Amygdala activity to angry and fearful faces relates to bullying and victimization in adolescents.

Relational bullying and victimization are common social experiences during adolescence, but relatively little functional magnetic resonance imaging (fMRI) research has examined the neural correlates of bullying and victimization in adolescents. The aim of the present study was to address this gap by examining the association between amygdala activity to angry and fearful faces and peer relational bullying and victimization in a community-based sample of adolescents. Participants included 49 adolescents, 12-15 years old, who underwent fMRI scanning while completing an emotional face matching task. Results indicated that interactions between amygdala activity to angry and fearful faces predicted self-reported relational bullying and victimization. Specifically, a combination of higher amygdala activity to angry faces and lower amygdala activity to fearful faces predicted more bullying behavior, whereas a combination of lower amygdala activity to angry faces and lower amygdala activity to fearful faces predicted less relational victimization. Exploratory whole-brain analyses also suggested that increased rostral anterior cingulate cortex activity to fearful faces was associated with less bullying. These results suggest that relational bullying and victimization are related to different patterns of neural activity to angry and fearful faces, which may help in understanding how patterns of social information processing predict these experiences

Lower structural integrity of the uncinate fasciculus is associated with a history of child maltreatment and future psychological vulnerability to stress

Abstract The experience of child maltreatment is a significant risk factor for the development of later internalizing disorders such as depression and anxiety. This risk is particularly heightened after exposure to additional, more contemporaneous stress. While behavioral evidence exists for such “stress sensitization,” little is known about the mechanisms mediating such relationships, particularly within the brain. Here we report that the experience of child maltreatment independent of recent life stress, gender, and age is associated with reduced structural integrity of the uncinate fasciculus, a major white matter pathway between the amygdala and ventromedial prefrontal cortex, in young adults. We further demonstrate that individuals with lower uncinate fasciculus integrity at baseline who subsequently experience stressful life events report higher levels of internalizing symptomatology at follow-up. Our findings suggest a novel neurobiological mechanism linking child maltreatment with later internalizing symptoms, specifically altered structural connectivity within the brain's threat-detection and emotion-regulation circuitry

Individual differences in regulatory focus predict neural response to reward

Although goal pursuit is related to both functioning of the brain's reward circuits and psychological factors, the literatures surrounding these concepts have often been separate. Here, we use the psychological construct of regulatory focus to investigate individual differences in neural response to reward. Regulatory focus theory proposes two motivational orientations for personal goal pursuit: (1) promotion, associated with sensitivity to potential gain, and (2) prevention, associated with sensitivity to potential loss. The monetary incentive delay task was used to manipulate reward circuit function, along with instructional framing corresponding to promotion and prevention in a within-subject design. We observed that the more promotion oriented an individual was, the lower their ventral striatum response to gain cues. Follow-up analyses revealed that greater promotion orientation was associated with decreased ventral striatum response even to no-value cues, suggesting that promotion orientation may be associated with relatively hypoactive reward system function. The findings are also likely to represent an interaction between the cognitive and motivational characteristics of the promotion system with the task demands. Prevention orientation did not correlate with ventral striatum response to gain cues, supporting the discriminant validity of regulatory focus theory. The results highlight a dynamic association between individual differences in self-regulation and reward system function

Emotion Regulation and the Experience of Future Negative Mood: The Importance of Assessing Social Support

Emotion regulation refers to the use of various strategies, such as cognitive reappraisal and expressive suppression, to help manage our negative experiences, emotions, and thoughts. Although such emotion regulation often occurs within broader social dynamics and interactions, little is known about how social contexts interact with specific regulation strategies to shape the experience of negative emotions. Using data from 544 young adult university students, we provide initial evidence that habitual use of cognitive reappraisal is associated with lower future experience of depression and anxiety primarily through higher perceived social support (PSS). In contrast, expressive suppression is associated with higher future depression and anxiety primarily through lower PSS. These patterns are consistent with the importance of interpersonal influences on emotion regulation and suggest that assessment of social support can help elucidate the mechanisms of successfully regulating negative mood

Brain-age in midlife is associated with accelerated biological aging and cognitive decline in a longitudinal birth-cohort

An individual’s brainAGE is the difference between chronological age and age predicted from machine-learning models of brain-imaging data. BrainAGE has been proposed as a biomarker of age-related deterioration of the brain. Having an older brainAGE has been linked to Alzheimer’s, dementia and mortality. However, these findings are largely based on cross-sectional associations which can confuse age differences with cohort differences. To illuminate the validity of brainAGE as a biomarker of accelerated brain aging, a study is needed of a large cohort all born in the same year who nevertheless vary on brainAGE. In the Dunedin Study, a population-representative 1972–73 birth cohort, we measured brainAGE at age 45 years, as well as the pace of biological aging and cognitive decline in longitudinal data from childhood to midlife (N=869). In this cohort, all chronological age 45 years, brainAGE was measured reliably (ICC=.81) and ranged from 24 to 72 years. Those with older midlife brainAGEs tended to have poorer cognitive function in both adulthood and childhood, as well as impaired brain health at age 3. Furthermore, those with older brainAGEs had an accelerated pace of biological aging, older facial appearance and early signs of cognitive decline from childhood to midlife. These findings help to validate brainAGE as a potential surrogate biomarker for midlife intervention studies that seek to measure dementia-prevention efforts in midlife. However, the findings also caution against the assumption that brainAGE scores represent only age-related deterioration of the brain as they may also index central nervous system variation present since childhood

Social isolation from childhood to mid-adulthood: is there an association with older brain age?

Background: Older brain age - as estimated from structural MRI data - is known to be associated with detrimental mental and physical health outcomes in older adults. Social isolation, which has similar detrimental effects on health, may be associated with accelerated brain aging though little is known about how different trajectories of social isolation across the life course moderate this association. We examined the associations between social isolation trajectories from age 5 to age 38 and brain age assessed at age 45. Methods: We previously created a typology of social isolation based on onset during the life course and persistence into adulthood, using group-based trajectory analysis of longitudinal data from a New Zealand birth cohort. The typology comprises four groups: 'never-isolated', 'adult-only', 'child-only', and persistent 'child-adult' isolation. A brain age gap estimate (brainAGE) - the difference between predicted age from structural MRI date and chronological age - was derived at age 45. We undertook analyses of brainAGE with trajectory group as the predictor, adjusting for sex, family socio-economic status, and a range of familial and child-behavioral factors. Results: Older brain age in mid-adulthood was associated with trajectories of social isolation after adjustment for family and child confounders, particularly for the 'adult-only' group compared to the 'never-isolated' group. Conclusions: Although our findings are associational, they indicate that preventing social isolation, particularly in mid-adulthood, may help to avert accelerated brain aging associated with negative health outcomes later in life

Associations between life-course-persistent antisocial behaviour and brain structure in a population-representative longitudinal birth cohort

BACKGROUND Studies with behavioural and neuropsychological tests have supported the developmental taxonomy theory of antisocial behaviour, which specifies abnormal brain development as a fundamental aspect of life-course-persistent antisocial behaviour, but no study has characterised features of brain structure associated with life-course-persistent versus adolescence-limited trajectories, as defined by prospective data. We aimed to determine whether life-course-persistent antisocial behaviour is associated with neurocognitive abnormalities by testing the hypothesis that it is also associated with brain structure abnormalities. METHODS We used structural MRI data collected at 45 years of age from participants in the Dunedin Study, a population-representative longitudinal birth cohort of 1037 individuals born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand, who were resident in the province and who participated in the first assessment at 3 years of age. Participants underwent MRI, and mean global cortical surface area and cortical thickness were extracted for each participant. Participants had been previously subtyped as exhibiting life-course-persistent, adolescence-limited, or no history of persistent antisocial behaviour (ie, a low trajectory group) based on informant-reported and self-reported conduct problems from the ages of 7 years to 26 years. Study personnel who processed the MRI images were masked to antisocial group membership. We used linear estimated ordinary least squares regressions to compare each antisocial trajectory group (life-course persistent and adolescence limited) with the low trajectory group to examine whether antisocial behaviour was related to abnormalities in mean global surface area and mean cortical thickness. Next, we used parcel-wise linear regressions to identify antisocial trajectory group differences in surface area and cortical thickness. All results were controlled for sex and false discovery rate corrected. FINDINGS Data from 672 participants were analysed, and 80 (12%) were classified as having life-course-persistent antisocial behaviour, 151 (23%) as having adolescence-limited antisocial behaviour, and 441 (66%) as having low antisocial behaviour. Individuals on the life-course-persistent trajectory had a smaller mean surface area (standardised β=–0·18 [95% CI −0·24 to −0·11]; p<0·0001) and lower mean cortical thickness (standardised β=–0·10 [95% CI −0·19 to −0·02]; p=0·020) than did those in the low group. Compared with the low group, the life-course-persistent group had reduced surface area in 282 of 360 anatomically defined parcels and thinner cortex in 11 of 360 parcels encompassing circumscribed frontal and temporal regions associated with executive function, affect regulation, and motivation. Widespread differences in brain surface morphometry were not observed for the adolescence-limited group compared with either non-antisocial behaviour or life-course-persistent groups. INTERPRETATION These analyses provide initial evidence that differences in brain surface morphometry are associated with life-course-persistent, but not adolescence-limited, antisocial behaviour. As such, the analyses are consistent with the developmental taxonomy theory of antisocial behaviour and highlight the importance of using prospective longitudinal data to define different patterns of antisocial behaviour development. FUNDING US National Institute on Aging, Health Research Council of New Zealand, New Zealand Ministry of Business, Innovation and Employment, UK Medical Research Council, Avielle Foundation, and Wellcome Trust

Using confirmatory factor analysis to measure contemporaneous activation of defined neuronal networks in functional magnetic resonance imaging

a b s t r a c t a r t i c l e i n f o Functional neuroimaging often generates large amounts of data on regions of interest. Such data can be addressed effectively with a widely-used statistical technique based on measurement theory that has not yet been applied to neuroimaging. Confirmatory factor analysis is a convenient hypothesis-driven modeling environment that can be used to conduct formal statistical tests comparing alternative hypotheses regarding the elements of putative neuronal networks. In such models, measures of each activated region of interest are treated as indicators of an underlying latent construct that represents the contemporaneous activation of the elements in the network. As such, confirmatory factor analysis focuses analyses on the activation of hypothesized networks as a whole, improves statistical power by modeling measurement error, and provides a theory-based approach to data reduction with a robust statistical basis. This approach is illustrated using data on seven regions of interest in a hypothesized mesocorticostriatal reward system in a sample of 262 adult volunteers assessed during a card-guessing reward task. A latent construct reflecting contemporaneous activation of the reward system was found to be significantly associated with a latent construct measuring impulsivity, particularly in males

Genetic Variants For Head Size Share Genes and Pathways With Cancer

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer