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  • Writer's pictureMaria Rutkowska

CRISPR/Cas9 mediated treatment of depression by the targeting of GABA receptors


About 1 in 6 people will experience major depressive disorder (MDD) at some point in their lives. Genetics is one element that might cause depression, among others. In contrast to other neurological illnesses, genetics is not a key contributing role, hence the low heritability rate makes it more challenging to identify the genes in charge. Although there are antidepressants and other therapy alternatives, many of them can be ineffective and occasionally dangerous. However, there are also effective treatments for depression, one of which is CRISPR gene editing, which enables precise DNA alterations. There are several areas that show promise, but so far there are no CRISPR-based treatments for depression. Even though CRISPR may be an excellent treatment for depression, it has several ethical and scientific downsides. The likelihood that CRISPR will treat depression increases as its development continues. In addition, the obstacle of overcoming the blood brain barrier in order to get through to the dopamine-associated system of the brain still remains a drawback of applying the CRISPR/Cas9 technology in the aims of treating depression.


The psychiatric condition known as Major Depressive Disorder (MDD) is categorized as common. It has a significant impact on the suicide death rate and is the third most common cause of disability. Regularly feeling depressed, losing enjoyment and interest in activities, having trouble thinking, and having suicidal thoughts are some common signs of depression (1). About 1 in 15 adults in a year are affected by MDD, and at least 1 in 6 people will encounter it at least once in their lifetime. Women are somewhat more likely than males to develop MDD. Numerous factors, including biochemistry, genetics, and environmental ones including traumatic experiences and the death of loved ones, contribute to depression (2).

It is difficult to identify the precise cause of depression because it has so many contributing variables, particularly when it comes to genetics. Given that depression is just 37% heritable, genetics accounts for only 37% of the disorder's causes. The low heritability rate means that a larger sample size is required in order to pinpoint precise genes to identify the genetic causes of the condition (3). Several factors can make this difficult to accomplish, one of which is recruiting enough participants for the study. The sample size for depression can be substantially larger than for schizophrenia, which has an 80% heredity rate, resulting in more research being available.

There are currently a few therapies, such as medicines (an example being antidepressants), that can regulate depression, but they do not provide a cure. Gene therapies and CRISPR may be effective treatments for depression because genetics and the condition are linked. A CAS nuclease, a protein that divides DNA, is guided by the RNA used in the CRISPR gene editing approach to correct the faulty gene sequence. Despite difficulties with delivery systems and ethical concerns, this method may help treat depression. This literature review will analyse the potential benefits and drawbacks of employing gene therapy to treat depression.

Genetics behind depression

According to current research, families that date back to the early 20th century have been shown to carry the genes for depression (4). Different groups of people can experience depression differently, and different family lines may experience depression due to a unique genetic mix. Studies have been done to clarify the genetic underpinnings of depression. The first kind of study is a GWAS (Genome-wide association study), which is conducted in two stages: a discovery phase during which the entire genome is screened, and a replication phase during which a small number of SNPs, which are the most prevalent genetic variations between individuals, are independently tested. Numerous of these investigations were unable to identify any frequent variations that increase the risk of MDD. These investigations were largely unsuccessful since the sample size was insufficient and the power to identify the variations was low.

Another recent study, the CONVERGE collaboration, has gathered a significant amount of genetic information about depression that may be useful in determining the cause of MDD. The study's methodology involved selecting a smaller group of participants who had similar symptoms. The study discovered two chromosome 10 SNPs that demonstrated association, indicating that study participants shared a mutation of a gene that causes MDD. Overall, the study contributed to knowing how to find more associations within restricted sample sizes (5).

Existing methods of treating depression

There are not many available options for the treatment of depression available right now, and those that are do not directly treat the condition. Antidepressants are the most widely used form of treatment for depression, but they come with a number of hazards, including potential medication toxicity and ineffectiveness non people with more severe depression deep brain stimulation, in which surgeons implant tiny electrodes in the frontal lobe of the brain—which control dopamine, serotonin, and mood—can be one of the disease's non-chemical treatments (6). Deep brain stimulation is a successful treatment but comes along with several hazards such as long term speech issues, migraines, and strokes. People are continuously exploring for alternatives because these treatments carry significant hazards.

CRISPR/Cas9 gene editing

CRISPR and the endonuclease Cas9 was first identified in E.coli, by Japanese scientist Yoshizumi Ishino and his team in 1987 (Figure 1). They accidentally cloned an unusual series of repeated sequences interspersed with spacer sequences while analyzing a gene responsible for the conversion of alkaline phosphate (7). The role of CRISPR as a safeguard for bacteria against bacteriophages was elucidated in 2007 (Figure 1) (8). Taking advantage of this bacterial immune system, scientists engineered the CRISPR system for scientific use. CRISPR uses a specific sequence of DNA and its associated endonuclease Cas9 to edit the base pairs of a gene. Compared to other genetic modification methods (i.e. TALENS), CRISPR works more precisely by cutting DNA using the Cas9 enzymes, and allowing the natural DNA repair processes to take over. To simplify, this genetic modification method consists of two main parts: the Cas9 enzyme and the guide RNA (9).

Applicable uses for CRISPR today are experimentation with gene-editing mosquitos in order to reduce, and hopefully eradicate, the risk of malaria. Apart from using CRISPR in the hopes of creating malaria-resistant mosquitoes, researchers have been trying to use CRISPR to engineer agricultural crops that can withstand climate change, and in human trials to treat a range of diseases, including ADHD (10). Therefore, CRISPR’s potential for genome editing from climate change resistant crops to treating mental health disorders, makes it a powerful tool.


Genetics is one of the many potential causes of the mental disease depression. Scientists are developing promising treatments for depression using CRISPR and gene editing technologies, such as targeting GABA receptors. Regarding CRISPR's future, there are numerous ongoing advances that could make the technology safer. Regarding the moral aspect, legislations are being implemented to prevent the abuse of the technology. Overall, CRISPR will be a safe and successful type of treatment in the years to come, helping to heal a variety of illnesses, including mental problems. There have been advancements in the development of CRISPR for various neurological illnesses, including schizophrenia.

CRISPR will soon be the standard treatment for neurological illnesses as novel delivery systems are created and several medical trials involving genetics and mental disorders are undertaken. When it comes to depression, the potential of its usage being implemented in the targeting of GABA receptors and dopamine system-associated receptors is promising. Not only does the blood brain barrier pose drawbacks to implementing gene editing in the aims of treating neurologically-associated disorders, but the ethical considerations behind implementing gene editing into humans remains in questions – as well as surrounded by heated debates.

Figure 1: Taken from “CRISPR-based therapeutic targeting of ADHD” by Maria Rutkowska. Figure represents general tiimline od events in the occourance of CRISPR revolutions and advancements.

Figure 2. Taken from “Using CRISPR/Cas9 associated gene-therapy approach in the Aims of treating Schizophrenia” by Maria Rutkowska. Figure represents encapsulated CRISPR/Cas9 reagents compared to the BBB-penetrating molecules located in the Blood Brain Barrier of the brain.


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