Sleep and Emotional Reactivity in Alcohol Use Disorder
试验速览
- 阶段
- 不适用
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Measures of functional connectivity among emotional networks in AUD
研究概览
简要总结
Alcohol use disorder (AUD) is a multifaceted, chronic relapsing disorder suffered by millions of men and women in the United States. AUD is associated with disrupted sleep continuity and architecture, which impact health-related quality of life, and contribute to relapse. However, many alcohol-sleep interactions and their underlying mechanisms remain unclear, especially those involving AUD and chronic sleep problems. Rapid eye movement (REM) sleep is altered long into abstinence, with excess duration and intensity of REM sleep, which is a predictor of relapse. Emotion deficits, including affective flattening and mesocorticolimbic hypo-responsiveness to emotional stimuli, are also consistent findings in AUD and predictors of relapse. Here, our investigators bring these two components together, building on an emerging literature showing that REM sleep is important for neural emotion regulation, calibrating emotions to promote next-day adaptive emotional functioning. Our investigators propose that the REM sleep-emotion pathway is dysfunctional in AUD, contributing to the deficits in emotion regulation in AUD shown by us and others, which could then lead to increased craving and relapse. Our investigators study male and female AUD patients compared to age- and gender-matched healthy controls, using 2 within-subject sleep conditions: uninterrupted sleep; selective REM sleep reduction, followed by functional neuroimaging with emotion reactivity and regulation tasks the following morning. Our investigators aim to determine specific effects of experimental REM sleep reduction on next-day neural emotional reactivity in AUD compared to healthy controls and compared to a night of uninterrupted sleep
详细描述
SPECIFIC AIMS Alcohol use disorder (AUD) is a multifaceted, chronic relapsing disorder suffered by 9.8 million men and 5.3 million women in the United States.4 Current treatment approaches have met with only limited success in preventing relapse,5 although pharmacotherapy that improved sleep in AUD was recently shown to help maintain abstinence.6-9 Targeting multidimensional pathways may more effectively treat AUD and prevent relapse than targeting singular pathways. Here, our investigators aim to investigate links between two factors important in AUD and relapse: altered sleep, specifically rapid eye movement (REM) sleep, and poor emotion regulation.
Chronic alcohol use is associated with disrupted sleep continuity and structure, which impact health-related quality of life, and contribute to relapse.10 Polysomnographic (PSG) studies show improvements with extended abstinence, however, sleep does not always return to normal levels, and sleep alterations are predictors of relapse.11-13 Our investigators and others have shown that REM sleep is persistently higher in recovering AUD patients relative to healthy controls (CTL), suggesting chronic changes to REM sleep homeostasis,2,10,13,14 which are likely maladaptive. Importantly, excess duration and intensity of REM sleep (high REM pressure) are predictors of relapse.15,16 Attention has mostly focused on sleep continuity and slow wave sleep measures in AUD recovery. The functional significance of excess REM sleep in AUD is poorly understood.
Our investigators and others1,17,18 have also found that AUD individuals show deficits in emotion regulation, including affective flattening and mesocorticolimbic hypo-responsiveness to emotional stimuli (i.e. dampened emotional reactivity), which contribute to increased craving and relapse.19,20 An emerging literature links REM sleep with neural emotion regulation.21-26 A proposed homeostatic model26 posits that the unique neurobiology of REM sleep (e.g. cholinergic activation combined with adrenergic suppression) enables it to fulfil a role in promoting next-day adaptive emotional functioning. In support of this model, selective reduction of REM sleep in healthy subjects leads to next-day hyper-reactivity to emotional stimuli.27 Also, lower prefrontal gamma (30-40Hz) electroencephalographic (EEG) activity in REM sleep, indexing reduced central adrenergic activity,28 relates to more appropriate reactivity to emotions, reduced amygdala (AMYG) activity, and increased ventromedial prefrontal cortex (vmPFC) functional connectivity the next day.29 Our pilot data suggest that central adrenergic activity is not effectively suppressed in REM sleep (higher frontal gamma), suggesting that the REM sleep-emotion recalibration link is dysfunctional in AUD.
Our investigators, therefore, propose here that REM sleep in recovering AUD patients is maladaptive for emotion regulation, affecting neural pathways of emotion processing, contributing to their poor emotion regulation. Baker and Műller-Oehring combine their expertise in AUD, sleep, fMRI, and emotion research, and use a novel experimental within-subject, counterbalanced design with two experimental conditions: uninterrupted sleep and selective REM sleep reduction, each followed by a morning fMRI scan. Our investigators will investigate relationships between PSG-measures of sleep, specifically REM sleep, and next-day emotional functioning (fMRI) in AUD patients, abstinent for > 6 months, compared to age- and sex-matched CTL. Our investigators will also evaluate whether the extent to which AUD individuals demonstrate a capacity to normalize neural emotional regulation after a REM sleep reduction challenge relates to normalization of behavioral measures of emotion reactivity, regulatory control ability, and levels of craving.
Aim 1: Unterinterrupted sleep: Determine relationships between sleep and next-day neural emotional functioning in AUD. Hypothesis (H)1: (a) Relative to CTL, AUD will have poorer sleep quality (shorter sleep duration, more awakenings) and exaggerated REM sleep features (excess duration and intensity [number of eye movements]) and (b) blunted next-day negative emotional tone defined as reduced neural reactivity to emotional content (blunted mesolimbic responsiveness and less functional connectivity among emotion networks [amygdala-PFC]), H2: Higher REM sleep prefrontal gamma (>30Hz) EEG activity will predict impaired next-day mPFC engagement and top-down control of the amygdala in AUD and CTL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 25 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria:
- •Age 25-65 years, with age range matching our past sleep and MRI protocols in AUD; encompassing the young-middle age range for adults, allowing at least a 5 year drinking history for AUD and outside of adolescence (younger cut-off) and before substantial age-related impact on sleep and health (older cut-off);
- •Male, female;
- •At least 8 years of education;
- •Meet cut-off criteria on cognitive tests (MoCA, > 23, WTAR,> 85)104,105,126
- •Meet clinical DSM 5 criteria for alcohol use disorder with at least a 5 year drinking history (AUD group) or not meet clinical DSM 5 criteria for any psychiatric disorder (Control group).
- •Be at least 6 months abstinent, up to 36 months abstinent, based on 2,13,35 showing that REM sleep excess is evident
排除标准
- •History of medical or neurological illness or trauma that would affect the central nervous system (e.g., stroke, multiple sclerosis, epilepsy)
- •History of loss of consciousness over 30 min, compound skull fracture or clear neurological sequelae;
- •Greater than mild past other substance use disorder and/or current other substance use disorder not in remission (< 1 year since meeting criteria) (AUD only)
- •Current post-traumatic stress disorder and/or generalized anxiety disorder;
- •Current clinical diagnosis of moderate-severe substance use disorder (other than alcohol)
- •History of schizophrenia or bipolar disorder;
- •Current severe medical conditions (e.g. uncontrolled Diabetes, chemotherapy for cancer);
- •Current use of benzodiazepine, hypnotic, or anti-depressant medications;
- •Shift work in the six months prior to the study;
- •Moderate-severe sleep-disordered breathing (apnea-hypopnea index 15 or greater at the clinical PSG);
- •Periodic Limb Movements (PLM) Disorder with a PLM arousal index greater than 10 events per hour at the clinical PSG;
- •Pregnant;
- •Current use of drugs or alcohol at clinical visits (positive drug screen or breathalyzer > 0);
- •MRI contraindications, such as: irremovable metal implements, cardiac pacemakers, claustrophobia, excessive body size compromising placement in scanner;
- •Corrected visual acuity of less than 20/40 as assessed by the Snellen Visual Acuity chart
- •Age limits: 25-65 years
结局指标
主要结局
Measures of functional connectivity among emotional networks in AUD
时间窗: Through study completion, an average of 1 year
Brain activation and functional connectivity measures in amygdala and prefrontal cortex derived from fMRI tasks on emotional reactivity and regulation after a night of uninterrupted sleep compared to a night of selective REM sleep reduction in a group of AUD individuals and healthy controls (CTL).
Measures of neural emotional reactivity among emotional networks in AUD
时间窗: Through study completion, an average of 1 year
Brain activation and functional connectivity measures in amygdala and prefrontal cortex derived from fMRI tasks on emotional reactivity and regulation after a night of uninterrupted sleep compared to a night of selective REM sleep reduction in a group of AUD individuals and healthy controls (CTL).
次要结局
未报告次要终点