Reduced subjective response to acute ethanol administration among young men with a broad bipolar phenotype

Abstract

Elevated lifetime prevalence rates of alcohol use disorders (AUDs) are a feature of bipolar disorder (BD). Individuals at-risk for AUDs exhibit blunted subjective responses to alcohol (low levels of response), which may represent a biomarker for AUDs. Thus, individuals at-risk for BD may exhibit low responses to alcohol. Participants were 20 unmedicated adult males who reported high rates of hypomanic experiences (bipolar phenotype participants; BPPs), aged 18 to 21 years, and 20 healthy controls matched on age, gender, IQ, BMI, and weekly alcohol intake. Subjective and pharmacokinetic responses to acute alcohol (0.8 g/kg) vs placebo administration were collected in a randomized, double-blind, cross-over, placebo-controlled, within-subjects design. BPP participants reported significantly lower subjective intoxication effects ('feel high': F=14.2, p=0.001; 'feel effects': F=8.1, p=0.008) across time, but did not differ in their pharmacokinetic, stimulant, or sedative responses. Paradoxically, however, the BPP participants reported significantly higher expectations of the positive effects of alcohol than controls. Our results suggest that unmedicated young males with previous hypomanic experiences exhibit diminished subjective responses to alcohol. These blunted alcohol responses are not attributable to differences in weekly alcohol intake, pharmacokinetic effects (eg, absorption rates), or familial risk of AUDs. These observations suggest that the dampened intoxication may contribute to the increased rates of alcohol misuse in young people at-risk for BD, and suggest possible shared etiological factors in the development of AUDs and BD.

Figures

Figure 1

Mean (±SE) BrAC following acute ethanol (0.8 g/kg) administration in HCs (n=20) and participants with the BPP (n=20). Both groups obtained similar peak BrAC levels following alcohol administration. Group: NS (p>0.1). BrAC, breath alcohol concentration; BPP, bipolar phenotype participant; HC, healthy control.

Figure 2

Mean (±SE) DEQ ‘high' subscale scores across time (alcohol–placebo ratings) following acute ethanol administration (0.8 g/kg) in HCs (n=20) and participants with the BPP (n=20). Beverages (alcohol or placebo) were divided into nine portions and consumed at 3-min intervals, with the last portion consumed at 27 min. BPP participants' ratings of ‘feel high' on the DEQ were significantly reduced compared with those of the healthy controls (F=14.21, p=0.001), and as a function of time following treatment (F=4.68, p=0.001). Participants who received alcohol first and placebo second reported higher ratings of ‘feel high' than those participants who received the treatments in the reverse order (F=4.82, p=0.035) as a function of time following treatment (F=3.35, p=0.007). However, the three-way interaction between group, order and time was not significant (F<1; p>0.1). BPP, bipolar phenotype participant; DEQ, drug effects questionnaire; HC, healthy control.

Figure 3

Mean (±SE) DEQ ‘feel effects' subscale scores across time (alcohol–placebo ratings) following acute ethanol administration (0.8 g/kg) in HCs (n=20) and participants with the BPP (n=20). Beverages (alcohol or placebo) were divided into nine portions and consumed at 3-min intervals, with the last portion consumed at 27 min. BPP participants' ratings of ‘feel effects' on the DEQ were significantly lower than those of HCs (F=8.11, p=0.008), although the two-way interaction between group and time only approached statistical significance (F=2.15, p=0.063). Participants who received alcohol first and placebo second reported higher ratings of ‘feel effects' than those participants who received the treatments in the reverse order (F=4.41, p=0.044). However, neither the two-way interaction between treatment order and time, nor the interaction between group, treatment order and time were significant (F<1.6; p>0.1). BPP, bipolar phenotype participant; DEQ, drug effects questionnaire; HC, healthy control.

Figure 4

Mean (±SE) AEQ subscale scores of HC (n=20) and participants with the BPP (n=20). BPP participants reported significantly more positive alcohol expectancies across multiple domains. GPC: F=9.36, p=0.004; SE: F=3.53, p=0.068; R: F=8.54, p=0.006; AA: F=4.84, p=0.034; SPP: NS (p>0.1); SA: NS (p>0.1). AA, arousal/aggression; AEQ, alcohol expectancy questionnaire; GPC, global positive changes; R, relaxation; SA, social assertiveness; SE, sexual enhancement; SPP, social and physical pleasure.