RESUMO
AIMS: Peripheral cortisol represents one biological measure of the hypothalamic-pituitary-adrenal (HPA) axis, a significant component of the stress system, which is altered by chronic alcohol consumption. However, whether heavy alcohol use affects the HPA axis differentially between the sexes and whether basal cortisol levels are a biomarker of prospective alcohol intake is unknown. METHODS: We recruited light moderate (LM) and binge-heavy (BH) drinkers of alcohol (n = 118). Repeated fasting morning cortisol levels were studied over a 2-hour period to assess basal levels while participants underwent a neuroimaging scan. RESULTS: Significantly higher average cortisol levels in BH compared to LM groups across four timepoints were observed (P < .018). Overall sex differences were observed with women showing higher initial cortisol levels at the first timepoint with a blunted decrease over the morning relative to men (P < .003). Average morning cortisol differentially predicted prospective future 30-day daily reports of alcohol consumption by sex and group, such that LM males had a positive significant relationship and BH males had a negative non-significant relationship between cortisol and drinking. CONCLUSIONS: Findings indicate that morning plasma cortisol is upregulated in the BH vs. LM group. Although females had higher initial morning cortisol levels, BH males showed a dysregulated negative relationship between stress and binge drinking in contrast to the LM group. Future work should further investigate the role of cortisol and other stress hormones as biomarkers of problematic drinking behaviors in men and women.
Assuntos
Consumo de Bebidas Alcoólicas , Consumo Excessivo de Bebidas Alcoólicas , Hidrocortisona , Caracteres Sexuais , Humanos , Masculino , Feminino , Hidrocortisona/sangue , Consumo Excessivo de Bebidas Alcoólicas/sangue , Adulto , Estudos Prospectivos , Consumo de Bebidas Alcoólicas/sangue , Adulto Jovem , Biomarcadores/sangue , Fatores Sexuais , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Pessoa de Meia-IdadeRESUMO
High stress is a key risk factor for alcohol use disorder (AUD) and often accompanied by physiological dysregulation including autonomic nervous system (ANS) disruptions. However, neural mechanisms underlying drinking behaviors associated with stress and ANS disruptions remain unclear. The current study aims to understand neural correlates of stress, ANS disruptions, and subsequent alcohol intake in social drinkers with risky drinking. Using functional magnetic resonance imaging (fMRI), we investigated brain and heart rate (HR) autonomic responses during brief exposure to stress, alcohol, and neutral cues utilizing a well-validated, individualized imagery paradigm in 48 social drinkers of which 26 reported high-risk drinking (HD) while 22 reported low-risk drinking (LD) patterns. Results indicated that HD individuals showed stress and ANS disruptions with increased basal HR, stress-induced craving, and decreased brain response to stress exposure in frontal-striatal regions including the ventromedial prefrontal cortex (VmPFC), anterior cingulate cortex, striatum, insula, and temporal gyrus. Furthermore, whole-brain correlation analysis indicated that greater basal HR was associated with hypoactive VmPFC, but hyperactive medulla oblongata (MOb) responses during stress, with an inverse association between activity in the VmPFC and Mob (whole-brain corrected (WBC), p < 0.05). Functional connectivity with the MOb as a seed to the whole brain indicated that HD versus LD had decreased functional connectivity between the VmPFC and MOb during stress (WBC, p < 0.05). In addition, those with more compromised functional connectivity between the VmPFC and MOb during stress consumed greater amount of alcohol beverage during an experimental alcohol taste test conducted on a separate day, as well as in their self-reported weekly alcohol intake. Together, these results indicate that stress-related, dysfunctional VmPFC control over brain regions of autonomic arousal contributes to greater alcohol motivation and may be a significant risk factor for hazardous alcohol use in non-dependent social drinkers. Findings also suggest that restoring VmPFC integrity in modulating autonomic arousal during stress may be critical for preventing the development of AUD.
RESUMO
OBJECTIVE: The main objective of this study is to better understand the effects of diet-induced weight loss on brain connectivity in response to changes in glucose levels in individuals with obesity. METHODS: A total of 25 individuals with obesity, among whom 9 had a diagnosis of type 2 diabetes, underwent functional magnetic resonance imaging (fMRI) scans before and after an 8-week low-calorie diet. We used a two-step hypereuglycemia clamp approach to mimic the changes in glucose levels observed in the postprandial period in combination with task-mediated fMRI intrinsic connectivity distribution (ICD) analysis. RESULTS: After the diet, participants lost an average of 3.3% body weight. Diet-induced weight loss led to a decrease in leptin levels, an increase in hunger and food intake, and greater brain connectivity in the parahippocampus, right hippocampus, and temporal cortex (limbic-temporal network). Group differences (with vs. without type 2 diabetes) were noted in several brain networks. Connectivity in the limbic-temporal and frontal-parietal brain clusters inversely correlated with hunger. CONCLUSIONS: A short-term low-calorie diet led to a multifaceted body response in patients with obesity, with an increase in connectivity in the limbic-temporal network (emotion and memory) and hormone and eating behavior changes that may be important for recovering the weight lost.
Assuntos
Encéfalo , Restrição Calórica , Diabetes Mellitus Tipo 2 , Fome , Imageamento por Ressonância Magnética , Obesidade , Redução de Peso , Humanos , Obesidade/fisiopatologia , Obesidade/dietoterapia , Masculino , Feminino , Redução de Peso/fisiologia , Adulto , Pessoa de Meia-Idade , Fome/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Leptina/sangue , Glicemia/metabolismo , Ingestão de Alimentos/fisiologiaRESUMO
OBJECTIVE: Stress and alcohol cue reactivity are associated with poor treatment outcomes in alcohol use disorder (AUD), but sex-specific neural correlates of stress and alcohol cue-induced craving compared with neutral cue-induced craving and of heavy drinking outcomes in AUD have not been examined. Thus, this study prospectively examined these associations and assessed sex differences. METHODS: Treatment-seeking adults with AUD (N=77; 46 men and 31 women) completed a functional MRI task involving stress, alcohol, and neutral cue exposure with repeated assessments of alcohol craving. Most of these participants (N=72; 43 men and 29 women) then participated in an 8-week standardized behavioral AUD treatment program, during which the percentage of heavy drinking days was assessed. RESULTS: Significant increases in both stress and alcohol cue-induced craving relative to neutral cue-induced craving were observed, with a greater alcohol-neutral contrast in craving relative to the stress-neutral contrast among men and equivalent stress-neutral and alcohol-neutral contrasts in craving among women. Whole-brain voxel-based regression analyses showed craving-associated hyperactivation in the neutral condition, but hypoactive prefrontal (ventromedial and lateral prefrontal, supplementary motor, and anterior cingulate regions) and striatal responses during exposure to stressful images (stress-neutral contrast) and alcohol cues (alcohol-neutral contrast), with significant sex differences. Additionally, a higher percentage of heavy drinking days was associated with hypoactivation of the subgenual anterior cingulate cortex and the bed nucleus of the stria terminalis in the stress-neutral contrast among women, hyperactivation of the hypothalamus in the stress-neutral contrast among men, and hyperactivation of the hippocampus in the alcohol-neutral contrast among men. CONCLUSIONS: Sex differences in stress- and alcohol cue-induced responses in the cortico-striatal-limbic network related to subjective alcohol craving and to heavy drinking indicated that distinct brain circuits underlie alcohol use outcomes in women and men. These findings underscore the need for sex-specific therapeutics to address this neural dysfunction effectively.
Assuntos
Alcoolismo , Fissura , Sinais (Psicologia) , Imageamento por Ressonância Magnética , Estresse Psicológico , Humanos , Fissura/fisiologia , Masculino , Feminino , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Adulto , Alcoolismo/fisiopatologia , Alcoolismo/psicologia , Pessoa de Meia-Idade , Consumo de Bebidas Alcoólicas/psicologia , Consumo de Bebidas Alcoólicas/fisiopatologia , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Fatores Sexuais , Caracteres Sexuais , Estudos ProspectivosRESUMO
BACKGROUND: The objective of this study was to pilot test newly developed personalized imagery procedures to investigate the impact of racial stress on alcohol craving and emotional and physiological response in Black adults with alcohol use disorder (AUD). METHODS: Twenty Black adults (45% women, meanage=37.05, SDage=13.19) with AUD participated in two sessions. In the first, participants described a stressful personal event involving their race and a neutral relaxing situation and these descriptions were used to develop scripts for the subsequent laboratory exposure session. The second session was an experimental provocation session in which participants reported on alcohol craving and emotional response before and after imagined exposure to stress and neutral conditions using personalized racial stress and neutral/relaxing scripts. Conditions were randomized and counterbalanced across subjects, and heart rate and blood pressure were assessed before and after each image. RESULTS: Alcohol craving and negative emotions significantly increased, and positive emotions decreased following the racial stress script relative to the neutral/relaxing script. We found no differences in physiological response. Exploratory analyses found that increase in alcohol craving was correlated with racial identity exploration but not racial identity commitment, men reported greater reductions in anger than women in the neutral condition only, and income was correlated with fear in the racial stress condition only. CONCLUSIONS: This study provides evidence that personalized racial stress procedures elicit a stress response and increases alcohol craving and emotional response but not physiological response among Black adults with AUD. These findings warrant replication in a larger study.
Assuntos
Alcoolismo , Negro ou Afro-Americano , Fissura , Estresse Psicológico , Humanos , Feminino , Masculino , Fissura/fisiologia , Projetos Piloto , Adulto , Alcoolismo/psicologia , Estresse Psicológico/psicologia , Pessoa de Meia-Idade , Negro ou Afro-Americano/psicologia , Frequência Cardíaca/fisiologia , Pressão Sanguínea/fisiologia , Imagens, Psicoterapia/métodos , Emoções/fisiologia , Racismo/psicologiaRESUMO
Childhood adversity is linked to psychological, behavioral, and physical health problems, including obesity and cardiometabolic disease. Epigenetic alterations are one pathway through which the effects of early life stress and adversity might persist into adulthood. Epigenetic mechanisms have also been proposed to explain why cardiometabolic health can vary greatly between individuals with similar Body Mass Index (BMIs). We evaluated two independent cross-sectional cohorts of adults without known medical illness, one of which explicitly recruited individuals with early life stress (ELS) and control participants (n = 195), and the other a general community sample (n = 477). In these cohorts, we examine associations between childhood adversity, epigenetic aging, and metabolic health. Childhood adversity was associated with increased GrimAge Acceleration (GAA) in both cohorts, both utilizing a dichotomous yes/no classification (both p < 0.01) as well as a continuous measure using the Childhood Trauma Questionnaire (CTQ) (both p < 0.05). Further investigation demonstrated that CTQ subscales for physical and sexual abuse (both p < 0.05) were associated with increased GAA in both cohorts, whereas physical and emotional neglect were not. In both cohorts, higher CTQ was also associated with higher BMI and increased insulin resistance (both p < 0.05). Finally, we demonstrate a moderating effect of BMI on the relationship between GAA and insulin resistance where GAA correlated with insulin resistance specifically at higher BMIs. These results, which were largely replicated between two independent cohorts, suggest that interactions between epigenetics, obesity, and metabolic health may be important mechanisms through which childhood adversity contributes to long-term physical and metabolic health effects.
RESUMO
Polysubstance use (PSU), the use of two or more substances proximally, is highly prevalent and has amplified the risk for morbidity and mortality. However, PSU patterns and associated risk factors are not well characterized. This may be especially relevant to women who are known to be vulnerable to stress/trauma, craving, pain, and anxious and depressive symptoms as associated risk factors for PSU. A cross-sectional observational study was conducted to characterize substance use patterns in women who regularly used cocaine, opioids, marijuana, alcohol, benzodiazepines and/or nicotine and were being assessed for a placebo-controlled study of guanfacine treatment (n = 94; ages 19-65). Data on stress/traumatic life events, drug cravings for each substance, pain ratings, and anxiety and depressive symptoms were also obtained using standardized well-validated surveys. High use per day of two or more drugs was observed (72.7% ± 33.3%) and opioid amounts were high relative to other drug amounts (p's < 0.001). Notably, higher stress/trauma events and higher cravings are each associated with cumulative PSU days, amounts and probability of an individual PSU day (p's < 0.02). This remained when PSU versus single substance use was compared. Pain, anxiety and depressive symptoms were not associated with PSU metrics. These findings characterize specific patterns of PSU in women and show that average drug craving and stress/trauma events are associated with PSU. Interventions that focus on stress/trauma and craving management could be of benefit in reducing PSU risk in women.
Assuntos
Ansiedade , Transtornos Relacionados ao Uso de Substâncias , Humanos , Feminino , Estudos Transversais , Ansiedade/epidemiologia , Analgésicos Opioides , Dor , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
Adversity, trauma, and emotion dysregulation are commonly cited risk factors for suicidal thoughts and behaviors. Thus, the role of these factors in conferring risk for suicidal ideation (SI) and suicide attempts (SA) amongst community adults was assessed. A cross-sectional cohort-based study with community adults (n=757; female=55.0%) assessed emotion dysregulation, cumulative adversity including highly stressful and traumatic events, as well as other known risk factors for suicidality (e.g., self-reported depression and anxiety history) to predict a lifetime history of SI or SA, SI but no SA, or SI and SA. Higher cumulative stress and trauma scores conferred risk for SI, specifically on the subscales major life events, recent life events, and chronic stressors. Higher emotion dysregulation was associated with an increased risk for a SA relative to no SI or SA, particularly nonacceptance of emotional responses. Lifetime trauma was the only predictor of SA relative to SI. Nonacceptance of emotions significantly mediated the association between life traumas and suicidality. Cumulative adversity and emotion dysregulation confer risk for suicidal ideation and attempts, and higher lifetime trauma predicted attempts over ideation. These findings suggest that targeting emotion dysregulation, and specifically nonacceptance of difficult emotions, may be a useful strategy in reducing suicidal behaviors in individuals with trauma history and concurrent suicidal ideation.
Assuntos
Ideação Suicida , Tentativa de Suicídio , Adulto , Humanos , Feminino , Estudos Transversais , Tentativa de Suicídio/psicologia , Emoções , Ansiedade , Fatores de RiscoRESUMO
BACKGROUND: Alcohol use disorder (AUD) is associated with significant liver pathology marked by elevated liver enzymes. Prazosin, an alpha1-noradrenergic antagonist significantly improves alcohol drinking outcomes in individuals with alcohol withdrawal symptoms (AW), but effects on liver enzymes are unknown. We assessed the effects of prazosin treatment on the liver enzymes alanine transaminase (ALT), aspartate transaminase (AST), and gamma-glutamyltransferase (GGT) in individuals with AUD. METHODS: Participants (N=100) with AUD were enrolled in a 12-week randomized controlled trial and received either placebo or 16 mg/day of prazosin. Whole blood was drawn from 92 participants to measure liver enzyme levels every 4 weeks, and severity of AW was assessed weekly. Analysis predicting liver function outcomes used linear mixed effects models. RESULTS: Controlling for alcohol consumption, a significant AW × treatment effect was seen for ALT (p < 0.05), AST (p < 0.05) and GGT (p < 0.01). Additionally, AST (b = 0.2, p < 0.01), ALT (b = 0.2, p < 0.05), and GGT (b = 0.3, p < 0.01) were elevated in individuals with higher AW in the placebo but not in the prazosin group (AST: p > 0.66; ALT: p > 0.65). Only in the prazosin group were lower GGT levels associated with higher withdrawal severity (b = -0.16, p < 0.05). CONCLUSIONS: We found an interaction of alcohol withdrawal symptoms and prazosin treatment on liver enzyme levels, which were not influenced by week in the trial or the amount of alcohol consumed. Together, these findings suggest that prazosin treatment reduces liver enzymes over the course of AUD treatment among individuals with significant AW, though replication to establish clinical utility is needed.
RESUMO
INTRODUCTION: To inform approaches for adapting substance use treatment for Black adults, the aim of this study was to thematically analyze the stressors, triggers for substance use, and neutral/relaxing events reported among Black adults who participated in a lab paradigm. METHODS: The sample included 36 Black adults (mean age [years] = 37.47, SD = 7.30; 53 % male, 12 (33 %) with alcohol use disorder, 12 (33 %) with cocaine use disorder, and 12 (33 %) healthy controls). All participants provided detailed stimulus and response context information on the most stressful event they experienced in the past year, an event that involved substance use, and a neutral/relaxing event in a structured interview using a scene development questionnaire, and this information was utilized to generate a personalized imagery script for each event using standardized procedures. Thematic analyses identified the key themes reported within scripts. RESULTS: Consistent with a prior thematic analysis on a majority White sample, we found the following themes for the stress scripts: Relational (Violation, Loss, Parenting, Betrayal, Isolation vs. support), Environmental (Housing, Legal), and Achievement (Employment, Role in household). However, our analyses also resulted in new stress themes: Relational (Violation-Racial Microaggressions) and Institutional (Time Wasted). The substance use scripts consisted of the following trigger themes: Social (Social Facilitation, Socially-Sanctioned Substance Use Event, Exposure to Substance Use Friends/Associates), Internal (Free Time, Boredom, Thoughts of Using Substance, Frustration, Reward), and Environment (Availability of Substance, Celebration, Party Environment, Food, Hot Day, Money/Payday). The neutral/relaxing scripts themes were: Outdoor Activities (Admiring Nature, People Watching, Observing Surroundings, Enjoying the Sun, Playing in the Sand, Walking), Quiet Activities (Silence/Quiet, Prayer, Reading), and Indoor Activities (Radio, Television, Bath/Shower, Bed/Chair, Observing from a Window). We found sex differences across scripts. CONCLUSIONS: The results suggest that Black people experience unique stressors (e.g., institutional and racial stressors) that are important to consider when modifying treatment to improve outcomes among this group. In addition to stressors, this study also identified high-risk situations involving triggers for use. Taken together these findings suggest targets for the tailoring of coping strategies that could be incorporated for the development of culturally relevant behavioral treatment for SUD.
Assuntos
Sinais (Psicologia) , Transtornos Relacionados ao Uso de Substâncias , Humanos , Masculino , Adulto , Feminino , Transtornos Relacionados ao Uso de Substâncias/terapia , Adaptação Psicológica , População Negra , Caracteres Sexuais , Negro ou Afro-AmericanoRESUMO
Alcohol use disorder is highly prevalent and high risk of relapse remains a significant treatment challenge. Therefore, the utility of human laboratory models of relapse to further the understanding of psychobiological mechanisms that precipitate relapse risk and allow testing of novel interventions could be of benefit in expediting the development of effective treatments to target high relapse risk. Stress is a risk factor for the development of AUD and for relapse, and furthermore, chronic alcohol use leads to adaptations in central and peripheral stress biology. Here, we review our efforts to assess the integrity of these stress pathways in individuals with alcohol use disorder and whether adaptations in these systems play a role in relapse risk. Using validated human laboratory procedures to model two of the most common situations that contribute to relapse risk, namely stress and alcohol cues, we review how such models in the laboratory can predict subsequent relapse, and how we can measure specific identified biobehavioral markers of relapse effectively and ecologically in the real world. Finally, we discuss the significant implications of these findings for the development of novel and effective interventions that target stress dysregulation and craving as risk factors to treatment.
RESUMO
Emerging fMRI brain dynamic methods present a unique opportunity to capture how brain region interactions across time give rise to evolving affective and motivational states. As the unfolding experience and regulation of affective states affect psychopathology and well-being, it is important to elucidate their underlying time-varying brain responses. Here, we developed a novel framework to identify network states specific to an affective state of interest and examine how their instantaneous engagement contributed to its experience. This framework investigated network state dynamics underlying craving, a clinically meaningful and changeable state. In a transdiagnostic sample of healthy controls and individuals diagnosed with or at risk for craving-related disorders (N=252), we utilized connectome-based predictive modeling (CPM) to identify craving-predictive edges. An edge-centric timeseries approach was leveraged to quantify the instantaneous engagement of the craving-positive and craving-negative networks during independent scan runs. Individuals with higher craving persisted longer in a craving-positive network state while dwelling less in a craving-negative network state. We replicated the latter results externally in an independent group of healthy controls and individuals with alcohol use disorder exposed to different stimuli during the scan (N=173). The associations between craving and network state dynamics can still be consistently observed even when craving-predictive edges were instead identified in the replication dataset. These robust findings suggest that variations in craving-specific network state recruitment underpin individual differences in craving. Our framework additionally presents a new avenue to explore how the moment-to-moment engagement of behaviorally meaningful network states supports our changing affective experiences.
RESUMO
Stress can powerfully influence episodic memory, often enhancing memory encoding for emotionally salient information. These stress-induced memory enhancements stand at odds with demonstrations that stress and the stress-related hormone cortisol can negatively affect the hippocampus, a brain region important for episodic memory encoding. To resolve this apparent conflict and determine whether and how the hippocampus supports memory encoding under cortisol, we combined behavioral assays of associative memory, high-resolution fMRI, and pharmacological manipulation of cortisol in a within-participant, double-blinded procedure (in both sexes). Behaviorally, hydrocortisone promoted the encoding of subjectively arousing, positive associative memories. Neurally, hydrocortisone led to enhanced functional connectivity between hippocampal subregions, which predicted subsequent memory enhancements for emotional associations. Cortisol also modified the relationship between hippocampal representations and associative memory: whereas hippocampal signatures of distinctiveness predicted memory under placebo, relative integration predicted memory under cortisol. Together, these data provide novel evidence that the human hippocampus contains the necessary machinery to support emotional associative memory enhancements under cortisol.SIGNIFICANCE STATEMENT Our daily lives are filled with stressful events, which powerfully shape the way we form episodic memories. For example, stress and stress-related hormones can enhance our memory for emotional events. However, the mechanisms underlying these memory benefits are unclear. In the current study, we combined functional neuroimaging, behavioral tests of memory, and double-blind, placebo-controlled hydrocortisone administration to uncover the effects of the stress-related hormone cortisol on the function of the human hippocampus, a brain region important for episodic memory. We identified novel ways in which cortisol can enhance hippocampal function to promote emotional memories, highlighting the adaptive role of cortisol in shaping memory formation.
Assuntos
Hidrocortisona , Memória Episódica , Masculino , Feminino , Humanos , Hidrocortisona/farmacologia , Encéfalo , Hipocampo , Emoções , Imageamento por Ressonância Magnética/métodosRESUMO
Chronic heavy alcohol use profoundly affects the cardiovascular system, contributing to several life-threatening cardiovascular diseases. Heart rate variability (HRV), or the fluctuations in heart rate, reflects dynamic autonomic nervous system processes that change to meet biological demands and environmental challenges. In the current study, we examined whether HRV metrics are altered in alcohol use disorder (AUD) during waking and sleeping with passive biomonitoring as participants went about their daily lives. Social drinkers (standard deviation: n = 10, 5 female) and treatment-seeking individuals with moderate to severe AUD (n = 16, 7 female) provided continuous, real-world heart rate monitoring for 5 days of monitoring on average (M = 5.27 ± 2.22). Five indices of respiration and HRV-respiratory sinus arrhythmia (RSA) amplitude, high frequency (HF), low frequency (LF), HF/LF ratio, root-mean-square standard deviation (RMSSD), and standard deviation of the N-N intervals (SDNN)-were analyzed separately for waking and sleeping hours. Both RMSSD and SDNN decreased the longer the participants were awake (Ps < .013). During sleeping hours, HF, RSA amplitude, RMSSD, and SDNN were significantly higher in light social drinkers as compared to patients with AUD (all Ps < .009), indicating higher parasympathetic activation during sleep in the SD versus AUD group. Sleep and waking HRV measures were significantly correlated with patient-reported symptoms of depression and sleep difficulties in the AUD group (Ps < .05). This natural observational study utilizing continuous autonomic biomonitoring in the real world indicates parasympathetic dysfunction that is clearly detectable during sleep in AUD and HRV measures, which are also related to clinical, patient-related symptoms of AUD.
Assuntos
Alcoolismo , Doenças Cardiovasculares , Humanos , Feminino , Consumo de Bebidas Alcoólicas , Frequência Cardíaca/fisiologia , SonoRESUMO
Motivation states for physical activity and sedentarism potentially vary from moment to moment. The CRAVE scale (Cravings for Rest and Volitional Energy Expenditure) was developed to assess transient wants and desires to move. Three studies were conducted with the aims of: (1) translating and validating the scale in Brazilian Portuguese, (2) examining changes with exercise, and (3) determining the best single-item for Move and Rest subscales for English and Portuguese. In Study 1, six bilingual speakers translated the scale into Brazilian Portuguese [named Anseios por Repouso e Gastos com Energia (ARGE)]. The ARGE had good content validity coefficients across three dimensions (0.89-0.91), as determined by three independent, bilingual referees. 1,168 participants (mean age = 30.6, SD = 12.2) from across Brazil completed an online version of the ARGE. An Exploratory Factor Analysis found two clear, oblique, and inversely related factors (Move and Rest; GFI = 1.00, RMSR = 0.03). Reliability was good (Cronbach α's: 0.93 and 0.92). Two models of the scale (10 vs. 13 items) were compared with Confirmatory Factor Analysis. The previously validated version using 10 scored items (GFI = 1.00, RMSEA = 0.07, RMSR = 0.02) outperformed the version scored with 13 items. State anxiety and exercise behavior had small associations with Move and Rest (-0.20 to 0.26). In Study 2, ARGE Move scores had high correspondence post-session (ICC = 0.83) for 9 women performing short Sprint Interval Training (sSIT; 6 sessions). Large, but non-significant, effects were detected for changes in motivation states with sSIT. In Study 3, IRT analyses found that for the United States sample, "be physically active" and "be still" were the most representative items for Move and Rest, respectively, while for the Brazil sample they were "exert my muscles" and "be a couch potato." Overall, it was found that: (A) the ARGE scale demonstrated good psychometric properties, (B) the original scoring (with 10 items) resulted in the best model, (C) it had small associations with exercise behavior, and (D) the subscales were reduced to single items that varied by country, indicating potential cultural differences in the concept of motivation states for physical activity.
RESUMO
In the last decade, alcohol consumption in the US has risen by 84% in women compared with 35% in men. Furthermore, research has shown that sex- and gender-related differences may disadvantage women in terms of developing a range of psychological, cognitive, and medical problems considerably earlier in their drinking history than men, and despite consuming a similar quantity of substances. While this "telescoping" process has been acknowledged in the literature, a concomitant understanding of the underlying biobehavioral mechanisms, and an increase in the development of specific treatments tailored to women, has not occurred. In the current chapter we focus on understanding why the need for personalized, sex-specific medications is imperative, and highlight some of the potential sex-specific gonadal and stress-related adaptations underpinning the accelerated progress from controlled to compulsive drug and alcohol seeking in women. We additionally discuss the efficacy of these mechanisms as novel targets for medications development, using exogenous progesterone and guanfacine as examples. Finally, we assess some of the challenges faced and progress made in terms of developing innovative medications in women. We suggest that agents such as exogenous progesterone and adrenergic medications, such as guanfacine, may provide some efficacy in terms of attenuating stress-induced craving for several substances, as well as improving the ability to emotionally regulate in the face of stress, preferentially in women. However, to fully leverage the potential of these therapeutics in substance-using women, greater focus needs to the placed on reducing barriers to treatment and research by encouraging women into clinical trials.
Assuntos
Guanfacina , Progesterona , Masculino , Humanos , Feminino , Guanfacina/farmacologia , Guanfacina/uso terapêutico , Progesterona/uso terapêutico , Consumo de Bebidas Alcoólicas , EtanolRESUMO
Black Americans suffer lower life expectancy and show signs of accelerated aging compared to other Americans. While previous studies observe these differences in children and populations with chronic illness, whether these pathologic processes exist or how these pathologic processes progress has yet to be explored prior to the onset of significant chronic illness, within a young adult population. Therefore, we investigated race-related differences in epigenetic age in a cross-sectional sample of young putatively healthy adults and assessed whether lifetime stress and/or trauma mediate those differences. Biological and psychological data were collected from self-reported healthy adult volunteers within the local New Haven area (399 volunteers, 19.8% Black, mean age: 29.28). Stress and trauma data was collected using the Cumulative Adversity Inventory (CAI) interview, which assessed specific types of stressors, including major life events, traumatic events, work, financial, relationship and chronic stressors cumulatively over time. GrimAge Acceleration (GAA), determined from whole blood collected from participants, measured epigenetic age. In order to understand the impact of stress and trauma on GAA, exploratory mediation analyses were then used. We found cumulative stressors across all types of events (mean difference of 6.9 p = 2.14e-4) and GAA (ß = 2.29 years [1.57-3.01, p = 9.70e-10] for race, partial η2 = 0.091, model adjusted R2 = 0.242) were significantly greater in Black compared to White participants. Critically, CAI total score (proportion mediated: 0.185 [0.073-0.34, p = 6e-4]) significantly mediated the relationship between race and GAA. Further analysis attributed this difference to more traumatic events, particularly assaultive traumas and death of loved ones. Our results suggest that, prior to development of significant chronic disease, Black individuals have increased epigenetic age compared to White participants and that increased cumulative stress and traumatic events may contribute significantly to this epigenetic aging difference.
RESUMO
Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole-brain, voxel-based, multi-tissue mega-analytic approach, thereby extending our recent surface-based region of interest findings on a nearly matching sample using a complementary methodological approach. T1-weighted magnetic resonance imaging (MRI) data from 653 people with AUD and 326 controls was analyzed using voxel-based morphometry. The effects of group, sex, group-by-sex, and substance use severity in AUD on brain volumes were assessed using General Linear Models. Individuals with AUD relative to controls had lower GM volume in striatal, thalamic, cerebellar, and widespread cortical clusters. Group-by-sex effects were found in cerebellar GM and WM volumes, which were more affected by AUD in females than males. Smaller group-by-sex effects were also found in frontotemporal WM tracts, which were more affected in AUD females, and in temporo-occipital and midcingulate GM volumes, which were more affected in AUD males. AUD females but not males showed a negative association between monthly drinks and precentral GM volume. Our results suggest that AUD is associated with both shared and distinct widespread effects on GM and WM volumes in females and males. This evidence advances our previous region of interest knowledge, supporting the usefulness of adopting an exploratory perspective and the need to include sex as a relevant moderator variable in AUD.
Assuntos
Alcoolismo , Humanos , Feminino , Masculino , Alcoolismo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Consumo de Bebidas Alcoólicas , Imageamento por Ressonância Magnética/métodosRESUMO
OBJECTIVE: Mindfulness is an established approach to reduce distress and stress reactivity by improving awareness and tolerability of thoughts and emotions. This study compares mindfulness training to sleep hygiene in persons with multiple sclerosis (PWMS) who report chronic insomnia, examining sleep efficiency (SE), self-reported sleep quality and quality of life. METHODS: Fifty-three PWMS were randomized (1:1) in a single-blinded, parallel group design to ten, two-hour weekly sessions of Mindfulness Based Stress Intervention for Insomnia (MBSI-I) over a span of ten weeks or a single, one hour sleep hygiene (SH) session over one day. The primary outcome measure was SE, measured by the Fitbit™ Charge 2 wrist device, at 10 and 16 weeks from the start of study interventions. Self-report outcomes included the Pittsburg Sleep Quality Rating Scale (PSQI), Insomnia Severity Index (ISI) and the Multiple Sclerosis Quality of Life Inventory (MSQLI). Nineteen participants in the MBSI-I group and 24 in the SH group completed the primary study. Subsequently, ten participants in the original SH group participated in the 10-week MSBI-I course and their data was added to the MBSI-I cohort (eMSBI-I). RESULTS: While neither SE nor the PSQI showed significant differences between MBSI-I, eMBSI-I and SH groups, ISI improved in both the MSBI-I and eMBSI-I vs SH at 10 weeks (p = 0.0014 and p = 0.0275) but not 16 weeks. However, pre and post assessments within the MBSI-I and eMBSI-I cohorts did show significant improvement in the PSQI and ISI at 10 and 16 weeks, while SH was significant in the ISI only at 16 weeks. Several quality of life measurements, including fatigue, mental health and cognitive function favored the mindfulness cohorts. CONCLUSION: This pilot study demonstrates beneficial effects of MBSR on insomnia, sleep quality and quality of life in PWMS. TRIAL REGISTRATION: NCT03949296. 14 May 2019.
Assuntos
Meditação , Atenção Plena , Esclerose Múltipla , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/terapia , Esclerose Múltipla/complicações , Projetos Piloto , Qualidade de VidaRESUMO
Background: Cortisol is a significant driver of the biological stress response that is potently activated by acute alcohol intake and increased with binge drinking. Binge drinking is associated with negative social and health consequences and risk of developing alcohol use disorder (AUD). Both cortisol levels and AUD are also associated with changes in hippocampal and prefrontal regions. However, no previous research has assessed structural gray matter volume (GMV) and cortisol concurrently to examine BD effects on hippocampal and prefrontal GMV and cortisol, and their prospective relationship to future alcohol intake. Methods: Individuals who reported binge drinking (BD: N = 55) and demographically matched non-binge moderate drinkers (MD: N = 58) were enrolled and scanned using high-resolution structural MRI. Whole brain voxel-based morphometry was used to quantify regional GMV. In a second phase, 65% of the sample volunteered to participate in prospective daily assessment of alcohol intake for 30 days post-scanning. Results: Relative to MD, BD showed significantly higher cortisol and smaller GMV in regions including hippocampus, dorsal lateral prefrontal cortex (dlPFC), prefrontal and supplementary motor, primary sensory and posterior parietal cortex (FWE, p < 0.05). GMV in bilateral dlPFC and motor cortices were negatively associated with cortisol levels, and smaller GMV in multiple PFC regions was associated with more subsequent drinking days in BD. Conclusion: These findings indicate neuroendocrine and structural dysregulation associated with BD relative to MD. Notably, BD-associated lower GMV regions were those involved in stress, memory and cognitive control, with lower GMV in cognitive control and motor regions also predicting higher levels of future alcohol intake in BD.