Striatal volumes in pediatric bipolar patients with and without comorbid ADHD

Abstract

The most prevalent comorbid disorder in pediatric bipolar disorder (BD) is attention-deficit/hyperactivity disorder (ADHD). As caudate volume abnormalities have been demonstrated in both BD and ADHD, this study sought to determine whether these findings could be attributed to separable effects from either diagnosis. High resolution anatomical magnetic resonance (MRI) images were obtained from youth in 4 groups: BD with comorbid ADHD (n = 17), BD without comorbid ADHD (n = 12), youth with ADHD alone (n = 11), and healthy control subjects (n = 24). Caudate, putamen, and globus pallidus volumes were manually traced for each subject using BrainImageJava software by a reliable rater blinded to diagnosis. There was a significant effect of diagnosis on striatal volumes, with ADHD associated with decreased caudate and putamen volumes, and BD associated with increased caudate, putamen, and globus pallidus volumes. Thus, the presence or absence of comorbid ADHD in patients with BD was associated with distinct alterations in caudate volumes, suggesting that these groups have different, but related, mechanisms of neuropathology.

Introduction

There has been a vast increase in our research knowledge of pediatric-onset bipolar disorder (BD) over the past decade. Nevertheless, many questions regarding the underlying pathophysiology of the disease remain unanswered. Finding a common biological marker of BD is complicated by the heterogeneity of the disorder, particularly as it presents frequently with comorbid disorders. The most prevalent comorbid disorder with pediatric BD is attention deficit/hyperactivity disorder (ADHD) (DelBello et al., 2004, Adler et al., 2005). These patients show impairments in attention, impulse control, and executive function in addition to the mood dysregulation that affects all patients with BD. Studying BD patient populations based on the presence or absence of ADHD may create greater homogeneity within patient groups. This may aid in distinguishing neural abnormalities unique to each disorder.

Several studies have used structural magnetic resonance imaging (sMRI) to examine regional brain volumes in both BD and ADHD. While a number of studies have demonstrated reduced caudate nucleus volumes in patients with ADHD as compared with healthy controls (Krain and Castellanos, 2006, Schneider et al., 2006), such studies on patients with BD have been few and inconsistent. Wilke and colleagues found overall volume increases in the basal ganglia of adolescents with BD (Wilke et al., 2004), while DelBello reported increased putamen volumes compared to healthy controls (DelBello et al., 2004). In contrast, other studies in pediatric BD samples found no abnormalities in putamen (Sanches et al., 2005) or caudate volumes (Chang et al., 2005, Sanches et al., 2005). Furthermore, in the most relevant recent study that examined striatal volumes among youths with BD and/or ADHD, caudate and putamen volumes were decreased in subjects with ADHD alone, but no differences in striatal volumes were found between the subjects with BD alone or those with BD+ADHD as compared with controls (Lopez-Larson et al., 2009). Additionally, two studies of first degree relatives or offspring of bipolar parents did not show significant changes in striatal volumes as compared with controls (Singh et al., 2008, Hajek et al., 2009).

In this study, we compared the volumes of the caudate and putamen in pediatric patients with BD+ADHD, BD alone, ADHD alone, and healthy controls. We hypothesized that subjects with ADHD would have decreased striatal volumes compared to healthy controls, while subjects with BD alone would have increased striatal volumes. Thus, when both disorders co-occur (ADHD+BD), we hypothesized that individuals would present with intermediate striatal volumes that do not significantly differ from healthy controls.