Objective 1: Identifying abnormalities in behaviours implicated in frequent psychiatric disorders

In order to understand the basis of neuropsychiatric disorders it is vital we move from simple disease classifications to ‘intermediate phenotypes’ – that is, measurable markers at the behavioural, psychological, and biological levels that may precede clinical diagnoses. Of particular relevance are individual differences in psychological traits that are implicated in frequent psychiatric disorders such as addiction disorders, anxiety disorders, hyperactivity disorders, schizophrenia, autism spectrum disorders, and personality disorders. The relevant psychological traits under study in IMAGEN are sensitivity to reward/punishment, impulsivity, and emotional response.

Objective 2: Longitudinal study design to determine the predictive value of psychological or biological traits

Because many frequent psychiatric disorders have their onset in early adulthood, it suggests that differences in psychological and/or biological processes during adolescence may have a causal or modulatory role in the development of these disorders. It is notable that adolescence is a unique and vulnerable period whereby much behavioural and brain maturation change takes place. Longitudinal studies like IMAGEN that follow adolescents over time (assessments at ages 14, 16, 19 and 22) are necessary to infer causality of these psychological and biological traits before the presentation of clinical symptoms.

Objective 3: Genetic studies to understand sensitivity to reward/punishment, impulsivity, and emotional responses.

Recent advances in technology allow the simultaneous analyses of nearly one million genes (genome-wide analysis). In addition to this approach, technology enables the identification of naturally occurring genetic variations called single nucleotide polymorphisms (SNPs), variations in the on/off switching of genes (epigenetics), and variations in the functional product of a gene (gene expression). The large number of participants in the IMAGEN study will allow researchers to relate these genetic variations to psychological traits known to be related to mental illness, such as sensitivity to reward/punishment, impulsivity, and emotional responses.

Objective 4: Brain imaging analyses to understand mental illness-related psychological traits

The adolescent participants undergo brain imaging at baseline and follow-up to study brain structure as well as the activity of the brain during various tasks. Researchers can measure individual differences in brain structure and activity, which can then be related to cognition as well as behaviours linked to frequent psychiatric disorders (i.e., responses to reward and punishment, risk-taking, impulsivity, novelty-seeking and emotional responses). Such analyses will be informative as to how the structure and activity of particular brain regions (at one time point and across time points) underlie these behaviours and, importantly, psychiatric disorders.

Objective 5: Genetic analyses of brain activity and structure

Recent research suggests that observed differences in brain activity and structure may be attributable to inter-individual differences in genetics (e.g., SNPs and epigenetics). Results from brain imaging analyses will be assessed for their association with such genetic data. Particular emphasis will be placed on genome-wide analyses as opposed to candidate gene approaches. Results obtained will be validated in other youth studies that have structural and functional MRI data.

Objective 6: How the environment shapes adolescent brain development and psychological traits linked to mental illness

An individual’s behaviour and their brain’s structure/activity are not solely determined by genetics but also by their environment and experience. Participants in the IMAGEN study are extensively characterized in terms of their experiences at school and home, their interactions with parents, friends, and peers, as well as their substance use. This wealth of data will help IMAGEN researchers understand how life’s events influence brain development and how genetics interact with the environment to modulate brain and behavioural development.