Broad Discipline of the Literature Review

The broad discipline that the authors considered for the literature review was on adolescent depression. Kohen et al. (2013) wanted to explore the genetic basis of depression in youths and adolescents. The background literature reflected that polymorphisms in the serotonin transporter gene (SERT) are strongly associated with the genesis and prevalence of depression. Hence, Kohen et al. (2013) explored the possible influence of polymorphisms in the SERT gene on the severity and course of symptoms of depression across a community sample of adolescents. The prevalence of depression across children and adolescents is a growing concern amongst healthcare professions all around the globe. Depression or major depressive disorder is a neuropsychiatric disorder that is featured by low mood and intention of self-harm. It is a debilitating disorder and significantly reduces the quality of life (QOL) across affected individuals(Kohen et al, 2013, Kohen et al, 2008).

The disorder stems from the unavailability of serotonin in the neuronal synapses of the reward-punishment pathway of the brain. Serotonin is a neurotransmitter that is secreted from the pre-synaptic neurons of the ventral tegmental nucleus and binds with the post-synaptic neurons to ensure neurotransmission that is necessary to ensure the mood levels of an individual. However, the SERT is located in the pre-synaptic neuron that actively reuptakes serotonin into those neurons. Such cycling of serotonin between the neuronal synapses and pre-synaptic ensure its homeostasis and turnover.

However, an overactivity of the SERT increases the reuptake of serotonin. As a result, the level of serotonin that is required to ensure the mood of an individual is reduced in the neuronal synapses. Studies have implicated that genetic polymorphisms are responsible for the overactivity of the SERT (Kohen et al, 2013, Kohen et al, 2008).

Gaps and Issues Identified from the Synthesis of Literature
Kohen et al. (2013) highlighted that adolescent depression is strongly associated with risky behaviors and impairments in social, familial, and school functioning. However, the authors also reflected that symptoms of depression do not always persist in adolescents. Rather, control arms of different intervention trials have demonstrated spontaneous recovery of such symptoms. Such findings suggest that placebo interventions were equally effective to therapeutic interventions in managing the symptoms of depression. Therefore, Kohen et al. (2013) wanted to explore whether genetic variations of the SERT is accountable for the persistence of depression in adolescents. This is because the authors contended that genetic variations in the SERT gene could account for the persistence and severity of depression in adolescents and therapeutic interventions may have a secondary role in alleviating the symptoms of depression. Different studies have shown that genetic polymorphisms in the 43bp-long segment of the SERT promoter region (5-HTTPLR) predispose the risk and prevalence of depression (Kohen et al, 2008).

On the contrary, genetic polymorphism in the STin2VNTR region (that is located in the 2nd intron of the SERT gene) has been less well studied. Different studies have reflected a strong association between the S-allelic variant of 5-HTTPLR and susceptibility to depression across adults. Likewise, carriers of the l-allelic variant have exhibited improved remission and recovery rates to SSRI (selective serotonin reuptake inhibitors) (Myung et al, 2010). However, two studies have reflected adults who are homozygous for the l allele is susceptible to chronic depression. Few authors have reported that there is no significant association between genetic polymorphisms in the 5-HTTPLR region and prevalence of adolescent depression (Porcelli, Fabbri, & Serretti, 2012). On the contrary, there is a strong association between exposure to environmental stressors and prevalence of childhood depression. Such inconclusive evidence on the role of genetic polymorphisms in the SERT gene on the genesis of adolescent depression prompted Kohen et al. (2013) to conduct the study. Hence, Kohen et al. (2013) in their study explored the primary research question “whether genetic polymorphisms in the 5-HTTPLR and STin2VNTR regions of the SERT gene either alone or in combination is associated with increased severity and greater persistence of the symptoms of depression in adolescents?”

Design and Methodology of the Kohen et al. (2013) study

The trial was conducted as a mixed-methodology study and purposive sampling was used to select the study participants. The study participants were selected from a longitudinal cohort study (comprising of 4000 individuals who were randomly selected from the community). Individuals (n=192) who presented with symptoms of depression (with a PHQ-9 score of >11) and belonged to the age group of 13 to 17 years were only included in the study. The study participants donated their saliva (0.5ml) for the genotyping analysis. The genotyping analysis explored genetic polymorphisms in the 5-HTTPLR and STin2VNTR regions of the SERT gene. The participants were assessed at baseline, after six weeks, and post six months from the initiation of the study. The PHQ-9 scores were considered as the primary outcome variables, while the different genotypic variants of the 5-HTTPLR and STin2VNTR regions were considered the primary exposure variables. The authors conducted two sets of analyses.
In one analysis, the prospective loci (base pairs) of the 5-HTTPLR and STin2VNTR regions and their relation to the severity and persistence of depression among study participants were studied independently. In the second analysis, the authors explored the interaction of the two loci on the severity and persistence of depression across the same study participants. The authors deployed chi-square analysis and Wilcoxon’s sum rank test as the statistical tests of inference to report the findings of the study.
Appraisal of the Sample, Sample Size, and Setting of the Kohen et al.

A critique on the design and methodology of the Kohen et al. (2013) study implicate that the study population (sample), the size of the sample, and the settings under which the authors conducted the study was appropriate. Moreover, the end-points and the intervention variables that were selected by the authors were appropriate too. Hence, the Kohen et al. (2013) study is both reliable and reproducible.

Findings and Conclusions of the Kohen et al. (2013) study

The authors reported that there was no significant association (p>0.05) between SERT genotype and the severity of depression (PHq-9 scores) at baseline. However, the authors reflected a significant interaction between time and genotype of the 5-HTTPLR region (p<0.05). Kohen et al. (2013) highlighted that individuals, who were heterozygotic (S/L) for the 5-HTTPLR region, exhibited significant reduction in the symptoms of depression compared to their counterparts who were homozygotic (L/L) for the 5-HTTPLR region (p<0.05). Such findings suggest that with time depressive symptoms fade away across most community-dwelling adolescents.

Implications for Future Research

However, the authors highlighted that possible interaction between time and SERT genotypes should be confirmed through large and longitudinal studies before arriving at such conclusions. Moreover, future research should aim to study the interaction between different anti-depressants and the genotypic variants of the 5-HTTPLR in alleviating symptoms of depression across adolescents. Such findings would help to ensure personalized and tailor-made interventions for concerned stakeholders that would also reduce the complications and adverse effects that are associated antidepressant therapy.

Importance of the Kohen et al. (2013) article in Advanced Nursing practice (ANP)

ANPs are often entrusted in ensuring evidence-based care across challenged populations. This study would help ANPs in recognizing the etiology and prognosis of depression in adolescent patients. Such information would be helpful in implementing person-centric care across concerned stakeholders or for reducing the apprehensions of their family members.

Conclusion
Since the present article (Kohen et al. 2013) falls in the category of level-1 evidence, I would certainly recommend this article to develop evidence-based knowledge across peers and allied individuals.

References
Kohen R, Myaing M, Richards J, Zhou C, McCauley E, Kayton W, and Richardson, L. (2013). Depression persistence and serotonin transporter genotype in adolescents under usual care conditions, J Child Adolesc Psychopharmacol 23 (4), 290-294).
Kohen R. Cain KC. Mitchell PH. Becker K. Buzaitis A. Millard SP. Navaja GP. Teri L. Tirschwell D. and Veith R. (2008) Association of serotonin transporter gene polymorphisms with poststroke depression. Arch Gen Psychiatry.  65, 1296–1302
Myung W. Lim SW. Kim J. Lee Y. Song J. and Chang KW. Kim DK (2010). Serotonin transporter gene polymorphisms and chronic illness of depression. J Korean Med Sci.  25,1824–1827
Porcelli S. Fabbri C. and Serretti A (2012). Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with antidepressant efficacy. Eur Neuropsychopharmacol.  22, 239–258.