Suggestive evidence for linkage of ADHD features in bipolar disorder to chromosome 10p14

Abstract

Higher rates of bipolar disorder amongst the first-degree relatives of probands with ADHD, and increased rates of ADHD in the relatives of bipolar probands have been reported in many studies. This suggests some commonality in the genetic basis for bipolar disorder and ADHD. We hypothesized that ADHD symptoms in bipolar disorder may access a quantitative subphenotype that is genetically less complex and therefore advantageous for mapping studies. The Wender Utah Rating Scale (WURS) was used to quantify ADHD features in 57 bipolar families collected for linkage studies. The factor structure of the WURS was first examined, and heritability was estimated. Linkage analysis was then conducted using the WURS total score and factor scores as quantitative traits. Three factors were identified: impulsivity and defiant behavior, mood instability and anxiety, and inattention. The total WURS and factor scores were each significantly heritable (0.34 <h(2r) < 0.49) in bipolar families. The inattention factor obtained maximum evidence of linkage on chromosome 10p14 (LOD = 3.35, 25 cM). A LOD score of 2.06 for the total WURS score was found on chromosome 12q24 region. Childhood ADHD features in patients with bipolar disorder are heritable and may represent a genetically distinct dimension of illness. 10p14, in particular may contain a locus for inattention in bipolar disorder. Quantitative dimensional phenotypes such as this may be useful for both mapping of genes and understanding the role of genes in bipolar disorder.

Effectiveness of Methylphenidate Supplemented by Zinc, Calcium, and Magnesium for Treatment of ADHD Patients in the City of Zahedan

“…The results also show that the reduction of symptoms in the case group was greater than that of the control group. Several similar studies have been conducted and it has been shown that micronutrients such as magnesium and zinc are associated with the treatment of ADHD symptoms (23)(24)(25)(26)(27)(28). Most of these studies have focused on zinc and are consistent with the findings of our study.…”

Association between the dopamine transporter gene (DAT1) and attention deficit hyperactivity disorder-related traits in healthy adults

“…According to the loading pattern, the three factors were tentatively named as follows: 'impulsivity and defiant behavior', first factor (IMP); 'inattention', second factor (INATT); and 'mood instability and anxiety', third factor (MOOD). It is important to note that these factors are compatible with similar factor analyses carried out in other studies (Caci et al, 2009;Joo et al, 2010). The mean values of each factor score for male and female participants were then compared.…”

“…However, an alternative explanation is that the WURS-25 total score and each specific factor score reflect different genetic effects. In a linkage study with bipolar families, a stronger signal with the inattention factor was found in a different region (10p14, LOD = 3.35), although a linkage signal with the WURS-25 total score was found in the 12q24 region (LOD =2.05; Joo et al, 2010).…”

Association of dopamine transporter gene variants with childhood ADHD features in bipolar disorder

“…We previously used the Wender Utah Rating Scale (WURS) to retrospectively measure the severity of childhood ADHD symptoms in BD and identified three heritable factors: impulsivity and defiant behavior, mood instability and anxiety, and inattention (Joo et al, 2009). Linkage analysis of the WURS measures in 57 BD families found modest evidence for linkage of the inattention factor to chromosome 5p15.3 near the dopamine transporter gene ( SLC6A3, DAT1 ) with a LOD score of 1.33 (Joo et al, 2009), where we have previously reported evidence for linkage of BD (Kelsoe et al, 1996; Kelsoe et al, 2001).…”