

There are two categories that cause wrongful identification in a DNA report: coincidental matches and false positives. Coincidental matches are DNA matches between two unrelated people. The probability of these matches is about 1 to 500,000 for white individuals and about 1 to 350,000 for black individuals. This small probability of coincidental matches makes people feel confident in DNA evidence. False positives, on the other hand, are matches between DNA and test DNA that result from issues in the forensics lab. There have been multiple cases of forensics labs accidentally switching victim and suspected rapist DNA which lead to convictions that were later overturned when the lab realized the error. There are also cases of misreading or misunderstanding a sample. In a case from 1993, a man was convicted of rape because someone interpreted a mixed sample of victim and perpetrator DNA as an individual sample. The conviction was again overturned. To prevent false convictions, retesting DNA is allowed, but it’s not an efficient solution. Many people are pushing for statistical information on the probability of false positives, so that the jurors can make accurate judgements based on DNA evidence (Thomas et al.).  

Conclusion:

DNA analysis is a useful tool for the criminal justice system, but subjectivity can be an issue in forensic testing. To combat wrongful convictions, there are organizations like The Innocence Project who use DNA testing to free the innocent, but reformed forensic testing standards should be put in place to prevent subjectivity and to ensure juries are correctly informed during trials. https://www.innocenceproject.org/    

Citation:

Augustyn , Adam, et al. “DNA Finerprinting.” Encyclopedia Britannica , 26 Apr. 2018, www.britannica.com/science/DNA-fingerprinting#ref153186. Dror, Itiel E., and Greg Hampikian. “Subjectivity and Bias in Forensic DNA Mixture Interpretation.” Science & Justice, vol. 51, no. 4, 2011, pp. 204–208., doi:10.1016/j.scijus.2011.08.004. Jobling, Mark A., and Peter Gill. “Encoded Evidence: DNA in Forensic Analysis.” Nature Reviews: Genetics, vol. 5, no. 10, Oct. 2004, pp. 739–751., doi:10.1038/nrg1455. Thompson, William C, et al. “How the Probability of a False Positive Affects the Value of DNA Evidence.” Journal of Forensic Sciences, vol. 48, no. 1, Jan. 2003, pp. 1–8., doi:10.1520/jfs2001171.