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ABSTRACT: Refugees experience distress from premigration trauma, often exacerbated by postmigration difficulties. To develop effective interventions, risk factors for mental health symptoms need to be determined. Male Iraqi refugees (N = 53) to the United States provided background information and reported predisplacement trauma and psychological health within 1 month of their arrival. An inflammatory biomarker-C-reactive protein (CRP) was assessed approximately 1.5 years after arrival, and a contextual factor-acculturation-and psychological health were assessed 2 years after arrival. We tested whether acculturation and CRP were associated with posttraumatic stress disorder (PTSD) and depression symptoms at the 2-year follow-up, controlling for baseline symptoms, age, body mass index, and predisplacement trauma. Acculturation was inversely related to depression, and CRP was positively related to both PTSD and depression at the 2-year follow-up. Interventions targeting acculturation could help reduce the development of depression symptoms in refugees. The role of CRP in the development of PTSD and depression symptoms warrants further research.
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Aculturação , Proteína C-Reativa/metabolismo , Depressão , Trauma Psicológico , Refugiados , Transtornos de Estresse Pós-Traumáticos , Adolescente , Adulto , Depressão/sangue , Depressão/etnologia , Depressão/fisiopatologia , Seguimentos , Humanos , Iraque/etnologia , Masculino , Pessoa de Meia-Idade , Trauma Psicológico/sangue , Trauma Psicológico/etnologia , Trauma Psicológico/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/sangue , Transtornos de Estresse Pós-Traumáticos/etnologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Estados Unidos/etnologia , Adulto JovemRESUMO
CONTEXT: An extensive body of literature indicates a relationship between insulin resistance and the up-regulation of the kynurenine pathway, i.e. the preferential conversion of tryptophan to kynurenine, with subsequent overproduction of diabetogenic downstream metabolites, such as kynurenic acid. CASE DESCRIPTION: We have measured the concentration of kynurenine pathway metabolites (kynurenines) in the brain and pancreas of two young (27 and 28 yrs) insulin resistant, normoglycemic subjects (M-values 2 and 4 mg/kg/min, respectively) using quantitative C-11-alpha-methyl-tryptophan PET/CT imaging. Both subjects underwent a preventive 12-week metformin treatment regimen (500 mg daily) prior to the PET/CT study. Whereas treatment was successful in one of the subject (M-value increased from 2 to 12 mg/kg/min), response was poor in the other subjects (M-value changed from 4 to 5 mg/kg/min). Brain and pancreas concentrations of kynurenines observed in the responder were similar to that in a healthy control subject, whereas kynurenines determined in the non-responder were about 25% higher and similar to those found in a severely insulin resistant patient. Consistent with this outcome, M-values were negatively correlated with both kynurenic acid levels (R2 = 0.68, p = 0.09) as well as with the kynurenine to tryptophan ratio (R2 = 0.63, p = 0.11). CONCLUSION: The data indicates that kynurenine pathway metabolites are increased in subjects with insulin resistance prior to overt manifestation of hyperglycemia. Moreover, successful metformin treatment leads to a normalization of tryptophan metabolism, most likely as a result of decreased contribution from the kynurenine metabolic pathway.
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Regulação para Baixo/efeitos dos fármacos , Resistência à Insulina , Cinurenina/metabolismo , Metformina/farmacologia , Adulto , Humanos , Metformina/administração & dosagemRESUMO
Divergent selection has created rat phenotypes of high- and low-capacity runners (HCR and LCR, respectively) that have differences in aerobic capacity and correlated traits such as adiposity. We analyzed visceral adipose tissue of HCR and LCR using label-free high-definition MS (elevated energy) profiling. The running capacity of HCR was ninefold greater than LCR. Proteome profiling encompassed 448 proteins and detected 30 significant (p <0.05; false discovery rate <10%, calculated using q-values) differences. Approximately half of the proteins analyzed were of mitochondrial origin, but there were no significant differences in the abundance of proteins involved in aerobic metabolism. Instead, adipose tissue of LCR rats exhibited greater abundances of proteins associated with adipogenesis (e.g. cathepsin D), ER stress (e.g. 78 kDa glucose response protein), and inflammation (e.g. Ig gamma-2B chain C region). Whereas the abundance antioxidant enzymes such as superoxide dismutase [Cu-Zn] was greater in HCR tissue. Putative adipokines were also detected, in particular protein S100-B, was 431% more abundant in LCR adipose tissue. These findings reveal low running capacity is associated with a pathological profile in visceral adipose tissue proteome despite no detectable differences in mitochondrial protein abundance.
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Tecido Adiposo Branco/metabolismo , Músculo Esquelético/metabolismo , Adipogenia/fisiologia , Animais , Proteínas Mitocondriais/metabolismo , Condicionamento Físico Animal , RatosRESUMO
Antipsychotics are associated with severe metabolic side effects including insulin resistance; however, the mechanisms underlying this side effect are not fully understood. The skeletal muscle plays a critical role in insulin-stimulated glucose uptake, and changes in skeletal muscle DNA methylation by antipsychotics may play a role in the development of insulin resistance. A double-blind, placebo-controlled trial of olanzapine was performed in healthy volunteers. Twelve healthy volunteers were randomized to receive 10 mg/day of olanzapine for 7 days. Participants underwent skeletal muscle biopsies to analyze DNA methylation changes using a candidate gene approach for the insulin signaling pathway. Ninety-seven methylation sites were statistically significant (false discovery rate < 0.05 and beta difference between the groups of ≥10%). Fifty-five sites had increased methylation in the skeletal muscle of olanzapine-treated participants while 42 were decreased. The largest methylation change occurred at a site in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha (PPARGC1A) gene, which had 52% lower methylation in the olanzapine group. Antipsychotic treatment in healthy volunteers causes significant changes in skeletal muscle DNA methylation in the insulin signaling pathway. Future work will need to expand on these findings with expression analyses.
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Neural systems that identify and respond to salient stimuli are critical for survival in a complex and changing environment. In addition, interindividual differences, including genetic variation and hormonal and metabolic status likely influence the behavioral strategies and neuronal responses to environmental challenges. Here, we examined the relationship between leptin allelic variation and plasma leptin levels with DAD2/3R availability in vivo as measured with [(11)C]raclopride PET at baseline and during a standardized pain stress challenge. Allelic variation in the leptin gene was associated with varying levels of dopamine release in response to the pain stressor, but not with baseline D2/3 receptor availability. Circulating leptin was also positively associated with stress-induced dopamine release. These results show that leptin serves as a regulator of neuronal function in humans and provides an etiological mechanism for differences in dopamine neurotransmission in response to salient stimuli as related to metabolic function. The capacity for leptin to influence stress-induced dopaminergic function is of importance for pathological states where dopamine is thought to play an integral role, such as mood, substance-use disorders, eating disorders, and obesity.
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Dopamina/fisiologia , Leptina/fisiologia , Estresse Psicológico/fisiopatologia , Adulto , Alelos , Índice de Massa Corporal , Feminino , Frequência do Gene , Genótipo , Humanos , Processamento de Imagem Assistida por Computador , Leptina/sangue , Leptina/genética , Masculino , Análise em Microsséries , Neostriado/diagnóstico por imagem , Neostriado/fisiologia , Núcleo Accumbens/diagnóstico por imagem , Núcleo Accumbens/fisiologia , Dor/fisiopatologia , Dor/psicologia , Polimorfismo Genético/genética , Polimorfismo de Nucleotídeo Único , Tomografia por Emissão de Pósitrons , Racloprida , Compostos Radiofarmacêuticos , Adulto JovemRESUMO
Antipsychotics are an important pharmacotherapy option for the treatment of many mental illnesses. Unfortunately, selecting antipsychotics is often a trial-and-error process due to a lack of understanding as to which medications an individual patient will find most effective and best tolerated. Metabolomics, or the study of small molecules in a biosample, is an increasingly used omics platform that has the potential to identify biomarkers for medication efficacy and toxicity. This systematic review was conducted to identify metabolites and metabolomic pathways associated with antipsychotic use in humans. Ultimately, 42 studies were identified for inclusion in this review, with all but three studies being performed in blood sources such as plasma or serum. A total of 14 metabolite classes and 12 lipid classes were assessed across studies. Although the studies were highly heterogeneous in approach and mixed in their findings, increases in phosphatidylcholines, decreases in carboxylic acids, and decreases in acylcarnitines were most consistently noted as perturbed in patients exposed to antipsychotics. Furthermore, for the targeted metabolomic and lipidomic studies, seven metabolites and three lipid species had findings that were replicated. The most consistent finding for targeted studies was an identification of a decrease in aspartate with antipsychotic treatment. Studies varied in depth of detail provided for their study participants and in study design. For example, in some cases, there was a lack of detail on specific antipsychotics used or concomitant medications, and the depth of detail on sample handling and analysis varied widely. The conclusions here demonstrate that there is a large foundation of metabolomic work with antipsychotics that requires more complete reporting so that an objective synthesis such as a meta-analysis can take place. This will then allow for validation and clinical application of the most robust findings to move the field forward. Future studies should be carefully controlled to take advantage of the sensitivity of metabolomics while limiting potential confounders that may result from participant heterogeneity and varied analysis approaches.
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BACKGROUND: Prenatal exposure to maternal metabolic conditions associated with inflammation and steroid dysregulation has previously been linked to increased autism risk. Steroid-related maternal serum biomarkers have also provided insight into the in utero steroid environment for offspring who develop autism. OBJECTIVE: This study examines the link between autism among offspring and early second trimester maternal steroid-related serum biomarkers from pregnancies enriched for prenatal metabolic syndrome (PNMS) exposure. STUDY DESIGN: Early second trimester maternal steroid-related serum biomarkers (i.e., estradiol, free testosterone, total testosterone, and sex hormone binding globulin) were compared between pregnancies corresponding to offspring with (N = 68) and without (N = 68) autism. Multiple logistic regression analyses were stratified by sex and gestational duration. One-way ANCOVA with post hoc tests was performed for groups defined by autism status and PNMS exposure. RESULTS: Increased estradiol was significantly associated with autism only in males (AOR = 1.13 per 100 pg/ml, 95% CI 1.01-1.27, p = 0.036) and only term pregnancies (AOR = 1.17 per 100 pg/ml, 95% CI 1.04-1.32, p = 0.010). Autism status was significantly associated with decreased sex hormone binding globulin (AOR = 0.65 per 50 nmol/L, 95% CI 0.55-0.78, p < 0.001) overall and when stratified by sex and term pregnancy status. The inverse association between sex hormone binding globulin and autism was independent of PNMS exposure. LIMITATIONS: The relative racial and ethnic homogeneity of Utah's population limits the generalizability of study results. Although significant differences by autism status were identified in concentrations of sex hormone binding globulin overall and of estradiol in participant subgroups, differences by PNMS exposure failed to reach statistical significance, which may reflect insufficient statistical power. CONCLUSION: Both elevated maternal serum estradiol in males only and low maternal serum sex hormone binding globulin in both sexes are associated with increased autism risk. Further investigation is merited to identify how steroid, metabolic, and inflammatory processes can interact to influence neurodevelopment in early second trimester.
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Transtorno Autístico , Globulina de Ligação a Hormônio Sexual , Masculino , Feminino , Gravidez , Humanos , Segundo Trimestre da Gravidez , Globulina de Ligação a Hormônio Sexual/análise , Globulina de Ligação a Hormônio Sexual/metabolismo , Estradiol , Testosterona , BiomarcadoresRESUMO
Antipsychotic medications demonstrate a variable range of efficacy and side effects in patients with mental illness. Research has attempted to identify biomarkers associated with antipsychotic effects in various populations. Research designs utilizing healthy volunteers may have the added benefit of measuring the effect of antipsychotics on a given biomarker (s) independent of the varied environmental and clinical factors that often accompany patient populations. The aim of this systematic review and meta-analysis was to synthesize the current evidence of hormonal, inflammatory, and metabolic biomarker studies of antipsychotic treatment in study designs using healthy volunteers. The systematic review was performed according to established guidelines and a random effects meta-analysis of biomarkers appearing in at least three studies was performed while biomarkers in two or less studies were qualitatively summarized. A total of 28 studies including 28 biomarkers were identified. Meta-analyses were carried out for 14 biomarkers, showing significant effects within six biomarkers (cortisol, C-peptide, free fatty acids, leptin, thyroid-stimulating hormone, and prolactin). Many of these effects were associated with olanzapine, the most used antipsychotic amongst the trials, observed on sub-analyses. When combining biomarkers into categories, some additional effects were observed, for example, when grouping inflammatory biomarkers. These findings suggest that antipsychotics exert potentially strong effects on several biomarkers of interest independent of psychiatric disease which could be used to spur future investigations, however, replication work is needed for many biomarkers included in this review.
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Antipsicóticos , Antipsicóticos/efeitos adversos , Humanos , OlanzapinaRESUMO
INTRODUCTION: Refugees are at increased risk for trauma-related mental health disorders, including anxiety, depression, and post-traumatic stress disorder (PTSD). The underlying biological mechanisms linking trauma to mental disorders need additional study, and the possible pathophysiological role of the immune system is attracting increasing interest. In this study, we investigated whether two well-known pro-inflammatory cytokines (interleukin (IL-8) and IL-6) are associated with mental health symptoms in Middle Eastern refugees displaced to the United States. METHODS: Refugees (n=64, mean age=37.6 years) ages ranged from 21 to 74 years (mean=37.62, SD=11.84) were interviewed one month after arrival in Michigan, United States, using a validated survey in Arabic. Questions covered pre-displacement trauma, current anxiety, depression, and PTSD symptoms. Blood, collected immediately following the interview, was analyzed for the levels of interleukins. Multivariate linear regression was used to determine the association between mental health symptoms and IL-6 and IL-8. RESULTS: In multivariate modeling, older age (ß=0.37; p<0.01) and anxiety (ß=0.31; p<0.05) were positively associated with IL-8. Age (ß=0.28; p<0.05) and pre-displacement trauma (ß=0.40; p<0.05) were positively associated with IL-6. Depression (ß=-0.38) was negatively associated with IL-6. CONCLUSION/RELEVANCE: This study of inflammatory biomarkers suggests the possibility of differential associations between mental health symptoms (anxiety and depression) and pro-inflammatory markers (IL-6 and IL-8). To enhance our ability to prevent and more effectively treat trauma-exposed refugees, we need to better understand the neuroinflammatory mechanisms contributing to mental disorders.
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Aim: Teaching of genetics and pharmacogenetics with personal genotyping (PGT) is becoming commonplace. We aimed to perform a systematic review and meta-analysis to understand the effects of PGT on student outcomes. Methods: A systematic review was performed on studies that reported the effects of PGT on student attitudes, perceptions or knowledge. Extracted data were summarized qualitatively and when possible, quantitatively. Results: Student PGT has a positive effect on student attitude and perceptions survey responses in studies without a control group (p = 0.009) and in studies with a control group (p = 0.025). Knowledge increased after the use of PGT (p < 0.001) in studies without a control group. Conclusion: The findings here suggest that perceptions, attitudes and knowledge increase with PGT in the classroom.
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Genética Médica/educação , Técnicas de Genotipagem , Farmacogenética/educação , Estudantes , Técnicas de Genotipagem/métodos , HumanosRESUMO
OBJECTIVES: The objective of this work was to compare bibliometrics based on doctoral degrees within United States colleges of pharmacy to understand productivity differences. Secondary objectives were to provide quantitative data based on degree that could be utilized by individual faculty, administration and other key stakeholders in academic pharmacy. METHODS: Bibliometric indices were obtained from Scopus and Web of Science for faculty from research-intensive United States pharmacy schools. Scholarly metrics that included publication number, total citations, highest cited article and H-index were compared between degrees using multivariate regression adjusted for academic rank and years since first publication. A correction for multiple testing was applied. KEY FINDINGS: All collected scholarly metrics were higher for Ph.D.-only and Pharm.D./Ph.D. faculty when compared to Pharm.D.-only faculty. Ph.D.-only faculty significantly differed compared to Pharm.D./Ph.D. faculty for Web of Science average citations per document. CONCLUSIONS: Differences are apparent between the major doctoral degrees at research-intensive, federally funded colleges of pharmacy; however, these differences were primarily identified for Pharm.D.-only compared to the other doctoral degree types Future work should analyse the potential variables that explain the scholarly metrics differences between degrees and aim to analyse other areas of faculty impact beyond scholarly metrics.
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Educação em Farmácia , Farmácia , Bibliometria , Docentes , Humanos , Faculdades de Farmácia , Estados UnidosRESUMO
BACKGROUND: Persons who inject drugs (PWID) in the groin, legs, and/or feet are at high risk for chronic venous ulcers (CVUs). The plasma C-reactive protein (CRP) level is a marker of systemic inflammation. OBJECTIVE: This pilot study examined CRP levels in plasma and CVU exudate of PWID. The aims were to (1) compare levels of CRP in plasma and exudate; (2) examine if the CRP level in exudate changed over 4 weeks with wound treatment; and (3) examine the relationship of the exudate CRP level with CVU area, CVU age, number of CVUs, and number of comorbidities. MATERIALS AND METHODS: Persons who inject drugs seeking wound care were enrolled in this Institutional Review Board approved prospective, longitudinal, descriptive study. A blood sample was collected on the first visit (week 1); the plasma was then separated. Wound exudate was collected on swabs during the first visit (week 1) and 4 weeks later (week 4). All samples were stored at -80° C. Samples were eluted from swabs using mass spectrometry grade water then aliquoted for CRP analysis. RESULTS: The participants of the study included 14 PWID (mean age, 62.14 ± 4.52 years; mean number of comorbidities, 5.71 ± 1.90; and mean number of ulcers 2.07 ± 1.07 that were present for a mean of 7.96 ± 11.91 years without healing). C-reactive protein level in plasma was a mean of 6.47 ± 8.56 mg/L, with lower levels found in wound exudate but highly correlated (rho = .925). Exudate CRP levels decreased from week 1 to week 4, and the 2 were highly correlated (rho = .895). Exudate CRP level week 1 was not significantly related to wound area, wound age, number of ulcers, or number of comorbidities. CONCLUSIONS: Plasma and exudate CRP levels were highly correlated. Exudate CRP levels decreased across time. Future large-scale wound healing studies should examine CRP levels over a longer duration and as they correlate to wound healing.
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Though obesity is common, some people remain resistant to weight gain even in an obesogenic environment. The propensity to remain lean may be partly associated with high endurance capacity along with high spontaneous physical activity and the energy expenditure of activity, called non-exercise activity thermogenesis (NEAT). Previous studies have shown that high-capacity running rats (HCR) are lean compared to low-capacity runners (LCR), which are susceptible to cardiovascular disease and metabolic syndrome. Here, we examine the effect of diet on spontaneous activity and NEAT, as well as potential mechanisms underlying these traits, in rats selectively bred for high or low intrinsic aerobic endurance capacity. Compared to LCR, HCR were resistant to the sizeable increases in body mass and fat mass induced by a high-fat diet; HCR also had lower levels of circulating leptin. HCR were consistently more active than LCR, and had lower fuel economy of activity, regardless of diet. Nonetheless, both HCR and LCR showed a similar decrease in daily activity levels after high-fat feeding, as well as decreases in hypothalamic orexin-A content. The HCR were more sensitive to the NEAT-activating effects of intra-paraventricular orexin-A compared to LCR, especially after high-fat feeding. Lastly, levels of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in the skeletal muscle of HCR were consistently higher than LCR, and the high-fat diet decreased skeletal muscle PEPCK-C in both groups of rats. Differences in muscle PEPCK were not secondary to the differing amount of activity. This suggests the possibility that intrinsic differences in physical activity levels may originate at the level of the skeletal muscle, which could alter brain responsiveness to neuropeptides and other factors that regulate spontaneous daily activity and NEAT.
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Gorduras na Dieta/administração & dosagem , Obesidade/etiologia , Condicionamento Físico Animal/fisiologia , Corrida/fisiologia , Adiposidade/genética , Adiposidade/fisiologia , Animais , Metabolismo Energético/genética , Metabolismo Energético/fisiologia , Hipotálamo/química , Hipotálamo/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/análise , Leptina/sangue , Masculino , Músculo Esquelético/enzimologia , Neuropeptídeos/análise , Obesidade/genética , Obesidade/metabolismo , Orexinas , Fosfoenolpiruvato Carboxiquinase (GTP)/análise , Fosfoenolpiruvato Carboxiquinase (GTP)/genética , Ratos , Termogênese/genética , Termogênese/fisiologia , Aumento de Peso/genética , Aumento de Peso/fisiologiaRESUMO
Refugees experience high rates of post-traumatic stress disorder (PTSD), anxiety, and depression due to exposure to civilian war trauma and forced migration. Inflammatory products may offer viable biological indicators of trauma-related psychopathology in this cohort, promoting rapid and objective assessment of psychopathology. Incoming Syrian and Iraqi refugees (n = 36) ages 18-65 completed self-report measures of PTSD, anxiety, and depression and provided saliva samples during an assessment at a primary care clinic within the first month of resettlement in the United States. Interleukin 1ß (IL-1ß) and C-reactive protein (CRP) differentially correlated with symptom severity by domain, and there was a non-significant trend for sex moderating the relation between inflammation and PTSD symptoms. Our findings show unique relations between trauma-related psychopathology and inflammation. There is a need for further research in diverse ethnic cohorts with differential trauma exposures for inflammation to be considered a biological indicator of psychopathology.
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BACKGROUND: Scholarly productivity is an essential component of college of pharmacy activities and may depend on university rank, faculty type, faculty rank and department. Bibliometric measures provide a means to analyze scholarly productivity from colleges of pharmacy while accounting for these various factors. OBJECTIVES: To analyze bibliometric data from two databases based on Carnegie Research Classification and NIH-funding rank; provide descriptions of bibliometric data based on department type and faculty classification; and examine the distribution of publications in the top 50 NIH-funded Colleges of Pharmacy. METHODS: Faculty rosters were gathered for the top 50 NIH-funded colleges of pharmacy, and names were searched in Scopus and Web of Science to establish bibliometric records. Bibliometric indices were compared based on Carnegie Basic Classification and between the NIH funding ranks 1-25 versus 26-50 using WOS bibliometric data. Descriptive statistics were presented, and Pareto distributions were developed for total publications across all schools included. RESULTS: Schools in the top 25 for NIH funding and schools with a Carnegie R1 classification had significantly higher bibliometric measures compared to schools ranked 26-50 and schools classified as R2, respectively. For faculty members with a bibliometric record (i.e., at least one publication), 20% provide approximately 60% of the publications. Additionally, approximately 90% of publications are provided by 50% of faculty records. Faculty records from basic science departments, as compared to clinical pharmacy departments, represent the highest contributing groups in the Pareto analysis. CONCLUSION: Bibliometric indices are higher at colleges of pharmacy with greater NIH funding or an R1 Carnegie classification. A minority of faculty provides most publications in colleges of pharmacy, which is composed of members from basic science departments. The descriptive data provided here is useful for understanding readily available bibliometric data based on department type and faculty classification and rank.
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Farmácia , Universidades , Bibliometria , Docentes , Humanos , Faculdades de Farmácia , Estados UnidosRESUMO
BACKGROUND: Psychological war trauma among displaced refugees is an established risk factor for mental health disorders, especially post-traumatic stress disorder (PTSD). Persons with trauma-induced disorders have heightened neuroplastic restructuring of limbic brain circuits (e.g., amygdala and hippocampus), which are critical factors in the pathophysiology of PTSD. Civilians in war are exposed to both psychological trauma and environmental hazards, such as metals. Little is known about the possible mental health impact from such environmental exposures, alone or in combination with trauma. It is of special interest to determine whether war exposures contribute to dysfunctional neuroplasticity; that is, an adverse outcome from sustained stress contributing to mental health disorders. The current study examined Middle Eastern refugees in the United States to determine the relationships among pre-displacement trauma and environmental exposures, brain derived neurotrophic growth factor (BDNF) and nerve growth factor (NGF)-two neurotrophins reported to mediate neuroplasticity responses to stress-related exposures-and mental health. METHODS: Middle Eastern refugees (n = 64; 33 men, 31 women) from Syria (n = 40) or Iraq (n = 24) were assessed 1 month after arrival to Michigan, US. Participants were interviewed in Arabic using a semi-structured survey to assess pre-displacement trauma and environmental exposure, PTSD, depression, anxiety, and self-rated mental health. Whole blood was collected, and concentrations of six heavy metals as well as BDNF and NGF levels were determined. Because these two neurotrophins have similar functions in neuroplasticity, we combined them to create a neuroplasticity index. Linear regression tested whether psychosocial trauma, environmental exposures and biomarkers were associated with mental health symptoms. FINDINGS: The neuroplasticity index was associated with PTSD (standardized beta, ß = 0.25, p < 0.05), depression (0.26, < 0.05) and anxiety (0.32, < 0.01) after controlling for pre-displacement trauma exposures. In addition, pre-displacement environmental exposure was associated with PTSD (0.28, < 0.05) and anxiety (0.32, < 0.05). Syrian refugees and female gender were associated with higher scores on depression (0.25, < 0.05; 0.30, < 0.05) and anxiety scales (0.35, < 0.01; 0.27, < 0.05), and worse on self-rated mental health (0.32, < 0.05; 0.34, < 0.05). In bivariate analysis, the neuroplasticity index was related to blood lead levels (r = 0.40; p < 0.01). CONCLUSIONS: The current study confirms the adverse effects of war trauma on mental health. Higher levels of biomarkers of neuroplasticity correlated with worse mental health and higher blood lead levels. Higher neurotrophin levels in refugees might indicate dysfunctional neuroplasticity with increased consolidation of adverse war memories in the limbic system. Such a process may contribute to psychiatric symptoms. Further research is needed to clarify the pathobiological mechanisms linking war trauma and environmental exposures to adverse mental health.
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Saúde Mental , Plasticidade Neuronal/fisiologia , Refugiados/psicologia , Adulto , Ansiedade/patologia , Fator Neurotrófico Derivado do Encéfalo/análise , Depressão/patologia , Exposição Ambiental , Feminino , Humanos , Entrevistas como Assunto , Iraque , Chumbo/sangue , Masculino , Pessoa de Meia-Idade , Trauma Psicológico/patologia , Autorrelato , Transtornos de Estresse Pós-Traumáticos/patologia , Síria , Estados UnidosRESUMO
BACKGROUND Intestinal bacterial communities are not homogenous throughout the gastrointestinal tract. Human research on the gut microbiome often neglects intra-intestinal variability by relying on a single measurement from stool samples. One source of complexity is the adherence to undigested, residual fiber. Currently, no procedure exists to extract RNA from distinct bacterial subpopulations in stool samples. MATERIAL AND METHODS A serial centrifugation procedure was developed in which bacterial RNA could be extracted from distinct stool-fractions - fiber-adherent and non-fiber-adherent bacteria. To test whether the separation procedure yielded distinct bacterial subpopulations, a set of RT-qPCR assays were developed for a fiber-adherent bacterial species, Bifidobacterium adolescentis, then a within-subject repeated-measures study was conducted with 3 human subjects undergoing 4 dietary regimens. At each timepoint, between-fraction differences in gene expression were evaluated. RESULTS The RNA isolation procedure was able to isolate intact RNA in 20 of 24 samples in the fiber-adherent fraction. PurB and sdh were identified as suitable reference genes for B. adolescentis RT-qPCR assays. When subjects were provided a high resistant starch diet, bacterial fractions exhibited different expression of the trp operon (p=0.031). CONCLUSIONS Our study provides human gut microbiome researchers a novel tool for evaluating functional characteristics of bacterial subpopulations in human stool. Moreover, these experiments provide modest support for the existence of a functionally unique fiber-adherent subpopulation of B. adolescentis. Until a more thorough evaluation of the adherent and non-adherent fraction can be performed, researchers should be cautious when generalizing functional data derived solely from unfractionated stool samples.
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Fibras na Dieta/microbiologia , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Bactérias/genética , Bactérias/isolamento & purificação , Bifidobacterium adolescentis/genética , Bifidobacterium adolescentis/isolamento & purificação , Dieta , Humanos , RNA/genética , RNA/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos TestesRESUMO
Epidemiologic studies link increased autism spectrum disorder (ASD) risk to obstetrical conditions associated with inflammation and steroid dysregulation, referred to as prenatal metabolic syndrome (PNMS). This pilot study measured steroid-related biomarkers in early second trimester maternal serum collected during the first and second trimester evaluation of risk study. ASD case and PNMS exposure status of index offspring were determined through linkage with autism registries and birth certificate records. ASD case (N = 53) and control (N = 19) groups were enriched for PNMS exposure. Higher estradiol and lower sex hormone binding globulin (SHBG) were significantly associated with increased ASD risk. Study findings provide preliminary evidence to link greater placental estradiol activity with ASD and support future investigations of the prenatal steroid environment in ASD.
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Transtorno do Espectro Autista/sangue , Estradiol/sangue , Segundo Trimestre da Gravidez/sangue , Globulina de Ligação a Hormônio Sexual/metabolismo , Adulto , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Projetos Piloto , Gravidez , Sistema de Registros , Adulto JovemRESUMO
The original version of the article has been published without funding source information.
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Atypical antipsychotics increase the risk of diabetes and cardiovascular disease through their side effects of insulin resistance and weight gain. The populations for which atypical antipsychotics are used carry a baseline risk of metabolic dysregulation prior to medication which has made it difficult to fully understand whether atypical antipsychotics cause insulin resistance and weight gain directly. The purpose of this work was to conduct a systematic review and meta-analysis of atypical antipsychotic trials in healthy volunteers to better understand their effects on insulin sensitivity and weight gain. Furthermore, we aimed to evaluate the occurrence of insulin resistance with or without weight gain and with treatment length by using subgroup and meta-regression techniques. Overall, the meta-analysis provides evidence that atypical antipsychotics decrease insulin sensitivity (standardized mean difference=-0.437, p<0.001) and increase weight (standardized mean difference=0.591, p<0.001) in healthy volunteers. It was found that decreases in insulin sensitivity were potentially dependent on treatment length but not weight gain. Decreases in insulin sensitivity occurred in multi-dose studies <13days while weight gain occurred in studies 14days and longer (max 28days). These findings provide preliminary evidence that atypical antipsychotics cause insulin resistance and weight gain directly, independent of psychiatric disease and may be associated with length of treatment. Further, well-designed studies to assess the co-occurrence of insulin resistance and weight gain and to understand the mechanisms and sequence by which they occur are required.