Elsevier

Biological Psychiatry

Volume 52, Issue 1, 1 July 2002, Pages 68-70
Biological Psychiatry

Brief report
Increased basal ganglia volumes in velo-cardio-facial syndrome (deletion 22q11.2)

https://doi.org/10.1016/S0006-3223(02)01361-6Get rights and content

Abstract

Background: This study evaluated differences in caudate volumes in subjects with velo-cardio-facial syndrome due to a 22q11.2 (22qDS) deletion. Because psychosis is observed in 30% of adult subjects with 22qDS, this neurogenetic disorder could represent a putative model for a genetically mediated subtype of schizophrenia.

Methods: Caudate volumes were measured on high-resolution magnetic resonance images in 30 children and adolescents with 22qDS and 30 gender- and age-matched normal comparison subjects.

Results: Caudate head volumes were increased in the 22qDS group independent of neuroleptic medications. Subjects with 22qDS also displayed an abnormal pattern of asymmetry in the anterior caudate, with left side greater than right.

Conclusions: Alterations in the basal ganglia circuitry have been implicated in learning, cognitive, and behavioral problems in children and therefore could be involved in the expression of the neurobehavioral phenotype expressed by subjects with 22qDS. Abnormal caudate volume is a neurodevelopmental feature shared with schizophrenia, further establishing 22qDS as a potential neurodevelopmental model for this disorder.

Introduction

Recent clinical and neuroimaging studies (Feinstein and Eliez 2000) suggest that velo-cardio-facial syndrome and other 22q11.2 deletion-related syndromes (22qDS) could serve as a model for a genetically mediated sub-type of schizophrenia. Twenty to thirty percent of adult subjects diagnosed with 22qDS develop schizophrenia during childhood or early adulthood (Feinstein et al 2000). Children and adolescents with 22qDS show brain alterations that are similar to those observed in schizophrenia Eliez et al 2000, Eliez et al 2001a, Eliez et al 2001b, Kates et al 2001, van Amelsvoort et al 2001. Typically, subjects with 22qDS have reduced parietal lobes and posterior fossa volumes Eliez et al 2000, Eliez et al 2001c, Kates et al 2001, as well as possible decreases in temporal lobes Eliez et al 2001b, Kates et al 2001, van Amelsvoort et al 2001; however, the caudate nucleus, aneuroanatomical structure altered in schizophrenia, has only recently been measured in two studies involving subjects with 22qDS Sugama et al 2000, van Amelsvoort et al 2001. The first study (Sugama et al 2000) identified abnormal asymmetry of the caudate in a pediatric 22qDS sample (17 subjects with 22qDS and 15 control subjects). The second study (van Amelsvoort et al 2001) reported the absence of caudate volume differences in a small group of 10 adults with 22qDS compared to 13 intelligence quotient (IQ)-matched control subjects.

Studies measuring caudate volumes in early and adult-onset schizophrenic subjects McCarley et al 1999, Wright et al 2000 have shown abnormal volumes of the caudate; however, results from the schizophrenia literature to date have been contradictory and are often confounded by the use of neuroleptics among study participants. Thus, we hypothesized that caudate volumes would be aberrant in 22qDS, although the directionality of the change (increase or decrease) could not be predicted a priori.

Section snippets

Methods and materials

The sample consisted of children and adolescents with velo-cardio-facial syndrome (n = 30, mean age = 12.1 ± 3.8 years), confirmed using fluorescent in situ hybridization, and a group of control subjects (n = 30, mean age = 12.2 ± 4.4) who were matched individually for age and gender. Only two subjects with 22qDS were treated with neuroleptic drugs (for mood problems and psychosis, respectively) before magnetic resonance imaging (see Feinstein et al, in press for a clinical description of this

Results

Overall brain gray matter was decreased in 22qDS [F(1,58) = 4.1, p < .05]. A comparison of adjusted caudate volumes revealed significant increases in the 22qDS group compared to control subjects (see Table 1). The differences in total caudate volumes were bilateral and driven by differences in the volume of the caudate head. Exploration of symmetry/asymmetry revealed that the total caudate was asymmetric [L > R; F(1,58) = 4.3, p < .05] in the 22qDS group as opposed to caudate symmetry observed

Discussion

The alteration of the caudate head volume is consistent with our hypothesis but inconsistent with prior findings. Previous investigations did not find structural increases of the caudate when comparing subjects with 22qDS to control subjects Sugama et al 2000, van Amelsvoort et al 2001. Several reasons could explain the discrepancy. First, the previous studies had smaller sample sizes and used comparison populations that were not composed solely of typically developing subjects or IQ-matched

Acknowledgements

The research presented here was supported by the National Swiss Research Fund to Dr. Stephan Eliez (3200-063135.00/1 and 3232-063134.00/1) and National Institutes of Health grants MH01142 and HD31715 to Dr. Allan Reiss. This work also was partially supported by a grant from the Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute to Dr. Reiss.

The authors thank Bronwyn Glaser, B.A., and Christine Blasey, Ph.D., for their help, and Tammy Lee, Alison Reid, Teena Gerhardt, and

References (15)

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