Developmental research has demonstrated the harmful effects of peer rejection during adolescence; however, the neural mechanisms responsible for this salience remain unexplored. In this study, 23 adolescents were excluded during a ball-tossing game in which they believed they were playing with two other adolescents during an fMRI scan; in reality, participants played with a preset computer program. Afterwards, participants reported their exclusion-related distress and rejection sensitivity, and parents reported participants’ interpersonal competence. Similar to findings in adults, during social exclusion adolescents displayed insular activity that was positively related to self-reported distress, and right ventrolateral prefrontal activity that was negatively related to self-reported distress. Findings unique to adolescents indicated that activity in the subgenual anterior cingulate cortex (subACC) related to greater distress, and that activity in the ventral striatum related to less distress and appeared to play a role in regulating activity in the subACC and other regions involved in emotional distress. Finally, adolescents with higher rejection sensitivity and interpersonal competence scores displayed greater neural evidence of emotional distress, and adolescents with higher interpersonal competence scores also displayed greater neural evidence of regulation, perhaps suggesting that adolescents who are vigilant regarding peer acceptance may be most sensitive to rejection experiences.
peer rejection; adolescence; functional magnetic resonance imaging
Peer rejection is particularly pervasive among adolescents with autism spectrum disorders (ASD). However, how adolescents with ASD differ from typically developing adolescents in their responses to peer rejection is poorly understood. The goal of the current investigation was to examine neural responses to peer exclusion among adolescents with ASD compared to typically developing adolescents. Nineteen adolescents with ASD and 17 typically developing controls underwent fMRI as they were ostensibly excluded by peers during an online game called Cyberball. Afterwards, participants reported their distress about the exclusion. Compared to typically developing adolescents, those with ASD displayed less activity in regions previously linked with the distressing aspect of peer exclusion, including the subgenual anterior cingulate and anterior insula, as well as less activity in regions previously linked with the regulation of distress responses during peer exclusion, including the ventrolateral prefrontal cortex and ventral striatum. Interestingly, however, both groups self-reported equivalent levels of distress. This suggests that adolescents with ASD may engage in differential processing of social experiences at the neural level, but be equally aware of, and concerned about, peer rejection. Overall, these findings contribute new insights about how this population may differentially experience negative social events in their daily lives.
Autism spectrum disorders; Peer rejection; Social exclusion; Adolescence; Functional magnetic resonance imaging
Rejection sensitivity is the heightened tendency to perceive or anxiously expect disengagement from others during social interaction. There has been a recent wave of neuroimaging studies of rejection. The aim of the current review was to determine key brain regions involved in social rejection by selectively reviewing neuroimaging studies that employed one of three paradigms of social rejection, namely social exclusion during a ball-tossing game, evaluating feedback about preference from peers and viewing scenes depicting rejection during social interaction. Across the different paradigms of social rejection, there was concordance in regions for experiencing rejection, namely dorsal anterior cingulate cortex (ACC), subgenual ACC and ventral ACC. Functional dissociation between the regions for experiencing rejection and those for emotion regulation, namely medial prefrontal cortex, ventrolateral prefrontal cortex (VLPFC) and ventral striatum, was evident in the positive association between social distress and regions for experiencing rejection and the inverse association between social distress and the emotion regulation regions. The paradigms of social exclusion and scenes depicting rejection in social interaction were more adept at evoking rejection-specific neural responses. These responses were varyingly influenced by the amount of social distress during the task, social support received, self-esteem and social competence. Presenting rejection cues as scenes of people in social interaction showed high rejection sensitive or schizotypal individuals to under-activate the dorsal ACC and VLPFC, suggesting that such individuals who perceive rejection cues in others down-regulate their response to the perceived rejection by distancing themselves from the scene.
Social distance; Gyrus cinguli; Prefrontal cortex; Social support
Neuroimaging studies implicate the subgenual anterior cingulate cortex (sgACC) as a critical brain region in adult depression. However, unlike adult depression, little is known about the underlying neural substrates of adolescent depression, and there are no published data examining differences in sgACC activation between depressed and healthy adolescents. This study used functional magnetic resonance imaging to examine sgACC activity in twenty-six depressed and normal 13- to 17-year olds during the performance of a stop-signal task. Significantly greater sgACC activation was found in the depressed adolescents relative to controls. These results establish for the first time abnormal functioning of the sgACC in depressed adolescents and have important implications for understanding the underlying neural correlates and potential treatments of adolescent depression.
adolescent; depression; FMRI; subgenual anterior cingulate cortex; prefrontal cortex; major depressive disorder; functional neuroimaging; functional MRI; pediatrics; mood disorder
Recent adult studies suggest that the subgenual anterior cingulate cortex (sgACC) is involved in fundamental mental operations such as affective processing and inhibitory control. However, little is known about inhibition-associated sgACC function in adolescents, and there are no published data regarding whether personality characteristics are related to inhibition-associated sgACC brain activity in adolescents. This study examined the relationship between personality and inhibition-associated sgACC response in healthy adolescents. Seventeen adolescents of 13–17 years of age underwent functional magnetic resonance imaging while performing a parametric stop-signal task. Greater harm avoidance levels were significantly associated with increased inhibition-related sgACC activity. These results establish, for the first time, a link between personality and differential sgACC activation in adolescents.
adolescents; emotion; functional MRI; harm avoidance; personality; subgenual anterior cingulate; temperament and character inventory
Major Depressive Disorder (MDD) begins frequently in adolescence and is associated with severe outcomes, but the developmental neurobiology of MDD is not well understood. Research in adults has implicated fronto-limbic neural networks in the pathophysiology of MDD, particularly in relation to the subgenual anterior cingulate cortex (ACC). Developmental changes in brain networks during adolescence highlight the need to examine MDD-related circuitry in teens separately from adults. Using resting state functional magnetic resonance imaging (fMRI), this study examined functional connectivity in adolescents with MDD (n=12) and healthy adolescents (n=14). Seed-based connectivity analysis revealed that adolescents with MDD have decreased functional connectivity in a subgenual ACC-based neural network that includes the supragenual ACC (BA 32), the right medial frontal cortex (BA 10), the left inferior (BA 47) and superior frontal cortex (BA 22), superior temporal gyrus (BA 22), and the insular cortex (BA 13). These preliminary data suggest that MDD in adolescence is associated with abnormal connectivity within neural circuits that mediate emotion processing. Future research in larger, un-medicated samples will be necessary to confirm this finding. We conclude that hypothesis-driven, seed-based analyses of resting state fMRI data hold promise for advancing our current understanding of abnormal development of neural circuitry in adolescents with MDD.
adolescence; brain imaging; depression; functional connectivity; resting-state functional MRI; subgenual anterior cingulate cortex
Peer feedback affects adolescents’ behaviors, cognitions and emotions. We examined neural circuitry underlying adolescents’ emotional response to peer feedback using a functional neuroimaging paradigm whereby, 36 adolescents (aged 9–17 years) believed they would interact with unknown peers postscan. Neural activity was expected to vary based on adolescents’ perceptions of peers and feedback type. Ventrolateral prefrontal cortex (vlPFC) activity was found when adolescents indicated how they felt following feedback (acceptance or rejection) from peers of low vs high interest. Greater activation in both cortical (e.g. superior temporal gyrus, insula, anterior cingulate) and subcortical (e.g. striatum, thalamus) regions emerged in response to acceptance vs rejection feedback. Response to acceptance also varied by age and gender in similar regions (e.g. superior temporal gyrus, fusiform, insula), with greater age-related increases in activation to acceptance vs rejection for females than males. Affective response to rejection vs acceptance did not yield significantly greater neural activity in any region. vlPFC response suggests cognitive flexibility in reappraising initial perceptions of peers following feedback. Striatal response suggests that acceptance is a potent social reward for adolescents, an interpretation supported by more positive self-reported affective response to acceptance than rejection from high- but not low-interest peers.
adolescence; cognitive flexibility; peer feedback; social reward
Early life adversities are risk factors for later mood and emotional disorders. Repeated separation of infant marmosets from their parents provides a validated primate model of depression vulnerability, producing in vivo biochemical and behavioural effects indicative of persistently altered stress reactivity and mild anhedonia. Here we report the long-term effect (in adolescence) of this intervention on the expression of synaptophysin, GAP-43, VGluT1, VGAT, MAP-2, spinophilin, and 5-HT1A and 5-HT2A receptors, in the anterior cingulate cortex (ACC; supragenual and subgenual areas) and amygdala (lateral, basal and central nuclei). These genes and regions are implicated in the response to stress or in mood disorder. The profile of 5-HT1A receptor binding in ACC was affected by early deprivation, notably in the subgenual region, with a decrease in deep laminae but an increase in superficial laminae. Following early deprivation, spinophilin was reduced in the subgenual ACC. In the amygdala, no significant effects of the manipulation were seen, but expression of several transcripts was sexually dimorphic. There were correlations between expression of some transcripts and in vivo measurements. The results show that early deprivation in a non-human primate has a selective long-term effect on expression of genes in the ACC, particularly the subgenual area. The results differ from those reported in the hippocampus of the same animals, indicating the presence of limbic region-specific long-term molecular responses to early life stress.
Subgenual area; serotonin 1A receptor; Depression; Mood disorder; Sexual dimorphism
Major Depressive Disorder (MDD) occurs frequently in adolescents, but the neurobiology of depression in youth is poorly understood. Structural neuroimaging studies in both adult and pediatric populations have implicated fronto-limbic neural networks in the pathophysiology of MDD. Diffusion Tensor Imaging (DTI), which measures white matter (WM) microstructure, is a promising tool for examining neural connections and how they may be abnormal in MDD.
We used two separate approaches to analyze DTI data in adolescents with MDD (n=14) compared with healthy volunteers (n=14).
The first, hypothesis-driven approach was to use probabilistic tractography to delineate tracts arising from the subgenual anterior cingulate cortex (ACC). Adolescents with MDD demonstrated lower fractional anisotropy (FA) in the WM tract connecting subgenual ACC to amygdala in the right hemisphere. The second, exploratory approach was to conduct a voxel-wise comparison of FA. This analysis revealed ten clusters where adolescents with MDD had significantly lower (uncorrected) FA than the healthy group within WM tracts including right and left uncinate and supragenual cingulum.
These preliminary data support the hypothesis that altered WM microstructure in fronto-limbic neural pathways may contribute to the pathophysiology of MDD in adolescents.
depression; adolescents; diffusion tensor imaging; white matter; neurodevelopment
Self-esteem is a facet of personality that influences perception of social standing and modulates the salience of social acceptance and rejection. As such, self-esteem may bias neural responses to positive and negative social feedback across individuals. During functional magnetic resonance imaging scanning, participants (n = 42) engaged in a social evaluation task whereby they ostensibly received feedback from peers indicating they were liked or disliked. Results demonstrated that individuals with low self-esteem believed that they received less positive feedback from others and showed enhanced activity to positive versus negative social feedback in the ventral anterior cingulate cortex/medial prefrontal cortex (vACC/mPFC). By contrast, vACC/mPFC activity was insensitive to positive versus negative feedback in individuals with high self-esteem, and these individuals consistently overestimated the amount of positive feedback received from peers. Voxelwise analyses supported these findings; lower self-esteem predicted a linear increase in vACC/mPFC response to positive versus negative social feedback. Taken together, the present findings propose a functional role for the vACC/mPFC in representing the salience of social feedback and shaping perceptions of relative social standing.
anterior cingulate cortex; fMRI; medial prefrontal cortex; self-esteem; social
Immune dysfunction, including monocytosis and increased blood levels of interleukin-1, interleukin-6 and tumour necrosis factor α has been observed during acute episodes of major depression. These peripheral immune processes may be accompanied by microglial activation in subregions of the anterior cingulate cortex where depression-associated alterations of glutamatergic neurotransmission have been described.
Microglial immunoreactivity of the N-methyl-D-aspartate (NMDA) glutamate receptor agonist quinolinic acid (QUIN) in the subgenual anterior cingulate cortex (sACC), anterior midcingulate cortex (aMCC) and pregenual anterior cingulate cortex (pACC) of 12 acutely depressed suicidal patients (major depressive disorder/MDD, n = 7; bipolar disorder/BD, n = 5) was analyzed using immunohistochemistry and compared with its expression in 10 healthy control subjects.
Depressed patients had a significantly increased density of QUIN-positive cells in the sACC (P = 0.003) and the aMCC (P = 0.015) compared to controls. In contrast, counts of QUIN-positive cells in the pACC did not differ between the groups (P = 0.558). Post-hoc tests showed that significant findings were attributed to MDD and were absent in BD.
These results add a novel link to the immune hypothesis of depression by providing evidence for an upregulation of microglial QUIN in brain regions known to be responsive to infusion of NMDA antagonists such as ketamine. Further work in this area could lead to a greater understanding of the pathophysiology of depressive disorders and pave the way for novel NMDA receptor therapies or immune-modulating strategies.
This study used longitudinal, multi-reporter data, in a community sample, to examine the role of rejection sensitivity in late adolescents’ social and emotional development. Rejection sensitivity was linked to a relative increase in adolescent depressive and anxiety symptoms over a three-year period, even after accounting for teens’ baseline level of social competence. Additionally, reciprocal relationships emerged between rejection sensitivity and internalizing symptoms. Rejection sensitivity was also linked to relative decreases in peer-reports of teens’ social competence over a three-year period. Consistent with research on gendered socialization, males reported higher levels of rejection sensitivity than females at age 16 and 17. Results are interpreted as highlighting the importance of rejection sensitivity in understanding late adolescent social and emotional development.
Late Adolescence; Rejection Sensitivity; Internalizing Disorders; Social Competence; Gendered Socialization
Obsessive–compulsive disorder (OCD) is associated with a range of emotional abnormalities linked to its defining symptoms, comorbid illnesses and cognitive deficits. The aim of this preliminary study was to examine functional changes in the brain that are associated with experimentally induced sad mood in patients with OCD compared with healthy controls in a frontolimbic circuit relevant to both OCD and mood regulation.
Participants underwent a validated sad mood induction procedure during functional magnetic resonance imaging. Analyses focused on mapping changes in the functional connectivity of the subgenual anterior cingulate cortex (ACC) within and between the 2 groups in response to successfully induced sadness.
We enrolled 11 patients with OCD and 10 age-, sex- and IQ-matched controls in our study. Unlike controls, patients with OCD did not demonstrate predicted increases in functional connectivity between the subgenual ACC and other frontal regions during mood induction. Instead, patients demonstrated heightened connectivity between the subgenual ACC and ventral caudate/nucleus accumbens region and the hypothalamus.
Our study included a small, partially medicated patient cohort that precluded our ability to investigate sex or drug effects, evaluate behavioural differences between the groups and perform a whole-brain analysis.
The ventral striatum and ventral frontal cortex were distinctly and differentially modulated in their connectivity with the subgenual ACC during the experience of sad mood in patients with OCD. These results suggest that, in patients with OCD, induced sadness appears to have provoked a primary subcortical component of the hypothesized “OCD circuit,” which may offer insights into why OCD symptoms tend to develop and worsen during disturbed emotional states.
Anterior cingulate cortex (ACC) is involved in emotion, emotional expression, mood and autonomic regulation in contrast to midcingulate cortex, which regulates response selection via cognitive and skeletomotor mechanisms. Although a subgenual part of ACC (sACC) may be vulnerable in depression and area 25 is cytologically unique, there are no assessments that contrast this region to pregenual ACC (pACC); both include parts of areas 32, 24, and 33 and the cingulate sulcus extends rostral to the corpus callosum and might contain area 24c. Independent verifications of cytoarchitectural differences among subregions, areas and laminar binding was undertaken with an observer-interactive approach and multireceptor autoradiography. Areas 24a and 24b have pregenual (p24a, p24b) and subgenual (s24a, s24b) components and subgenual areas have a very thin layer III. Area 24c is rostral to the genu (p24c) and has dorsal (pd24c) and ventral (pv24c) parts. Area pd24c has more and larger neurofilament-expressing neurons in layer Va and neurons in Vb form aggregates in area pv24c rather than solitary pyramids as in pd24c. Area pd24c occupies both banks of the cingulate sulcus with pv24c on the ventral bank. Layer III distinguishes these areas with pd24cd having many larger neurofilament-expressing neurons and a richer dendritic plexus in the entire layer III. Area 32 has pregenual (p32) and subgenual (s32) components. Layer II in s32 is of particular note because it has a neuron dense IIa and sparse IIb. Area 25 is comprised of anterior (25a) and posterior (25p) parts; 25p has the thinnest layer III in the cingulate gyrus and larger and more dense neurons in layer II. Area 33 continues around the genu and ventrally to encompass the full caudal extent of area 25. The multivariate, observer-interactive method accurately identified all borders except those of area 25. Finally, sACC has significantly higher GABAA, GABAB, BZ, α1, and 5-HT1A densities than pACC. The GABAB, BZ and α1 binding in the cingulate sulcus confirms the subdivision of area pd24c into ventral and dorsal components. Receptor binding also supports subdivision of area 25 with 25a containing significantly higher AMPA, kainate, NMDA, GABAA, GABAB, and α1 receptor densities than area 25p. In conclusion, ACC is comprised of two parts that are unique in terms of their cytoarchitecture and neurotransmitter receptor organization.
cytoarchitecture; neurofilament proteins; autoradiography; neurotransmitter; brain mapping; cingulate motor area; cortical layers
Frontolimbic dysfunction is observed in borderline personality disorder (BPD), with responses to emotional stimuli that are exaggerated in the amygdala and impaired in the anterior cingulate cortex (ACC). This pattern of altered function is consistent with animal models of stress responses and depression, where hypertrophic changes in the amygdala and atrophic changes in the ACC are observed. We tested the hypothesis that BPD patients exhibit gross structural changes that parallel the respective increases in amygdala activation and impairment of rostral/subgenual ACC activation.
12 unmedicated outpatients with BPD by DSM-IV and 12 normal control (NC) subjects underwent a high-resolution T1-weighted structural MRI scan. Relative gray matter concentration (GMC) in spatially-normalized images was evaluated by standard voxel-based morphometry, with voxel-wise subject group comparisons by t test constrained to amygdala and rostral/subgenual ACC.
The BPD group was significantly higher than NC in GMC in the amygdala. In contrast, the BPD group showed significantly lower GMC than the NC group in left rostral/subgenual ACC.
This sample of BPD patients exhibits gross structural changes in gray matter in cortical and subcortical limbic regions that parallel the regional distribution of altered functional activation to emotional stimuli among these same subjects. While the histological basis for GMC changes in adult clinical populations is poorly-known at present, the observed pattern is consistent with the direction of change, in animal models of anxiety and depression, of neuronal number and/or morphological complexity in both the amygdala (where it is increased) and ACC (where it is decreased).
borderline personality disorder; frontolimbic; amygdala; anterior cingulate cortex; gray matter; voxel-based morphometry
Prior neuroimaging and electrophysiological evidence suggests that potentiated responses in the anterior cingulate cortex (ACC), particularly the rostral ACC, may contribute to abnormal responses to negative feedback in individuals with elevated negative affect and depressive symptoms. The feedback-related negativity (FRN) represents an electrophysiological index of ACC-related activation in response to performance feedback. The purpose of the present study was to examine the FRN and underlying ACC activation using low resolution electromagnetic tomography source estimation techniques in relation to negative emotionality (a composite index including negative affect and subclinical depressive symptoms). To this end, 29 healthy adults performed a monetary incentive delay task while 128-channel event-related potentials were recorded. We found that enhanced FRNs and increased rostral ACC activation in response to negative—but not positive—feedback was related to greater negative emotionality. These results indicate that individual differences in negative emotionality—a putative risk factor for emotional disorders—modulate ACC-related processes critically implicated in assessing the motivational impact and/or salience of environmental feedback.
feedback-related negativity; depression; negative affect; anterior cingulate cortex; negative feedback; reward
Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression. Increased metabolism in the anterior cingulate cortex (ACC) is a known predictor for antidepressant response. The authors assessed whether increased theta power within the ACC predicts rTMS response in participants with vascular depression. Sixty-five participants were randomized to active or sham rTMS. Outcome was assessed using the Hamilton Depression Rating Scale. Electroencephalography was obtained, and comparisons were made among each group with a normative database using low-resolution electromagnetic tomography. Results suggest that vascular depression participants respond well to rTMS and that increased low-theta power in the subgenual ACC predicts response to rTMS.
The subgenual anterior cingulate cortex (sgACC) presents altered functional connections with other regions of the brain in individuals with depression. However, the developmental nature of this phenomenon remains largely unexplored. Functional connections of the sgACC were examined in 36 school age children, 17 with a history of preschool depression (PO-MDD). The sgACC exhibited increased connections with cognitive control regions in healthy children and increased connections with thalamic and parietal regions in the PO-MDD group. A significant correlation between dysregulated emotional behavior and connectivity of the sgACC and dorsal medial prefrontal cortex was also found. These findings demonstrate that atypical sgACC functional connections are evident as early as school age in children with a history of PO-MDD and suggest an association with a very early episode of depression.
Functional Connectivity; Depression; Cingulate; fMRI; Pediatric; Preschool; Psychopathology
A heightened propensity for risk-taking and poor decision-making underlies the peak morbidity and mortality rates reported during adolescence. Delayed maturation of cortical structures during the adolescent years has been proposed as a possible explanation for this observation. Here, we test the hypothesis of adolescent delayed maturation by using fMRI during a monetary decision-making task that directly examines risk-taking behavior during choice selection. Orbitofrontal/ventrolateral prefrontal cortex (OFC/VLPFC) and dorsal anterior cingulate cortex (ACC) were examined selectively since both have been implicated in reward-related processes, cognitive control, and resolution of conflicting decisions. Group comparisons revealed greater activation in the OFC/VLPFC (BA 47) and dorsal ACC (BA 32) in adults than adolescents when making risky selections. Furthermore, reduced activity in these areas correlated with greater risk-taking performance in adolescents and in the combined group. Consistent with predictions, these results suggest that adolescents engage prefrontal regulatory structures to a lesser extent than adults when making risky economic choices.
reward; decision-making; cognitive control; affective regulation; conflict monitoring
This study was designed to evaluate the usefulness of assessing subgenual anterior cingulate cortex (sACC) volume reduction by magnetic resonance imaging (MRI) as an objective auxiliary means of diagnosis of depression. The study was additionally designed to analyze the association of sACC volume reduction with the effectiveness of treatments for depression and other diseases presenting with similar symptoms, and to examine the possibility of using sACC volume reduction in the distinction between depression and bipolar disorder and determining optimum medication for these conditions.
Three-dimensional T1-weighted sagittal images, taken with Achieva 1.5T NOVA (Philips), were analyzed with VSRAD plus® to evaluate a reduction in sACC volume. The finding from this analysis was compared with the clinical data, including the longitudinal course follow-up data based on the treatment algorithm.
The study involved 88 patients aged over 54 who received MRI during 2010, ie, 71 patients with major depressive disorder (MDD), 11 patients bipolar disorder, and 6 patients in whom the initial diagnosis (MDD) was later modified. Thirty-three normal individuals served as controls.
sACC volume reduction was noted in 66 of the 71 patients receiving treatment of MDD, with sensitivity of 93%, specificity of 85%, and accuracy of 90%. In the 66 patients diagnosed as having MDD and exhibiting sACC volume reduction, the disease showed remission in response to treatment with antidepressants, but medication needed to be continued after achievement of remission. In cases initially diagnosed as having MDD but not exhibiting sACC volume reduction, the necessity of modifying the diagnosis was considered. Typical cases of bipolar disorder did not exhibit sACC volume reduction.
That patients receiving treatment of MDD often showed reduction in sACC volume suggests the usefulness of this parameter as an objective auxiliary means of diagnosis for MDD.
depression; subgenual anterior cingulate cortex (sACC); MRI; VSRAD; neuroimaging
This study assessed the impact of serotonin transporter genotype (5-HTTLPR) on regional responses to emotional faces in the amygdala and subgenual cingulate cortex (sgACC), while subjects performed a gender discrimination task. Although we found no evidence for greater amygdala reactivity or reduced amygdala–sgACC coupling in short variant 5-HTTLPR homozygotes (s/s), we observed an interaction between genotype and emotion in sgACC. Only long variant homozygotes (la/la) exhibited subgenual deactivation to fearful versus neutral faces, whereas the effect in s/s subjects was in the other direction. This absence of subgenual deactivation in s/s subjects parallels a recent finding in depressed subjects [Grimm, S., Boesiger, P., Beck, J., Schuepbach, D., Bermpohl, F., Walter, M., et al. Altered negative BOLD responses in the default-mode network during emotion processing in depressed subjects. Neuropsychopharmacology, 34, 932–943, 2009]. Taken together, the findings suggest that subgenual cingulate activity may play an important role in regulating the impact of aversive stimuli, potentially conferring greater resilience to the effects of aversive stimuli in la/la subjects. Using dynamic causal modeling of functional magnetic resonance imaging data, we explored the effects of genotype on effective connectivity and emotion-specific changes in coupling across a network of regions implicated in social processing. Viewing fearful faces enhanced bidirectional excitatory coupling between the amygdala and the fusiform gyrus, and increased the inhibitory influence of the amygdala over the sgACC, although this modulation of coupling did not differ between the genotype groups. The findings are discussed in relation to the role of sgACC and serotonin in moderating responses to aversive stimuli [Dayan, P., & Huys, Q. J., Serotonin, inhibition, and negative mood. PLoS Comput Biol, 4, e4, 2008; Mayberg, H. S., Liotti, M., Brannan, S. K., McGinnis, S., Mahurin, R. K., Jerabek, P. A., et al. Reciprocal limbic–cortical function and negative mood: Converging PET findings in depression and normal sadness. Am J Psychiatry, 156, 675–682, 1999].
Involvement with friends carries many advantages for adolescents, including protection from the detrimental effects of being rejected by peers. However, little is known about the mechanisms through which friendships may serve their protective role at this age, or the potential benefit of these friendships as adolescents transition to adulthood. As such, this investigation tested whether friend involvement during adolescence related to less neural sensitivity to social threats during young adulthood. Twenty-one adolescents reported the amount of time they spent with friends outside of school using a daily diary. Two years later they underwent an fMRI scan, during which they were ostensibly excluded from an online ball-tossing game by two same-age peers. Findings from region of interest and whole brain analyses revealed that spending more time with friends during adolescence related to less activity in the dorsal anterior cingulate cortex and anterior insula—regions previously linked with negative affect and pain processing—during an experience of peer rejection 2 years later. These findings are consistent with the notion that positive relationships during adolescence may relate to individuals being less sensitive to negative social experiences later on.
adolescence; friendship; peer rejection; functional magnetic resonance imaging
Peer victimization experiences represent developmentally salient stressors among adolescents and are associated with the development of internalizing symptoms. However, the mechanisms linking peer victimization to adolescent psychopathology remain inadequately understood. This study examined emotion dysregulation as a mechanism linking peer stress to changes in internalizing symptoms among adolescents in a longitudinal design. Peer victimization was assessed in a large (N = 1,065) racially diverse (86.6% non-White) sample of adolescents ages 11 to 14 using the Revised Peer Experiences Questionnaire. Emotion dysregulation and symptoms of depression and anxiety were also assessed. Structural equation modeling was used to create a latent construct of emotion dysregulation from measures of discrete emotion processes and of peer victimization and internalizing symptoms. Peer victimization was associated with increased emotion dysregulation over a 4-month period. Increases in emotion dysregulation mediated the relationship between relational and reputational, but not overt, victimization and changes in internalizing symptoms over a 7-month period. Evidence for a reciprocal relationship between internalizing symptoms and relational victimization was found, but emotion dysregulation did not mediate this relationship. The implications for preventive interventions are discussed.
peer victimization; emotion regulation; depression; anxiety; internalizing symptoms
In a large sample of early adolescents (T2: n = 1023; M age = 13.51; 55.5% girls) it was investigated whether the effects of parental and peer acceptance and rejection on psychopathology (externalizing and internalizing problems) remain when taking into account both contexts simultaneously. Moreover, we examined whether acceptance in one context can buffer rejection in the other. It was found that when analyzing peer and parent effects simultaneously (1) the protective effect of parental acceptance and the risk effect of peer rejection were diminished; (2) the protective effect of peer acceptance and the risk-effect of parental rejection remained strong; and (3) peer acceptance buffered parental rejection but parental acceptance did not buffer peer rejection. The results imply that the parent and peer contexts are interdependent. Implications and directions for future research are given.
Parental rejection; Parental acceptance; Peer rejection; Peer acceptance; Risk-buffering effects
Pregenual anterior cingulate cortex (pgACC) hyperactivity differentiates treatment responders from non-responders to various pharmacological antidepressant interventions, including ketamine, an N-methyl--aspartate receptor antagonist. Evidence of pgACC hyperactivition during non-emotional working memory tasks in patients with major depressive disorder (MDD) highlights the importance of this region for processing both emotionally salient and cognitive stimuli. However, it is unclear whether pgACC activity might serve as a potential biomarker of antidepressant response during working memory tasks as well, in line with previous research with emotionally arousing tasks. This study tested the hypothesis that during the N-back task, a widely used working memory paradigm, low pretreatment pgACC activity, as well as coherence between the pgACC and the amygdala, would be correlated with the clinical improvement after ketamine. Magnetoencephalography (MEG) recordings were obtained from 15 drug-free patients with MDD during working memory performance 1 to 3 days before receiving a single ketamine infusion. Functional activation patterns were analyzed using advanced MEG source analysis. Source coherence analyses were conducted to quantify the degree of long-range functional connectivity between the pgACC and the amygdala. Patients who showed the least engagement of the pgACC in response to increased working memory load showed the greatest symptomatic improvement within 4 h of ketamine administration (r=0.82, p=0.0002, false discovery rate (FDR) <0.05). Pretreatment functional connectivity between the pgACC and the left amygdala was negatively correlated with antidepressant symptom change (r=−0.73, p=0.0021, FDR <0.05).These data implicate the pgACC and its putative interaction with the amygdala in predicting antidepressant response to ketamine in a working memory task context.
major depressive disorder (MDD); magnetoencephalography (MEG); N-back; biomarker; beta desynchronization; Biological Psychiatry; Mood/Anxiety/Stress Disorders; Imaging; Clinical or Preclinical; Glutamate; magnetoencephalography; N-back; beta desynchronization; biomarker