Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Impairments in attention/vigilance and response disinhibition are commonly observed in several neuropsychiatric disorders. Validating animal models could help in developing therapeutics for cognitive deficits and improving functional outcomes in such disorders. The 5-choice continuous performance test (5C-CPT) in mice offers the opportunity to assess vigilance and two forms of impulsivity. Since reduced dopamine D4 receptor (DRD4) function is implicated in several disorders, DRD4 is a potential therapeutic target for cognition enhancement. We trained wildtype (WT), heterozygous (HT), and knockout (KO) mice of the murine Drd4 to perform the 5C-CPT under baseline and variable stimulus duration conditions. To dissect motor impulsivity (premature responding) from behavioral disinhibition (false alarms), we administered the 5-HT(2C) antagonist SB242084 during an extended inter-trial-interval session. We also examined the preattentive and exploratory profile of these mice in prepulse inhibition (PPI) and the Behavioral Pattern Monitor (BPM). Reduced Drd4 expression in HT mice, as confirmed by quantitative RT-PCR, resulted in response disinhibition and impaired 5C-CPT performance, while premature responding was unaffected. Conversely, SB242084 increased premature responding without affecting response inhibition or attentional measures. No genotypic differences were observed in PPI or BPM behavior. Thus, reduced Drd4 expression impairs attentional performance, but not other behaviors associated with neuropsychiatric disorders. Moreover, the use of signal and non-signal stimuli in the 5C-CPT enabled the differentiation of response disinhibition from motor impulsivity in a vigilance task.
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PMID:The effect of reduced dopamine D4 receptor expression in the 5-choice continuous performance task: Separating response inhibition from premature responding. 2145

Studies examining the biological and neuropsychological processes underlying attention-deficit/hyperactivity disorder (ADHD) suggest that error indices from the A-X Continuous Performance Test (A-X CPT) might represent useful endophenotypes for ADHD. The current study extended such findings by evaluating the utility of these putative endophenotypes in the context of a molecular genetic study. One hundred and forty-eight clinic-referred ADHD probands and 56 siblings were recruited as part of an ongoing study. Between- and within-family tests of association were conducted to test for relations between polymorphisms in two candidate genes, the dopamine transporter gene (DAT1) and the dopamine D4 receptor gene (DRD4), and indices of inattention and impulsivity derived from the A-X CPT. Association analyses of these polymorphisms with the A-X CPT indices suggested a double dissociation such that an index of inattention was associated with DRD4 but not DAT1, and an index of impulsivity was associated with DAT1 but not DRD4. Further analyses suggested that an A-X CPT index of impulsivity partially mediated previously observed associations between hyperactive-impulsive ADHD symptoms and DAT1. Additionally, an A-X CPT index of inattention moderated the relation between inattentive ADHD symptoms and DRD4 such that children with high levels of the endophenotype showed a stronger association between inattentive symptoms and DRD4. The potential utility of endophenotypes derived from the A-X CPT in molecular genetic studies of ADHD is discussed. (PsycINFO Database Record (c) 2012 APA, all rights reserved).
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PMID:Double dissociation between lab measures of inattention and impulsivity and the dopamine transporter gene (DAT1) and dopamine D4 receptor gene (DRD4). 2256 79

The objective of this study was to characterize an attention deficit hyperactivity disorder (ADHD) endophenotype in non-affected parents of adolescents with a history of ADHD, based on the relationship between performance on a sustained attention test (continuous performance task, or CPT) and polymorphisms of the DRD4 gene. In a sample of 25 non-affected parents of adolescents with ADHD history obtained from a longitudinal study of a nonclinical population, and 25 non-affected parents of adolescents with no ADHD history, four groups were evaluated with respect to the presence or absence of the long allele polymorphism of the DRD4 gene (i.e., over seven repeats). Comparisons of CPT performance among the four study groups included the number of commission errors, the number of omission errors, mean reaction time on correct responses (MRT), and reaction time (RT) variability (mean standard deviation of RT in each block [SDRT, as variability], and the sigma and tau components of the ex-Gaussian approach). The group of non-affected parents of adolescents with ADHD history and at least one long allele of the DRD4 gene showed greater RT variability (measured by SDRT), which is best explained by the greater frequency of abnormally slow responses (measured by tau). An association between the presence of the long allele of the DRD4 gene polymorphism and ADHD-like failure in CPT performance was evident in the non-affected parents of adolescents with ADHD in childhood. These findings suggest that certain traits of CPT performance could be considered an ADHD endophenotype.
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PMID:"Like parent, like child": Attention deficit hyperactivity disorder-like characteristics in parents of ADHD cases. 3033