The differential impact of oxytocin receptor (OXTR) genotypes on the risk of autism spectrum disorder (ASD) and resulting social communication deficits

Background: Autism spectrum disorder (ASD) is multifactorial and is likely the result of complex interactions between multiple environmental and genetic factors. Recently, it has been suggested that each symptom cluster of the disorder, such as poor social communication, may be mediated by different genetic influences. Genes in the oxytocin pathway, which mediates social behaviours in humans, have been studied with single nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR) being implicated in ASD. This thesis examines the presence of different oxytocin receptor genotypes, and their associations with ASD and resulting social communication deficits. Methods: The relationship between four OXTR variants and ASD was evaluated in 607 ASD simplex (SPX) families. Cases were compared to their unaffected siblings using a conditional logistic approach. Odds ratios and associated 95 percent confidence intervals were obtained. A second sample of 235 individuals with a diagnosis of ASD was examined to evaluate whether these four OXTR variants were associated with social communication scores on the Autism Diagnostic Interview – Revised (ADI-R). Parameter estimates and associated 95 percent confidence intervals were generated using a linear regression approach. Multiple testing issues were addressed using false discovery adjustments. Results: The rs53576 AG genotype was significantly associated with a lower risk of ASD (OR = 0.707, 95% CI: 0.512-0.975). A single genotype (AG) provided by the rs2254298 marker was found to be significantly associated with higher social communication scores (Parameter estimate = 1.833, SE = 0.762, p = 0.0171). This association was also seen in a Caucasian only and mothers as the respondent samples. No association was significant following false discovery rate adjustments. Conclusion: The findings from these studies provide limited support for the role of OXTR SNPs in ASD, especially in social communication skills. The clinical significance of these associations remains unknown, however, it is likely that these associations do not play a role in the severity of symptoms associated with ASD. Rather, they may be important in the appearance of social deficits due to the rs2254298 markers association with enlarged amygdalas.

Randomized Trial for a Mobile Health Approach to Increase Uptake of Cervical Cancer Screening in Tanzania

Background: Largely due to low availability and uptake of screening in low- and middle-income countries, cervical cancer is the second ranked cancer among women in these countries. This is a tragedy because cervical cancer is one of the most preventable carcinomas. This thesis will investigate behaviour change methods, which capitalize on the recent exponential increase in ownership of mobile phones in Tanzania, to increase uptake of cervical cancer screening (CCS) in the Kilimanjaro region of Tanzania. Objectives: 1) To evaluate the effectiveness of behaviour change messages delivered via short message service (SMS) on the uptake of CCS in the Kilimanjaro region; 2) to evaluate the effectiveness of a transportation eVoucher on the uptake of CCS in the Kilimanjaro region; 3) to explore characteristics associated with CCS uptake in the Kilimanjaro region; and 4) to determine the attitudes towards and perceived benefit of behaviour change SMS messages and eVouchers intended to increase uptake of CCS. Methods: In the Kilimanjaro Region, 853 women participated in a randomized controlled trial. Baseline data was collected through self-report through systematic stratified random sampling. Participants were randomized to one of three groups: a control group, a group receiving behaviour change messages delivered via SMS, or a group receiving a travel eVoucher and identical SMS as the SMS group. A fieldworker recorded participants attending screening at the CCS clinics and administered a post-screening survey. The follow-up period was two months from the time of the participant’s enrolment. Logistic regression (both for the combined and stratified data sets) was used to determine associations between the behaviour change interventions, baseline characteristics and cervical cancer screening uptake. Results: All participants receiving SMS messages (SMS or eVoucher group) were more likely to attend cervical cancer screening in comparison with the control group. 83% of participants who attended screening shared the information contained in the messages with others. Conclusions: Behaviour change messages delivered via SMS and transportation eVouchers have the potential to increase uptake of cervical cancer screening in the Kilimanjaro region of Tanzania. Harnessing this potential will require implementing these interventions alongside other methods to achieve maximum impact.