Excessive alcohol intake is considered the most pervasive harmful habit in the world and has been identified as a social problem (1), causing 5.3% of all deaths worldwide (3 million deaths annually) according to the World Health Organization (WHO). This percentage rises among younger people (20–39 years of age), accounting for 13.5% of all fatalities in this age group, besides the effect on public health that this entails (2).

In recent years, college students have started to be considered a risk population for problematic alcohol use (3–5). The university stage is a time when the student builds a new social network and creates the foundation of their adult identity (6). Since most young people use alcohol as a recreational substance, alcohol use is quite prevalent at this period of life (7, 8). Additionally, the beginning of university studies also marks the onset of the legal drinking age, which allows them easy access and purchase of alcohol. A frequent pattern of alcohol consumption among young people is characterized by episodes of intense and compulsive drinking over a short period of time which is known as binge drinking (BD) and it has been correlated with high-risk behavior, such as aggression, reckless driving, or unprotected sex (9, 10). This represents a harmful alcohol-consumption pattern, and people who engage in this behavior may experience a variety of short- and long-term impacts, such as issues with their physical and mental health, violent behavior, or difficulty adjusting to family or school life (11, 12). Although quantitative definitions of BD differ significantly among nations, the most common threshold for defining BD is the intake of four to five alcohol doses (for men and women, respectively), in 2 h, at least once per month over a period of 6 months (13).

There is a great need for identification of biological markers associated with early alcohol-related brain damage. Concerning to this, BD is known to alter the frontal pathways (fronto-limbic) of white matter in adolescents and young adults (14, 15). The connections between the prelimbic and infralimbic regions, as well as those between the infralimbic region and the orbitofrontal cortex, appear to be affected by this diminished fronto-limbic connectivity (16). Besides, reduced or compromised inhibitory control seems to be associated with this decline in fronto-striatal connection (17). On the other hand, high alcohol consumption in university students has also been linked to a loss of gray matter in the prefrontal areas (18, 19) and cholinergic and serotonergic neurons persisting into adulthood (20). However, little is known about the impact of BD on physiological stress-related responses despite the relevance of this factor on alcohol abuse (21, 22). Some studies have pointed that young people and adolescents may be motivated to drink alcohol by their desire for new experiences and feelings, but, in general, they frequently drink alcohol to cope with the stress or unpleasant feelings they may have throughout their first year of college (due to the perception of responsibility, greater freedom, study, work, or the creation of new social networks) (23, 24). In comparison to the general population, university students often exhibit higher levels of anxiety and worst mental health (25, 26), and the primary source of this distress appears to be anxiety about academic success (27). Thus, lack of adequate strategies to deal with situations of stress can lead to the adoption of inappropriate or harmful coping mechanisms, such as excessive alcohol use.

Emotions include a psychophysiological component that can be studied using measurements of skin conductance (SC) and heart rate indices (HR) (28). SC is mainly influenced by the amount of moisture produced by the eccrine sweat glands under the control of the sympathetic branch of the autonomic nervous system (ANS) (29). HR is regulated by both the sympathetic and parasympathetic branches of the ANS, and it reflects stress reactivity in psychosocial and cognitive circumstances (30). Salivary cortisol is also frequently utilized as a biomarker of anxiety, and salivary cortisol levels seem an accurate indicator of the hypothalamus—pituitary–adrenal axis (HPA) response to stress (31). In summary, these three peripheral responses (SC, HR, and level of cortisol) are frequently used as measures of ANS reactivity (32) and, additionally, they are useful measurements for examining how drinking is related to emotional functioning (33, 34). Physiological arousal levels have been positively correlated with dependence and alcohol consumption levels (35), and gender differences in these responses also have been reported (36, 37).

In recent years, new research approaches have explored more ecological contexts and reliable measurements of stress-related responses. In this context, virtual reality (VR) has been increasingly employed because it is able to induce stress reactivity despite the virtual context (38). Currently, there is a dearth of studies that have investigated stress reactivity and anxiety-related behaviors in young individuals with substance use through exposure to virtual scenarios, being specially focus on treatment, craving or cognition (39–41). In a previous study of our group with young people with problematic alcohol consumption, without BD, we observed more anxious-related behaviors when they were exposed to our virtual environment, as well as a different pattern of physiological responses compared to the healthy youths (42). In consequence, we are interested in analyzing similar physiological responses when alcohol is consumed in BD way.

Therefore, our main goal was to analyze the physiological responses induced by a stressful VR environment in young people with BD. Along with this, we will consider the influence of participants’ sex in our results owing to both stress reactivity and regulation have been shown to differ between men and women, despite the neural networks supporting these processes remain unclear (43). We expect that these variables can constitute possible biomarkers that allow us to detect young people at risk of developing alcohol use disorder in the future.

In the current study, we explored the behavioral and neuropsychophysiological responses of young individuals with BD during the exposition to a stressful VR environment compared to a healthy CO group. Our stress-related variables, registered at different moments of the VR task (behavioral pattern of ambulation, EEG, HR, and EDA response, as well as salivary cortisol), could be possible used as possible biomarkers that allow us to detect young people at risk of developing alcohol use disorder in the future, as well as anxiety-related disorders (57–59). As expected, our results showed several behavioral and physiological differences between groups, highlighting the variable sex as an important factor modulating our results.

Concerning the behavioral performance during the VR task, our results showed that the BD group spent significantly less time walking forward the table with respect to the CO group, whereas the time spent looking down was similar in both groups. Nevertheless, when we controlled the variable sex, the BD women group displayed higher amount of time looking down than BD men. As we know, this is the first study that has employed the software Richie’s Plank Experience to analyze the behavioral pattern of exploration of young participants with alcohol consumption in BD way. Studies in animal models (60, 61) and in humans (42, 62, 63) have shown that the higher the level of anxiety, the more we tend to avoid unprotected open spaces. Hence, our BD participants did not spend much of the experience walking the plank, let alone getting to the end of it. On the contrary, although it was not significant, they showed a tendency to walk backwards toward the protected space without turning around as an indicator of anxiety and fear of falling. Previous study of our group using another VR experience revealed similar results with a more anxious pattern of exploration in young subjects with problematic alcohol use (42). It results interesting that BD women displayed higher time looking down during the experience respect to BD men. This result could be understood in two ways. On the one hand, it is possible that the women from the experimental group exhibited more risk-taking and sensation seeking-related behavior, or on the other hand, this behavior could have reflected an attempt to check that they were not going to fall while walking slowly on the board. Regarding the first interpretation, some studies have observed that women in the mid- and late-20s usually, as in our study, usually show higher scores in sensation seeking behaviors (64, 65) which, in turn, is related to seek out novel and exciting stimuli, including risk-taking behavior (66). Further research on this matter is necessary due to the clinical implications that this variable presents as a risk factor (67).

EEG measurements were not different between groups, as well as EDA response and the salivary cortisol levels. It is possible that the lack of differences in salivary cortisol levels were due to methodological errors associated with the pattern of release of this hormone. We recollected the T2 sample immediately after the end of the VR task, whereas cortisol peak occurs between 20 and 30 min after stressor onset and can continue to be elevated for an hour or more (68, 69). A previous study of our group also found no differences in EDA response between young participants with problematic alcohol consumption and the CO group (42). Some studies have suggested that blunted reactivity is a general characteristic of alcohol dependency, particularly in adults with a long-standing history of consumption, rather than in individuals with time-limited excessive alcohol use as in our studies (70). Regarding EEG registered variables, recent literature has described that, similar to individuals with alcohol addiction, BD also displayed increased resting-state EEG signal (59). For instance, high-BD subjects presented greater spectral power over the frontal, central and parietal regions in the delta (0–4 Hz), and fast-beta (20–35 Hz) frequency bands, suggesting that high-BDs display an EEG spectral pattern similar to that observed in subjects with alcohol use disorder (70, 71). Similarly, Affan et al. (58) found a slower Alpha Peak Frequency as well as increased frontal theta and beta power in the BD group. Hence, resting-state EEG studies seem to indicate that BDs present abnormal spontaneous EEG signal, mainly characterized by increased power in slow (delta/theta) and fast (beta) frequency bands which could be associated with a brain overactivity eventually caused by an excitatory-inhibitory imbalance (72). In our study, the CO and BD group were similar in Alpha power which is not consistent with previous studies. However, reduced alpha power was observed mainly when anxiety symptoms are present in the BD sample (73, 74). This aspect was controlled in our study (see STAI and BDI-II results in Table 1) and could have contributed to the non-significant difference between groups. On the other hand, the short history of alcohol use in our BD sample could be also related to the lack of differences with the CO group (72, 75).

Sex-related differences were found in HR response to VR scenario, in which BD women displayed the highest peak of response to the stressor. Also, the change in heartbeat was higher in BD women than men. This enhanced HR response in BD women could be related to their risky behaviors during the exploration of the VR environment. Thus, it has been widely described that to cope with stressful stimuli our body releases adrenaline, a hormone that temporarily causes higher heart rate to speed up and your blood pressure to rise (76). Hence, it could be a normal biomarker of their pattern of ambulation during the VR environment. These findings are consistent with the theory that increased HR reflects engagement of self-regulatory efforts to cope with an emotional or stressful situation (77). Considering the historical under-representation of women in alcohol abuse research, the identification of HR as a potential biomarker for addiction and relapse risk (78), and the close relationship between stress, alcohol abuse, and relapse in women (79), these issues hold significant research and clinical relevance.

In general, VR is a technological tool which can open new avenues to better understand the neurobiological mechanisms of emotional responding in healthy and pathological conditions (42). It results attractive to young people and, while its employment is more prevalent in the intervention context, it could be employed as a tool to identify behavioral patterns or physiological responses related to future clinical conditions. Moreover, it is notorious to highlight the role of sex variable in addiction related studies in which girls usually show a tendency toward increased alcohol consumption associated with negative mood states (80). Additionally, their different psychophysiological responses to a stressor may be useful as a future predictor of severity. As limitations of our study, we would like to mention the reduced sample size. Moreover, variables such as the menstrual phase, as a variable influencing stress response or drug-related variables, as the quantity of alcohol consumed by the participants, should have been considered in our study.

The present study focused on examining the behavioral signs of anxiety through a VR task and investigating the psychophysiological responses associated with a virtual stressful context. Exploring biomarkers provides crucial insights into the intricate relationship between the body and mind, and VR appears to be a useful tool for investigating anxiety in humans. Therefore, understanding and addressing the biological mechanisms involved in stress-related responses holds the promise of improving treatments, predicting problematic use, and provide personalized care to address the specific needs of women.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The study received approval from the Ethics Committee of the Autonomous University of Madrid (Code: CEI-122-2490) and Universidad Francisco de Vitoria (UFV 23-2022) in accordance with the Ethical Principles for Medical Research Involving Human Subjects adopted in the Declaration of Helsinki by the World Medical Association (64th WMA General Assembly, Fortaleza, Brazil, October 2013), Recommendation No. R (97) 5 of the Committee of Ministers to Member States on the Protection of Medical Data (1997), and the Spanish Data Protection Act (Ley Orgánica 15/1999 de Protección de Datos, LOPD). All participants were informed about the study prior to their inclusion in the study and then provided their written informed consent. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

RM-F: Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing. EB-B: Investigation, Writing – original draft. MC-C: Investigation, Methodology, Writing – original draft. FB-S: Formal analysis, Writing – original draft. PS-P: Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Writing – original draft, Writing – review & editing.