Subjective Response to Alcohol and Associated Neural Systems in Bipolar Disorder
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Level of Intoxication (Subjective Response) on Each Condition Day After Drinking Relative to How They Felt When Arriving to the Lab on That Respective Day )Prior to Drinking)
研究概览
简要总结
Alcohol use disorders (AUDs) affect up to 60% of individuals with bipolar disorder during their lifetime-a rate 3 to 5 times higher than what occurs in the general population. The mechanisms that contribute to elevated rates of comorbidity are not known. Early identification in individuals with bipolar disorder who are at risk for AUDs could inform novel intervention strategies and improve life-long outcomes. The primary objective of this protocol is to use alcohol administration procedures and functional MRI techniques to investigate subjective response to alcohol, compared to placebo, and relationship with functional responses of, and connectivity among, brain regions in ventral prefrontal emotional networks in young adults with bipolar disorder and healthy comparison young adults. Baseline clinical and structural MRI assessments will be completed in 30 bipolar and 30 healthy young adults (21-26 years of age, 50% women). Then, following standard beverage administration procedures, participants will complete within-person, counter-balanced, fMRI scans and complete measures of subjective response to alcohol while under the influence of alcohol or placebo. Specifically, individual differences in the experience of stimulating, sedative, and anxiolytic effects of alcohol (measured with self-report surveys) and individual differences in neural responses to alcohol within ventral prefrontal emotional networks will be investigated and differences in bipolar disorder compared to healthy participants assessed. Functional MRI scans during a continuous performance task with emotional and neutral distractors (CPT-END) and at rest will be collected while under the influence of alcohol and placebo and compared. Experience of stimulating, sedative, and anxiolytic effects of alcohol from self-report survey data and neural responses to emotional stimuli while under the influence of alcohol compared to placebo will be the primary data outcomes assessed. Additionally, associations between subjective and neural response to alcohol and drinking patterns will be explored (secondary outcomes). The primary endpoint of the study will be after completion of both alcohol and placebo beverage conditions.
详细描述
A total of 60 bipolar and healthy comparison subjects (n=30 per group, 21-26 years of age, 50% women, with no history of a moderate/severe AUD) will be recruited from the greater Austin area. Once recruited and enrolled, subjects will undergo detailed structured clinical evaluations to verify inclusion and exclusion criteria, comprehensive assessment of alcohol and other drug use history, and cognitive testing, followed by structural MRI assessments. Following standard beverage administration procedures, they will then complete measures of subjective response to alcohol and fMRI scans while under the influence of alcohol or a placebo condition (counter-balanced). For each participant the first beverage session assignment (whether the participant is given alcohol or the placebo beverage first) will be randomized. Alcohol and placebo sessions will occur within 3 days of each other. FMRI assessments will include a continuous performance task with emotional and neutral distractors (CPT-END) and a resting state scan.
For both the alcohol and the placebo beverage conditions, the protocol will be the same. The beverage administration sessions will occur in a private room at the University of Texas at Austin in the Imaging Research Center. The table in the testing room will be wiped down with alcohol prior to the participant's arrival (olfactory cue). Study staff will use an algorithm to calculate individual alcohol doses based on the participants' age, sex, height, and weight. Participants fast from food for 4 hours prior to their session. Before beginning consumption of their beverages, they will eat a weight-adjusted, 1 calorie per pound snack of pretzels. While participants eat their pretzels, study staff will mix beverages in front of participants. Vodka and placebo (decarbonated tonic water) will be stored in absolute vodka bottles, measured out, and combined with mixer in front of participants. Mixed drinks will be poured into glasses that have been sitting face down with rims soaking in vodka. Prior to giving the beverage to the participant, all drinks will get an alcohol floater (squirt of absolute vodka on top of the drink). Participants will be given 20 minutes to orally consume two beverages (10 minutes per beverage).
Following oral consumption and a 10 minute absorption period, breathalyzer tests will be conducted to identify a .06g% ascending limb breath alcohol concentration (BrAC). Self-report of subjective response to alcohol will be collected and participants will immediately enter the scanner and complete the fMRI scan (acquisition parameters are identical during alcohol and placebo conditions). BrAC will be tracked after the MRI scan and subjective response to alcohol collected again at peak BrAC and at descending BrAC of .06g%. Consistent with NIAAA guidelines for human alcohol studies, BrAC readings will continue every 30 minutes until participants are below 0.04% at which time they will be escorted home. During the placebo condition, participants will be given false BrAC readings. False BrAC readings given to participants during the placebo session will be based on the average BrACs we record during the alcohol sessions. The average time participants stay in the laboratory will be the same for the placebo and alcohol beverage conditions. Participants are debriefed after completing all sessions and the need for deception to ensure the placebo-controlled alcohol session will be explained.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 26 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria for all participants:
- •between 21 and 26 years of age
- •having consumed at least 4 (men) or 3 (women) drinks on a single occasion over the last year
- •euthymic at the time of study
- •Inclusion criteria for bipolar disorder participants:
- •- Meeting Diagnostic and Statistical Manual-5 Research Version (DSM-V-RV) diagnostic criteria for bipolar disorder, confirmed by structured interview
排除标准
- •For all subjects exclusion criteria include:
- •history of significant medical illness, particularly if possible changes in cerebral tissue
- •neurologic abnormality including significant head trauma (loss of consciousness of ≥5-min)
- •full Scale intelligence quotient (IQ) <85
- •contraindication to MRI scanning
- •positive pregnancy test
- •current cannabis use disorder>moderate
- •history of severe AUDs
- •scores > 15 on the alcohol Use Disorders Identification Test (AUDIT; part of phone screen)
- •ever being in an abstinence-oriented treatment program for alcohol use
- •reporting wanting to quit drinking but not being able to
- •any medical, religious, or other reasons for not drinking alcohol
- •history of heart attack, heart trouble, high blood pressure, diabetes, or liver disease
- •an adverse reaction to alcoholic beverages
- •reporting never consuming 4 (men) or 3 (women) or more drinks on a single occasion over the last year
- •unwillingness to have a friend or family member drive them home after the alcohol administration sessions
- •a past year substance use disorder (other than alcohol, cannabis, or nicotine)
- •Additional exclusion criteria for bipolar disorder participants:
- •- not taking medications for greater than or equal to 4 weeks (i.e. participants must be stable on medications)
- •Additional exclusion criteria for healthy comparison subjects also include:
- •any prior psychiatric hospitalizations
- •lifetime history of a neurodevelopmental disorder, affective disorder, psychotic disorder, eating disorder
- •greater than 1 month of lifetime psychotropic medication. -
结局指标
主要结局
Level of Intoxication (Subjective Response) on Each Condition Day After Drinking Relative to How They Felt When Arriving to the Lab on That Respective Day )Prior to Drinking)
时间窗: up to 1 week
Participants fill out self-report surveys \[specifically the Subjective Effects of Alcohol Scale (SEAS)\] on how they feel when they arrive to their beverage administration sessions (alcohol and placebo sessions). They then feel out the same self-report surveys on how intoxicated they feel during their beverage sessions (alcohol and placebo). Changes in how intoxicated they feel is calculated for both the alcohol and placebo condition (compared to how they felt pre-beverage). 4 subscores are calculated by summing individual items: positive valence/positive arousal (stimulation), SEAS positive valence/negative arousal (anxiolytic), negative valence/negative arousal (aggression/agitation), and negative valence/negative arousal (sedative effects). Summed subscores on the SEAS range between 0 and 40. Change scores can therefore range between -40 and 40 (post-beverage compared to pre-beverage feelings). Scores greater than 0 on any one subscale indicates feeling more effects of alcohol.
Change in Functional Coupling Between Regions of Interest During Viewing of Emotional Stimuli (Neural Responses While Viewing Emotional Stimuli Were Contrasted Against Neural Responses When Viewing Squares)
时间窗: up to 1 week
Neural responses to emotional stimuli during the alcohol and placebo sessions were modeled. Fisher transformed correlation coefficients between regions of interest while viewing emotional stimuli (compared to squares) were calculated for each beverage session and data extracted for posthoc analysis. Values represent change scores in correlation coefficients during each beverage session.
次要结局
未报告次要终点
研究者
Elizabeth Thomas Cox Lippard
Assistant Professor
University of Texas at Austin