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1.
Artigo em Inglês | MEDLINE | ID: mdl-33548492

RESUMO

OBJECTIVE: Amygdala-ventrolateral prefrontal cortex (VLPFC) circuitry is disrupted in pediatric anxiety disorders, yet how selective serotonin reuptake inhibitors (SSRIs), impact this circuitry is unknown. We examined the impact of SSRI on functional connectivity (FC) within this circuit, and whether early FC changes predict treatment response in adolescents with generalized anxiety disorder (GAD). METHOD: Resting-state functional MR images were acquired before and after 2-weeks of treatment in 41 adolescents with GAD (age: 12-17) who received double-blind escitalopram or placebo over 8 weeks. Change in amygdala-based whole-brain FC and anxiety severity were analyzed. RESULTS: Controlling for age, sex and pretreatment anxiety, escitalopram increased amygdala-VLPFC connectivity compared to placebo (F=17.79, p=0.002 FWE-corrected). This early FC change predicted 76.7% of the variability in improvement trajectory in patients who received escitalopram (p<0.001) but not placebo (p=0.169); the predictive power of early amygdala-VLPFC FC change significantly differed between placebo and escitalopram (p=0.013). Further, this FC change predicted improvement better than baseline FC or demographics. Exploratory analyses of amygdala subfields' FC revealed connectivity of left basolateral amygdala (BLA)-VLPFC (F=19.64, p<0.001 FWE-corrected) and superficial amygdala-posterior cingulate cortex (F=22.92, p=0.001 FWE-corrected) were also increased by escitalopram, but only BLA-VLPFC FC predicted improvement in anxiety over 8 weeks of treatment. CONCLUSION: In adolescents with GAD, escitalopram increases amygdala-prefrontal connectivity within the first 2 weeks of treatment, and the magnitude of this change predicts subsequent clinical improvement. Early normalization of amygdala-VLPFC circuitry might represent a useful tool for identifying future treatment responders as well as a promising biomarker for drug development.

2.
Brain Res ; : 147386, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33631208

RESUMO

BACKGROUND/OBJECTIVE: The "neural noise" hypothesis suggests that individuals with dyslexia have high glutamate concentrations associated with their reading challenges. Different reading intervention programs have showed low GLX (a combined measure for glutamine and glutamate obtained with in vivo magnetic resonance spectroscopy) in association with reading improvement. Several studies demonstrated improved reading and increased activation in the anterior cingulate cortex following an-executive-function (EF)-based reading intervention. The goals of the current study are two-fold: 1) to determine if the effect of the EF-based reading program extends also to the metabolite concentrations and in particular, on the GLX concentrations in the anterior cingulate cortex; 2) to expand the neural noise hypothesis in dyslexia also to neural networks supporting additional parts of the reading networks, i.e. in specific regions related to executive function skills. METHODS: Children with dyslexia and typical readers were trained on the EF-based reading program. Reading ability was assessed before and after training while spectroscopy data was obtained at the end of the program. The association between change in reading scores following intervention and GLX concentrations was examined. RESULTS: Greater "gains" in word reading were associated with low GLX, Glu, Cr, and NAA concentrations for children with dyslexia compared to typical readers. CONCLUSIONS: These results suggest that the improvement reported following the EF-based reading intervention program also involved a low GLX concentration, as well as additional metabolites previously associated with better reading ability (Glx, Cr, NAA) which may point at the decreased neural noise, especially in the anterior cingulate cortex, as a possible mechanism for the effect of this program.

3.
Neurotoxicol Teratol ; : 106960, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33617950

RESUMO

Using a variety of research designs and measures of lead absorption, numerous studies link childhood lead exposure to a range of cognitive and behavioral deficits, including low IQ, impulsivity, juvenile delinquency, and criminal behavior in adolescence and early adulthood. In this study, we tested the association between multiple measures of blood lead concentration assessed in childhood with criminal behavior in adulthood and across the life-course. Prospective data from the Cincinnati Lead Study (CLS) included blood lead measures quarterly across the first 78 months of life and the number of times a person was arrested across the life-course (from age 18 to 33 years) and in later adulthood (age 27 to 33 years). Childhood blood lead concentration prospectively predicted variation in adult arrests and arrests over the life-course, indicating lead absorption is implicated in the etiology of crime-especially in geographic areas where environmental sources of lead are more prevalent and concentrated. Efforts to decrease lead exposure in both developed and developing countries should be part of a comprehensive strategy to reduce social dislocation and crime.

4.
Environ Int ; 147: 106344, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33418195

RESUMO

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) may adversely influence cardiometabolic risk. However, few studies have examined if the timing of early life PFAS exposure modifies their relation to cardiometabolic risk. We examined the influence of gestational and childhood PFAS exposure on adolescents' cardiometabolic risk. METHODS: We quantified concentrations of four PFAS (perfluorooctanoate [PFOA], perfluorooctane sulfonate [PFOS], perfluorononanoate [PFNA], and perfluorohexane sulfonate [PFHxS]) in sera collected during pregnancy, at birth, and at ages 3, 8, and 12 years from 221 mother-child pairs in the HOME Study (enrolled 2003-06, Cincinnati, Ohio). We measured cardiometabolic risk factors using physical examinations, fasting serum biomarkers, and dual-energy X-ray absorptiometry scans at age 12 years. Cardiometabolic risk summary scores were calculated by summing age- and sex-standardized z-scores for individual cardiometabolic risk factors. We used multiple informant models to estimate covariate-adjusted associations of serum PFAS concentrations (log2-transformed) at each visit with cardiometabolic risk scores and their individual components, and tested for differences in associations across visits. RESULTS: The associations of serum PFOA concentrations with cardiometabolic risk scores differed across visits (P for heterogeneity = 0.03). Gestational and cord serum PFOA concentrations were positively associated with cardiometabolic risk scores (ßs and 95% confidence intervals [95% CIs]: gestational 0.8 [0.0, 1.6]; cord 0.9 [-0.1, 1.9] per interquartile range increase). These positive associations were primarily driven by homeostatic model assessment for insulin resistance index (ß = 0.3 [0.1, 0.5]) and adiponectin to leptin ratio (ß = -0.5 [-1.0, 0.0]). Other individual cardiometabolic risk factors associated with gestational PFOA included insulin and waist circumference. Gestational and cord PFHxS were also associated with higher cardiometabolic risk scores (ßs: gestational 0.9 [0.2, 1.6]; cord 0.9 [0.1, 1.7]). CONCLUSION: In this cohort of children with higher gestational PFOA exposure, fetal exposure to PFOA and PFHxS was associated with unfavorable cardiometabolic risk in adolescence.

5.
NMR Biomed ; 34(1): e4419, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32990357

RESUMO

X-linked creatine transporter deficiency (CTD) is one of the three types of cerebral creatine deficiency disorders. CTD arises from pathogenic variants in the X-linked gene SLC6A8. We report the first phosphorus (31 P) MRS study of patients with CTD, where both phosphocreatine and total creatine concentrations were found to be markedly reduced. Despite the diminished role of creatine and phosphocreatine in oxidative phosphorylation in CTD, we found no elevation of lactate or lowered pH, indicating that the brain energy supply still largely relied on oxidative metabolism. Our results suggest that mitochondrial function is a potential therapeutic target for CTD.

6.
Environ Sci Technol ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33269902

RESUMO

Per- and polyfluoroalkyl substances (PFAS) exposure may increase adiposity and obesity risk in children. However, no studies have extended these findings into adolescence or identified periods of heightened susceptibility. We estimated associations of repeated pre- and postnatal serum PFAS concentrations with adolescent adiposity and risk of overweight/obesity. We studied 212 mother-offspring pairs from the HOME Study. We quantified serum concentrations of four PFAS in mothers at ∼16 week gestation and their children at birth and ages 3, 8, and 12 years. We assessed adiposity at 12 years using anthropometry and dual-energy X-ray absorptiometry. Using multiple informant models, we estimated covariate-adjusted associations of an interquartile range (IQR) increase in log2-transformed PFAS for each time period with adiposity measures and tested differences in these associations. Serum perfluorooctanoate (PFOA) and perfluorohexane sulfonate (PFHxS) concentrations during pregnancy were associated with modest increases in central adiposity and risk of overweight/obesity, but there was no consistent pattern for postnatal concentrations. We observed nonlinear associations between PFOA in pregnancy and some measures of adiposity. Overall, we observed a pattern of modest positive associations of gestational PFOA and PFHxS concentrations with central adiposity and the risk of obesity in adolescents, while no pattern was observed for postnatal PFAS concentrations.

7.
Environ Res ; 194: 110628, 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33345894

RESUMO

BACKGROUND: Evidence on the relationship between exposure to greenness and adolescent mental health is limited. The purpose of this study was to examine the association between greenness throughout childhood and mental health at age 12 years. METHODS: We assessed greenness using the satellite-based measure of Normalized Difference Vegetation Index (NDVI) within 200m, 400m, and 800m of home address at birth, age 12 years, and across childhood (averaged for each year from birth to age 12) among the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) cohort. Self-reported symptoms of anxiety and depression were assessed at age 12 years using the Spence Children's Anxiety Scale (SCAS) and Children's Depression Inventory 2 (CDI 2), respectively. Associations were estimated using linear regression, adjusting for covariates including traffic-related air pollution, neurological hazard exposure, blood lead level, household income, and community deprivation. RESULTS: In adjusted models, NDVI was largely not associated with self-reported anxiety and depression symptoms, except for the SCAS separation anxiety subscale at 400m and 800m (0.1 unit increase mean NDVI 400m: ß = -0.97, 95% CI: -1.86, -0.07; 800m: ß = -1.33, 95% CI: -2.32, -0.34). CONCLUSION: While we found no direct relationship between greenness and overall symptoms of anxiety and depression in adolescents upon adjustment for relevant covariates at the 200m distance, greenness may lesson symptoms of separation anxiety within 400m and 800m distance from the home address at age 12 years. Future research should examine mechanisms for these relationships at the community- and individual-level.

8.
Int J Obes (Lond) ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208860

RESUMO

BACKGROUND/OBJECTIVES: Gestational exposure to perfluoroalkyl substances (PFAS), a ubiquitous class of persistent endocrine disrupting chemicals, is associated with increased risk of obesity and cardiometabolic disease. However, it is unclear if gestational PFAS exposure is associated with adiposity trajectories related to adult obesity and cardiometabolic health. SUBJECTS/METHODS: We measured perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononaoic acid, and perfluorohexanesulfonic acid (PFHxS) concentrations in maternal serum collected between 16 weeks gestation and delivery in a cohort of 345 mother-child pairs in Cincinnati, OH (enrolled 2003-06). From age 4 weeks to 12 years, we measured weight and length or height up to eight times and calculated child body mass index (BMI) (1865 repeated measures). Using covariate-adjusted linear mixed models and splines to account for repeated BMI measures and nonlinear BMI patterns, respectively, we estimated the age/magnitude of infancy BMI zenith (~1 year) and childhood BMI nadir (~5 years), BMI accrual from 8 to 12 years, and BMI at age 12 years by PFAS terciles. RESULTS: BMI trajectories varied by PFOA concentrations (age × PFOA interaction p value = 0.03). Children born to women with higher PFOA concentrations had lower infancy and early childhood BMI, earlier BMI nadir, accelerating BMI gains in mid-childhood and adolescence, and higher BMI at age 12 years. Some of these associations were non-monotonic. PFOS and PFHxS were not associated with alterations in BMI trajectories, but were monotonically associated with lower BMI across infancy, childhood, and adolescence. Compared to children in the first PFOS tercile, those in the second (ß: -0.83; 95% confidence interval (CI): -2.11, 0.51 kg/m2), and third (ß: -1.41; 95% CI: -2.65, -0.14 kg/m2) had lower BMI at age 12 years. CONCLUSIONS: These results suggest that gestational PFOA exposure may be associated with BMI trajectories related to adult obesity and cardiometabolic disease, while PFOS and PFHxS exposure is associated with lower BMI in the first 12 years of life.

9.
Am J Intellect Dev Disabil ; 125(6): 475-480, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33211814

RESUMO

Although norm-referenced scores are essential to the identification of disability, they possess several features which affect their sensitivity to change. Norm-referenced scores often decrease over time among people with neurodevelopmental disorders who exhibit slower-than-average increases in ability. Further, the reliability of norm-referenced scores is lower at the tails of the distribution, resulting in floor effects and increased measurement error for people with neurodevelopmental disorders. In contrast, the person ability scores generated during the process of constructing a standardized test with item response theory are designed to assess change. We illustrate these limitations of norm-referenced scores, and relative advantages of ability scores, using data from studies of autism spectrum disorder and creatine transporter deficiency.

10.
Neurol Clin ; 38(4): 913-936, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33040869

RESUMO

A review of published articles examining the effects of manganese exposure to workers and community residents shows adverse neurologic outcomes. Innovative biomarkers, including those from neuroimaging, were incorporated into many of these studies to assess both manganese exposure and neurologic outcomes. A variety of health effects were evaluated, including cognitive and motor impairments. Studies of community participants residing near manganese point sources show variability in outcomes, reflecting the complexities of exposure measurement, individual absorption, and assessment of neurologic effects. The aging population provides insight into the impacts of chronic exposure in younger populations.

11.
J Child Adolesc Psychopharmacol ; 30(10): 606-616, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32721213

RESUMO

Objectives: Placebo response is one of the most significant barriers to detecting treatment effects in pediatric (and adult) clinical trials focusing on affective and anxiety disorders. We sought to identify neurofunctional predictors of placebo response in adolescents with generalized anxiety disorder (GAD) by examining dynamic and static functional brain connectivity. Methods: Before randomization to blinded placebo, adolescents, aged 12-17 years, with GAD (N = 25) underwent resting state functional magnetic resonance imaging. Whole brain voxelwise correlation analyses were used to determine the relationship between change in anxiety symptoms from baseline to week 8 and seed-based dynamic and static functional connectivity maps of regions in the salience and ventral attention networks (amygdala, dorsal anterior cingulate cortex [dACC], and ventrolateral prefrontal cortex [VLPFC]). Results: Greater dynamic functional connectivity variability in amygdala, dACC, VLPFC, and regions within salience, default mode, and frontoparietal networks was associated with greater placebo response. Lower static functional connectivity between amygdala and dorsolateral prefrontal cortex, amygdala and medial prefrontal cortex, dACC and posterior cingulate cortex and greater static functional connectivity between VLPFC and inferior parietal lobule were associated with greater placebo response. Conclusion: Placebo response is associated with a distinct dynamic and static connectivity fingerprint characterized by "variable" dynamic but "weak" static connectivity in the salience, default mode, frontoparietal, and ventral attention networks. These data provide granular evidence of how circuit-based biotypes mechanistically relate to placebo response. Finding biosignatures that predict placebo response is critically important in clinical psychopharmacology and to improve our ability to detect medication-placebo differences in clinical trials.

12.
BMJ Open ; 10(5): e034838, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32385062

RESUMO

PURPOSE: Environmental chemical exposures may adversely affect an array of adolescent health outcomes. Thus, we used the Health Outcomes and Measures of the Environment (HOME) study, a prospective cohort that recruited pregnant women and conducted longitudinal follow-up on children over the first 12 years of life, to determine if and when chemical exposures affect adolescent health. PARTICIPANTS: We recruited 468 pregnant women (age range: 18-45 years) from the Cincinnati, Ohio region to participate in a cohort study between March 2003 and January 2006. Follow-up included two clinic and one home visits during pregnancy, a delivery hospital visit, and four home and six clinic visits when children were aged 4 weeks and 1, 2, 3, 4, 5 and 8 years. Of 441 children available for follow-up, 396 (90%) completed at least one follow-up and 256 (58%) completed the most recent follow-up at 12 years of age (range: 11-14). FINDINGS TO DATE: Our new measures include maternal/child report of internalising symptoms, neuroimaging, dual-energy X-ray absorptiometry-derived estimates of lean/adipose tissue and bone mineral density, and cardiometabolic risk biomarkers. We assessed adolescent exposure to perfluoroalkyl substances, phenols, phthalates and flame retardants. Participants completing follow-up at 12 years of age were similar to the original cohort in terms of baseline factors. Most children had typical and expected values for this age on measures of internalising symptoms, body composition, bone density and cardiometabolic risk markers. Notably, 36% and 11% of children had scores indicative of potential anxiety and depressive disorders, respectively. Approximately 35% of children were overweight or obese, with higher prevalence among girls. Thirty-three per cent of children had borderline or high triglyceride concentrations (>90 mg/dL). FUTURE PLANS: We will examine associations of early life environmental chemical exposures with adolescent health measures while considering potential periods of heightened susceptibility and mixture effects. TRIAL REGISTRATION NUMBER: NCT00129324.

13.
Semin Pediatr Neurol ; 33: 100798, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32331612

RESUMO

The basic principles of proton magnetic resonance spectroscopy are presented in this work to briefly familiarize the clinician and to distinguish spectroscopy from magnetic resonance imaging. For those knowledgeable about proton magnetic resonance spectroscopy, this article will also provide the reader an update on recent technical and translational developments relevant to pediatric neurologic conditions. These developments were selected for their potential impact towards the clinical care of patients in pediatric-based practices. At this point in time, these new spectroscopic approaches are currently applied to established populations with known diseases. This information will inform our knowledge about diseases and guide therapeutic options for the future.

14.
Radiology ; 295(1): 171-180, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32043950

RESUMO

Background The hardware and software differences between MR vendors and individual sites influence the quantification of MR spectroscopy data. An analysis of a large data set may help to better understand sources of the total variance in quantified metabolite levels. Purpose To compare multisite quantitative brain MR spectroscopy data acquired in healthy participants at 26 sites by using the vendor-supplied single-voxel point-resolved spectroscopy (PRESS) sequence. Materials and Methods An MR spectroscopy protocol to acquire short-echo-time PRESS data from the midparietal region of the brain was disseminated to 26 research sites operating 3.0-T MR scanners from three different vendors. In this prospective study, healthy participants were scanned between July 2016 and December 2017. Data were analyzed by using software with simulated basis sets customized for each vendor implementation. The proportion of total variance attributed to vendor-, site-, and participant-related effects was estimated by using a linear mixed-effects model. P values were derived through parametric bootstrapping of the linear mixed-effects models (denoted Pboot). Results In total, 296 participants (mean age, 26 years ± 4.6; 155 women and 141 men) were scanned. Good-quality data were recorded from all sites, as evidenced by a consistent linewidth of N-acetylaspartate (range, 4.4-5.0 Hz), signal-to-noise ratio (range, 174-289), and low Cramér-Rao lower bounds (≤5%) for all of the major metabolites. Among the major metabolites, no vendor effects were found for levels of myo-inositol (Pboot > .90), N-acetylaspartate and N-acetylaspartylglutamate (Pboot = .13), or glutamate and glutamine (Pboot = .11). Among the smaller resonances, no vendor effects were found for ascorbate (Pboot = .08), aspartate (Pboot > .90), glutathione (Pboot > .90), or lactate (Pboot = .28). Conclusion Multisite multivendor single-voxel MR spectroscopy studies performed at 3.0 T can yield results that are coherent across vendors, provided that vendor differences in pulse sequence implementation are accounted for in data analysis. However, the site-related effects on variability were more profound and suggest the need for further standardization of spectroscopic protocols. © RSNA, 2020 Online supplemental material is available for this article.


Assuntos
Encéfalo/metabolismo , Comércio , Espectroscopia de Ressonância Magnética/métodos , Adulto , Feminino , Humanos , Masculino , Estudos Prospectivos , Adulto Jovem
15.
Environ Res ; 184: 109255, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32087441

RESUMO

Organophosphate esters (OPEs) are a group of chemicals used as flame retardants and plasticizers that replaced polybrominated diphenyl ethers in consumer products such as furniture and electronics. To characterize exposure to OPEs during fetal development, we measured urinary OPE metabolite concentrations in women twice during pregnancy (16 and 26 weeks' gestation) and at delivery (n = 357). We also previously quantified house dust OPE parent compound concentrations at 20 weeks' gestation (n = 317). Diphenyl phosphate (DPHP) had the highest geometric mean urinary concentrations (1.5-2.3 µg/g creatinine), followed by bis(1,3-dichloro-2-propyl) phosphate (BDCIPP; 0.75-0.99 µg/g creatinine), and bis(2-chloroethyl) phosphate (BCEP; 0.72-0.97 µg/g creatinine), while dibutyl phosphate (DNBP) had the lowest concentrations (0.25-0.28 µg/g creatinine). Urinary OPE metabolites were moderately correlated with each other at 26 weeks (rs: 0.23-0.38, p < 0.001) while the correlations at 16 weeks and delivery were slightly weaker. Intra-class correlations for urinary metabolites measured at three time points were poor (0.16-0.34), indicating high variability within individuals. Dust concentrations of OPE parent compounds were associated with BCEP, BDCIPP, and DPHP concentrations in urine at some but not all time points. In linear mixed models of urinary OPE metabolite concentrations, household size was inversely associated with BCEP concentrations, and being non-white was associated with lower BDCIPP and DPHP concentrations. Urine samples collected in the summer had the highest OPE metabolite concentrations. This study highlights the need to collect multiple urine samples during pregnancy to define exposure patterns and investigate potential periods of susceptibility.


Assuntos
Exposição Ambiental , Poluentes Ambientais , Ésteres , Desenvolvimento Fetal , Retardadores de Chama , Organofosfatos , Estudos de Coortes , Poluentes Ambientais/toxicidade , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Previsões , Humanos , Organofosfatos/toxicidade , Plastificantes , Gravidez
16.
Chemosphere ; 239: 124701, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31499316

RESUMO

Polybrominated diphenyl ethers, a class of flame retardants and endocrine disruptors, have been substituted in new products by organophosphate (OPFR) and replacement brominated flame retardants (RBFR). OPFRs and RBFRs readily migrate from consumer products into dust where humans are exposed via incidental ingestion and inhalation. We quantified concentrations and loadings of OPFRs and RBFRs in house dust samples (n = 317) collected from the homes of Cincinnati women between 2003 and 2006 and examined their associations with demographic and house characteristics. Tris-(1-chloro-2-propyl)-phosphate (TCIPP, geometric mean [GM]: 2140 ng g-1, range: 70.1-166,000 ng g-1), tris-(1,3-dichloro-2-propyl)-phosphate (TDCIPP, GM: 1840 ng g-1, range: 55.2-228,000 ng g-1), triphenyl phosphate (TPHP, GM: 1070 ng g-1, range: 34.1-62,100 ng g-1), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB, GM: 59.5 ng g-1, range: 2.82-7800 ng g-1), and bis-(2-ethylhexyl)-tetrabromophthalate (BEH-TEBP, GM: 121 ng g-1, range 2.17-13,600 ng g-1) were all detected in >90% of dust samples; tris-(2-chloroethyl)-phosphate (TCEP, GM: 669 ng g-1, range: 56.8-160,000 ng g-1) was detected in 80.1% of samples. Concentrations of EH-TBB and BEH-TEBP increased in house dust from 2003 to 2006. The number of people living in the home, race, education, floor type, and year of sample collection were associated with some OPFR and RBFR concentrations and loadings. This study suggests that OPFRs and RBFRs were ubiquitous in house dust during the PBDE phase-out and justifies more research on the consequences of exposure to these environmental chemicals.


Assuntos
Poeira/análise , Retardadores de Chama/análise , Éteres Difenil Halogenados/análise , Organofosfatos/análise , Adulto , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental , Poluentes Ambientais/análise , Feminino , Halogenação , Humanos , Ohio
18.
Environ Res ; 175: 71-78, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31103795

RESUMO

BACKGROUND: Exposure to traffic-related air pollution (TRAP) has been linked to childhood anxiety symptoms. Neuroimaging in patients with anxiety disorders indicate altered neurochemistry. OBJECTIVES: Evaluate the impact of TRAP on brain metabolism and its relation to childhood anxiety symptoms in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). METHODS: Adolescents (n = 145) underwent magnetic resonance spectroscopy. Brain metabolites, including myo-inositol, N-acetylaspartate, creatine, choline, glutamate, glutamate plus glutamine, and glutathione were measured in the anterior cingulate cortex. Anxiety symptoms were assessed using the Spence Children's Anxiety Scale. TRAP exposure in early-life, averaged over childhood, and during the 12 months prior to imaging was estimated using a validated land use regression model. Associations between TRAP exposure, brain metabolism, and anxiety symptoms were estimated using linear regression and a bootstrapping approach for testing mediation by brain metabolite levels. RESULTS: Recent exposure to high levels of TRAP was associated with significant increases in myo-inositol (ß = 0.26; 95%CI 0.01, 0.51) compared to low TRAP exposure. Recent elevated TRAP exposure (ß = 4.71; 95% CI 0.95, 8.45) and increased myo-inositol levels (ß = 2.98; 95% CI 0.43, 5.52) were also significantly associated with increased generalized anxiety symptoms with 12% of the total effect between TRAP and generalized anxiety symptoms being mediated by myo-inositol levels. CONCLUSIONS: This is the first study of children to utilize neuroimaging to link TRAP exposure, metabolite dysregulation in the brain, and generalized anxiety symptoms among otherwise healthy children. TRAP may elicit atypical excitatory neurotransmission and glial inflammatory responses leading to increased metabolite levels and subsequent anxiety symptoms.


Assuntos
Ansiedade , Encéfalo , Inositol , Poluição Relacionada com o Tráfego , Adolescente , Ansiedade/etiologia , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Inositol/análise , Espectroscopia de Ressonância Magnética , Masculino , Poluição Relacionada com o Tráfego/efeitos adversos
19.
Neuroimage ; 191: 537-548, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30840905

RESUMO

Accurate and reliable quantification of brain metabolites measured in vivo using 1H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited γ-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T1-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels.


Assuntos
Encéfalo/metabolismo , Espectroscopia de Ressonância Magnética/normas , Ácido gama-Aminobutírico/análise , Adolescente , Adulto , Conjuntos de Dados como Assunto , Feminino , Humanos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Valores de Referência , Água , Adulto Jovem
20.
Front Hum Neurosci ; 12: 466, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30532701

RESUMO

Children with dyslexia exhibit slow and inaccurate reading, as well as problems in executive functions. Decreased signal activation in brain regions related to visual processing and executive functions has been observed with functional magnetic resonance imaging with reports of sex differences in brain patterns for visual processing regions. However, the underlying neurochemistry associated with deficits in executive functions for children with dyslexia has not been thoroughly evaluated. Reading ability and executive functions were assessed in fifty-three children [ages 8-12 years old, dyslexia (n = 24), and typical readers (n = 30)]. We employed short echo, single voxel, proton magnetic resonance spectroscopy to evaluate the perigenual anterior cingulate cortex (ACC). Pearson correlations were calculated between metabolite concentrations and measures of reading, processing speed, and executive function. Logistic regression models were used to determine the effects of brain metabolite concentrations, processing speed, and reading scores on dyslexia status. Differences by child's sex were also examined. Compared to typical readers, higher global executive composite t-score is associated with greater odds for dyslexia (OR 1.14; 95% CI 1.05, 1.23); increased processing speed appears to be protective for dyslexia (OR 0.95; 95% 0.89-1.00). After adjustment for multiple comparisons, females with dyslexia showed strong and significant negative correlations between processing speed and myo-inositol (r = -0.55, p = 0.005) and choline (r = -0.54, p = 0.005) concentrations; effect modification by sex was confirmed in linear regression models (psex∗Cho = 0.0006) and (psex∗mI = 0.01). These associations were not observed for males or the group as a whole. These findings suggest that children with dyslexia share difficulty in one or more areas of executive function, specifically those related to response time. Also, metabolite changes in the ACC may be present in children with dyslexia, especially for females, and may hold value as possible markers for dyslexia.

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