Alessandra M. Passarotti

Background: Recent research evidence suggests that executive function (EF) is impaired in both pediatric bipolar disorder (PBD) and attention deficit-hyperactivity disorder (ADHD), although the underlying cognitive mechanisms are still unclear. In this study we examined EF, including cognitive and emotional control, in three pediatric groups with overlapping symptoms. Methods: Sixteen children and adolescents with PBD, 17 children and adolescents with ADHD, Type Combined, and 13 children and adolescents with PBD and comorbid ADHD (PBD+ADHD) (mean age=12.70, SD=2.21) were assessed using the Behavioral Rating Inventory of Executive Function - Parental Report (BRIEF-PR), clinical scales and neuropsychological tests of attention, working memory and executive function. Results: All groups showed impairment on the Trails A and B tests. However, there were no significant group differences. On the BRIEF-PR while all three groups were impaired in General Executive Functioning and Metacognition only the two PBD groups revealed more extensive EF dysfunction, in both cognitive and emotional control domains, relative to the ADHD group. Conversely, the ADHD group exhibited selective deficits in cognitive domains such as working memory, planning/organization, monitoring, and metacognition. The two PBD groups showed greater impairment than the ADHD group in the domains of Inhibition, Shifting, Monitoring and Emotional Control. Furthermore, results from regression analyses suggest cognitive predictors of EF impairment in ADHD and mood predictors for inhibition in PBD. Conclusions: The current results contribute new knowledge on domain-specific similarities and differences in executive dysfunction between PBD, ADHD, and the comorbid phenotype, which may inform the diagnostic process and cognitive intervention.

This study examined whether processing of emotional words impairs cognitive performance in acutely ill patients with pediatric bipolar disorder (PBD), with or without comorbid attention-deficit hyperactivity disorder (ADHD), relative to healthy controls (HC). Forty youths with PBD without ADHD, 20 youths with PBD and ADHD, and 29 HC (mean age = 12.97 ± 3.13) performed a Synonym Matching task, where they decided which of two probe words was the synonym of a target word. The three words presented on each trial all had the same emotional valence, which could be negative, positive, or neutral. Relative to HC both PBD groups exhibited worse accuracy for emotional words relative to neutral ones. This effect was greater with negative words and observed regardless of whether PBD patients had comorbid ADHD. In the PBD group without ADHD, manic symptoms correlated negatively with accuracy for negative words, and positively with reaction time (RT) for all word types. Our findings suggest a greater disruptive effect of emotional valence in both PBD groups relative to HC, reflecting the adverse effect of altered emotion processing on cognitive function in PBD. Future studies including an ADHD group will help clarify how ADHD symptoms may affect emotional interference independently of PBD. (JINS, 2013, 19, 1–12)

This study examined whether adolescents with pediatric bipolar disorder (PBD) have abnormal regional functional connectivity in distributed brain networks during an affective working memory task. Adolescents with PBD (n=41) and healthy controls (HC; n=16) performed a two-back functional magnetic resonance imaging working memory task with blocks of either angry or neutral faces. Independent component analysis methodology identified two temporally independent and functionally connected brain networks that showed differential functional connectivity in PBD and HC. Within a network for “affect evaluation and regulation,” PBD showed decreased functional connectivity relative to HC in regions involved in emotion processing such as the right amygdala, and in emotion regulation regions such as the right ventrolateral prefrontal cortex (VLPFC), while functional connectivity was increased in emotion evaluation regions such as the bilateral medial PFC. Furthermore, in an “Affective Working Memory Network,” PBD exhibited greater connectivity relative to HC in left dorsolateral PFC (DLPFC), caudate, and right VLPFC; and simultaneously reduced connectivity in emotion processing regions, such as the right amygdala, bilateral temporal regions, and the junction of DLPFC/VLPFC, which interfaces affective and cognitive processes. Dysfunction in network engagement in PBD patients illustrates that they are expending greater effort in face emotion evaluation, while being less able to engage affect regulation regions.

(2011). Brain functional domains inform therapeutic interventions in attention-deficit/hyperactivity disorder and pediatric bipolar disorder. Expert Review of Neurotherapeutics: Vol. 11, No. 6, pp. 897-914.

Rationale Neural deficits at the interface of affect and cognition may improve with pharmacotherapy in pediatric bipolar disorder (PBD). Objectives We examined lamotrigine treatment impact on the neural interface of working memory and affect in PBD. Methods Un-medicated, acutely ill, patients with mania and hypomania (n = 17), and healthy controls (HC; n = 13; mean age = 13.36 ± 2.55) performed an affective two-back functional magnetic resonance imaging task with blocks of angry vs neutral faces (i.e., angry face condition) or happy vs neutral faces (i.e., happy face condition) before treatment and at follow-up, after 8-week treatment with second-generation antipsychotics followed by 6 weeks of lamotrigine monotherapy. Results At baseline, for the angry face condition, PBD, relative to HC, showed reduced activation in the left ventrolateral prefrontal cortex (VLPFC) and right caudate; for the happy face condition, PBD showed increased activation in bilateral PFC and right amygdala and middle temporal gyrus. Post-treatment, PBD showed greater activation in right amygdala relative to HC for both conditions. Patients, relative to HC, exhibited greater changes over time in the right VLPFC and amygdala, left subgenual anterior cingulate cortex and left caudate for the angry face condition, and in right middle temporal gyrus for the happy face condition. Conclusions Pharmacotherapy resulted in symptom improvement and normalization of higher cortical emotional and cognitive regions in patients relative to HC, suggesting that the VLPFC dysfunction may be state-specific in PBD. Amygdala was overactive in PBD, relative to HC, regardless of reduction in manic symptoms, and may be a trait marker of PBD.

Our knowledge on the development of the affective and cognitive circuitries that underlie affect regulation is still limited. This functional magnetic resonance imaging (fMRI) study examined whether there is more efficient prefrontal modulation of affective circuits with development. Ten adolescents (mean age 14 ± 2 years) and 10 adults (mean age 30 ± 6 years) underwent two scanning conditions that required different levels of cognitive control over face emotion processing. A ‘directed’ emotion processing condition required judgment of facial expressions. An ‘incidental’ emotion processing condition required an age judgment. For the incidental emotion processing condition, adolescents, compared with adults, showed less activation in right ventrolateral prefrontal cortex (VLPFC) and greater activation in paralimbic regions, suggesting greater emotional reactivity and immature prefrontal circuitries for affect regulation. For the directed emotion processing condition, adolescents, compared with adults, showed decreased recruitment of both the dorsal and pregenual right anterior cingulate cortex (ACC), suggesting immature modulatory functions of the ACC during directed face emotion processing. These results indicate that the neural circuitries for affect regulation are still developing in adolescence and have not yet reached the adult level.

This fMRI study investigates the neural bases of cognitive control of emotion processing in pediatric bipolar disorder (PBD) and attention deficit hyperactivity disorder (ADHD). Seventeen un-medicated PBD patients, 15 un-medicated ADHD patients, and 14 healthy controls (HC) (mean age = 13.78 ± 2.47) performed an emotional valence Stroop Task, requiring them to match the color of an emotionally valenced word to the color of either of two adjacent circles. Both patient groups responded significantly slower than HC, but there were no group differences in accuracy. A voxel-wise analysis of variance on brain activation revealed a significant interaction of group by word valence [F(2,41) = 4.44; p = .02]. Similar group differences were found for negative and positive words. For negative versus neutral words, both patient groups exhibited greater activation in dorsolateral prefrontal cortex (DLPFC) and parietal cortex relative to HC. The PBD group exhibited greater activation in ventrolateral prefrontal cortex (VLPFC) and anterior cingulate cortex (ACC) relative to HC. The ADHD group exhibited decreased VLPFC activation relative to HC and the PBD group. During cognitive control of emotion processing, PBD patients deployed the VLPFC to a greater extent than HC. The ADHD patients showed decreased VLPFC engagement relative to both HC and PBD patients. (JINS, 2010, 16, 106–117.)