Genetic and Neurochemical Modulation of Prefrontal Cognitive Functions in Children

Diamond, Adele; Briand, Lisa A.; Fossella, John; Gehlbach, Lorrie

doi:10.1176/appi.ajp.161.1.125

Cited by 338 publications

(300 citation statements)

References 61 publications

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“…This is the opposite of what is typically reported in the non-VCFS population; in both children 44 and adults 45 , homozygosity for the Met allele is associated with optimal cognitive function. It has been hypothesized that the Met allele is the risk allele in VCFS by virtue of the inverted-U shape relationship between cortical dopamine signaling and cognitive functioning 96 .…”

Section: Comtcontrasting

confidence: 82%

Cognitive and Psychiatric Predictors to Psychosis in Velocardiofacial Syndrome: A 3-Year Follow-Up Study

Antshel

Shprintzen

Fremont

et al. 2010

Journal of the American Academy of Child & Adolescent Psych

133

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Objective-To predict prodromal psychosis in adolescents with velocardiofacial syndrome (VCFS).Method-70 youth with VCFS, 27 siblings of youth with VCFS and 25 community controls were followed from childhood (Mean age = 11.8 years) into mid-adolescence (mean age 15.0 years). Psychological tests measuring intelligence, academic achievement, learning/memory, attention and executive functioning as well as measures of parent and clinician ratings of child psychiatric functioning were completed at both time points.Results-Major depressive disorder, oppositional defiant disorder and generalized anxiety disorder diagnoses increased in the VCFS sample. With very low false positives, the best predictor of adolescent prodromal psychotic symptoms was parent ratings of childhood odd/eccentric symptoms and child performance on a measure of executive functioning, the Wisconsin Card Sorting Test.Conclusions-Similar to the non-VCFS prodromal psychosis literature, a combination of cognitive and psychiatric variables appears to predict psychosis in adolescence. A child with VCFS who screens positive is noteworthy and demands clinical attention. KeywordsVelocardiofacial syndrome (VCFS); 22q11 deletion syndrome; cognition; psychosis; longitudinal Velo-cardio-facial syndrome (VCFS) is caused by an interstitial deletion from chromosome 22 at the 22q11 band. The most common microdeletion syndrome yet identified in humans, VCFS has a population prevalence of approximately 1:2000 to 1:6000 live births 1, 2 . In most cases, VCFS is caused by a hemizygous deletion of 3 million base pairs of DNA encompassing 40 genes but approximately 8% have smaller nested deletions of 1.5 million base pairs spanning 34 genes 3 . Structural anomalies affect nearly every part and system of the body and may Correspondence to: Kevin Antshel, Ph.D. SUNY -Upstate Medical University Department of Psychiatry and Behavioral Sciences, 750 East Adams Street, Syracuse, NY 13210; AntshelK@upstate.edu. Disclosure: Dr. Faraone, in the past year, has received consulting fees and has been on Advisory Boards for Eli Lilly, Ortho-McNeil, and Shire Development, and has received research support from Eli Lilly, Pfizer, Shire and the National Institutes of Health. In previous years, Dr. Faraone has received consulting fees or has been on advisory boards, or has been a speaker for the following sources: Shire, McNeil, Janssen, Novartis, Pfizer, and Eli Lilly. In previous years he has received research support from Eli Lilly, Shire, Pfizer and the National Institutes of Health. Drs. Antshel, Shprintzen, Fremont, and Kates, and Ms. Higgins report no biomedical financial interests or potential conflicts of interest.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the prod...

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Section: Comtcontrasting

confidence: 82%

Cognitive and Psychiatric Predictors to Psychosis in Velocardiofacial Syndrome: A 3-Year Follow-Up Study

Antshel

Shprintzen

Fremont

et al. 2010

Journal of the American Academy of Child & Adolescent Psych

133

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“…29 There is evidence of the influence of the COMT Val 158 Met polymorphism in the execution of cognitive tasks dependent on the prefrontal cortex, with the Val allele being associated with decreased performance in specific neuropsychological tests and in the physiological response of this cortical region measured by functional magnetic resonance imaging. 9,26,[30][31][32] This association, together with the fact that the Met allele at position 158 seems to constitute an exclusively human mutation (it has not been found in the higher primates), 33 has given consistency to the theory that such mutation may have an important evolutive implication in the prefrontal human cortex. From the impact of the COMT genotype on the prefrontal information process, and given the association of schizophrenia with alterations in the prefrontal Table 3 Description of the specific neuroleptics used as the maintenance treatment and comparison between patient groups in relationship to the Val 158 Met genotype Other include amisulpride, chlorpromazine, fluphenazine, levomepromazine, perphenazine, pimozide, thioridazine, trifluoperazine, tiprasidone, zuclopenthixol.…”

Section: Discussionmentioning

confidence: 99%

Clinical involvement of catechol-O-methyltransferase polymorphisms in schizophrenia spectrum disorders: influence on the severity of psychotic symptoms and on the response to neuroleptic treatment

et al. 2007

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Genetic variation in the catechol-O-methyltransferase (COMT) gene may influence the susceptibility to schizophrenia and the response to neuroleptic treatment. The authors tested for an association between a COMT haplotype and schizophrenia-spectrum disorders and for an eventual influence of a specific COMT genotype in the clinical outcome and in the response to treatment. The genotypes for single nucleotide polymorphisms rs737865, rs4633, rs6267, rs4680 (Val 158 Met) and rs165599 were determined in 207 patients with schizophrenia-spectrum disorders and 204 paired controls. Statistical tests for linkage disequilibrium and for case-control differences in haplotype frequencies were performed using log-linear modelling embedded within the expectation-maximization algorithm. P-values based on permutations were calculated using the software UNPHASED, and odds ratios were estimated using the SHEsis platform. The response to neuroleptic treatment was assessed by the Global Assessment of Functioning scale and the severity of psychotic symptoms by the positive and negative syndrome scale (PANSS) scale. The overall disease status was significantly associated with the T-G (Val) diplotype for rs4633-rs4680 (P ¼ 0.0049). A significant association was observed between schizophrenia, but not other related disorders, and genotypes GG (Val/Val) for rs4680 and TT for rs4633. Val/Val patients with schizophrenia showed a higher severity of the psychotic symptoms and a worse response to the neuroleptic treatment. COMT genetic variation seems to be involved in the psychotic symptomatology of the schizophreniaspectrum disorders and specifically in the narrow schizophrenia phenotype. Our results show an influence of the Val 158 Met polymorphism on the severity of psychotic symptoms and on the response to treatment.

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“…Polymorphisms in dopamine receptors (DRD4), transporters (DAT1), and enzymes (COMT) are able to account for variability in tasks that tap into various executive control (Diamond, Briand, Fossella, & Gehlbach, 2004;Fossella et al, 2002). Thus, there is good evidence that these three attention constructs have separate instantiations in the brain.…”

mentioning

confidence: 99%

Mixing measures: testing an assumption of the attention network test

McConnell

Shore

2011

Atten Percept Psychophys

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The human attention system has been subdivided into three networks that appear to be functionally and anatomically independent: alerting, orienting, and executive control. The Attention Network Test (ANT) is a quick and easy tool that measures the efficiency of these three networks by averaging reaction time and accuracy scores across several different cue and flanker conditions. Using ANOVAs and correlation procedures, we found that (a) intranetwork correlations were surprisingly low, and (b) Cue X Flanker interactions were found within alerting, orienting, and executive control measures. Taken together, these findings highlight the interaction between the three networks and the potential difficulty in accurately measuring them with this task.

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Genetic and Neurochemical Modulation of Prefrontal Cognitive Functions in Children

Cited by 338 publications

References 61 publications

Cognitive and Psychiatric Predictors to Psychosis in Velocardiofacial Syndrome: A 3-Year Follow-Up Study

Cognitive and Psychiatric Predictors to Psychosis in Velocardiofacial Syndrome: A 3-Year Follow-Up Study

Clinical involvement of catechol-O-methyltransferase polymorphisms in schizophrenia spectrum disorders: influence on the severity of psychotic symptoms and on the response to neuroleptic treatment

Mixing measures: testing an assumption of the attention network test

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