Cross-sectional study of retrospective self-reported childhood emotional neglect and inhibitory neurometabolite levels in the pregenual anterior cingulate cortex in adult humans.

High childhood emotional maltreatment (CM-EMO) is reported in mood and anxiety disorders. The associations with an increased risk for psychopathology are not fully understood. One potential factor may be through alterations in gamma-Aminobutyric acid (GABA). The pregenual anterior cingulate cortex (pgACC) is an important brain region for emotion processing and its' GABA levels were previously implicated in mood and anxiety disorders pathophysiology. We examined the association between the self-reported CM-EMO in adulthood and GABA + levels in the pgACC and in a control region, anterior mid cingulate cortex. GABA+ and total creatine (tCr) were measured in the pgACC and aMCC voxels in seventy-four healthy volunteers (32 (43%) women, ages 19-54, age [standard deviation] = 27.1 [6.5]) using proton magnetic resonance spectroscopy at 7 T. Childhood Trauma Questionnaire was completed by adult participants to measure retrospective self-reported experience of emotional neglect (CM-EMO-NEG) and emotional abuse (CM-EMO-AB) during childhood. Linear mixed models tested the interaction between the region and the two subscales, and GABA+/tCr ratios, with an adjusted alpha = 0.025. Following, linear models, including with covariates were tested. There was an interaction effect between region and CM-EMO-NEG (B = -0.007, p = 0.009), driven by a negative relationship between CM-EMO-NEG and GABA+/tCr in the pgACC (B = -0.004, p = 0.013). Results for CM-EMO-NEG were robust to inclusion of different covariates (ps < 0.035). There was no interaction effect for the CM-EMO-AB (B = 0.007, p = 0.4). Limitations include cross-sectional measurement and retrospective nature of the CTQ. The findings indicate preliminary importance of inhibitory neurometabolite concentrations in the pgACC for retrospective reporting of CM-EMO-NEG.

Beyond the average: The role of variable reward sensitivity in eating disorders.

Eating disorders are often characterized by episodes of overeating and undereating. To date, most theories have explained the liability for such episodes by differences in traits such as reward sensitivity or cognitive control. Here, we review the evidence for a more parsimonious account of the waxing and waning in food intake by linking it to state-like variability of alleged traits such as reward sensitivity. To formally demonstrate that our variability model of eating disorders could explain a wide range of observed reward-related behavior, we conducted simulations of value-based choices and learning. These simulations based on well-established computational models of reinforcement learning and Bayesian sequential updating show how variability may arise and manifest in eating behavior. We argue that by reconceptualizing stable traits as distributions over likely states promoting adaptation, our proposed model integrates disparate findings and leads to novel predictions in a quantitative framework. Collectively, these emerging results call for a stronger emphasis on within-person variability to improve mechanistic insights into eating disorders.

LGALS3BP regulates centriole biogenesis and centrosome hypertrophy in cancer cells.

Centrosome morphology and number are frequently deregulated in cancer cells. Here, to identify factors that are functionally relevant for centrosome abnormalities in cancer cells, we established a protein-interaction network around 23 centrosomal and cell-cycle regulatory proteins, selecting the interacting proteins that are deregulated in cancer for further studies. One of these components, LGALS3BP, is a centriole- and basal body-associated protein with a dual role, triggering centrosome hypertrophy when overexpressed and causing accumulation of centriolar substructures when downregulated. The cancer cell line SK-BR-3 that overexpresses LGALS3BP exhibits hypertrophic centrosomes, whereas in seminoma tissues with low expression of LGALS3BP, supernumerary centriole-like structures are present. Centrosome hypertrophy is reversed by depleting LGALS3BP in cells endogenously overexpressing this protein, supporting a direct role in centrosome aberration. We propose that LGALS3BP suppresses assembly of centriolar substructures, and when depleted, causes accumulation of centriolar complexes comprising CPAP, acetylated tubulin and centrin.