Characterizing the impact of adversity, abuse, and neglect on adolescent amygdala resting-state functional connectivity.
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ABSTRACT:
SUBMITTER: Cheng TW
PROVIDER: S-EPMC7786040 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceMajor depressive disorder (MDD) frequently emerges during adolescence and can lead to persistent illness, disability, and suicide. The maturational changes that take place in the brain during adolescence underscore the importance of examining neurobiological mechanisms during this time of early illness. However, neural mechanisms of depression in adolescents have been understudied. Research has implicated the amygdala in emotion processing in mood disorders, and adult depression studies have suggested amygdala-frontal connectivity deficits. Resting-state functional magnetic resonance imaging is an advanced tool that can be used to probe neural networks and identify brain-behavior relationships.ObjectiveTo examine amygdala resting-state functional connectivity (RSFC) in adolescents with and without MDD using resting-state functional magnetic resonance imaging as well as how amygdala RSFC relates to a broad range of symptom dimensions.Design, setting, and participantsA cross-sectional resting-state functional magnetic resonance imaging study was conducted within a depression research program at an academic medical center. Participants included 41 adolescents and young adults aged 12 to 19 years with MDD and 29 healthy adolescents (frequency matched on age and sex) with no psychiatric diagnoses.Main outcomes and measuresUsing a whole-brain functional connectivity approach, we examined the correlation of spontaneous fluctuation of the blood oxygen level-dependent signal of each voxel in the whole brain with that of the amygdala.ResultsAdolescents with MDD showed lower positive RSFC between the amygdala and hippocampus, parahippocampus, and brainstem (z >2.3, corrected P < .05); this connectivity was inversely correlated with general depression (R = -.523, P = .01), dysphoria (R = -.455, P = .05), and lassitude (R = -.449, P = .05) and was positively correlated with well-being (R = .470, P = .03). Patients also demonstrated greater (positive) amygdala-precuneus RSFC (z >2.3, corrected P < .05) in contrast to negative amygdala-precuneus RSFC in the adolescents serving as controls.Conclusions and relevanceImpaired amygdala-hippocampal/brainstem and amygdala-precuneus RSFC have not previously been highlighted in depression and may be unique to adolescent MDD. These circuits are important for different aspects of memory and self-processing and for modulation of physiologic responses to emotion. The findings suggest potential mechanisms underlying both mood and vegetative symptoms, potentially via impaired processing of memories and visceral signals that spontaneously arise during rest, contributing to the persistent symptoms experienced by adolescents with depression.
| S-EPMC4378862 | biostudies-literature
Project description:BACKGROUND:The incidence of major depressive disorder (MDD) rises during adolescence, yet the neural mechanisms of MDD during this key developmental period are unclear. Altered amygdala resting-state functional connectivity (RSFC) has been associated with both adolescent and adult MDD, as well as symptom improvement in response to treatment in adults. However, no study to date has examined whether amygdala RSFC is associated with changes in depressive symptom severity in adolescents. METHOD:We examined group differences in amygdala RSFC between medication-naïve depressed adolescents (N=48) and well-matched healthy controls (N=53) cross-sectionally. We then longitudinally examined whether baseline amygdala RSFC was associated with change in depression symptoms three months later in a subset of the MDD group (N=24). RESULTS:Compared to healthy controls, depressed adolescents showed reduced amygdala-based RSFC with the dorsolateral prefrontal cortex (DLPFC)and the ventromedial prefrontal cortex (VMPFC). Within the depressed group, more positive baseline RSFC between the amygdala and insulae was associated with greater reduction in depression symptoms three months later. LIMITATIONS:Only a subset of depressed participants was assessed at follow-up and treatment type and delivery were not standardized. CONCLUSIONS:Adolescent depression may be characterized by dysfunction of frontolimbic circuits (amygdala-DLPFC, amygdala-VMPFC) underpinning emotional regulation, whereas those circuits (amygdala-insula) subserving affective integration may index changes in depression symptom severity and may therefore potentially serve as a candidate biomarker for treatment response. Furthermore, these results suggest that the biomarkers of MDD presence are distinct from those associated with change in depression symptoms over time.
| S-EPMC5149416 | biostudies-literature
Project description:The amygdala is composed of structurally and functionally distinct nuclei that contribute to the processing of emotion through interactions with other subcortical and cortical structures. While these circuits have been studied extensively in animals, human neuroimaging investigations of amygdala-based networks have typically considered the amygdala as a single structure, which likely masks contributions of individual amygdala subdivisions. The present study uses resting state functional magnetic resonance imaging (fMRI) to test whether distinct functional connectivity patterns, like those observed in animal studies, can be detected across three amygdala subdivisions: laterobasal, centromedial, and superficial. In a sample of 65 healthy adults, voxelwise regression analyses demonstrated positively-predicted ventral and negatively-predicted dorsal networks associated with the total amygdala, consistent with previous animal and human studies. Investigation of individual amygdala subdivisions revealed distinct differences in connectivity patterns within the amygdala and throughout the brain. Spontaneous activity in the laterobasal subdivision predicted activity in temporal and frontal regions, while activity in the centromedial nuclei predicted activity primarily in striatum. Activity in the superficial subdivision positively predicted activity throughout the limbic lobe. These findings suggest that resting state fMRI can be used to investigate human amygdala networks at a greater level of detail than previously appreciated, allowing for the further advancement of translational models.
| S-EPMC2735022 | biostudies-other
Project description:Early adolescence, with the onset of puberty, is an important period when sex differences in anxiety emerge, with girls reporting significantly higher anxiety symptoms than boys. This study examined the role of puberty on fronto-amygdala functional connectivity and risk of anxiety symptoms in 70 girls (age 11-13) who completed a resting state fMRI scan, self-report measures of anxiety symptoms and pubertal status, and provided basal testosterone levels (64 girls). Resting state fMRI data were preprocessed using fMRIPrep and connectivity indices were extracted from ventromedial prefrontal cortex (vmPFC) and amygdala regions-of-interest. We tested moderated mediation models and hypothesized that vmPFC-amygdala would mediate the relation between three indices of puberty (testosterone and adrenarcheal/gonadarcheal development) and anxiety, with puberty moderating the relation between connectivity and anxiety. Results showed a significant moderation effect of testosterone and adrenarcheal development in the right amygdala and a rostral/dorsal area of the vmPFC and of gonadarcheal development in the left amygdala and a medial area of the vmPFC on anxiety symptoms. Simple slope analyses showed that vmPFC-amygdala connectivity was negatively associated with anxiety only in girls more advanced in puberty suggesting that sensitivity to the effects of puberty on fronto-amygdala function could contribute to risk for anxiety disorders among adolescent girls.
| S-EPMC10063408 | biostudies-literature
Project description:Subthreshold depression (StD) affects people who experience clinically relevant depressive symptoms, which does not meet the diagnostic criteria for major depressive disorder (MDD). StD represents an ideal model for understanding the pathophysiological mechanisms of depression. Impaired emotion processing is a core feature of depression; careful investigation is required to better understand the neural correlates of emotion processing in depressed populations. In the current study, we explored whether the resting-state functional connectivity of the amygdala, a hub that taps a wide range of brain areas involved in emotion processing, is altered in individuals with StD when compared with healthy controls. Resting-state imaging data was collected from 59 individuals with StD and 59 age- and gender-matched controls. We found that the resting-state functional connectivity of the left amygdala with the cognitive control network and the left insula was significantly lower in people with StD than that in healthy controls. Such association was not observed in the right amygdala. Furthermore, functional connectivity strength between the left amygdala and the left precuneus was positively associated with depressive symptoms in individuals with StD. Our findings are in line with those reported in subjects with MDD, which may assist in further elucidating the pathophysiological mechanisms of depression, and contribute to the development of tailored treatments for individuals with StD who are at high risk of developing MDD.
| S-EPMC7560839 | biostudies-literature
Project description:Extensive research has demonstrated that rs1360780, a common single nucleotide polymorphism within the FKBP5 gene, interacts with early-life stress in predicting psychopathology. Previous results suggest that carriers of the TT genotype of rs1360780 who were exposed to child abuse show differences in structure and functional activation of emotion-processing brain areas belonging to the salience network. Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting-state functional connectivity (rsFC) between the amygdala and other areas of the salience network. We analyzed data of young European adults from the general population (N = 774; mean age = 18.76 years) who took part in the IMAGEN study. In the absence of main effects of genotype and abuse, a significant interaction effect was observed for rsFC between the right centromedial amygdala and right posterior insula (p < .025, FWE-corrected), which was driven by stronger rsFC in TT allele carriers with a history of abuse. Our results suggest that the TT genotype of rs1360780 may render individuals with a history of abuse more vulnerable to functional changes in communication between brain areas processing emotions and bodily sensations, which could underlie or increase the risk for psychopathology.
| S-EPMC8193540 | biostudies-literature
Project description:The Research Domain Criteria (RDoC) adopts a dimensional approach for examining pathophysiological processes underlying categorically defined psychiatric diagnoses. We used this framework to examine relationships among symptom dimensions, diagnostic categories, and resting state connectivity in behaviorally and emotionally dysregulated youth selected from the Longitudinal Assessment of Manic Symptoms study (n=42) and healthy control youth (n=18). Region of interest analyses examined relationships among resting state connectivity, symptom dimensions (behavioral and emotional dysregulation measured with the Parent General Behavior Inventory-10 Item Mania Scale [PGBI-10M]; dimensional severity measures of mania, depression, anxiety), and diagnostic categories (Bipolar Spectrum Disorders, Attention Deficit Hyperactivity Disorder, Anxiety Disorders, and Disruptive Behavior Disorders). After adjusting for demographic variables, two dimensional measures showed significant inverse relationships with resting state connectivity, regardless of diagnosis: 1) PGBI-10M with amygdala-left posterior insula/bilateral putamen; and 2) depressive symptoms with amygdala-right posterior insula connectivity. Diagnostic categories showed no significant relationships with resting state connectivity. Resting state connectivity between amygdala and posterior insula decreased with increasing severity of behavioral and emotional dysregulation and depression; this suggests an intrinsic functional uncoupling of key neural regions supporting emotion processing and regulation. These findings support the RDoC dimensional approach for characterizing pathophysiologic processes that cut across different psychiatric disorders.
| S-EPMC4272653 | biostudies-literature
Project description:During adolescence, considerable social and biological changes occur that interact with functional brain maturation, some of which are sex-specific. The amygdala is one brain area that has displayed sexual dimorphism, specifically in socio-affective (superficial amygdala [SFA]), stress (centromedial amygdala [CMA]), and learning and memory (basolateral amygdala [BLA]) processing. The amygdala has also been implicated in mood and anxiety disorders which display sex-specific features, most prominently observed during adolescence. Using functional magnetic resonance imaging (fMRI), the present study examined the interaction of age and sex on resting state functional connectivity (RSFC) of amygdala sub-regions, BLA and SFA, in a sample of healthy adolescents between the ages 10 and 16 years (n = 122, 71 boys). Whole-brain, voxel-wise partial correlation analyses were conducted to determine RSFC of bilateral BLA and SFA seed regions, created using the Eickhoff-Zilles maximum probability maps based on cytoarchitectonic mapping and FMRIB's Integrated Registration and Segmentation Tool (FIRST). Monte Carlo simulation was implemented to correct for multiple comparisons (threshold of 53 contiguous voxels with a z-value ≥ 2.25). Results indicated that with increasing age, there was a corresponding decrease in RSFC between both amygdala sub-regions and parieto-occipital cortices, with a concurrent increase in RSFC with medial prefrontal cortex (mPFC). Specifically, boys and girls demonstrated increased coupling of mPFC and left and right SFA with age, respectively; however, neither sex showed increased connectivity between mPFC and BLA, which could indicate relative immaturity of fronto-limbic networks that is similar across sex. A dissociation in connectivity between BLA- and SFA-parieto-occipital RSFC emerged, in which girls had weaker negative RSFC between SFA and parieto-occipital regions and boys had weaker negative RSFC of BLA and parieto-occipital regions with increased age, both standing in contrast to adult patterns of amygdala sub-regional RSFC. The present findings suggest relative immaturity of amygdala sub-regional RSFC with parieto-occipital cortices during adolescence, with unique patterns in both sexes that may support memory and socio-affective processing in boys and girls, respectively. Understanding the underlying normative functional architecture of brain networks associated with the amygdala during adolescence may better inform future research of the neural features associated with increased risk for internalizing psychopathology.
| S-EPMC4461484 | biostudies-literature
Project description:The amygdala plays a key role in emotion processing. Its functional connectivity with other brain regions has been extensively demonstrated to be associated with extraversion and neuroticism. However, how the amygdala affects other regions and is affected by others within these connectivity patterns associated with extraversion and neuroticism remains unclear. To address this issue, we investigated the effective connectivity of the amygdala using Granger causality analysis on the resting-state functional magnetic resonance imaging data of 70 participants. Results showed that extraversion was positively correlated with the influence from the right inferior occipital gyrus (IOG) to the left amygdala, and from the bilateral IOG to the right amygdala; such result may represent the neural correlates of social interactions in extraverts. Conversely, neuroticism was associated with an increased influence from right amygdala to right middle frontal gyrus and a decreased influence from right precuneus to right amygdala. This influence might affect the modulations of cognitive regulation function and self-referential processes in neurotic individuals. These findings highlight the importance of the causal influences of amygdala in explaining the individual differences in extraversion and neuroticism, and offer further insights into the specific neural networks underlying personality.
| S-EPMC5073227 | biostudies-literature
Project description:Connectivity of the prefrontal cortex (PFC) matures through adolescence, coinciding with emergence of adult executive function and top-down inhibitory control over behavior. Alcohol exposure during this critical period of brain maturation may affect development of PFC and frontolimbic connectivity. Adult rats exposed to adolescent intermittent ethanol (AIE; 5 g/kg ethanol, 25 percent v/v in water, intragastrically, 2-day-on, 2-day-off, postnatal day 25-54) or water control underwent resting-state functional MRI to test the hypothesis that AIE induces persistent changes in frontolimbic functional connectivity under baseline and acute alcohol conditions (2 g/kg ethanol or saline, intraperitoneally administered during scanning). Data were acquired on a Bruker 9.4-T MR scanner with rats under dexmedetomidine sedation in combination with isoflurane. Frontolimbic network regions-of-interest for data analysis included PFC [prelimbic (PrL), infralimbic (IL), and orbitofrontal cortex (OFC) portions], nucleus accumbens (NAc), caudate putamen (CPu), dorsal hippocampus, ventral tegmental area, amygdala, and somatosensory forelimb used as a control region. AIE decreased baseline resting-state connectivity between PFC subregions (PrL-IL and IL-OFC) and between PFC-striatal regions (PrL-NAc, IL-CPu, IL-NAc, OFC-CPu, and OFC-NAc). Acute ethanol induced negative blood-oxygen-level-dependent changes within all regions of interest examined, along with significant increases in functional connectivity in control, but not AIE animals. Together, these data support the hypothesis that binge-like adolescent alcohol exposure causes persistent decreases in baseline frontolimbic (particularly frontostriatal) connectivity and alters sensitivity to acute ethanol-induced increases in functional connectivity in adulthood.
| S-EPMC5760482 | biostudies-literature