Psychiatry Research 301 (2021) 113979 Available online 3 May 2021 0165-1781/© 2021 Elsevier B.V. All rights reserved. Smaller subcortical volumes and enlarged lateral ventricles are associated with higher global functioning in young adults with 22q11.2 deletion syndrome with prodromal symptoms of schizophrenia Carina Heller a, b, c, * , Thomas Weiss c , Elisabetta C. del Re a, d , Sophia Swago a , Ioana L. Coman e, f , Kevin M. Antshel g , Wanda Fremont e , Sylvain Bouix a , Wendy R. Kates e , Marek R. Kubicki a, h, i , Zora Kikinis a a Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States b Department of Psychiatry and Psychotherapy, Jena University Hospital, Germany c Department of Clinical Psychology, Friedrich-Schiller-University Jena, Am Steiger 3, Haus 1, Jena 07743, Germany d VA Boston Healthcare System, Brockton, MA, United States e Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, United States f Department of Computer Science, SUNY Oswego, Oswego, NY, United States g Department of Psychology, Syracuse University, Syracuse, NY, United States h Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States i Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States A R T I C L E INFO Keywords: Schizophrenia Prodromal symptoms 22q11.2 deletion syndrome Subcortical structures Lateral ventricles Global functioning Premorbid adjustment ABSTRACT The 22q11.2 deletion syndrome (22q11DS) is a developmental genetic syndrome associated with a 30% risk for developing schizophrenia. Lateral ventricles and subcortical structures are abnormal in this syndrome as well as in schizophrenia. Here, we investigated whether these structures are related in young adults with 22q11DS with and without prodromal symptoms (PS) for schizophrenia and whether abnormalities in volumes are associated with global functioning. MR images were acquired on a 3T scanner from 51 individuals with 22q11DS and 30 healthy controls (mean age: 21±2 years). Correlations were performed to evaluate the relationship between ventricular and subcortical volumes, with Global Assessment of Functioning (GAF) and Premorbid Adjustment Scale (PAS) in each group. Lateral ventricular volumes correlated negatively with subcortical volumes in in- dividuals with 22q11DS. In individuals with 22q11DS with PS only, GAF correlated positively with volumes of the lateral ventricles and negatively with subcortical volumes. PAS correlated negatively with lateral ventricle volumes, and positively with volumes of subcortical structures. The results suggest a common neuro- developmental mechanism related to the growth of these brain structures. Further, the ratio between the volumes and clinical measures could potentially be used to characterize individuals with 22q11DS and those from the general population for the risk of the development of schizophrenia. 1. Introduction Of all morphometric abnormalities observed in schizophrenia, most frequent are the enlarged lateral ventricles (Shenton et al., 2001; Van Erp et al., 2016). Increases in lateral ventricular volumes were among the first identified abnormalities in schizophrenia (Johnstone et al., 1976). They remain the most reliable and consistent abnormalities re- ported in schizophrenia (Kempton et al., 2010) although the mecha- nisms of these ventricular enlargements remain mostly unknown. In addition to enlarged volumes of the lateral ventricles, abnormalities in subcortical brain structures are well characterized in individuals with schizophrenia (Gurholt et al., 2020; Okada et al., 2016; Shenton et al., 2001; Van Erp et al., 2016). The subcortical structures, which include thalamus, caudate nucleus, putamen, pallidum, nucleus accumbens, hippocampus, and amygdala, are directly adjacent to the ventricle sys- tem. While increases in volumes of the lateral ventricles and abnor- malities in subcortical structures were reported in people with schizophrenia, the relationship between the volumes of these structures * Corresponding author. E-mail address: carina.heller@uni-jena.de (C. Heller). Contents lists available at ScienceDirect Psychiatry Research journal homepage: www.elsevier.com/locate/psychres https://doi.org/10.1016/j.psychres.2021.113979 Received 8 January 2021; Accepted 25 April 2021