The use of neurocognitive measures to complement clinical information has the potential to improve our understanding of the etiology of mental disorders and clarify the diagnostic process. This is particularly true with pediatric bipolar disorder (BD), where the pathophysiology of the disorder is unclear and the diagnostic boundaries remain a topic of debate.
Epidemiological studies indicate low rates of BD in youth (approximately 1%) (Lewinsohn et al. 1995
; Costello et al. 1996
). However, results of recent studies indicate that the diagnosis is being assigned to young people with increasing frequency, with up to a forty-fold increase in diagnosis in outpatient settings (Moreno et al. 2007
A possible explanation for the upsurge in rates of BD is that the boundaries for diagnosing mania in youth have expanded such that youth with mood and behavior dysregulation, but without distinct episodes of mania, are being diagnosed with BD. Youth with severe mood dysregulation (SMD) (Leibenluft et al. 2003
) may exemplify these individuals in whom the appropriate diagnosis is unclear. SMD youth exhibit chronic, severe irritability and anger, along with the subset of Attention Deficit Hyperactivity Disorder (ADHD) symptoms that overlap with the DSM-IV “B” criteria of BD listed in the DSM-IV (i.e. intrusiveness, pressured speech, distractibility, psychomotor agitation) (American Psychiatric Association 1994
). SMD youth also display extreme hyper-reactivity to negative emotional stimuli which, while similar to the “loses temper” criterion of Oppositional Defiant Disorder (ODD) (McMahon and Wells 1998
), is operationalized more precisely in the SMD classification.
SMD youth reflect an important research sample because they are “nosological orphans” (Carlson et al. 2004
). That is, while many SMD youth have ADHD and/or Oppositional Defiant Disorder (ODD), these diagnoses fail to capture the severity of their mood impairment, i.e. their extreme irritability. In addition, although SMD youth have many symptoms which overlap with BD, they fail to meet DSM-IV criteria for mania because SMD irritability is unremitting and non-episodic. Classifying and studying youth according to the SMD categorization is advantageous to relying on established diagnoses such as ADHD or ODD because the SMD criteria operationalize specifically extreme irritability, and the role of irritability in the diagnosis of pediatric BD is central to the controversy over the diagnosis.
The lack of consensus regarding the diagnostic status of SMD youth has significant clinical ramifications, including the escalation of prevalence rates of pediatric BD and the implementation of potentially ineffective treatments for SMD youth. Regarding the latter, SMD youth diagnosed with BD may be prescribed psychotropic medications (e.g. lithium, atypical anti-psychotic medications) that are not efficacious, while medications that might treat their depression, anxiety, and ADHD (e.g. anti-depressants, stimulants) may be withheld for fear of causing a manic reaction. Direct comparisons of BD and SMD youth are needed to clarify the nosological relationship of these two conditions and to ultimately inform optimal treatments.
Data from a number of domains suggest that the validity of the SMD classification is distinct from BD. For example, two longitudinal epidemiological studies have examined the developmental progression of SMD and chronic irritability. First, an examination of the Great Smoky Mountains Study found that children with SMD at a mean age of 11 were at significant risk for unipolar depressive disorders by early adulthood (Brotman et al. 2006
). A separate study with the Children in the Community longitudinal dataset assessed associations between chronic irritability, such as is seen in SMD, assessed at mean age 13, and psychiatric diagnosis assessed at mean age 33. These data indicated that chronic irritability in adolescence predicts MDD, dysthymia, and generalized anxiety disorder (GAD), but not BD, in adulthood (Stringaris et al. 2009
). Thus, two separate longitudinal epidemiological studies suggest that SMD-like youth in early adolescence are at risk for unipolar depressive disorders and anxiety in adulthood.
A small preliminary study indicates a lack of familial aggregation of BD in SMD youth. Specifically, we found that the rate of BD diagnosis is significantly lower in the parents of SMD youth than in the parents of youth with strictly-defined BD (3% vs. 33%) (Brotman et al. 2007a
). In fact, the rate seen in SMD youth is comparable to that seen in the general population (Kessler et al. 2005
Other studies find behavioral, cognitive, and pathophysiological differences in BD and SMD youth. For example, studies of cognitive flexibility, the ability to adapt to changing environmental contingencies, find that whereas both SMD and BD youth show deficits in cognitive flexibility, across tasks these deficits are more consistent in BD youth (Dickstein et al. 2007
). In addition, although both SMD and BD youth have deficits in accurately identifying and categorizing facial emotional displays (Rich et al. 2008
; Guyer et al. 2007
), the neural mechanisms of this impairment may differ. Specifically, SMD youth display decreased amygdala activation, relative to both BD youth and controls, when rating their fear of neutral faces (Brotman et al. 2009
). These studies provide neurocognitive data differentiating SMD and BD youth.
Finally, we have also found differences in how BD and SMD youth respond to frustration (Rich et al. 2007
). In this study, we used a standard attention task with an added emotional component, the affective Posner (Perez-Edgar and Fox 2005
), to induce frustration. We found that while both BD and SMD youth displayed more negative affective responses to the frustrating context than did controls, the two patient groups displayed different psychophysiological deficits, as measured by cortical event-related potentials (ERP’s). Further, whereas psychophysiological perturbations in BD subjects were isolated to the emotional condition, SMD deficits were seen in both emotional and nonemotional contexts. Thus, the global attention deficit in SMD youth was relatively impervious to the emotionality of the context. In sum, similar affect in BD and SMD youth may have divergent attention-related neurocognitive deficits which are differentially impacted by emotional stimuli.
These results support the use of a paradigm which systematically manipulates emotional and attention conditions to provide information about the pathophysiological relationship between SMD and BD youth. The emotion-attention interface is important in the development of mood and behavior regulation, since a child’s ability to deploy attention properly in emotional contexts is central to his/her ability to moderate mood and behavior (Mischel et al. 1989
; Kopp 2002
; Sethi et al. 2000
; Posner and Rothbart 1998
). Evidence indicates that environmental stimuli compete for limited attentional resources (Desimone and Duncan 1995
). One potential consequence is that emotionally salient stimuli preferentially engage attention, which subsequently impacts information processing and the resulting cognition, affect, and behavior (Pessoa et al. 2002
; Vuilleumier et al. 2001
). A hallmark of many affective disorders is impaired attention to task-relevant stimuli when salient emotional stimuli are also present (Yamasaki et al. 2002
We compared responsivity to emotional stimuli in SMD, BD, and healthy control participants. We used the Emotional Interrupt task (Mitchell et al. 2006
), which examines the impact of positive and negative emotional stimuli on attention and thus allows for an examination of attentional biases and their impact on cognitive functioning. Consistent with prior work (Vuilleumier et al. 2001
; Simpson et al. 2000
), we predicted that controls would display attention biases to emotional stimuli; as such they would show greater interference from emotional relative to neutral distracters (Mitchell et al. 2006
). Further, given the results of our prior work with the affective Posner task (Rich et al. 2007
), we predicted that BD youth would display attention biases to emotional stimuli greater than in controls (i.e., they would show greater interference by emotional distracters relative to controls). In contrast, again as seen on the affective Posner task (Rich et al. 2007
), we hypothesized that in SMD youth, attention performance would not differ in the presence of emotional vs. neutral stimuli, meaning SMD youth would display diminished reactivity to emotional stimuli compared to controls. Finally, to examine a possible relationship between attention biases and the real-world clinical experience of BD and SMD youth, exploratory analyses compared performance on the Emotional Interrupt task to parent and clinician ratings of social functioning.