Background A population-based study to describe the impact of SARS-CoV-2 infection on pregnancy outcomes. Methods Prospective, population-based study including pregnant women consecutively attended at first/second trimester or at delivery at three hospitals in Barcelona, Spain. SARS-CoV-2 antibodies (IgG and IgM/IgA) were measured in all participants and nasopharyngeal RT-PCR was performed at delivery. The primary outcome was a composite of pregnancy complications in SARS-CoV-2 positive versus negative women: miscarriage, preeclampsia, preterm delivery, perinatal death, small-for-gestational age, neonatal admission. Secondary outcomes were components of the primary outcome plus abnormal fetal growth, malformation, intrapartum fetal distress. Outcomes were also compared between positive symptomatic and positive asymptomatic SARS-CoV-2 women. Results Of 2,225 pregnant women, 317 (14.2%) were positive for SARS-CoV-2 antibodies (n=314, 99.1%) and/or RT-PCR (n=36, 11.4%). Among positive women, 217 (68.5%) were asymptomatic, 93 (29.3%) had mild COVID-19 and 7 (2.2%) pneumonia, of which 3 required intensive care unit admission. In women with and without SARS-CoV-2 infection, the primary outcome occurred in 43 (13.6%) and 268 (14%), respectively [risk difference -0.4%, (95% CI: -4.1% to 4.1)]. As compared with non-infected women, women with symptomatic COVID-19 had increased rates of preterm delivery (7.2% vs. 16.9%, p=0.003) and intrapartum fetal distress (9.1% vs. 19.2%, p=0.004), while asymptomatic women had similar rates to non-infected cases. Among 143 fetuses from infected mothers, none had anti-SARS-CoV-2 IgM/IgA in cord blood. Conclusions The overall rate of pregnancy complications in women with SARS-CoV-2 infection was similar to non-infected women. However, symptomatic COVID-19 was associated with modest increases in preterm delivery and intrapartum fetal distress.

Parkinson’s disease dementia is neuropathologically characterized by aggregates of α-synuclein (Lewy bodies) in limbic and neocortical areas of the brain with additional involvement of Alzheimer’s disease-type pathology. Whilst immune activation is well-described in Parkinson’s disease (PD), how it links to protein aggregation and its role in PD dementia has not been explored. We hypothesized that neuroinflammatory processes are a critical contributor to the pathology of PDD. To address this hypothesis, we examined 7 brain regions at postmortem from 17 PD patients with no dementia (PDND), 11 patients with PD dementia (PDD), and 14 age and sex-matched neurologically healthy controls. Digital quantification after immunohistochemical staining showed a significant increase in the severity of α-synuclein pathology in the hippocampus, entorhinal and occipitotemporal cortex of PDD compared to PDND cases. In contrast, there was no difference in either tau or amyloid-β pathology between the groups in any of the examined regions. Importantly, we found an increase in activated microglia in the amygdala of demented PD brains compared to controls which correlated significantly with the extent of α-synuclein pathology in this region. Significant infiltration of CD4+ T lymphocytes into the brain parenchyma was commonly observed in PDND and PDD cases compared to controls, in both the substantia nigra and the amygdala. Amongst PDND/PDD cases, CD4+ T cell counts in the amygdala correlated with activated microglia, α-synuclein and tau pathology. Upregulation of the pro-inflammatory cytokine interleukin 1β was also evident in the substantia nigra as well as the frontal cortex in PDND/PDD versus controls with a concomitant upregulation in Toll-like receptor 4 (TLR4) in these regions, as well as the amygdala. The evidence presented in this study show an increased immune response in limbic and cortical brain regions, including increased microglial activation, infiltration of T lymphocytes, upregulation of pro-inflammatory cytokines and TLR gene expression, which has not been previously reported in the postmortem PDD brain.

Background: Research to date has largely conceptualized irritability in terms of intraindividual differences. However, the role of interpersonal dyadic processes has received little consideration. Nevertheless, difficulties in how parentchild dyads synchronize during interactions may be an important correlate of irritably in early childhood. Innovations in developmentally sensitive neuroimaging methods now enable the use of measures of neural synchrony to quantify synchronous responses in parent-child dyads and can help clarify the neural underpinnings of these difficulties. We introduce the Disruptive Behavior Diagnostic Observation Schedule: Biological Synchrony (DB-DOS:BioSync) as a paradigm for exploring parent-child neural synchrony as a potential biological mechanism for interpersonal difficulties in preschool psychopathology. Methods: Using functional near-infrared spectroscopy (fNIRS) 4-to 5year-olds (N = 116) and their mothers completed the DB-DOS:BioSync while assessing neural synchrony during mild frustration and recovery. Child irritability was measured using a latent irritability factor that was calculated from four developmentally sensitive indicators. Results: Both the mild frustration and the recovery contexts resulted in neural synchrony. However, less neural synchrony during the recovery context only was associated with more child irritability. Conclusions: Our results suggest that recovering after a frustrating period might be particularly challenging for children high in irritability and offer support for the use of the DB-DOS:BioSync task to elucidate interpersonal neural mechanisms of developmental psychopathology.

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The psychometric characteristics of the Spanish version are similar to those of the original version. In the Spanish adaptation of the MDQ, seven positive responses to hypomanic symptoms show a good discriminative capacity for BD in patients attending psychiatric outpatient facilities; therefore, this cut-off score is proposed for the detection of BD in psychiatric outpatients.

IntroductionVariants in the GBA1 gene have been identified as a common risk factor for Parkinson’s disease (PD). In addition to pathogenic mutations (those associated with Gaucher disease), a number of ‘non-pathogenic’ variants also occur at increased frequency in PD. Previous studies have reported that pathogenic variants adversely affect the clinical course of PD. The role of ‘non-pathogenic’ GBA1 variants on PD course is less clear. In this study, we report the effect of GBA1 variants in incident PD patients with long-term follow-up.MethodsThe study population consisted of patients in the Cambridgeshire Incidence of Parkinson’s disease from General Practice to Neurologist and Parkinsonism: Incidence, Cognition and Non-motor heterogeneity in Cambridgeshire cohorts. Patients were grouped into non-carriers, carriers of ‘non-pathogenic’ GBA1 variants and carriers of pathogenic GBA1 mutations. Survival analyses for time to development of dementia, postural instability and death were carried out. Cox regression analysis controlling for potential confounders were used to determine the impact of GBA1 variants on these outcome measures.ResultsGBA1 variants were identified in 14.4% of patients. Pathogenic and ‘non-pathogenic’ GBA1 variants were associated with the accelerated development of dementia and a more aggressive motor course. Pathogenic GBA1 variants were associated with earlier mortality in comparison with non-carriers, independent of the development of dementia.DiscussionGBA1 variants, including those not associated with Gaucher disease, are common in PD and result in a more aggressive disease course.

Children from lower-SES families exhibit smaller hippocampal volume than do their higher-SES peers. Few studies, however, have compared hippocampal developmental trajectories as a function of SES. Thus, it is unclear whether initial rank-order stability is preserved, or whether volumes diverge/converge over the course of adolescence. In a sample of 101 girls ages 10–24 years, we examined the longitudinal association between family income and parental education, proxies for SES, and changes in hippocampal volume. Hippocampal volume was obtained using MRI; using mixed modeling, we examined the effects of income and education on hippocampal volume across age. As expected, changes in volume were non-linear across development. Further, trajectories diverged in mid-adolescence, with lower-income girls exhibiting reductions in hippocampal volume. Maximal income-related differences were observed at 18 years, and trajectories converged thereafter. This interaction remained significant when accounting for maternal hippocampal volume, suggesting a unique contribution of environment over potential heritable differences. In contrast, the association between parental education and offspring hippocampal volume appeared to be stable across adolescence, with higher levels of parental education predicting consistently larger hippocampal volume. These findings constitute preliminary evidence that girls from lower-income homes exhibit unique trajectories of hippocampal growth, with differences most evident in late adolescence.

These findings reinforce the use of P-YFAS in non-clinical and clinical populations. Future directions for extending YFAS validation are discussed.