Brain, behavior, & immunity - health最新文献

Caregiving adversity (CA) exposure is robustly linked to increased risk for poor oral, physical, and mental health outcomes. Increasingly, the gut microbiome has garnered interest as a contributor to risk for and resilience to such health outcomes in CA-exposed individuals. Though often overlooked, the oral microbiome of CA-exposed individuals may be just as important a contributor to health outcomes as the gut microbiome. Indeed, outside the context of CA, the oral microbiome is well-documented as a regulator of both oral and systemic health, and preliminary data suggest its association with mental health. However, research examining the association between CA and the oral microbiome is extremely sparse, especially in childhood, when the community composition of such organisms is still stabilizing. To address that sparsity, in the current study, we examined composition and differential abundance metrics of the oral microbiome in 152 youth aged 6–16 years, who had either been exposed to significant caregiving adversity (significant separation from or maltreatment by a caregiver; N = 66, CA) or who had always remained with their biological/birth families (N = 86, Comparison). We identified a significant negative association between hair cortisol and oral microbiome richness in the Comparison group that was significantly blunted in the CA group. Additionally, youth in the CA group had altered oral microbiome composition and elevated abundance of potentially pathogenic bacteria relative to youth in the Comparison group. Questionnaire measures of fatigue, somatic complaints, and internalizing symptoms had limited associations with oral microbiome features that were altered in CA. Although we found differences in the oral microbiomes of CA-exposed youth, further research is required to elucidate the implications of those differences for health and well-being.

Post-menopausal persons living with HIV (PWH) report elevated levels of psychological stress and monocyte activation compared to persons living without HIV (PWOH). Resting state functional connectivity (rsFC) of mesolimbic brain regions underpinning stress and emotion regulation are susceptible to inflammatory insult. Although psychological stress is elevated, rsFC reduced, and CD16⁺ monocytes overexpressed in the brains of PWH, it is unclear whether the relationships amongst these variables differ compared to PWOH.

An ethnically diverse sample of postmenopausal women, 24 PWH and 30 PWOH provided self-report mood surveys and provided peripheral blood specimens to quantify LPS-stimulated CD16^+/− expression of TNF-α via flow cytometric analysis. An anatomical and resting state functional MRI scan were used to derive time-series metrics of connectivity between the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAcc) as well as the amygdala.

A positive association was observed between levels of perceived stress and CD16^+/− TNF-α in both LPS-stimulated and unstimulated cells. PLWH showed lower connectivity between mPFC and NAcc. In turn, lower rsFC between these regions predicted greater psychological stress and proportion of CD16⁻, but not CD16⁺, cells expression of TNF-α.

Neuroimmune effects of monocyte inflammation on the functional connectivity of mesolimbic regions critical for discrimination of uncertainty-safety and reward signals were observed in an ethnically diverse sample of postmenopausal women living with and without HIV. PWH showed lower mPFC-NAcc functional connectivity, which in turn was associated with greater perceived stress.

Conventional human stress responses are mediated by the sympathetic adrenal medullar (SAM) axis and the hypothalamic pituitary adrenal (HPA) axis. The SAM axis mediates the immediate response to stress through norepinephrine and epinephrine while the HPA axis mediates the slow response through corticosteroids, primarily cortisol, to effect systemic changes. Post Traumatic Stress Disorder (PTSD), a psychiatric disorder that develops in a small subset of people exposed to a traumatic event, may dysregulate these systems and result in increased risk of various clinical conditions. These conditions include but are not limited to cardiovascular disease, metabolic conditions, autoimmune diseases, neurocognitive disorders, and women's health complications such as preterm birth, polycystic ovarian syndrome, and endometriosis to name a few. This review focuses on how PTSD dysregulates the HPA axis, and further, how these alterations affect the immune system and physical health outcomes.

Background

Using machine learning methods based on neurocognitive deficits and neuroimmune biomarkers, two distinct classes were discovered within schizophrenia patient samples. Increased frequency of psychomotor retardation, formal thought disorders, mannerisms, psychosis, hostility, excitation, and negative symptoms defined the first subgroup, major neurocognitive psychosis (MNP). Cognitive deficits in executive functions and memory and diverse neuroimmune aberrations were other MNP features. Simple neurocognitive psychosis (SNP) was the less severe phenotype.

Aims

The study comprised a sample of 40 healthy controls and 90 individuals diagnosed with schizophrenia, divided into MNP and SNP based on previously determined criteria. Soft Independent Modelling of Class Analogy (SIMCA) was performed using neurocognitive test results and measurements of serum M1 macrophage and T helper-17 cytokines as discriminatory/modelling variables. The model-to-model distances between controls and MNP + SNP and between MNP and SNP were computed, and the top discriminatory variables were established.

Results

A notable SIMCA distance of 146.1682 was observed between MNP + SNP and the control group. The top-3 discriminatory variables were lowered motor speed, an activated T helper-17 axis, and lowered working memory. This study successfully differentiated MNP from SNP yielding a SIMCA distance of 19.3. M1 macrophage activation, lowered verbal fluency, and executive functions were the prominent features of MNP versus SNP.

Discussion

Based on neurocognitive assessments and the immune-linked neurotoxic M1 and T helper-17 profiles, we found that MNP and SNP are qualitatively distinct classes. Future biomarker research should focus on examining biomarkers specifically in the MNP and SNP subgroups, rather than in the schizophrenia group.

Inflammation is one biological pathway thought to impact the brain to contribute to major depressive disorder (MDD) and is reliably associated with resistance to standard antidepressant treatments. While peripheral immune cells, particularly monocytes, have been associated with aspects of increased inflammation in MDD and symptom severity, significant gaps in knowledge exist regarding the mechanisms by which these cells are activated to contribute to behavioral symptoms in MDD. One concept that has gained recent appreciation is that metabolic rewiring to glycolysis in activated myeloid cells plays a crucial role in facilitating these cells’ pro-inflammatory functions, which may underlie myeloid contribution to systemic inflammation and its effects on the brain. Given emerging evidence from translational studies of depression that peripheral monocytes exhibit signs of glycolytic activation, better understanding the immunometabolic phenotypes of monocytes which are known to be elevated in MDD with high inflammation is a critical step toward comprehending and treating the impact of inflammation on the brain. This narrative review examines the extant literature on glycolytic metabolism of circulating monocytes in depression and discusses the functional implications of immunometabolic shifts at both cellular and systemic levels. Additionally, it proposes potential therapeutic applications of existing immunomodulators that target glycolysis and related metabolic pathways in order to reverse the impact of elevated inflammation on the brain and depressive symptoms.

Mothers with asthma or atopy have a higher likelihood of having autistic children, with maternal immune activation in pregnancy implicated as a mechanism. This study aimed to determine, in a prospective cohort of mothers with asthma and their infants, whether inflammatory gene expression in pregnancy is associated with likelihood of future autism.

Mothers with asthma were recruited to the Breathing for Life Trial. RNA was extracted from blood samples collected at mid-pregnancy. 300 ng total RNA was hybridized with the nCounter Human Inflammation gene expression panel (Nanostring Technologies, 249 inflammation-related genes). Parents completed the First Year Inventory (FYI) at 12-month follow-up, which assessed an infant's likelihood for autism across 2 behavioural domains: social communication and sensory regulation. A total score ≥19.2 indicated increased likelihood for future autism.

Inflammatory gene expression was profiled from 24 mothers: four infants scored in the high autism likelihood range; 20 scored in the low autism likelihood range. Six inflammatory genes were differentially expressed and significantly up-regulated in the high autism likelihood group: CYSLTR2, NOX1, C1QA, CXCL10, C8A, IL23R. mRNA count significantly correlated with social communication FYI score for CYSLTR2 (Pearson r = 0.46, p = 0.024) and CXCL10 (r = 0.43, p = 0.036) and with sensory regulation score for ALOX5 (r = −0.43, p = 0.038) and MAFK (r = −0.46, p = 0.022).

In this proof-of-concept study, inflammatory gene expression during pregnancy in mothers with asthma was associated with an infant's likelihood of future autism as well as scores relating to social communication and sensory regulation.

Background

Mood disorders (MD) are multifactorial disorders. Identifying new biomarkers for the early diagnosis of MD and predicting response to treatment is currently a significant research topic. Both eosinopenia and MD are associated with increased activity of the hypothalamic-pituitary-adrenal axis. The present study, therefore, used a clear definition of chronic idiopathic eosinopenia (CIE) to determine the rate of MD in a large cohort of individuals with CIE.

Methods

This retrospective population-based, case-control study uses data of seven consecutive years from the database of Leumit Health Services (LHS) - a nationwide health maintenance organization in Israel.

Results

Participants were 13928 LHS members with CIE and 27858 negative controls. The CIE group exhibited significantly higher rates of MD than the control group throughout the whole study period, except for atypical depressive disorder at baseline.

Conclusions

CIE might be associated with a higher prevalence of MD. Further basic research should elucidate the pathophysiologic mechanisms linking CIE and MD.

Background

Prenatal exposure to phthalates, a group of synthetic chemicals widely used in consumer products, has previously been associated with adverse infant and child development. Studies also suggest that maternal depression and anxiety, may amplify the harmful effects of phthalates on infant and child neurodevelopment.

Study design

Our analysis included a subset of dyads enrolled in the Atlanta African American Maternal-Child Cohort (N = 81). We measured eight phthalate metabolites in first and second trimester (8–14 weeks and 24–32 weeks gestation) maternal urine samples to estimate prenatal exposures. Phthalate metabolite concentrations were averaged across visits and natural log-transformed for analysis. Maternal symptoms of depression and anxiety were assessed using validated questionnaires (Edinberg Postnatal Depression Scale and State Trait Anxiety Inventory, respectively) and the total score on each scale was averaged across study visits. The NICU Network Neurobehavioral Scale (NNNS) was administered at two weeks of age. Our primary outcomes included two composite NNNS scores reflecting newborn attention and arousal. Linear regression was used to estimate associations between individual phthalate exposures and newborn attention and arousal. We assessed effect modification by maternal depression and anxiety.

Results

Higher levels of urinary phthalate metabolites were not associated with higher levels of infant attention and arousal, but true associations may still exist given the limited power of this analysis. In models examining effect modification by maternal depression, we observed that an interquartile range increase in mono (2-ethlyhexyl) phthalate (MEHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was associated with a significant increase in newborn arousal only among those with high depressive symptoms (MEHP: β = 0.71, 95% confidence interval [CI] = 0.10, 1.32 for high, β = −0.30, 95% CI = −0.73, 0.12 for low; MEOHP: β = 0.60, 95% CI = −0.03, 1.23 for high, β = −0.12, 95% CI = −0.58, 0.33 for low; MEHHP: β = 0.54, 95% CI = −0.04, 1.11 for high, β = −0.11, 95% CI = −0.54, 0.32 for low). Similar patterns were observed in models stratified by maternal anxiety, although CIs were wide.

Conclusion

Our results suggest maternal anxiety and depression symptoms may exacerbate the effect of phthalates on infant neurodevelopment. Future studies are needed to determine the optimal levels of attention and arousal in early infancy.

Ischemic stroke, as one of the most severe and prevalent neurological disorders, poses a significant threat to the health and quality of life of affected individuals. Stemming from the obstruction of blood flow, ischemic stroke, leads to cerebral tissue hypoxia and ischemia, instigating a cascade of pathophysiological changes that markedly exacerbate neuronal damage and may even culminate in cell death. In recent years, emerging research has increasingly focused on novel cell death mechanisms such as ferroptosis and cuproptosis. Mounting evidence underscores the independent roles of ferroptosis and cuproptosis in ischemic stroke. This review aims to elucidate potential cross-regulatory mechanisms between ferroptosis and cuproptosis, exploring their regulatory roles in ischemic stroke. The objective is to provide targeted therapeutic intervention strategies.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in communication, sociability, and repetitive/stereotyped behavior. The etiology of autism is diverse, with genetic susceptibility playing an important role alongside environmental insults and conditions. Human and preclinical studies have shown that ASD is commonly accompanied by inflammation, and inhibition of the inflammatory response can ameliorate, or prevent the phenotype in preclinical studies. The kynurenine pathway, responsible for tryptophan metabolism, is upregulated by inflammation. Hence, this metabolic route has drawn the attention of investigators across different disciplines such as cancer, immunology, and neuroscience. Over the past decade, studies have identified evidence that the kynurenine pathway is also altered in autism spectrum disorders. In this mini review, we will explore the current status quo of the link between the kynurenine pathway and ASD, shedding light on the compelling but still preliminary evidence of this relationship.