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Lindsey Kent

Publications and source records attributed to Lindsey Kent.

9 recordsLinked to original sources
PubMed2007

An investigation of the neurotrophic factor genes GDNF, NGF, and NT3 in susceptibility to ADHD.

Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable, neurodevelopmental disorder with onset in early childhood. Genes involved in neuronal development and growth are, thus, important etiological candidates and neurotrophic factors have been hypothesized to play a role in the pathogenesis of ADHD. Glial derived neurotrophic factor (GDNF), nerve growth factor (NGF (beta subunit)), and neurotrophic factor 3 (NT3) are members of the neurotrophin family and are involved in the survival, differentiation, and maintenance of neuronal cells. We have examined 10 coding and intronic single nucleotide polymorphisms (SNPs) across GDNF, NGF, and NT3 in a family-based association sample of 120 DSM-IV ADHD probands and their biological parents, as well as a case-control analysis with 120 sex-matched controls. Borderline significant overtransmission of the C allele of a non-synonymous C/T SNP (rs6330) in NGF which codes an alanine/valine change was found in the family-based sample (Chi-square = 3.69, odds ratio (OR) = 1.65, P = 0.05). Although this SNP is located in the 5' pro-NGF sequence and not the mature NGF protein, it may affect intracellular processing and secretion of NGF.

Adolescent↗
PubMed2006

No association between TPH2 gene polymorphisms and ADHD in a UK sample.

Tryptophan Hydroxylase 2 (TPH2) is the rate-limiting enzyme in the biosynthesis of serotonin which is exclusively expressed in the brain. Recent molecular studies reported significant association between markers mapped to TPH2 and psychiatric conditions including ADHD. We have examined four single nucleotide polymorphisms (SNPs) two of which (rs1843809, rs1386493) were reported to associate with ADHD in an Irish ADHD sample. Transmission disequilibrium analysis revealed no significant association between any of these markers and ADHD. Dividing by the sex of the transmitting parent has also failed to replicate the previously reported paternal over-transmission of the associated alleles to ADHD probands. A larger sample size will be required to clarify if TPH2 alleles are or are not associated with ADHD.

Adolescent↗
PubMed2006

Variations in the human cannabinoid receptor (CNR1) gene modulate striatal responses to happy faces.

Happy facial expressions are innate social rewards and evoke a response in the striatum, a region known for its role in reward processing in rats, primates and humans. The cannabinoid receptor 1 (CNR1) is the best-characterized molecule of the endocannabinoid system, involved in processing rewards. We hypothesized that genetic variation in human CNR1 gene would predict differences in the striatal response to happy faces. In a 3T functional magnetic resonance imaging (fMRI) scanning study on 19 Caucasian volunteers, we report that four single nucleotide polymorphisms (SNPs) in the CNR1 locus modulate differential striatal response to happy but not to disgust faces. This suggests a role for the variations of the CNR1 gene in underlying social reward responsivity. Future studies should aim to replicate this finding with a balanced design in a larger sample, but these preliminary results suggest neural responsivity to emotional and socially rewarding stimuli varies as a function of CNR1 genotype. This has implications for medical conditions involving hypo-responsivity to emotional and social stimuli, such as autism.

Brain Mapping↗
PubMed2005

Insights into the control of attentional set in ADHD using the attentional blink paradigm.

BACKGROUND: Previous work on visual selective attention in Attention Deficit Hyperactivity Disorder (ADHD) has utilised spatial search paradigms. This study compared ADHD to control children on a temporal search task using Rapid Serial Visual Presentation (RSVP). In addition, the effects of irrelevant singleton distractors on search performance were examined. METHOD: In each condition, subjects reported the identity of a red letter 'probe' in a sequence of white letters which appeared one after the other at a central fixation point. The temporal position of the probe varied from an initial target, which was distinguished by surrounding asterisks. The target was reported in addition to the probe in condition 2, but not in the baseline condition 1. In a third condition, the initial target was not reported, but one of the asterisks appeared as a colour singleton on some trials. RESULTS: All children displayed an 'attentional blink' with probe detection reduced when it appeared at close temporal relations relative to the target. This 'blink' reduced over time, and there were no group differences in the recovery of performance, although ADHD children made more errors overall. The ADHD group were also more vulnerable than controls to distraction from irrelevant singletons in condition 3. CONCLUSION: Although the basic mechanisms of selective attention were not impaired in children with ADHD, these children appeared to require more resources to execute the task and were more vulnerable to distraction by irrelevant singletons, indicating deficits in the maintenance of attentional control.

Adolescent↗
PubMed2004

Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable, heterogeneous disorder of early onset, consisting of a triad of symptoms: inattention, hyperactivity, and impulsivity. The disorder has a significant genetic component, and theories of etiology include abnormalities in the dopaminergic system, with DRD4, DAT1, SNAP25, and DRD5 being implicated as major susceptibility genes. An initial report of association between ADHD and the common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5 gene has been followed by several studies showing nonsignificant trends toward association with the same allele. To establish the postulated association of the (CA)(n) repeat with ADHD, we collected genotypic information from 14 independent samples of probands and their parents, analyzed them individually and, in the absence of heterogeneity, analyzed them as a joint sample. The joint analysis showed association with the DRD5 locus (P=.00005; odds ratio 1.24; 95% confidence interval 1.12-1.38). This association appears to be confined to the predominantly inattentive and combined clinical subtypes.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

Recent advances in the genetics of attention deficit hyperactivity disorder.

In the past few years, interest in the molecular genetics of attention deficit hyperactivity disorder (ADHD) has grown enormously, with many groups searching for susceptibility genes, often through large collaborative efforts facilitated by the International ADHD Genetics Consortium. Association findings for several candidate genes within the dopaminergic system, the DRD4 and DRD5 receptor genes and the dopamine transporter gene, DAT1, have been well replicated, and the first of several ongoing genome linkage scan study results have been published. Current challenges in this field are to identify the actual functional variant(s) in these genes conferring susceptibility and other genetic and environmental risk factors for ADHD.

Attention Deficit Disorder with Hyperactivity↗
PubMed2003

Is there a relationship between attention deficit hyperactivity disorder and bipolar disorder?

With the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults and psychotic disorders in children and adolescents, the possibility of a relationship between bipolar disorder (BP) and ADHD has attracted growing interest. This paper critically reviews the scientific literature concerning this postulated relationship by examining evidence from clinico-epidemiological, follow up, family and laboratory studies, including neuroimaging, neuropsychology and genetic studies. The evidence suggests that although the diagnostic categories of BP and ADHD appear to be unrelated, there is support for a possible relationship between some ADHD and manic-like symptoms. However, several fundamental methodological issues require rectification in future research in order to further elucidate the relationship between these disorders.

Adolescent↗
PubMed2002

Association study of a SNAP-25 microsatellite and attention deficit hyperactivity disorder.

Several lines of evidence implicate synaptosomal-associated protein of 25 kDa (SNAP-25) in the etiology of attention deficit hyperactivity disorder (ADHD). Most notably, the coloboma mouse mutant, considered to be a good animal model of hyperactivity, has a deletion spanning this gene. Introducing a SNAP-25 transgene into these animals alleviates hyperlocomotion. We have identified a novel microsatellite repeat in SNAP-25 located between the 5'UTR and the first coding exon, and tested for association with ADHD. Case-control analyses suggest there may be a role of this polymorphism in ADHD, with one allele over-represented in controls and another over-represented in probands. Within-family tests of linkage and association confirmed these findings. Further work is needed to ascertain the role of SNAP-25 in ADHD and assess the functional significance of this polymorphism.

Alleles↗