Pubertal maturation and sex effects on the default-mode network connectivity implicated in mood dysregulation

This study examines the effects of puberty and sex on the intrinsic functional connectivity (iFC) of brain networks, with a focus on the default-mode network (DMN). Consistently implicated in depressive disorders, the DMN’s function may interact with puberty and sex in the development of these disorders, whose onsets peak in adolescence, and which show strong sex disproportionality (females > males). The main question concerns how the DMN evolves with puberty as a function of sex. These effects are expected to involve within- and between-network iFC, particularly, the salience and the central-executive networks, consistent with the Triple-Network Model. Resting-state scans of an adolescent community sample (n = 304, male/female: 157/147; mean/std age: 14.6/0.41 years), from the IMAGEN database, were analyzed using the AFNI software suite and a data reduction strategy for the effects of puberty and sex. Three midline regions (medial prefrontal, pregenual anterior cingulate, and posterior cingulate), within the DMN and consistently implicated in mood disorders, were selected as seeds. Within- and between-network clusters of the DMN iFC changed with pubertal maturation differently in boys and girls (puberty-X-sex). Specifically, pubertal maturation predicted weaker iFC in girls and stronger iFC in boys. Finally, iFC was stronger in boys than girls independently of puberty. Brain–behavior associations indicated that lower connectivity of the anterior cingulate seed predicted higher internalizing symptoms at 2-year follow-up. In conclusion, weaker iFC of the anterior DMN may signal disconnections among circuits supporting mood regulation, conferring risk for internalizing disorders

Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr

Feature-based representations of emotional facial expressions in the human amygdala.

The amygdala plays a central role in processing facial affect, responding to diverse expressions and features shared between expressions. Although speculation exists regarding the nature of relationships between expression- and feature-specific amygdala reactivity, this matter has not been fully explored. We used functional magnetic resonance imaging and principal component analysis (PCA) in a sample of 300 young adults, to investigate patterns related to expression- and feature-specific amygdala reactivity to faces displaying neutral, fearful, angry or surprised expressions. The PCA revealed a two-dimensional correlation structure that distinguished emotional categories. The first principal component separated neutral and surprised from fearful and angry expressions, whereas the second principal component separated neutral and angry from fearful and surprised expressions. This two-dimensional correlation structure of amygdala reactivity may represent specific feature-based cues conserved across discrete expressions. To delineate which feature-based cues characterized this pattern, face stimuli were averaged and then subtracted according to their principal component loadings. The first principal component corresponded to displacement of the eyebrows, whereas the second principal component corresponded to increased exposure of eye whites together with movement of the brow. Our results suggest a convergent representation of facial affect in the amygdala reflecting feature-based processing of discrete expressions

Prefrontal Responses during Proactive and Reactive Inhibition Are Differentially Impacted by Stress in Anorexia and Bulimia Nervosa.

Binge eating is a distressing, transdiagnostic eating disorder symptom associated with impulsivity, particularly in negative mood states. Neuroimaging studies of bulimia nervosa (BN) report reduced activity in frontostriatal regions implicated in self-regulatory control, and an influential theory posits that binge eating results from self-regulation failures under stress. However, there is no direct evidence that psychological stress impairs self-regulation in binge-eating disorders, or that any such self-regulatory deficits generalize to binge eating in underweight individuals (i.e., anorexia nervosa bingeing/purging subtype; AN-BP). We therefore determined the effect of acute stress on inhibitory control in 85 women (BN, 33 women; AN-BP, 22 women; 30 control participants). Participants underwent repeated functional MRI scanning during performance of the Stop-signal anticipation task, a validated measure of proactive (i.e., anticipation of stopping) and reactive (outright stopping) inhibition. Neural and behavioral responses to induced stress and a control task were evaluated on 2 consecutive days. Women with BN had reduced proactive inhibition, while prefrontal responses were increased in both AN-BP and BN. Reactive inhibition was neurally and behaviorally intact in both diagnostic groups. Both AN-BP and BN groups showed distinct stress-induced changes in inferior and superior frontal activity during both proactive and reactive inhibition. However, task performance was unaffected by stress. These results offer novel evidence of reduced proactive inhibition in BN, yet inhibitory control deficits did not generalize to AN-BP. Our findings identify intriguing alterations of stress responses and inhibitory function associated with binge eating, but they counsel against stress-induced failures of inhibitory control as a comprehensive explanation for loss-of-control eating.SIGNIFICANCE STATEMENT Binge eating is a common psychiatric syndrome that feels uncontrollable to the sufferer. Theoretically, it has been related to reduced self-regulation under stress, but there remains no direct evidence for this link in binge-eating disorders. Here, we examined how experimentally induced stress affected response inhibition in control participants and women with anorexia nervosa and bulimia nervosa. Participants underwent repeated brain scanning under stressful and neutral conditions. Although patient groups had intact action cancellation, the slowing of motor responses was impaired in bulimia nervosa, even when the likelihood of having to stop increased. Stress altered brain responses for both forms of inhibition in both groups, yet performance remained unimpaired. These findings counsel against a simple model of stress-induced disinhibition as an adequate explanation for binge eating.Funding was provided by the Bernard Wolfe Health Neuroscience Fund to PCF and HZ and a Wellcome Trust Investigator Award to PCF (Reference No. 206368/Z/17/Z). MLW was supported through the NIH-Oxford-Cambridge Scholars Program and a Cambridge Trust fellowship. FM was supported by research grants from Versus Arthritis, the Experimental Psychological Society and a Career Development Award from the Medical Research Council (MR/T010614/1). AG, CG and ME were supported by the Intramural Research Program of the NIMH (Ref. ZIAMH002798). The Wellcome Trust/NIHR Clinical and Translational Research Facilities and the Wolfson Brain Imaging Centre provided equipment and support staff for the study. This research was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014)