UCLA

Coordinated, large-scale efforts to study brain disorders are rare, with most neuroimaging studies collecting fewer than 100 study participants. Neuroimaging research is one of many biomedical fields that have suffered from low study power and reproducibility. Genetic variation and psychiatric disorders confer subtle effects on markers of brain structure and function, further complicating the discovery and validation of reproducible neuroimaging biomarkers.

The Enhancing Neuro Imaging Genetics through Meta Analysis Consortium (ENIGMA) has developed harmonized processing and analysis protocols to empower large-scale neuroimaging studies of genetic variation and psychiatric illness. By using standardized methods, prospective meta- and mega-analysis carried out by the ENIGMA consortium improve upon conventional retrospective meta-analyses. ENIGMA working groups include both conventional studies of psychiatric disorders such as the ENIGMA Bipolar Disorder Working Group, as well as genetics-first approaches like the ENIGMA 22q11.2 deletion working group, which study populations at high risk for psychiatric illness. These ENIGMA studies represent the largest collaborative efforts to study neuroimaging markers in their respective disorders.

The ENIGMA bipolar working group has reported altered cortical and subcortical volumes, which show significant predictive power in discriminating patient populations. The ENIGMA 22q11.2 deletion syndrome working group has reported robust cortical, subcortical and white matter differences between 22q11.2 deletion subjects and healthy controls, differences between common microdeletion subtypes, as well as associations between 22q11.2 deletion-related psychosis and idiopathic schizophrenia. Large-scale, harmonized processing and analysis efforts such as these make cross-diagnostic comparisons possible on an unprecedented scale. Given the known overlap between major psychiatric disorders, such cross-disorder studies may provide robust markers that improve diagnoses, help monitor disease progression, and provide insights into novel therapeutic targets.