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Children in the United States sleep less than the recommended amount and sleep deficiencies may be worse among disadvantaged children. Prior studies that compared sleep time in children of different race/ethnic groups mostly relied on questionnaires or were limited to small sample sizes. Our study takes advantage of the Adolescent Brain Cognitive Development study to compare total sleep time using a week of actigraphy data among American children (n = 4,207, 9 to 13 y old) of different racial/ethnic and income groups. We also assessed the effects of neighborhood deprivation, experience of discrimination, parent's age at child's birth, body mass index (BMI), and time the child fell asleep on sleep times. Daily total sleep time for the sample was 7.45 h and race/ethnicity, income, sex, age, BMI, were all significant predictors of total sleep time. Black children slept less than White children (â¼34 min; Cohen's d = 0.95), children from lower income families slept less than those from higher incomes (â¼16 min; Cohen's d = 0.44), boys slept less than girls (â¼7 min; Cohen's d = 0.18), and older children slept less than younger ones (â¼32 min; Cohen's d = 0.91); mostly due to later sleep times. Children with higher BMI also had shorter sleep times. Neither area deprivation index, experience of discrimination, or parent's age at child's birth significantly contributed to sleep time. Our findings indicate that children in the United States sleep significantly less than the recommended amount for healthy development and identifies significant racial and income disparities. Interventions to improve sleep hygiene in children will help improve health and ameliorate racial disparities in health outcomes.
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População Negra , Higiene do Sono , Sono , População Branca , Adolescente , Fatores Etários , Índice de Massa Corporal , Criança , Etnicidade , Feminino , Humanos , Renda , Masculino , Fatores Raciais , Fatores Sexuais , Estados Unidos/epidemiologiaRESUMO
PURPOSE: The purpose of this study was to determine the effect of acute nicotinamide riboside (NR) supplementation on cerebral nicotinamide adenine dinucleotide (NAD+) levels in the human brain in vivo by means of downfield proton MRS (DF 1H MRS). METHODS: DF 1H MRS was performed on 10 healthy volunteers in a 7.0 T MRI scanner with spectrally selective excitation and spatially selective localization to determine cerebral NAD+ levels on two back-to-back days: once after an overnight fast (baseline) and once 4 h after oral ingestion of nicotinamide riboside (900 mg). Additionally, two more baseline scans were performed following the same paradigm to assess test-retest reliability of the NAD+ levels in the absence of NR. RESULTS: NR supplementation increased mean NAD+ concentration compared to the baseline (0.458 ± 0.053 vs. 0.392 ± 0.058 mM; p < 0.001). The additional two baseline scans demonstrated no differences in mean NAD+ concentrations (0.425 ± 0.118 vs. 0.405 ± 0.082 mM; p = 0.45), and no difference from the first baseline scan (F(2, 16) = 0.907; p = 0.424). CONCLUSION: These preliminary results confirm that acute NR supplementation increases cerebral NAD+ levels in healthy human volunteers and shows the promise of DF 1H MRS utility for robust detection of NAD+ in humans in vivo.
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BACKGROUND: Previous preclinical and human studies have shown that a high-fat ketogenic diet and ketone supplements (KS) are efficacious in reducing alcohol craving, alcohol consumption, and signs of alcohol withdrawal. However, the effects of KS on alcohol sensitivity are unknown. METHODS: In this single-blind, cross-over study, 10 healthy participants (3 females) were administered a single, oral dose of a KS (25 g of ketones from D-ß-hydroxybutyric acid and R-1,3-butanediol) or placebo 30 minutes before an oral alcohol dose (0.25 g/kg for women; 0.31 g/kg for men). Assessments of breath alcohol concentration and blood alcohol levels (BAL) and responses on the Drug Effect Questionnaire were repeatedly obtained over 180 minutes after alcohol consumption. In a parallel preclinical study, 8 Wistar rats (4 females) received an oral gavage of KS (0.42 g ketones/kg), water, or the sweetener allulose (0.58 g/kg) followed 15 minutes later by an oral alcohol dose (0.8 g/kg). BAL was monitored for 240 minutes after alcohol exposure. RESULTS: In humans, the intake of KS before alcohol significantly blunted breath alcohol concentration and BAL, reduced ratings of alcohol liking and wanting more, and increased disliking for alcohol. In rats, KS reduced BAL more than either allulose or water. CONCLUSION: KS altered physiological and subjective responses to alcohol in both humans and rats, and the effects were likely not mediated by the sweetener allulose present in the KS drink. Therefore, KS could potentially reduce the intoxicating effects of alcohol.
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Alcoolismo , Síndrome de Abstinência a Substâncias , Masculino , Humanos , Ratos , Feminino , Animais , Estudos Cross-Over , Cetonas/farmacologia , Voluntários Saudáveis , Método Simples-Cego , Ratos Wistar , Etanol/farmacologia , Edulcorantes , Concentração Alcoólica no Sangue , Suplementos Nutricionais , ÁguaRESUMO
Background: Substance use disorders (SUDs) are heterogeneous across multiple functional domains. Various frameworks posit that domains (e.g., executive function) contribute to the persistence of SUDs; however, the domains identified in different studies vary.Objectives: We used factor analysis to identify the underlying latent domains present in a large sample (N = 5,244, 55.8% male) with a variety of SUDs to yield findings more generalizable than studies with a narrower focus.Method: Participants (1,384 controls and 3,860 participants with one or more SUDs including alcohol, cocaine, cannabis, and/or opioid use disorders) completed the Semi-Structured Assessment for Drug Dependence and Alcoholism, the NEO Personality Inventory, and the Wisconsin Card Sorting Test. Exploratory factor analysis (EFA) and fit indices (root mean-squared error of approximation (RMSEA), Comparative Fit Index (CFI), and Tucker-Lewis Index (TLI)) were used to examine different latent variable models. A multiple indicators, multiple causes (MIMIC) approach-tested associations of the latent variables with sociodemographics, substance use, and a history of abuse/neglect.Results: A six-factor model (predominant alcohol, predominant cocaine, predominant opioid, externalizing, personality, and executive function) provided the best fit [RMSEA = 0.063 (90% CI 0.060, 0.066), CFI = 0.98, TLI = 0.96]. All factors were moderately correlated (coefficient = 0.25-0.55, p < .05) with the exception of executive function. MIMIC analysis revealed different patterns of associations (all p < .0001) with sociodemographics, substance use, and a history of abuse/neglect among the factors.Conclusions: The domains identified, particularly executive function, were parallel to those observed previously. These factors underscore the heterogeneous nature of SUDs and may be useful in developing more targeted clinical interventions.
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Current theories suggest that altering choices requires value modification. To investigate this, normal-weight female participants' food choices and values were tested before and after an approach-avoidance training (AAT), while neural activity was recorded during the choice task using functional magnetic resonance imaging (fMRI). During AAT, participants consistently approached low- while avoiding high-calorie food cues. AAT facilitated low-calorie food choices, leaving food values unchanged. Instead, we observed a shift in indifference points, indicating the decreased contribution of food values in food choices. Training-induced choice shifts were associated with increased activity in the posterior cingulate cortex (PCC). In contrast, the medial PFC activity was not changed. Additionally, PCC gray matter density predicted individual differences in training-induced functional changes, suggesting anatomic predispositions to training impact. Our findings demonstrate neural mechanisms underlying choice modulation independent of valuation-related processes, which has substantial theoretical significance for decision-making frameworks and translational implications for health-related decisions resilient to value shifts.
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Comportamento de Escolha , Preferências Alimentares , Humanos , Feminino , Alimentos , Giro do Cíngulo/diagnóstico por imagem , Sinais (Psicologia) , Imageamento por Ressonância MagnéticaRESUMO
The human dopamine transporter gene SLC6A3 has been consistently implicated in several neuropsychiatric diseases but the disease mechanism remains elusive. In this risk synthesis, we have concluded that SLC6A3 represents an increasingly recognized risk with a growing number of familial mutants associated with neuropsychiatric and neurological disorders. At least five loci were related to common and severe diseases including alcohol use disorder (high activity variant), attention-deficit/hyperactivity disorder (low activity variant), autism (familial proteins with mutated networking) and movement disorders (both regulatory variants and familial mutations). Association signals depended on genetic markers used as well as ethnicity examined. Strong haplotype selection and gene-wide epistases support multimarker assessment of functional variations and phenotype associations. Inclusion of its promoter region's functional markers such as DNPi (rs67175440) and 5'VNTR (rs70957367) may help delineate condensate-based risk action, testing a locus-pathway-phenotype hypothesis for one gene-multidisease etiology.
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Transtorno do Deficit de Atenção com Hiperatividade , Proteínas da Membrana Plasmática de Transporte de Dopamina , Transtorno do Deficit de Atenção com Hiperatividade/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Haplótipos , Humanos , Mutação , FenótipoRESUMO
Sex differences in the prevalence of dopamine-related neuropsychiatric diseases and in the sensitivity to dopamine-boosting drugs such as stimulants is well recognized. Here we assessed whether there are sex differences in the brain dopamine system in humans that could contribute to these effects. We analyzed data from two independent [11C]raclopride PET brain imaging studies that measured methylphenidate-induced dopamine increases in the striatum using different routes of administration (Cohort A = oral 60 mg; Cohort B = intravenous 0.5 mg/kg; total n = 95; 65 male, 30 female), in blinded placebo-controlled designs. Females when compared to males reported stronger feeling of "drug effects" and showed significantly greater dopamine release in the ventral striatum (where nucleus accumbens is located) to both oral and intravenous methylphenidate. In contrast, there were no significant differences in methylphenidate-induced increases in dorsal striatum for either oral or intravenous administration nor were there differences in levels of methylphenidate in plasma. The greater dopamine increases with methylphenidate in ventral but not dorsal striatum in females compared to males suggests an enhanced sensitivity specific to the dopamine reward system that might underlie sex differences in the vulnerability to substance use disorders and to attention-deficit/hyperactivity disorder (ADHD).
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Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Estriado Ventral , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/farmacologia , Corpo Estriado , Dopamina/farmacologia , Feminino , Humanos , Masculino , Metilfenidato/farmacologia , Metilfenidato/uso terapêutico , Racloprida , Caracteres SexuaisRESUMO
Chronic heavy alcohol consumption is associated with increased mortality and morbidity and often leads to premature aging; however, the mechanisms of alcohol-associated cellular aging are not well understood. In this study, we used DNA methylation derived telomere length (DNAmTL) as a novel approach to investigate the role of alcohol use on the aging process. DNAmTL was estimated by 140 cytosine phosphate guanines (CpG) sites in 372 individuals with alcohol use disorder (AUD) and 243 healthy controls (HC) and assessed using various endophenotypes and clinical biomarkers. Validation in an independent sample of DNAmTL on alcohol consumption was performed (N = 4219). Exploratory genome-wide association studies (GWAS) on DNAmTL were also performed to identify genetic variants contributing to DNAmTL shortening. Top GWAS findings were analyzed using in-silico expression quantitative trait loci analyses and related to structural MRI hippocampus volumes of individuals with AUD. DNAmTL was 0.11-kilobases shorter per year in AUD compared to HC after adjustment for age, sex, race, and blood cell composition (p = 4.0 × 10-12). This association was partially attenuated but remained significant after additionally adjusting for BMI, and smoking status (0.06 kilobases shorter per year, p = 0.002). DNAmTL shortening was strongly associated with chronic heavy alcohol use (ps < 0.001), elevated gamma-glutamyl transferase (GGT), and aspartate aminotransferase (AST) (ps < 0.004). Comparison of DNAmTL with PCR-based methods of assessing TL revealed positive correlations (R = 0.3, p = 2.2 × 10-5), highlighting the accuracy of DNAmTL as a biomarker. The GWAS meta-analysis identified a single nucleotide polymorphism (SNP), rs4374022 and 18 imputed ones in Thymocyte Expressed, Positive Selection Associated 1(TESPA1), at the genome-wide level (p = 3.75 × 10-8). The allele C of rs4374022 was associated with DNAmTL shortening, lower hippocampus volume (p < 0.01), and decreased mRNA expression in hippocampus tissue (p = 0.04). Our study demonstrates DNAmTL-related aging acceleration in AUD and suggests a functional role for TESPA1 in regulating DNAmTL length, possibly via the immune system with subsequent biological effects on brain regions negatively affected by alcohol and implicated in aging.
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Proteínas Adaptadoras de Transdução de Sinal , Envelhecimento , Alcoolismo , Encurtamento do Telômero , Humanos , Consumo de Bebidas Alcoólicas/genética , Alcoolismo/genética , Metilação de DNA/genética , Estudo de Associação Genômica Ampla , Telômero/genética , Proteínas Adaptadoras de Transdução de Sinal/genéticaRESUMO
Incidence of opioid-related overdoses in the United States has increased dramatically over the past two decades. Despite public emphasis on overdose fatalities, most overdose cases are not fatal. Although there are case reports of amnestic syndromes and acute injury to the hippocampus following non-fatal opioid overdose, the effects of such overdoses on brain structure are poorly understood. Here, we investigated the neuroanatomical correlates of non-fatal opioid overdoses by comparing hippocampal volume in opioid use disorder (OUD) patients who had experienced an opioid overdose (OD; N = 17) with those who had not (NOD; N = 32). Voxel-based morphometry showed lower hippocampal volume in the OD group than in the NOD group, which on post hoc analysis was evident in the left but not the right hippocampus. These findings strengthen the evidence that hippocampal injury is associated with non-fatal opioid overdose, which is hypothesized to underlie overdose-related amnestic syndrome.
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Overdose de Drogas , Overdose de Opiáceos , Transtornos Relacionados ao Uso de Opioides , Humanos , Hipocampo/diagnóstico por imagem , Transtornos Relacionados ao Uso de Opioides/diagnóstico por imagem , Lobo TemporalRESUMO
Background: Cigarette smoking (CS) and opioid use disorder (OUD) significantly alter brain structure. Although OUD and cigarette smoking are highly comorbid, most prior neuroimaging research in OUD did not control for smoking severity. Specifically, the combined effect of smoking and OUD on the brain gray matter volume (GMV) remains unknown.Objectives: We used structural magnetic resonance imaging (sMRI) to examine: (1) the GMV differences between OUD and non-OUD individuals with comparable smoking severity; and (2) the differential effect of smoking severity on the brain GMV between individuals with and without OUD.Methods: We performed a secondary analysis of existing sMRI datasets of 116 individuals who smoked cigarettes daily, among whom 60 had OUD (CS-OUD; 37 male, 23 female) and 56 did not (CS; 31 male, 25 female). Brain GMV was estimated by voxel-based morphometry analysis.Results: Compared to the CS group, the CS-OUD group had a higher GMV in the occipital cortex and lower GMV in the prefrontal and temporal cortex, striatum, and pre/postcentral gyrus (whole-brain corrected-p < .05). There was a significant interaction between group and smoking severity on GMV in the medial orbitofrontal cortex (whole-brain corrected-p < .05), such that heavier smoking was associated with lower medial orbitofrontal GMV in the CS-OUD but not CS participants (r=-0.32 vs. 0.12).Conclusions: Our findings suggest a combination of independent and interactive effects of cigarette smoking and OUD on the brain gray matter. Elucidating the neuroanatomical correlates of comorbid opioid and tobacco use may shed the light on the development of novel interventions for affected individuals.
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Substância Cinzenta , Transtornos Relacionados ao Uso de Opioides , Humanos , Masculino , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Fumar , Encéfalo , Córtex Pré-Frontal/patologia , Imageamento por Ressonância Magnética/métodos , NicotianaRESUMO
Chronic excessive alcohol use has neurotoxic effects, which may contribute to cognitive decline and the risk of early-onset dementia. Elevated peripheral iron levels have been reported in individuals with alcohol use disorder (AUD), but its association with brain iron loading has not been explored. We evaluated whether (1) serum and brain iron loading are higher in individuals with AUD than non-dependent healthy controls and (2) serum and brain iron loading increase with age. A fasting serum iron panel was obtained and a magnetic resonance imaging scan with quantitative susceptibility mapping (QSM) was used to quantify brain iron concentrations. Although serum ferritin levels were higher in the AUD group than in controls, whole-brain iron susceptibility did not differ between groups. Voxel-wise QSM analyses revealed higher susceptibility in a cluster in the left globus pallidus in individuals with AUD than controls. Whole-brain iron increased with age and voxel-wise QSM indicated higher susceptibility with age in various brain areas including the basal ganglia. This is the first study to analyze both serum and brain iron loading in individuals with AUD. Larger studies are needed to examine the effects of alcohol use on iron loading and its associations with alcohol use severity, structural and functional brain changes, and alcohol-induced cognitive impairments.
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Alcoolismo , Ferro , Humanos , Ferro/química , Projetos Piloto , Mapeamento Encefálico/métodos , EnvelhecimentoRESUMO
The biological mediators that support cognitive-control and long-term weight-loss after laparoscopic sleeve gastrectomy (LSG) remain unclear. We measured peripheral appetitive hormones and brain functional-connectivity (FC) using magnetic-resonance-imaging with food cue-reactivity task in 25 obese participants at pre, 1 month, and 6 month after LSG, and compared with 30 normal weight controls. We also used diffusion-tensor-imaging to explore whether LSG increases brain structural-connectivity (SC) of regions involved in food cue-reactivity. LSG significantly decreased BMI, craving for high-calorie food cues, ghrelin, insulin, and leptin levels, and increased self-reported cognitive-control of eating behavior. LSG increased FC between the right dorsolateral prefrontal cortex (DLPFC) and the pregenual anterior cingulate cortex (pgACC) and increased SC between DLPFC and ACC at 1 month and 6 month after LSG. Reduction in BMI correlated negatively with increased FC of right DLPFC-pgACC at 1 month and with increased SC of DLPFC-ACC at 1 month and 6 month after LSG. Reduction in craving for high-calorie food cues correlated negatively with increased FC of DLPFC-pgACC at 6 month after LSG. Additionally, SC of DLPFC-ACC mediated the relationship between lower ghrelin levels and greater cognitive control. These findings provide evidence that LSG improved functional and structural connectivity in prefrontal regions, which contribute to enhanced cognitive-control and sustained weight-loss following surgery.
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Encéfalo/diagnóstico por imagem , Fissura/fisiologia , Gastrectomia/tendências , Rede Nervosa/diagnóstico por imagem , Obesidade/diagnóstico por imagem , Redução de Peso/fisiologia , Adulto , Biomarcadores/sangue , Encéfalo/metabolismo , Feminino , Hormônios/sangue , Humanos , Laparoscopia/tendências , Imageamento por Ressonância Magnética/tendências , Masculino , Rede Nervosa/metabolismo , Obesidade/sangue , Obesidade/cirurgiaRESUMO
Here we assessed changes in subcortical volumes in alcohol use disorder (AUD). A simple morphometry-based classifier (MC) was developed to identify subcortical volumes that distinguished 32 healthy controls (HCs) from 33 AUD patients, who were scanned twice, during early and later withdrawal, to assess the effect of abstinence on MC-features (Discovery cohort). We validated the novel classifier in an independent Validation cohort (19 AUD patients and 20 HCs). MC-accuracy reached 80% (Discovery) and 72% (Validation). MC features included the hippocampus, amygdala, cerebellum, putamen, corpus callosum, and brain stem, which were smaller and showed stronger age-related decreases in AUD than HCs, and the ventricles and cerebrospinal fluid, which were larger in AUD and older participants. The volume of the amygdala showed a positive association with anxiety and negative urgency in AUD. Repeated imaging during the third week of detoxification revealed slightly larger subcortical volumes in AUD patients, consistent with partial recovery during abstinence. The steeper age-associated volumetric reductions in stress- and reward-related subcortical regions in AUD are consistent with accelerated aging, whereas the amygdalar associations with negative urgency and anxiety in AUD patients support its involvement in the "dark side of addiction".
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Envelhecimento/patologia , Alcoolismo/diagnóstico por imagem , Tonsila do Cerebelo/diagnóstico por imagem , Comportamento Aditivo/diagnóstico por imagem , Aprendizado de Máquina/tendências , Adulto , Envelhecimento/psicologia , Alcoolismo/psicologia , Comportamento Aditivo/psicologia , Feminino , Humanos , Imageamento por Ressonância Magnética/tendências , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
Iron loading has been consistently reported in those with alcohol use disorder (AUD), but its effect on the clinical course of the disease is not yet fully understood. Here, we conducted a cohort study to examine whether peripheral iron measures, genetic variation in HFE rs1799945 and their interaction differed between 594 inpatient participants with alcohol use disorder (AUD) undergoing detoxification and 472 healthy controls (HC). We also assessed whether HFE rs1799945 was associated with elevated peripheral iron and can serve as a predictor of withdrawal severity. AUD patients showed significantly higher serum transferrin saturation than HC. Within the AUD group, transferrin saturation significantly predicted withdrawal symptoms (CIWA-Ar) and cumulative dose of benzodiazepine treatment during the first week of detoxification, which is an indicator of withdrawal severity. HFE rs1799945 minor allele carriers showed elevated transferrin saturation compared to non-carriers, both in AUD and healthy controls. Exploratory analyses indicated that, within the AUD cohort, HFE rs1799945 predicted CIWA withdrawal scores, and this relationship was significantly mediated by transferrin saturation. We provide evidence that serum transferrin saturation predicts alcohol withdrawal severity in AUD. Moreover, our findings replicated previous studies on elevated serum transferrin saturation in AUD and an involvement of HFE rs1799945 in serum transferrin saturation levels in both AUD and healthy controls. Future studies may use transferrin saturation measures as predictors for treatment or potentially treat iron overload to ameliorate withdrawal symptoms.
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Alcoolismo , Sobrecarga de Ferro , Síndrome de Abstinência a Substâncias , Alcoolismo/genética , Estudos de Coortes , Genótipo , Proteína da Hemocromatose/genética , Humanos , Sobrecarga de Ferro/genética , Síndrome de Abstinência a Substâncias/genética , Transferrina/análise , Transferrina/genéticaRESUMO
The human brain is organized into segregated networks with strong within-network connections and relatively weaker between-network connections. This "small-world" organization may be essential for maintaining an energetically efficient system, crucial to the brain which consumes 20% of the body's energy. Brain network segregation and glucose energy utilization both change throughout the lifespan. However, it remains unclear whether these processes interact to contribute to differences in cognitive performance with age. To address this, we examined fluorodeoxyglucose-positron emission tomography and resting-state functional magnetic resonance imaging from 88 participants aged 18-73 years old. Consistent with prior work, brain network segregation showed a negative association with age across both sensorimotor and association networks. However, relative glucose metabolism demonstrated an interaction with age, showing a negative slope in association networks but a positive slope in sensorimotor networks. Overall, brain networks with lower segregation showed significantly steeper age-related differences in glucose metabolism, compared with highly segregated networks. Sensorimotor network segregation mediated the association between age and poorer spatial cognition performance, and sensorimotor network metabolism mediated the association between age and slower response time. These data provide evidence that sensorimotor segregation and glucose metabolism underlie some age-related changes in cognition. Interventions that stimulate somatosensory networks could be important for treatment of age-related cognitive decline.
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Envelhecimento/fisiologia , Encéfalo/fisiologia , Cognição/fisiologia , Glucose/metabolismo , Rede Nervosa/fisiologia , Vias Neurais/fisiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Adulto JovemRESUMO
The translocator protein (TSPO) transports cholesterol into mitochondria and is involved in steroidogenesis. The TSPO polymorphism rs6971 influences binding of cholesterol and other TSPO ligands including positron-emission tomography (PET) imaging radiotracers. Although it is recognized that alcohol increases plasma high-density lipoproteins (HDLs), its effects on total cholesterol and triglycerides along with its relationship to TSPO genotype have not been assessed. Here, we evaluated whether plasma cholesterol and triglycerides are disrupted in alcohol use disorder (AUD) and their association with rs6971 in 932 AUD participants (DSM IV or 5) and 546 controls. AUD participants compared with controls had significantly higher plasma levels of total cholesterol, HDL, and triglycerides, but not of low-density lipoprotein (LDL). In the AUD group only, TSPO rs6971 had a significant effect on plasma levels of cholesterol, LDL, and triglycerides (AA (n = 62) > AG (n = 319) > GG (n = 551)), but not on HDL levels. Additionally, we showed a significant effect of TSPO rs6971 on withdrawal scores (Clinical Institute Withdrawal Assessment for Alcohol [CIWA]), with higher scores in AA (n = 50) compared with AG (n = 238) and GG (n = 428). CIWA scores in AUD participants correlated negatively with LDL and positively with HDL, but not with total cholesterol or triglycerides. These findings corroborate elevated plasma cholesterol and HDL levels in AUD and document significant increases in triglycerides. We also reveal for the first time an association in AUD participants between TSPO rs6971 genotype and plasma cholesterol, LDL, and triglyceride levels (not for HDL) and with withdrawal severity. Mediation analyses revealed that LDL (but not HDL) influenced the association between TSPO and alcohol withdrawal severity.
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Alcoolismo/genética , Colesterol/sangue , Polimorfismo Genético , Receptores de GABA/genética , Síndrome de Abstinência a Substâncias/genética , Adulto , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Triglicerídeos/sangueRESUMO
The effects of acute sleep deprivation on ß-amyloid (Aß) clearance in the human brain have not been documented. Here we used PET and 18F-florbetaben to measure brain Aß burden (ABB) in 20 healthy controls tested after a night of rested sleep (baseline) and after a night of sleep deprivation. We show that one night of sleep deprivation, relative to baseline, resulted in a significant increase in Aß burden in the right hippocampus and thalamus. These increases were associated with mood worsening following sleep deprivation, but were not related to the genetic risk (APOE genotype) for Alzheimer's disease. Additionally, baseline ABB in a range of subcortical regions and the precuneus was inversely associated with reported night sleep hours. APOE genotyping was also linked to subcortical ABB, suggesting that different Alzheimer's disease risk factors might independently affect ABB in nearby brain regions. In summary, our findings show adverse effects of one-night sleep deprivation on brain ABB and expand on prior findings of higher Aß accumulation with chronic less sleep.
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Peptídeos beta-Amiloides/metabolismo , Hipocampo/metabolismo , Privação do Sono/diagnóstico por imagem , Privação do Sono/metabolismo , Tálamo/metabolismo , Adulto , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/genética , Apolipoproteínas E/genética , Feminino , Genótipo , Hipocampo/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Privação do Sono/genética , Tálamo/diagnóstico por imagemRESUMO
OBJECTIVE: Obesity is associated with impaired inhibitory control over food intake. We hypothesized that the neural circuitry underlying inhibition of food craving would be impaired in obesity. Here we assessed whether obese men show altered brain responses during attempted cognitive inhibition of craving when exposed to food cues. METHODS: Sixteen obese men (32 ± 8.7 years old, BMI = 38.6 ± 7.2) were compared with 11 age-matched non-obese men (BMI 24.2 ± 2.5) using PET and FDG. Brain glucose metabolism was evaluated in a food deprived state: no food stimulation, food stimulation with no inhibition (NI), and food stimulation with attempted inhibition (AI), each on a separate day. Individualized favorite food items were presented prior to and after FDG injection for 40 min. For AI, participants were asked to attempt to inhibit their desire for the food presented. Self-reports for hunger and food desire were recorded. RESULTS: Food stimulation compared with no stimulation increased glucose metabolism in inferior and superior frontal gyrus, default mode network and cerebellum, in both groups. For both groups, AI compared with NI-suppressed metabolism in right subgenual anterior cingulate, orbitofrontal areas, bilateral insula, and temporal gyri. There was a stimulation-by-group interaction effect in obese (but not in non-obese) men showing increased metabolism in pregenual anterior cingulate cortex (pgACC) and caudate during AI relative to NI. Changes in the food desire from NI to AI correlated negatively with changes in metabolism in pgACC/caudate in obese but not in non-obese men. CONCLUSIONS: Obese men showed higher activation in pgACC/caudate, which are regions involved with self-regulation and emotion/reward during AI. Behavioral associations suggest that successful AI is an active process requiring more energy in obese but not in non-obese men. The additional required effort to increase cognitive control in response to food stimulation in obese compared with non-obese men may contribute to their uncontrolled eating behavior.
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Encéfalo/metabolismo , Encéfalo/fisiopatologia , Fissura/fisiologia , Comportamento Alimentar/fisiologia , Obesidade/fisiopatologia , Adulto , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Glucose/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Adulto JovemRESUMO
The role of sleep in brain physiology is poorly understood. Recently rodent studies have shown that the glymphatic system clears waste products from brain more efficiently during sleep compared to wakefulness due to the expansion of the interstitial fluid space facilitating entry of cerebrospinal fluid (CSF) into the brain. Here, we studied water diffusivity in the brain during sleep and awake conditions, hypothesizing that an increase in water diffusivity during sleep would occur concomitantly with an expansion of CSF volume - an effect that we predicted based on preclinical findings would be most prominent in cerebellum. We used MRI to measure slow and fast components of the apparent diffusion coefficient (ADC) of water in the brain in 50 healthy participants, in 30 of whom we compared awake versus sleep conditions and in 20 of whom we compared rested-wakefulness versus wakefulness following one night of sleep-deprivation. Sleep compared to wakefulness was associated with increases in slow-ADC in cerebellum and left temporal pole and with decreases in fast-ADC in thalamus, insula, parahippocampus and striatal regions, and the density of sleep arousals was inversely associated with ADC changes. The CSF volume was also increased during sleep and was associated with sleep-induced changes in ADCs in cerebellum. There were no differences in ADCs with wakefulness following sleep deprivation compared to rested-wakefulness. Although we hypothesized increases in ADC with sleep, our findings uncovered both increases in slow ADC (mostly in cerebellum) as well as decreases in fast ADC, which could reflect the distinct biological significance of fast- and slow-ADC values in relation to sleep. While preliminary, our findings suggest a more complex sleep-related glymphatic function in the human brain compared to rodents. On the other hand, our findings of sleep-induced changes in CSF volume provide preliminary evidence that is consistent with a glymphatic transport process in the human brain.
Assuntos
Encéfalo/metabolismo , Líquido Cefalorraquidiano/metabolismo , Sistema Glinfático/fisiologia , Sono/fisiologia , Adulto , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , MasculinoRESUMO
Excessive alcohol consumption is associated with neuroinflammation, which likely contributes to alcohol-related pathology. However, positron emission tomography (PET) studies using radioligands for the 18-kDa translocator protein (TSPO), which is considered a biomarker of neuroinflammation, reported decreased binding in alcohol use disorder (AUD) participants compared to controls. In contrast, autoradiographic findings in alcohol exposed rats reported increases in TSPO radioligand binding. To assess if these discrepancies reflected differences between in vitro and in vivo methodologies, we compared in vitro autoradiography (using [3 H]PBR28 and [3 H]PK11195) with in vivo PET (using [11 C]PBR28) in male, Wistar rats exposed to chronic alcohol-vapor (dependent n = 10) and in rats exposed to air-vapor (nondependent n = 10). PET scans were obtained with [11 C]PBR28, after which rats were euthanized and the brains were harvested for autoradiography with [3 H]PBR28 and [3 H]PK11195 (n = 7 dependent and n = 7 nondependent), and binding quantified in hippocampus, thalamus, and parietal cortex. Autoradiography revealed significantly higher binding in alcohol-dependent rats for both radioligands in thalamus and hippocampus (trend level for [3 H]PBR28) compared to nondependent rats, and these group differences were stronger for [3 H]PK11195 than [3 H]PBR28. In contrast, PET measures obtained in the same rats showed no group difference in [11 C]PBR28 binding. Our in vitro data are consistent with neuroinflammation associated with chronic alcohol exposure. Failure to observe similar increases in [11 C]PBR28 binding in vivo suggests the possibility that a mechanism mediated by chronic alcohol exposure interferes with [11 C]PBR28 binding to TSPO in vivo. These data question the sensitivity of PBR28 PET as a methodology to assess neuroinflammation in AUD.