Meta-Analysis of Differences in Brain Structure in Severe Antisocial Behaviour

The Enhancing Neuro-Imaging Genetics through Meta-Analysis (ENIGMA) initiative represents an international team-science effort aiming to uncover how genetics and disease influence the brain by meta-analysing neuroimaging data from research groups across the globe (Bearden & Thompson, 2017). This approach aims to overcome the limitations of small-scale and methodologically heterogenous neuroscientific research by facilitating collaborative analyses, which may ultimately produce more robust and replicable findings. ENIGMA currently comprises more than 50 working groups, covering various areas of neuroscience and a number of psychiatric disorders (Thompson et al., 2019). Recently, the ENIGMA Antisocial Behaviour working group has been established, which provides the context for this project.

Antisocial behaviour (AB) comprises violence, aggression, and rule-breaking, including severe violations of others' rights. Severe AB is central to the DSM diagnoses of conduct disorder (CD) in children or adolescents, and antisocial personality disorder (ASPD) or psychopathy in adults. These disorders are prevalent and associated with various negative outcomes including delinquency, substance abuse and poor physical and mental health, meaning that it is important to study them.

Neuroimaging research has identified structural brain differences in those with severe AB compared to healthy controls. However, findings are inconsistent, and many have not been replicated. This may be linked to limitations of previous research. First, due to small samples, many studies were statistically underpowered to detect the small brain differences that might be expected based on research into other psychiatric disorders. Second, methodological differences (e.g., in MRI data acquisition or analysis methods) limit the comparability of findings. Lastly, studies often investigate heterogenous participant groups (e.g., differing age-of-onsets) without accounting for such differences. This may confound results and limits our understanding of the influence of these factors.

In the context of ENIGMA, this project addresses these limitations by combining neuroimaging data from leading research groups studying AB (with a projected sample size of over N = 5000). The study aims to identify structural brain markers that robustly distinguish individuals with AB-related diagnoses (CD, ASPD/psychopathy) from healthy controls, and determine whether these markers differ across the lifespan and whether they are impacted by factors such as age-of-onset or comorbidity.

As it will involve the most comprehensive analysis of structural brain alterations in individuals with AB performed to date, this project will help us identify robust structural correlates of AB. It will be the first study to simultaneously investigate different age groups, allowing us to examine the developmental stability of brain alterations in AB. Moreover, the exploration of various participant characteristics offers the potential to inform future revisions of the diagnostic and classification systems (e.g., DSM) by identifying biologically-meaningful subtypes of AB. Lastly, we might be able to identify neural markers that predict outcomes (e.g., persistence versus desistance) or treatment response.