School of Biological and Chemical Sciences

Gene-Environment Interaction and Mental Health Across the Life Course

Supervisor: Dr Michael Pluess

Co-supervisor: Dr Charlotte Clark

Project description

The project combines the field of molecular genetics with developmental psychology and epidemiology of mental health using life course data from the 1958 National Child Development Study (NCDS), a large-scale representative cohort study. Applying a life course approach this studentship project seeks to break new ground in the study of gene-environment interaction pertaining to mental health outcomes by applying a Differential Susceptibility framework (Belsky & Pluess, 2009), testing 1) whether specific gene variants increase an individual’s environmental sensitivity to both negative and positive aspects of the environment, 2) whether such individual differences in environmental sensitivity are restricted to specific developmental periods across the life course, and 3) by investigating individual candidate genes as well as polygenic scores based on many different genetic variants.

The notion that some individuals will be affected differently by the same environment as a function of genetic differences has gained significant interest over the years. Research on such gene-environment interplay has generally been cast in Diathesis-Stress terms, focused on genetic “risk” factors which seem to make individuals carrying them disproportionately prone to negative outcomes when they experience contextual adversity. For example, Caspi et al. (2003) reported in their ground-breaking and pioneering gene-environment interaction work that a polymorphism in the serotonin transporter gene (5-HTTLPR) moderated the effects of childhood maltreatment on depression in adulthood. However, in the absence of life stress there was no difference in depression between individuals carrying different variants of the 5-HTTLPR. The Differential Susceptibility perspective provides a fundamentally different view than diathesis-stress, stipulating that individuals differ in their environmental sensitivity to negative as well as positive environmental quality rather than just being more vulnerable to negative effects of adverse environments (Belsky & Pluess, 2009; Pluess & Belsky, 2013). An ever growing number of gene-environment interaction studies provide evidence often more consistent with differential susceptibility than diathesis-stress (for review, see Belsky et al., 2009; Belsky & Pluess, 2009; Pluess, Belsky, Way, & Taylor, 2010). However, current studies reporting gene-environment interactions—irrespective whether more consistent with differential susceptibility or diathesis-stress—are often severely limited by (1) inadequately low sample sizes (Duncan & Keller, 2011), (2) cross-sectional designs that ignore developmental aspects (Belsky & Pluess, 2013), (3) retrospective measures of environmental quality (Uher & McGuffin, 2010) that (4) reflect negative but not positive aspects of the environment (Belsky et al., 2009).

The aim of the current research project is to overcome all four limitations of existing work by empirically evaluating differential susceptibility using the 1958 NCDS cohort study. The primary objective of the current proposal is to investigate whether a selection of candidate genes, including the 5-HTTLPR, DRD2, COMT, BDNF as well as recently developed polygenic scores based on genome-wide data (GWAS), increase susceptibility to both negative and positive experiences across life on mental health outcomes at different points across the life course. In particular, it will be investigated whether the different susceptibility variants—individually and combined in polygenic scores—moderate sensitivity to environmental influences on both mental health problems and positive mental states from age 7 to 55 years.

The proposed PhD project has three aims:

  • Genetic Moderation: Investigate whether gene variants increase an individual’s environmental sensitivity in response to both negative and positive contexts regarding the development of mental health.
  • Developmental Perspective: Investigate whether such genetic moderation effects are restricted to specific developmental periods across the life course.
  • Cumulative Genetic Effects: Investigate the moderating effects of polygenic scores based on the combination of many different genetic variants.

The moderating effects of the different gene variants and polygenic scores will be tested with hierarchical regression models, growth curve models for repeated outcomes, structural equation modelling and a more recently developed data modelling approach to test more specifically for genetic moderation (Belsky, Pluess, & Widaman, 2013; Widaman et al., 2012). Given that mental health can be defined as either the absence of problems (i.e. low depression) or the presence of positive psychological states (i.e. high life satisfaction) the study will focus on both measures of mental health problems (i.e. malaise scores, ICD-10 psychological disorders) as well as measures of well-being (i.e. life satisfaction, positive emotionality).

Eligibility and applying

Given the focus on secondary data analysis, this PhD project requires advanced skills in biostatistics, data management, computer based data analysis, and pronounced ability and motivation to acquire new data analysis skills. Furthermore, this project requires excellent scientific writing skills and the ability to work independently.

Applicants must send a cover letter to Dr Michael Pluess outlining their suitability for the project. Applicants should also include a statement of motivation and CV, which should include the contact details of at least two academic referees, before submitting an application.

Contact/query instructions: Dr Michael Pluess

See also