Abstract
Aims: Abundant research indicates that ghrelin hormone levels are associated with alcohol use and addiction. One of the mediators of this association may be impulsivity, which is one of the common traits observed in alcohol addiction and some eating disorders. This study evaluated participants with alcohol dependency and healthy volunteers to determine whether trait impulsivity and ghrelin levels are associated. Methods: This study analyzed trait impulsivity scores and fasting serum ghrelin levels of 44 males with alcohol dependency and 48 healthy male participants. The Barratt Impulsiveness Scale and the UPPS Impulsive Behaviour Scale (UPPS) were used to measure trait impulsivity levels. Penn Alcohol Craving Scale and Yale Brown Obsessive Compulsive Drinking Scale for heavy drinking were used to assess craving at the baseline and after the detoxification period. Results: Alcohol-dependent patients’ fasting ghrelin levels were significantly higher than that of healthy participants. Ghrelin plasma levels were positively correlated with UPPS total impulsivity scores and sensation-seeking among healthy individuals. In alcohol-dependent participants, there was a positive correlation between UPPS urgency scores obtained at the baseline and fasting ghrelin levels before and after the detoxification period. Conclusions: Ghrelin–impulsivity relationship could be observed in certain dimensions of impulsivity in both alcohol-dependent and healthy individuals and even independent of the effect of alcohol. Although the associated impulsivity dimensions differ in different groups, the results are parallel to other studies in terms of demonstrating the relationship between ghrelin and impulsivity.
Introduction
Impulsivity is one of the most common behavioural characteristics associated with alcohol use disorders. It can be defined as a tendency to provide fast and unplanned responses to internal and external stimuli without considering negative consequences (Moeller et al., 2001). Impulsivity is a multidimensional behaviour consisting of different but related components (De Wit, 2009). It is also a feature of many psychiatric disorders, such as attention deficit and hyperactivity disorder, alcohol and substance use disorders, and various personality disorders.
Impulsivity is associated with the prefrontal cortex (PFC), striatum, and limbic regions of the brain. The PFC is a region that provides appropriate behaviour for a given situation and is associated with the nucleus accumbens, one of the subcortical structures involved in the reward mechanism (Pattij and Vanderschuren, 2008). Some of the reward-related brain regions, particularly the ventral striatum and medial PFC, associated with impaired impulse control, are closely related to addiction development (Volkow et al., 2002). Impulsivity has been suggested as an essential mechanism for the excessive use of addictive substances and their reuse (Volkow et al., 2002). In addition, impulsivity is a significant feature that affects food intake and food reward behaviour. Eating behaviour in binge eating disorder resembles addiction in this respect (Galanti et al., 2007).
Ghrelin is an orexigenic hormone consisting of 28 amino acids, mainly produced by enteroendocrine cells of the gastric mucosa (Kojima and Kangawa, 2005). The acylated form of ghrelin hormone is active and acts on the growth hormone secretagogue receptor (GHSR), which is the main receptor of the hormone. It stimulates neuropeptide Y and agouti-related protein production in the arcuate nucleus of the hypothalamus, causing an increase in food intake (Hagemann et al., 2003). In addition to its role in food intake and energy balance, ghrelin has a regulatory role in reward processing (Diz-Chaves, 2011). Ghrelin stimulates the mesolimbic dopamine reward pathway through the GHS-R1A receptors located in the ventral tegmental area (VTA) (Stievenard et al., 2017). Dopaminergic projections originating from the VTA in the mesolimbic system reach the limbic forebrain structures such as the nucleus accumbens in the ventral striatum, amygdala, and PFC (Beier et al., 2015). Because of these connections, ghrelin is expected to affect not only homeostatic appetite control but also reward-related behaviours, such as hedonic food intake and substance use disorder (Vengeliene, 2013).
Recently, interest in ghrelin has increased in addiction research (Helinski and Spanagel, 2011). Ghrelin levels were found to be significantly different in patients with alcohol dependency and healthy controls and a change was observed during alcohol withdrawal and after alcohol intake (Kraus et al., 2005; Akkisi Kumsar and Dilbaz, 2015; Deschaine et al., 2022). Many studies report that ghrelin levels are associated with alcohol craving, although their results are not always consistent (Kraus et al., 2005; Hillemacher et al., 2007; Koopmann et al., 2012; Leggio et al., 2012; Akkisi Kumsar and Dilbaz, 2015). Besides, intravenous ghrelin administration was shown to increase craving and the number and rate of alcohol self-administration in alcohol-dependent heavy-drinking individuals (Leggio et al., 2014; Farokhnia et al., 2018). Preclinical studies report that alcohol consumption is reduced in knock-out rodents with damaged ghrelin or ghrelin receptor genes and when a ghrelin receptor blockade is applied (Jerlhag et al., 2009; Skibicka et al., 2012; Suchankova et al., 2013; Zallar et al., 2019). In humans, decrease in peripheral ghrelin concentrations is observed with oral or intravenous alcohol intake (Calissendorff et al., 2006; Deschaine et al., 2022).
Numerous studies have been conducted on the effects of ghrelin on addiction processes, but to the best of our knowledge, there are very few publications on the relationship of ghrelin with certain character traits. Langren et al. (2008) associated some genetic variations in the GHSR and GHRL genes with personality traits such as self-directedness and self-transcendence (Landgren et al., 2008). In a recent preclinical study, ghrelin injection to the lateral ventricle in trained rats caused an increase in impulsive behaviour and impulsive decision-making. In addition, central ghrelin receptor blockage caused a decrease in impulsive behaviour (Anderberg et al., 2016).
Ralevski and colleagues revealed that serum ghrelin levels are strongly related to impulsive features, such as lack of planning and less self-control among social drinkers, and that higher ghrelin levels were related to higher sensitivity to reward and lower sensitivity to punishment. The authors suggested that impulsivity traits may play a role in the relationship between ghrelin and alcohol-related behaviours (Ralevski et al., 2018). However, the results of this clinical study are just preliminary findings, and the information on this subject is extremely limited.
The current study aimed to evaluate the association between ghrelin hormone levels and trait impulsivity among alcohol-dependent patients and healthy individuals. We hypothesized that fasting ghrelin levels would be associated with impulsivity in both groups.
Materials and methods
The alcohol-dependent participant group (n = 44) consisted of male patients applied to the Ankara University Faculty of Medicine Psychiatry Department between June 2018 and September 2019 who met both the ICD-10 (International Classification of Diseases) criteria for alcohol dependency and DSM-5 (the Diagnostic and Statistical Manual of Mental Disorders) criteria for alcohol use disorder. Male patients aged 18–65 years who were abstinent from alcohol for more than 8 hours and less than 5 days at admission were included in the study. Exclusion criteria were (i) illiteracy; (ii) intellectual disability, major cognitive or psychiatric disorder, or any neurological disorder affecting the central nervous system; (iii) gastrointestinal or endocrinological disorder or history of surgical procedure (e.g. gastric operation) that affects plasma ghrelin level; and (iv) use of addictive substances other than alcohol and cigarettes. The non-dependent (healthy) participant group (n = 48) consisted of healthy male volunteers aged 18–65 years. They were screened for alcohol use issues using the CAGE questionnaire which is a brief screening instrument for alcohol abuse and dependence (Ewing, 1968) and were interviewed to confirm the absence of alcohol use disorder or any psychiatric disorder history. Other exclusion criteria were the same as those for alcohol-dependent participants. Twenty-five of the participants in the healthy volunteer group did not consume alcohol at all. The Ethics Committee of the Ankara University Faculty of Medicine approved the study procedure (approval ID: 03-141-18). All participants provided written informed consent prior to the study procedure.
Procedure
Blood samples were collected from participants with alcohol dependence in ethylenediaminetetraacetic acid (EDTA) aprotinin tubes after at least 8 hours and at most 5 days of alcohol abstinence (T0) and after 8 hours of overnight fasting. Sociodemographic characteristics and alcohol and cigarette use were also assessed. Participants were asked to complete the Barratt Impulsiveness Scale and the UPPS Impulsive Behaviour Scale, Penn Alcohol Craving Scale, and Yale Brown Obsessive Compulsive Scale for heavy drinking at T0 (at first admission). Medically supervised withdrawal treatment was performed using benzodiazepines (either diazepam or lorazepam) at varying doses and multivitamin support for 2–4 weeks according to the patient’s needs. Patients who received their treatment as inpatients and outpatients, according to their availability, were followed up as outpatients afterwards. After the medically supervised withdrawal period (T1), i.e. 21.7 ± 6.1 days after the first admission, 4 weeks (T2) after T1, and 8 weeks (T3) after T1 fasting blood ghrelin level measurements, Penn Alcohol Craving Scale and Yale Brown Obsessive Compulsive Scale for heavy drinking were repeated. Follow-up continued for the periods specified above unless they used alcohol again. During the entire follow-up period, patients were regularly questioned about their alcohol intake and patients who consumed alcohol were excluded from the study after that period. All the participants who dropped out of the study were the participants who stated that they used alcohol during the follow-up (Fig. 1).
Flowchart of excluded patients during the follow-up.
Healthy individuals who reported no consumption of any alcohol-containing beverage at least 2 days before admission were included and their blood samples were collected after 8 hours of fasting. The same evaluations and scales were applied to the healthy participants.
Biochemical analysis
The venous blood samples in EDTA aprotinin tubes were delivered to the Ankara University Cebeci Central Biochemistry Laboratory within 15 min of acquisition. In our study, the acylated (active) form of ghrelin was measured, but according to the nomenclature consensus, we use the word ‘ghrelin’ for this hormone (Perelló et al., 2022). The samples were centrifuged at 2500g for 10 min and stored at −80°C until the ghrelin levels were measured. An experienced biochemist measured plasma ghrelin concentration using an enzyme-linked immunosorbent assay (ELISA). All the samples were analyzed on the same day using a Human Acylated Ghrelin Kit (Bertin Pharma, France). The absorbance was measured at 405 nm using the ELISA reader. Plasma ghrelin concentrations are expressed as picograms per millilitre. Variations in coefficients within and between analyses were <10%.
Assessments
Two experienced psychiatrists assessed the participants’ alcohol dependence status according to ICD-10 and DSM-5 criteria. The CAGE score was ≥2 in the alcohol-dependent group and lower than <2 in the healthy group. Participants eligible for the study were evaluated for additional psychiatric disorder histories. The Mini Mental State Examination was applied to participants considered to have symptoms of dementia, and those who scored below 25 were not included.
On the day the blood samples were collected, the researchers inquired about participants’ sociodemographic characteristics and height and weight were measured. Penn Alcohol Craving Scale and Yale Brown Obsessive Compulsive Scale for heavy drinking were administered at admission (T0) and after the withdrawal period at T1, T2, and T3 to investigate whether craving had an effect on ghrelin levels in the patient group.
The Barratt Impulsiveness Scale and the UPPS Impulsive Behaviour Scale were used only at the first admission (T0) to assess trait impulsivity. These scales were administered to participants with alcohol dependence 5 days after admission to reduce the possible effect of withdrawal symptoms on scores.
Characteristics of participants with alcohol dependency and healthy participants.
| AD (T0) (n = 44) | H (n = 48) | P value | |
|---|---|---|---|
| Age | 43.87 ± 9.36 | 40.34 ± 9.16 | 0.071 |
| BMI (kg/m2) | 25.52 ± 3.78 | 26.47 ± 3.10 | 0.192 |
| Smoking status Smokers/non-smokers | 42/2 | 46/2 | 0.658 |
| Alcohol consumption (unita/week) | 116.76 ± 56.86 | 1.78 ± 2.74 | <0.001* |
| Serum ghrelin (pg/ml) | 30.32 ± 26.62 | 20.39 ± 3.92 | 0.030* |
| AD (T0) (n = 44) | H (n = 48) | P value | |
|---|---|---|---|
| Age | 43.87 ± 9.36 | 40.34 ± 9.16 | 0.071 |
| BMI (kg/m2) | 25.52 ± 3.78 | 26.47 ± 3.10 | 0.192 |
| Smoking status Smokers/non-smokers | 42/2 | 46/2 | 0.658 |
| Alcohol consumption (unita/week) | 116.76 ± 56.86 | 1.78 ± 2.74 | <0.001* |
| Serum ghrelin (pg/ml) | 30.32 ± 26.62 | 20.39 ± 3.92 | 0.030* |
AD: alcohol-dependent individuals, H: healthy individuals, BMI: body mass index
Values represent means±standard deviation or numbers of subjects, where appropriate
1 unit of alcohol: 330 ml of beer (5% alcohol)/1 glass (140 ml) of wine (12% alcohol)/1 glass of (40 ml) vodka, whisky, or gin (40% alcohol)/1 glass (40 ml) of raki (45% alcohol)
Characteristics of participants with alcohol dependency and healthy participants.
| AD (T0) (n = 44) | H (n = 48) | P value | |
|---|---|---|---|
| Age | 43.87 ± 9.36 | 40.34 ± 9.16 | 0.071 |
| BMI (kg/m2) | 25.52 ± 3.78 | 26.47 ± 3.10 | 0.192 |
| Smoking status Smokers/non-smokers | 42/2 | 46/2 | 0.658 |
| Alcohol consumption (unita/week) | 116.76 ± 56.86 | 1.78 ± 2.74 | <0.001* |
| Serum ghrelin (pg/ml) | 30.32 ± 26.62 | 20.39 ± 3.92 | 0.030* |
| AD (T0) (n = 44) | H (n = 48) | P value | |
|---|---|---|---|
| Age | 43.87 ± 9.36 | 40.34 ± 9.16 | 0.071 |
| BMI (kg/m2) | 25.52 ± 3.78 | 26.47 ± 3.10 | 0.192 |
| Smoking status Smokers/non-smokers | 42/2 | 46/2 | 0.658 |
| Alcohol consumption (unita/week) | 116.76 ± 56.86 | 1.78 ± 2.74 | <0.001* |
| Serum ghrelin (pg/ml) | 30.32 ± 26.62 | 20.39 ± 3.92 | 0.030* |
AD: alcohol-dependent individuals, H: healthy individuals, BMI: body mass index
Values represent means±standard deviation or numbers of subjects, where appropriate
1 unit of alcohol: 330 ml of beer (5% alcohol)/1 glass (140 ml) of wine (12% alcohol)/1 glass of (40 ml) vodka, whisky, or gin (40% alcohol)/1 glass (40 ml) of raki (45% alcohol)
The Barratt Impulsiveness Scale (BIS) is a 30-question self-report scale with three subscales: attentional impulsiveness, motor impulsiveness, and non-planning impulsiveness. All items are answered on a four-point scale (Rarely/Never, Occasionally, Often, Almost Always/Always), and a score of 4 indicates the most impulsive response (Patton et al., 1995). The Turkish version of this scale has been confirmed to be valid and reliable for psychiatric patients and the general population (Gulec et al., 2008).
The UPPS Impulsive Behaviour Scale (UPPS), developed by Whiteside and Lynam, consists of 45 questions scored between 1 and 4. The scale’s four subscales were urgency, (lack of) premediation, (lack of) perseverance, and sensation-seeking (Whiteside et al., 2005). The scale’s validity and reliability study in the Turkish language was performed by Yargıc and colleagues (Yargıç et al., 2011).
The Penn Alcohol Craving Scale (PACS), which is used to evaluate craving, is a self-report scale consisting of five questions scored between 0 and 6 (Flannery et al., 1999). The Turkish version of this scale has been confirmed to be valid and reliable for the patients with alcohol use disorder (Evren et al., 2008).
The Yale Brown Obsessive Compulsive Scale for heavy drinking (YBOCS-hd) is a 10-item self-report scale developed to measure craving by evaluating obsessive and compulsive dimensions of alcohol consumption (Modell et al., 1992). The Turkish form of the scale was found to be valid and reliable by Ozgur Ilhan and colleagues (Ilhan et al., 2006).
Statistical analysis
The participants’ sociodemographic data and clinical features were collected. Continuous data are summarized as mean ± standard deviation. In the statistical analysis, P <0.05 was accepted as statistically significant. Kolmogorov–Smirnov normality analyses revealed that ghrelin levels were not normally distributed; therefore, nonparametric tests were used.
The Mann–Whitney U test was used to compare the impulsivity scores between the groups. Friedman test and Wilcoxon test were used to determine the change of ghrelin with time in the patient group. The relationships between plasma ghrelin levels and impulsivity scores, and between ghrelin and craving scores were evaluated using Spearman correlation analysis for both groups. All analyses were conducted using SPSS 20.0 (IBM Corp., Armonk, NY, USA).
Results
The characteristics of the alcohol-dependent patients (AD) and healthy individuals (H) are presented in Table 1. All participants were male, and there were no significant differences between groups with respect to age (t = 1.830, P = 0.071), body mass index (t = −1.315, P = 0.192), or smoking status (P = 0.658). Alcohol consumption (z = −8.341, P < 0.001*) and ghrelin levels at T0 (z = −2.174, P = 0.030*) are significantly different between groups. During the follow-up, ghrelin levels of alcohol-dependent participants were measured at T1 (n = 33, mean ± SD: 26.27 ± 26.99), T2 (n = 20, mean ± SD: 25.92 ± 27.61), and T3 (n = 12, mean ± SD: 25.84 ± 32.96), respectively. A significant difference is observed in ghrelin levels between T0, T1, T2, and T3 (P < 0.001*). Ghrelin levels were significantly decreased from T0 to T1 (z = −4.137, p < 0.001*), from T1 to T2 (z = −3.267, P = 0.001*), and from T2 to T3 (z = −2.197, P = 0.028*). There was no significant relationship between ghrelin levels and PACS scores at T0, T1, T2, and T3 (P = 0.963, P = 0.640, P = 0.541, and P = 0.327, respectively). YBOCS-hd scores also had no significant association with ghrelin levels at T0, T1, T2, and T3 (P = 0.688, P = 0.656, P = 0.375, and P = 0.252, respectively).
Alcohol-dependent participants had significantly higher impulsivity scores than healthy participants in the attentional, motor, and non-planning subscales of the BIS, and the BIS total score. They also had significantly higher scores on the urgency and premediation subscales of the UPPS (Table 2).
Differences between alcohol-dependent patients and healthy individuals in impulsivity scores.
| AD (T0) (n = 44) | H (n = 48) | |||
|---|---|---|---|---|
| Mean ± SD | Mean ± SD | z | p | |
| BIS | ||||
| Attention | 31.30 ± 6.55 | 23.35 ± 5.08 | z = −5.476** | p < 0.001 |
| Motor | 14.41 ± 2.88 | 11.19 ± 2.18 | z = −5.244** | p < 0.001 |
| Non-planning | 22.07 ± 3.12 | 18.92 ± 2.85 | z = −4.680** | p < 0.001 |
| Total | 67.77 ± 10.84 | 53.46 ± 8.10 | z = −5.815** | p < 0.001 |
| UPPS | ||||
| Urgency | 31.14 ± 5.89 | 21.52 ± 5.76 | z = −6.145** | p < 0.001 |
| Premediation | 32.45 ± 5.72 | 36.48 ± 4.80 | z = −3.404* | p = 0.001 |
| Perseverence | 29.41 ± 4.75 | 31.27 ± 4.49 | z = −1.811 | p = 0.070 |
| Sensation seeking | 30.70 ± 6.90 | 31.19 ± 7.06 | z = −0.818 | p = 0.413 |
| Total | 123.70 ± 11.57 | 120.46 ± 9.53 | z = −1.345 | p = 0.178 |
| AD (T0) (n = 44) | H (n = 48) | |||
|---|---|---|---|---|
| Mean ± SD | Mean ± SD | z | p | |
| BIS | ||||
| Attention | 31.30 ± 6.55 | 23.35 ± 5.08 | z = −5.476** | p < 0.001 |
| Motor | 14.41 ± 2.88 | 11.19 ± 2.18 | z = −5.244** | p < 0.001 |
| Non-planning | 22.07 ± 3.12 | 18.92 ± 2.85 | z = −4.680** | p < 0.001 |
| Total | 67.77 ± 10.84 | 53.46 ± 8.10 | z = −5.815** | p < 0.001 |
| UPPS | ||||
| Urgency | 31.14 ± 5.89 | 21.52 ± 5.76 | z = −6.145** | p < 0.001 |
| Premediation | 32.45 ± 5.72 | 36.48 ± 4.80 | z = −3.404* | p = 0.001 |
| Perseverence | 29.41 ± 4.75 | 31.27 ± 4.49 | z = −1.811 | p = 0.070 |
| Sensation seeking | 30.70 ± 6.90 | 31.19 ± 7.06 | z = −0.818 | p = 0.413 |
| Total | 123.70 ± 11.57 | 120.46 ± 9.53 | z = −1.345 | p = 0.178 |
AD: Alcohol-dependent individuals, H: Healthy individuals, SD: Standard deviation, BIS: Barratt Impulsiveness Scale, UPPS: UPPS Impulsive Behavior Scale
Differences between alcohol-dependent patients and healthy individuals in impulsivity scores.
| AD (T0) (n = 44) | H (n = 48) | |||
|---|---|---|---|---|
| Mean ± SD | Mean ± SD | z | p | |
| BIS | ||||
| Attention | 31.30 ± 6.55 | 23.35 ± 5.08 | z = −5.476** | p < 0.001 |
| Motor | 14.41 ± 2.88 | 11.19 ± 2.18 | z = −5.244** | p < 0.001 |
| Non-planning | 22.07 ± 3.12 | 18.92 ± 2.85 | z = −4.680** | p < 0.001 |
| Total | 67.77 ± 10.84 | 53.46 ± 8.10 | z = −5.815** | p < 0.001 |
| UPPS | ||||
| Urgency | 31.14 ± 5.89 | 21.52 ± 5.76 | z = −6.145** | p < 0.001 |
| Premediation | 32.45 ± 5.72 | 36.48 ± 4.80 | z = −3.404* | p = 0.001 |
| Perseverence | 29.41 ± 4.75 | 31.27 ± 4.49 | z = −1.811 | p = 0.070 |
| Sensation seeking | 30.70 ± 6.90 | 31.19 ± 7.06 | z = −0.818 | p = 0.413 |
| Total | 123.70 ± 11.57 | 120.46 ± 9.53 | z = −1.345 | p = 0.178 |
| AD (T0) (n = 44) | H (n = 48) | |||
|---|---|---|---|---|
| Mean ± SD | Mean ± SD | z | p | |
| BIS | ||||
| Attention | 31.30 ± 6.55 | 23.35 ± 5.08 | z = −5.476** | p < 0.001 |
| Motor | 14.41 ± 2.88 | 11.19 ± 2.18 | z = −5.244** | p < 0.001 |
| Non-planning | 22.07 ± 3.12 | 18.92 ± 2.85 | z = −4.680** | p < 0.001 |
| Total | 67.77 ± 10.84 | 53.46 ± 8.10 | z = −5.815** | p < 0.001 |
| UPPS | ||||
| Urgency | 31.14 ± 5.89 | 21.52 ± 5.76 | z = −6.145** | p < 0.001 |
| Premediation | 32.45 ± 5.72 | 36.48 ± 4.80 | z = −3.404* | p = 0.001 |
| Perseverence | 29.41 ± 4.75 | 31.27 ± 4.49 | z = −1.811 | p = 0.070 |
| Sensation seeking | 30.70 ± 6.90 | 31.19 ± 7.06 | z = −0.818 | p = 0.413 |
| Total | 123.70 ± 11.57 | 120.46 ± 9.53 | z = −1.345 | p = 0.178 |
AD: Alcohol-dependent individuals, H: Healthy individuals, SD: Standard deviation, BIS: Barratt Impulsiveness Scale, UPPS: UPPS Impulsive Behavior Scale
Fasting ghrelin levels of alcohol-dependent participants at baseline were significantly related only to the urgency subscale of the UPPS (Table 3). At T1, fasting ghrelin levels of the alcohol-dependent participants were positively related to the UPPS urgency subscale score measured at baseline (n = 33, r = 0.367, P = 0.036*). A stronger positive correlation was observed between the initial urgency score and fasting ghrelin measured at T2 (n = 20, r = 0.533, P = 0.015*), and T3 (n = 12, r = 0.646, P = 0.023*).
Among healthy participants, fasting ghrelin levels were positively correlated with the UPPS sensation-seeking subscale and the UPPS total scores (Table 3). Among the healthy participants, 25 people did not consume alcohol, and additional analyses revealed that their fasting ghrelin levels were positively correlated with the attentional impulsivity subscale of the BIS (r = 0.411, P = 0.041*) and the BIS total score (r = 0.561, P = 0.004*), as well as the UPPS sensation-seeking subscale score (r = 0.480, P = 0.015*) (Table 4).
Correlations of impulsivity scores and fasting ghrelin levels in alcohol-dependent and healthy individuals.
| Fasting Ghrelin | ||
|---|---|---|
| AD (T0) (n = 44) | H (n = 48) | |
| BIS | ||
| Attention | r = 0.224 p = 0.144 | r = 0.248 p = 0.900 |
| Motor | r = −0.50 p = 0.746 | r = 0.044 p = 0.764 |
| Non-planning | r = 0.290 p = 0.056 | r = 0.137 p = 0.354 |
| Total | r = 0.214 p = 0.163 | r = 0.250 p = 0.087 |
| UPPS | ||
| Urgency | r = 0.384* p = 0.010 | r = 0.033 p = 0.824 |
| Lack of premediation | r = −0.199 p = 0.195 | r = −0.177 p = 0.230 |
| Lack of perseverance | r = −0.225 p = 0.143 | r = 0.144 p = 0.328 |
| Sensation Seeking | r = −0.194 p = 0.207 | r = 0.345* p = 0.016 |
| Total | r = −0.138 p = 0.372 | r = 0.307* p = 0.034 |
| Fasting Ghrelin | ||
|---|---|---|
| AD (T0) (n = 44) | H (n = 48) | |
| BIS | ||
| Attention | r = 0.224 p = 0.144 | r = 0.248 p = 0.900 |
| Motor | r = −0.50 p = 0.746 | r = 0.044 p = 0.764 |
| Non-planning | r = 0.290 p = 0.056 | r = 0.137 p = 0.354 |
| Total | r = 0.214 p = 0.163 | r = 0.250 p = 0.087 |
| UPPS | ||
| Urgency | r = 0.384* p = 0.010 | r = 0.033 p = 0.824 |
| Lack of premediation | r = −0.199 p = 0.195 | r = −0.177 p = 0.230 |
| Lack of perseverance | r = −0.225 p = 0.143 | r = 0.144 p = 0.328 |
| Sensation Seeking | r = −0.194 p = 0.207 | r = 0.345* p = 0.016 |
| Total | r = −0.138 p = 0.372 | r = 0.307* p = 0.034 |
AD: Alcohol-dependent individuals, H: Healthy individuals, BIS: Barratt Impulsiveness Scale, UPPS: UPPS Impulsive Behavior Scale
Correlations of impulsivity scores and fasting ghrelin levels in alcohol-dependent and healthy individuals.
| Fasting Ghrelin | ||
|---|---|---|
| AD (T0) (n = 44) | H (n = 48) | |
| BIS | ||
| Attention | r = 0.224 p = 0.144 | r = 0.248 p = 0.900 |
| Motor | r = −0.50 p = 0.746 | r = 0.044 p = 0.764 |
| Non-planning | r = 0.290 p = 0.056 | r = 0.137 p = 0.354 |
| Total | r = 0.214 p = 0.163 | r = 0.250 p = 0.087 |
| UPPS | ||
| Urgency | r = 0.384* p = 0.010 | r = 0.033 p = 0.824 |
| Lack of premediation | r = −0.199 p = 0.195 | r = −0.177 p = 0.230 |
| Lack of perseverance | r = −0.225 p = 0.143 | r = 0.144 p = 0.328 |
| Sensation Seeking | r = −0.194 p = 0.207 | r = 0.345* p = 0.016 |
| Total | r = −0.138 p = 0.372 | r = 0.307* p = 0.034 |
| Fasting Ghrelin | ||
|---|---|---|
| AD (T0) (n = 44) | H (n = 48) | |
| BIS | ||
| Attention | r = 0.224 p = 0.144 | r = 0.248 p = 0.900 |
| Motor | r = −0.50 p = 0.746 | r = 0.044 p = 0.764 |
| Non-planning | r = 0.290 p = 0.056 | r = 0.137 p = 0.354 |
| Total | r = 0.214 p = 0.163 | r = 0.250 p = 0.087 |
| UPPS | ||
| Urgency | r = 0.384* p = 0.010 | r = 0.033 p = 0.824 |
| Lack of premediation | r = −0.199 p = 0.195 | r = −0.177 p = 0.230 |
| Lack of perseverance | r = −0.225 p = 0.143 | r = 0.144 p = 0.328 |
| Sensation Seeking | r = −0.194 p = 0.207 | r = 0.345* p = 0.016 |
| Total | r = −0.138 p = 0.372 | r = 0.307* p = 0.034 |
AD: Alcohol-dependent individuals, H: Healthy individuals, BIS: Barratt Impulsiveness Scale, UPPS: UPPS Impulsive Behavior Scale
Correlations of impulsivity scores and fasting ghrelin levels in participants who do not consume alcohol.
| Fasting ghrelin (n = 25) | BIS | ||||
| Attention r = 0.411* P = 0.041 | Motor r = 0.277 P = 0.181 | Non-planning r = 0.272 P = 0.188 | Total r = 0.561* P = 0.004 | ||
| UPPS | |||||
| Urgency r = 0.327 P = 0.111 | Premediation r = −0.290 P = 0.160 | Perseverance r = −0.116 P = 0.580 | Sensation-seeking r = 0.480* P = 0.015 | Total r = 0.351 P = 0.085 | |
| Fasting ghrelin (n = 25) | BIS | ||||
| Attention r = 0.411* P = 0.041 | Motor r = 0.277 P = 0.181 | Non-planning r = 0.272 P = 0.188 | Total r = 0.561* P = 0.004 | ||
| UPPS | |||||
| Urgency r = 0.327 P = 0.111 | Premediation r = −0.290 P = 0.160 | Perseverance r = −0.116 P = 0.580 | Sensation-seeking r = 0.480* P = 0.015 | Total r = 0.351 P = 0.085 | |
BIS: Barratt Impulsiveness Scale, UPPS: UPPS Impulsive Behaviour Scale
Correlations of impulsivity scores and fasting ghrelin levels in participants who do not consume alcohol.
| Fasting ghrelin (n = 25) | BIS | ||||
| Attention r = 0.411* P = 0.041 | Motor r = 0.277 P = 0.181 | Non-planning r = 0.272 P = 0.188 | Total r = 0.561* P = 0.004 | ||
| UPPS | |||||
| Urgency r = 0.327 P = 0.111 | Premediation r = −0.290 P = 0.160 | Perseverance r = −0.116 P = 0.580 | Sensation-seeking r = 0.480* P = 0.015 | Total r = 0.351 P = 0.085 | |
| Fasting ghrelin (n = 25) | BIS | ||||
| Attention r = 0.411* P = 0.041 | Motor r = 0.277 P = 0.181 | Non-planning r = 0.272 P = 0.188 | Total r = 0.561* P = 0.004 | ||
| UPPS | |||||
| Urgency r = 0.327 P = 0.111 | Premediation r = −0.290 P = 0.160 | Perseverance r = −0.116 P = 0.580 | Sensation-seeking r = 0.480* P = 0.015 | Total r = 0.351 P = 0.085 | |
BIS: Barratt Impulsiveness Scale, UPPS: UPPS Impulsive Behaviour Scale
Discussion
Our study is the first to investigate the association between ghrelin and trait impulsivity in both alcohol-dependent and healthy individuals. Our findings revealed that the relationship between impulsivity and ghrelin varies with different impulsivity dimensions in two different groups. Among healthy volunteers, ghrelin levels were associated with sensation-seeking and total impulsivity levels on one of the scales. In contrast, initial measurements of ghrelin for the alcohol-dependent patient group were associated only with urgency. We observed a positive association between ghrelin and urgency after the withdrawal period among alcohol-dependent participants, and this relationship increase in strength as the duration of alcohol abstinence increased. When the analyses were repeated only with individuals that had never used alcohol among the healthy volunteers to reset all possible alcohol effects on ghrelin hormone, the correlation between ghrelin and impulsivity was strengthened, and ghrelin levels were significantly associated with the attentional impulsivity as well as total impulsivity and sensation-seeking.
In our study, impulsivity scores were higher among alcohol-dependent participants than healthy volunteers. The BIS total scores and the BIS subscales (attentional impulsivity, motor impulsivity, non-planning) both differed significantly between groups. However, there was no difference in the UPPS total score. A significant between-group difference was detected in only the premediation and urgency subscales of the UPPS. Higher levels of impulsivity among alcohol-dependent participants have been reported in many studies (Curcio and George, 2011; Coskunpinar et al., 2013). Alcohol and substance use have often been associated with sensation-seeking (Curcio and George, 2011; Coskunpinar et al., 2013; Lac and Donaldson, 2021). Sensation-seeking can be defined as seeking exciting activities, enjoying them, and being open to new experiences although they can be dangerous (Zuckerman, 1994). By definition, it was thought to be related to alcohol dependence; nevertheless, it has not been found to be associated with alcohol-related problems in many recent studies (Magid et al., 2007; Curcio and George, 2011; McCarty et al., 2017). Parallel to these findings, no significant difference was found in sensation-seeking between alcohol-dependent subjects and healthy participants in our study. Most of the studies have shown that urgency is the most prominent dimension of impulsivity associated with alcohol-related problems (Curcio and George, 2011; Coskunpinar et al., 2013). Fischer and colleagues demonstrated that the only dimension of impulsivity associated with three different pathological behaviours, binge eating, alcohol use disorder, and pathological gambling, is urgency (Fischer and Smith, 2008). Unlike other impulsivity features, urgency has an affective component. Urgency is associated with impulsive movements in strong affect states, so positive and negative reinforcers may be associated with its effects on alcohol use and impulsive behaviour (Kaiser et al., 2016).
In our study, ghrelin levels were significantly higher in alcohol-dependent patients than healthy participants and significantly decreased during early and late withdrawal periods. These findings are supported those reported by Akkisi Kumsar and colleagues (Akkisi Kumsar and Dilbaz, 2015). Kraus and colleagues also found higher ghrelin levels in alcohol dependency; however, they claimed that the levels increased during withdrawal (Kraus et al., 2005). Another study showed that, contrary to our findings, ghrelin levels were lower in the alcohol-dependent group compared to healthy subjects, but the levels are decreased during alcohol withdrawal, which is parallel with our study (Badaoui et al., 2008). There was no significant association between ghrelin levels and craving at the time of admission and during both early and late abstinence periods in our study. According to some studies, a significant relationship between ghrelin hormone levels and craving scores in alcohol-dependent patients at admission, early abstinence (Koopmann et al., 2012; Akkisi Kumsar and Dilbaz, 2015), and late abstinence period was detected (Leggio et al., 2012). However, some studies did not find an association between ghrelin and craving, or the relationship differed in different patient groups (Kraus et al., 2005; Hillemacher et al., 2007). Different results seen in these studies related to this subject may be due to differences between biochemical measurement methods, follow-up times, and scales used in these studies.
Preclinical studies have demonstrated that food reward behaviour and food addiction-like behaviours are associated with nucleus accumbens stimulation in the mesolimbic system (Skibicka and Dickson, 2011). In rats, these behaviours are associated with high levels of impulsivity (Velázquez-Sánchez et al., 2014). Ghrelin increases dopamine release in the nucleus accumbens via the GHS-R1A (Stievenard et al., 2017). In a preclinical study, Anderberg et al. (2016) injected ghrelin into the lateral ventricle of rats, measured impulsive decision-making levels, and observed an increase in impulsive behaviour (Anderberg et al., 2016). In the same study, central ghrelin receptor blockade caused a decrease in impulsive behaviour. Another study revealed significantly higher ghrelin levels in patients who attempted suicide than in controls (Atmaca et al., 2006). An essential aspect of the research mentioned above may be the relationship between impulsivity and ghrelin since suicide attempts are known to be associated with impulsivity levels (Coryell et al., 2018). Recently, Ralevski and colleagues revealed that ghrelin levels of 20 social drinkers were positively correlated with reward sensitivity, lack of self-control, and non-planning (Ralevski et al., 2018). A recently published study has shown positive correlation between ghrelin and desacyl-ghrelin levels and impulsivity and aggression in patients with antisocial personality disorder (Tasci et al., 2022). In that study, the relationship between impulsivity and ghrelin was found only in the BIS motor impulsivity subscale, and no significant relationship was found between these two variables in healthy controls. The differences in the ghrelin–impulsivity relationship in different groups in these studies and in our study may indicate that there are different factors whose effect we do not know yet, especially in the sample with alcohol dependency and personality problems.
Our study results are consistent with those of previous studies in terms of revealing the relationship between ghrelin and impulsivity. However, in the limited number of studies on this subject, the impulsivity dimensions with which ghrelin is related differ from each other. Even in our study, the results of the two impulsivity scales (BIS and UPPS) were different. Both scales were designed to measure impulsivity, but these scales and their subscales appear to assess different aspects of impulsivity. The BIS is the most commonly used impulsivity scale, but it is used for general impulsivity assessment, rather than its subscales. Furthermore, the BIS mostly examines topographical features of behaviour and classifies impulsivity as planning, decision-making, and taking action, but in the UPPS, more emphasis is placed on what the behaviour serves (Whiteside et al., 2005). Aside from the differences between scales, although the theory and definition are agreed upon, the dimensions of impulsivity and the nature of these dimensions remain controversial.
It is noteworthy that the ghrelin–urgency relationship was strengthened as the duration of alcohol abstinence increases. However, the reason for this result may be the decreased sample size during the follow-up period. Nevertheless, the relationship between impulsivity and ghrelin in healthy participants, especially in participants who had never consumed alcohol, is important in terms of demonstrating the association in a more homogeneous group. Further studies are needed to clarify the role of impulsivity in the complex relationship between ghrelin and alcohol use disorder. Although the findings of our study are preliminary, they can provide a basis for further investigation of the relationship between ghrelin and impulsivity in a community sample.
Our study has some limitations. First, only male participants were included in the study. This is because alcohol dependence is far more common among male individuals in Turkey. Second, information on alcohol use and 8-hour fasting status in both groups, and information on alcohol use in the initial and follow-up periods in the group with alcohol use disorder were obtained by self-report, which may be considered as a limitation. However, the participants were informed in detail that whether or not they met the conditions for participation in the study or continued the follow-up process would not cause a change in the treatment process. The impulsivity scales were applied after at least 5 days of abstinence to reduce the possible impact of withdrawal on results, but the effect may not be overridden, and this may be considered a limitation. In addition, the decrease in the number of alcohol-dependent participants is a limitation; however, the loss in the number of participants is inevitable in this process. Further studies are needed to clarify the ghrelin–impulsivity relationship in other impulsivity-related disorders.
Conflict of interest
None declared.
Funding
This work was supported by Ankara University Scientific Research Projects Coordinatorship (grant number 18L0230010).
Data availability
Data described in the manuscript will be made available by contacting the corresponding author.
