22q11 deletion syndrome in childhood onset schizophrenia: an update

Sporn, Alexandra; Addington, Anjené; Reiss, Allan L.; Dean, Michael; Gogtay, Nitin; Potočnik, Uroš; Greenstein, Deanna; Hallmayer, Joachim; Gochman, Peter; Lenane, Marge; Baker, Natalie; Tossell, Julia W.; Rapoport, Judith L.

doi:10.1038/sj.mp.4001477

Cited by 80 publications

(63 citation statements)

References 9 publications

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“…11 COS patients show a striking loss of gray matter volume, which plateaus in adolescence. 12,13 Although rare, the higher rates of familial illness or biological markers of illness, extreme severity and 10% rate of chromosomal abnormalities seen in this sample 14 suggest that genetic influences may be more salient. 6 NRG1 participates in glutamatergic signaling by regulating the N-methyl-D-aspartate (NMDA) receptor through the interaction of the NRG1 protein and its receptors.…”

Section: Introductionmentioning

confidence: 84%

Neuregulin 1 (8p12) and childhood-onset schizophrenia: susceptibility haplotypes for diagnosis and brain developmental trajectories

Addington¹,

Gornick²,

Shaw³

et al. 2006

Mol Psychiatry

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110

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Childhood-onset schizophrenia (COS), defined as onset of psychosis by the age of 12, is a rare and malignant form of the illness, which may have more salient genetic influence. Since the initial report of association between neuregulin 1 (NRG1) and schizophrenia in 2002, numerous independent replications have been reported. In the current study, we genotyped 56 markers (54 single-nucleotide polymorphisms (SNPs) and two microsatellites) spanning the NRG1 locus on 78 COS patients and their parents. We used family-based association analysis for both diagnostic (extended transmission disequilibrium test) and quantitative phenotypes (quantitative transmission disequilibrium test) and mixed-model regression. Most subjects had prospective anatomic brain magnetic resonance imaging (MRI) scans at 2-year intervals. Further, we genotyped a sample of 165 healthy controls in the MRI study to examine genetic risk effects on normal brain development. Individual markers showed overtransmission of alleles to affecteds (P = 0.009-0.05). Further, several novel four-marker haplotypes demonstrated significant transmission distortion. There was no evidence of epistasis with SNPs in erbB4. The risk allele (0) at 420M9-1395 was associated with poorer premorbid social functioning. Further, possession of the risk allele was associated with different trajectories of change in lobar volumes. In the COS group, risk allele carriers had greater total gray and white matter volume in childhood and a steeper rate of subsequent decline in volume into adolescence. By contrast, in healthy children, possession of the risk allele was associated with different trajectories in gray matter only and was confined to frontotemporal regions, reflecting epistatic or other illness-specific effects mediating NRG1 influence on brain development in COS. This replication further documents the role of NRG1 in the abnormal brain development in schizophrenia. This is the first demonstration of a disease-specific pattern of gene action in schizophrenia.

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Section: Introductionmentioning

confidence: 84%

Neuregulin 1 (8p12) and childhood-onset schizophrenia: susceptibility haplotypes for diagnosis and brain developmental trajectories

Addington¹,

Gornick²,

Shaw³

et al. 2006

Mol Psychiatry

Self Cite

110

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“…In summary, it is unlikely that TBX1 plays a major role in the genetic etiology of nonsyndromic schizophrenia and other psychiatric disorders observed in patients with 22q11DS. However, it is important to point out that schizophrenia associated with 22q11DS may represent a genetic subclass that is very similar but genetically distinct from the nonsyndromic form (13,74,75). In this case TBX1 may still contribute to the risk of developing psychiatric disease in patients with 22q11DS.…”

Section: Discussionmentioning

confidence: 99%

Analysis of TBX1 Variation in Patients with Psychotic and Affective Disorders

Funke

Lencz

Finn

et al. 2007

Mol Med

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“…Several (but not all) reports [7,10] have indicated that with respect to schizophrenia's major clinical features, 22qDS-schizophrenia is largely indistinguishable from other forms of schizophrenia [11]. Ascertainment may play a role in differences observed.…”

Section: Clinical Signs and Symptoms Of Schizophreniamentioning

confidence: 96%

“…Ascertainment may play a role in differences observed. For example, median age at onset varies from 12 years for a sample restricted to childhood-onset schizophrenia [10] to 26 years when case identification involved parents who had transmitted the deletion to affected children [7]. The latter ascertainment strategy may also explain a finding of less severe negative symptoms [7] that was not found in a larger sample with no transmitting parents [12].…”

Section: Clinical Signs and Symptoms Of Schizophreniamentioning

confidence: 99%

Schizophrenia and 22q11.2 deletion syndrome

Bassett

Chow²

2008

Curr Psychiatry Rep

212

166

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Abstract22q11.2 deletion syndrome (22qDS) is a genetic syndrome associated with a chromosome 22q11.2 deletion and variable phenotypic expression that commonly includes schizophrenia. Approximately 1% of patients with schizophrenia have 22qDS. The schizophrenia in 22qDS appears broadly similar to that found in the general population with respect to core signs and symptoms, treatment response, neurocognitive profile, and MRI brain anomalies. However, individuals with a 22qDS form of schizophrenia typically have distinguishable physical features, have a lower IQ, and may differ in auxiliary clinical features. IQ, length of 22q11.2 deletions, and COMT functional allele do not appear to be major risk factors for schizophrenia in 22qDS.Ascertainment biases and small sample sizes are limitations of most studies. Larger studies over the lifespan and continuing education about this underrecognized condition are needed. 22qDS-schizophrenia is an important genetic subtype and a valuable model of neurodevelopmental mechanisms involved in the pathogenesis of schizophrenia.

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22q11 deletion syndrome in childhood onset schizophrenia: an update

Cited by 80 publications

References 9 publications

Neuregulin 1 (8p12) and childhood-onset schizophrenia: susceptibility haplotypes for diagnosis and brain developmental trajectories

Neuregulin 1 (8p12) and childhood-onset schizophrenia: susceptibility haplotypes for diagnosis and brain developmental trajectories

Analysis of TBX1 Variation in Patients with Psychotic and Affective Disorders

Schizophrenia and 22q11.2 deletion syndrome

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