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Gene x environment interactions for ADHD: synergistic effect of 5HTTLPR genotype and youth appraisals of inter-parental conflict.

Nikolas M, Friderici K, Waldman I, Jernigan K, Nigg JT - Behav Brain Funct (2010)

Bottom Line: Because the development of behavioral and emotional regulation depends heavily both on the child's experience within the family context and the child's construals of that experience, children's appraisals of inter-parental conflict are a compelling candidate potentiator of the effects of variation within the serotonin transporter gene promoter polymorphism (5HTTLPR) on liability for ADHD. 304 youth from the local community underwent a multi-informant diagnostic assessment procedure to identify ADHD cases and non-ADHD controls.Youth also completed the Children's Perception of Inter-Parental Conflict (CPIC) scale to assess appraisals of self-blame in relation to their parents' marital disputes.Both high and low serotonergic activity may exert risk for ADHD when coupled with psychosocial distress such as children's self-blame in relation to inter-parental conflict.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Psychology, Michigan State University, East Lansing, Michigan, USA. nikolasm@msu.edu

ABSTRACT

Background: Serotonin genes have been hypothesized to play a role in the etiology of attention-deficit hyperactivity disorder (ADHD); prior work suggests that serotonin may interact with psychosocial stressors in ADHD, perhaps via mechanisms involved in emotional dysregulation. Because the development of behavioral and emotional regulation depends heavily both on the child's experience within the family context and the child's construals of that experience, children's appraisals of inter-parental conflict are a compelling candidate potentiator of the effects of variation within the serotonin transporter gene promoter polymorphism (5HTTLPR) on liability for ADHD.

Method: 304 youth from the local community underwent a multi-informant diagnostic assessment procedure to identify ADHD cases and non-ADHD controls. Youth also completed the Children's Perception of Inter-Parental Conflict (CPIC) scale to assess appraisals of self-blame in relation to their parents' marital disputes. The trialleic configuration of 5HTTLPR (long/short polymorphism with A> G substitution) was genotyped and participants were assigned as having high (La/La N = 78), intermediate (La/Lg, La/short, N = 137), or low (Lg/Lg, Lg/short, short/short, N = 89) serotonin transporter activity genotypes. Teacher reported behavior problems were examined as the target outcome to avoid informant overlap for moderator and outcome measures.

Results: Hierarchical linear regression analyses indicated significant 5HTTLPR x self-blame interactions for ADHD symptoms. Examination of the interactions indicated positive relations between reports of self-blame and ADHD symptoms for those with the high and low serotonin activity genotypes. There was no relation between self-blame and ADHD for those with intermediate activity 5HTTLPR genotypes.

Conclusion: Both high and low serotonergic activity may exert risk for ADHD when coupled with psychosocial distress such as children's self-blame in relation to inter-parental conflict. Results are discussed in relation to the role of serotonin in the etiology of the ADHD and related externalizing behaviors.

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5HTTLPR × self-blame interaction predicting teacher cognitive problems score. Scatter plot of the CPIC self-blame and Cognitive Problems (teacher report) data are displayed and color-coded by genotype group. Solid lines represent best-fitting regression line for each genotype group.
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Figure 2: 5HTTLPR × self-blame interaction predicting teacher cognitive problems score. Scatter plot of the CPIC self-blame and Cognitive Problems (teacher report) data are displayed and color-coded by genotype group. Solid lines represent best-fitting regression line for each genotype group.

Mentions: We then proceeded to examine the Conners ADHD symptom dimensions of inattention and hyperactivity (measured via the Cognitive Problems and Hyperactivity raw subscale scores on the Conners'). For Cognitive Problems, there was a significant main effect of self-blame [b = .21, 95% confidence interval .09-.32, p < .001, total R2 = .07]. There was no main effect of 5HTTLPR genotype group using either the linear (p = .29) or non-linear (p = .54) coding schemes. The linear × self-blame interaction was nonsignificant (p = .54). The non-linear × self-blame interaction showed a trend, but was also not significant [b = .07, 95% confidence interval -.01-.14, p = .08, ΔR2 = .008, total R2 = .08] (see Figure 2).


Gene x environment interactions for ADHD: synergistic effect of 5HTTLPR genotype and youth appraisals of inter-parental conflict.

Nikolas M, Friderici K, Waldman I, Jernigan K, Nigg JT - Behav Brain Funct (2010)

5HTTLPR × self-blame interaction predicting teacher cognitive problems score. Scatter plot of the CPIC self-blame and Cognitive Problems (teacher report) data are displayed and color-coded by genotype group. Solid lines represent best-fitting regression line for each genotype group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2865439&req=5

Figure 2: 5HTTLPR × self-blame interaction predicting teacher cognitive problems score. Scatter plot of the CPIC self-blame and Cognitive Problems (teacher report) data are displayed and color-coded by genotype group. Solid lines represent best-fitting regression line for each genotype group.
Mentions: We then proceeded to examine the Conners ADHD symptom dimensions of inattention and hyperactivity (measured via the Cognitive Problems and Hyperactivity raw subscale scores on the Conners'). For Cognitive Problems, there was a significant main effect of self-blame [b = .21, 95% confidence interval .09-.32, p < .001, total R2 = .07]. There was no main effect of 5HTTLPR genotype group using either the linear (p = .29) or non-linear (p = .54) coding schemes. The linear × self-blame interaction was nonsignificant (p = .54). The non-linear × self-blame interaction showed a trend, but was also not significant [b = .07, 95% confidence interval -.01-.14, p = .08, ΔR2 = .008, total R2 = .08] (see Figure 2).

Bottom Line: Because the development of behavioral and emotional regulation depends heavily both on the child's experience within the family context and the child's construals of that experience, children's appraisals of inter-parental conflict are a compelling candidate potentiator of the effects of variation within the serotonin transporter gene promoter polymorphism (5HTTLPR) on liability for ADHD. 304 youth from the local community underwent a multi-informant diagnostic assessment procedure to identify ADHD cases and non-ADHD controls.Youth also completed the Children's Perception of Inter-Parental Conflict (CPIC) scale to assess appraisals of self-blame in relation to their parents' marital disputes.Both high and low serotonergic activity may exert risk for ADHD when coupled with psychosocial distress such as children's self-blame in relation to inter-parental conflict.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Psychology, Michigan State University, East Lansing, Michigan, USA. nikolasm@msu.edu

ABSTRACT

Background: Serotonin genes have been hypothesized to play a role in the etiology of attention-deficit hyperactivity disorder (ADHD); prior work suggests that serotonin may interact with psychosocial stressors in ADHD, perhaps via mechanisms involved in emotional dysregulation. Because the development of behavioral and emotional regulation depends heavily both on the child's experience within the family context and the child's construals of that experience, children's appraisals of inter-parental conflict are a compelling candidate potentiator of the effects of variation within the serotonin transporter gene promoter polymorphism (5HTTLPR) on liability for ADHD.

Method: 304 youth from the local community underwent a multi-informant diagnostic assessment procedure to identify ADHD cases and non-ADHD controls. Youth also completed the Children's Perception of Inter-Parental Conflict (CPIC) scale to assess appraisals of self-blame in relation to their parents' marital disputes. The trialleic configuration of 5HTTLPR (long/short polymorphism with A> G substitution) was genotyped and participants were assigned as having high (La/La N = 78), intermediate (La/Lg, La/short, N = 137), or low (Lg/Lg, Lg/short, short/short, N = 89) serotonin transporter activity genotypes. Teacher reported behavior problems were examined as the target outcome to avoid informant overlap for moderator and outcome measures.

Results: Hierarchical linear regression analyses indicated significant 5HTTLPR x self-blame interactions for ADHD symptoms. Examination of the interactions indicated positive relations between reports of self-blame and ADHD symptoms for those with the high and low serotonin activity genotypes. There was no relation between self-blame and ADHD for those with intermediate activity 5HTTLPR genotypes.

Conclusion: Both high and low serotonergic activity may exert risk for ADHD when coupled with psychosocial distress such as children's self-blame in relation to inter-parental conflict. Results are discussed in relation to the role of serotonin in the etiology of the ADHD and related externalizing behaviors.

Show MeSH
Related in: MedlinePlus