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The presence of a 22q11.2 microdeletion (22q11.2 deletion syndrome [22q11DS]) ranks among the greatest known genetic risk factors for the development of psychotic disorders. There is emerging evidence that the cerebellum is important in the pathophysiology of psychosis. However, there is currently limited information on cerebellar neuroanatomy in 22q11DS specifically.

Objective: Velocardiofacial syndrome is a common genetic condition often accompanied by mild cognitive impairment. Children and adolescents with velocardiofacial syndrome also are at greater risk for developing serious neuropsychiatric disorders in adulthood, particularly schizophrenia-like disorders. The purpose of this preliminary study was to 1) elucidate through brain imaging the neurobiological basis of cognitive and neuropsychiatric problems in velocardiofacial syndrome, and 2) consider the association between variations in neuroanatomy in velocardiofacial syndrome subjects and the associated neurobehavioral phenotype. Method: Fifteen children and adolescents with velocardiofacial syndrome were matched by age and gender with 15 comparison subjects. High-resolution magnetic resonance imaging scans were analyzed to provide quantitative measures of specified brain tissues and regions. Rater-blind morphometric analyses were conducted to examine tissue volumes of the four lobes and the cerebellum. Results: Total brain volume was approximately 11% smaller in the children with velocardiofacial syndrome. Gray matter volume was reduced to a lesser extent (7.5%) than white matter volume (16.3%). Multivariate analyses of variance indicated a distinct pattern of regional morphological variation among the children with velocardiofacial syndrome. Specifically, frontal lobe tissue tended to be enlarged relative to the overall reduction in brain volume. Normal symmetry of parietal lobe tissue observed in the comparison group was not evident in the velocardiofacial syndrome group. This loss of symmetry was attributable to a significant reduction of gray matter in the left parietal lobe. Conclusions: Aberrant brain morphology is associated with velocardiofacial syndrome. These changes are potentially related to the language and learning deficits associated with the syndrome and may provide clues about neurodevelopmental pathways associated with schizophrenia.

The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date. The imaging data were collected from 10 centers worldwide, including 474 subjects with 22q11DS (age = 18.2 ± 8.6; 46.9% female) and 315 typically developing, matched controls (age = 18.0 ± 9.2; 45.9% female). Compared to controls, 22q11DS individuals showed thicker cortical gray matter overall (left/right hemispheres: Cohen’s d= 0.61/0.65), but focal thickness reduction in temporal and cingulate cortex. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d= −1.01/−1.02). 22q11DS cases vs. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3 Mb deletions. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. These consistent cross-site findings highlight the homogeneity of this single genetic etiology, and support the suitability of 22q11DS as a biological model of schizophrenia.

Objective: Down's syndrome, the most common genetic cause of mental retardation, results in characteristic physical and neuropsychological findings, including mental retardation and deficits in language and memory. This study was undertaken to confirm previously reported abnormalities of regional brain volumes in Down's syndrome by using high-resolution magnetic resonance imaging (MRI), determine whether these volumetric abnormalities are present from childhood, and consider the relationship between neuroanatomic abnormalities and the cognitive profile of Down's syndrome. Method: Sixteen children and young adults with Down's syndrome (age range=5-23 years) were matched for age and gender with 15 normal comparison subjects. High-resolution MRI scans were quantitatively analyzed for measures of overall and regional brain volumes and by tissue composition. Results: Consistent with prior imaging studies, subjects with Down's syndrome had smaller overall brain volumes, with disproportionately smaller cerebellar volumes and relatively larger subcortical gray matter volumes. Also noted was relative preservation of parietal lobe gray and temporal lobe white matter in subjects with Down's syndrome versus comparison subjects. No abnormalities in pattern of brain asymmetry were noted in Down's syndrome subjects. Conclusions: The results largely confirm findings of previous studies with respect to overall patterns of brain volumes in Down's syndrome and also provide new evidence for abnormal volumes of specific regional tissue components. The presence of these abnormalities from an early age suggests that fetal or early postnatal developmental differences may underlie the observed pattern of neuroanatomic abnormalities and contribute to the specific cognitive and developmental deficits seen in individuals with Down's syndrome. (Am J Psychiatry 2001; 158:1659-1665)

Brain growth charts derived from pediatric clinical brain MRI scans with limited imaging pathology were highly correlated with charts derived from scans in research control participants.

Understanding patterns of gyrification in neurogenetic disorders helps to uncover the neurodevelopmental etiology underlying behavioral phenotypes. This is particularly true in Williams syndrome (WS), a condition caused by de novo deletion of approximately 1 to 2Mb in the 7q11.23 region. Individuals with WS characteristically possess an unusual dissociation between deficits in visual‐spatial ability and relative preservations in language, music, and social drive. A preliminary postmortem study reported anomalous gyri and sulci in individuals with WS. The present study examined gyrification patterns in 17 participants with WS (10 females, 7 males; mean age 28 years 11 months, SD 8 years 6 months) and 17 age‐ and sex‐matched typically developing control participants (mean age 29 years 1 month, SD 8 years 1 month) using new automated techniques in MRI. Significantly increased cortical gyrification was found globally with abnormalities being more marked in the right parietal (p=0.0227), right occipital (p=0.0249), and left frontal (p=0.0086) regions. These results suggest that one or more genes in the 7q11.23 region are involved during the critical period when cortical folding occurs, and may be related to the hypothesized dorsal/ventral dissociation in this condition.

Williams syndrome is a rare neurogenetic condition caused by a hemizygous microdeletion on chromosome 7. The resultant behavioral phenotype includes hypersociality, anxiety, and impaired visual-spatial ability. Recent work has generated increasing knowledge about Williams syndrome on several levels. Geneticists are coming ever closer to understanding the etiology of this condition; meanwhile, the known pattern of cognitive and behavioral features in Williams syndrome is being revised as more detailed information is acquired. Advances in the neuroanatomic characterization of Williams syndrome is providing a bridge between genetics and cognition. In this paper, the most prominent features of Williams syndrome are reviewed, with a focus on the most recent findings in the neuropsychological, genetic, psychiatric, and neuroanatomical fields.

As the largest interhemispheric commissure in the brain, the corpus callosum is of particular interest in disorders that may preferentially affect white matter development such as Williams syndrome (WS). Individuals with WS possess a remarkable array of neurobehavioral peaks and valleys, including deficits in visuospatial ability, mathematics, and attention, but with relative preservation of language and affect. Our study measured the corpus callosum and its primary subdivisions using high‐resolution MRI in 20 individuals with WS (13 females and seven males; mean age 28.5, SD 8.3 years; range 19 to 44 years) and 20 age‐ and sex‐matched control participants (mean age 28.5, SD 8.2 years; range 19 to 48 years). Total midsagittal corpus callosum area was reduced (F=4.5, p=0.04, df=36) in the WS population. The area of the splenium (F=12.4, p=0.001,df=36) and isthmus (F=9.4, p=0.004, df=36) were disproportionately reduced in WS beyond the absolute reduction of the entire corpus callosum. These reductions are in concordance with other neuroanatomical findings of decreased parietooccipital volumes as well as the observed visuospatial problems associated with WS.

Children with velocardiofacial syndrome (VCFS) often have deficits in mathematical reasoning. Previous research has suggested that structural abnormalities in the parietal lobe region might underlie these deficits. The present study utilized functional magnetic resonance imaging (fMRI) to explore the relationship between brain function and mathematical performance in VCFS.

•Cervical stenosis is a common condition that affects many, including MS patients.•MS lesions are more likely than expected to occur at levels of cervical cord with stenosis.•A mechanism is proposed for this association.

AbstractSeveral large studies have demonstrated that the liability to smoke cigarettes is strongly genetically influenced. However, the role of genetic and environmental risk factors in the use of other common forms of tobacco use has yet to be studied. Data on the regular use of cigarettes, cigars, pipes, dip (moist snuff), and chewing tobacco from 2634 male twins were analyzed with ACE structural equation models. Twin similarity for regular cigarette and dip use was largely genetic in origin. However, twin resemblance for chewing tobacco was just about equally the result of genes and shared environment, and twin similarity for use of pipes and cigars was entirely the result of shared environmental factors. Thus, the genetic influences on the liability for regular tobacco use appear to vary based on tobacco type. The causes for the use of different forms of tobacco are complex and worthy of further study.