Individual Differences In Subjective Responses Research Articles

Raw scores on subjective sleepiness, fatigue, and vigor metrics consistently define resilience and vulnerability to sleep loss.

Although trait-like individual differences in subjective responses to sleep restriction (SR) and total sleep deprivation (TSD) exist, reliable characterizations remain elusive. We comprehensively compared multiple methods for defining resilience and vulnerability by subjective metrics. A total of 41 adults participated in a 13-day experiment: 2 baseline, 5 SR, 4 recovery, and one 36 h TSD night. The Karolinska Sleepiness Scale (KSS) and the Profile of Mood States Fatigue (POMS-F) and Vigor (POMS-V) were administered every 2 h. Three approaches (Raw Score [average SR score], Change from Baseline [average SR minus average baseline score], and Variance [intraindividual SR score variance]), and six thresholds (±1 standard deviation, and the highest/lowest scoring 12.5%, 20%, 25%, 33%, and 50%) categorized Resilient/Vulnerable groups. Kendall's tau-b correlations compared the group categorization's concordance within and between KSS, POMS-F, and POMS-V scores. Bias-corrected and accelerated bootstrapped t-tests compared group scores. There were significant correlations between all approaches at all thresholds for POMS-F, between Raw Score and Change from Baseline approaches for KSS, and between Raw Score and Variance approaches for POMS-V. All Resilient groups defined by the Raw Score approach had significantly better scores throughout the study, notably including during baseline and recovery, whereas the two other approaches differed by measure, threshold, or day. Between-measure correlations varied in strength by measure, approach, or threshold. Only the Raw Score approach consistently distinguished Resilient/Vulnerable groups at baseline, during sleep loss, and during recovery‒‒we recommend this approach as an effective method for subjective resilience/vulnerability categorization. All approaches created comparable categorizations for fatigue, some were comparable for sleepiness, and none were comparable for vigor. Fatigue and vigor captured resilience/vulnerability similarly to sleepiness but not each other.

Comparison of subjective response to alcohol in Caucasian and Hispanic/Latino samples.

Individual differences in subjective response (SR) to alcohol (e.g., stimulation, sedation) are a significant predictor of negative alcohol outcomes. Previous studies have reported ethnic differences in SR (e.g., between some Asian populations and Caucasians), but very few studies have examined SR among Hispanic/Latino individuals. To address this gap in the literature, the present study utilized data from a large-scale, placebo-controlled alcohol administration study to examine differences in SR between Hispanic/Latino and Caucasian individuals. Social drinkers (N = 447) aged 21 to 25 years were randomized to receive either a dose of alcohol targeting a blood alcohol concentration (BAC) of .08 g% or placebo. Only non-Hispanic Caucasian participants (n = 234) and Hispanic/Latino participants (n = 87) were utilized in analyses. SR was assessed at baseline, on the ascending limb of the blood alcohol curve, at peak BAC, and on the descending limb. Repeated measures ANCOVA was utilized to examine interactions between beverage condition, ethnicity, and time predicting SR. The interaction between beverage condition, ethnicity, and time was significant only for low-arousal negative SR (negative sedative effects), such that Hispanic/Latino individuals experienced stronger sedative effects under alcohol (vs. placebo) compared with Caucasian individuals. Caucasians and Hispanic/Latinos showed a similar profile of response with respect to positive aspects of SR (e.g., stimulation). In summary, Hispanic/Latino individuals reported stronger negative SR to alcohol compared with Caucasian individuals, which may be protective against alcohol-related problems. However, future studies are needed to investigate why Hispanic/Latino males remain at relatively high risk for alcohol problems despite stronger negative SR relative to Caucasians. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Striatal activity correlates with stimulant-like effects of alcohol in healthy volunteers.

Individuals who experience greater stimulation and less sedation from alcohol are at increased risk for alcohol-related problems. However, little is known regarding the neurobiological mechanisms underlying subjective response to alcohol. The current study examined the degree to which alcohol-induced brain activation correlates with ratings of stimulation and sedation, using a within-subjects, double-blind, placebo-controlled design. Participants (N = 34 healthy adults with no history of alcohol use disorder) completed three sessions: a calibration session to determine the duration of infusion needed to bring the breath alcohol to 80 mg/dl for each subject, and two counterbalanced fMRI sessions with placebo and alcohol administration. During the fMRI sessions, participants underwent 50 min scans, which included a 10 min baseline period, the IV infusion period needed to bring breath alcohol concentration (BrAC) to a peak 80 mg/dl (on the alcohol session), followed by a post-peak decline period. Participants rated their subjective stimulation and sedation at regular intervals throughout the scan. A priori VOI analyses showed that the time course of stimulation correlated with BOLD signal in the striatum. The time course of sedation did not correlate with BOLD signal in any VOIs. There were no correlations in primary visual cortex, which served as a control. These findings are the first to show that alcohol effects in the striatum are linked to the positive, stimulant-like effects of the drug and advance our understanding of the neurobiological mechanisms underlying individual differences in subjective responses to alcohol, and more broadly, risk for alcohol use disorders.

Developmentally Specific Associations Between CNR1 Genotype and Cannabis Use Across Emerging Adulthood.

Previous studies have found preliminary evidence for associations between common single-nucleotide polymorphisms (SNPs) in the cannabinoid receptor gene CNR1 and cannabis use and dependence. The present study examined a set of eight independent SNPs in or near CNR1 in relation to cannabis use measured longitudinally across emerging adulthood. Using latent growth curve modeling of 10 waves of longitudinal data spanning mean ages 18.4-23.8 years in a sample of non-Hispanic White individuals (n = 334), we tested if genotype at each CNR1 SNP was associated with both level and growth of cannabis use over time. Peer group drug use, a known correlate of individual use, was evaluated as a time-varying predictor of cannabis use and as a moderator of the relationship between SNPs and individual use. After correction for multiple comparisons, one SNP, rs806374, was significantly associated with individual differences in level-but not growth-of cannabis use over time, such that C carriers were more likely to use cannabis more frequently at study onset (around age 18). Peer drug use was a predictor of individual cannabis use that grew in terms of effect size with time, but did not significantly moderate the effect of rs806374 genotype. C carriers at rs806374 may be at specific risk for increased odds of use during the transition out of high school (around age 18). Future studies should investigate potential mechanisms at this developmental stage, including individual differences in subjective response, innate tolerance, reinforcement mechanisms, or general liability for substance misuse.

Acute subjective response to alcohol as a function of reward and punishment sensitivity

Individual differences in subjective response to alcohol play a crucial role in the development of heavy drinking and related problems. In light of this, a growing focus of research has been identifying factors that contribute to differences in response. The aim of the present study was to determine whether individual differences in the subjective experience of rewarding and aversive effects of alcohol are a specific manifestation of general differences in reward and punishment sensitivity. Eighty-nine participants (M age=22.4, SD=1.9; 47.2% women) consumed a moderate dose of alcohol, i.e., peak breath alcohol concentration (BrAC)≈0.080g%, and rated their level of stimulation and sedation at seven timepoints over the BrAC curve. Sensitivity to reward and punishment were assessed by a self-report questionnaire prior to consumption. Multilevel growth models showed that post-consumption changes in stimulation ratings varied as a function of participants' level of reward and punishment sensitivity. Drinkers more sensitive to reward reported feeling more stimulated shortly after drinking and exhibited an attenuated rate of decline in stimulation over the blood alcohol curve, relative to drinkers with less strong reward sensitivity. Reward sensitivity was not related to subjective ratings of sedation, and punishment sensitivity was not related to either stimulation or sedation ratings. Findings suggest that reward sensitivity may increase risk for alcohol misuse among young adult social drinkers by increasing their subjective feelings of stimulation while drinking.

Subjective Response to Alcohol as a Research Domain Criterion.

Individual differences in the subjective experience of the pharmacological effects of alcohol have long been implicated in the likelihood that one will drink heavily and develop alcoholism. The theme of this conceptual review and perspective article is to synthesize the literature on subjective responses to alcohol and to set an agenda for the next generation of research in the area. Specifically, we contend that in order for subjective response to alcohol to play a prominent role in alcoholism research, it is critical that it be studied as a multimodal phenotype. First, we review the human research on subjective response to alcohol measured under controlled laboratory conditions and draw recommendations for the application of these findings to understanding alcoholism neurobiology in humans. Second, we highlight multimodal approaches, including studies of the genetic and neural substrates of individual differences in subjective response to alcohol. Third, we review treatment implications with a focus on subjective response to alcohol as an intervention target. Upon review of the research on subjective response to alcohol across levels of analyses, we provide recommendations for leveraging these phenotypes in a systematic and methodologically rigorous fashion that can address central questions about alcoholism etiology, disease progression, and personalized treatment. The approach recommended herein is largely consistent with the Research Domain Criteria (RDoC) initiative across the National Institute of Mental Health. The defining feature of such domains is that they inform behavior yet be amenable to examination through multiple units of analysis, such as molecular, genetic, circuit-level, and behavioral measurements. To that end, we contend that subjective response to alcohol represents a behaviorally and biologically plausible phenotype upon which to build using the RDoC framework for understanding alcohol use disorder.

Emotional traits predict individual differences in amphetamine-induced positive mood in healthy volunteers.

Previous research on emotional correlates of individual differences in subjective responses to D-amphetamine has focused on relatively broad personality traits. Yet, emotional functioning is best characterized by several narrow subcomponents, each of which may contribute uniquely to amphetamine response. Here, we examine several specific subdomains of emotional functioning in relation to acute amphetamine response. At a baseline session, healthy stimulant-naive volunteers (N = 97) completed measures of several subdomains of baseline trait emotional functioning and then completed two counterbalanced experimental sessions during which they received a single oral dose of 20mg D-amphetamine or placebo. Acute subjective drug response measures were completed at repeated intervals before and after drug administration. Data from subjective measures that were significantly modulated by amphetamine were reduced using principal component analysis (amphetamine or placebo) into three higher-order factors of "positive mood," "arousal," and "drug high." Amphetamine did not significantly alter any "negative" subjective states. Separate multiple regression analyses were conducted regressing these three drug factors on baseline trait emotional functioning scales. The combined set of trait emotional functioning indicators accounted for approximately 22% of the variance in acute amphetamine-induced positive mood changes. Greater anticipatory pleasure and greater anxious distress each uniquely predicted greater amphetamine-induced positive mood. Trait emotional functioning did not significantly predict amphetamine-induced changes in arousal or drug high. Emotional traits appear to moderate drug-induced positive mood but not other dimensions of amphetamine effects. Different facets of emotional functioning may differentially modulate amphetamine's subjective effect profile.

Relationships between impulsivity and subjective response in an IV ethanol paradigm

Impulsivity and individual differences in subjective response to alcohol are risk factors for alcohol problems and possibly endophenotypes for alcohol dependence. Few prior studies have addressed relationships between the two constructs. To predict subjective responses to ethanol, we tested self-reported impulsiveness, ethanol dose condition (high dose, low dose, or placebo), and time (seven time points) along with interactions among these variables. The present study is a secondary analysis of data from a within-subject, placebo-controlled, dose-ranging ethanol administration study using IV infusion with a clamping technique to maintain steady-state breath alcohol concentration. The sample consisted of healthy, non-alcohol dependent social alcohol drinkers between the ages of 21 and 30 (N=105). Participants at varying levels of impulsivity were compared with regard to stimulant and subjective responses to three ethanol dose conditions over time. Individuals with higher impulsivity reported elavated stimulant and dampened sedative response to alcohol, particularly at the higher dose. Higher impulsivity was associated with a steeper increase in stimulant effects during the first half of clamped ethanol infusion with the higher dose. These results suggest that impulsive individuals may experience enhanced reinforcing, stimulant effects, and relatively muted aversive sedative effects from alcohol. These subjective responses may relate to enhanced risk of alcohol problems among more impulsive individuals.

The Subjective Effects of Alcohol Scale: Development and psychometric evaluation of a novel assessment tool for measuring subjective response to alcohol.

Three decades of research demonstrate that individual differences in subjective response (SR) to acute alcohol effects predict heavy drinking and alcohol-related problems. However, the SR patterns conferring the greatest risk remain under debate. Morean and Corbin (2010) highlighted that extant SR measures commonly have limitations within the following areas: assessment of a comprehensive range of effects, assessment of effects over the complete course of a drinking episode, and/or psychometric validation. Furthermore, the consistent pairing of certain SR measures and theoretical models has made integration of findings difficult. To address these issues, we developed the Subjective Effects of Alcohol Scale (SEAS), a novel, psychometrically sound SR measure for use in alcohol administration studies. Pilot data ensured that the SEAS comprised a comprehensive range of effects that varied in terms of valence and arousal and were perceived as plausible effects of drinking. For validation purposes, the SEAS was included in a 2-site, placebo-controlled, alcohol administration study (N = 215). Exploratory and confirmatory factor analyses identified a 14-item, 4-factor model categorizing effects into affective quadrants (high/low arousal positive; high/low arousal negative). SEAS scores evidenced the following: (a) scalar measurement invariance by limb of the blood alcohol curve (BAC) and beverage condition; (b) good internal consistency; (c) convergence/divergence with extant SR measures, alcohol expectancies, and alcohol use; and (d) concurrent/incremental utility in accounting for alcohol-related outcomes, highlighting the novel high arousal negative and low arousal.

GABRA2 markers moderate the subjective effects of alcohol

Individual differences in subjective responses (SRs) to alcohol are moderated by genetic variants and may be risk factors for the development of alcohol use disorders. Variation in the GABA(A) α2 receptor subunit gene (GABRA2) has been associated with alcohol dependence (AD). Therefore, we examined whether individual differences in SRs, which reflect sensitivity to the effects of alcohol, are associated with variation in GABRA2. Sixty-nine healthy subjects (21-30 years) underwent a laboratory-based within-session cumulative oral alcohol dosing procedure, achieving a mean peak blood alcohol level of 100.4 mg/dl (standard error = 2.5). Subjective assessments were obtained throughout the session, including ascending and descending limbs of the alcohol curve. We genotyped single nucleotide polymorphisms (SNPs) across the chromosome 4 region spanning GABRA2 and analyzed the effect of genotype and haplotypes on subjective responses to alcohol. Population substructure was characterized through the use of ancestry informative markers. Individual SNP analysis demonstrated that carriers of the minor alleles for SNPs rs279858, rs279844, rs279845, rs279826, rs279828 and rs279836 had lower 'Negative' alcohol effects scores than individuals homozygous for the common allele at each SNP (P = 0.0060, P = 0.0035, P = 0.0045, P = 0.0043, P = 0.0037 and P = 0.0061, respectively). Haplotype effects of block 1 showed concordant results with SNPs in this block (P = 0.0492 and P = 0.0150 for haplotypes 1 and 4, respectively). The minor alleles for several of these SNPs have previously been associated with AD. Our findings provide further evidence that variation within GABRA2 is associated with attenuated negative responses to alcohol, a known risk factor for vulnerability to alcohol use disorders.

Subjective and Neural Responses to Intravenous Alcohol in Young Adults with Light and Heavy Drinking Patterns

Heavy alcohol consumption during young adulthood is a risk factor for the development of serious alcohol use disorders. Research has shown that individual differences in subjective responses to alcohol may affect individuals' vulnerability to developing alcoholism. Studies comparing the subjective and objective response to alcohol between light and heavy drinkers (HDs), however, have yielded inconsistent results, and neural responses to alcohol in these groups have not been characterized. We performed a double-blind, placebo-controlled, randomized crossover alcohol challenge study comparing functional magnetic resonance imaging and subjective response to intravenously administered 6% v/v ethanol to a target blood alcohol concentration of 0.08% or placebo between HDs and social drinkers (SDs). During the imaging, we presented emotional cues in order to measure how emotion modulated the effects of alcohol on the brain's reward circuitry. We found that, at equivalent blood alcohol concentrations, HDs reported lower subjective alcohol effects than SDs. Alcohol significantly activated the nucleus accumbens in SDs, but not in HDs. Self-reported ratings of intoxication correlated with striatal activation, suggesting that activation may reflect subjective experience of intoxication. Fearful faces significantly activated the amygdala in the SDs only, and this activation was attenuated by alcohol. This study shows that HDs not only experience reduced subjective effects of alcohol, but also demonstrate a blunted response to alcohol in the brain's reward system. Our findings indicate that reduced subjective and neural response to alcohol in HDs may be suggestive of either the development of tolerance to alcohol, or of pre-existing decreased sensitivity to alcohol's effects.

Subjective Response to Alcohol Challenge: A Quantitative Review

Individual differences in subjective response to alcohol, as measured by laboratory-based alcohol challenge, have been identified as a candidate phenotypic risk factor for the development of alcohol-use disorders (AUDs). Two models have been developed to explain the role of subjective response to alcohol, but predictions from the 2 models are contradictory, and theoretical consensus is lacking. This investigation used a meta-analytic approach to review the accumulated evidence from alcohol-challenge studies of subjective response as a risk factor. Data from 32 independent samples (total N = 1,314) were aggregated to produce quantitative estimates of the effects of risk-group status (i.e., positive family history of AUDs or heavier alcohol consumption) on subjective response. As predicted by the Low Level of Response Model (LLRM), family history-positive groups experienced reduced overall subjective response relative to family history-negative groups. This effect was most evident among men, with family history-positive men responding more than half a standard deviation less than family history-negative men. In contrast, consistent with the Differentiator Model (DM), heavier drinkers of both genders responded 0.4 standard deviations less on measures of sedation than did the lighter drinkers but nearly half a standard deviation more on measures of stimulation, with the stimulation difference appearing most prominent on the ascending limb of the blood alcohol concentration curve. The accumulated results from 3 decades of family history comparisons provide considerable support for the LLRM. In contrast, results from typical consumption comparisons were largely consistent with predictions of the DM. The LLRM and DM may describe 2 distinct sets of phenotypic risk, with importantly different etiologies and predictions for the development of AUDs.

Subjective Responses to Alcohol Consumption as Endophenotypes: Advancing Behavioral Genetics in Etiological and Treatment Models of Alcoholism

Individual differences in subjective responses to alcohol consumption represent genetically mediated biobehavioral mechanisms of alcoholism risk (i.e., endophenotype). The objective of this review is three-fold: (1) to provide a critical review the literature on subjective response to alcohol and to discuss the rationale for its conceptualization as an endophenotype for alcoholism; (2) to examine the literature on the neurobiological substrates and associated genetic factors subserving individual differences in subjective response to alcohol; and (3) to discuss the treatment implications of this approach and to propose a framework for conceptualizing, and systematically integrating, endophenotypes into alcoholism treatment.

Subjective Responses to Alcohol Prime Event-Specific Alcohol Consumption and Predict Blackouts and Hangover

Individual differences in subjective response to alcohol and the occurrence of blackouts and hangover are associated with the development of alcohol-use disorders. As such, subjective responses to alcohol, blackouts, and hangover may share a biological vulnerability to excessive alcohol consumption. The purpose of the current study was to examine subjective responses to alcohol as predictors of estimated blood alcohol concentration (BAC), blackouts, and hangover for a single heavy drinking event. Data were collected on 150 (50% female) college students at a large, public university who reported consuming alcohol during their 21st birthday celebration. Using semi-structured interviews and self-report measures, subjective responses to alcohol (at midpoint of a 21 st birthday celebration) were examined as predictors of final estimated BAC, blackouts, and hangover. Stimulant effects reported for the midpoint of the drinking event predicted final estimated BAC. Both stimulant and sedative alcohol effects directly predicted blackouts during the drinking event and the occurrence of a hangover. Neither stimulant nor sedative effects were mediated by final estimated BAC. Retrospective reports of subjective responses to alcohol were associated with the level of intoxication, blackouts, and hangover during a heavy drinking event. Findings therefore suggest the utility of incorporating subjective responses to alcohol into event-specific interventions that are designed to reduce or prevent heavy episodic drinking.

Norepinephrine Transporter Gene Variation Modulates Acute Response to d-Amphetamine

Individual differences in subjective responses to stimulant drugs such as amphetamine may influence risk of abuse as well as clinical-treatment response to these drugs. Because the effects of amphetamine are mediated in part by the norepinephrine transporter (SLC6A2), we examined interindividual differences in mood response to amphetamine in relation to SLC6A2 gene polymorphisms. Ninety-nine healthy volunteers participated in three sessions in which they randomly received either placebo or D-amphetamine (10 mg or 20 mg) under double-blind conditions. Every subject completed self-report measures on subjective effects (Profile of Mood States). Afterward, all individuals were genotyped for eight SLC6A2 gene polymorphisms. Individual genotypes and haplotypes were investigated. The intronic 36001C/C (rs47958) genotype was associated with increases in positive mood and elation after 20 mg of D-amphetamine. Positive mood and elation levels were also found to be associated with the haplotype GCC formed from 28257G/C (rs36017), 28323C/T (rs2270935), and 36001A/C (rs47958). These findings remained significant after adjustment for multiple testing. Polymorphisms in the SLC6A2 gene were associated with mood responses to D-amphetamine. If confirmed, this observation may contribute to a better understanding of interindividual variations in the clinical response to amphetamine and in the risk of becoming addicted to amphetamine.

Preliminary data on the association among the serotonin transporter polymorphism, subjective alcohol experiences, and drinking behavior.

Individual differences in subjective responses to alcohol are believed to have a genetic basis and have been associated with increased risk of alcohol-related problems. There are, however, conflicting results from past studies, perhaps owing to differences in subjective alcohol effects by limb of the blood alcohol curve and the passage of time. The current pilot study evaluated relations among serotonin transporter (SERT) genotype, subjective alcohol responses, and drinking behavior across both the ascending and descending limbs of the blood alcohol curve. Participants (N=222; 68% male) were administered alcohol (target blood alcohol concentration of .06%) with a subsample (n=86) providing genetic data. Following a social stressor, participants were provided the opportunity to engage in ad libitum alcohol consumption. SERT transporter was not significantly associated with ad lib drinking or subjective alcohol effects at individual time points, although a trend toward a SERT by blood alcohol concentration limb interaction was observed for ad lib drinking. In addition, SERT genotype predicted acute tolerance to alcohol effects, with participants homozygous for the long SERT allele developing acute tolerance more rapidly than other genotypes. Although SERT genotype was not reliably associated with ad lib drinking behavior, the results suggest that individuals with the long-long (LL) genotype may develop acute tolerance to alcohol effects more rapidly than heterozygotes or individuals homozygous for the short SERT allele.