Early-life stress biases responding to negative feedback and increases amygdala volume and vulnerability to later-life stress.

Early-life stress (ELS) or adversity, particularly in the form of childhood neglect and abuse, is associated with poor mental and physical health outcomes in adulthood. However, whether these relationships are mediated by the consequences of ELS itself or by other exposures that frequently co-occur with ELS is unclear. To address this question, we carried out a longitudinal study in rats to isolate the effects of ELS on regional brain volumes and behavioral phenotypes relevant to anxiety and depression. We used the repeated maternal separation (RMS) model of chronic ELS, and conducted behavioral measurements throughout adulthood, including of probabilistic reversal learning (PRL), responding on a progressive ratio task, sucrose preference, novelty preference, novelty reactivity, and putative anxiety-like behavior on the elevated plus maze. Our behavioral assessment was combined with magnetic resonance imaging (MRI) for quantitation of regional brain volumes at three time points: immediately following RMS, young adulthood without further stress, and late adulthood with further stress. We found that RMS caused long-lasting, sexually dimorphic biased responding to negative feedback on the PRL task. RMS also slowed response time on the PRL task, but without this directly impacting task performance. RMS animals were also uniquely sensitive to a second stressor, which disproportionately impaired their performance and slowed their responding on the PRL task. MRI at the time of the adult stress revealed a larger amygdala volume in RMS animals compared with controls. These behavioral and neurobiological effects persisted well into adulthood despite a lack of effects on conventional tests of 'depression-like' and 'anxiety-like' behavior, and a lack of any evidence of anhedonia. Our findings indicate that ELS has long-lasting cognitive and neurobehavioral effects that interact with stress in adulthood and may have relevance for understanding the etiology of anxiety and depression in humans.

Multicentre evaluation of renal impairment in thoracic surgery (MERITS): a retrospective cohort study.

OBJECTIVES: To measure the unit-level variation in Acute Kidney Injury (AKI) incidence post-thoracic surgery over a contemporary 1-year period. Secondary aims include examining the associations with sex, age group, operation type, length of stay and mortality. DESIGN: A multicentre, observational, retrospective study in thoracic surgery. SETTING: 17 of 35 Society for Cardiothoracic Surgery of Great Britain and Ireland (SCTS) units participated. The student wing, known as SCTS STUDENTS, supported data collection. PARTICIPANTS: Overall, 15 229 patients were collected of which 15 154 were included for analysis after exclusions. All patients (age≥18 years) undergoing any thoracic surgery from 1 April 2016 to 31 March 2017 were included. For analysis, we excluded patients with preoperative end-stage renal failure and those with incomplete data. MAIN OUTCOME MEASURES: The primary outcome is the incidence of AKI within 7 days of the procedure or discharge date if earlier. Secondary outcomes include assessing associations with patient demographics (age, sex), type of procedure (open and minimally invasive), length of stay and mortality. RESULTS: Out of 15 154 patients AKI was diagnosed in 1090 patients (7.2%) within 7 days of surgery with AKI stage 1 (4.8%), stage 2 (1.7%) and stage 3 (0.7%). There was a statistically significant variation in AKI incidence between units from 3.1 to 16.1% (p<0.05). Significant differences between AKI and non-AKI were found in post-operative length of stay (7 vs 3 days, p<0.001), 30-day mortality (9 vs 1.6%, p<0.001), 90-day mortality (14.7 vs 4.4%, p<0.001) and 1-year mortality (23.1 vs 12.2 %, p<0.001). CONCLUSIONS: Following thoracic surgery, AKI incidence ranged from 3.1% to 16.1% between units (p<0.05) with associations between AKI and both length of stay and mortality. We propose AKI as a suitable comparative and absolute quality measure in thoracic surgery. Reducing rates of AKI may improve patient outcomes, length of stay and reduce costs.

Early-life stress and inflammation: A systematic review of a key experimental approach in rodents.

Repeated maternal separation is the most widely used pre-clinical approach to investigate the relationship between early-life chronic stress and its neuropsychiatric and physical consequences. In this systematic review, we identified 46 studies that conducted repeated maternal separation or single-episode maternal separation and reported measurements of interleukin-1b, interleukin-6, interleukin-10, tumour necrosis factor-alpha, or microglia activation and density. We report that in the short-term and in the context of later-life stress, repeated maternal separation has pro-inflammatory immune consequences in diverse tissues. Repeated maternal separation animals exhibit greater microglial activation and elevated pro-inflammatory cytokine signalling in key brain regions implicated in human psychiatric disorders. Notably, repeated maternal separation generally has no long-term effect on cytokine expression in any tissue in the absence of later-life stress. These observations suggest that the elevated inflammatory signalling that has been reported in humans with a history of early-life stress may be the joint consequence of ongoing stressor exposure together with potentiated neural and/or immune responsiveness to stressors. Finally, our findings provide detailed guidance for future studies interrogating the causal roles of early-life stress and inflammation in disorders such as major depression.