| Proline affects brain function in 22q11DS children with the low activity COMT 158 allele. | |
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MedLine Citation:
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PMID: 18769474 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The association between the 22q11.2 deletion syndrome (22q11DS) and psychiatric disorders, particularly psychosis, suggests a causal relationship between 22q11DS genes and abnormal brain function. The genes catechol-O-methyl-transferase (COMT) and proline dehydrogenase both reside within the commonly deleted region of 22q11.2. COMT activity and proline levels may therefore be altered in 22q11DS individuals. Associations of both COMT(158) genotype and elevated serum proline levels with abnormal brain function have been reported. Fifty-six 22q11DS children and 75 healthy controls were assessed on physiological measures of brain function, including prepulse inhibition (PPI) of startle, P50 auditory sensory gating and smooth pursuit eye movements (SPEM). COMT(158) genotype and plasma proline levels were determined in the 22q11DS children. We hypothesized an interaction between the COMT(158) genotype and proline, predicting the strongest negative effect of high proline on brain function to occur in 22q11DS children who are carriers of the COMT(met) allele. Of the three physiological measures, only SPEM and PPI were abnormal in the patient sample. With regard to the SPEM performance, there was a significant interaction between the COMT(158) genotype and proline level with significantly decreased SPEM performance in children with high plasma proline levels and the low activity COMT(met) allele. A similar interaction effect was not observed with regard to PPI. These findings are consistent with a model in which elevated proline negatively affects brain function by an increase in dopamine in the prefrontal cortex. 22q11DS patients with low dopamine catabolic capacity are therefore especially vulnerable to this functional disruption. |
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Authors:
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Jacob A S Vorstman; Bruce I Turetsky; Monique E J Sijmens-Morcus; Monique G de Sain; Bert Dorland; Mirjam Sprong; Eric F Rappaport; Frits A Beemer; Beverly S Emanuel; René S Kahn; Herman van Engeland; Chantal Kemner |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-09-03 |
Journal Detail:
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Title: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Volume: 34 ISSN: 1740-634X ISO Abbreviation: Neuropsychopharmacology Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-01-12 Completed Date: 2009-03-30 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 8904907 Medline TA: Neuropsychopharmacology Country: United States |
Other Details:
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Languages: eng Pagination: 739-46 Citation Subset: IM |
Affiliation:
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Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands. J.A.S.vorstman@umcutrecht.nl |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Alleles Catechol O-Methyltransferase / genetics*, metabolism, physiology Child DiGeorge Syndrome / genetics*, physiopathology* Dopamine / metabolism Electroencephalography Female Genotype Humans Male Ocular Motility Disorders / genetics, physiopathology Prefrontal Cortex / metabolism Proline / blood* Proline Oxidase / genetics, physiology Sensory Gating / genetics, physiology Startle Reaction / genetics, physiology |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA039926-20/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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147-85-3/Proline; EC 1.5.3.-/Proline Oxidase; EC 2.1.1.6/Catechol O-Methyltransferase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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