RESUMO
Protein glycosylation is the co- and/or post-translational modification of proteins with oligosaccharides (glycans). This process is not template based and can introduce a heterogeneous set of glycan modifications onto substrate proteins. Glycan structures preserve biomolecular information from the cell, with glycoproteins from different cell types and tissues displaying distinct patterns of glycosylation. Several decades of research have revealed that glycan structures also differ between normal physiology and disease. This suggests that the information stored in glycoproteins and glycans can be utilized for disease diagnosis and monitoring. Methods that enable sensitive and site-specific measurement of protein glycosylation in clinical settings, such as nano-flow liquid chromatography tandem mass spectrometry, are therefore essential. The purpose of this perspective is to discuss recent advances in mass spectrometry and the potential of these advances to facilitate the detection and monitoring of disease-specific glycoprotein glycoforms. Glycoproteomics, the system-wide characterization of glycoprotein identity inclusive of site-specific characterization of carbohydrate modifications on proteins, and glycomics, the characterization of glycan structures, will be discussed in this context. Quantitative measurement of glycopeptide markers via parallel reaction monitoring is highlighted. The development of promising glycopeptide markers for autoimmune disease, liver disease, and liver cancer is discussed. Synthetic glycopeptide standards, ambient ionization mass spectrometry, and consideration of glyco-biomarkers in two- and three-dimensional space within tissue will be critical to the advancement of this field. The authors envision a future in which glycoprotein mass spectrometry workflows will be integrated into clinical settings, to aid in the rapid diagnosis and monitoring of disease.
Assuntos
Glicoproteínas , Polissacarídeos , Proteômica , Humanos , Glicoproteínas/análise , Glicoproteínas/química , Glicoproteínas/metabolismo , Glicosilação , Proteômica/métodos , Polissacarídeos/análise , Polissacarídeos/química , Biomarcadores/análise , Espectrometria de Massas/métodos , Glicômica/métodos , Glicopeptídeos/análise , Glicopeptídeos/química , Processamento de Proteína Pós-Traducional , Espectrometria de Massas em Tandem/métodos , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/química , Hepatopatias/diagnóstico , Hepatopatias/metabolismo , Cromatografia Líquida/métodosRESUMO
Fcγ-receptors (FcγRs) including FcγRII (CD32) gene family members are expressed on leukocytes, bind the crystallizable fragment (Fc) region of immunoglobulin G (IgG), and bridge humoral and cellular immunity. FcγRIIA and FcγRIIB have opposing roles, with the former responsible for activation and the latter for inhibition of immune cell signaling and effector functions. The extracellular domains of human and murine FcγRIIs share multiple conserved N-glycosylation sites. Understanding the role(s) of FcγRIIA and FcγRIIB glycosylation in autoimmune diseases is precluded by a lack of effective methods to study disease-associated changes in glycosylation. To address this barrier, we developed a method to assess site-specific glycosylation of human FcγRIIA and FcγRIIB, and the mouse ortholog of human FcγRIIB. Among the receptors, conserved glycosylation sites are compared, with the N144/145 site displaying predominantly complex glycans in recombinant FcγRIIs. Differences in sialylation between recombinant human FcγRIIA H/R134 (H/R131) variants at a nearby N145 N-glycosylation site are reported. Further, a potential human FcγRIIA O-glycosylation site, S179 (S212), is reported in recombinant FcγRIIA. The robust method to assess site-specific glycosylation of FcγRIIs reported here, can be utilized to study the potential role of FcγRII family glycosylation in disease. Data are available via ProteomeXchange with identifier PXD049429.
Assuntos
Receptores de IgG , Glicosilação , Receptores de IgG/metabolismo , Receptores de IgG/genética , Receptores de IgG/química , Humanos , Animais , Camundongos , Polissacarídeos/metabolismo , Polissacarídeos/química , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/químicaRESUMO
One-third of people with schizophrenia have elevated levels of anti-gliadin antibodies (AGA IgG). A 5-week randomized double-blind pilot study was performed in 2014-2017 in an inpatient setting to test the effect of a gluten-free diet (GFD) on participants with schizophrenia or schizoaffective disorder who also had elevated AGA IgG (≥ 20 U) but were negative for celiac disease. This earlier pilot study reported that the GFD-group showed improved gastrointestinal and psychiatric symptoms, and also improvements in TNF-α and the inflammatory cytokine IL-23. Here, we performed measurements of these banked plasma samples to detect levels of oxidative stress (OxSt) using a recently developed iridium (Ir)-reducing capacity assay. Triplicate measurements of these samples showed an Intraclass Correlation Coefficient of 0.84 which indicates good reproducibility. Further, a comparison of the OxSt measurements at the baseline and 5-week end-point for this small sample size shows that the GFD-group (N = 7) had lowered OxSt levels compared to the gluten-containing diet group (GCD; N = 9; p = 0.05). Finally, we showed that improvements in OxSt over these 5 weeks were correlated to improvements in gastrointestinal (r = +0.64, p = 0.0073) and psychiatric (r = +0.52, p = 0.039) symptoms. Also, we showed a possible association between the decrease in OxSt and the lowered levels of IL-23 (r = +0.44, p = 0.087), although without statistical significance. Thus, the Ir-reducing capacity assay provides a simple, objective measure of OxSt with the results providing further evidence that inflammation, redox dysregulation and OxSt may mediate interactions between the gut and brain.
Assuntos
Dieta Livre de Glúten , Estresse Oxidativo , Esquizofrenia , Humanos , Esquizofrenia/dietoterapia , Esquizofrenia/sangue , Projetos Piloto , Estresse Oxidativo/fisiologia , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Método Duplo-Cego , Transtornos Psicóticos/dietoterapia , Transtornos Psicóticos/sangue , Transtornos Psicóticos/imunologia , Gliadina/imunologiaRESUMO
Fc γ-receptors (FcγRs) on leukocytes bind immunoglobulin G (IgG) immune complexes to mediate effector functions. Dysregulation of FcγR-mediated processes contributes to multiple inflammatory diseases, including rheumatoid arthritis, lupus, and immune thrombocytopenia. Critically, immunoregulatory N-glycan modifications on both FcγRs and IgGs alter FcγR-IgG binding affinity. Rapid methods for the characterization of N-glycans across multiple Fcγ receptors are needed to propel investigations into disease-specific contributions of FcγR N-glycans. Here, we utilize nanoliquid chromatography tandem mass spectrometry (nLC-MS/MS) to characterize FcγR glycosylation and report quantitative and site-specific N-glycan characterization of recombinant human FcγRI, FcγRIIIA V158, and FcγRIIIA F158 from CHO cells and murine FcγRI, FcγRIII, and FcγRIV from NS0 cells. Data are available via ProteomeXchange with identifier PXD043966. Broad glycoform distribution (≥30) was observed at mouse FcγRIV site N159 and human FcγRIIIA site N162, an evolutionarily conserved site. Further, mouse FcγRIII N-glycopeptides spanning all four predicted N-glycosylation sequons were detected. Glycoform relative abundances for hFcγRIIIA V/F158 polymorphic variants are reported, demonstrating the clinical potential of this workflow to measure differences in glycosylation between common human FcγRIIIA allelic variants with disease-associated outcomes. The multi-Fcγ receptor glycoproteomic workflow reported here will empower studies focused on the role of FcγR N-glycosylation in autoimmune diseases.
Assuntos
Receptores de IgG , Espectrometria de Massas em Tandem , Humanos , Animais , Camundongos , Cricetinae , Glicosilação , Receptores de IgG/genética , Cricetulus , Imunoglobulina G/genética , PolissacarídeosAssuntos
Trauma Psicológico , Transtornos Relacionados ao Uso de Substâncias , Humanos , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Trauma Psicológico/complicaçõesRESUMO
INTRODUCTION: Individuals with serious mental illness (SMI) smoke cigarettes at a much higher rate than the general population, increasing their risk for medical illnesses and mortality. However, individuals with SMI do not get enough support to quit smoking, partially because of concerns from medical providers that reducing smoking may worsen their symptoms or quality of life. METHODS: Veterans with SMI and nicotine dependence (n = 178) completed a 12-week smoking cessation trial (parent trial dates: 2010-2014) including assessments of smoking status, psychiatric symptoms (Brief Psychiatric Rating Scale), and quality of life (Lehman Quality of Life Interview-Short Version) at up to four time points: baseline, post-treatment, three-month follow-up, and 9-month follow-up. Bayesian multilevel modeling estimated the impact of changes in the self-reported number of cigarettes per day in the past seven days on psychiatric symptoms and quality of life. RESULTS: Between subjects, each additional pack of cigarettes smoked per day was associated with a 0.83 point higher score (95%CI: 0.03 to 1.7) on a negative symptoms scale ranging from 0 to 35. Within subjects, each one-pack reduction in the number of cigarettes smoked per day was associated with an improvement of 0.32 (95%CI = 0.12 to 0.54) on the health-related quality of life scale, which ranges from 0 to 7 points. There were no other significant between- or within-subjects effects of smoking on psychiatric symptoms or quality of life. CONCLUSIONS: Individuals with SMI and their providers should pursue smoking cessation without fear of worsening psychiatric symptoms or quality of life.
Assuntos
Fumar Cigarros , Transtornos Mentais , Humanos , Teorema de Bayes , Fumar Cigarros/epidemiologia , Fumar Cigarros/terapia , Transtornos Mentais/psicologia , Qualidade de Vida , Fumar/epidemiologia , Fumar/terapiaRESUMO
OBJECTIVE: Black/African American (AA) individuals are a group at risk for co-occurring posttraumatic stress disorder (PTSD) symptoms and alcohol use due to unique cultural and system-level barriers. Although associations between trauma exposure, PTSD symptoms, and alcohol use are well established across various populations, Black/AA individuals are underrepresented in this literature, and related findings in this population are inconclusive. Thus, the goal of this study was to examine the associations among trauma exposure, PTSD symptoms, and alcohol use in a sample of treatment-seeking, Black/AA adults. We hypothesized that trauma exposure and alcohol use would be positively associated and that this relationship would be mediated by PTSD symptoms. METHODS: This study conducted secondary analysis of screening data from a PTSD and alcohol use disorder clinical trial. Participants were 96 Black/AA adults (57.3% male; 2.0% Hispanic; M age = 44.73, SD = 11.83) who were seeking treatment for alcohol use and endorsed trauma exposure. Associations between trauma exposure, PTSD symptom severity, and quantity and frequency of alcohol use were tested using bivariate correlations and linear regressions. Hypothesized indirect effects were tested using IBM SPSS Statistics Version 27 PROCESS model 4 with bootstrapping. RESULTS: Findings illustrated a significant positive association between trauma exposure and PTSD symptoms and between PTSD symptoms and drinks per typical drinking day. PTSD symptoms were not significantly associated with number of drinking days. Tests of indirect effects were significant for trauma exposure on drinks per typical drinking day through PTSD symptoms. CONCLUSIONS: Results from the test of indirect effects suggest that among Black/AA adults with heavy alcohol use and trauma exposure, trauma exposure is associated with PTSD symptoms, which in turn is associated with quantity of alcohol use. These findings are consistent with research conducted with White/mixed groups and align with tenets of the self-medication model of PTSD-AUD comorbidity. These findings support current practices that highlight the importance of screening for and addressing PTSD and alcohol use in individuals exposed to trauma. Findings from this paper provide initial data on understudied relationships in an underserved sample and several suggestions are made to generate future research and improve clinical care for Black/AA adults. CLINICAL TRIALS REGISTRY NAME: Pharmacogenetic Treatment With Anti-Glutaminergic Agents for Comorbid PTSD & AUD; ClinicalTrials.gov Identifier: NCT02884908.
Assuntos
Alcoolismo , Transtornos de Estresse Pós-Traumáticos , Adulto , Humanos , Masculino , Feminino , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Negro ou Afro-Americano , Consumo de Bebidas Alcoólicas/epidemiologia , Alcoolismo/complicações , Alcoolismo/epidemiologia , Alcoolismo/diagnóstico , ComorbidadeRESUMO
BACKGROUND: Protozoan parasites are known to attach specific and diverse group of proteins to their plasma membrane via a GPI anchor. In malaria parasites, GPI-anchored proteins (GPI-APs) have been shown to play an important role in host-pathogen interactions and a key function in host cell invasion and immune evasion. Because of their immunogenic properties, some of these proteins have been considered as malaria vaccine candidates. However, identification of all possible GPI-APs encoded by these parasites remains challenging due to their sequence diversity and limitations of the tools used for their characterization. METHODS: The FT-GPI software was developed to detect GPI-APs based on the presence of a hydrophobic helix at both ends of the premature peptide. FT-GPI was implemented in C ++and applied to study the GPI-proteome of 46 isolates of the order Haemosporida. Using the GPI proteome of Plasmodium falciparum strain 3D7 and Plasmodium vivax strain Sal-1, a heuristic method was defined to select the most sensitive and specific FT-GPI software parameters. RESULTS: FT-GPI enabled revision of the GPI-proteome of P. falciparum and P. vivax, including the identification of novel GPI-APs. Orthology- and synteny-based analyses showed that 19 of the 37 GPI-APs found in the order Haemosporida are conserved among Plasmodium species. Our analyses suggest that gene duplication and deletion events may have contributed significantly to the evolution of the GPI proteome, and its composition correlates with speciation. CONCLUSION: FT-GPI-based prediction is a useful tool for mining GPI-APs and gaining further insights into their evolution and sequence diversity. This resource may also help identify new protein candidates for the development of vaccines for malaria and other parasitic diseases.
Assuntos
Proteínas Ligadas por GPI , Plasmodium falciparum , Plasmodium vivax , Proteoma , Proteínas de Protozoários , Proteínas Ligadas por GPI/genética , Plasmodium falciparum/genética , Plasmodium vivax/genética , Proteoma/análise , Proteínas de Protozoários/genéticaRESUMO
Bottom-up nLC-MS/MS-based glycoprotein mass spectrometry workflows rely on the generation of a mixture of non-glycosylated and glycosylated peptides via proteolysis of glycoproteins. Such methods are challenged by suppression of hydrophilic glycopeptide ions by more abundant, hydrophobic, and readily ionizable non-glycosylated peptides. Commercially available high-field asymmetric waveform ion mobility spectrometry (FAIMS) devices have recently been introduced and present a potential benefit for glycoproteomic workflows by enabling orthogonal separation of non-glycosylated peptides and glycopeptides following chromatographic separation, and prior to MS/MS analysis. However, knowledge is lacking regarding optimal FAIMS conditions for glycopeptide analyses. Here, we document optimal FAIMS compensation voltages for the transmission and analysis of human alpha-1-acid glycoprotein (AGP) tryptic N-glycopeptide ions. Further, we evaluate the effect of FAIMS on AGP glycopeptide assignment confidence by comparing the number of assigned glycopeptides at different confidence levels using a standard nLC-MS/MS method or an otherwise identical method employing FAIMS. Optimized methods will potentiate glycoproteomic analyses by increasing the number of unique glycopeptide identifications and the confidence of glycopeptide assignments. Data are available via ProteomeXchange with identifier PXD036667. Analysis of alpha-1-acid glycoprotein (AGP) tryptic digests via nLC-FAIMS-MS/MS (top) led to the establishment of ideal FAIMS voltages for the analysis of AGP N-glycopeptides (bottom), suggesting that FAIMS can improve the depth of glycoproteome characterization. Pairs of CV magnitudes are shown along the x-axis.
Assuntos
Glicopeptídeos , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Orosomucoide , Espectrometria de Mobilidade Iônica , Peptídeos/química , Íons/química , Proteínas Reguladoras de ApoptoseRESUMO
Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) often co-occur. This comorbidity negatively influences treatment outcomes, functioning, and quality of life. To better understand the relation between PTSD and AUD, research has begun to examine the influence of PTSD symptom clusters on alcohol-related problems. The current study is the first to analyze the associations between PTSD symptom clusters and alcohol consumption and AUD symptom severity in a treatment-seeking sample of Black/African American (AA) adults with co-occurring AUD and PTSD symptoms. Examination of these associations may help to facilitate greater recovery in this underserved population by identifying more precise targets for treatment. PTSD symptom clusters were identified from both the current 4-factor model identified in the DSM-5 and from a recently proposed 7-factor model. Participants were Black/AA adults (50.6% male) who endorsed trauma exposure and were seeking treatment for alcohol misuse. The majority (66%) were unemployed and almost half (45%) reported an income at or lower than $20,000. In the 4-factor model, results showed Cluster D symptoms of PTSD (i.e., negative alterations in cognitions and mood) were independently associated with alcohol consequences. Use of the 7-factor model, which divides Cluster D into symptoms of negative affect and anhedonia, further demonstrated that only anhedonic symptoms were independently associated with alcohol consequences. No symptom clusters were uniquely associated with alcohol consumption. Results suggest the absence of positive emotions, rather than the presence of negative emotions, are primarily associated with alcohol-related problems in a sample of trauma-exposed, Black/AA adults seeking treatment for alcohol misuse.
Assuntos
Transtornos Relacionados ao Uso de Álcool , Alcoolismo , Transtornos de Estresse Pós-Traumáticos , Adulto , Negro ou Afro-Americano , Transtornos Relacionados ao Uso de Álcool/psicologia , Alcoolismo/epidemiologia , Alcoolismo/psicologia , Feminino , Humanos , Masculino , Qualidade de Vida , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , SíndromeRESUMO
AIMS: Women often experience poorer smoking cessation outcomes in comparison to men. Menstrual cycle phase and sex hormones may influence smoking behavior and alter response to opioid antagonist medications. Less is known about the effects of sex hormones in response to pharmacotherapy for female heavy drinking smokers. METHODS: This study is a secondary analysis of premenopausal female heavy drinking smokers who completed a 12-week randomized clinical trial comparing varenicline plus placebo versus varenicline plus naltrexone for smoking cessation and drinking reduction. Participants (n = 26; total observations = 66) provided saliva samples for assays of progesterone (P4) and estradiol (E2) post-randomization at Weeks 4, 8 and 12. We examined the effects of P4/E2 ratio and medication on smoking and drinking outcomes. RESULTS: For drinking outcomes, there was a significant interaction for percent days abstinent (b = 0.017, P = 0.05), suggesting that greater P4/E2 ratio is associated with greater percent days abstinent for women assigned to the varenicline plus naltrexone condition. There were no interaction effects for the remaining drinking outcomes (P's ≥ 0.12). Results found no significant interaction effect of P4/E2 ratio and medication on smoking abstinence (P = 0.19). CONCLUSION: Our results imply that when women show a greater P4/E2 ratio, typically observed during the luteal phase of the menstrual cycle, they experience an added benefit of naltrexone, versus placebo, for drinking outcomes as shown by greater percent days abstinent. Additional studies in larger samples are warranted as sex hormones offer important information above and beyond comparing women versus men.
Assuntos
Naltrexona , Fumantes , Método Duplo-Cego , Feminino , Hormônios , Humanos , Masculino , Ciclo Menstrual , Naltrexona/farmacologia , Naltrexona/uso terapêutico , Vareniclina/uso terapêuticoRESUMO
BACKGROUND: Polysubstance use is a common, problematic behavior that increases risk of harm to self and others. Research suggests that rates may vary based on gender, sex and sexuality. Understanding the current state of this literature may inform prevention and treatment of polysubstance use, leading to reduced public health burden. OBJECTIVES: This review aimed to synthesize research on gender, sex and sexuality differences in polysubstance use in adults and adolescents. METHODS: A scoping review was conducted using all EBSCO databases, PubMed and Google Scholar to identify articles examining the effects of gender, sex and sexuality on polysubstance use. Polysubstance use was defined broadly as the use of any combination of substances over any time period and included licit (alcohol, tobacco) and illicit substances, concurrent and simultaneous use, from lifetime to daily use and use at any frequency. Studies were considered if they were published in peer-reviewed journals between January 1990 and October 2020 and were written in English. Publicly available data sources were also utilized to fully capture prevalence data that has not been published elsewhere. RESULTS: Findings were mostly inconsistent and often conflicting. Only two findings were generally consistent: adult men were overall more likely to report polysubstance use than adult women, and sexual and gender minorities report more frequent polysubstance use than non-minorities. CONCLUSIONS: Research has been unable to clearly elucidate differences in polysubstance use prevalence and patterns according to gender, sex and sexuality. Several recommendations are offered to advance future research and address limitations of current research.
Assuntos
Minorias Sexuais e de Gênero , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Adulto , Feminino , Humanos , Masculino , Comportamento Sexual , Sexualidade , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Uso de TabacoRESUMO
Social associations within mixed-species bird flocks can promote information flow about food availability and provide predator avoidance benefits. The relationship between flocking propensity, foraging habitat quality, and interspecific competition can be altered by human-induced habitat degradation. Here we take a close look at sociality within two ecologically important flock-leader (core) species, the Carolina chickadee (Poecile carolinensis) and tufted titmouse (Baeolophus bicolor), to better understand how degradation of foraging habitat quality affects mixed-species flocking dynamics. We compared interactions of free ranging wild birds across a gradient of foraging habitat quality in three managed forest remnants. Specifically, we examined aspects of the social network at each site, including network density, modularity, and species assortativity. Differences in the social networks between each end of our habitat gradient suggest that elevated levels of interspecific association are more valuable in the habitat with low quality foraging conditions. This conclusion is supported by two additional findings: First, foraging height for the subordinate Carolina chickadee relative to the tufted titmouse decreased with an increase in the number of satellite species in the most disturbed site but not in the other two sites. Second, the chickadee gargle call rate, an acoustic signal emitted during agonistic encounters between conspecifics, was relatively higher at the high-quality site. Collectively, these results suggest an increase in heterospecific associations increases the value of cross-species information flow in degraded habitats.
Assuntos
Passeriformes/fisiologia , Comportamento Social , Aves Canoras/fisiologia , Animais , Ecossistema , Estações do AnoRESUMO
The Hamilton Anxiety Inventory (HAM-A) is one of the oldest and most commonly used anxiety rating scales in clinical research. Despite its ubiquity, no studies have examined the scale's underlying factor structure and criterion validity among Black and African American adults with psychopathology (Mage = 42.25, SD = 11.44). Therefore, we estimated a confirmatory factor analysis of the commercially available Structured Interview Guide for the Hamilton Anxiety scale (SIGH-A; Williams, 1996) among African American adults (n = 88; 43% female) with co-occurring heavy alcohol use and trauma-related symptoms. Next, we examined the criterion validity of its Psychic and Somatic factors and overall anxiety severity score from participants who completed a single screening session (i.e., cross-sectional analysis) for a larger study. Results indicated that a two-factor solution provided an adequate fit to the data. Regression analyses indicated that the total SIGH-A score, but not its subscales, significantly predicted posttraumatic stress disorder (PTSD) severity. Neither the SIGH-A subscales nor total scores were significant predictors of alcohol consumption. The current findings suggest that the SIGH-A factor structure among African American adults with alcohol and trauma-related conditions is similar to previous reports that have tested largely White samples but highlight potential shortcomings when its subscales are used independently. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Assuntos
Negro ou Afro-Americano , Transtornos de Estresse Pós-Traumáticos , Humanos , Adulto , Feminino , Masculino , Estudos Transversais , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Ansiedade/diagnóstico , AnsiedadeRESUMO
OBJECTIVE: Panic disorder is a debilitating psychiatric disorder that often co-occurs with substance use disorders. Given the current opioid epidemic, the high reported rates of comorbid panic disorder and opioid use disorder are particularly concerning. In this narrative review, we describe the literature on panic disorder and opioid use disorder co-occurrence. METHODS: 86 studies, 26 reviews, 2 commentaries, and 5 guidelines pertaining to opioid use disorder, panic disorder, and their comorbidity were identified using all EBSCO databases, PubMed, and Google Scholar. RESULTS: First, we review epidemiological literature on the prevalence of the comorbid condition above and beyond each disorder on its own. Additionally, we discuss the challenges that complicate the differential diagnosis of panic disorder and opioid use disorder and contribute to difficulties establishing rates of comorbidity. Second, we review three theoretical models that have been proposed to explain high rates of co-occurring panic disorder and opioid use disorder: the precipitation hypothesis, the self-medication hypothesis, and the shared vulnerability hypothesis. Third, we outline how co-occurring panic and opioid use disorder may impact treatment for each condition. CONCLUSION: Based on findings in the field, we provide recommendations for future research as well as treatment considerations for co-occurring panic and opioid use disorders.
Assuntos
Transtornos Relacionados ao Uso de Opioides , Transtorno de Pânico , Humanos , Transtornos Relacionados ao Uso de Opioides/complicações , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/terapia , Transtorno de Pânico/complicações , Transtorno de Pânico/epidemiologia , AutomedicaçãoRESUMO
Saltmarsh sparrows (Ammospiza caudacuta) and seaside sparrows (A. maritima) are species of conservation concern primarily due to global sea-level rise and habitat degradation. Environmental mercury (Hg) contamination may present additional threats to their reproductive success and survival. To assess site-specific total mercury (THg) exposure and identify environmental correlates of THg detection, we sampled blood from adult male saltmarsh and seaside sparrows at 27 sites between Maine and Virginia, USA. The mean THg concentration (±1 SD) throughout the entire sampling range was 0.531 ± 0.287 µg/g wet weight (ww) for saltmarsh sparrows and 0.442 ± 0.316 µg/g ww for seaside sparrows. Individual THg concentrations ranged from 0.135-1.420 µg/g ww for saltmarsh sparrows and 0.153-1.530 µg/g ww for seaside sparrows. Model averaging from a suite of linear mixed models showed that saltmarsh sparrows averaged 20.1% higher blood THg concentrations than seaside sparrows, potentially due to differences in diet or foraging behavior. We found no evidence for a relationship between sparrow THg concentrations and land cover surrounding sampled marshes or average precipitation-based Hg deposition. Overall, our results suggest considerable, unexplained variation in tidal marsh sparrow blood THg concentrations over their co-occurring breeding ranges.
Assuntos
Poluentes Ambientais , Mercúrio , Pardais , Animais , Monitoramento Ambiental , Poluentes Ambientais/análise , Plumas/química , Masculino , Mercúrio/análise , New England , Áreas AlagadasRESUMO
BACKGROUND: Alcohol administration paradigms have been used for early efficacy testing of novel compounds for alcohol use disorder (AUD). There has been an ongoing debate about sample characteristics and methodological features that affect the likelihood of detecting an early efficacy signal for AUD medications. We conducted a meta-regression to test whether the drinking level of the study sample and the peak breath alcohol concentration (BrAC) in the alcohol administration study predict the efficacy of AUD pharmacotherapies on the subjective responses to alcohol. METHODS: We computed the effects of 21 medications on alcohol-induced stimulation, sedation, negative mood, and craving during alcohol administration in 49 studies. RESULTS: Meta-regression analyses indicated a significant and positive effect of pre-study drinks per month on alcohol-induced stimulation (ß = 0.142, p < 0.0001), such that as drinking increases, the benefit of medication over placebo decreases. There was an effect of drinks per month on negative mood (ß = -0.164, p = 0.0248), such that at higher levels of drinks per month, the effects of medications on negative mood are stronger. For sedation, there was an effect of peak BrAC (ß = 0.119, p = 0.0002), such that at low levels of peak BrAC, the effects of medication on sedation were null. For craving, there was a peak BrAC × drinks per month interaction such that at low levels of BrAC, a heavier drinking sample is required to detect the effects of medication on craving. Sensitivity analyses comparing naltrexone studies and non-naltrexone studies suggested that naltrexone was less sensitive to drinks per month across subjective response domains. CONCLUSIONS: These analyses show that design features are critical in studies that test the effects of medications on the subjective responses to alcohol. By specifying the significance and directionality of these effects, as well as the specific points in BrAC or drinks per month at which medication effects are detectable, the study offers recommendations for design features of alcohol administration studies that aim to inform AUD medication development.
Assuntos
Alcoolismo/tratamento farmacológico , Comportamento/efeitos dos fármacos , Resultado do Tratamento , Adolescente , Adulto , Afeto/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Testes Respiratórios , Criança , Fissura/efeitos dos fármacos , Relação Dose-Resposta a Droga , Etanol/administração & dosagem , Etanol/análise , Humanos , Hipnóticos e Sedativos , Pessoa de Meia-Idade , Naltrexona/uso terapêutico , Adulto JovemRESUMO
Behavioral pharmacology paradigms have been used for early efficacy testing of novel compounds for alcohol use disorder (AUD). However, the degree to which early efficacy in the human laboratory predicts clinical efficacy remains unclear. To address this gap in the literature we employed a novel meta-analytic approach. We searched the literature for medications tested for AUD using both behavioral pharmacology (i.e., alcohol administration) and randomized clinical trials (RCTs). For behavioral pharmacology, we computed medication effects on alcohol-induced stimulation, sedation, and craving during the alcohol administration (k = 51 studies, 24 medications). For RCTs, we computed medication effects on any drinking and heavy drinking (k = 118 studies, 17 medications). We used medication as the unit of analysis and applied the Williamson-York bivariate weighted least squares estimation to preserve the errors in both the independent and dependent variables. Results, with correction for publication bias, revealed a significant and positive relationship between medication effects on alcohol-induced stimulation (ß = 1.18 p < 0.05), sedation (ß = 2.38, p < 0.05), and craving (ß = 3.28, p < 0.001) in the laboratory, and drinking outcomes in RCTs, such that medications that reduced stimulation, sedation, and craving during the alcohol administration were associated with better clinical outcomes. A leave-one-out Monte Carlo analysis examined the predictive utility of these laboratory endpoints for each medication. The observed clinical effect size was within one standard deviation of the mean predicted effect size for all but three pharmacotherapies. This proof-of-concept study demonstrates that behavioral pharmacology endpoints of alcohol-induced stimulation, sedation, and craving track medication effects from the human laboratory to clinical trial outcomes. These results apply to alcohol administration phenotypes and may be especially useful to medications for which the mechanisms of action involve alterations in subjective responses to alcohol (e.g., antagonist medication). These methods and results can be applied to a host of clinical questions and can streamline the process of screening novel compounds for AUD. For instance, this approach can be used to quantify the predictive utility of cue-reactivity screening models and even preclinical models of medication development.