No abstract

The absence of differences in the deficits of neurocognitive profiles between acutely ill unmedicated patients and euthymic medicated patients suggests that these impairments are trait-like characteristics of pediatric bipolar disorder. The cognitive deficits found in individuals with pediatric bipolar disorder suggest significant involvement of frontal lobe systems supporting working memory and mesial temporal lobe systems supporting verbal memory, regardless of ADHD comorbidity.

Objective-To investigate microstructure of white matter fiber tracts in pediatric bipolar disorder (PBD) and attention deficit hyperactivity disorder (ADHD).Methods-A diffusion tensor imaging (DTI) study was conducted at 3 Tesla on age and IQ-matched children and adolescents with PBD (n=13), ADHD (n=13), and healthy controls (HC) (n=15). Three DTI parameters, fractional anisotropy (FA), apparent diffusion coefficient (ADC), and regional fiber coherence index (r-FCI), were examined in eight fiber tracts: Anterior corona radiata (ACR); anterior limb of the internal capsule (ALIC); superior region of the internal capsule (SRI); posterior limb of the internal capsule (PLIC); superior longitudinal fasciculus (SLF); inferior longitudinal fasciculus (ILF); cingulum (CG); splenium (SP).Results-Significantly lower FA was observed in ACR in both PBD and ADHD relative to HC. In addition, FA and r-FCI values were significantly lower in ADHD relative to PBD and HC in both the ALIC and the SRI. Further, ADC was significantly greater in ADHD relative to both the PBD and HC in ACR, ALIC, PLIC, SRI, CG, ILF, and SLF. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusions-Decreased FA in ACR implies an impaired fiber density or reduced myelination in both PBD and ADHD in this prefrontal tract. These abnormalities, together with the reduced fiber coherence, extended to cortico-bulbar tracts in ADHD. Increased ADC across multiple white matter tracts in ADHD indicates extensive cellular abnormalities with less diffusion restriction in ADHD relative to PBD. NIH Public Access

The pathophysiology of pediatric bipolar disorder (PBD) impacts both affective and cognitive brain systems. Understanding disturbances in the neural circuits subserving these abilities is critical for characterizing developmental aberrations associated with the disorder and developing improved treatments. Our objective is to use functional neuroimaging with pediatric bipolar disorder patients employing a task that probes the functional integrity of attentional control and affect processing. Ten euthymic unmedicated pediatric bipolar patients and healthy controls matched for age, sex, race, socioeconomic status, and IQ were scanned using functional magnetic resonance imaging. In a pediatric color word matching paradigm, subjects were asked to match the color of a word with one of two colored circles below. Words had a positive, negative or neutral emotional valence, and were presented in 30-s blocks. In the negative affect condition, relative to the neutral condition, patients with bipolar disorder demonstrated greater activation of bilateral pregenual anterior cingulate cortex and left amygdala, and less activation in right rostral ventrolateral prefrontal cortex (PFC) and dorsolateral PFC at the junction of the middle frontal and inferior frontal gyri. In the positive affect condition, there was no reduced activation of PFC or increased amygdala activation. The pattern of reduced activation of ventrolateral PFC and greater amygdala activation in bipolar children in response to negative stimuli suggests both disinhibition of emotional reactivity in the limbic system and reduced function in PFC systems that regulate those responses. Higher cortical cognitive areas such as the dorsolateral PFC may also be adversely affected by exaggerated emotional responsivity to negative emotions. This pattern of functional alteration in affective and cognitive circuitry may contribute to the reduced capacity for affect regulation and behavioral self-control in pediatric bipolar disorder.

Objective To use functional neuroimaging to probe the affective circuitry dysfunctions underlying disturbances in emotion processing and emotional reactivity in pediatric bipolar disorder (PBD). Method Equal numbers of controls (HC) and unmedicated patients with euthymia and PBD were matched for age, sex, race, socioeconomic status, and IQ (n = 10 per group; mean age 14.2 years [SD 2.0 years]). The task consisted of a “directed” emotion processing condition where subjects judged whether emotion in facial expression was positive or negative and an “incidental” condition where subjects judged whether faces expressing similar affect were older or younger than 35 years. Results Relative to the directed condition, the incidental condition elicited greater activation in the right amygdala and the right insula, the left middle frontal gyrus, and the left posterior cingulate cortex in patients with PBD, in contrast to the HC that showed greater activation in the right superior frontal gyrus. In both incidental and directed conditions, relative to visual fixation, patients with PBD showed less activation in the right prefrontal cortex (superior, middle, and inferior frontal gyri) and the pregenual anterior cingulate cortex and greater activation in the posterior visual and face-processing regions (i.e., right precuneus/cuneus, fusiform gyrus). Conclusions Increased amygdala activation observed in patients with PBD elicited by incidental emotional processing relative to directed emotional processing may indicate more intense automatic emotional reactivity. Furthermore, the right prefrontal systems that are believed to modulate affect seem to be less engaged in patients with PBD regardless of whether the emotion processing is incidental or directed, which may signify reduced top-down control of emotional reactivity in PBD.