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.

Childhood maltreatment (CM) has been associated with diminished executive functioning in children and adults; however, there is a relative paucity of study of executive function in adolescents exposed to CM. Yet, executive dysfunction in adolescence may have important adverse consequences including increased vulnerability to risky behaviors and impaired school functioning. This study investigates the relationship between self-reported CM and an executive function, cognitive flexibility, in adolescents without identified psychiatric disorders. Effects of physical and emotional, abuse and neglect, maltreatment subtypes were explored. Thirty adolescents ages 12–17 years, 50% females, completed the retrospective self-report Childhood Trauma Questionnaire (CTQ) and were administered the Wisconsin Card Sorting Test (WCST). Correlational analyses assessed the relationship between WCST perseverative error scores norm-referenced for age and education with CTQ total scores. The relationship with non-perseverative errors, as well as with physical and emotional abuse and neglect CM subscores, were explored. Total CTQ scores showed significant associations with perseverative errors on the WCST, but not with non-perseverative errors. Significant associations with perseverative errors were seen for physical abuse and physical neglect among the CTQ subscales. The results suggest both physical abuse and physical neglect are associated with diminished cognitive flexibility in adolescents. These effects were detected in adolescents without identified psychiatric diagnoses suggesting the importance of considering executive dysfunction in adolescents exposed to CM who may not meet diagnostic criteria for an Axis I disorder and that tests of perseverative errors, such as those of the WCST, may be sensitive indicators of this dysfunction.

Tang, Y.; Kong, L.; Womer, F.; Jiang, W.; Cao, Y.; Ren, L.; Wang, J.; Fan, G.; Blumberg, H. P.; Xu, K.; and Wang, F., ,"Decreased functional connectivity between the amygdala and the left ventral prefrontal cortex in treatment-naive patients with major depressive disorder: A resting-state functional magnetic resonance imaging study. " Psychological Medicine.43,9. 1921-1927. (2012 Background. Convergent studies provide support for abnormalities in the structure and functioning of the prefrontal cortex (PFC) and the amygdala, the key components of the neural system that subserves emotional processing in major depressive disorder (MDD). We used resting-state functional magnetic resonance imaging (fMRI) to examine potential amygdala-PFC functional connectivity abnormalities in treatment-naive subjects with MDD.Methods. Resting-state fMRI data were acquired from 28 individuals with MDD and 30 healthy control (HC) subjects. Amygdala-PFC functional connectivity was compared between the MDD and HC groups.Results. Decreased functional connectivity to the left ventral PFC (VPFC) from the left and right amygdala was observed in the MDD group, compared with the HC group (p<0.05, corrected).Conclusions. The treatment-naive subjects with MDD showed decreased functional connectivity from the amygdala to the VPFC, especially to the left VPFC. This suggests that these connections may play an important role in the neuropathophysiology of MDD at its onset.

Background:Insight into the neural mechanisms underlying the shared and disparate features of schizophrenia (SZ) and bipolar disorder (BD) is limited. The amygdala and prefrontal cortex (PFC) appear to have crucial roles in SZ and BD, yet abnormalities appear to manifest differently in the 2 disorders.Methods:Eighteen participants with SZ, 18 participants with BD, and 18 healthy controls (HC) underwent resting-state functional magnetic resonance imaging. Resting-state functional connectivity (rsFC) between the PFC and the amygdala divided into 3 subregions (the laterobasal, centromedial, and superficial amygdala) was examined using probabilistic anatomic maps. For each participant, rsFC maps of the 3 amygdala subregions were computed and compared across the 3 groups.Results:Compared with the HC group, we found significant differences in rsFC between the amygdala and PFC in the SZ and BD groups. In direct comparison between the SZ and BD groups, distinct patterns of rsFC between the amygdala and PFC were observed, particularly in the superficial amygdala. RsFC between the amygdala and the dorsal lateral PFC was significantly decreased in the SZ group, whereas rsFC between the amygdyala and the ventral PFC was significantly decreased in the BD group.Conclusions:These results strongly suggest dorsal vs ventral PFC differentiation in amygdala-PFC neural system abnormalities between SZ and BD. These regional differences in SZ and BD may give rise to the differences in clinical characteristics observed in SZ and BD, and may implicate potential avenues for differentiating the 2 disorders during early stages of illness.

There are limited resting-state functional magnetic resonance imaging (fMRI) studies in major depressive disorder (MDD). Of these studies, functional connectivity analyses are mostly used. However, a new method based on the magnitude of low frequency fluctuation (LFF) during restingstate fMRI may provide important insight into MDD. In this study, we examined the amplitude of LFF (ALFF) within the whole brain during resting-state fMRI in 30 treatment-na€ ıve MDD subjects and 30 healthy control (HC) subjects. When compared with HC, MDD subjects showed increased ALFF in the frontal cortex (including the bilateral ventral/dorsal anterior cingulate cortex, orbitofrontal cortex, premotor cortex, ventral prefrontal cortex, left dorsal lateral frontal cortex, left superior frontal cortex), basal ganglia (including the right putamen and left caudate nucleus), left insular cortex, right anterior entorhinal cortex and left inferior parietal cortex, together with decreased ALFF in the bilateral occipital cortex, cerebellum hemisphere, and right superior temporal cortex. These findings may relate to characteristics of MDD, such as excessive self-referential processing and deficits in cognitive control of emotional processing, which may contribute to the persistent and recurrent nature of the disorder. Hum Brain Mapp 35: 4979-4988, 2014.

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Sex differences are observed in both epidemiological and clinical aspects of major depressive disorder (MDD). The cortico-limbic-striatal neural system, including the prefrontal cortex, amygdala, hippocampus, and striatum, have shown sexually dimorphic morphological features and have been implicated in the dysfunctional regulation of mood and emotion in MDD. In this study, we utilized a whole-brain, voxel-based approach to examine sex differences in the regional distribution of gray matter (GM) morphological abnormalities in medication-naïve participants with MDD. Participants included 29 medication-naïve individuals with MDD (16 females and 13 males) and 33 healthy controls (HC) (17 females and 16 males). Gray matter morphology of the cortico-limbic-striatal neural system was examined using voxel-based morphometry analyses of high-resolution structural magnetic resonance imaging scans. The main effect of diagnosis and interaction effect of diagnosis by sex on GM morphology were statistically significant (p<0.05, corrected) in the left ventral prefrontal cortex, right amygdala, right hippocampus and bilateral caudate when comparing the MDD and HC groups. Posthoc analyses showed that females with MDD had significant GM decreases in limbic regions (p<0.05, corrected), compared to female HC; while males with MDD demonstrated significant GM reduction in striatal regions, (p<0.05, corrected), compared to HC males. The observed sex-related patterns of abnormalities within the cortico-limbic-strial neural system, such as predominant prefrontal-limbic abnormalities in MDD females vs. predominant prefrontal-striatal abnormalities in MDD males, suggest differences in neural circuitry that may mediate sex differences in the clinical presentation of MDD and potential targets for sex-differentiated treatment of the disorder.

Our findings of common alterations in SZ, BD, and MDD support the presence of core neurobiological disruptions in these disorders and suggest that neural structural distinctions between these disorders may be less prominent than initially postulated, particularly between SZ and BD.