Performance In Adulthood Research Articles

Inhibition of the NLRP3/caspase-1 cascade related pyroptosis relieved propofol-induced neuroinflammation and cognitive impairment in developing rats

BackgroundNumerous preclinical studies have demonstrated that prolonged exposure to propofol (A general anaesthetics) can lead to hippocampus injury in immature brains and impact long-term learning and memory functions. Neuroinflammation plays a pivotal role in the impairment of brain function associated with early exposure to anesthetic drugs. Nevertheless, the involvement of hippocampal pyroptosis and neuroinflammation mediated by the NLRP3/caspase-1 signaling cascade in propofol-induced developmental neurotoxicity remains unclear. MethodsPostnatal day (PND) 7 SD rats, PC12 cells, and HAPI cells were used to establish propofol neurotoxicity models in vivo and in vitro, respectively. We examined the potential hippocampal injury and cognitive dysfunction caused by propofol in neonatal rats through the NLRP3/caspase-1 signaling pathway using MCC950 and VX765 to inhibit the pathway. This investigation involved assessing histological changes in the hippocampus, behavioral performance in adulthood, NLRP3-related pyroptosis indicators, and neuroinflammatory cytokines. ResultsBoth in vivo and in vitro studies have demonstrated that exposure to propofol activates the NLRP3/caspase-1 signaling cascade in the hippocampus of PND7 rats, leading to pyroptosis, neuroinflammation, and subsequent hippocampal injury and behavioral changes in adulthood. However, MCC950 and VX765 inhibit the NLRP3/caspase-1 signaling cascade, reversing the developmental neurotoxicity of propofol. ConclusionOur study findings suggest that negative regulation of NLRP3/caspase-1 activation may serve as a potential therapeutic strategy for developmental neuroinflammation induced by propofol.

Gender differences in literacy in PIAAC: do assessment features matter?

BackgroundPrevious research based on large-scale studies consistently suggests that on average, male students tend to have lower literacy compared to their female students during secondary schooling. However, this gender gap in literacy seems to “disappear” during adulthood. Up until today, only a few studies investigated the role of assessment features in gender differences in literacy performance in adulthood. This study aims to understand the relationship between assessment features and gender differences in literacy skills.MethodsUsing the German 2012 PIAAC data (N = 4,512), we applied item-level analyses using linear probability models to examine gender differences in the probability of solving a literacy item correctly with six assessment features including (1) text format, (2) text topics, (3) text length, (4) cognitive strategies, (5) numerical content of the text/questions, and (6) gender typicality of content.ResultsWe found that men had a 13.4% higher probability of solving items with a noncontinuous text format correctly than women. Men also had a 9.4% higher probability of solving short text items correctly and a 4.6% higher probability of solving items with a medium/high numerical content in the question correctly than women. There were small to negligible gender differences in literacy performance in terms of text topics, cognitive strategies, and gender typicality of content.ConclusionsOur findings highlight the role of text format, text length, and numerical content in gender differences in literacy skills, suggesting that further refining these practices can enhance the fairness and accuracy of literacy assessments. Specifically, we advocate for ongoing research aimed at understanding and minimizing the potential bias introduced by these assessment features. Such efforts are not only crucial for developing instruments that accurately measure literacy skills, but they also yield insights that hold significant implications for educational researchers and practitioners dedicated to creating more equitable assessment environments.

Grape seed extract protects rat offspring hippocampus from the silicon dioxide nanoparticles' neurotoxicity.

Silicon dioxide nanoparticles (SiO2-NPs) can be found in many products, such as composites, paints, ceramics, consumer products, and food additives. We recently demonstrated that via breastfeeding, SiO2-NPs transfer to the offspring's brain, interfering negatively with hippocampus development. In this work, we evaluated the protective effect of grape seed extract (GSE) against the adverse effects of SiO2-NPs. After delivery, animals were administered 25mg/kg SiO2-NPs with/without GSE (300mg/kg) for 20days (from 2nd to 21st days post-delivery) by gavage. SiO2-NPs increased malondialdehyde concentration and decreased antioxidant activity in the offspring's hippocampi. The mean number of dark neurons (DNs) was significantly higher in the hippocampi of the SiO2-NPs group, whereas the mean number of DCX + cells was significantly lower than in the control group. The offspring in the SiO2-NPs groups had a weak cognitive performance in adulthood. Interestingly, these adverse effects of SiO2-NPs were alleviated in the GSE-treated groups. Therefore, GSE can attenuate the damaging effects of maternal exposure to SiO2-NPs during lactation.

Exposure to neighborhood violence, and laboratory-based and ambulatory cognitive task performance in adulthood

ObjectiveExposure to neighborhood violence may have negative implications for adults’ cognitive functioning, but the ecological sensitivity of these effects has yet to be determined. We first evaluated the link between exposure to neighborhood violence and two latent constructs of cognitive function that incorporated laboratory-based and ambulatory, smartphone-based, cognitive assessments. Second, we examined whether the effect of exposure to violence was stronger for ambulatory assessments compared to in-lab assessments. MethodsWe used data from 256 urban-dwelling adults between 25 and 65 years old (M = 46.26, SD = 11.07); 63.18% non-Hispanic Black, 9.21% non-Hispanic White, 18.41% Hispanic White, 5.02% Hispanic Black, and 4.18% other. Participants completed baseline surveys on neighborhood exposures, cognitive assessments in a laboratory/research office, and ambulatory smartphone-based cognitive assessments five-times a day for 14 days. ResultsExposure to neighborhood violence was associated with poorer performance in a latent working memory construct that incorporated in-lab and ambulatory assessments, but was not associated with the perceptual speed construct. The effect of exposure to neighborhood violence on the working memory construct was explained by its effect on the ambulatory working memory task and not by the in-lab cognitive assessments. ConclusionThis study shows the negative effect that exposure to neighborhood violence may have on everyday working memory performance in urban-dwelling adults in midlife. Results highlight the need for more research to determine the sensitivity of ambulatory assessments to quantify the effects of neighborhood violence on cognitive function.

The influence of early life socio-environmental factors on executive performance in a healthy adult sample.

Attempts have been made (with research efforts encouraged) to deconstruct the "race" concept into language, cultural, and life experience variables that can help explain performance differences found between ethnic groups (Romero et al., 2009). The extant empirical literature reveals that early environmental factors and life experiences (e.g., socioeconomic status) are related to cognitive test performance in adulthood (Byrd et al., 2006). This study examined the explanatory value of early life childhood resources in the relationship between ethnicity and neuropsychological test performance in adulthood. Neurologically and psychologically healthy African American (n = 40), Caucasian (n = 14), and Hispanic (n = 107) college students ranging from 19-38 years of age. On average, participants had completed around 13 years of education, indicating that the majority were in the early stages of their undergraduate studies and mostly consisted of females (72%). Each participant completed a comprehensive neuropsychological battery that included tests of executive function and an extensive background questionnaire. A one-way analysis of variance (ANOVA) revealed that the CA group was significantly older (F (2, 160) = 18.38, p = .045) compared to the AA and H groups, but the groups did not differ in terms of number of years of educations or gender. Also, an ANOVA revealed significant group test performance differences on the Stroop-C [F (2, 160) = 1.53, p = .047], but not on the TMT-B and COWAT. Furthermore, a Tukey post hoc revealed that there were no significant differences in test performance on Stroop-C between the groups. Hierarchical multiple regression analyses revealed that group performance differences on executive function tests were medium or non-existent and only partially explained by years of education and early life financial resources. The results are discussed in light of the existing literature, study strengths and limitations, as well as directions for future research. This research can aid in pinpointing variables crucial for interpreting differences in neuropsychological assessments among diverse populations, holding potential implications for intervention research and policy settings. It is particularly relevant in the context of the continuously evolving social, political, and economic landscapes of societies.

The Impacts of Periconceptional Alcohol on Neonatal Ovaries and Subsequent Adult Fertility in the Rat.

Maternal exposures during pregnancy can impact the establishment of the ovarian reserve in offspring, the lifetime supply of germ cells that determine a woman's reproductive lifespan. However, despite alcohol consumption being common in women of reproductive age, the impact of prenatal alcohol on ovarian development is rarely investigated. This study used an established rat model of periconceptional ethanol exposure (PCEtOH; 12.5% v/v ethanol) for 4 days prior to 4 days post-conception. Ovaries were collected from neonates (day 3 and day 10), and genes with protein products involved in regulating the ovarian reserve analyzed by qPCR. Adult offspring had estrous cycles monitored and breeding performance assessed. PCEtOH resulted in subtle changes in expression of genes regulating apoptosis at postnatal day (PN) 3, whilst those involved in regulating growth and recruitment of primordial follicles were dysregulated at PN10 in neonatal ovaries. Despite these gene expression changes, there were no significant impacts on breeding performance in adulthood, nor on F2-generation growth or survival. This contributes additional evidence to suggest that a moderate level of alcohol consumption exclusively around conception, when a woman is often unaware of her pregnancy, does not substantially impact the fertility of her female offspring.

Childhood ADHD and subthreshold symptoms are associated with cognitive functioning at age 40-a cohort study on perinatal birth risks.

In this prospective cohort study over 40 years we investigated the effect of childhood attention-deficit/hyperactivity disorder (ADHD) and subthreshold ADHD on cognitive performance in adulthood. The cohort comprised individuals with mild perinatal risks. Childhood ADHD group (cADHD, n = 39) was compared to a group with subthreshold childhood attention or hyperactivity symptoms (cAP; n = 79), a group with similar perinatal risks but no ADHD symptoms (n = 255), and to controls without ADHD symptoms or perinatal risks (n = 69). The groups were assessed with multiple neuropsychological measures in domains of verbal reasoning, perceptual skills, memory, working memory, attention, executive functions, and speed. Group-level differences and frequencies of deficient functioning were analyzed. Overall, the groups' performance differed in all cognitive domains at age 40. Verbal reasoning, perceptual skills, memory, and speed had the largest effect sizes (0.51-0.62). The cADHD group's performance was lower than the other groups' on 13 out of 21 measures. The cAP group performed poorer than controls on five measures. In the cADHD group, 23% had three or more deficient cognitive domains, compared to 4-6% in the other groups. Childhood ADHD is associated with impaired cognitive functioning in adulthood on several cognitive domains whereas childhood subthreshold ADHD is linked to fewer cognitive deficits. Task complexity was linked to poorer performance within the ADHD group. Our results add to the scarce longitudinal evidence of cognitive outcomes related to childhood ADHD and subthreshold symptoms.

Defects in AMPAR trafficking and microglia activation underlie socio-cognitive deficits associated to decreased expression of phosphodiesterase 2 a

Phosphodiesterase 2 A (PDE2A) is an enzyme involved in the homeostasis of cAMP and cGMP and is the most highly expressed PDE in human brain regions critical for socio-cognitive behavior. In cerebral cortex and hippocampus, PDE2A expression level is upregulated in Fmr1-KO mice, a model of the Fragile X Syndrome (FXS), the most common form of inherited intellectual disability (ID) and autism spectrum disorder (ASD). Indeed, PDE2A translation is negatively modulated by FMRP, whose functional absence causes FXS. While the pharmacological inhibition of PDE2A has been associated to its pro-cognitive role in normal animals and in models of ID and ASD, homozygous PDE2A mutations have been identified in patients affected by ID, ASD and epilepsy. To clarify this apparent paradox about the role of PDE2A in brain development, we characterized here Pde2a+/− mice (homozygote animals being not viable) at the behavioral, cellular, molecular and electrophysiological levels. Pde2a+/− females display a milder form of the disorder with reduced cognitive performance in adulthood, conversely males show severe socio-cognitive deficits throughout their life. In males, these phenotypes are associated with microglia activation, elevated glutathione levels and increased externalization of Glutamate receptor (GluR1) in CA1, producing reduced mGluR-dependent Long-term Depression. Overall, our results reveal molecular targets of the PDE2A-dependent pathway underlying socio-cognitive performance. These results clarify the mechanism of action of pro-cognitive drugs based on PDE2A inactivation, which have been shown to be promising therapeutic approaches for Alzheimer's disease, schizophrenia, FXS as well as other forms of ASD.

Childhood and life‐course socioeconomic position and cognitive function in adult population of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

AbstractBackgroundThe Hispanic/Latino population experiences extensive socioeconomic adversity across the lifespan and is at greater risk of cognitive decline. Yet little is known about the role of life‐course socioeconomic position (SEP) and cognitive function in this population. We assessed the association between childhood SEP and cognitive function in Hispanic/Latino adults, whether this association is mediated by midlife SEP, and whether socioeconomic mobility is associated with cognitive function.MethodWe used baseline data (2008‐2011) from 9556 adults aged 45‐74 years of the Hispanic Community Health Study/Study of Latino (HCHS/SOL), a multi‐center cohort study conducted in four major U.S cities. We determined childhood SEP using parental educational attainment. Midlife SEP was determined through an index combining participants’ education and household income. We classified participants into socioeconomic mobility categories from childhood to adulthood (e.g., persisting low, upward mobility). Cognitive function was ascertained using neurocognitive tests, including the Six‐Item Screener; Brief‐Spanish English Verbal Learning Test Sum and Recall, Controlled Oral Word Association (or Word Frequency), and the Digit Symbol Substitution Test. Using confirmatory factor analysis and these tests we created a global cognition score. We also standardized z‐score of these neurocognitive measures. Survey linear regression models were performed adjusting for age, sex, Hispanic background, U.S born, smoking, depression, and cardiovascular factors. We also conducted mediation analysis to decompose the direct effect of childhood SEP on cognition and the indirect effect through midlife SEP.ResultChildhood SEP showed a graded association with cognitive function in adulthood with a dose‐response relationship across levels of parental education (β and [95% Confidence Interval (CI)]): Elementary/middle school vs. No schooling 0.34 [0.25‐0.43]; High school (HS) vs. No schooling: 0.53 [0.42‐0.64]; and >HS vs. No schooling: 0.68 [0.57‐0.79]). High midlife SEP was also associated with greater cognitive function relative to low midlife SEP. 37% (95% CI 32%‐44%) of the association between childhood SEP and cognition was mediated through midlife SEP. Holding a high SEP over the life‐course was associated with greater cognitive performance (β: 0.90, 95% CI: 0.79‐1.00) as compared with a persisting low SEP.ConclusionThis study provides evidence that childhood and life‐course SEP influence cognitive performance in adulthood

Talent development in childhood: Early specialization or sampling? From an either… or… question to a 2 × 2 × 3 question cuboid

A central, yet still unresolved, question about optimal youth talent development asks whether children should specialize and train systematically in one sport— early specialization—or gain different playful experiences in several sports— early sampling. Based upon theoretical considerations, we problematize dichotomous discussions and offer a complex 2 × 2 × 3 question cuboid differentiating between two goals (performance in adulthood and positive youth development), two continuum-based dimensions (task-specificity and exercise mode), and three perspectives (nomothetic, group-specific, and idiographic). Accordingly, resolving the question about optimal youth talent development involves assembling answers derived from 12 different questions. Through our theoretical contribution, we identified several nomothetic principles offering stakeholders initial recommendations and orientations to estimate the appropriate need for high task-specificity and exercise mode in relation to each goal. We suggest adapting these recommendations according to group-specific characteristics, such as sport and age, and idiographic fine-tuning according to children's biopsychosocial characteristics.

Adolescent network positions and memory performance in adulthood: Evidence from sibling fixed effects models with sociometric network data

Although research has explored social factors influencing memory performance during adolescence, the impact of adolescent social network positions remains largely unknown. This study examines whether adolescent network position is associated with memory performance in adulthood, while also considering potential gender differences. The study used a sibling sample from the National Longitudinal Study of Adolescent to Adult Health (N = 2462) and employed sibling fixed effects models to account for unobserved family background factors, such as genetics, parental characteristics, family environment, and childhood neighborhood. Four dimensions of adolescent network position—i.e., popularity, sociality, degree centrality, and closeness centrality—were sociometrically assessed in schools. Memory performance in adulthood was measured using the Rey Auditory Verbal Learning Test. The sibling fixed effects estimates indicate that sociality, degree centrality, and closeness centrality are significantly associated with increased memory performance in adulthood, even after controlling for unobserved family heterogeneity as well as a set of individual-level covariates. In contrast, controlling for unobserved family heterogeneity attenuated the association for popularity, making it statistically insignificant. This study also provides evidence of gender differences in the association between social network position and memory performance. The associations for popularity, sociality, and degree centrality are more pronounced among men than women. This study’s findings highlight the importance of adolescent network positions as social determinants in shaping cognitive outcomes over the life course. Interventions that encourage positive peer interactions and reduce social isolation during adolescence may help improve cognitive health in the population.

Aromatase Inhibition and Electroconvulsive Seizures in Adolescent Rats: Antidepressant and Long-Term Cognitive Sex Differences.

We recently showed sex differences in the antidepressant-like potential of electroconvulsive seizures (ECS) in adolescent rats; whereas it worked for male rats, it was inefficacious in females. Because sex steroids might be important modulators of these sex disparities, we evaluated the role of estrogens in the differential response induced by adolescent ECS. Moreover, given the literature suggesting certain cognitive sequelae from ECS exposure, we aimed at evaluating its long-term safety profile in adulthood. Adolescent Sprague-Dawley rats were pretreated with letrozole (1 mg/kg/day) or vehicle (1 mL/kg/day) for 8 days (i.p.) and treated during the last 5 days (3 hours later) with ECS (95 mA, 0.6 s, 100 Hz) or SHAM. Antidepressant-like responses were measured in the forced swim test, and long-term cognitive performance was assessed in the Barnes maze. During adolescence, whereas ECS alone exerted an antidepressant-like response in male rats, its combination with letrozole permitted ECS to also induce efficacy in females. Moreover, adolescent ECS treatment improved cognitive performance in adulthood although exclusively in male rats. Adolescent ECS demonstrated an antidepressant-like potential together with certain long-term beneficial cognitive effects but exclusively in male rats. For females, efficacy was restricted to a situation in which the biosynthesis of estrogens was reduced. Therefore, estrogens and/or testosterone levels play a crucial role in the sex disparities induced by ECS in Sprague-Dawley rats. Based on this study and on the literature supporting its safety, ECS should be encouraged for use in cases of treatment-resistant depression during adolescence, while adhering to sex-specific considerations.

The epigenetic hallmark of early-life α-hexabromocyclododecane exposure: From cerebellar 6-mA levels to locomotor performance in adulthood

There is a growing evidence that methylation at the N6 position of adenine (6-mA), whose modulation occurs primarily during development, would be a reliable epigenetic marker in eukaryotic organisms. The present study raises the question as to whether early-life exposure to α-hexabromocyclododecane (α-HBCDD), a brominated flame retardant, may trigger modifications in 6-mA epigenetic hallmarks in the brain during the development which, in turn could affect the offspring behaviour in adulthood. Pregnant Wistar rats were split into two groups: control and α-HBCDD (66 ng/kg/per os, G0-PND14). At PND1, α-HBCDD levels were assessed in brain and liver by LC-MS/MS. At PND14, DNA was isolated from the offspring’s cerebellum. DNA methylation was measured by 6-mA-specific immunoprecipitation and Illumina® sequencing (MEDIP-Seq). Locomotor activity was finally evaluated at PND120. In our early-life exposure model, we confirmed that α-HBCDD can cross the placental barrier and be detected in pups at birth. An obvious post-exposure phenotype with locomotor deficits was observed when the rats reached adulthood. This was accompanied by sex-specific over-methylation of genes involved in the insulin signaling pathway, MAPK signaling pathway as well as serotonergic and GABAergic synapses, potentially altering the normal process of neurodevelopment with consequent motor impairments crystalized at adulthood.

Childhood and Life-Course Socioeconomic Position and Cognitive Function in the Adult Population of the Hispanic Community Health Study/Study of Latinos.

The Hispanic/Latino population experiences socioeconomic adversities across the lifespan and is at greater risk of cognitive impairment, yet little is known about the role of life-course socioeconomic position (SEP) in cognitive function in this population. Using baseline data (2008-2011) from adults (aged 45-74 years) of the Hispanic Community Health Study/Study of Latinos, we assessed the association between childhood SEP and socioeconomic mobility with cognitive function, and whether this association was mediated by midlife SEP. Childhood SEP was assessed using parental education. An index combining participants' education and household income represented midlife SEP. Socioeconomic mobility was categorized as stable low, downward or upward mobility, and stable high-SEP. Cognitive function measures were modeled using survey linear regression with inverse-probability weighting, accounting for covariates. We used mediation analysis to estimate the indirect effect of childhood SEP on cognition through midlife SEP. High childhood SEP was associated with global cognition in adulthood (coefficient for parental education beyond high school vs. less than high school = 0.26, 95% confidence interval: 0.15, 0.37). This association was partially mediated through midlife SEP (indirect effect coefficient = 0.16, 95% confidence interval: 0.15, 0.18). Low SEP through the life course was associated with the lowest cognitive function. This study provides evidence that life-course SEP influences cognitive performance in adulthood.

Deficits in integrative NMDA receptors caused by Grin1 disruption can be rescued in adulthood

Glutamatergic NMDA receptors (NMDAR) are critical for cognitive function, and their reduced expression leads to intellectual disability. Since subpopulations of NMDARs exist in distinct subcellular environments, their functioning may be unevenly vulnerable to genetic disruption. Here, we investigate synaptic and extrasynaptic NMDARs on the major output neurons of the prefrontal cortex in mice deficient for the obligate NMDAR subunit encoded by Grin1 and wild-type littermates. With whole-cell recording in brain slices, we find that single, low-intensity stimuli elicit surprisingly-similar glutamatergic synaptic currents in both genotypes. By contrast, clear genotype differences emerge with manipulations that recruit extrasynaptic NMDARs, including stronger, repetitive, or pharmacological stimulation. These results reveal a disproportionate functional deficit of extrasynaptic NMDARs compared to their synaptic counterparts. To probe the repercussions of this deficit, we examine an NMDAR-dependent phenomenon considered a building block of cognitive integration, basal dendrite plateau potentials. Since we find this phenomenon is readily evoked in wild-type but not in Grin1-deficient mice, we ask whether plateau potentials can be restored by an adult intervention to increase Grin1 expression. This genetic manipulation, previously shown to restore cognitive performance in adulthood, successfully rescues electrically-evoked basal dendrite plateau potentials after a lifetime of NMDAR compromise. Taken together, our work demonstrates NMDAR subpopulations are not uniformly vulnerable to the genetic disruption of their obligate subunit. Furthermore, the window for functional rescue of the more-sensitive integrative NMDARs remains open into adulthood.

Large offspring have enhanced lifetime reproductive success: Long-term carry-over effects of weaning size in gray seals (Halichoerus grypus).

An individual's size in early stages of life may be an important source of individual variation in lifetime reproductive performance, as size effects on ontogenetic development can have cascading physiological and behavioral consequences throughout life. Here, we explored how size-at-young influences subsequent reproductive performance in gray seals (Halichoerus grypus) using repeated encounter and reproductive data on a marked sample of 363 females that were measured for length after weaning, at ~4 weeks of age, and eventually recruited to the Sable Island breeding colony. Two reproductive traits were considered: provisioning performance (mass of weaned offspring), modeled using linear mixed effects models; and reproductive frequency (rate at which a female returns to breed), modeled using mixed effects multistate mark-recapture models. Mothers with the longest weaning lengths produced pups 8 kg heavier and were 20% more likely to breed in a given year than mothers with the shortest lengths. Correlation in body lengths between weaning and adult life stages, however, is weak: Longer pups do not grow to be longer than average adults. Thus, covariation between weaning length and future reproductive performance appears to be a carry-over effect, where the size advantages afforded in early juvenile stages may allow enhanced long-term performance in adulthood.

P.14 Analysis of the longitudinal CINRG Becker natural history study dataset

The phenotype of Becker muscular dystrophy (BMD) varies from Duchenne-like severity (loss of ambulation in second decade) to much milder disease with ambulation retained into adulthood. We performed a prospective, natural history study (BNHS) of males with in-frame dystrophin deletions causing BMD to better characterize the clinical course. Analysis of the longitudinal dataset offers the opportunity to develop robust outcomes crucial to clinical treatment trials. The BNHS followed 83 ambulatory and non-ambulatory males with BMD aged 5.5 to 75.5 years at enrolment for up to three years with annual assessments. Baseline characteristics of these participants have been published. In this post-baseline analysis, we studied binned repeated cross-sectional clinical outcome data, shift-based analyses of NSAA, longitudinal mixed-effect modeling of clinical outcomes, and survival analysis of time to stand. Analyses were stratified by age (<18 or ≥18 years old). In this dataset, we found that the most common deletion mutations were deletion of dystrophin exons 45-47 or exons 45-48. In those <18 years, the NSAA showed a ceiling effect not observed with other outcomes. In longitudinal modeling of percentage predicted FVC, 3 timed function tests, 6-minute walk distance, and NSAA, age was found to be significantly associated with outcome performance in adulthood but not in those <18 years. Mutation status (del 45-47, 45-48, vs. others) was significantly associated with some outcomes. The median age at which it took 10 seconds or longer to stand was estimated as 51 years (95% CI: 45 years, infinity) by time to event analysis. In conclusion, while the sample size was small, our data demonstrated variable progression of different outcomes based on age groups, and mutation groups, and found that disease progression seems to largely manifest in adulthood for BMD. Our study has clinical trial design implications for enrolment criteria, efficacy determination, and sample size calculations.

Obstetric complications and cognition in schizophrenia: a systematic review and meta-analysis.

Schizophrenia (SZ) is a complex brain disorder linked to cognitive and neurostructural abnormalities that involves genetic and environmental factors with obstetric complications (OCs) at birth conferring a high risk for the disease. Indeed, current research in the general population describes the deleterious effect of OCs on cognitive performance in adulthood. With this rationale, we aim to review the relationship between OCs and cognition in SZ and related psychotic disorders. A systematic review and meta-analysis describing cognitive function and OCs in patients with SZ and related disorders were conducted. PubMed, EmBase, SCOPUS, and the Cochrane Library were systematically searched to identify eligible studies up to January 2022. We calculated the effect sizes (Hedges' g) of cognitive domains within each study and quantified the proportion of between-study variability using the I2 statistic. Homogeneity was assessed using the Q-statistic (X2). The study was registered on PROSPERO (CRD42018094238). A total of 4124 studies were retrieved, with 10 studies meeting inclusion criteria for the systematic review and eight for meta-analysis. SZ subjects with OCs showed poor verbal memory [Hedges' g = -0.89 (95% CI -1.41 to -0.37), p < 0.001] and working memory performance [Hedges' g = -1.47 (95% CI -2.89 to -0.06), p = 0.01] in a random-effect model compared to those without OCs. OCs appear to have a moderate impact on specific cognitive such as working memory and verbal memory. Our findings suggest that OCs are associated with brain development and might underlie the cognitive abnormalities described at onset of psychosis.

The relationship between cognitive reserve and cognition in healthy adults: a systematic review

The concept of Cognitive Reserve (CR) refers to the individual differences allowing some people to cope better with brain pathology. The aim of the present review was to explore the relationship between CR and cognition in adulthood. This association has been addressed in several neuro(psycho)logical disorders and in healthy elderly people. However, few studies explored this issue in adulthood (age range 18–65), when individuals might take advantage the most from psychoeducational approaches aimed at increasing CR. For our systematic review, we selected studies assessing CR and adopting neuropsychological and experimental tasks for evaluation of cognitive functioning in healthy individuals. In the selected articles, we examined the relationship of singular proxies, composite indexes or standardized scales of CR with measures of general cognition, attention, inhibitory control, verbal fluency, constructional abilities, and verbal and spatial memory. The results suggested a positive relationship between singular CR proxies, composite indexes or standardized scales, and almost all the explored cognitive domains. No clear conclusion could be made on constructional abilities due to the scarcity of available studies. CR seems associated with better cognitive performance in adulthood, but definite methodological improvements and the use of standardized scales for CR are necessary to reduce inconsistencies among studies.

MGlu1 Activation Reverses Persistent Deficits in Prefrontal Cortex Inhibitory Transmission and Working Memory Induced by Adolescent Cocaine Exposure

The prefrontal cortex (PFC), a brain region central to cognitive processes such as working memory, and executive function, undergoes complex structural and functional maturation across adolescence, rendering it particularly vulnerable to disruption by external events. Exposure to psychostimulants, such as cocaine, during adolescence produces persistent changes in PFC structure and function which parallel cognitive deficits seen in adulthood. However, the mechanisms of how drug exposure during critical developmental periods alter PFC function and cognition performance in adulthood are not fully understood. Extensive evidence suggests that the balance between excitatory and inhibitory neurotransmission in the PFC plays a fundamental role in many cognitive processes. Furthermore, adolescent exposure to psychostimulants impairs GABA interneuron function and inhibitory transmission in the PFC in adulthood, suggesting that enhancing PFC inhibitory transmission may be a promising strategy to mitigate drug‐induced cognitive deficits observed later in life. Recently, we found that activation of the mGlu1 subtype of metabotropic glutamate receptor increases PFC inhibitory transmission and working memory by selective excitation of somatostatin‐expressing GABA interneurons (SST‐INs), highlighting mGlu1 as a novel target for restoring inhibitory transmission in the PFC and enhancing cognition. These findings lead us to hypothesize that repeated exposure to cocaine during a critical developmental period in adolescence disrupts inhibitory transmission in the PFC via SST‐INs and that this contributes to working memory impairments in adulthood. We further propose that selective activation of mGlu1 with highly selective positive allosteric modulators (PAMs) will reverse cocaine‐induced physiological and behavioral deficits.Here, we leveraged transgenic mouse lines in combination with whole‐cell patch‐clamp electrophysiology, maze‐ and touchscreen‐based automated cognition testing. We found that repeated administration of cocaine during a critical adolescent period (PND 35‐42) significantly impaired PFC SST‐IN, but not parvalbumin‐expressing interneuron (PV‐IN), firing compared to saline‐treated mice. Additionally, adolescent cocaine exposure significantly decreased the frequency of spontaneous excitatory postsynaptic currents onto SST‐INs but not PV‐INs. In parallel, adolescent cocaine‐induced impairments in spatial working memory in adulthood. Importantly, these physiological and behavioral effects of adolescent cocaine exposure were reversed by selective mGlu1 activation. Lastly, repeated amphetamine administration during the same adolescent critical period did not impair SST‐IN function or working memory in adulthood. In sum, these findings provide strong evidence that: 1) cocaine exposure during an adolescent critical period induces persistent and selective deficits in PFC SST‐IN function and spatial working memory in adulthood and 2) selective activation of mGlu1 with PAMs represents a promising novel strategy for reversing cocaine‐induced cognitive impairments.