Frontal and Caudate Alterations in Velocardiofacial Syndrome (Deletion at Chromosome 22q11.2)

Kates, Wendy R.; Burnette, Courtney P.; Bessette, Brandy A.; Folley, Bradley S.; Strunge, Leslie; Jabs, Ethylin Wang; Pearlson, Godfrey D.

doi:10.1177/088307380401900506

Cited by 85 publications

(79 citation statements)

References 42 publications

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“…The 22q11.2 deletion mouse model displayed several differences that mirrored what has been found in human 22q11.2 deletion syndrome [139][140][141]. Specifically, the larger striatum, smaller cerebellum, and smaller amygdala in the mouse model are all consistently found in human patients.…”

Section: Recent Investigations (2010-14)mentioning

confidence: 66%

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

2015

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In order to understand the consequences of the mutation on behavioral and biological phenotypes relevant to autism, mutations in many of the risk genes for autism spectrum disorder have been experimentally generated in mice. Here, we summarize behavioral outcomes and neuroanatomical abnormalities, with a focus on highresolution magnetic resonance imaging of postmortem mouse brains. Results are described from multiple mouse models of autism spectrum disorder and comorbid syndromes, including the 15q11-13, 16p11.2, 22q11.2, Cntnap2, Engrailed2, Fragile X, Integrinβ3, MET, Neurexin1a, Neuroligin3, Reelin, Rett, Shank3, Slc6a4, tuberous sclerosis, and Williams syndrome models, and inbred strains with strong autism-relevant behavioral phenotypes, including BTBR and BALB. Concomitant behavioral and neuroanatomical abnormalities can strengthen the interpretation of results from a mouse model, and may elevate the usefulness of the model system for therapeutic discovery.

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Section: Recent Investigations (2010-14)mentioning

confidence: 66%

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

2015

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“…The observation of thicker cortex partially modifies the classical view that patients with 22q11DS consistently show differences in the reduced direction. Indeed, volumetric studies have always reported reduced cortical volume in the syndrome (Eliez et al, 2000;Kates et al, 2004Kates et al, , 2001Simon et al, 2005;van Amelsvoort et al, 2001). If cortical volume is undeniably the product of its surface and thickness, surface changes are more susceptible to result in volumetric changes than thickness alterations (Im et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Deviant trajectories of cortical maturation in 22q11.2 deletion syndrome (22q11DS): A cross-sectional and longitudinal study

Schaer

Debbané

Cuadra

et al. 2009

Schizophrenia Research

108

129

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22q11.2 deletion syndrome (22q11DS) is associated with an increased susceptibility to develop schizophrenia. Despite a large body of literature documenting abnormal brain structure in 22q11DS, cerebral changes associated with brain maturation in 22q11DS remained largely unexplored. To map cortical maturation from childhood to adulthood in 22q11.2 deletion syndrome, we used cerebral MRI from 59 patients with 22q11DS, aged 6 to 40, and 80 typically developing controls; three year follow-up assessments were also available for 32 patients and 31 matched controls. Cross-sectional cortical thickness trajectories during childhood and adolescence were approximated in age bins. Repeated-measures were also conducted with the longitudinal data. Within the group of patients with 22q11DS, exploratory measures of cortical thickness differences related to COMT polymorphism, IQ, and schizophrenia were also conducted. We observed deviant trajectories of cortical thickness changes with age in patients with 22q11DS. In affected preadolescents, larger prefrontal thickness was observed compared to age-matched controls. Afterward, we observed greater cortical loss in 22q11DS with a convergence of cortical thickness values by the end of adolescence. No compelling evidence for an effect of COMT polymorphism on cortical maturation was observed. Within 22q11DS, significant differences in cortical thickness were related to cognitive level in children and adolescents, and to schizophrenia in adults. Deviant trajectories of cortical thickness from childhood to adulthood provide strong in vivo cues for a defect in the programmed synaptic elimination, which in turn may explain the susceptibility of patients with 22q11DS to develop psychosis.

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“…206 Imaging studies of caudate in adults with BD have been ambiguous, with some studies also showing an increased volume, 207 but other suggesting either a difference in the opposite direction-decreased caudate in older bipolar patients, particularly those with illness onset after 45 years of age 208 -or no differences in patients with minimal exposure to antipsychotics, 209 hospitalized manic patients, 210 bipolar patients, 211 or first-episode manic patients. 212 The heritability of caudate volume is unknown, but enlarged caudate volumes are associated with both genetic 213,214 and environmental factors, 215 including antipsychotic use. No association between antipsychotics or mood-stabilizing medications and caudate volume was reported in the above reviewed studies of BD, however.…”

Section: Basal Gangliamentioning

confidence: 99%

The phenotypes of bipolar disorder: relevance for genetic investigations

2005

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The search for susceptibility genes for bipolar disorder (BD) depends on appropriate definitions of the phenotype. In this paper, we review data on diagnosis and clinical features of BD that could be used in genetic studies to better characterize patients or to define homogeneous subgroups. Clinical symptoms, long-term course, comorbid conditions, and response to prophylactic treatment may define groups associated with more or less specific loci. One such group is characterized by symptoms of psychosis and linkage to 13q and 22q. A second group includes mainly bipolar II patients with comorbid panic disorder, rapid mood switching, and evidence of chromosome 18 linkage. A third group comprises typical BD with an episodic course and favourable response to lithium prophylaxis. Reproducibility of cognitive deficits across studies raises the possibility of using cognitive profiles as endophenotypes of BD, with deficits in verbal explicit memory and executive function commonly reported. Brain imaging provides a more ambiguous data set consistent with heterogeneity of the illness. Keywords: bipolar disorder; genetics; endophenotype; neurocognitive function; brain imaging Bipolar disorder (BD) has a genetic basis with heritability of at least 80%. 1 A number of studies have attempted to map the susceptibility loci giving evidence of linkage in multiple genomic regions. In particular, findings in 4p, 4q, 8q, 10p, 12q24, 13q, 18p, 18q, 21q, and 22q have been supported by more than one study. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] However, these studies have not identified any specific genes, and a recent metaanalysis of available genome scans showed no regions with a conclusive evidence of linkage. 20 The relatively slow progress of gene-mapping efforts is often explained by the 'complex' nature of the illness and of the genotype-phenotype relation. The complexity most likely includes heterogeneity, interactions of multiple loci, incomplete penetrance, as well as phenotypes resulting from environmental effects-either alone or in interaction with the genetic predisposition. The goal of psychiatric genetic research is identification of (heritable) variations in DNA sequence or function that influence behaviour or give rise to mental illness. By definition, in complex (multifactorial) traits, this link is not unique and specific. That is, a particular change in gene sequence does not necessarily lead to a specific behaviour, and similar behaviours (symptoms) may be due to distinct (sets of) genes. Moreover, we must consider the possibility that the path between the genotype and behaviour is not unidirectional. Emerging examples point not only to general effects of environment, for instance stress, on behaviour, but also to specific behaviours influencing gene function that can be transmitted onto the next generation. 21 No single method is considered clearly superior in identifying susceptibility genes for complex traits such as BD. Most researchers agree that a combination of strategies is most lik...

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Frontal and Caudate Alterations in Velocardiofacial Syndrome (Deletion at Chromosome 22q11.2)

Cited by 85 publications

References 42 publications

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

Deviant trajectories of cortical maturation in 22q11.2 deletion syndrome (22q11DS): A cross-sectional and longitudinal study

The phenotypes of bipolar disorder: relevance for genetic investigations

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