Discussion
The authors hypothesize that the factors that affect Glycogen synthase kinase 3-β (GSK3-β) and 5-HT activities might interact in humans in the way that the genetic inhibition of the GSK3-β counteracts the genetic inhibitions pathways of the 5-HT (Benedetti et al., 2011). The authors provide that data they collected supports their hypothesis since they found out that those carriers of wild rs334558*T variant, which is a form of 5-HTTLPR, responded dismally to antidepressants, while carriers of rs334558*C, another variant of 5-HTTLPR, responded very well to antidepressants (Benedetti et al., 2011). This is because GSK3-β activity is reduced by the gene promoter polymorphism, thus alienating the harmful effects of 5-HT on the response of antidepressants.
These observations made from the data show that the gene to gene interaction, such as the one between 5-HTTLPR and GSK3-β, will determine the reaction of an individual to clinical antidepressants. The observations also agree with the hypothesis since they show that increasing the GSK3 inhibitory control is a vital factor of the therapeutic action of mood disordering drugs. According to Benedetti et al., (2010) and Smeraldi et al., (2002), both, the GSK3-β rs334558 and 5-HTTLPR have a major influence not only on antidepressant response, but also on vital clinical characteristics including recurrence and onset of illness. This gene to gene influence can also be extended to several individual features of other psychiatric illness.
Other Researches
The results by the authors correspond with other previous research done on animals. According to Beaulieu et al. (2008), in their pivotal study of rodents, the inhibition of 5-HT by tph2 increased the GSK3 activity, which resulted in an increase of depressive behaviors (Benedetti et al., 2011). The depressive behavior was antagonized by the GSK3-β inhibition or knockout. This interaction between the 5-HT and GSK3-β impacts behavior and brain of the mice and is similar to the interaction of the two genes in humans.
Significance of Findings
It was ascertained that carriers of wild rs334558*T variant which is a form of 5-HTTLPR responded to antidepressants poorly, while carriers of rs334558*C another variant of 5-HTTLPR, responded to antidepressants very well (Benedetti et al., 2011). These effects of 5-HTTLPR can be eliminated by giving GSK3-β inhibitor lithium to humans as it overcomes the 5-HTTLPR gene polymorphism influence on the antidepressant response. This leads to the best response in patients treated with 5-HTTLPR s/s. GSK-3 is located at the crossroads of numerous pathways that regulate metabolism and trophism, thus it is a key factor in influencing the neurons susceptibility to dangerous stimuli (Benedetti et al., 2011). It is important to inhibit the GSK-3 to prevent harmful stimuli to the neurons as this causes depression.
Results
I draw the same conclusions as the authors since their results showed that rs334558 and 5-HTTLPR influenced the response of antidepressants treatment. If these two affect the response of antidepressant treatment, then their influence can be neutralized by using the GSK3-β inhibitor lithium, which will increase the response of the patients to antidepressants. The authors also focused on the research questions stated in the hypothesis and deeply assessed the effect of 5-HTTLPR on the response of antidepressants. However, although the outcomes of the study are credible and in agreement with the hypothesis, there are some limitations that cannot be overlooked such as the use of a small sample size, lack of stratification in the population, lack of adequate funding and ignoring other gene- gene interactions, except for those under study (Benedetti et al., 2011). All these factors are likely to limit the accuracy and precision of the outcomes of the study.
Reference
Benedetti, F., et al. (2011). Gene–gene interaction of glycogen synthase kinase 3-β and serotonin transporter on human antidepressant response to sleep deprivation. Journal of Affective Disorders, 10 (39): 1-5.