Search

Perturbations to the gut microbiome are implicated in altered neurodevelopmental trajectories that may shape life span risk for emotion dysregulation and affective disorders. However, the sensitive periods during which the microbiome may influence neurodevelopment remain understudied. We investigated relationships between gut microbiome composition across infancy and temperament at 12 months of age. In 67 infants, we examined if gut microbiome composition assessed at 1–3 weeks, 2, 6, and 12 months of age was associated with temperament at age 12 months. Stool samples were sequenced using the 16S Illumina MiSeq platform. Temperament was assessed using the Infant Behavior Questionnaire-Revised (IBQ-R). Beta diversity at age 1–3 weeks was associated with surgency/extraversion at age 12 months. Bifidobacterium and Lachnospiraceae abundance at 1–3 weeks of age was positively associated with surgency/extraversion at age 12 months. Klebsiella abundance at 1–3 weeks was negatively associated with surgency/extraversion at 12 months. Concurrent composition was associated with negative affectivity at 12 months, including a positive association with Ruminococcus-1 and a negative association with Lactobacillus. Our findings support a relationship between gut microbiome composition and infant temperament. While exploratory due to the small sample size, these results point to early and late infancy as sensitive periods during which the gut microbiome may exert effects on neurodevelopment.

The fetal phase of life has long been recognized as a sensitive period of development. Here we posit that pregnancy represents a simultaneous sensitive period for the adult female with broad and persisting consequences for her health and development, including risk for psychopathology. In this review, we examine the transition to motherhood through the lens of developmental psychopathology. Specifically, we summarize the typical and atypical changes in brain and behavior that characterize the perinatal period. We highlight how the exceptional neuroplasticity exhibited by women during this life phase may account for increased vulnerability for psychopathology. Further, we discuss several modes of signaling that are available to the fetus to affect maternal phenotypes (hormones, motor activity, and gene transfer) and also illustrate how evolutionary perspectives can help explain how and why fetal functions may contribute to maternal psychopathology. The developmental psychopathology perspective has spurred advances in understanding risk and resilience for mental health in many domains. As such, it is surprising that this major epoch in the female life span has yet to benefit fully from similar applications.

Microorganisms resident in our bodies participate in a variety of regulatory and pathogenic processes. Here, we describe how etiological pathways implicated in Alzheimer's disease (AD) may be regulated or disturbed by symbiotic microbial activity. Furthermore, the composition of symbiotic microbes has changed dramatically across human history alongside the rise of agriculturalism, industrialization, and globalization. We postulate that each of these lifestyle transitions engendered progressive depletion of microbial diversity and enhancement of virulence, thereby enhancing AD risk pathways. It is likely that the human life span extended into the eighth decade tens of thousands of years ago, yet little is known about premodern geriatric epidemiology. We propose that microbiota of the gut, oral cavity, nasal cavity, and brain may modulate AD pathogenesis, and that changes in the microbial composition of these body regions across history suggest escalation of AD risk. Dysbiosis may promote immunoregulatory dysfunction due to inadequate education of the immune system, chronic inflammation, and epithelial barrier permeability. Subsequently, proinflammatory agents-and occasionally microbes-may infiltrate the brain and promote AD pathogenic processes. APOE genotypes appear to moderate the effect of dysbiosis on AD risk. Elucidating the effect of symbiotic microbiota on AD pathogenesis could contribute to basic and translational research.

Evolution by natural selection eliminates maladaptive traits from a species, and yet Alzheimer’s Disease (AD) persists with rapidly increasing prevalence globally. This apparent paradox begs an explanation within the framework of evolutionary sciences. Here, I summarize and critique previously proposed theories to explain human susceptibility to AD, grouped into 8 distinct hypotheses based on the concepts of novel extension of the lifespan; lack of selective pressure during the post-reproductive phase; antagonistic pleiotropy; rapid brain evolution; delayed neuropathy by selection for grandmothering; novel alleles selected to delay neuropathy; by-product of selection against cardiovascular disease; and thrifty genotype. Subsequently, I describe a new hypothesis inspired by the concept of mismatched environments. Many of the factors that enhance AD risk today may have been absent or functioned differently before the modern era, potentially making AD a less common affliction for age-matched individuals before industrialization and for the majority of human history. Future research is needed to further explore whether changes in environments and lifestyles across human history moderate risk factors and susceptibility to AD.

Author(s): Fox, Molly; Sandman, Curt A; Davis, Elysia Poggi; Glynn, Laura M | Abstract: BACKGROUND:An issue of critical importance for psychiatry and women's health is whether postpartum depression (PPD) represents a unique condition. The Diagnostic and Statistical Manual of Mental Disorders asserts that major depressive disorder (MDD) may present with peripartum onset, without suggesting any other differences between MDD and PPD. The absence of any distinct features calls into question the nosologic validity of PPD as a diagnostic category. The present study investigates whether symptom profiles differ between PPD and depression occurring outside the postpartum phase. METHODS:In a prospective, longitudinal study of parturient women (Nn=n239), we examine the manifestation of depression symptoms. We assess factor structure of symptom profiles, and whether factors are differentially pronounced during and after the postpartum period. RESULTS:Factors were revealed representing: Worry, Emotional/Circadian/Energetic Dysregulation, Somatic/Cognitive, Appetite, Distress Display, and Anger symptoms. The factor structure was validated at postpartum and after-postpartum timepoints. Interestingly, the Worry factor, comprising anxiety and guilt, was significantly more pronounced during the postpartum timepoint, and the Emotional/Circadian/Energetic Dysregulation factor, which contained sadness and anhedonia, was significantly less pronounced during the postpartum period. CONCLUSIONS:These results suggest that PPD may be a unique syndrome, necessitating research, diagnosis, and treatment strategies distinct from those for MDD. Results indicate the possibility that Worry is an enhanced feature of PPD compared to depression outside the postpartum period, and the crucial role of sadness/anhedonia in MDD diagnosis may be less applicable to PPD diagnosis.

Background and objectives: Alzheimer’s disease (AD) shares certain etiological features with autoimmunity. Prevalence of autoimmunity varies between populations in accordance with variation in environmental microbial diversity. Exposure to microorganisms may improve individuals’ immunoregulation in ways that protect against autoimmunity, and we suggest that this may also be the case for AD. Here, we investigate whether differences in microbial diversity can explain patterns of age-adjusted AD rates between countries. Methodology: We use regression models to test whether pathogen prevalence, as a proxy for microbial diversity, across 192 countries can explain a significant amount of the variation in age-standardized AD disability-adjusted life-year (DALY) rates. We also review and assess the relationship between pathogen prevalence and AD rates in different world populations. Results: Based on our analyses, it appears that hygiene is positively associated with AD risk. Countries with greater degree of sanitation and lower degree of pathogen prevalence have higher age-adjusted AD DALY rates. Countries with greater degree of urbanization and wealth exhibit higher age-adjusted AD DALY rates. Conclusions and implications: Variation in hygiene may partly explain global patterns in AD rates. Microorganism exposure may be inversely related to AD risk. These results may help predict AD burden in developing countries where microbial diversity is rapidly diminishing. Epidemiological forecasting is important for preparing for future healthcare needs and research prioritization.