Throughout history, psychiatric disorders have been cast aside or ignored entirely, causing even more problems for the individuals who suffer from them. Decades ago, rather than being considered as something health-related, psychiatric disorders and their symptoms were often thought to be caused by the moon, spirits, witchcraft, or even punishment from an angry god. The tragic stories of those who suffered from these ailments have in many cases been forgotten over time. Today, it’s estimated that one in five people in the U.S (over 50 million) suffer from a mental illness. These can either be Any Mental Illness (AMI), a behavioral or emotional disorder that is considered more mild or Serious Mental Illness (SMI), a disorder that severely interferes with someone’s mental functions and life.
Fortunately, as time has progressed, so have people’s perspectives on these disorders, both in the public eye and the medical field. Research has shown rather than being caused by the “interference of spirits,” psychiatric disorders are naturally-occurring illnesses that impact the mind and its functions, including thinking, feeling, mood, and sociability. The most well-known disorders include schizophrenia, attention deficit hyperactivity disorder (ADHD), major depressive disorder and autism. Dr. Will Norton, an associate professor and researcher affiliated with the Department of Neuroscience, Psychology and Behaviour at the University of Leicester, explains these disorders stem from “a combination of the environment you grow up in and your genetic makeup.”
Dr. Norton explains, “You can think of it like a biscuit or a cake. In order to make a perfect cake, firstly you make the dough or the batter and then you cook it in the oven. So the ingredients which go into the dough are like your genotype and if you change the ingredients, the cake will be different. You can think the environment is like the oven. If you change the temperature of the oven maybe you’ll get a different type of biscuit, maybe it’s softer, more burnt, more brittle…”
Despite growing public awareness around psychiatric disorders today, we lack a wide variety of interventions when it comes to treating them. Most current treatments are often only palliative, meaning they relieve the burden of the illness to a certain extent, but do not treat the illness itself. Another major concern is the lack of significant improvement in available treatments offered for the past 40 years.
There are three different reasons why it has been difficult to identify new therapies for psychiatric disorders. Often, it’s challenging to find a genotype, a genetic component related to the disorder. Understanding and identifying the molecular pathology is another concern. Developing the therapies and treatments themselves can also be a hurdle.
In order to learn more about psychiatric disorders and overcome these three main challenges, animal models are often used. One of these models is a peculiar candidate which has so far turned out to be incredibly helpful: zebrafish. Also known as Danio rerio,zebrafish are fascinating creatures that Dr. Norton has studied extensively.
While fish may appear to differ greatly from us, Dr. Norton says they can have fairly similar gene sequences to humans. These gene sequences show orthologues – genes in different species that came and evolved from one ancestral gene – corresponding to around 82% of disease‐related genes in humans, a staggering amount. Apart from the similarity between genetic components, there are also likenesses to systems such as neurotransmitter receptors, transporters and enzymes of synthesis and metabolism, all of which can be found in humans and other mammals. These systems are all essential for brain function and ensuring the body is functioning properly.
On top of their genetic makeup being useful, one of the most beneficial aspects of zebrafish is their morphology (their physical appearance and attributes). Zebrafish are transparent in the early stages of their lives, allowing scientists to easily study their brains and manipulate them at a cellular level.
One of the most fascinating things about these fish is that they can also display specific symptoms of psychiatric disorders and are clearly influenced by their environments. For example, they can show signs of aggression and can display symptoms of anxiety such as erratic movement and even changes in coloration. Their larvae are also easy to come by because of how quickly zebrafish reproduce and how large a batch of larvae is. This allows scientists to focus on more minor details and manipulations in the fish.
By researching these genes further and determining whether or not they have the same function as their counterparts in humans, we can come closer to understanding what makes up psychiatric disorders and how to treat them.
Not only are zebrafish able to help us further understand psychiatric disorders, they can also be used to improve drug treatment. Compounds can be dissolved in the fish’s water, allowing scientists to observe the effects over time, as the fish grow. Another advantage is the speed with which zebrafish reproduce, allowing scientists to quickly test a variety of treatments and see how they impact different populations.
Dr. Norton and his colleagues hope they will manage to create and improve a potential cure or medication for victims of psychiatric disorders. He explains that a more optimistic purpose for his research is to get people to think more about mental health issues and how they are a normal part of life.
“When you show that something is due to a concrete change in a genome or a cell, it’s easier for people to think and talk about.” said Dr. Norton
- Despite growing public awareness around psychiatric disorders, a significant number of medical interventions do not yet exist.
- A variety of animal models are often used to develop new medications, including zebrafish.
- Studies in zebrafish can be helpful because these animals have fairly similar gene sequences to humans. These fish are also transparent in the early stages of their lives, allowing scientists to easily study their brains and manipulate them at a cellular level.
Durairaj, Brindha. Dhanabal, Madhumitha.“Zebrafish as a prodigious tool in neuropsychiatric research.” The Journal of Basic and Applied Zoology. August 27, 2020 https://basicandappliedzoology.springeropen.com/articles/10.1186/s41936-020-00189-5
Interview with Dr. William Norton. Interview by Flavia Tripon. August 18, 2021
Khan, Kanza. Collier, Adam. Meshalkina, Darya. Kysil, Elana. Khatsko, Sergey. Kolesnikova, Tatyana. Morzherin, Yury. Warnick, Jason. Kalueff, Allan. Echevarria, David. “Zebrafish models in neuropsychopharmacology and CNS drug discovery.” British Pharmacological Society. February 27, 2017 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466539/
McCammon, Jasmine. Sive, Hazel. “Challenges in understanding psychiatric disorders and developing therapeutics: a role for zebrafish.” The Company of Biologists. July 1, 2015 https://journals.biologists.com/dmm/article/8/7/647/3711/Challenges-in-understanding-psychiatric-disorders
“Mental Illness.” National Institute of Mental Health. https://www.nimh.nih.gov/health/statistics/mental-illness
Norton, William. “Toward developmental models of psychiatric disorders in zebrafish.” Frontiers. April 26, 2013
Speilman, Rose. Dumper, Kathryn. Jenkins, William. Lacombe, Arlene. Lovett, Marilyn. Perlmutter, Marion. “Psychology.” Openstax. Last modified December 2, 2020. 16.1 https://openstax.org/books/psychology/pages/16-1-mental-health-treatment-past-and-present#0
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Joe Kays has been director of research communications at the University of Florida and founding editor of the UF research magazine for 25 years. During that time he has written or edited hundreds of science stories from across one of the nation’s most comprehensive universities. Prior to that, he served as a senior writer and editor of the UF alumni magazine and as a daily newspaper reporter. He holds a bachelor’s degree in journalism from Penn State and a master’s in science and health communications from UF. He is immediate past president of the University Research Magazine Association and is active in the National Association of Science Writers.
Will Norton, Ph.D., is an associate professor of animal biology affiliated with the Department of Neuroscience, Psychology and Behaviour at the University of Leicester. He has researched zebrafish for many years and currently studies aggression and its links to psychiatric disorders through genetics.