-PURPOSE:Autism, a neuropsychiatric illness, is a complex ailment of mainly indefinite cause. Although precise pathophysiological mechanism is unclear but the role of genetics is undeniable therefore pharmacogenetics may assist to a better management of symptoms. Risperidone is widely used in autism. Considering the significance of dopaminergic system in psychological and neurological diseases and its association with autism, the hypothesis that genetic variant of dopamine receptor (DRD3), Ser9Gly (rs6280), may influence treatment of autism may be assumed. METHOD: In the present study, 56 autistic Persian children within the age range of 2.5 to 14 years were included. Diagnosis of autism was based on DSM-V criteria and the severity degree was measured by ABC-C checklists at base line and after 8 weeks of treatment with risperidone. Based on their scores patients were categorized as responsive and non-responsive groups. DRD3 Ser9Gly (rs6280) was determined by PCR-RFLP. RESULTS: Carriers of Gly allele as well as carriers of Gly/Gly and Ser/Gly genotypes showed significantly better response to risperidone compared with carriers of Ser allele and Ser/Ser genotype (P=0.027; OR= 4.18; 95%CI=1.16-15.03 and P=0.014; OR=6.825; 95%CI=1.36-34.13). CONCLUSION: Our results advocate the possible influence of genetic variation of DRD3 in clinical response to antipsychotics like risperidone in autistic individuals.

Hyperactivity of the hypothalamic pituitary adrenocortical (HPA) axis is one of the main clinical findings in depression. The HPA axis is interrelated with glucocorticoid signaling via glucocorticoid receptors (GCRs). Thus, functional genetic variants on GCRs might influence therapeutic outcomes in depression. The aim of the present study was to investigate the association between three functional polymorphisms (rs41423247, rs6195, and rs6189/rs6190) on GCR and response to fluoxetine in a group of depressed patients. One hundred newly diagnosed patients completed 6 weeks of fluoxetine treatment. Response to treatment was defined as a 50% decrease in the Hamilton Depression Rating Scale score. Variants of rs41423247, rs6195, and rs6189/rs6190 polymorphisms were determined in extracted DNAs using PCR-RFLP method. Regarding rs41423247 polymorphism, carriers of the CG and GG genotype responded significantly better to fluoxetine compared with CC carriers (p=0.008, OR=3.3, 95% CI=1.35-8.07). Moreover, the G allele of rs41423247 polymorphism was strongly associated with response to fluoxetine (p=0.032, OR=2.2, 95% CI=1.09-4.44). There was no significant association between different genotypes and alleles of rs6195, rs6189/rs6190 variants, and response to fluoxetine (p=0.213 and 0.99, respectively). In conclusion, rs41423247 polymorphism might be a predictor for better response to fluoxetine. These findings support the idea that some variants of the GCR might contribute to interindividual variability of response to antidepressants.

-Purpose: The adrenoceptor family, as one of the main contributors in regulating the noradrenergic system, has been studied in involvement of depression and its treatment. A functional polymorphism of G1165C on beta adrenoceptor (βAR) enhances post receptor signalling and is assumed to be involved in pharmacotherapy of depression. The aim of the present study was to discern the influence of G1165C polymorphism in the β1AR gene on individual differences in response to sertraline. Methods: One hundred newly diagnosed patients completed 6 weeks of sertraline treatment. Response to treatment was defined as a 50% decrease in Hamilton Rating Scale for depression (HRSD). Results: The patients who carried CC genotype responded five times more to sertraline comparing with other variants (P=0.005; OR=5.7; 95%CI=1.4-23.9). Moreover, carriers of C allele responded three times more to sertraline than patients with the G allele (P=0.001; OR= 3.3; 95%CI= 1.72-6.50). Conclusion:In conclusion, our results support the hypothesis that genetic variation of β1AR might influence clinical response to sertraline.

Background: Pharmacogenetics has proven role in the treatment of different illnesses. Patients with special genotypes may achieve a better response to a specific drug. On the other hand, genetic parameters markedly contribute to the development of major depressive disorder (MDD). The significance of adrenergic system compartments in cognition and behavior, and their role in etiology of depression denote that adrenergic receptors beta gene polymorphism(s) might also have an association with drug response. Thus this study aims to evaluate the association between β1AR gene polymorphisms, G1165C, Arg389Gly and response to fluoxetine in MDD patients. Materials and Methods: Among different antidepressants, we focused on fluoxetine as it is prescribed frequently in MDD and belongs to one of the most efficient antidepressant categories with minimum side effects. MDD was diagnosed at study entry using DSM-IV criteria. One hundred and one new MDD patients were treated with fluoxetine for a period of 6 weeks. A 50% decrease in Hamilton Rating Scale for Depression (HRSD) was considered as response to treatment. Genotyping of G1165C polymorphism was performed by PCR-RFLP method. Results: Results of the study indicated no significant relationship between β1AR polymorphism and the patient’s response to fluoxetine neither at genotypic nor allelic level (P=0.568). Conclusion: Our study did not support the hypothesis of involvement of β1AR Arg389Gly polymorphism and response to fluoxetine in MDD patients. [GMJ.2020;9:e1781]