Limits...
Relationship between endophenotype and phenotype in ADHD.

Rommelse NNj, Altink ME, Martin NC, Buschgens CJ, Faraone SV, Buitelaar JK, Sergeant JA, Oosterlaan J - Behav Brain Funct (2008)

Bottom Line: It has been hypothesized that genetic and environmental factors relate to psychiatric disorders through the effect of intermediating, vulnerability traits called endophenotypes.The endophenotypic construct classified children with moderate accuracy (about 50% for each of the three groups).Although a potentially moderating effect (age) and several mediating effects (gender, age, IQ) were found affecting the relation between endophenotypic construct and phenotype, none of the effects studied could account for the finding that affected children had a more severe phenotype than endophenotype.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Neuropsychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands. nnj.rommelse@psy.vu.nl.

ABSTRACT

Background: It has been hypothesized that genetic and environmental factors relate to psychiatric disorders through the effect of intermediating, vulnerability traits called endophenotypes. The study had a threefold aim: to examine the predictive validity of an endophenotypic construct for the ADHD diagnosis, to test whether the magnitude of group differences at the endophenotypic and phenotypic level is comparable, and to investigate whether four factors (gender, age, IQ, rater bias) have an effect (moderation or mediation) on the relation between endophenotype and phenotype.

Methods: Ten neurocognitive tasks were administered to 143 children with ADHD, 68 non-affected siblings, and 120 control children (first-borns) and 132 children with ADHD, 78 non-affected siblings, and 113 controls (second-borns) (5 - 19 years). The task measures have been investigated previously for their endophenotypic viability and were combined to one component which was labeled 'the endophenotypic construct': one measure representative of endophenotypic functioning across several domains of functioning.

Results: The endophenotypic construct classified children with moderate accuracy (about 50% for each of the three groups). Non-affected children differed as much from controls at the endophenotypic as at the phenotypic level, but affected children displayed a more severe phenotype than endophenotype. Although a potentially moderating effect (age) and several mediating effects (gender, age, IQ) were found affecting the relation between endophenotypic construct and phenotype, none of the effects studied could account for the finding that affected children had a more severe phenotype than endophenotype.

Conclusion: Endophenotypic functioning is moderately predictive of the ADHD diagnosis, though findings suggest substantial overlap exists between endophenotypic functioning in the groups of affected children, non-affected siblings, and controls. Results suggest other factors may be crucial and aggravate the ADHD symptoms in affected children.

No MeSH data available.


Related in: MedlinePlus

Group differences at the endophenotypic level (operationalized as a composite score of ten task variables) and at the phenotypic level (operationalized as a composite of parental and teacher ADHD questionnaire).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2267799&req=5

Figure 3: Group differences at the endophenotypic level (operationalized as a composite score of ten task variables) and at the phenotypic level (operationalized as a composite of parental and teacher ADHD questionnaire).

Mentions: The group by level interaction was analyzed to assess whether group differences were comparable at the endophenotypic and phenotypic level. This interaction was significant (first-borns F (2, 327) = 45.46, p < .001, ηp2 = .22; second-borns F (2, 319) = 56.89, p < .001, ηp2 = .26), suggesting group contrasts to be different at the endophenotypical and phenotypical level. When the analysis was repeated with affected children and controls, the interaction remained significant (first-borns F (1, 260) = 67.68, p < .001, ηp2 = .21; second-borns F (1, 242) = 92.13, p < .001, ηp2 = .28). As is visible in Figure 3, affected children deviated more from controls at the phenotypic level than at the endophenotypic level. No such interaction was present for non-affected siblings compared to controls (first-borns F (1, 185) = 0.24, p = .63, ηp2 < .01; second-borns F (1, 188) = 0.02, p = .89, ηp2 < .01).


Relationship between endophenotype and phenotype in ADHD.

Rommelse NNj, Altink ME, Martin NC, Buschgens CJ, Faraone SV, Buitelaar JK, Sergeant JA, Oosterlaan J - Behav Brain Funct (2008)

Group differences at the endophenotypic level (operationalized as a composite score of ten task variables) and at the phenotypic level (operationalized as a composite of parental and teacher ADHD questionnaire).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2267799&req=5

Figure 3: Group differences at the endophenotypic level (operationalized as a composite score of ten task variables) and at the phenotypic level (operationalized as a composite of parental and teacher ADHD questionnaire).
Mentions: The group by level interaction was analyzed to assess whether group differences were comparable at the endophenotypic and phenotypic level. This interaction was significant (first-borns F (2, 327) = 45.46, p < .001, ηp2 = .22; second-borns F (2, 319) = 56.89, p < .001, ηp2 = .26), suggesting group contrasts to be different at the endophenotypical and phenotypical level. When the analysis was repeated with affected children and controls, the interaction remained significant (first-borns F (1, 260) = 67.68, p < .001, ηp2 = .21; second-borns F (1, 242) = 92.13, p < .001, ηp2 = .28). As is visible in Figure 3, affected children deviated more from controls at the phenotypic level than at the endophenotypic level. No such interaction was present for non-affected siblings compared to controls (first-borns F (1, 185) = 0.24, p = .63, ηp2 < .01; second-borns F (1, 188) = 0.02, p = .89, ηp2 < .01).

Bottom Line: It has been hypothesized that genetic and environmental factors relate to psychiatric disorders through the effect of intermediating, vulnerability traits called endophenotypes.The endophenotypic construct classified children with moderate accuracy (about 50% for each of the three groups).Although a potentially moderating effect (age) and several mediating effects (gender, age, IQ) were found affecting the relation between endophenotypic construct and phenotype, none of the effects studied could account for the finding that affected children had a more severe phenotype than endophenotype.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Neuropsychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands. nnj.rommelse@psy.vu.nl.

ABSTRACT

Background: It has been hypothesized that genetic and environmental factors relate to psychiatric disorders through the effect of intermediating, vulnerability traits called endophenotypes. The study had a threefold aim: to examine the predictive validity of an endophenotypic construct for the ADHD diagnosis, to test whether the magnitude of group differences at the endophenotypic and phenotypic level is comparable, and to investigate whether four factors (gender, age, IQ, rater bias) have an effect (moderation or mediation) on the relation between endophenotype and phenotype.

Methods: Ten neurocognitive tasks were administered to 143 children with ADHD, 68 non-affected siblings, and 120 control children (first-borns) and 132 children with ADHD, 78 non-affected siblings, and 113 controls (second-borns) (5 - 19 years). The task measures have been investigated previously for their endophenotypic viability and were combined to one component which was labeled 'the endophenotypic construct': one measure representative of endophenotypic functioning across several domains of functioning.

Results: The endophenotypic construct classified children with moderate accuracy (about 50% for each of the three groups). Non-affected children differed as much from controls at the endophenotypic as at the phenotypic level, but affected children displayed a more severe phenotype than endophenotype. Although a potentially moderating effect (age) and several mediating effects (gender, age, IQ) were found affecting the relation between endophenotypic construct and phenotype, none of the effects studied could account for the finding that affected children had a more severe phenotype than endophenotype.

Conclusion: Endophenotypic functioning is moderately predictive of the ADHD diagnosis, though findings suggest substantial overlap exists between endophenotypic functioning in the groups of affected children, non-affected siblings, and controls. Results suggest other factors may be crucial and aggravate the ADHD symptoms in affected children.

No MeSH data available.


Related in: MedlinePlus