Although results of animal research show that interactions between stress and sex hormones are implicated in the development of affective disorders in women, translation of these findings to patients has been scarce. As a basic step toward advancing this field of research, we analyzed findings of studies which reported circulating cortisol levels in healthy women in the follicular vs. luteal phase of the menstrual cycle. We deemed this analysis critical not only to advance our understanding of basic physiology, but also as an important contrast to the findings of future studies evaluating stress and sex hormones in women with affective disorders. We hypothesized that cortisol levels would be lower in the follicular phase based on the proposition that changes in levels of potent GABAergic neurosteroids, including allopregnanolone, during the menstrual cycle dynamically change in the opposite direction relative to cortisol levels. Implementing strict inclusion criteria, we compiled results of high-quality studies involving 778 study participants to derive a standardized mean difference between circulating cortisol levels in the follicular vs. luteal phase of the menstrual cycle. In line with our hypothesis, our meta-analysis found that women in the follicular phase had higher cortisol levels than women in the luteal phase, with an overall Hedges' g of 0.13 (p < 0.01) for the random effects model. No significant between-study difference was detected, with the level of heterogeneity in the small range. Furthermore, there was no evidence of publication bias. As cortisol regulation is a delicate process, we review some of the basic mechanisms by which progesterone, its potent metabolites, and estradiol regulate cortisol output and circulation to contribute to the net effect of higher cortisol in the follicular phase.

Objective In a longitudinal population-based study of 2905 children, we investigated if infants’ neuromotor development was associated with autistic traits in childhood. Methods Overall motor development and muscle tone were examined by trained research assistants with an adapted version of Touwen’s Neurodevelopmental Examination between ages 2–5 months. Tone was assessed in several positions and items were scored as normal, low or high tone. Parents rated their children’s autistic traits with the Social Responsiveness Scale (SRS) and the Pervasive Developmental Problems (PDP) subscale of the Child Behavior Checklist at 6 years. We defined clinical PDP if scores were >98th percentile of the norm population. Diagnosis of autism spectrum disorder (ASD) was clinically confirmed in 30 children. Results We observed a modest association between overall neuromotor development in infants and autistic traits. Low muscle tone in infancy predicted autistic traits measured by SRS (adjusted beta=0.05, 95% CI for B: 0.00–0.02, p=0.01), and PDP (adjusted beta=0.08, 95% CI for B: 0.04–0.10, p<0.001). Similar results emerged for the association of low muscle tone and clinical PDP (adjusted OR=1.36, 95% CI: 1.08–1.72, p=0.01) at age 6 years. Results remained unchanged if adjusted for child intelligence. There was no association between high muscle tone and SRS or PDP. Exclusion of children with ASD diagnosis did not change the association. Conclusion This large study showed a prospective association of infant muscle tone with autistic traits in childhood. Our findings suggest that early detection of low muscle tone might be a gateway to improve early diagnosis of ASD.

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BackgroundPrevious studies have shown that poor family environments are related to more sleep problems; however, little is known about how family irregularity in early life affects the development of sleep problems over childhood using objective sleep measures. The current study tests the hypothesis that early family irregularity contributes to the development of sleep problems.MethodsThis population‐based study comprises 5,443 children from the Generation R Study. Family irregularity was measured with seven maternal‐reported questions on family routines when children were 2 and 4 years old. Mothers reported on sleep problems at child age 3, 6, and 10 years, whereas children completed questionnaires on sleep problems at age 10. Additionally, we used tri‐axial wrist accelerometers for five nights in 851 children (mean age 11.7 years) to assess sleep objectively.ResultsFamily irregularity was associated with more mother‐ and child‐reported sleep problems at ages 3, 6, and 10 years as well as with a shorter sleep duration and later objective sleep onset, but not with sleep efficiency or waking time. The association between family irregularity and multi‐informant subjective sleep problems at age 10 years was mediated by mother‐reported child psychopathology at age 6 years.ConclusionsOur findings show a long‐term robust association of preschool family irregularity with more sleep problems during childhood as well as shorter sleep duration and later sleep onset as measured objectively with actigraphy. In part, these sleep problems were associated with family irregularity by way of child psychopathology. These findings suggest that interventions improving preschool family irregularity, which are targeted to reduce child psychopathology, may also impact the development of sleep problems beneficially.

BACKGROUND: Impaired neuromotor development is often one of the earliest observations in children with autism spectrum disorder (ASD). We investigated whether a genetic predisposition to developmental disorders was associated with nonoptimal neuromotor development during infancy and examined the genetic correlation between nonoptimal neuromotor development and autistic traits in the general population. METHODS: In a population-based cohort in The Netherlands (2002-2006), we calculated polygenic risk scores (PRSs) for ASD and attention-deficit/hyperactivity disorder (ADHD) using genome-wide association study summary statistics. In 1921 children with genetic data, parents rated autistic traits at 6 years of age. Among them, 1174 children (61.1%) underwent neuromotor examinations (tone, responses, senses, and other observations) during infancy (9-20 weeks of age). We used linear regressions to examine associations of PRSs with neuromotor scores and autistic traits. We performed a bivariate genome-based restricted maximum likelihood analysis to explore whether genetic susceptibility underlies the association between neuromotor development and autistic traits. RESULTS: Higher PRSs for ASD were associated with less optimal overall infant neuromotor development, in particular low muscle tone. Higher PRSs for ADHD were associated with less optimal senses. PRSs for ASD and those for ADHD both were associated with autistic traits. The single nucleotide polymorphism-based heritability of overall motor development was 20% (SE = .21) and of autistic traits was 68% (SE = .26). The genetic correlation between overall motor development and autistic traits was .35 (SE = .21, p , .001). CONCLUSIONS: We found that genetic liabilities for ASD and ADHD covary with neuromotor development during infancy. Shared genetic liability might partly explain the association between nonoptimal neuromotor development during infancy and autistic traits in childhood.

Children with Autism Spectrum Disorder (ASD) often exhibit problematic eating behaviors, an observation mostly based on male dominated, clinical ASD study samples. It is, however, important to evaluate both children with an ASD diagnosis and children with subclinical autistic traits as both often experience difficulties. Moreover, considering the suggestion of a possible girl-specific ASD phenotype, there is a need to determine whether autistic traits are related with problematic eating behaviors in girls as well. This study explores the sex-specific association between autism (both autistic traits and diagnosed ASD) and eating behavior in middle childhood in Generation R, a prospective population-based cohort from fetal life onwards. We collected parental reports of autistic traits at six years (Social Responsiveness Scale) and of eating behavior at ten years (Children's Eating Behaviour Questionnaire). In this cohort of 3559 children, autistic traits at six years were associated with more Picky Eating, Emotional Eating and Food Responsiveness in later childhood (e.g. adjusted B for Picky Eating = 0.07; 95% CI: 0.03, 0.11). Stratified analyses showed that in girls, autistic traits were associated with more Emotional Overeating and Emotional Undereating (e.g. adjusted B for Emotional Undereating = 0.12; 95% CI: 0.04, 0.20), while no associations were found for boys. Results comparing children with and without an ASD diagnosis in the cohort largely confirm these associations (e.g. in girls, adjusted B for Emotional Undereating = 0.72; 95% CI: 0.01, 1.42). Our results point to a sex-specific association between autism and eating behavior in middle childhood. Also, our study is the first study to show that autistic traits are associated with emotionally based eating problems in girls and possibly represent part of a girl-specific ASD phenotype.

Recently, LEUNG et al. [1] proposed that α7-subtype nicotinic acetylcholine receptor (α7-nAChR) antagonists might decrease angiotensin-converting enzyme (ACE)2 receptor expression in respiratory epithelium and, hence, prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion of pulmonary epithelial cells. Let us further theoretically evaluate this assertion and contribute to the quest for potential medications that might reduce virulence and pathogenicity of coronavirus disease 2019 (COVID-19). Smoking may be associated with progression and negative outcome of COVID-19 [1]. The receptor-binding domain of the S protein (spike) on the surface of SARS-CoV-2 interacts with the ACE2 receptor, which is an entry point of the virus into host respiratory cells [2]. On the respiratory epithelium cells of smokers and patients with COPD there is higher expression of this "viral receptor" (ACE2 receptor) [1]. Nicotine binds and stimulates nAChR, specifically the α7 subtype, which are localised in lungs and various other tissues, especially in the central nervous system. Increased expression of ACE2 receptors is mediated by stimulation of α7-nAChR. Nicotine, by its agonism on α7-nAChR, might promote entry of SARS-CoV-2 into the respiratory epithelium through ACE2 receptors [1]. Additionally, some evidence suggests that SARS-CoV-2, along with other human coronaviruses, is neurotropic and neurovirulent [3]. Altogether, it is of utmost importance to search for medications that might exert protective effects both at the periphery, at the entry point of SARS-CoV-2 infection, but also in the central nervous system where the virus might propagate.

Schizophrenia and bipolar disorder (BD) are heritable disorders with similarities in clinical symptoms and typical onset after puberty. 1 While research shows that impaired motor coordination can have an association with schizophrenia, 2 there are limited data on childhood development preceding BD. Murray et al 1 proposed a developmental model for similarities and dissimilarities between schizophrenia and BD, but it remains unknown if dissimilarities exist in early infancy and if they covary with genetic liability for these disorders. Using polygenic risk scores (PRSs), we explored whether genetic risk for schizophrenia and genetic risk for BD are associated with neuromotor development in infancy.