Examining the associations between microglia genetic capacity, early life exposures and white matter development at the level of the individual.

There are inter-individual differences in susceptibility to the influence of early life experiences for which the underlying neurobiological mechanisms are poorly understood. Microglia play a role in environmental surveillance and may influence individual susceptibility to environmental factors. As an index of neurodevelopment, we estimated individual slopes of mean white matter fractional anisotropy (WM-FA) across three time-points (age 4.5, 6.0, and 7.5 years) for 351 participants. Individual variation in microglia reactivity was derived from an expression-based polygenic score(ePGS) comprised of Single Nucleotide Polymorphisms (SNPs) functionally related to the expression of microglia-enriched genes.A higher ePGS denotes an increased genetic capacity for the expression of microglia-related genes, and thus may confer a greater capacity to respond to the early environment and to influence brain development. We hypothesized that this ePGS would associate with the WM-FA index of neurodevelopment and moderate the influence of early environmental factors.Our findings show sex dependency, where a significant association between WM-FA and microglia ePGS was only obtained for females.We then examined associations with perinatal factors known to decrease (optimal birth outcomes and familial conditions) or increase (systemic inflammation) the risk for later mental health problems.In females, individuals with high microglia ePGS showed a negative association between systemic inflammation and WM-FA and a positive association between more advantageous environmental conditions and WM-FA. The microglia ePGS in females thus accounted for variations in the influence of the quality of the early environment on WM-FA.Finally, WM-FA slopes mediated the association of microglia ePGS with interpersonal problems and social hostility in females. Our findings suggest the genetic capacity for microglia function as a potential factor underlying differential susceptibility to early life exposuresthrough influences on neurodevelopment.

The effect of self-focused attention during mirror gazing on body image evaluations, appearance-related imagery, and urges to mirror gaze.

BACKGROUND AND OBJECTIVES: Mirror gazing has been linked to poor body image. Cognitive-behavioral models propose that mirror gazing induces self-focused attention. This activates appearance-related imagery, increases body dissatisfaction, and promotes further mirror gazing. However, evidence for these relationships remains scarce. Our study experimentally investigated how self-focused attention impacts overall and facial appearance satisfaction, perceived attractiveness, distress about appearance and disliked features, vividness and emotional quality of appearance-related imagery, and urges to mirror gaze. Baseline body dysmorphic concerns were studied as a moderator. METHODS: Singaporean undergraduates (Mage = 21.22, SDage = 1.62; 35 females, 28 males) were randomly assigned to high or low self-focused attention during a mirror gazing task. Dependent variables were measured with visual analogue scales, and body dysmorphic concerns with the Body Image Disturbance Questionnaire (BIDQ). Analysis of variance and moderation analyses were conducted. RESULTS: Self-focused attention lowered overall and facial appearance satisfaction. Perceived attractiveness decreased only in individuals with high baseline body dysmorphic concerns. Contrary to predictions, distress, appearance-related imagery, and urges to mirror gaze were unaffected. LIMITATIONS: This study used a non-clinical sample. The BIDQ has not been psychometrically validated in Singaporean samples. CONCLUSIONS: Self-focused attention during mirror gazing lowers positive body image evaluations. Individuals with higher body dysmorphic concerns are particularly vulnerable to low perceived attractiveness.

IFNε, IFNω and IFNλ: interferons defending the mucosa.

The unconventional type I interferons IFNε and IFNω and type III interferon IFNλ are gradually emerging as tissue-specific cytokines in defence of mucosal tissues. This review provides an overview of the distinct features and functions that define these IFNs as protective factors in the respiratory, gastrointestinal and reproductive tracts, highlighting their immunoregulatory roles against pathogens while maintaining tolerance against commensal microbes. In particular, we discuss recent advances in our understanding of the constitutively expressed IFNε and its role in protecting against mucosal infections, inflammation and cancers. We identify an emerging theme for this unique cytokine as a key contributor to the 'first line of defence' against pathogens and maintenance of mucosal tissue homeostasis, primarily through its regulation of immune cell populations.

Immunoregulation by type I interferons in the peritoneal cavity.

The peritoneal cavity, a fluid-containing potential space surrounding the abdominal and pelvic organs, is home to a rich network of immune cells that maintain tissue homeostasis and provide protection against infection. However, under pathological conditions such as peritonitis, endometriosis, and peritoneal carcinomatosis, the peritoneal immune system can become dysregulated, resulting in nonresolving inflammation and disease progression. An enhanced understanding of the factors that regulate peritoneal immune cells under both homeostatic conditions and in disease contexts is therefore required to identify new treatment strategies for these often life-limiting peritoneal pathologies. Type I interferons (T1IFNs) are a family of cytokines with broad immunoregulatory functions, which provide defense against viruses, bacteria, and cancer. There have been numerous reports of immunoregulation by T1IFNs within the peritoneal cavity, which can contribute to both the resolution or propagation of peritoneal disease states, depending on the specifics of the disease setting and local environment. In this review, we provide an overview of the major immune cell populations that reside in the peritoneal cavity (or infiltrate it under inflammatory conditions) and highlight their contribution to the initiation, progression, or resolution of peritoneal diseases. Additionally, we will discuss the role of T1IFNs in the regulation of peritoneal immune cells, and summarize the results of laboratory studies and clinical trials which have investigated T1IFNs in peritonitis/sepsis, endometriosis, and peritoneal carcinomatosis.