Prenatal maternal immune activation predicts observed fearfulness in infancy.

Fear reactivity is an early emerging temperament trait that predicts longer term behavioral and health outcomes. The current analysis tests the hypothesis, an extension of prior research on maternal immune activation (MIA), that the prenatal maternal immune system is a reliable predictor of observed fear reactivity in infancy. The analysis is based on a prospective longitudinal cohort study that collected data from the first trimester and conducted observational assessments of temperament at approximately 12 months of age (n = 281 infants). MIA was assessed from immune biomarkers measured in maternal blood at each trimester; infant temperament was assessed using the Laboratory Temperament Assessment Battery assessment at 12 months; covariates included family and sociodemographic factors. Patterns of inflammatory markers across gestation reliably predicted observed temperament: elevated prenatal MIA was associated with high fear reactivity to novel stimuli. The findings provide novel evidence of prenatal origins of fear reactivity and suggest developmental mechanisms that may underlie early emerging individual differences in child temperament. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Adverse Childhood Experiences Predict Diurnal Cortisol Throughout Gestation.

OBJECTIVE: Adverse childhood experiences (ACEs) are associated with negative prenatal and perinatal health outcomes and may, via these pathways, have intergenerational effects on child health and development. We examine the impact of ACEs on maternal salivary cortisol, a key measure of prenatal biology previously linked with pregnancy-related health outcomes. METHODS: Leveraging assessments across three trimesters, we used linear mixed-effects models to analyze the influence of ACEs on maternal prenatal diurnal cortisol patterns in a diverse cohort of pregnant women (analytic sample, n = 207). Covariates included comorbid prenatal depression, psychiatric medications, and sociodemographic factors. RESULTS: Maternal ACEs were significantly associated with flatter diurnal cortisol slopes (i.e., less steep decline), after adjusting for covariates, with effects consistent across gestation (estimate = 0.15, standard error = 0.06, p = .008). CONCLUSIONS: ACEs experienced before pregnancy may have a robust and lasting influence on maternal prenatal hypothalamic-pituitary-adrenal activity throughout gestation, a key biological marker associated with perinatal and child health outcomes. The findings suggest one route of intergenerational transmission of early adverse experiences and underscore the potential value of assessing prepregnancy adverse experiences for promoting perinatal and maternal and child health.

Assessment of Oncology Advanced Practice Professional Willingness to Participate in Medical Aid in Dying.

Importance: In 2021, New Mexico passed legislation allowing nurse practitioners and physician assistants (referred to herein as advanced practice professionals [APPs]) to prescribe medications for medical aid in dying (MAID). Other US states with existing MAID laws (eg, Washington) are also considering expanding MAID prescribing authority to APPs. There is a lack of research exploring APP knowledge of, willingness to, and comfort with acting as a prescribing or consulting clinician for MAID. Objective: To assess perspectives of oncology APPs regarding MAID, including their willingness to prescribe and/or consult for MAID and factors associated with willingness. Design, Setting, and Participants: This cross-sectional, self-report survey study used data collected from APPs working at a comprehensive cancer center in Washington State in fall 2021. Main Outcomes and Measures: The primary survey question was whether APPs would be willing to participate in death with dignity, the term used for MAID in Washington. Survey questions evaluated how influential specific factors were on APP views on MAID as well as respondents' knowledge of and comfort with aspects of the MAID process. Results: Of 167 eligible APPs, 77 (46.1%) responded to the survey. Most respondents (68 [88.3%]) reported their race and ethnicity as White; 72 (93.5%) identified as a woman. Medical oncology (28 [36.4%]) was the most common field of practice, and 21 respondents (27.3%) reported having practiced as an APP for 6 to 10 years. Of all respondents, 61 (79.2%) reported having at least 1 patient who inquired about MAID; depending on the question, less than a third of respondents (5.0%-27.0%) endorsed feeling knowledgeable or very knowledgeable about any aspect of the MAID process. In this study, 39 APPs (50.6%) endorsed being willing to participate in MAID either as a consulting or prescribing clinician, whereas 31 (40.3%) were uncertain of whether they would participate. Willingness to participate was associated with having had more patients pursue MAID (33 of the 39 willing participants [84.6%] vs 15 of the 31 unsure participants [48.4%] reported having 1 or more patients pursue MAID). Higher knowledge and comfort scores were both significantly associated with increased odds of being willing to participate (odds ratio, 1.14 per 1-point score increase [95% CI, 1.03-1.27]; P = .01) vs unsure (1.18 [95% CI, 1.07-1.30; P = .001). Conclusions and Relevance: The results of this survey study suggest that oncology APPs may require preparation for the addition of MAID to their scope of practice. This study also raises questions for future research regarding support for APPs who may be considering participation in MAID but question their role or want physician involvement.

Prenatal diurnal cortisol: Normative patterns and associations with affective symptoms and stress.

The hypothalamic-pituitary-adrenal (HPA) axis in pregnancy has attracted considerable research attention, in part, because it may be a mechanism by which diverse prenatal exposures alter perinatal and child health outcomes. Symptoms of affective disturbance and stress are among the most-studied prenatal factors associated with HPA axis alterations, but there remains uncertainty about the nature of the association because of the limitations to, and variability in, data collection and analytic approaches. The current study capitalized on a prospective, longitudinal pregnancy cohort that examined salivary diurnal cortisol, collected at 5 time points across the day, at each trimester in a diverse sample of women. Detailed data on affective symptoms and major life events were collected at each trimester, as were data on health behaviors, medication, and socio-demographics. Results indicated modest stability of individual differences in diurnal cortisol across pregnancy, which was evident for diurnal slope (ICC = .20) and measures of total output (area under the curve, ICC = .25); substantial gestation-related increases in total cortisol output across pregnancy was also observed (p < .001). Adjusting for health behaviors, medication, and socio-demographic covariates, elevated levels of depressive symptoms and major life events were significantly (p < .05) associated with a higher morning awakening value and flatter diurnal slope, which was evident across all trimesters. In addition to the normative gestation-related changes in cortisol production, our results demonstrate selective but robust associations between psychological symptoms, stressors, and the HPA axis across gestation, and suggest both methodological and mechanistic strategies for future study.

Influences on childhood depressive symptoms: The effects of trauma and distress tolerance across age and sex groups.

BACKGROUND: Depression affects many children and adolescents, leading to poor academic performance, impaired psychosocial functioning, and an increased frequency of suicidal behavior. Depression has also been notably associated with trauma and distress tolerance. Our study sought to understand the relationships of these variables across age and sex categories in youth and adolescents. METHODS: The current study examined data from a total of 324 participants between the ages of 7 and 17 years-old who were a part of a larger study. Data related to age, sex, depression, trauma, and distress tolerance were examined. RESULTS: A multiple regression revealed a significant interaction between age and sex on depression severity. Further, trauma and age by sex categories significantly predicted depression score, as well as distress tolerance predicting depression score. Lastly, a regression analysis, including trauma, distress tolerance, and age by sex categories were significant predictors of depression. LIMITATIONS: The results are limited by the cross-sectional design. CONCLUSION: Clinicians should consider age by sex effects when treating childhood depression. Future research should further the understanding of depression across age and sex groups, as well as among children with extensive trauma experiences. Future research should also seek to further understand the implications of distress tolerance therapy on childhood depression.

Are "Superwomen" without social support at risk for postpartum depression and anxiety?

Postpartum depression and anxiety are common among women. Previous research has found perfectionism and the lack of social support to be associated with psychological distress. This study examined (1) social support as a protective factor against postpartum depressive and anxiety symptoms and perfectionism as a risk factor; (2) associations between different types of social support and postpartum depressive and anxiety symptoms; and (3) social support as a moderator between the relationship of perfectionism and postpartum depressive and anxiety symptoms. A total of 596 postpartum participants were included. Participants completed measures on postpartum depression, anxiety, social support, and perfectionism. Multivariate regressions revealed perfectionism was not significantly associated with depressive symptoms but predicted anxiety symptoms. Social support was a significant protective factor against depressive and anxiety symptoms. All support subscales were significantly associated with depressive and anxiety symptoms, with support from friends having the largest effect size (partial η2  = .061). High levels of support significantly moderated the relationship between perfectionism and depressive symptoms, ß = .003, 95% CI [.0006, .005], t (592) = 2.53, p = .012, and average and high levels of support significantly moderated the relationship between perfectionism and anxiety symptoms, ß = .0023, 95% CI [.0002, .004], t (592) = 2.13, p = .03. These results emphasize the importance of social support for postpartum women's mental health, especially for "Superwomen" with perfectionistic tendencies. Implications for healthcare and policies are discussed.

Grant Report on d-Serine Augmentation of Neuroplasticity-Based Auditory Learning in Schizophrenia †.

We report on the rationale and design of an ongoing NIMH sponsored R61-R33 project in schizophrenia/schizoaffective disorder. This project studies augmenting the efficacy of auditory neuroplasticity cognitive remediation (AudRem) with d-serine, an N-methyl-d-aspartate-type glutamate receptor (NMDAR) glycine-site agonist. We operationalize improved (smaller) thresholds in pitch (frequency) between successive auditory stimuli after AudRem as improved plasticity, and mismatch negativity (MMN) and auditory θ as measures of functional target engagement of both NMDAR agonism and plasticity. Previous studies showed that AudRem alone produces significant, but small cognitive improvements, while d-serine alone improves symptoms and MMN. However, the strongest results for plasticity outcomes (improved pitch thresholds, auditory MMN and θ) were found when combining d-serine and AudRem. AudRem improvements correlated with reading and other auditory cognitive tasks, suggesting plasticity improvements are predictive of functionally relevant outcomes. While d-serine appears to be efficacious for acute AudRem enhancement, the optimal dose remains an open question, as does the ability of combined d-serine + AudRem to produce sustained improvement. In the ongoing R61, 45 schizophrenia patients will be randomized to receive three placebo-controlled, double-blind d-serine + AudRem sessions across three separate 15 subject dose cohorts (80/100/120 mg/kg). Successful completion of the R61 is defined by ≥moderate effect size changes in target engagement and correlation with function, without safety issues. During the three-year R33, we will assess the sustained effects of d-serine + AudRem. In addition to testing a potentially viable treatment, this project will develop a methodology to assess the efficacy of novel NMDAR modulators, using d-serine as a "gold-standard".

Distinct Functional Connectivity Patterns Are Associated With Social and Cognitive Lifestyle Factors: Pathways to Cognitive Reserve.

The importance of diverse lifestyle factors in sustaining cognition during aging and delaying the onset of decline in Alzheimer's disease and related dementias cannot be overstated. We explored the influence of cognitive, social, and physical lifestyle factors on resting-state lagged linear connectivity (LLC) in high-density electroencephalography (EEG) in adults, ages 35-75 years. Diverse lifestyle factors build cognitive reserve (CR), protecting cognition in the presence of physical brain decline. Differences in LLC were examined between high- and low-CR groups formed using cognitive, social, and exercise lifestyle factors. LLC is a measure of lagged coherence that excludes zero phase contributions and limits the effects of volume conduction on connectivity estimates. Significant differences in LLC were identified for cognitive and social factors, but not exercise. Participants high in social CR possessed greater local and long-range connectivity in theta and low alpha for eyes-open and eyes-closed recording conditions. In contrast, participants high in cognitive CR exhibited greater eyes-closed long-range connectivity between the occipital lobe and other cortical regions in low alpha. Greater eyes-closed local LLC in delta was also present in men high in cognitive CR. Cognitive factor scores correlated with sustained attention, whereas social factors scores correlated with spatial working memory. Gender was a significant covariate in our analyses, with women displaying higher local and long-range LLC in low beta. Our findings support distinct relationships between CR and LLC, as well as CR and cognitive function for cognitive and social subcomponents. These patterns reflect the importance of diverse lifestyle factors in building CR.