Looking for Childhood-Onset Schizophrenia: The First 71 Cases Screened

McKenna, K.F.; Gordon, Charles T.; Lenane, Marge; Kaysen, Debra; Fahey, Kimberly; Rapoport, Judith L.

doi:10.1097/00004583-199406000-00003

Cited by 207 publications

(115 citation statements)

References 26 publications

Supporting

Mentioning

108

Contrasting

Unclassified

Order By: Relevance

“…The schizophrenic patients who participated were required to have a premorbid full-scale intelligence quotient (IQ) of 70 or above and an onset of psychotic symptoms by the age of 12. The diagnosis of COS was confirmed by two psychiatrists (k = 0.8) 20 through an extensive evaluation that included clinical and structured interviews of the children and parents using portions of the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS-E and K-SADS-PL) 21,22 and in-hospital observation during a 1-to 3-week medication-free period. Information on these subjects included cognitive and behavioral ratings of early development, history of medication response, neuropsychological test performance, smooth pursuit eye movements and MRI scans.…”

Section: Methodsmentioning

confidence: 99%

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

Addington¹,

Gornick²,

Shaw³

et al. 2006

Mol Psychiatry

110

View full text Add to dashboard Cite

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.

show abstract

Section: Methodsmentioning

confidence: 99%

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

Addington¹,

Gornick²,

Shaw³

et al. 2006

Mol Psychiatry

110

View full text Add to dashboard Cite

show abstract

“…The schizophrenic patients who participated were required to have a premorbid full-scale IQ of 70 or above and an onset of psychosis by the age of 12 (average age of onset of psychotic symptoms was 10 years.) The diagnosis of COS was confirmed by two psychiatrists (k ¼ 0.8) 27 through an extensive evaluation that included clinical and structured interviews of the children and parents using portions of the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS-E and K-SADS-PL) 28,29 and in-hospital observation during a 1-3-week medication-free period. Information on these subjects included cognitive and behavioral ratings of early development, history of medication response, neuropsychological test performance, smooth pursuit eye movements, and MRI scans.…”

Section: Methodsmentioning

confidence: 99%

GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss

Addington¹,

Gornick²,

et al. 2004

View full text Add to dashboard Cite

Postmortem brain studies have shown deficits in the cortical c-aminobutyric acid (GABA) system in schizophrenic individuals. Expression studies have shown a decrease in the major GABA-synthesizing enzyme (glutamic acid decarboxylase (GAD 67 ) mRNA levels in neurons in dorsolateral prefrontal cortex in schizophrenics relative to controls. In the present study, SNPs in and around the GAD1 gene, which encodes the protein GAD 67 , were tested on a rare, severely ill group of children and adolescents with childhood-onset schizophrenia (COS) (n ¼ 72), in a family-based association analysis. Compared to adult-onset samples, the COS sample has evidence for more salient familial, and perhaps genetic, risk factors for schizophrenia, as well as evidence for frontal cortical hypofunction, and greater decline in cortical gray matter volume on anatomic brain MRI scans during adolescence. We performed family-based TDT and haplotype association analyses of the clinical phenotype, as well as association analyses with endophenotypes using the QTDT program. Three adjacent SNPs in the 5 0 upstream region of GAD1 showed a positive pairwise association with illness in these families (P ¼ 0.022-0.057). Significant transmission distortion of 4-SNP haplotypes was also observed (P ¼ 0.003-0.008). Quantitative trait TDT analyses showed an intriguing association between several SNPs and increased rate of frontal gray matter loss. These observations, when taken together with the positive results reported recently in two independent adult-onset schizophrenia pedigree samples, suggest that the gene encoding GAD 67 may be a common risk factor for schizophrenia. Molecular Psychiatry (2005) 10, 581-588.

show abstract

“…Differential diagnosis of psychotic disorders in the pediatric population is frequently difficult due to the lack of longitudinal information about disease course. Indeed, some studies have found that as many as 55% of individuals initially presenting with psychotic symptoms are given different diagnoses upon follow-up evaluation 2-6 years later (Werry et al, 1991;McKenna et al, 1994). Many investigators and potential participants also have ethical concerns about withholding treatment by utilizing a placebo or limiting the use of concurrent antidepressants and mood stabilizers, which have become the community standard of care, given the significant risk of suicide and violence in this population.…”

Section: Introductionmentioning

confidence: 99%

A Pilot Study of Risperidone, Olanzapine, and Haloperidol in Psychotic Youth: A Double-Blind, Randomized, 8-Week Trial

Sikich

Hamer

Bashford

et al. 2003

Neuropsychopharmacol

278

148

View full text Add to dashboard Cite

This pilot study was undertaken to estimate the acute antipsychotic effect size and side effect propensity of risperidone and olanzapine in the pediatric population, in comparison to haloperidol, a conventional antipsychotic with established efficacy. Risperidone and olanzapine are widely used as first-line treatments to ameliorate psychotic symptoms in youth, but their abilities to specifically treat children and adolescents presenting due to psychotic symptoms have not been rigorously studied. Subjects, selected because of prominent positive psychotic symptoms, were randomly assigned to double-blind, parallel treatment with risperidone, olanzapine, or haloperidol for 8 weeks. The primary outcome was reduction in the Brief Psychiatric Rating Scale for Children total score from baseline to termination. An exploratory, descriptive analysis was done to compare the three treatments. A total of 50 patients, 8-19 years, participated. All treatments reduced symptoms significantly with p-values (corrected for multiple comparisons) of 0.0018 for each of the atypical agents and 0.012 for haloperidol. In all, 88% of subjects treated with olanzapine, 74% treated with risperidone, and 53% treated with haloperidol met response criteria. The primary side effects observed in all patients were mild to moderate sedation, extrapyramidal symptoms, and weight gain. Risperidone and olanzapine acutely reduced psychotic symptoms in this pediatric sample. Exploratory comparisons indicate the magnitude of the antipsychotic response with these atypical agents is comparable to that observed with haloperidol. However, youth treated with risperidone and olanzapine experienced weight gain and extrapyramidal effects that appear more prevalent and severe than reported in adults.

show abstract

Looking for Childhood-Onset Schizophrenia: The First 71 Cases Screened

Cited by 207 publications

References 26 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

GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss

A Pilot Study of Risperidone, Olanzapine, and Haloperidol in Psychotic Youth: A Double-Blind, Randomized, 8-Week Trial

Contact Info

Product

Resources

About