Genetic modifiers in rare disorders: the case of fragile X syndrome.

Methods employed in genome-wide association studies are not feasible ways to explore genotype-phenotype associations in rare disorders due to limited statistical power. An alternative approach is to examine relationships among specific single nucleotide polymorphisms (SNPs), selected a priori, and behavioural characteristics. Here, we adopt this strategy to examine relationships between three SNPs (5-HTTLPR, MAOA, COMT) and specific clinically-relevant behaviours that are phenotypic of fragile X syndrome (FXS) but vary in severity and frequency across individuals. Sixty-four males with FXS participated in the current study. Data from standardised informant measures of challenging behaviour (defined as physical aggression, property destruction, stereotyped behaviour, and self-injury), autism symptomatology, attention-deficit-hyperactivity-disorder characteristics, repetitive behaviour and mood/interest and pleasure were compared between each SNP genotype. No association was observed between behavioural characteristics and either 5-HTTLPR (serotonin) or MAOA (monoamine oxidase) genotypes. However, compared to the COMT (dopamine) AG and GG genotypes, the AA genotype was associated with greater interest and pleasure in the environment, and with reduced risk for property destruction, stereotyped behaviour and compulsive behaviour. The results suggest that common genetic variation in the COMT genotype affecting dopamine levels in the brain may contribute to the variability of challenging and repetitive behaviours and interest and pleasure in this population. This study identifies a role for additional genetic risk in understanding the neural and genetic mechanisms contributing to phenotypic variability in neurodevelopmental disorders, and highlights the merit of investigating SNPs that are selected a priori on a theoretical basis in rare populations

Experiences of domestic violence and body dissatisfaction : women from the South Asian diaspora

Chapter 1 is a systemic literature review of seventeen research studies, which explored the coping strategies employed by South Asian women residing in western countries, who had experienced domestic violence. Following a meta-ethnographic synthesis, three themes emerged: Honouring Family Values, Overt Safety Strategies, and Seeking Connection. Clinical and policy implications were discussed in relation to the findings, which highlighted the need for culturally sensitive and appropriate support for South Asian women facing domestic violence. Emphasis should be placed on understanding the role of individual, family and cultural contexts when reflecting on how South Asian women cope with moments of violence. Recommendations for future research were also discussed. Chapter 2 is an empirical, qualitative research study which explored the lived experiences of appearance-related body dissatisfaction in eight young British Indian women. Semi-structured interviews were employed, and Interpretative Phenomenological Analysis of the data resulted in two emerging themes: Shamed and Ashamed and The Process of Changing and/or Accepting the Self. Findings revealed that compassionate and sensitive approaches are required from services when holding in mind the pervasive role of shame resulting from women’s experiences. It is recommended that clinicians and services support women during their complex journey towards body acceptance, utilising culturally sensitive interventions. Chapter 3 is a reflective paper which discusses the process of conducting a doctoral thesis based on the author’s perspectives. This chapter includes models of social difference to guide reflections on the author’s position particularly during the completion of the empirical research. Particular consideration was placed on navigating challenges that arose during the research journey