Negative Emotion Impairs Working Memory in Pediatric Patients with Bipolar Disorder Type I

Pediatric bipolar disorder (BD) is a debilitating illness characterized by rapid mood swings, significant functional impairment, and chronic morbidity (see Leibenluft & Rich, 2008 and Pavuluri, Birmaher, & Naylor, 2005 for reviews). Deficits in social and interpersonal functioning are core features of the illness, and are thought to reflect disturbances in cognitive and affect processing circuitry (Rich et al., 2008a, 2010; Schenkel et al., 2007, 2008). Significant impairments in attention and working memory (Dickstein et al., 2004; Pavuluri et al., 2006), along with deficits in emotion processing have been documented in BD youth (Rich et al., 2008b; Schenkel et al., 2007), as well as unaffected first-degree relatives (Bora et al., 2009; Brotman et al., 2008a; Doyle et al., 2009). Moreover, disturbances in emotion identification have been found across emotions in pediatric BD patients, and are thought to be an endophenotype for the disorder (Brotman et al., 2008a, 2008b; Rich et al., 2008b). Recent models of the pathophysiology of pediatric BD suggest abnormalities in frontolimbic circuitry, and point to important functional interactions in emotion processing between higher cortical cognitive areas and regions associated with the evaluation and processing of affective stimuli (Pavuluri et al., 2007). A number of functional magnetic resonance imaging (fMRI) studies of emotion processing in youth with BD have identified abnormal activation in cortical areas such as the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), ventromedial prefrontal cortex (VMPFC) and anterior cingulate cortex (ACC), along with subcortical areas that include the striatum, and most notably the amygdala (Chang et al., 2004; Passarotti, Sweeney, & Pavuluri, 2010, 2011; Pavuluri et al., 2007, 2008, 2010b; Rich et al., 2006). Additionally, studies have documented smaller hippocampal volume among adolescents with BD relative to controls (Bearden et al., 2008). Together, these regions are involved in receiving, attending to, evaluating, and modulating emotional stimuli, including top-down regulation of emotional responses and the appraisal of reward and punishment (Adolphs, 2009; Botvinick et al., 2004; Cools et al., 2002; Packard & Cahill, 2001; Weissman, Perkins, & Woldorff, 2008; Vollm et al.). Additionally, Rich et al., (2008a) reported reduced connectivity between the left amygdala and right posterior cingulate/precuneus and right parahippocampal gyrus, indicating that working memory may be an important factor associated with emotion identification deficits in BD youth. Given the complexity and interconnectivity of emotion centers and higher cortical regions, it is likely that emotion processing impairments and cognitive dysfunction among BD youth are interrelated and bidirectional in nature. For example, the excessive emotional reactivity characteristic of a manic/acute state may have a negative effect on cognitive functioning, and deficient executive control could reduce top-down modulation of the intensity and duration of emotional experiences (Pavuluri et al., 2008). Past behavioral and imaging studies are consistent with this model. For example, Rich et al., (2005) reported more impaired attentional performance among BD youth when placed in emotionally challenging and frustrating contexts. In addition, our group recently found that BD adolescents show reduced activation in higher cortical centers (e.g., DLPFC, VLPFC) when exposed to emotional stimuli, such as emotional faces or words, and increased activation in the amygdala, suggesting that cortical centers become less active and fail to provide adequate top-down regulation over subcortical emotion areas (Passarotti et al., 2010, 2011; Pavuluri et al., 2007, 2008). Deficient top-down modulation has been observed for positive and negative emotional stimuli among pediatric BD patients, however, findings appear to be more robust for negative ones, suggesting a heightened sensitivity for negative contexts (Passarotti et al., 2011; Pavuluri et al., 2008; Pavuluri, Passarotti, Fitzgerald, Weqbreit, & Sweeney, 2012). Understanding the interface between emotional and cognitive functioning in youth with BD can help to elucidate the underlying mechanisms associated with the disorder, and may also help to distinguish between clinical phenotypes in pediatric BD. To date, there has been limited research on the relationships between attention and memory, and emotion processing in pediatric BD. This is surprising as a number of independent investigations have consistently documented working memory and emotion processing deficits in acute and euthymic pediatric BD patients (Pavuluri et al., 2006; Rich et al., 2008b; Schenkel et al., 2007, 2012). Cognitive and affective systems work in tandem, and the successful interaction between these systems is paramount for adaptive behavior (Passarotti et al., 2011; Pavuluri et al., 2010b). The ability to attend to, store, and process information in short-term memory is essential for successful day-to-day activities. Adaptive behavior also requires the ability to accurately process and respond to emotional cues. Given the rich interaction of these systems, we sought to investigate affect identification and working memory for emotional faces in youth with BD type I (BD I) and type II (BD II) and matched healthy control (HC) subjects. Consistent with past work, we hypothesized that BD youth would perform significantly more poorly compared to healthy subjects when identifying both happy and angry emotional expressions. In addition, we hypothesized that compared to healthy subjects, BD youth would show difficulty attending to and recalling positive and negative emotional facial stimuli, and that these deficits would be most pronounced with negative stimuli. Given the severity of manic symptoms in BD I versus BD II patients, we also hypothesized that youth with BD I would show the most impaired performance on the emotion processing and working memory tasks.