Biomedical subjects

Jonna Kuntsi

Publications and source records attributed to Jonna Kuntsi.

9 recordsLinked to original sources

PubMed2006

The IMAGE project: methodological issues for the molecular genetic analysis of ADHD.

The genetic mechanisms involved in attention deficit hyperactivity disorder (ADHD) are being studied with considerable success by several centres worldwide. These studies confirm prior hypotheses about the role of genetic variation within genes involved in the regulation of dopamine, norepinephrine and serotonin neurotransmission in susceptibility to ADHD. Despite the importance of these findings, uncertainties remain due to the very small effects sizes that are observed. We discuss possible reasons for why the true strength of the associations may have been underestimated in research to date, considering the effects of linkage disequilibrium, allelic heterogeneity, population differences and gene by environment interactions. With the identification of genes associated with ADHD, the goal of ADHD genetics is now shifting from gene discovery towards gene functionality--the study of intermediate phenotypes ('endophenotypes'). We discuss methodological issues relating to quantitative genetic data from twin and family studies on candidate endophenotypes and how such data can inform attempts to link molecular genetic data to cognitive, affective and motivational processes in ADHD. The International Multi-centre ADHD Gene (IMAGE) project exemplifies current collaborative research efforts on the genetics of ADHD. This European multi-site project is well placed to take advantage of the resources that are emerging following the sequencing of the human genome and the development of international resources for whole genome association analysis. As a result of IMAGE and other molecular genetic investigations of ADHD, we envisage a rapid increase in the number of identified genetic variants and the promise of identifying novel gene systems that we are not currently investigating, opening further doors in the study of gene functionality.

Journal Article↗

PubMed2006

Reaction time, inhibition, working memory and 'delay aversion' performance: genetic influences and their interpretation.

BACKGROUND: For candidate endophenotypes to be useful for psychiatric genetic research, they first of all need to show significant genetic influences. To address the relative lack of previous data, we set to investigate the extent of genetic and environmental influences on performance in a set of theoretically driven cognitive-experimental tasks in a large twin sample. We further aimed to illustrate how test-retest reliability of the measures affects the estimates. METHOD: Four-hundred 7- to 9-year-old twin pairs were assessed individually on tasks measuring reaction time, inhibition, working memory and 'delay aversion' performance. Test-retest reliability data on some of the key measures were available from a previous study. RESULTS: Several key measures of reaction time, inhibition and working-memory performance indicated a moderate degree of genetic influence. Combining data across theoretically related tasks increased the heritability estimates, as illustrated by the heritability estimates of 60% for mean reaction time and 50% for reaction-time variability. Psychometric properties (reliability or ceiling effects) had a substantial influence on the estimates for some measures. CONCLUSIONS: The data support the usefulness of several of the variables for endophenotype studies that aim to link genes to cognitive and motivational processes. Importantly, the data also illustrate specific conditions under which the true extent of genetic influences may be underestimated and hence the usefulness for genetic mapping studies compromised, and suggest ways to address this.

Child↗

PubMed2006

Attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a behavioral diagnosis based on the presence of developmentally inappropriate levels of impulsivity, overactivity, and inattentiveness. It is a familial condition with a complex pattern of inheritance. Variation of several genes involved in the regulation of dopamine, norepinephrine, and serotonin neurotransmission is associated with ADHD. We highlight the two most prominent findings with the dopamine D4 receptor (DRD4) gene and the dopamine transporter (DAT1) gene, and their implications for the understanding of the cellular and neurobiological basis for ADHD. Cognitive and functional studies using electrophysiology and brain imaging frequently indicate altered processing in ADHD during performance on cognitive tasks hypothesized to measure a "core" deficit, such as response inhibition. Yet, children with ADHD appear to suffer from a more general deficit, including impairment in attentional alerting, orienting, response preparation, and control. Reward processes are also altered and, further, a strong association emerges with intraindividual variability, with several causal hypotheses being proposed. Task performance correlates with underactivation of, especially, frontostriatal areas of the brain, but an extended network of brain regions is also implicated. Electroencephalography studies indicate abnormalities in ADHD in relation to slow-wave activity, linked to underarousal. These advances in the areas of genetics, cognitive function, neurophysiology, and neuroanatomy of ADHD give important leads for interdisciplinary research that aims to delineate the causal pathways. Such research is only at its beginning, but is illustrated by recent findings of an association between DAT1 and increased response variability in ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

Testing assumptions for endophenotype studies in ADHD: reliability and validity of tasks in a general population sample.

BACKGROUND: Advances in both genetic and cognitive-experimental studies on attention deficit hyperactivity disorder (ADHD) have opened new opportunities for cognitive endophenotype research. In such genetic designs the focus is on individual differences in characteristics, associated with ADHD, that can be measured reliably over time. Genetic studies that take a 'quantitative trait loci' approach hypothesise that multiple susceptibility genes contribute to a continuous dimension of ADHD symptoms. As an important initial step, we aimed to investigate the underlying assumptions that (1) key cognitive-experimental tasks indicate adequate test-retest reliability and (2) ADHD symptom scores in a general population sample are associated with performance on these tasks. METHODS: Forty-nine children were assessed on a go/no-go task and a reaction time task (the 'fast task') that included manipulations with event rate and incentives. The children were assessed twice, with a test-retest interval of two weeks. RESULTS: The majority of the task variables demonstrated moderate-to-good test-retest reliability. The correlations between teacher ratings of ADHD symptoms and key task variables were .4-.6: ADHD symptoms were associated with poor performance (especially high reaction time variability) in a slow baseline condition, whereas there was low or no association in conditions with a faster event rate or incentives. In contrast, no clear pattern of findings emerged based on parent ratings of ADHD symptoms. CONCLUSION: The data support the usefulness of the go/no-go and fast tasks for genetic studies, which require reliable and valid indices of individual differences. The overall pattern of associations between teacher ratings of ADHD symptoms and task variables is consistent with effects of event rate and incentives on performance, as predicted by the model of activation and arousal regulation. The lack of a clear pattern of findings with parent ratings of ADHD symptoms warrants further study.

Adolescent↗

PubMed2005

Genetic influences on the stability of attention-deficit/hyperactivity disorder symptoms from early to middle childhood.

BACKGROUND: The high heritability of the core symptoms of attention-deficit/hyperactivity disorder (ADHD) has been repeatedly demonstrated, but few studies to date have investigated the extent to which the same genetic influences operate across development or new genes emerge at different developmental periods. METHODS: We report data from a large, population-based study of approximately 4,000 twin pairs, who have been followed up from early to middle childhood. RESULTS: Parents' ratings of ADHD symptoms showed moderate stability across the ages, which was mainly due to shared genetic influences. There was also evidence of additional genetic influences, which were not shared with those acting earlier on, emerging at later age periods. The contribution of environmental influences to the stability of the ADHD symptoms over time was small. Parents' ratings on the Conners' DSM-IV ADHD subscale at the last assessment point, at an average age of 8 years, did not show the rater contrast effects that were observed in the parents' ratings at earlier ages with briefer measures. Similar estimates of genetic and environmental influences were obtained for girls and boys. CONCLUSIONS: We discuss the implications of the findings for molecular genetic studies on ADHD symptomatology.

Age Factors↗

PubMed2005

Continuity and change in preschool ADHD symptoms: longitudinal genetic analysis with contrast effects.

The genetic and environmental mediation of continuity and change in parent-reported ADHD symptoms were investigated in a cohort of over 6000 twin pairs at 2, 3 and 4 years of age. Genetic analyses of the cross-sectional data yielded heritability estimates of 0.78-0.81 at each age, with contrast effects. A common pathway model provided the best fit to the longitudinal data, indicating that genetic influences underlie 91% of the stable variance in ADHD symptomatology. In other words, what is stable for ADHD symptoms is largely genetic. Contrast effects acting in the same direction at different ages contributed to the observed continuity:longitudinal correlations were greater for dizygotic than monozygotic twins.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

Unravelling the complexity of attention-deficit hyperactivity disorder: a behavioural genomic approach.

International research has established that there is a strong genetically inherited contribution to attention-deficit hyperactivity disorder (ADHD) and the genetic mechanisms involved are being sought with considerable success. It is now established that certain alleles of the genes coding for the dopamine D4 receptor and the dopamine transporter occur more frequently in children with ADHD than in healthy controls, and we are finding other DNA changes associated with ADHD. A major challenge for the field now is to clarify how genetic susceptibility is translated into disorder by integrating the fields of quantitative and molecular genetics, neuropsychology and environmental risks.

Attention Deficit Disorder with Hyperactivity↗

PubMed2003

Face and emotion recognition deficits in Turner syndrome: a possible role for X-linked genes in amygdala development.

Face recognition is thought to rely on configural visual processing. Where face recognition impairments have been identified, qualitatively delayed or anomalous configural processing has also been found. A group of women with Turner syndrome (TS) with monosomy for a single maternal X chromosome (45, Xm) showed an impairment in face recognition skills compared with normally developing women. However, normal configural face-processing abilities were apparent. The ability to recognize facial expressions of emotion, particularly fear, was also impaired in this TS subgroup. Face recognition and fear recognition accuracy were significantly correlated in the female control group but not in women with TS. The authors therefore suggest that anomalies in amygdala function may be a neurological feature of TS of this karyotype.

Adolescent↗

PubMed2002

The classification of 'fear' from faces is associated with face recognition skill in women.

Two experiments were conducted to explore the relationship between the discrimination of the facial expression of 'fear' in faces and facial recognition. On the basis of the reported role of the amygdala in both processes in patients, we hypothesised that the two skills would be correlated in normal adults. In Experiment 1, a series of tests of facial expression categorisation, of face matching and of familiar and unfamiliar face recognition was conducted on normal young women, for whom psychometric scores were also obtained (n=23). Accuracy of categorisation of fear from faces predicted variance in face recognition accuracy-especially in tasks of unfamiliar face recognition (immediate old-new discrimination). No other correlations between face processing and expression classification were significant. Experiment 2 repeated the expression classification tests and an unfamiliar face recognition test on a new sample of men (n=13) and women (n=16). While there were no sex differences in face recognition, the correlation between 'fear' and face recognition was replicated only for women. These data indicate that the amygdala supports both the specific apprehension of fear in faces and face recognition in adult human females, but that the association may not hold for men. Sex differences in the structure of the amygdala-hippocampal complex suggest a likely cortical substrate for the observed differences. We speculate that social learning, which involves identifying the faces of potentially salient others, and also their attitude to the observer, engages the amygdala more readily in women than in men.

Adolescent↗