Discordant monozygotic twin studies of epigenetic mechanisms in mental health

The discordant monozygotic twin design is a strong method to assess causality. The design has been applied in a number of studies to investigate epigenetic mechanisms associated with mental health. These studies initially mainly focused on candidate genes and increasingly on genome-wide DNA methylation, gene expression, and X-chromosome inactivation, in various surrogate tissues such as blood and buccal cells, but also in brain tissue. In this chapter we review monozygotic twin studies of autism, aggressive behavior, ADHD, schizophrenia, bipolar disorder, and depression. We discuss the insights obtained by these studies and describe current limitations and challenges, including sample size, the use of surrogate tissues, causality, and confounders that apply to studies of cognitive and mental health such as medication use, lifestyle, and cellular heterogeneity of commonly investigated tissues.