Reflecting a paradigm shift in clinical neuroscience, many chronic psychiatric illnesses are now hypothesized to result from perturbed neural development. However, most work in this area focuses on schizophrenia. Here, we extend this paradigm to pediatric bipolar disorder (BD), thus demonstrating traction in the developmental psychobiology perspective. To study amygdala dysfunction, we examined neural mechanisms mediating face processing in 22 youths (mean age 14.21 ؎ 3.11 yr) with BD and 21 controls of comparable age, gender, and IQ. Event-related functional MRI compared neural activation when attention was directed to emotional aspects of faces (hostility, subjects' fearfulness) vs. nonemotional aspects (nose width). Compared with controls, patients perceived greater hostility in neutral faces and reported more fear when viewing them. Also, compared with controls, patients had greater activation in the left amygdala, accumbens, putamen, and ventral prefrontal cortex when rating face hostility, and greater activation in the left amygdala and bilateral accumbens when rating their fear of the face. There were no between-group behavioral or neural differences in the nonemotional conditions. Results implicate deficient emotion-attention interactions in the pathophysiology of BD in youth and suggest that developmental psychobiology approaches to chronic mental illness have broad applicability.amygdala ͉ faces ͉ functional MRI R ecently, psychology and psychiatry have witnessed a major paradigm shift: virtually all chronic adult mental illnesses are now thought to result from long-term perturbations in neural development. Two lines of research support this perspective: family-based͞longitudinal studies and neurobiological studies. Family-based and longitudinal studies implicate developmental perturbations in a range of conditions, including behavior disorders, substance abuse, mood disorders, and psychoses (1-3). However, virtually all research on developmental neurobiology focuses on schizophrenia, where data implicate a neural circuit connecting the dorsolateral prefrontal cortex, striatum, and hippocampus (4, 5). Neurocognitive correlates of schizophrenia, such as deficient working memory, are thought to result from dysfunction in this circuit (6). An important next step is the extension of the developmental neurobiological approach to other mental illnesses and other neural systems associated with information processing and emotion regulation.For several reasons, bipolar disorder (BD) is an ideal illness in which to expand the emerging developmental paradigm by conducting neurobiologically oriented developmental research. BD causes marked disruption in social, academic, and family function. Major questions persist concerning the boundaries of the condition in children; neurobiological data might ultimately resolve them. Most importantly, research in adult patients and animals implicates a circuit encompassing the amygdala, striatum, and ventral prefrontal cortex (VPFC) in the pathophysiology of BD (7). This circu...

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Objective To compare the characteristics of US adults by frequency of emergency department (ED) utilisation, specifically the prevalence of chronic diseases and outpatient primary care and mental health utilisation. Methods We analysed 157 818 adult participants of the 2004-2009 US National Health Interview Survey, an annual nationally representative sample. We defined ED utilisation during the past 12 months as non-users (0 ED visits), infrequent users (1-3 visits), frequent users (4-9 visits) and super-frequent users (≥10 visits). We compared demographic data, socioeconomic status, chronic diseases and access to care between these ED utilisation groups using multivariable logistic regression. Results Overall, super-frequent use was reported by 0.4% of US adults, frequent use by 2% and infrequent ED use by 19%. Patients reporting ≥4 ED visits were more likely to have Medicaid insurance (OR 1.57; 95% CI 1.34 to 1.85 vs private); fair or poor self-reported health (OR 2.98; 95% CI 2.57 to 3.46 vs excellent-very good); and chronic diseases such as coronary artery disease (OR 1.61; 95% CI 1.40 to 1.86), stroke (OR 1.58; 95% CI 1.36 to 1.83) or asthma (OR 1.64; 95% CI 1.46 to 1.85). While patients reporting the ED as their usual source of sick care were more likely to have ≥4 ED visits (OR 7.09; 95% CI 5.61 to 8.95 vs outpatient clinic as source), ≥10 outpatient visits in the past 12 months was also associated with frequent ED use (OR 11.4; 95% CI 9.09 to 14.2 vs no outpatient visits). Conclusions Frequent ED users had a large burden of chronic diseases that also required high outpatient resources. Interventions designed to divert frequent ED users should focus on chronic disease management and access to outpatient services, particularly for Medicaid beneficiaries and other high risk subpopulations.

Dickstein, Daniel P.; Tone, Erin; and Pine, Daniel S., "Neural circuitry engaged during unsuccessful motor inhibition in pediatric bipolar disorder" (2007 Objective: Deficits in motor inhibition may contribute to impulsivity and irritability in children with bipolar disorder (BPD). Therefore, studies of the neural circuitry engaged during failed motor inhibition in pediatric BPD may contribute to our understanding of the pathophysiology of the illness. We tested the hypothesis that children with BPD and controls would differ in ventral prefrontal cortex (vPFC), striatal, and anterior cingulate activation during unsuccessful motor inhibition. We also compared activation in medicated vs.unmedicated children with BPD, and in children with BPD and ADHD (BPD+ADHD) vs.those with BPD but without ADHD (BPD-ADHD).Method: Event-related fMRI study comparing neural activation in children with BPD and controls while they performed a motor inhibition task. The sample included 26 children with BPD (13 unmedicated, 15 with ADHD) and 17 age, gender, and IQ matched controls. Results:On failed inhibitory trials, controls showed greater bilateral striatal and right vPFC activation than did patients. While our findings were somewhat more prominent in unmedicated than medicated, patients, and in BPD+ADHD than BPD-ADHD, the findings did not differ significantly (?) among these subgroups of children with BPD.

Objective-Data documenting the functional impairment associated with the diagnosis of bipolar disorder (BD) in children and adolescents highlight the need for greater understanding of its pathophysiology. Toward that end, we demonstrated previously that BD youth have behavioral deficits on reversal learning tasks. On such tasks, participants must first acquire a stimulus/ response relationship through trial-and-error learning, and then discern when the stimulus/reward relationship reverses. Here, we use event-related functional magnetic resonance imaging (fMRI) to elucidate neural correlates of reversal learning deficits in euthymic BD youth compared to typically developing controls.Method-We compared euthymic pediatric BD participants (n = 16) versus age-, sex-, and IQmatched controls (n = 16). Our main outcome measure was blood oxygen level-dependent (BOLD) signal measured with fMRI during an event-related probabilistic reversal task.Results-Pediatric BD participants had significantly greater neural activity than controls in fronto-parietal regions during the reversal phase, particularly in response to punished reversal errors (p < 0.05 corrected for multiple comparisons).Conclusions-Our current study suggests that during reversal learning, BD youths inefficiently recruit regions associated with processing response conflict and implementing alternative responses, including subdivisions of the frontal cortex and the parietal cortex. Such deficits are present in euthymic BD youth. Further work is necessary to evaluate the specificity of such alterations. Keywordsadolescent; bipolar disorder; child; magnetic resonance imaging; reversal learning Pediatric bipolar disorder (BD) has become a growing health concern (1-4). Greater neurobiological understanding could aid the diagnostic process and the development of new treatments. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptFunctional impairments seen in pediatric BD include dysfunction in cognitive flexibility, defined as the ability to adapt one's thinking and behavior in response to changing environmental conditions, such as rewards (5,6). The ability to alter one's response to changing reinforcement contingencies is one aspect of cognitive flexibility that can be measured in the laboratory using reversal learning tasks. In such tasks, two stimuli, A and B, are presented, and participants must use trial-and-error learning to determine that stimulus A but not B is rewarded. Then, without warning, the stimulus/response relationship is reversed, so that participants must learn that now B but not A is rewarded (7).From an affective neuroscience perspective, many clinical symptoms of BD suggest impaired cognitive flexibility and adaptation to changing stimulus-response-reward contingencies, as occurs on reversal learning tasks. For example, mania can be viewed as a hyperhedonic state characterized by excessive involvement in pleasurable activities with high potential for painful consequences and abnormally inflated self-esteem or gr...

These results indicate that functional deficits within the left DLPFC may mediate deficits in response flexibility in pediatric BD. This deficit may extend beyond the realm of motor control and also affect emotion regulation.

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