DNA methylation in psychiatric disorders, and mediation of gene by environment effects, from birth to adulthood.

Psychiatric disorders are major contributors to human suffering and morbidity. Their prevalence is increasing, while their causes remain far from understood. A main reason for our limited understanding of these conditions is their complex aetiology where genetic, environmental, and epigenetic factors are contributing. In order to improve quality of life for the patients we need to better understand their biology, to improve their early diagnosis and treatment towards better outcome and prevention. This project will explore novel aspects in genetic and environmental contributions by examining how the environment can modulate gene expression by adding tags on the DNA, so called DNA methylation (an epigenetic modification). We investigate several major psychiatric conditions: schizophrenia (SCZ), bipolar disorder (BD), obsessive compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). We investigate also how DNA methylation can be modulated by the environment. We have identified DNA methylation differences associated with SCZ that are influenced by sex. We have also identified DNA methylation differences associated with exposure to childhood trauma and complications at birth. This project benefits from multidisciplinary expertise in statistical and functional genetics as well as clinical research. Better comprehension of methylation patterns may offer new insight into the biology of psychiatric disorders and potential for advances in their diagnosis, prevention and therapy.

Psychiatric disorders are major contributors to human suffering and morbidity. Their prevalence is increasing, while their causes remain far from understood. A main reason for our limited understanding of these conditions is their complex aetiology where genetic, environmental, and epigenetic factors are contributing. In order to improve quality of life for the patients we need to better understand their biology, to improve their early diagnosis and treatment towards better outcome and prevention. This project proposes to explore novel aspects in genetic and environmental contributions by examining epigenetics of 3 major psychiatric conditions: schizophrenia (SCZ), bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD). We want to address how epigenetic modifications (DNA methylation) can be implicated in these disorders and how these modifications can be modulated by the environment. This project will benefit from multidisciplinary expertise in statistical and functional genetics as well as clinical research. We will focus on identifying changes in DNA methylations in SCZ, BD and ADHD, and their changes across traits, in interaction with environmental factors and as potential targets for drug development and predictive tools. This research capitalizes on the infrastructure and experience from the Norwegian center for mental health research (NORMENT) and the K.G.Jebsen Centre of Neuropsychiatric Disorders (KGJN), in collaboration with leading national and international research groups. The proposed project will provide a unique opportunity to unite several scientific communities in Norway and worldwide by utilizing the data of NORMENT, KGJN, the Norwegian Mother Child Cohort, the Avon Longitudinal Study of Parents and Children and the consortium on persistent ADHD. Better comprehension of methylation patterns may offer new insight into the biology of psychiatric disorders and potential for advances in their diagnosis, prevention and therapy.