Cognitive dysfunction is worse among pediatric patients with bipolar disorder Type I than Type II.

Recently, there has been increased interest in identifying possible endophenotypes of pediatric bipolar disorder (BD; Leibenluft & Rich, 2008). In particular, greater attention is being given to the identification of disease associated traits that are more directly linked to the underlying molecular genetics of BD and its associated subtypes than the phenotypic disease state itself (Balanza–Martiez et al., 2008). Indeed, the identification of neurocognitive profiles across differing subtypes of pediatric BD is one way to elucidate the underlying pathophysiological domains that may be loosely linked to specific genes (Deo, Costa, DeLisi, DeSalle, & Haghighi, 2010; Glahn et al., 2004, 2010; Schulze, 2010). Understanding cognitive profiles across separate subtypes of BD can also aid in the development of more tailored cognitive interventions (Cahill et al., 2009; Henin et al., 2009a; Joseph et al., 2008). Deficits in attention, executive function, working memory, verbal learning and memory, visual memory, response inhibition, and processing speed have been documented in both child and adult BD patients (Arts et al., 2007; Cahill et al., 2009; Joseph et al., 2008; Henin et al., 2009a; Kurtz & Gerraty, 2009). Cognitive deficits are observed in first-degree relatives (Bora, Yucel, & Pantelis, 2009; Doyle et al., 2009), as well as symptomatic and euthymic patients, and appear to be a “trait-like” feature of the disorder (Martinez-Aran et al., 2004; Pavuluri et al., 2006). Deficits in verbal memory and executive functioning are the most prominent and consistent finding in BD patients across the life span (Joseph et al., 2008; Kurtz & Gerraty, 2009; Robinson et al., 2006). These deficits persist even after remission in adults (Martinez-Aran et al., 2004; van Gorp et al, 1998), and become more severe over the course of development in early onset pediatric BD patients (Pavuluri et al., 2009a). While there are a limited number of adult studies that have attempted to differentiate cognitive profiles among BD I versus II patients, none exist in pediatric BD. The majority of investigations of cognitive dysfunction among pediatric BD youth have focused exclusively on BD I patients (Bearden et al., 2007; McClure et al., 2005; Pavuluri et al., 2006) or have used heterogeneous samples of varying BD subtypes (Dickstein et al., 2004; Doyle et al., 2005; Glahn et al., 2005; McClure et al., 2005; Rucklidge et al., 2006). Differentiating cognitive profiles among pediatric BD subtypes may therefore help us to understand potential differences between BD I and II patients and may also help to clarify past findings on neurocognitive deficits. The majority of findings in BD adults lean towards a more impaired pattern of cognitive dysfunction among BD I patients, most notably on tasks of verbal learning and memory and executive functioning (Hsiao et al., 2009, Simonsen et al., 2008; Torrent et al., 2006). However, results have been inconsistent, with some studies reporting more impaired cognitive dysfunction among BD II patients (Harkavy-Friedman et al., 2006; Summers et al., 2006). Methodological issues such as the inclusion of patients in heterogeneous clinical states and medication effects may have contributed to some of the discrepancies. The potential impact of pharmacotherapy on cognitive functioning in BD patients has been gaining increased attention (Donaldson et al., 2003; Holmes et al., 2008; Pavuluri et al., 2010). Recent evidence indicates that higher doses of mood stabilizers (Henin et al., 2009b; Holmes et al., 2008) and antipsychotic medications (Donaldson et al., 2003), can lead to greater cognitive impairment in adult as well as pediatric patients. Because BD I and II patients often vary in the type and number of medications they receive, we sought to study unmedicated acutely ill patients as an important first-step in identifying possible cognitive endophenotypes of the disorder, prior to investigating this in medicated euthymic patients. Therefore, the aim of this study was to investigate neurocognitive functioning in unmedicated BD I and II youth and matched healthy controls (HC). Given the findings from adult studies of BD, we hypothesized that BD I patients would show more severe and widespread cognitive dysfunction, displaying greater deficits on tasks of attention, executive function, working memory, visual memory, and verbal learning and memory compared to BD II patients and HC. Given that there have been no prior studies of this issue in pediatric BD populations, we expected that this study would further inform us on the commonalities and differences in cognitive dysfunction across subtypes of BD, beyond the level of symptom severity.