1. Participants
We conducted a cross-sectional study enrolling 53 recently detoxified sAUD inpatients and 38 healthy controls (HC). None of them had a history of neurological, endocrinal, or infectious diseases, neither depression assessed using both the Beck Depression Inventory (BDI) (25) and a psychiatric assessment, nor other forms of substance use disorder (except tobacco). All participants were informed about the study approved by the local ethics committee of Caen University Hospital (CPP Nord Ouest III, no. IDRCB: 2011-A00495-36) before their inclusion and signed a written informed consent form.
sAUD patients were recruited by clinicians while they were receiving withdrawal treatment as inpatients at Caen University Hospital. Although recently detoxified, patients no longer showed signs of withdrawal at inclusion as assessed by the Cushman’s scale (26). sAUD patients met “alcohol dependence” criteria according to the DSM-IV-TR (27) or “severe AUD” criteria according to the DSM-5 (28) for at least five years.
sAUD patients and HC subjects were matched for age, gender and education (p=0.33, p=0.21 and p=0.12 respectively). Patients tended to live more frequently alone than HC (p=0.05) (Table 1).
Table 1. Socio-demographic, cognitive and clinical features of the severe Alcohol Use Disorder (sAUD) patients and Healthy Controls (HC).
|
sAUD patients (n=33)
(M ± SD)
|
HC subjects (n=38)
(M ± SD)
|
Between-group
comparisons
|
SOCIO-DEMOGRAPHIC
|
|
|
|
Age (years)
|
46.15 ± 10.13
|
44.34 ± 6.07
|
p= 0.33
|
Gender, men (%)
|
86.79 %
|
94.73 %
|
p= 0.21
|
Education (years)
|
11.32 ± 2.09
|
11.82 ± 0.73
|
p= 0.12
|
Family status, living alone (%)
|
54.72%
|
34.21%
|
p=0.05
|
COGNITIVE
|
|
|
|
Episodic memory (z-score)
|
-1.55 ± 1.22
|
0 ± 1
|
HC > sAUD*
|
Working memory (z-score)
|
-1.27 ± 0.82
|
0 ± 1
|
HC > sAUD*
|
Executive functions (z-score)
|
-1.08 ± 1.49
|
0 ± 1
|
HC > sAUD*
|
Processing speed (z-score)
|
-1.57 ± 1.65
|
0 ± 1
|
HC > sAUD*
|
CLINICAL
|
|
|
|
Sleep
|
|
|
|
PSQI
|
8.74 ± 3.27 (2MD)
|
2.37 ± 1.51
|
HC < sAUD*
|
Depression and anxiety
|
|
|
|
BDI
|
17.30 ± 10.91 (1MD)
|
2.89 ± 3.09
|
HC < sAUD*
|
STAI B (trait anxiety)
|
51.21 ± 10.62
|
32.16 ± 6.87
|
HC < sAUD*
|
Impulsivity
|
|
|
|
S-UPPS-P
|
48.45 ± 10.99
|
33.24 ± 11.15
|
HC < sAUD*
|
Negative Urgency
|
10.38 ± 3.41
|
7.13 ± 3.23
|
HC < sAUD*
|
Lack of Premeditation
|
8.98 ± 2.54
|
6.24 ± 2.11
|
HC < sAUD*
|
Lack of perseverance
|
8.32 ± 2.92
|
5.68 ± 1.95
|
HC < sAUD*
|
Sensation Seeking
|
10.64 ± 8.04
|
6.79 ± 2.36
|
HC < sAUD*
|
Positive Urgency
|
11.43 ± 2.94
|
7.5 ± 3.35
|
HC < sAUD*
|
Alcohol history
|
|
|
|
AUDIT
|
28.58 ± 5.75
|
2.42 ± 1.64
|
HC < sAUD*
|
Age of onset of AUD (years)
|
31.30 ± 8.87 (3MD)
|
/
|
/
|
Daily alcohol consumption during the month preceding withdrawal (units a)
|
19.30 ± 7.01 (1MD)
|
/
|
/
|
AUD: Alcohol Use Disorder; n: sample size; M: mean; SD- standard deviation; HC: healthy controls; T: Tendency; BDI: Beck Depression Inventory; STAI: State-Trait Anxiety Inventory; AUDIT: Alcohol Use Disorders Identification Test; PSQI: Pittsburgh Sleep Quality Index; S-UPPS-P: Short form of negative Urgency, lack of Premeditation, lack of Perseverance, sensation Seeking, Positive urgency. MD: Missing Data; *: p<0.01; a: an alcohol unit = 10 g of pure alcohol.
HC subjects were interviewed with the Alcohol Use Disorder Identification Test (AUDIT) (29) to ensure that they did not meet the criteria for alcohol abuse (AUDIT <7 for men and <6 for women). None of the controls had a BDI score > 29 (25) nor sleep complaint (Pittsburgh Sleep Quality Index [PSQI] score ⩽ 5) (30).
2. Experimental protocol
2.1 Assessment of Health-Related Quality of Life (HRQoL) in sAUD patients
HRQoL was assessed using AQoLS, which is a self-assessment questionnaire including 34 items and measuring the specific impact of alcohol on HRQoL over the last 4 weeks. AQoLS has been specifically developed for AUD patients as all the items have been directly generated by patients and reflect, therefore, their concerns. AQoLS explores 7 domains: activities, relationships, living conditions, negative emotions, self-esteem, control and sleep. The number of items for each domain and some examples are presented in Table 2. For each item, the level of agreement is reported based on a 4-point Likert scale, ranging from 0 (not at all) to 3 (very much). Thus, a high total AQoLS score reflects poor HRQoL.
Table 2. AQoLS domains, number of items and examples.
AQoLS domains
|
Number of items
|
Examples
|
Activities
|
10
|
I have felt I miss out on everyday activities with family and friends
|
Relationships
|
6
|
Alcohol has interfered with my relationships with friends
|
Living conditions
|
4
|
Alcohol has had a negative effect on my housing situation
|
Negative emotions
|
2
|
I have worried about alcohol causing problems in my life
|
Self-esteem
|
5
|
I have neglected my general health
|
Control
|
5
|
I have planned my days around alcohol
|
Sleep
|
2
|
I have not been getting enough sleep
|
AQoLS: Alcohol Quality of Life Scale
2.2 Neuropsychological assessment
Participants underwent a detailed neuropsychological examination targeting verbal episodic memory, working memory, executive functions, and processing speed.
Episodic memory
Verbal episodic memory was assessed using the French version of the Free and Cued Selective Reminding Test (FCSRT) (31). We used the sum of the three free recalls of learning trials.
Working memory
Verbal working memory was assessed with the digit span tasks (forward and backward) of WAIS III (32).
Executive functions
We evaluated mental flexibility using the number of perseverative errors on the Modified Card Sorting Tests (MCST) (33). Inhibition was measured using the time (in seconds) needed to complete the interference condition minus the time needed for the denomination condition of the Stroop Test (34).
Processing speed
Processing speed was assessed using the denomination condition of the Stroop Test (time in seconds) (34).
2.3 Assessment of subjective sleep quality
Subjective sleep quality was assessed using the PSQI, which is a 19-item questionnaire exploring sleep quality and sleep disturbances. Seven components are explored (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medications, and daytime dysfunction) and scored on a scale ranging from 0 to 3. The PSQI total score corresponds to the sum of the scores obtained for each component, and ranges from 0 (no difficulty) to 21 (major sleep difficulties).
Of note, the original version of the PSQI questioning the previous month has been proposed to HC subjects and 11 sAUD patients. A modified version assessing sleep quality during the previous week (made with the authors’ agreement) was administered to 20 sAUD patients (two patients had missing data). Since a comparison between the original and modified versions of the PSQI did not reveal any significant difference (t (49) = 1.04, p=0.30), PSQI data were pooled together.
2.4 Assessment of mood
Participants completed the BDI (25), a 21-item self-reported questionnaire that evaluates symptoms and overt behavioural manifestations of depression. Each item has four possible responses, ranging from 0 (e.g. “I do not feel sad”) to 3 (e.g. “I am so sad or unhappy that I can’t stand it”). The total score ranges from 0 to 63 with higher scores indicating higher levels of depression.
Participants also filled out the STAI B (35), a 20-item self-completed questionnaire that measures trait anxiety defined as the propensity to be generally anxious. Each item has four possible responses ranging from 1 (almost never) to 4 (almost always): a higher score indicates greater trait anxiety.
2.5 Assessment of impulsivity
Participants completed the short version of the Urgency, Premeditation, Perseverance, Sensation Seeking, and Positive Urgency impulsivity behavioral scale (36), which is a 20-item self-reported questionnaire that measures personality facets associated with impulsivity. The S-UPPS-P includes five subscales (negative urgency: tendency to act rashly under extreme negative emotions, lack of premeditation: tendency to act without thinking, lack of perseverance: inability to remain focused on a task, sensation seeking: tendency to seek out novel and thrilling experiences, and positive urgency: tendency to act rashly under extreme positive emotions). Each item of the S-UPPS-P has four possible responses ranging from 1 (strongly agree) to 4 (strongly disagree) with higher scores indicating a higher level of impulsivity.
2.6 Alcohol history
Alcohol use was first explored using the AUDIT (29). The total score ranges from 0 to 40 with higher scores indicating greater hazardous drinking. We also collected the age of onset of AUD, and daily alcohol consumption during the month preceding alcohol withdrawal.
3. Statistical analyses
Cognitive data were converted into standardized z-scores using the mean and standard deviation of the HC. When necessary, the direction of the z-score was reversed (e.g number of errors) so that all the z-scores had the same direction: the higher the z-score, the better the performance. When a domain included several variables (e.g executive functions), a composite score was calculated by averaging the z-scores obtained for each variable.
We first used descriptive statistics to analyze HRQoL (AQoLS total score and scores for each domain) in sAUD patients. Since the domains of the AQoLS do not have the same number of items (see Table 2), we normalized the subscores, dividing, for each patient, the score of each domain by the maximum score that could be obtained for that domain. Thus, for each domain the score ranges from 0 to 1. Then, in order to compare all the domains to each other, repeated measures analysis of variances (ANOVA) were conducted followed by Bonferroni post hoc tests.
Then, Student’s t-tests were carried out to compare cognitive and clinical variables between sAUD patients and HC.
In sAUD patients, the relationships between HRQoL and socio-demographic (age and education), cognitive and clinical variables were examined using Pearson’s correlations. Student’s t-tests were performed to examine a potential effect of gender and living conditions (alone vs with a partner) on HRQoL. Variables that were significantly correlated with AQoLS were entered in a stepwise linear regression analysis to determine the best predictor(s) of HRQoL. Both, backward and forward models were used to ensure congruence.
An exploratory analysis was also performed to examine the relationships between the different AQoLS domains and socio-demographic, cognitive, and clinical variables. For this analysis, we notably used the scores on the subscales of the S-UPPS-P questionnaire.
Given the number of statistical analyses, the threshold of statistical significance was set at p<0.01 for all analyses. Statistical analyses were carried out using JASP (version 0.13.1).