A. Allen, M. Rootham, U. Wu & B. Zhang
Is the 5-HTTLPR variation of SLC6A4 correlated or causally related to ASPD?
Research Background:
Antisocial personality disorder (ASPD) is one of the most volatile and obscure mental disorders currently listed in the DSM-V. It is characterized by a long history of impulsive behavior, disregard for others, lack of empathy and amorality among many symptoms. The underlying genetic causes of ASPD has been extensively researched, but few results are conclusive. While ASPD most likely develops under a combination of hereditary and environmental factors, it is unclear whether genetic factors directly contribute to ASPD.The solute-carrier gene SLC6A4 located on chromosome 17 is vital to the rate of serotonin transportation. Allelic variations may affect an individual’s ability to regulate emotions. The variation 5-HTTLPR, which is a polymorphic degenerate repeat section, can reduce grey matter in the amygdala, increase risk for depression as well as hinder social interactions. It can also cause negative and positive sensitivity to stimuli and to external experiences.
Relying on past studies conducted on the correlation between 5-HTTLPR, it was found
that the region is associated with higher risk for antisocial personality disorder.
Proposed Study:
The main goal of the study is to determine if the 5-HTTLPR variation of the SLC6A4 gene is correlated with ASPD or is a direct cause. Existing research finds that the two are correlated; this study would determine if the connection is enough to conclude causation. Participants would be ASPD patients between the ages of 25-40 with no comorbidity. In the third step of the study, CRISPR gene editing technology will be used to deactivate 5-HTTLPR (see figure below).
Methods:
1. Test for 5-HTTLPR variation in participants. If participants have the variation, they will continue in the study. If not, their participation will be terminated.
2.
a.Control Group: No genetic editing
b. Experimental Group: 5-HTTLPR variation is turned off through CRISPR-Cas9 gene editing. The process will include using viruses substituted with methylation methods that could pinpoint faulty, differentiated cells within the amygdala and stop the DNA transcription process, bringing the serotonin transportation rate back to normal.
3. Observe over a 10 year period to determine if the groups show signs of ASPD symptoms subsiding.
Anticipated results:
It is anticipated that the control group will show little to no improvement, but that the genetic editing group will see a reduction in number and/or severity of ASPD symptoms.
The exact timetable of improvement is unknown; hence, the study will observe participants over 10 years to ensure enough time is allotted for results.
Implications:
These results could be used to effectively target and treat ASPD patients with this mutation by “turning off” the genetic cause using CRISPR gene editing technology.
This would provide a stronger understanding and treatment for a condition not entirely understood in the scientific community.
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