In 2001, the National Institute of Mental Health (NIMH) Roundtable on Prepubertal Bipolar Disorder proposed the diagnosis of BD in children (NIMH Roundtable 2001
). The diagnosis, however, still remains somewhat controversial and often misused because of a lack of research in the heterogeneity of the disorder in youth (e.g., Geller et al. 2000
; Wozniak et al. 1995
). The clinical presentation of BD in adults often has an episodic course, with individuals switching from distinct affective episodes of depression, mania or hypomania, and euthymia. In children, however, agreement on the clinical presentation of BD is less clear, with some studies indicating a more chronic course of symptoms with ultra-rapid shifting of mood states from euphoria to irritability (Geller et al. 2004
) or a more irritable and violent presentation during manic states (Wozniak et al. 1995
). Perhaps unsurprisingly, more recent studies have indicated that narrowly defining the presentation to adult DSM-IV criteria yields different results in cognitive deficits and brain activation patterns than when the criteria are more loosely defined (Leibenluft et al. 2007
; Rich et al. 2007
). Despite the heterogeneity of the clinical presentation in children, BD is still considered a valid diagnosis in pediatric populations (see Youngstrom et al. 2008
, for a review).
An added complication in the diagnosis of bipolar disorder in pediatric populations is the considerable overlap of symptoms with Attention-Deficit Hyperactivity Disorder (ADHD). Hypomania and mania in BD share with ADHD the symptoms of excessive talking, increased activity, inappropriate actions and verbal responses in social situations, lack of inhibition, and distractibility (Geller et al. 2002
; see Kent and Craddock 2003
). Additionally, the hallmark feature of chronic irritability in childhood mania can often mimic the chronic low frustration tolerance and emotional lability of ADHD (Geller et al. 2002
; Wozniak et al. 1995
). It is estimated that the comorbidity between BD and ADHD in youth ranges from 60–93% (Axelson et al. 2006
; Faraone et al. 1997
; Geller et al. 2000
; Wozniak et al. 1995
). Although it has been described as a distinct diagnostic category (Geller et al. 2002
; Youngstrom et al. 2008
), only a limited number of studies have examined BD in youth without this comorbidity or compared the two disorders directly (see Kent and Craddock 2003
; Rucklidge 2006
). If pediatric BD is to be considered a distinct diagnostic entity, further work must examine its presentation in the absence of comorbidity with ADHD. Given the limited understanding of BD in youth, the differential diagnosis between BD and ADHD remains a controversial issue.
The primary aim of this review is to directly examine the quantitative similarities and differences in executive functioning between BD and ADHD in order to determine if a distinct neurocognitive profile exists for each. Both disorders are currently diagnosed using a clinical interview and self-report checklists completed by the individual, a parent, or teacher. Unfortunately, the diagnostician must rely on self-report evidence and clinical judgment to arrive at a diagnosis, as there is no valid biological or behavioral test for arriving at the diagnosis. It is tenuous, however, to rely solely on self-reported characteristics to form a differential diagnosis for these disorders given the behaviorally similar presentation in childhood. Much of the controversy regarding the diagnosis of pediatric BD lies in the Bipolar Disorder Not Otherwise Specified (BDNOS) category. As this is a more broad-reaching category including symptoms of BD that do not reach the threshold for full diagnostic criteria, there is often confusion on whether BD or a disruptive behavior disorder, such as ADHD, should be diagnosed when children present as chronically irritable and emotionally labile (Galantar and Leibenluft 2008
). While several researchers have made attempts to define the BD phenotype as more narrowly conforming to the adult criteria for BD (Leibenluft and Rich 2008
; Stringaris et al. 2009
), there remains no clear-cut answer for the definition of BDNOS in pediatric samples.
The inherent problems in differential diagnosis from BD warrant the use of more objective supporting evidence, such as neuroimaging and cognitive testing, to assist in diagnosis in children and adolescents, although some have questioned this approach in ADHD (Barkley and Grodzinsky 1994
). This objective data, however, would provide supporting evidence for differing neural networks that occur in pediatric BD and ADHD, despite similar behavioral presentations. Research in magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI), indicate differences in structural abnormalities in BD versus ADHD, with volumetric abnormalities of the limbic system and smaller volume of the ventrolateral prefrontal cortex (VLPFC) and rostral prefrontal cortex (PFC) implicated in pediatric BD and smaller volume of striatal structures implicated in ADHD but not BD (Blumberg et al. 2005
; Kalmar et al. 2009
; Lopez-Larson et al. 2009
). Disruption in white matter appears more diffuse across the brain regions in ADHD as compared to BD, whereas white matter abnormalities are more restricted to cortico-limbic connections in the PFC for BD (Pavuluri et al. 2009b
). Evidence from functional imaging studies reveal relatively greater activation in the bilateral VLPFC and right dorsolateral PFC (DLPFC) for pediatric BD relative to the ADHD during response inhibition tasks (Passarotti et al. 2009
). Other tasks of executive function indicate greater activation in left DLPFC, bilateral ACC, and left putamen and thalamus for children with BD (Blumberg et al. 2003
; Chang et al. 2004
; Nelson et al. 2007
), whereas children with ADHD exhibit lower activation in right DLPFC and ACC, and striatal areas (Casey et al. 1997
; Konrad et al. 2007
; Smith et al. 2008
). Although there is evidence that individuals with ADHD and BD differ on neuroanatomical structure and function, such neurobiological measurements (e.g., MRI, SPECT) remain impractical and inefficient in the typical clinical setting. Thus, developing a neurocognitive profile for each disorder would aide in differential diagnosis and avoid the pitfalls of misdiagnosis in youth.
Executive Function as a Model
The PFC and its related neural circuitry are critically involved in executing many of the components underlying executive function. Pennington’s (1997
) concept of the “frontal metaphor” applies to the term “executive function”, in that executive function is a latent construct born from theory and, thus, is not an exact representation of the activity in PFC. Measurement of executive function thus proves difficult, as it is a latent construct composed of several components, which are not clearly defined. Factor analyses of test batteries of executive function do not result in a single factor, but at least five factors: 1) inhibition, 2) working memory, 3) planning, 4) set-shifting, and 5) fluency. (Pennington 1997
; Pennington et al. 1996
; Welsh et al. 1991
) A recent review of a highly similar latent construct, cognitive control, suggests similar dimensions based on literature mining (Sabb et al. 2008
). Although five distinct dimensions, these components of executive function are interrelated processes that depend on interactions with the others to execute control over behavior. Thus, here we use the term ‘executive function’ to refer to the overarching representation of PFC function, recognizing that this latent construct is multifactorial and remains ill-defined.
Executive Function, BD, and ADHD
The present review examines BD and ADHD as disorders of the PFC, although it is clear that many areas of the brain are implicated. Although both BD and ADHD show both abnormal PFC functioning and deficits in executive function, there may be distinct signatures in the patterns of deficits that suggest two different disorders. Pennington (1997
) notes that, in general, while two separate disorders may both involve dysfunction of the PFC and have similar behavioral presentations, discriminant validity may arise from deficits in different areas of executive function. For example, individuals with schizophrenia have been shown to have greater impairment in some aspects of problem-solving than individuals with BD, but not in the areas of set-shifting and attention (see Bearden et al. 2001
, for review).
Here we review five facets of executive function through neurocognitive tasks found in both the pediatric BD and ADHD literatures (see Table for a summary of domains of executive functioning and tasks examined in this review). To the best of our knowledge, this is the first review comparing the neurocognitive function of individuals with pediatric BD and ADHD, and while several studies have emerged to provide support for a neurocognitive profile of pediatric BD research in this new field remains scant. We end our review with a discussion of the executive functioning differences in BD and ADHD and their implications for differential diagnosis of these two disorders.
Tasks of executive function across pediatric BD and ADHD literature