Relation Between Amygdala Structure and Function in Adolescents With Bipolar Disorder

Department of Psychiatry, Yale School of Medicine, 300 George Street, Suite 901, New Haven, CT 06511, USA.
Journal of the American Academy of Child and Adolescent Psychiatry (Impact Factor: 7.26). 07/2009; 48(6):636-42. DOI: 10.1097/CHI.0b013e31819f6fbc
Source: PubMed


Previous study supports the presence of reduced volume and elevated response to emotional stimuli in amygdala in adolescents with bipolar disorder (BD). In the present study, structural and functional magnetic resonance imaging scans were obtained during the same neuroimaging session to examine amygdala structure-function relations in adolescents with BD. We hypothesized that amygdala volume would be inversely associated with amygdala response to emotional stimuli, such that BD participants with the smallest amygdala volumes would exhibit the highest amygdala response.
Fifty-one adolescents (21 with BD I and 30 control adolescents, ages 10-18 years) underwent structural and functional magnetic resonance imaging scans. Amygdala volume (n = 49) and signal change (n = 44) during emotional face processing were compared between groups, and structure-function correlations were examined within the BD group (n = 16).
Adolescents with BD showed decreased amygdala volume (p =.009) and increased amygdala response to emotional faces (p =.043). There was no significant interaction between diagnosis and emotion type. A significant inverse association between amygdala volume and activation during emotional face processing was observed (r = -0.54, p =.029).
Decreased volume and increased response to emotional stimuli in the amygdala in adolescents with BD are consistent with previous reports. This study represents the first report, to our knowledge, of the two findings in the same adolescent BD sample and supports an amygdala structure-function relation characterized by an inverse association between volume and response to emotional stimuli. This preliminary finding requires replication and suggests a possible pathophysiological link between abnormalities in amygdala structure and response to emotional stimuli in BD.

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Available from: Robert Todd Constable, Jun 11, 2015
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    • "The amygdala is a region of specialized nuclei in the medial temporal lobe, and is a critical component of the neurocircuitry that regulates emotional valence. Both a significantly reduced amygdala volume and a significantly increased amygdala response to emotional stimuli have been reported in a sample of adolescents with BD relative to healthy controls (Kalmar et al., 2009).Thus, the presence of structural abnormalities of the amygdala during childhood and adolescence in those with BD provides further evidence that the amygdala might play a crucial role early in the disorder. Most of the studies in adults with BD have shown amygdala volume increases, whereas studies in children and adolescents Contents lists available at ScienceDirect journal homepage: "
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    ABSTRACT: The amygdala is repeatedly implicated as a critical component of the neurocircuitry regulating emotional valence. Studies have frequently reported reduced amygdala volumes in children and adolescents with bipolar disorder (BD). Brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) play critical roles in growth, differentiation, maintenance, and synaptic plasticity of neuronal systems in adolescent brain development. The aim of the present study was to assess amygdala volumesand its correlation with serum levels of NGF and BDNF in euthymic adolescents with BD and healthy controls. Using structural MRI, we compared the amygdala volumes of 30 euthymic subjects with BD with 23 healthy control subjects aged between 13 and 19 years during a naturalistic clinical follow-up. The boundaries of the amygdala were outlined manually. Serum BDNF and NGF levels were measured using sandwich-ELISA and compared between the study groups. The right or left amygdala volume did not differ between the study groups.The right and left amygdala volumes were highly correlated with levels of BDNF in the combined BD group and the valproate-treated group.Both R and L amygdala volumes were correlated with BDNF levels in healthy controls. The left amygdala volumes were correlated with BDNF levels in the lithium-treated group. This cross-sectional study cannot inform longitudinal changes in brain structure. Further studies with larger sample sizes are needed to improve reliability. The correlations between amygdala volumes and BDNF levels might be an early neuromarker for diagnosis and/or treatment response in adolescents with BD. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Apr 2015 · Journal of Affective Disorders
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    • "We expected, but did not observe, three additional findings in the amygdala: (1) that the implicit task (nose width), like the explicit and passive viewing tasks, would elicit amygdala hyperactivity; (2) that during implicit processing amygdala dysfunction would be more marked in pediatric versus adult BD; and (3) that BD would show amygdala hyperactivity to happy faces. While multiple reasons, including Type II error, may have contributed to not observing amygdala hyperactivity during implicit processing, one potential explanation is that our implicit task involves nose width rating rather than the more commonly used gender labeling (Lawrence et al. 2004; Kalmar et al. 2009; Surguladze et al. 2010; Ladouceur et al. 2011; Kim et al. 2012). We used nose width, as opposed to gender labeling (a binary option), to parallel the 1–5 ratings in the explicit rating conditions. "
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    ABSTRACT: Research in bipolar disorder (BD) implicates fronto-limbic-striatal dysfunction during face emotion processing but it is unknown how such dysfunction varies by task demands, face emotion and patient age. Method During functional magnetic resonance imaging (fMRI), 181 participants, including 62 BD (36 children and 26 adults) and 119 healthy comparison (HC) subjects (57 children and 62 adults), engaged in constrained and unconstrained processing of emotional (angry, fearful, happy) and non-emotional (neutral) faces. During constrained processing, subjects answered questions focusing their attention on the face; this was processed either implicitly (nose width rating) or explicitly (hostility; subjective fear ratings). Unconstrained processing consisted of passive viewing. Pediatric BD rated neutral faces as more hostile than did other groups. In BD patients, family-wise error (FWE)-corrected region of interest (ROI) analyses revealed dysfunction in the amygdala, inferior frontal gyrus (IFG), anterior cingulate cortex (ACC) and putamen. Patients with BD showed amygdala hyperactivation during explicit processing (hostility ratings) of fearful faces and passive viewing of angry and neutral faces but IFG hypoactivation during implicit processing of neutral and happy faces. In the ACC and striatum, the direction of dysfunction varied by task demand: BD demonstrated hyperactivation during unconstrained processing of angry or neutral faces but hypoactivation during constrained processing (implicit or explicit) of angry, neutral or happy faces. Findings suggest amygdala hyperactivation in BD while processing negatively valenced and neutral faces, regardless of attentional condition, and BD IFG hypoactivation during implicit processing. In the cognitive control circuit involving the ACC and putamen, BD neural dysfunction was sensitive to task demands.
    Full-text · Article · Aug 2013 · Psychological Medicine
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    • "In recent years, a debate has arisen criticizing a potential overdiagnosis of bipolar disorders in children and adolescents with chronic irritability (Blader and Carlson 2007; Moreno et al. 2007; Carlson et al. 2009; Leibenluft 2011). However, on the other hand, our results could also be related to the loss of behavioral control that is associated with immature and hyperactive emotional processes underlying bipolar disorder (Kalmar et al. 2009). Studies in adults have frequently failed to relate inpatient aggression to psychiatric diagnoses and among those that have found diagnostic differences between aggressive and nonaggressive inpatients, schizophrenia has been associated most frequently with aggressive inpatient incidents (Bowers et al. 2011). "
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    ABSTRACT: Background: Inpatient aggression is a serious challenge in pediatric psychiatry. Methods: A chart review study in adolescent psychiatric inpatients consecutively admitted over 24 months was conducted, to describe aggressive events requiring an intervention (AERI) and to characterize their management. AERIs were identified based on specific institutional event forms and/or documentation of as-needed (STAT/PRN) medication administration for aggression, both recorded by nursing staff. Results: Among 408 adolescent inpatients (age: 15.2±1.6 years, 43.9% male), 1349 AERIs were recorded, with ≥1 AERI occurring in 28.4% (n=116; AERI+). However, the frequency of AERIs was highly skewed (median 4, range: 1-258). In a logistical regression model, the primary diagnosis at discharge of disruptive behavior disorders and bipolar disorders, history of previous inpatient treatment, length of hospitalization, and absence of a specific precipitant prior to admission were significantly associated with AERIs (R(2)=0.32; p<0.0001). The first line treatment of patients with AERIs (AERI+) was pharmacological in nature (95.6%). Seclusion or restraint (SRU) was used at least once in 59.4% of the AERI+ subgroup (i.e., in 16.9% of all patients; median within-group SRU frequency: 3). Treatment and discharge characteristics indicated a poorer prognosis in the AERI+ (discharge to residential care AERI+: 22.8%, AERI-: 5.6%, p<0.001) and a greater need for psychotropic polypharmacy (median number of psychotropic medications AERI+: 2; AERI-: 1, p<0.001). Conclusions: Despite high rates of pharmacological interventions, SRU continue to be used in adolescent inpatient care. As both of these approaches lack a clear evidence base, and as adolescents with clinically significant inpatient aggression have increased illness acuity/severity and service needs, structured research into the most appropriate inpatient aggression management is sorely needed.
    Full-text · Article · May 2013 · Journal of child and adolescent psychopharmacology
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