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Abel Ickowicz

Publications and source records attributed to Abel Ickowicz.

16 recordsLinked to original sources
PubMed2007

The serotonin receptor HTR1B: gene polymorphisms in attention deficit hyperactivity disorder.

Serotonin plays an essential role in cognition, locomotor activity, and the regulation of sleep, pain, mood, and aggression. Polymorphisms of the HTR1B gene have been implicated in a variety of psychiatric disorders including attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). The objectives of this study were to: (i) expand our original investigation of the relationship between the HTR1B receptor gene and attention deficit/hyperactivity and; (ii) to investigate a possible association of obsessive behaviors/perfectionism and the HTR1B gene in a sample of 203 families with an ADHD proband. Six single nucleotide polymorphisms (SNPs) of the HTR1B receptor gene were genotyped using standard methods. Evidence for an association between the HTR1B gene and ADHD as a qualitative diagnosis, or the inattentive and hyperactive-impulsive quantitative traits was not supported by either TDT single marker analysis or haplotype analysis. In addition we did not find evidence to suggest an association between HTR1B and perfectionism in this sample of ADHD families.

Adolescent↗
PubMed2006

Investigation of the G protein subunit Galphaolf gene (GNAL) in attention deficit/hyperactivity disorder.

The dopamine system plays an important role in the regulation of attention and motor behavior, subsequently, several dopamine-related genes have been associated with Attention Deficit/Hyperactivity Disorder (ADHD). Among them are the dopamine receptors D1 and D5 that mediate adenylyl cyclase activation through coupling with G(s)-like proteins. We thus hypothesized that the G(s)-like subunit Galpha(olf), expressed in D1-rich areas of the brain, contributes to the genetic susceptibility of ADHD. To evaluate the involvement of the Galpha(olf) gene, GNAL, in ADHD, we examined the inheritance pattern of 12 GNAL polymorphisms in 258 nuclear families ascertained through a proband with ADHD (311 affected children) using the transmission/disequilibrium test (TDT). Categorical analysis of individual marker alleles demonstrated biased transmission of one polymorphism in GNAL intron 3 (rs2161961; P=0.011). We also observed significant relationships between rs2161961 and dimensional symptoms of inattention and hyperactivity/impulsivity (P=0.003 and P=0.008). In addition, because of recent evidence of imprinting at the GNAL locus, secondary analyses were split into maternal and paternal transmissions to assess a contribution of parental effects. We found evidence of strong maternal effect, with preferential transmission of maternal alleles for rs2161961A (P=0.005) and rs8098539A (P=0.035). These preliminary findings suggest a possible contribution of GNAL in the susceptibility to ADHD, with possible involvement of parent-of-origin effects.

Adolescent↗
PubMed2006

Gene for the serotonin transporter and ADHD: no association with two functional polymorphisms.

Evidence from both human and animal studies implicates the serotonergic system in the development of attention-deficit hyperactivity disorder (ADHD) including positive association studies for several key serotonergic genes. The serotonin transporter (HTT) regulates the availability of serotonin by reuptake of the neurotransmitter from the synaptic cleft. Several studies have reported an association of this gene to ADHD, specifically the long variant of a common insertion/deletion polymorphism located in the promoter of this gene that results in increased transcription and higher HTT expression. An additional study found no evidence for an association with this polymorphism. Recently, an A/G single nucleotide polymorphism (SNP) was found within the promoter polymorphism with functional studies indicating that the long variant containing the G allele at this site behaves like the short variant. This previously unidentified functional change may have confounded earlier association studies. We investigated the relationship of several variants to ADHD: the promoter polymorphisms, SNP in the 3' untranslated region (3'UTR) with a reported association to ADHD and a rare, non-synonymous coding SNP. These polymorphisms were genotyped in 209 ADHD families identified through an affected proband. We did not find evidence for an association of these polymorphisms, or haplotypes of these polymorphisms, to ADHD in this sample.

Adolescent↗
PubMed2006

Stimulant treatment over 5 years: effects on growth.

OBJECTIVE: Long-term effects of psychostimulants on growth in height and in weight are investigated in children with attention-deficit/hyperactivity disorder. METHOD: Participants were 79 children, 6 to 12 years of age, with attention-deficit/hyperactivity disorder, who were followed annually for up to 5 years, between the years 1993 and 1994 and 1998 and 1999. Annual height and weight measurements were standardized by age and gender using the 2000 Centers for Disease Control and Prevention Growth Charts for the United States and reported as z scores. For children taking stimulants throughout the previous school year, dose potency was standardized to methylphenidate in milligrams per kilogram per day. We used hierarchical linear modeling to investigate the influence of dose and duration of stimulant treatment on the rate of growth in height and weight. RESULTS: Controlling for time since initiation of treatment, daily dose of stimulant medication was negatively associated with z scores for height (beta = -.11, SE = 0.03, p <.01) and for weight (beta = -.29, SE = 0.04, p <.01). Estimates based on the statistical model suggest that children receiving > or = 1.5 mg/kg/day methylphenidate will show diminished weight gain after 1 year; those receiving > or = 2.5 mg/kg/day methylphenidate will show diminished gains in height after 4 years. CONCLUSION: Long-term use of high doses of stimulants during a period of 1 to 5 years is likely to have measurable effects on the rate of growth in school-age children with attention-deficit/hyperactivity disorder.

Attention Deficit Disorder with Hyperactivity↗
PubMed2006

The parent interview for child symptoms: a situation-specific clinical research interview for attention-deficit hyperactivity and related disorders.

OBJECTIVE: To describe the properties of a semistructured research interview of parents designed to evaluate attention-deficit hyperactivity disorder (ADHD) and related psychopathology. METHOD: We examined interrater reliability in 48 videotaped interviews randomly selected from a large clinic sample. We examined convergence of the Parent Interview for Child Symptoms (PICS) and Conners' Parent Rating Scale (CPRS) scores in 594 clinic-referred cases and 26 control subjects, comparing the groups generated by cross-tabulation on measures of intelligence, academic achievement, and inhibitory control. RESULTS: Intraclass correlation coefficients for symptom scores of ADHD, oppositional defiant disorder (ODD), and conduct disorder (CD) were excellent. We found good reliability for diagnoses of ADHD (e = 0.73) and CD (kappa = 0.73) and excellent reliability for the diagnosis of ODD (kappa = 0.80). Two-thirds of cases were classified similarly on the PICS and the CPRS. Greater impairment in inhibitory control was observed in cases identified as ADHD by the PICS, compared with those identified by the CPRS-ADHD index. CONCLUSIONS: The PICS displays good reliability and validity, indicating that a balance between clinical applicability and reliability can be achieved in the development of clinical research instruments.

Adolescent↗
PubMed2005

Sequence variation in the 3'-untranslated region of the dopamine transporter gene and attention-deficit hyperactivity disorder (ADHD).

The dopamine transporter gene (DAT1) has been reported to be associated with attention-deficit hyperactivity disorder (ADHD) in a number of studies [Cook et al. (1995): Am J Human Genet 56(4):9993-998; Gill et al. (1997): Mol Psychiatry 2(4):311-313; Waldman et al. (1998): Am J Human Genet 63(6):1767-1776; Barr et al. (2001): Biol Psychiatry 49(4):333-339; Curran et al. (2001): Mol Psychiatry 6(4):425-428; Chen et al. (2003): Mol Psychiatry 8(4):393-396]. Specifically, the 10-repeat allele of the 40-bp variable number of tandem repeats (VNTR) polymorphism located in the 3' untranslated region (UTR) of the gene has been found to be associated with ADHD. There is evidence from in vitro studies indicating that variability in the repeat number, and sequence variation in the 3'-UTR of the DAT1 gene may influence the level of the dopamine transporter protein [Fuke et al. (2001): Pharmacogenomics J 1(2):152-156; Miller and Madras (2002): Mol Psychiatry 7(1):44-55]. In this study, we investigated whether DNA variation in the DAT1 3'UTR contributed to ADHD by genotyping DNA variants around the VNTR region in a sample of 178 ADHD families. These included a MspI polymorphism (rs27072), a DraI DNA change (T/C) reported to influence DAT1 expression levels, and a BstUI polymorphism (rs3863145) in addition to the VNTR. We also screened the VNTR region by direct resequencing to determine if there was sequence variation within the repeat units that could account for the association. Our results indicate that DAT1 is associated with ADHD in our sample but not with alleles of the VNTR polymorphism. We did not find any variation in the sequence for either the 10- or 9-repeat alleles in the probands screened nor did we observe the reported DraI (T/C) variation. Our results therefore refute the possibility of the reported DraI variation or alleles of the VNTR as the functional variants contributing to the disorder.

3' Untranslated Regions↗
PubMed2005

Inhibition of motor responses in siblings concordant and discordant for attention deficit hyperactivity disorder.

OBJECTIVE: The authors sought to determine whether nonaffected siblings of ADHD probands have a motor response inhibition deficit and to assess concordance for this inhibition deficit in ADHD-concordant and ADHD-discordant sibling pairs. METHOD: ADHD-concordant pairs (21 probands and their affected siblings), ADHD-discordant pairs (18 probands and their nonaffected siblings), and a group of unrelated, demographically balanced, healthy individuals (N=24) were compared on measures of response inhibition, ADHD behavior, impairment, and environmental risk. RESULTS: Concordant-pair probands, their affected siblings, and discordant-pair probands exhibited inhibitory control impairment relative to healthy comparison subjects. The performance of nonaffected siblings was intermediate between that of ADHD children and the healthy comparison subjects. Group differences persisted after age was controlled, and performance was not correlated with the number of ADHD symptoms. In ADHD-concordant sibling pairs, there was a significant relationship between proband and sibling inhibition deficit. In ADHD-discordant sibling pairs, inhibition deficit was evident in half of the nonaffected siblings of probands with an inhibition deficit. Groups did not differ in exposure to environmental risks. CONCLUSIONS: Impaired inhibitory control aggregates in the family members of individuals with ADHD and may serve as an indicator of genetic vulnerability to the disorder.

Attention Deficit Disorder with Hyperactivity↗
PubMed2005

Attention-deficit hyperactivity disorder with and without obsessive-compulsive behaviours: clinical characteristics, cognitive assessment, and risk factors.

OBJECTIVES: To determine the prevalence of obsessive--compulsive behaviours (OCB) in a clinical sample of children with attention-deficit hyperactivity disorder (ADHD) and to compare ADHD children (with and without OCB) with respect to clinical and cognitive characteristics and risk factors. METHOD: We compared ADHD children (n = 134) with and without OCB, and we compared all ADHD children with a group of normal control subjects (n = 26) on various clinical, cognitive, and inhibitory control measures; neurobiological and psychosocial risk factors; and family histories of psychiatric illness. RESULTS: Clinically significant OCB was identified in 11.2% (15/134) of children with ADHD. Comorbid OCB was associated with significantly increased perfectionism, improved teacher ratings of inattention, and a decreased likelihood of having a first-degree relative with ADHD. Comorbid ADHD and OCB may also be associated with increased oppositional behaviour at home and better inhibitory control, though these differences were not statistically significant. CONCLUSIONS: Comorbid OCB is common in clinically referred children with ADHD and is associated with increased impairment relative to ADHD alone. Further, children with ADHD and OCB may develop symptoms as the result of different genetic and environmental risk factors, compared with children with ADHD only.

Adolescent↗
PubMed2004

Evidence for an error monitoring deficit in attention deficit hyperactivity disorder.

We studied error monitoring in ADHD and control children in a task requiring inhibition of a motor response. The extent of slowing following successful (stopped) and failed (nonstopped) inhibition was compared across groups. We also measured the time required to inhibit a response (stop signal reaction time, SSRT). Compared to controls, ADHD participants slowed less following nonstopped responses. Slowing did not vary with comorbid reading, oppositional, conduct or anxiety disorder, sex or ADHD subtype. Slowing after nonstopped responses was marginally, although significantly correlated with total ADHD symptoms and with age. ADHD participants had significantly longer SSRT than controls, but SSRT was not significantly correlated with slowing. The apparent deficit in error monitoring in ADHD and its independence from the inhibition deficit observed in ADHD has implications for executive control models of ADHD, performance problems associated with the disorder and for component theories of executive control.

Adolescent↗
PubMed2004

Methylphenidate improves visual-spatial memory in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: To investigate the effect of methylphenidate (MPH) on visual-spatial memory, as measured by subtests of the Cambridge Neuropsychological Testing Automated Battery (CANTAB), in children with attention-deficit/hyperactivity disorder (ADHD). Visual-spatial memory is a core component of working memory that has been shown to be impaired in ADHD, irrespective of comorbid reading and/or language problems. METHOD: A clinic-referred sample of school-age children with a confirmed DSM-IV diagnosis of ADHD (n = 26) completed tests of visual-spatial memory, planning ability, and recognition memory in an acute, randomized, placebo-controlled, crossover trial with three single fixed doses of MPH. MPH effects on right-handed and left-handed motor control were also assessed. RESULTS: MPH significantly improved performance on a self-ordered, updating visual-spatial working memory task and on maintenance of visual-spatial information but had no effects on measures of visual-spatial planning ability or recognition memory. Also, MPH significantly improved left-handed motor control. CONCLUSIONS: Beneficial effects of MPH on visual-spatial processing in ADHD are selective and restricted to visual-spatial memory.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

Stimulant treatment over five years: adherence, effectiveness, and adverse effects.

OBJECTIVE: To evaluate the impact of adherence and medication status on effectiveness and adverse effects of stimulant use in children with attention-deficit/hyperactivity disorder (ADHD) over 5 years. METHOD: Seventy-nine of 91 participants in a 12-month randomized controlled trial of methylphenidate and parent groups enrolled in a follow-up study. Adherence to stimulants, treatment response, and adverse effects were evaluated annually for 5 years. Changes in teacher-reported symptoms and parent-reported adverse effects were compared at 2, 3, 4, and 5 years for 3 groups: adherents, nonadherents on medication, or nonadherents off medication. Controlling for age, gender, and baseline severity, adherence status and medication status were evaluated as correlates of teacher-reported ADHD symptom scores at each year using multiple regression analyses. RESULTS: At 2 years, adherents (n = 41) showed greater improvement in teacher-reported symptoms than those off medication (n = 16) and equivalent response to nonadherents on stimulants (n = 16) (p =.02). At 5 years, adherents (n = 16) showed greater improvement in teacher-reported symptoms than nonadherents on stimulants (n = 15) and those off medication (n = 14) (p =.04). At year 2 medication status (beta = 4.67 [0.40-8.95, p =.033]) and at year 5 adherence status (beta = 7.23 [3.01-11.44, p =.001]) correlated with higher teacher-reported symptom scores. Clinically significant adverse effects were present for 5 years, most commonly loss of appetite. CONCLUSIONS: Psychostimulants improve ADHD symptoms for up to 5 years, but adverse effects persist.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

Replication test for association of the IL-1 receptor antagonist gene, IL1RN, with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) has a strong genetic basis, and aberrant brain dopaminergic and noradrenergic activity is implicated in its etiology. Interleukin-1 (IL-1), its antagonist, IL-1Ra, and IL-1 receptors are all present in the brain, and IL-1 has been shown to influence both dopaminergic and noradrenergic function. Recently, Segman et al. [1] tested the IL-1Ra gene, IL1RN, as a candidate for involvement in ADHD. Using the transmission/disequilibrium test (TDT) to examine 77 nuclear ADHD families for the inheritance of alleles of an intronic 86-bp VNTR polymorphism, they found significant evidence for biased transmission of the 4-repeat allele (p=0.04) and non-transmission of the 2-repeat allele (p=0.03). Here, we sought to replicate this in an independent sample of families. In contrast to the previous findings, our analysis of 178 ADHD families showed no evidence for biased transmission of these alleles (p=0.81 and p=1.00, respectively). Our lack of evidence for association of this IL1RN polymorphism with ADHD, based on a much larger sample of families, suggests that the original finding may have been a spurious (i.e. false-positive) result. These findings highlight the need for further investigations of this marker, in additional independent ADHD samples, in the future.

Adolescent↗
PubMed2003

Selective inhibition in children with attention-deficit hyperactivity disorder off and on stimulant medication.

Selective inhibition requires discrimination between auditory signals and is assessed using a modification of the stop-signal task. Selective inhibition was assessed in a group of 59 clinic-referred, DSM-IV-diagnosed children with attention-deficit hyperactivity disorder (ADHD) and compared to that of a community sample of 59 children. Methylphenidate (MPH) effects on selective inhibition were assessed in a subset of the ADHD sample that participated in an acute, randomized, placebo-controlled, crossover trial with 3 fixed doses of MPH. Children with ADHD performed more poorly than controls on the majority of selective stop-signal task parameters: they exhibited more anticipatory (invalid) responses, with less accurate and more variable responses on the response execution task, as well as a slower selective inhibition process. MPH improved speed of both inhibition and response execution processes; it also reduced variability of response execution and decreased nonselective inhibition. On the one hand, findings are consistent with purported inhibition deficit in ADHD, but on the other hand, suggest that neither the impairment itself, nor MPH effects, were restricted to inhibition.

Attention Deficit Disorder with Hyperactivity↗
PubMed2002

The norepinephrine transporter gene and attention-deficit hyperactivity disorder.

The adrenergic system plays a known role in attentional systems and a suspected causal role in attention-deficit hyperactivity disorder (ADHD), based on evidence from pharmacological interventions and animal models. The efficacy of the highly selective noradrenergic reuptake inhibitor, tomoxetine, in treating ADHD symptoms supports the system's role in ADHD and points to the norephinephrine transporter as a candidate gene. This study tested the gene for the norepinephrine transporter (NET1) as a susceptibility factor in ADHD using three polymorphisms located in exon 9, intron 9, and intron 13. We examined the inheritance of these polymorphisms in a sample of 122 families with a total of 155 children with ADHD identified through an ADHD proband. Use of the transmission disequilibrium test failed to show significant evidence for biased transmission of any of the alleles or the haplotypes of these polymorphisms. We further investigated this gene by screening the probands for five known amino acid variants to determine if they contributed to the ADHD phenotype but observed only one (Thr99Ile) in our sample. Since the frequency of this variant (1.8%) was similar to that previously reported in a control sample (2.2%), it is unlikely that this variant is related to the ADHD phenotype. Our results do not support the NET1 gene as a major genetic susceptibility factor in ADHD.

Alleles↗
PubMed2002

Methylphenidate improves Stroop naming speed, but not response interference, in children with attention deficit hyperactivity disorder.

OBJECTIVE: The goal of this study was to investigate the effect of methylphenidate (MPH) on response interference, as measured by the Stoop Color and Word Test, in children with attention deficit hyperactivity disorder (ADHD). Response interference is a core component of response inhibition that has been shown to be impaired in children with ADHD. METHODS: A clinic-referred sample of school-aged children with a confirmed Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnosis of ADHD and good reading skills (n = 31) completed the Stroop Color and Word Test in an acute, randomized, placebo-controlled, crossover trial with three single fixed doses of MPH. RESULTS: MPH did not improve response interference on the Stroop Color and Word Test but did significantly improve color naming and word naming abilities. CONCLUSION: Response interference, as measured by the Stroop Color and Word Test, is not improved by MPH in children with ADHD. In addition, findings demonstrate strongly positive MPH effects on the highly effortful process of color naming, which has previously been demonstrated as impaired in children with ADHD. MPH was also shown to have a positive but smaller effect on word naming speed.

Attention Deficit Disorder with Hyperactivity↗