Limbic hyperactivation during processing of neutral facial expressions in children with bipolar disorder

Abstract

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...

Increased white matter connectivity in euthymic bipolar patients: diffusion tensor tractography between the subgenual cingulate and the amygdalo-hippocampal complex

“…2,50 Consistently with the leftward asymmetry of our tractography result, an increased activity in ventral-limbic brain structures, such as the amygdala and the ventrolateral prefrontal cortex has often been detected in the left hemisphere in bipolars. 2,50,51 Equally, structural imaging studies in adult BP have observed predominantly left-sided modifications of these two structures. 3,52 In this regard, results from lesion studies have revealed secondary mania symptoms after lesions of right hemisphere regions connected to limbic areas 53,54 and it has been proposed that subcortical and cortical right hemisphere lesions might be implicated in the pathophysiology of bipolar affective disorder and unipolar mania.…”

Prevention of bipolar disorder in at-risk children: Theoretical assumptions and empirical foundations

“…Whereas studies in adults with BD have reported increased, decreased, or unchanged amygdalar volume, studies in pediatric BD have been more consistent in finding relatively decreased amygdalar volume . This decreased volume may mean a heightened activity in the amygdala in response to affective stress, as demonstrated in functional imaging studies in healthy adults (Yurgelon-Todd et al, 2004) as well as children with BD (Rich et al, 2006). Theoretically, such heightened activation without compensatory prefrontal regulation could lead to a heightened experience of mood states (euphoria or sadness), that could then continue to a fully syndromal mood episode.…”

A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder

“…BD children and adolescents demonstrate deficits in executive function 206 and emotion processing, 207 and impaired social cognition and response flexibility. 208 As with adult BD, it has been proposed, therefore, that pediatric BD may be associated with functional abnormalities in neural systems supporting emotion regulation processes.…”