Effects of Alcohol on Tests of Executive Functioning in Men and Women: A Dose Response Examination

Alcohol has been shown to affect performance on tasks associated with executive functioning. However, studies in this area have generally been limited to a single dose or gender or have used small sample sizes. The purpose of this study was to provide a more nuanced and systematic examination of alcohol\u27s effects on commonly used tests of executive functioning at multiple dosages in both men and women. Research volunteers (91 women and 94 men) were randomly assigned to one of four drink conditions (alcohol doses associated with target blood alcohol concentrations of .000%, .050%, .075%, and .100%). Participants then completed three tasks comprising two domains of executive functioning: two set shifting tasks, the Trail Making Test and a computerized version of the Wisconsin Card Sorting Task, and a response inhibition task, the Go Stop Impulsivity Paradigm. Impaired performance on set shifting tasks was found at the .100% and .075% dosages, but alcohol intoxication did not impair performance on the Go Stop. No gender effects emerged. Thus, alcohol negatively affects set shifting at moderately high levels of intoxication in both men and women, likely attributable to alcohol\u27s interference with prefrontal cortex function. Although it is well established that alcohol negatively affects response inhibition as measured by auditory stop-signal tasks, alcohol does not appear to exert a negative effect on response inhibition as measured by the Go Stop, a visual stop-signal task

An Electrophysiological Investigation of the Cognitive Processes Underlying Provoked Aggression in Humans

Recently, the event-related potential (ERP) technique has been applied to questions of social information processing. Several studies have examined standard and social information processing variables in aggressive individuals, but little is known about the neurophysiological processes that take place in real-time during an aggressive encounter. In this study, 48 men and women high and low in aggression history exchanged noise blasts of varying intensity with a (fictitious) opponent in a modified version of a well-validated laboratory-controlled behavioral measure of aggression, the Taylor Reaction-time Task (Taylor, 1967), while ERPs were simultaneously being recorded at scalp sites. Mixed model ANOVAs were used to analyze differences between aggressive and non-aggressive men and women in the neurophysiological processes related to perceiving provocation and responding to threat. Dependent variables included mean amplitude and latency for the following ERP components: P3 (to provocation), N2, No-Go P3, N450, and the negative slow wave (NSW). Aggressive participants were more likely to make errors in identifying the high provocation stimuli while non-aggressive participants were not. Non-aggressive participants showed greater and slower processing of provocative stimuli as evidenced by larger P3 amplitude and later P3 peak. During the aggression trials, aggressive participants were more likely to administer a “high” noise blast to the opponent under conditions of low provocation. Both the aggressive and non-aggressive groups made greater use of the “high” noise blast following high provocation. Effects were also observed for components iii previously linked to inhibitory processes (N2, No-Go P3, N450, and NSW). The results suggest that aggressive and non-aggressive individuals process personally relevant threat information differently. More research is needed to understand how ERP components putatively linked to inhibitory cognitive processes relate to aggression in real-world encounters. Further implications and future directions are discussed

Perceived Threat Mediates the Relationship Between Psychosis Proneness and Aggressive Behavior

Psychotic symptoms are associated with aggressive tendencies, but this relationship is both complex and imperfect. In contrast to psychotic disorders, little is known about aggressive behavior and sub-clinical psychotic symptoms (e.g., psychosis proneness ), which are relatively common in the general population. Threat/control-override (TCO), which is the propensity to overestimate the likelihood that an outside agent will (1) inflict harm (threat) or (2) control one\u27s behaviors (control-override), has been associated with aggression in both psychiatric and community samples. The purpose of this study was to determine if psychosis proneness is related to aggression, and if one or both aspects of TCO mediate this relationship. We hypothesized that the propensity to overestimate threat would mediate this relationship, but control-override would not. Sixty men and sixty women (mean age = 20.00 years, sd = 3.00) with no history of psychotic disorder completed measures assessing psychosis proneness, threat control/override, aggressive history, aggressive ideation, and aggressive behavior. Three structural equation models were tested: (1) Threat and control-override modeled as separate mediating variables, (2) TCO as a unitary mediating latent construct, and (3) TCO considered as part of a psychosis proneness latent variable. Results indicated that psychosis proneness is positively related to aggression and that the best model fit was obtained when threat and control-override were modeled as separate variables, with mediation through threat alone. The utility of TCO for explaining the relation between psychosis spectrum symptoms and aggression is discussed. (C) 2010 Elsevier Ireland Ltd. All rights reserved

Maternal Black Race and Persistent Wheezing Illness in Former Extremely Low Gestational Age Newborns: Secondary Analysis of a Randomized Trial.

ObjectiveTo evaluate the relationship between maternal self-reported race/ethnicity and persistent wheezing illness in former high-risk, extremely low gestational age newborns, and to quantify the contribution of socioeconomic, environmental, and biological factors on this relationship.Study designWe assessed persistent wheezing illness determined at 18-24 months corrected (for prematurity) age in survivors of a randomized trial. Parents/caregivers were surveyed for wheeze and inhaled asthma medication use quarterly to 12 months, and at 18 and 24 months. We used multivariable analysis to evaluate the relationship of maternal race to persistent wheezing illness, and identified mediators for this relationship via formal mediation analysis.ResultsOf 420 infants (25.2 ± 1.2 weeks of gestation and 714 ± 166 g at birth, 57% male, 34% maternal black race), 189 (45%) had persistent wheezing illness. After adjustment for gestational age, birth weight, and sex, infants of black mothers had increased odds of persistent wheeze compared with infants of nonblack mothers (OR = 2.9, 95% CI 1.9, 4.5). Only bronchopulmonary dysplasia, breast milk diet, and public insurance status were identified as mediators. In this model, the direct effect of race accounted for 69% of the relationship between maternal race and persistent wheeze, whereas breast milk diet, public insurance status, and bronchopulmonary dysplasia accounted for 8%, 12%, and 10%, respectively.ConclusionsAmong former high-risk extremely low gestational age newborns, infants of black mothers have increased odds of developing persistent wheeze. A substantial proportion of this effect is directly accounted for by race, which may reflect unmeasured environmental influences, and acquired and innate biological differences.Trial registrationClinicalTrials.gov: NCT01022580

Metformin in women with type 2 diabetes in pregnancy (MiTy): a multicentre, international, randomised, placebo-controlled trial

Background: Although metformin is increasingly being used in women with type 2 diabetes during pregnancy, little data exist on the benefits and harms of metformin use on pregnancy outcomes in these women. We aimed to investigate the effects of the addition of metformin to a standard regimen of insulin on neonatal morbidity and mortality in pregnant women with type 2 diabetes. Methods: In this prospective, multicentre, international, randomised, parallel, double-masked, placebo-controlled trial, women with type 2 diabetes during pregnancy were randomly assigned from 25 centres in Canada and four in Australia to receive either metformin 1000 mg twice daily or placebo, added to insulin. Randomisation was done via a web-based computerised randomisation service and stratified by centre and pre-pregnancy BMI (<30 kg/m2 or ≥30 kg/m2) in a ratio of 1:1 using random block sizes of 4 and 6. Women were eligible if they had type 2 diabetes, were on insulin, had a singleton viable pregnancy, and were between 6 and 22 weeks plus 6 days' gestation. Participants were asked to check their fasting blood glucose level before the first meal of the day, before the last meal of the day, and 2 h after each meal. Insulin doses were adjusted aiming for identical glucose targets (fasting glucose <5·3 mmol/L [95 mg/dL], 2-h postprandial glucose <6·7 mmol/L [120 mg/dL]). Study visits were done monthly and patients were seen every 1–4 weeks as was needed for standard clinical care. At study visits blood pressure and bodyweight were measured; patients were asked about tolerance to their pills, any hospitalisations, insulin doses, and severe hypoglycaemia events; and glucometer readings were downloaded to the central coordinating centre. Participants, caregivers, and outcome assessors were masked to the intervention. The primary outcome was a composite of fetal and neonatal outcomes, for which we calculated the relative risk and 95% CI between groups, stratifying by site and BMI using a log-binomial regression model with an intention-to-treat analysis. Secondary outcomes included several relevant maternal and neonatal outcomes. The trial was registered with ClinicalTrials.gov, NCT01353391. Findings: Between May 25, 2011, and Oct 11, 2018, we randomly assigned 502 women, 253 (50%) to metformin and 249 (50%) to placebo. Complete data were available for 233 (92%) participants in the metformin group and 240 (96%) in the placebo group for the primary outcome. We found no significant difference in the primary composite neonatal outcome between the two groups (40% vs 40%; p=0·86; relative risk [RR] 1·02 [0·83 to 1·26]). Compared with women in the placebo group, metformin-treated women achieved better glycaemic control (HbA1c at 34 weeks' gestation 41·0 mmol/mol [SD 8·5] vs 43·2 mmol/mol [–10]; 5·90% vs 6·10%; p=0·015; mean glucose 6·05 [0·93] vs 6·27 [0·90]; difference −0·2 [–0·4 to 0·0]), required less insulin (1·1 units per kg per day vs 1·5 units per kg per day; difference −0·4 [95% CI −0·5 to −0·2]; p<0·0001), gained less weight (7·2 kg vs 9·0 kg; difference −1·8 [–2·7 to −0·9]; p<0·0001) and had fewer caesarean births (125 [53%] of 234 in the metformin group vs 148 [63%] of 236 in the placebo group; relative risk [RR] 0·85 [95% CI 0·73 to 0·99]; p=0·031). We found no significant difference between the groups in hypertensive disorders (55 [23%] in the metformin group vs 56 [23%] in the placebo group; p=0·93; RR 0·99 [0·72 to 1·35]). Compared with those in the placebo group, metformin-exposed infants weighed less (mean birthweight 3156 g [SD 742] vs 3375 g [742]; difference −218 [–353 to −82]; p=0·002), fewer were above the 97th centile for birthweight (20 [9%] in the metformin group vs 34 [15%] in the placebo group; RR 0·58 [0·34 to 0·97]; p=0·041), fewer weighed 4000 g or more at birth (28 [12%] in the metformin group vs 44 [19%] in the placebo group; RR 0·65 [0·43 to 0·99]; p=0·046), and metformin-exposed infants had reduced adiposity measures (mean sum of skinfolds 16·0 mm [SD 5·0] vs 17·4 [6·2] mm; difference −1·41 [–2·6 to −0·2]; p=0·024; mean neonatal fat mass 13·2 [SD 6·2] vs 14·6 [5·0]; p=0·017). 30 (13%) infants in the metformin group and 15 (7%) in the placebo group were small for gestational age (RR 1·96 [1·10 to 3·64]; p=0·026). We found no significant difference in the cord c-peptide between groups (673 pmol/L [435] in the metformin group vs 758 pmol/L [595] in the placebo group; p=0·10; ratio of means 0·88 [0·72 to 1·02]). The most common adverse event reported was gastrointestinal (38 events in the metformin group and 38 events in the placebo group). Interpretation: We found several maternal glycaemic and neonatal adiposity benefits in the metformin group. Along with reduced maternal weight gain and insulin dosage and improved glycaemic control, the lower adiposity and infant size measurements resulted in fewer large infants but a higher proportion of small-for-gestational-age infants. Understanding the implications of these effects on infants will be important to properly advise patients who are contemplating the use of metformin during pregnancy.The trial was funded by the Canadian Institutes of Health Research, the Lunenfeld-Tanenbaum Research Institute, Toronto, ON, Canada, and the Department of Medicine, University of Toronto, Toronto, ON, Canada