Environmental Influences on the Relation between the 22q11.2 Deletion Syndrome and Mental Health: A Literature Review

Abstract

22q11.2 deletion syndrome (22q11DS) is a clinically heterogeneous genetic syndrome, associated with a wide array of neuropsychiatric symptoms. The clinical presentation is likely to be influenced by environmental factors, yet little is known about this. Here, we review the available research literature on the role of the environment in 22q11DS. We find that within-patient design studies have mainly investigated the role of parental factors, stress, and substance use, reporting significant effects of these factors on the clinical profile. Case-control studies have been less successful, with almost no reports of significant moderating effects of the environment. We go on to hypothesize which specific environmental measures are most likely to interact with the 22q11 deletion, based on the genes in this region and their involvement in molecular pathways. We end by discussing potential reasons for the limited findings so far, including modest sample sizes and limited availability of environmental measures, and make recommendations how to move forward.

Keywords: 22q11DS; clinical heterogeneity; copy number variation; gene-environment interaction; neuropsychiatric disorders.

Figure 1

Visualisation of types of environmental factors, with on the left side those studied in relation to 22q11DS clinical heterogeneity (stress, parents’ education, peer violence, parents’ psychopathology, substance use, socio-economic status) and on the right side those that remain under investigated (birth complications, infection, social interactions, migration, urbanicity, family structure).