1. Introduction
Due to their high exposure to stress in their professional lives, healthcare workers constitute an interesting research group in the context of studies on methods of coping with stress, as well as the psychological and biological determinants of stress responses.
Working in the health professions involves a great deal of responsibility and, consequently, exposure to stress. Furthermore, staff shortages and working under time pressure are associated with high overloads for healthcare workers. A significant phenomenon among occupations that require intensive contact with people is burnout syndrome. It occurs under the influence of prolonged and poorly managed stress [
1], in which the employee feels chronically overtired and dissatisfied with the job, and becomes distant and less and less committed to work [
2,
3]. Although occupational burnout is not recognized as a disease by the WHO in the ICD-11 classification of diseases, it is a serious medical and social problem that is a response to chronic occupational stress [
4]. Hence, it seems very important to assess the severity of stress and coping methods among medics.
It is often said that medical professionals experience high levels of stress, but it should be noted that environmental factors are not the only ones that play a role here. How we deal with stress and certain personality traits can be influenced not only by psycho-social factors, but also by biological factors, including genetics. Studies described the association of the
DRD4 (Dopamine Receptor D4) gene with temperament or personality traits [
5,
6,
7]. There are several types of polymorphisms involving the
DRD4 gene. The 48-base pair variable number tandem repeat (VNTR) in exon 3 of the
DRD4 gene in humans ranges from 2 to 11 repeats [
8]. The so-called “Nomad gene” explored in this study is
DRD4, with seven repeats (
DRD4-7R). The name comes from a population of wanderers, the Nomads, who have higher frequencies of 7R alleles than the ones in sedentary tribes [
9]. Research suggests that the long allele (seven or more repeats) is associated with novelty seeking and risk taking, and limited emotional responses, but it is also associated with retained attention processing of emotional stimuli and effective problem solving [
10,
11]. These are very important traits in medical professions.
It should also be noted that people working in healthcare are often characterized by a high level of ambition and a strong drive to achieve difficult and important goals. A large meta-analysis focusing on profiling non-cognitive features, i.e., personality traits, behavioral patterns and emotional intelligence, of medical professionals revealed many shared characteristics (homogeneity) among different representatives of this professional group. All medical professions exhibit personality traits such as agreeableness, cooperativeness and independence, as well as lower levels of neuroticism [
12].
Due to the high level of work-related stress among healthcare workers and the specific nature of this professional group, it seems reasonable to investigate the associations between certain temperament traits (impulsivity, risk taking), stress-coping strategies, type of work performed, and biological factors. In general, research into the relationship between gene polymorphism and psychological traits is important because it allows researchers to better understand the basis of our individuality.
Given the abovementioned features, the ‘Nomad gene’, i.e., the long allele (more than seven repeats) of the
DRD4 gene, seems to be an ideal candidate for this type of research. The polymorphism of this gene has already been studied among investors [
13] and Senegalese fishermen [
14], but never among healthcare workers.
The aim of this study was to assess the DRD4-7R polymorphism and its impact on propensity for risk taking and ways of coping with stress in medical professionals.
3. Discussion
Exposure to risky situations, including those in professional life, can affect risk tolerance. However, research also indicates that risk-coping attitudes are partly heritable [
15]. Given the role of the dopaminergic system in reward and motivation mechanisms and impulse control [
16], genes related to this neurotransmitter are potential candidates for studying the genetic basis of differential stress sensitivity and risk-taking propensity. High polymorphism, expression in the frontal cortex (an extremely important area in decision-making) and its large region of variable number of tandem repeats (VNTRs) make the
DRD4 gene a very good research target [
17]. The GWAS study did not show a statistically significant genetic contribution of genes involved in the dopaminergic pathway to risk attitudes, but we know that such studies, by eliminating any environmental conditions or gene interactions, can mask some genetic factors [
18].
Studies indicate, for instance, that the effect of the
DRD4 gene polymorphism can be modulated already at a very early, even prenatal, stage (e.g., gyrification ceases by about the age of two) [
19,
20,
21].
DRD4-7R carriers with diagnosed ADHD have less prefrontal gyrification than individuals with the other
DRD4 allele, suggesting the
DRD4-7R allele could be involved in this hypogyrification [
19].
A study by Zohsel et al. (2014) [
20] indicates an association between a mother’s stress during pregnancy and the propensity for aggressive behavior in her offspring, especially with the co-occurrence of adverse environmental factors. Carriers of at least one allele containing seven repeats (
DRD4-7R), whose mothers indicated a state of increased stress during pregnancy using the questionnaire method, were found to be at increased risk for a diagnosis of conduct disorder and/or oppositional defiant disorder. Furthermore, homozygous carriers of the
DRD4-7R allele showed more antisocial behavior after exposure to higher levels of prenatal maternal stress, while homozygous carriers of the DRD4 4R allele appeared insensitive to the effects of prenatal stress [
20]. Bakermans-Kranenburg et al. (2011) [
21] tested 124 adopted adults, showing that carriers of the
DRD4-7R allele who had experienced parental problems had the highest scores for unresolved loss or trauma, while
DRD4-7R carriers who had not experienced parental problems showed the lowest trauma scores. Importantly, among participants without the
DRD4-7R allele, parental problems in childhood made no difference. This study supports the hypothesis for heightened susceptibility to environmental influences for carriers of the
DRD4-7R allele instead of only increased vulnerability [
21]. The findings provide independent evidence for interaction of
DRD4 7R and maternal sensitivity affecting externalizing behavior in children, with carriers of the
DRD4-7R allele having greater externalizing problems in the face of maternal insensitivity [
21,
22]. Zandstra and colleagues pointed out the significance of chronic multi-context stressors, showing that higher levels of chronic stressors were associated with higher levels of externalization in
DRD4-7R allele carriers (high sensitivity to adverse environmental conditions), but not in non-carriers (low sensitivity) [
23].
Many researchers also emphasize that some inconsistency in the data regarding
DRD4-7R may reflect individual differences in sensitivity to environmental influences [
24]. Clochard et al. (2023) [
14] showed that the increase in risk tolerance due to the
DRD4-7R allele was moderated in an additive matter (not dominant, as previously thought) and was not directly related to environmental risk. Their study was conducted on two populations of fishermen from small villages in northern Senegal, one of which was at very high risk due to unsafe fishing [
14]. In addition, their data did not support the association of the
DRD4-7R allele with novelty seeking, as previously found [
14,
24]. A meta-analysis of 20 studies reported that only 13 analyzed scientific studies showed a link between the presence of longer alleles (with more repeats, e.g., R7) and higher novelty-seeking scores [
24]. The authors of the meta-analysis also pointed out the validity of searching for factors that moderate this relationship [
24], which makes research on different populations even more important.
Armbruster and associates studied 84 healthy adult volunteers demonstrating the effect of the
DRD4 gene polymorphism on stress reactivity. They examined salivary cortisol levels during and after the Trier social stress test. Carriers of the
DRD4-7R allele demonstrated lower cortisol responses [
25]. This would suggest greater resistance to stress.
The dopamine receptor D4 is a dopamine D2-like G protein-coupled receptor encoded by the
DRD4 gene located on chromosome 11 at 11p15.5 [
26].
Individuals with the
DRD4-7R allele were found to have increased daytime sleepiness compared to those without the allele. However, it is not known whether this is due to the expression of the
DRD4 receptor in the retina, thus affecting circadian rhythms, or whether the increased sensitivity to the environment simply results in greater cognitive processing that causes fatigue [
27,
28,
29].
Gehricke et al. performed an fMRI study on healthy volunteers, showing increased brain activity in response to unpleasant images compared to neutral images in the right temporal lobe in participants with the
DRD4–4R/7R genotype versus participants with the
DRD4–4R/4R genotype (without the long allele). This finding suggests greater involvement of the
DRD4-7R allele in processing negative emotional stimuli [
30].
Colzato et al. (2010) found that carriers of the
DRD4-7R allele exhibited higher dysfunctional impulsivity (the tendency to act without thinking when such action is inappropriate) [
31]. Several meta-analyses identified the
DRD4-7R allele as a risk allele for attention deficit hyperactivity disorder (ADHD), a disorder characterized by high impulsivity [
32,
33]. In our study, carriers of the
DRD4-7R allele were mainly medical doctors (physicians). This group was also characterized by greater venturesomeness (statistically significant difference) and impulsivity.
In our study, as many as 30 out of 82 participants (36,59%) were carriers of at least one long
DRD4-7R allele (see
Table 1 and
Table 2 in the
Section 2.1). The study group consisted of Caucasian healthcare workers employed in medical centers in central Poland. This is important because, although the 4R allele is the most common in all geographical regions [
27], 7R alleles vary significantly in frequency across populations and ethnic groups. The 7R allele has low prevalence in Asia (2%), but high prevalence in America (48%) [
29,
34].
The present study indicates that
DRD4-R7 allele carriers were significantly less likely to use stimulants and other substances to help themselves with stress coping. This contradicts previous reports that carriers of the
DRD4-7R allele were more susceptible to addictions [
35,
36,
37,
38]. As previously mentioned, a longer allele of the
DRD4 gene resulted in lower dopamine receptor affinity; so, people with this version of the allele needed more dopamine for optimal well-being [
39,
40].
According to our study, carriers of the
DRD4-7R allele are less likely to seek emotional support in stressful situations. This may be due to a greater tendency towards impulsive behavior, greater involvement in processing negative stimuli or stress resistance. The results of the study by Su et al. suggest that motion control serves as one modulator by which genetic predisposition and gene–environment interactions affect behavior [
40]. Women who carried the long allele of the
DRD4 gene (genetic factor) and experienced more adverse life events (environmental factor) were less sensitive in interactions with their children [
41]. Moreover, a study by Tompson et al. showed that East Asian carriers (compared to non-carriers) of the 7/2R
DRD4 allele reported experiencing greater emotional balance (i.e., a weaker positive attitude) than non-carriers of these alleles [
42].
One of the main limitations of this study is the small sample size. Nevertheless, we believe that this study may contribute to further research on a larger scale.
4. Materials and Methods
4.1. Participants
The preliminary stage of this study involved 82 volunteers from among active healthcare professionals (66 females and 16 males), including 33 medical doctors (MDs). Other participants were occupationally active: nurses (
n = 37), paramedics (
n = 4), physiotherapists (
n = 3), clinical psychologists (
n = 4), and a midwife (
n = 1). All participants had a direct contact with patients, which may constitute a risk factor for professional burnout. Approximately half of the participants (
n = 40, 48.78%) were working in non-surgical medical specialties. All participants filled out the questionnaire regarding their social, family and occupational situation.
Table 11 shows sociodemographic characteristics of the study group. Considering the predominance of female participants, an analysis of the cohort sociodemographic data by gender was also conducted (
Table 12). The only statistically significant difference (
p < 0.05) between genders was observed when comparing the type of work performed (surgical, non-surgical and emergency/IC—intensive care). The predominance of women is no coincidence. Women constitute a significant and growing proportion of Poland’s healthcare workforce, particularly in nursing [
43].
4.2. Methods
The study participants were asked to fill out a questionnaire about their professional situation (including occupation, education, length of working-time in the profession (seniority), and type of work position: surgical, non-surgical or emergency/intensive care). Furthermore, they were asked to fill out psychological questionnaires for assessment of anxiety levels, coping effectiveness, risk-taking propensity and signs of burnout syndrome:
- −
IVE—Impulsivity Questionnaire—consists of 54 questions with Yes or No answers. The results are captured on three scales: Impulsivity, Willingness to Risk (venturesomeness) and Empathy (54 questions) [
44,
45].
- −
Mini-COPE—Inventory for the Measurement of Coping with Stress—consists of 28 statements included in 14 strategies (2 statements in each strategy). The method is most commonly used to measure dispositional coping, i.e., assessing typical ways of reacting and feeling in situations of experiencing severe stress (28 questions in total). Problem-focused coping strategies include active coping, planning, positive reframing and the use of instrumental support. Emotion-focused coping technics are acceptance, humor, religion, the use of emotional support, venting and self-blame. Avoidance coping covers self-distraction, denial, substance use and behavioral disengagement [
46].
A cheek swab was collected from the study participants to determine the polymorphism within the gene for the dopamine D4 receptor gene (DRD4). Genomic DNA was isolated from nasal swabs by using the EXTRACTME swab & semen kit (Blirt, Gdansk, Poland) as per the protocol provided by the manufacturer. After evaluating the quantity and purity of the samples by measuring the ratio between absorbance at 260 nm and 280 nm on a Picodrop UV/Vis spectrophotometer, the samples were stored at −20 °C. To determine the distribution of DRD4 polymorphisms, these specific primers were designed using Primer-BLAST: forward 5′-CGTACTGTGCGGCCTCAACGA-3′, reverse 5′-GACACAGCGCCTGCGTGATGT-3′. The product length was 705 bp (base pairs) for variant 4R, 609 bp for 2R and 849 bp for 7R, and after performing a gradient melting curve to validate the primers on the MJ Mini Thermal Cycler (Bio-Rad, Hercules, CA, USA), the proper PCR reaction was performed using PCR Mix Plus HGC (A&A Biotechnology, Gdansk, Poland). Each of the reactions included 10 ng of genomic DNA, PCR-grade water and PCR Mix containing Polymerase Taq, MgCl2 and dNTPs (Deoxynucleotide Triphosphates) provided in the kit. The following thermal conditions were applied: initial denaturation at 95 °C for 180 s, followed by 40 cycles consisting of 95 °C for 25 s, 45 s of annealing at 65 °C and 45 s at 72 °C, ending with an additional 10 min of extending at 72 °C. The products were subsequently separated on 2% agarose gel stained with SimplySafe (EURx, Gdansk, Poland) dye during an hour-long electrophoresis at 100 V, preceded by 5 min at 80 V to avoid smearing. Finally, visualization was performed on ImageMaster VDS (Pharmacia Biotech, Uppsala, Sweden).
The method of obtaining genetic material from a buccal swab was chosen because it is safe, non-invasive, simple, and quick. At the same time, it is assumed that the genetic makeup is the same across the body.
A statistical analysis was performed. Categorical traits were described through integer numbers and percentages. Numerical traits were depicted by using their mean, median, standard deviation, and lower-to-upper quartile values. The Chi-squared test of independence was performed for contingency tables with the required number of observations per cell. Otherwise, Fisher’s exact test was applied. The normality of distribution of a numerical trait was assessed by using the Shapiro–Wilk W test. Levene’s test was used in order to appraise the homogeneity of variances. The Mann–Whitney test was used when data was not normally distributed to compare two independent groups. In order to compare more than two independent groups, the Kruskal–Wallis non-parametric test was used. Spearman’s rank correlation coefficient was used to measure the dependence between two not-normally distributed variables. A best subset regression model was carried out in order to test the significance of differences in normally distributed numerical traits between selected study groups, controlling for important patients’ characteristics and confounders. Binary logistic regression models were performed for dichotomous dependent variables, whereas ordinal regression models were fitted for ordinal dependent variables. A level of p < 0.05 was deemed statistically significant. All the procedures were performed by using Statistica™, release 13 (TIBCO Software Inc., Palo Alto, CA, USA).