Objective Abnormalities in the morphology and function of two gray matter structures central to emotional processing, the perigenual anterior cingulate cortex (pACC) and amygdala, have consistently been reported in bipolar disorder (BD). Evidence implicates abnormalities in their connectivity in BD. This study investigates the potential disruptions in pACC-amygdala functional connectivity and associated abnormalities in white matter that provides structural connections between the two brain regions, in BD. Methods Thirty-three individuals with BD and 31 healthy comparison participants (HC) participated in a scanning session during which functional magnetic resonance imaging (fMRI) during processing of face stimuli and diffusion tensor imaging (DTI) were performed. The strength of pACC-amygdala functional connections was compared between BD and HC groups, and associations between these functional connectivity measures from the fMRI scans and regional fractional anisotropy (FA) from the DTI scans were assessed. Results Functional connectivity was decreased between the pACC and amygdala in the BD group, compared to HC group, during the processing of fearful and happy faces (p<0.005). Moreover, a significant positive association between pACC-amygdala functional coupling and FA in ventrofrontal white matter including the region of the uncinate fasciculus was identified (p<0.005). Conclusion This study provides evidence for abnormalities in pACC-amygdala functional connectivity during emotional processing in BD. The significant association between pACC-amygdala functional connectivity and the structural integrity of white matter that contains pACC-amygdala connections suggest that disruptions in white matter connectivity may contribute to disturbances in the coordinated responses of the pACC and amygdala during emotional processing in BD.

Trait abnormalities in bipolar disorder (BD) within ventral prefrontal cortex (vPFC) and amygdala suggest dysfunction in their connectivity. This study employed low frequency resting state functional magnetic resonance imaging (LFRS-fMRI) to analyze functional connectivity between ventral prefrontal cortex (vPFC) and amygdala in BD. LFRS-fMRI identified a negative correlation in vPFC-amygdala activity, and the magnitude of this correlation was greater in healthy participants than in subjects with BD. Additionally, whole brain analysis revealed higher correlations between left and right vPFC in BD, as well as with ventral striatum.

Objective-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 (MRI) scans were obtained during the same neuroimaging session in order to examine amygdala structure-function relationships 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.Method-51 adolescents [21 with BDI, 30 healthy comparison (HC) adolescents, ages 10-18] underwent structural and functional MRI 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).Results-Adolescents with BD displayed 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=−.54, p=.029).Conclusions-Decreased volume and increased response to emotional stimuli in amygdala in BD adolescents 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 relationship 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.

Background Convergent evidence implicates white matter abnormalities in bipolar disorder. The cingulum is an important candidate structure for study in bipolar disorder as it provides substantial white matter connections within the corticolimbic neural system that subserves emotional regulation involved in the disorder. Aims To test the hypothesis that bipolar disorder is associated with abnormal white matter integrity in the cingulum. Method Fractional anisotropy in the anterior and posterior cingulum was compared between 42 participants with bipolar disorder and 42 healthy participants using diffusion tensor imaging. Results Fractional anisotropy was significantly decreased in the anterior cingulum in the bipolar disorder group compared with the healthy group (P=0.003); however, fractional anisotropy in the posterior cingulum did not differ significantly between groups. Conclusions Our findings demonstrate abnormalities in the structural integrity of the anterior cingulum in bipolar disorder. They extend evidence that supports involvement of the neural system comprising the anterior cingulate cortex and its corticolimbic gray matter connection sites in bipolar disorder to implicate abnormalities in the white matter connections within the system provided by the cingulum. Declaration of interest H.P.B. has been consultant to Pfizer Inc. and has received honoraria from Eli Lilly and Abbott Laboratories.

Bipolar disorder (BD) is associated with abnormalities of the ventral anterior cingulate cortex (vACC) and its connection sites, including the amygdala, which are key components of a corticolimbic neural system that subserves emotional regulation. Decreased functional connectivity from the vACC to the amygdala in healthy individuals is associated with the short "s" allele-as opposed to the long "l" allele-of a well-known serotonin transporter promoter polymorphism (5-HTTLPR, locus SLC6A4), as are features of BD. This study tests the hypothesis that the s allele influences dysfunction in the vACC-amygdala neural system in BD. Thirty euthymic individuals with BD (20 s carriers, 10 ll) and 48 healthy comparison (HC) participants (34 s, 14 ll) participated in an event-related functional magnetic resonance imaging scan while processing fearful, happy, or neutral faces. During fear and happy face processing, vACC activation was significantly lower in the BD compared to the HC group, and in s carriers compared to ll individuals within both the HC and BD groups, such that BD s carriers exhibited the greatest magnitude of vACC dysfunction. No significant differences were detected in amygdala activation. The findings suggest that the 5-HTTLPR s allele may contribute to a traitrelated, genetically-derived, neurobiological subgroup within BD characterized by prominent vACC dysfunction. Future treatment may be optimized for this BD subgroup by targeting the serotonergic system and the vACC.