PLOS ONE RESEARCH ARTICLE Depression, anxiety, burnout and empathy among Spanish medical students Patricia Capdevila-Gaudens1, J. Miguel Garcı́a-Abajo2, Diego Flores-Funes3, Mila Garcı́a- Barbero4, Joaquı́n Garcı́a-Estañ ID5* 1 6th Year Student at Pompeu Fabra University, Spanish Council of Medical Students (CEEM), Barcelona, Spain, 2 6th Year Student at the Autonomous University of Madrid, Spanish Council of Medical Students (CEEM), Madrid, Spain, 3 University Expert in Statistics and Specialist in General Surgery and Digestive System, Murcia Health Service, Murcia, Spain, 4 Former Chairwoman of the Spanish Society of Medical Education (SEDEM), University Miguel Hernandez, Alicante, Spain, 5 SEDEM and Center of Studies on Medical Education, University of Murcia, Murcia, Spain a1111111111 a1111111111 * jgestan@um.es a1111111111 a1111111111 a1111111111 Abstract Medical Education studies suggest that medical students experience mental distress in a proportion higher than in the rest of the population In the present study, we aimed to conduct OPEN ACCESS a nationwide analysis of the prevalence of mental health problems among medical students. The study was carried out in 2020 in all 43 medical schools in Spain, and analyzes the prev- Citation: Capdevila-Gaudens P, Garcı́a-Abajo JM, Flores-Funes D, Garcı́a-Barbero M, Garcı́a-Estañ J alence of depression, anxiety, empathy and burnout among medical students (n = 5216). To (2021) Depression, anxiety, burnout and empathy measure these variables we used the Beck Depression Inventory Test for assessing among Spanish medical students. PLoS ONE depression, the Maslach Burnout Inventory Survey for Students was used for burnout, the 16(12): e0260359. https://doi.org/10.1371/journal. State-Trait Anxiety Inventory (STAI) was used to assess anxiety state and trait and the Jef- pone.0260359 ferson Empathy Scale 12 to obtain empathy scores. In relation to depression, the data indi- Editor: Kamran Sattar, King Saud University, cate an overall prevalence of 41%, with 23.4% of participants having moderate to severe SAUDI ARABIA levels, and 10% experiencing suicidal ideation. Burnout prevalence was 37%, significantly Received: April 11, 2021 higher among 6th year than among 1st year students. Anxiety levels were consistent with Accepted: November 9, 2021 those reported previously among medical students (25%), and were higher than in the gen- Published: December 2, 2021 eral population for both trait and state anxiety. The prevalence of trait anxiety was higher Peer Review History: PLOS recognizes the among women. Empathy scores were at the top end of the scale, with the highest-scoring benefits of transparency in the peer review group (>130) containing a greater percentage of women. Similarly to those published previ- process; therefore, we enable the publication of ously for other countries, these results provide a clear picture of the mental disorders affect- all of the content of peer review and author ing Spanish medical students. Medicine is an extremely demanding degree and it is responses alongside final, published articles. The editorial history of this article is available here: important that universities and medical schools view this study as an opportunity to ensure https://doi.org/10.1371/journal.pone.0260359 conditions that help minimize mental health problems among their students. Some of the Copyright: © 2021 Capdevila-Gaudens et al. This is factors underlying these problems can be prevented by, among other things, creating an an open access article distributed under the terms environment in which mental health is openly discussed and guidance is provided. Other of the Creative Commons Attribution License, factors need to be treated medically, and medical schools and universities should therefore which permits unrestricted use, distribution, and reproduction in any medium, provided the original provide support to students in need through the medical services available within their author and source are credited. institutions. Data Availability Statement: The data underlying the results presented in the study are available at the following repository of the Universidad de PLOS ONE | https://doi.org/10.1371/journal.pone.0260359 December 2, 2021 1 / 16 PLOS ONE Depression, anxiety, burnout and empathy among Spanish medical students Murcia. https://digitum.um.es/digitum/handle/ Introduction 10201/112325. Depression is highly prevalent in our society, with an estimated 300 million people suffering Funding: The authors received no specific funding from this disease [1]. In the general population, depression also affects young people and spe- for this work. cifically medical students. Indeed, depression is the second leading cause of death among Competing interests: The authors have declared those aged between 15 and 34 years, the age range to which most medical students belong [2]. that no competing interests exist. Medicine is one of the most demanding university degree courses and mental disorders are more frequent among medical students than is generally recognized. Not only depression has been frequently found in medical students. Burnout and anxiety are also important problems frequently addressed in the medical education field. Some factors that may affect the mental health of this population include high academic work load, proximity to patients’ suffering, limited social life, poor family life, lack of sleep, and inconsistent and distant romantic rela- tionships, among others. These factors can be seen as obstacles that test medical students dur- ing their training stage, setting them apart from other university students. A recent JAMA meta-analysis [1] found that 27% of 122,356 participating medical students had depressive symptoms, a higher proportion than in the general population. This exhaustive work, which analyzed a total of 168 cross-sectional and 16 longitudinal studies from 43 different countries, also provided data about suicidal ideation (11.1%). Unfortunately, these authors were unable to include any publications focusing on medical students in Spain, due to the scarcity of stud- ies in this field. A search in PubMed (October 6, 2020) revealed 859 articles featuring the Spanish word for "depression" and 517 featuring the Spanish term for “medical students". The union of the two terms returned only one record. The same search in EBSCO Health Sciences returned only one article that measured academic stress during the exam period. A search using the popular Google engine, however, revealed several studies not published in scientific journals; all were local analyses and reported prevalence data for poor mental health (anxiety and depression) of between 25% and 47% [3–6]. This study therefore aims to conduct a nationwide analysis of the prevalence of mental health problems among medical students. The project was approved by the Spanish Council of Medical Students (CEEM) in December 2019. As the representative of all medical students in Spain, the participation of the CEEM in the project was essential, since it ensured data were collected from a significant proportion of this population. The project, called DABE (standing for Depression, Anxiety, Burnout and Empathy, the four variables analyzed), was therefore established with the aim of determining the prevalence of these mental variables among medi- cal students from all 43 medical schools in Spain. Medical training in Spain follows the so-called Bologna Scheme, with 6 years of theoretical and practical training in a medical school, comprised of two basic years (1st and 2nd), a third one also basic that includes an introduction to clinical specialities, two mainly clinical years (4th and 5th) and a final 6th year, a whole clinical practical year composed of rotations in hospi- tal services and primary care centers. In that way, medical training is usually referred as to hav- ing two cycles, a preclinical one (first three years) and a clinical cycle (last three years). Methods The DABE project was a multi-center cross-sectional study. All the procedures carried out complied with the 1964 Declaration of Helsinki [7] and were approved by the Ethics Commit- tee of the University of Murcia. The instrument used was a self-administered survey developed from a web questionnaire in Google Forms, based on a previously published questionnaire. The authors of the original questionnaire gave their explicit consent for its use [8]. The partici- pants, all medical students, were recruited through text messages sent by the Student PLOS ONE | https://doi.org/10.1371/journal.pone.0260359 December 2, 2021 2 / 16 PLOS ONE Depression, anxiety, burnout and empathy among Spanish medical students Delegation Offices in each Faculty. They also gave their informed consent before completing the survey. Participation was voluntary and anonymous, and no financial remuneration was offered. The survey was active between February 17 and March 5, 2020. At that time, we esti- mate the total number of university undergraduates studying medicine in Spain around 42,000 subjects. Questionnaire The questionnaire was divided into three parts and administered in spanish. The first part included sociodemographic and academic questions (age, year of degree course, gender, schol- arship, sexual orientation, percentage of attendance at activities and part-time or full-time job). The second part comprised the DABE variables that were the object of study. To measure these variables we used the Beck Depression Inventory Test (BDI-II), a 21-question multiple- choice instrument, one of the most used psychometric scales for assessing depression [9]. Burnout was analyzed by the Maslach Burnout Inventory Survey for Students (MBI-SS) [8, 10], a tool with 15 items [8, 10]. The State-Trait Anxiety Inventory (STAI), an instrument with 20 items [11] was used to assess anxiety state (in the moment of the test or STAI-Y1) and trait (feelings habitually, STAI-Y2). Finally, the Jefferson Empathy Scale [12] was used to obtain empathy scores The scale is made up of 20 items with scoring using a 7-points Likert scale and ten of the 20 questions are valued negatively (and rectified positively in the subsequent analy- sis), in order to reduce the effect of acquiescence when responding. The range of possible scores goes from 20 to 140 points. The highest scores are associated with a greater degree of empathy. The third part of the questionnaire focused on potential predictors, such as academic and curricular performance and some items covering recently (previous 6 months) perceived difficulties or problems with substance abuse, skills/organization, learning, relationships, health, psychological help, social support, and adverse life events. Cutoff values and ranges • Depression. For the BDI-II we used the original scoring range [9], which runs from 0 to 63. Participants are classified as having no/minimal (0–13), mild (14–19), moderate (20–28), or severe depression (29–63). • Burnout. The three dimensions of burnout, emotional exhaustion (EX), cynicism (CY) and academic inefficiency (AI) were assessed using the MBI-SS [8, 10]. According to Galán et al. [10], the lower and upper quartiles of each burnout dimension are EX = <1.2 and = >2.8; CY = <0.6 and = >2.25; and AI = <3.84 and = >5.16. In our study, high scores on the exhaustion and cynicism subscales were considered to indicate burnout. • Anxiety. The STAI scale [11] was used to identify individuals with high anxiety levels. It measures two types of anxiety–state anxiety, or anxiety about an event, and trait anxiety, or anxiety level as a personal characteristic. Higher scores are positively correlated with higher levels of anxiety. According to their scores, participants were classified as having very low (score 20–31), low (score 32–43), moderate (score 44–55), high (score 56–67), and very high (score 68–80) anxiety. A distinction was made between participants in the first two catego- ries (no anxiety) and those in the latter three (suffering from anxiety), by using p75 (75th percentile). • Empathy. It was measured using the Jefferson Empathy Scale [12], with the total empathy score being the sum of all the item scores up to a maximum possible score of 140. Higher PLOS ONE | https://doi.org/10.1371/journal.pone.0260359 December 2, 2021 3 / 16 PLOS ONE Depression, anxiety, burnout and empathy among Spanish medical students scores represent a more empathetic orientation. In our study, scores of over 130 were consid- ered indicative of high empathy (percentile 80). Psychometric properties All the tests used have been previously analyzed both in the general population and specifically in medical students, and found to have good psychometric properties. For instance, Galán et al [10] for Burnout, Tempski et al [13] for Anxiety, Silva et al [8] for Depression and both Fer- reira-Valente et al [14] and Blanco et al [15)] for Empathy. Statistical analysis First, descriptive statistics were calculated for all the variables studied, with qualitative variables being expressed in terms of absolute and relative frequency (percentages). Quantitative vari- ables were expressed as means and standard deviations, or medians and interquartile ranges (IQR), depending on whether or not they followed a normal distribution (according to the Kolmogorov-Smirnov test). Subsequently, the inferential statistics were calculated through a series of bivariate analyses designed to test all variables in accordance with gender (female or male), year of degree (1st to 6th), Burnout Traits (Yes/No), Depression (No/Mild/Moderate/ Severe), Empathy (Yes/No), Anxiety (State, Y1, Yes/No) and Anxiety (Trait, Y2, Yes/No), obtaining the Pearson’ chi square. Finally, a multivariate analysis with binary logistic regres- sion was performed for each of the main study variables, taking the main variable as the depen- dent variable (Burnout Yes/No, Depression Yes/No, Empathy Yes/No, Anxiety (State, Y1) Yes/No and Anxiety (Trait, Y2) Yes/No) and variables for which statistically significant results (p<0.05) had been found previously in the bivariate test or those with special relevance due to their relationship with the dependent variable, as independent variables. The results were expressed in terms of the odds ratio of each independent variable, with a 95% confidence inter- val. Cronbach’s alpha coefficient was also calculated as a means of determining internal consis- tency. IBM SPSS Statistics (version 24) was used for the calculations. A p-value of <0.05 was considered indicative of statistical significance. Results A total of 5,216 students completed the survey; 76.3% were women, 22.9% men, 0.5% preferred not to say and 0.3% identified themselves as “other”. The mean age (and standard deviation) of all the participants was 21.41 ± 3.44. In men, it was 21.76 ± 3.73 (IC95%, 21.6–22.0) and 21.3 ± 3.13 in women (IC95%, 21.2–21.4). Academic and sociodemographic data (Table 1) The sample was drawn from all 43 medical schools in Spain, with an average of 121.3 responses per school. In relation to degree year, the highest percentage of participants were in their 1st year (20.4%), with the percentages decreasing progressively after that. As regards the percent- age of engagement in non-compulsory teaching activities, over 67% of participants claimed to attend more than 50% of these classes, and 30% said they attended over 90% of them. The highest percentage of attendance was found in the 1st year of the degree course, with 43% attending more than 90% of the classes (data not shown). Most (85%) participants did not have a job; 32.7% had a scholarship of some kind and 67.3% did not, with this latter group (data not shown) having significantly more men (35.7%) than women (31.8%). Students from the 1st year of the degree course had the highest percentage of scholarships (43%), with this PLOS ONE | https://doi.org/10.1371/journal.pone.0260359 December 2, 2021 4 / 16 PLOS ONE Depression, anxiety, burnout and empathy among Spanish medical students Table 1. Sociodemographic and general academic data. Frequency Percentage Sex Man 1195 22,9 Woman 3979 76.3 I prefer not to say 24 0.5 Year of study 1st 1063 20.4 2nd 985 18.9 3rd 929 17.8 4th 841 16.1 5th 885 17.0 6th 513 9.8 Approximate percentage of attendance to non-compulsory classroom teaching activities <10% 530 10.2 10–25% 549 10.5 25–50% 593 11.4 50–75% 790 15.1 75–90% 1180 22.6 >90% 1574 30.2 Besides studying, do you work? No 4428 84.9 Yes, full time 61 1.2 Yes part time 727 13.9 Do you have a scholarship of any kind? No 3511 67.3 Yes 1705 32.7 Sexual orientation Heterosexual 4029 77.2 Homosexual 254 4.9 Bisexual 737 14.1 I prefer not to say 196 3.8 https://doi.org/10.1371/journal.pone.0260359.t001 figure being around 30% in subsequent years (data not shown). In relation to sexual orienta- tion, 77% identified themselves as heterosexual, 14.1% as bisexual, 4.9% as homosexual and 3.8% preferred not to answer. The percentage of those identifying themselves as homosexual was significantly higher in men (14.6%) than in women (1.9%), whereas the percentage of women who identified themselves as bisexual was significantly higher (14.6% as compared to 11.4% among men). These last data are not shown. Perceived mental health (Table 2) 1. Depression: The mean value was 13.46 ± 10.61, with a 95% CI from 13.17 to 13.75. A total of 41% of students reported some symptoms of depression and the percentage of women was significantly higher (43.1%) than that of men (33.6%). Moreover, 17.6% were found to have mild depression, 13.2% moderate depression and 10.2% severe depression, with all percentages being higher among women. In relation to question 9 of Beck’s test (suicidal ideation), 89% claimed not to have had ideas about harming themselves, although the rest (11%) did acknowledge suicidal ideation to varying degrees. 2. Anxiety: 24.7% of students had high anxiety at the time of the survey (state), while 21.5% had high levels of anxiety on a regular basis (trait). The percentage of women with trait anx- iety was significantly higher than that of men. No significant differences were observed between students in different years of their degree course. PLOS ONE | https://doi.org/10.1371/journal.pone.0260359 December 2, 2021 5 / 16 PLOS ONE Depression, anxiety, burnout and empathy among Spanish medical students Table 2. Percentages of DABE variables in men and women. Men DEPRESSION No/Minimal Mild Moderate Severe 1st 72,07 % 13,06 % 8,11 % 6,76 % 2nd 68,32 % 13,86 % 10,89 % 6,93 % 3rd 63,72 % 15,81 % 10,70 % 9,77 % 4th 60,48 % 16,67 % 12,38 % 10,48 % 5th 63,59 % 18,89 % 9,22 % 8,29 % 6th 72,09 % 10,85 % 8,53 % 8,53 % Mean 66,36 % 15,15 % 10,04 % 8,45 % Women DEPRESSION No/Minimal Mild Moderate Severe 1st 63,23 % 15,57 % 12,46 % 8,74 % 2nd 53,85 % 18,46 % 14,23 % 13,46 % 3rd 51,84 % 19,12 % 17,28 % 11,76 % 4th 55,04 % 17,76 % 16,64 % 10,56 % 5th 58,75 % 19,48 % 11,87 % 9,89 % 6th 58,78 % 21,81 % 11,97 % 7,45 % Mean 56,92 % 18,35 % 14,17 % 10,56 % ANXIETY state All Men Women 1st 26,90 % 27,48 % 26,71 % 2nd 25,79 % 27,72 % 25,26 % 3rd 25,62 % 20,00 % 26,91 % 4th 22,71 % 23,33 % 22,40 % 5th 21,92 % 19,35 % 22,83 % 6th 24,56 % 23,26 % 25,27 % Mean 24,71 % 23,51 % 25,01 % ANXIETY trait All Men Women 1st 21,54 % 18,47 % 22,51 % 2nd 22,03 % 18,81 % 22,82 % 3rd 23,90 % 19,53 % 24,93 % 4th 20,21 % 16,19 % 21,76 % 5th 21,02 % 16,59 % 22,37 % 6th 19,30 % 13,18 % 21,28 % Mean 21,53 % 17,41 % 22,74 % BURNOUT All Men Women 1st 22,58 % 22,52 % 22,40 % 2nd 35,23 % 29,70 % 36,67 % 3rd 38,21 % 34,42 % 39,38 % 4th 39,60 % 36,67 % 40,48 % 5th 46,67 % 48,85 % 46,12 % 6th 44,83 % 40,31 % 46,28 % Mean 36,77 % 35,06 % 37,22 % EMPATHY All Men Women 1st 14,02 % 13,51 % 14,13 % 2nd 15,33 % 7,92 % 17,31 % 3rd 20,02 % 11,16 % 22,80 % 4th 19,98 % 12,86 % 22,56 % 5th 22,03 % 14,29 % 24,51 % (Continued ) PLOS ONE | https://doi.org/10.1371/journal.pone.0260359 December 2, 2021 6 / 16 PLOS ONE Depression, anxiety, burnout and empathy among Spanish medical students Table 2. (Continued) 6th 26,12 % 23,26 % 27,66 % Mean 18,85 % 13,22 % 20,61 % https://doi.org/10.1371/journal.pone.0260359.t002 3. Burnout: 36.8% of participants had high burnout, defined as high scores for two of its com- ponents (exhaustion and cynicism). No differences were observed between men and women. The percentage of high burnout increased progressively from 1st (23%) to 6th (45%) year. 4. Empathy: The mean numerical value for this variable was 120.6 ± 11.8 points (maximum 140), with 18.8% of participants having high levels of empathy (>130). The percentage of women was significantly higher than that of men, and percentages increased progressively year by year (from 14% in the 1st to 26% in the 6th year of the course). Bivariant analysis between mental variables (Table 3) Depression was significantly related to anxiety trait, burnout and empathy, so that individuals having signs of depression had greater levels of anxiety trait and burnout but lower empathy levels. Having anxiety state was related only to high anxiety trait. High anxiety trait was signifi- cantly associated with depression, anxiety state and burnout, thus individuals with high anxi- ety trait had greater levels of these three variables. Burnout was significantly associated with both depression and anxiety trait, whereas empathy was significantly related only to depres- sion, so that high empathic individuals showed lower depression signs. Potential risk predictors (Table 4) The main problem or difficulty perceived by medical students was how to organize academic work (time management), with the percentage of women being significantly higher than that of men (77% vs. 70%). Academic performance problems varied across the years of the degree course, with peaks among students in their 2nd, 3rd and 4th years. In relation to events that had occurred over the past 6 months, 25% of participants mentioned someone important to them having had a serious illness or accident, with no differences observed in this sense between men and women. Moreover, 21.7% mentioned financial problems, 17% the end of a stable Table 3. Association between variables. DEPRESSION HIGH ANXIETY STATE HIGH ANXIETY TRAIT HIGH BURNOUT HIGH EMPATHY NO YES Chi2 p NO YES Chi2 p NO YES Chi2 p NO YES Chi2 p NO YES Chi2 p level level level level level Depression Yes - - - 1623– 518– 0.469 1514– 627– 0.000 809– 1332– 0.000 1783– 358– 0.001 41.3% 40.2% 37.0% 55.8% 24.5% 69.4% 42.1% 36.4% Anxiety High 771– 518– 0.469 745– 544– 0.000 824– 465– 0.55 1047– 242– 0.94 (State) 25.1% 24.2% 18.2% 48.4% 25.0% 24.2% 24.7% 24.6% Anxiety High 496– 627– 0.000 579– 544– 0.000 614– 509– 0.000 910– 213– 0.907 (Trait) 16.1% 29.3% 14.7% 42.2% 18.6% 26,5% 21.5% 21.7% Burnout High 586– 1332– 0.000 1453– 465– 0.55 1409– 509– 0.000 1561– 357– 0.743 19.1% 62.2% 37.0% 36.1% 34.4% 45.3% 36.9% 36.3% Empathy Yes 625– 358– 0.001 741– 242– 0.94 770– 213– .907 626– 357– 0.743 20.3% 16.7% 18.9% 18.8% 18.8% 19.0% 19.0% 18.6% Data are number and percentage. https://doi.org/10.1371/journal.pone.0260359.t003 PLOS ONE | https://doi.org/10.1371/journal.pone.0260359 December 2, 2021 7 / 16 PLOS ONE Depression, anxiety, burnout and empathy among Spanish medical students Table 4. Predictive factors. Frequency Percentage Problems or difficulties encountered Academic time management 3938 75.5% Academic performance 3250 62.3% Physical health 2935 56.3% Task organization 2535 48.6% Money management 1759 33.7% Family relationships 1596 30.6% Colleagues relationships 1533 29.4% Partner relationships 1207 23.1% Death of a family member 846 16.2% Tobacco abuse 361 6.9% Teachers relationship 304 5.8% Alcohol abuse 242 4.6% List of events Serious illness or accident in someone 1309 25.1% close to me Economic problems 1131 21.7% End of a stable love relationship 896 17.2% Serious illness or accident of mine 506 9.7% Abuse of other drugs 100 1.9% Social support 1. How many people are you close enough to if you experience serious >5 2122 40.7% personal problems? 3–5 2079 39.9% 1o2 948 18.2% None 67 1.3% Social support 2. What is your interest and participation in your everyday experiences? Much 1963 37.6% Something 1849 35.4% I don’t know 868 16.6% Little 483 9.3% None 53 1.0% Social support 3. How satisfied are you with the social activities you currently participate Much 1815 34.8% in? Something 1878 36.0% I don’t know 483 9.3% Little 858 16.4% None 182 3.5% Social support 4, At this moment, how satisfied are you with the support you receive from Much 2407 46.1% your social relationships? Something 1575 30.2% I don’t know 493 9.5% Little 601 11.5% None 140 2.7% Academic performance 1. Academic classification in relation to the effort made in the Lower than the effort made 2528 48.5% course Concordant effort 2390 45.8% Greater than the effort made 298 5.7% Academic performance 2. Satisfaction with academic grades at this time Very much satisfied 493 9.5% Satisfied 2214 42.4% Little satisfied 1810 34.7% No satisfied 699 13.4% (Continued ) PLOS ONE | https://doi.org/10.1371/journal.pone.0260359 December 2, 2021 8 / 16 PLOS ONE Depression, anxiety, burnout and empathy among Spanish medical students Table 4. (Continued) Frequency Percentage Academic performance 3. Level of satisfaction of your parents with your academic Very much satisfied 2422 46.4% performance Satisfied 1915 36.7% Little satisfied 638 12.2% No satisfied 241 4.6% Tobacco smoker Yes 407 7.8% No 4392 84.2% Ocassional 417 8.0% Cannabis smoker No, never 3135 60.1% I have tried 1782 34.2% Ocassionally, < = 1 per week 227 4.4% Habitually, 2 or more times per week 68 1.3% Alcohol Never 829 15.9% 1 or less a month 1762 33.8% 2–4 a month 1984 38.0% 2 a week 526 10.1% More than 3 a week 115 2.2% Psychopharmaceuticals Yes 1063 20.4% No 4153 79.6% Tranquilizers / Anxiolytics 851 16.3% Mood stabilizers 28 0.5% Antidepressants 532 10.2% Neuroleptics / antipsychotics 57 1.1% Other 121 2.3% https://doi.org/10.1371/journal.pone.0260359.t004 romantic relationship and 16% the death of a family member. Just under 10% mentioned hav- ing had a serious personal illness or accident (9.7%). In relation to social support, almost 80% said they had more than 3 people they could count on if they had serious personal problems, with no differences being observed between men and women. The percentage of students with more than 5 people they could count on increased the further along on their degree course they were. In terms of interest and participation in daily experiences, almost 10% claimed to have little or no interest, with this percentage being significantly lower among women. One fifth (20%) reported gaining little or no satisfaction from the social activities in which they participated and 13% reported receiving little or no support from their social relationships, with no differ- ences being observed between men and women in these last two cases. As for academic performance, almost 50% of students claimed to have grades that were lower than they had expected given the effort made, and considered themselves to be little or not at all satisfied with their current academic performance. Drugs and substance abuse (Table 4) Of the sample, 16% said they smoked, with this percentage being higher among men (20%) than among women (14%), and increasing as students progressed through their degree. As regards cannabis, 60% claimed never to have tried it and 1.3% said they used it habitually, with this percentage being higher among men than in women and also increasing over time (data not shown). Just over a tenth of all participants (12%) reported consuming alcohol two or more times per week, with this percentage again being higher among men (18%) than among PLOS ONE | https://doi.org/10.1371/journal.pone.0260359 December 2, 2021 9 / 16 PLOS ONE Depression, anxiety, burnout and empathy among Spanish medical students Table 5. Risk factors for depression. DEPRESSION P value Odds Ratio I.C. 95% for Odds Ratio Lower Upper Low interest and participation in daily activities <0.001 5.115 3.836 6.819 High Burnout <0.001 3.739 3.207 4.359 Physical health problems <0.001 2.673 2.292 3.116 Low satisfaction with academic grades <0.001 2.208 1.896 2.571 Take psychotropic drugs <0.001 2.185 1.819 2.624 Problems of relationship with colleagues <0.001 2.097 1.785 2.463 Academic performance problems <0.001 1.994 1.683 2.362 Problems of relationship with family <0.001 1.921 1.637 2.253 High Anxiety (Trait) <0.001 1.780 1.472 2.153 Problems of relationship with partner <0.001 1.767 1.485 2.102 Being woman <0.001 1.561 1.295 1.882 Academic homework organization problems <0.001 1.469 1.263 1.708 Homo-bisexual orientation <0.001 1.442 1.212 1.716 Habitual tobacco use 0.011 1.300 1.062 1.592 Academic work organization problems 0.024 1.241 1.029 1.496 Academic homework organization problems <0.001 1.469 1.263 1.708 4th-6th year 0.004 .797 .684 .928 https://doi.org/10.1371/journal.pone.0260359.t005 women (10%). One fifth (20%) of participants reported taking psychotropic drugs, mainly anxiolytics (16.3%) and antidepressants (10.2%). Women took more psychotropic drugs (21%) than men (16%) and those in later years of the degree course took more than their counter- parts in earlier ones, with the percentage increasing from 13% in the 1st to 23% in the 6th year of the course in relation to anxiolytics, and from 7% to 12% in relation to antidepressants. Multivariable relationships between DABE variables and risk predictors Tables 5 to 8 show the strength of association among the DABE variables and between them and the risk factors studied. Only factors found to be significant are included. In the case of depression (Table 5), low interest and participation in daily activities were the main risk factors Table 6. Risk factors for burnout. BURNOUT P value Odds Ratio I.C. 95% for Odds Ratio Lower Upper Depression symptoms <0.001 3.770 3.242 4.385 Problems of academic performance <0.001 2.163 1.851 2.528 4th-6th year <0.001 1.895 1.653 2.173 Academic satisfacción lower to effort <0.001 1.713 1.496 1.961 Low satisfaction with social activities <0.001 1.667 1.411 1.969 Taking psychopharmaceuticals <0.001 1.431 1.217 1.682 Academic homework organization problems <0.001 1.387 1.167 1.649 Physical health problems 0.001 1.292 1.117 1.494 Homo-bisexual orientation 0.004 1.259 1.078 1.469 High Anxiety (Trait) 0.034 1.206 1.014 1.435 Problems of relationship with family 0.026 1.181 1.020 1.366 Assistance to no compulsory activities >50% 0.001 0.785 0.682 0.904 https://doi.org/10.1371/journal.pone.0260359.t006 PLOS ONE | https://doi.org/10.1371/journal.pone.0260359 December 2, 2021 10 / 16 PLOS ONE Depression, anxiety, burnout and empathy among Spanish medical students Table 7. Risk factors for anxiety. ANXIETY-STATE P value Odds Ratio I.C. 95% for Odds Ratio Lower Upper High Anxiety Trait <0.001 6.621 5.322 8.238 Work in addition to studying 0.002 1.540 1.166 2.033 Money management problems 0.026 1.290 1.031 1.614 4th-6th year 0.004 0.721 0.575 0.903 Low social support 3 <0.001 0.551 0.404 0.752 ANXIETY-TRAIT P value Odds Ratio I.C. 95% for Odds Ratio Lower Upper High Anxiety State <0.001 6.748 5.395 8.441 Depression symptoms <0.001 1.737 1.432 2.106 https://doi.org/10.1371/journal.pone.0260359.t007 (associated with a five-fold risk of having depressive symptoms, with a range of 3.8 to 6.8), fol- lowed by high burnout and physical health problems, to cite only the first three. The odds ratio for burnout (Table 6) again revealed an association with depression (odds ratio of 4), with aca- demic performance problems and engaging in clinical rotations being the following two most important factors. The odds ratio values for anxiety (Table 7) indicated that both types, trait and state, were closely related to each other, as well as to working while studying and having financial problems. Finally, as shown in Table 8, empathy was closely associated with being a woman, engaging in clinical rotations and having a high level of social support. Discussion In this study, which was carried out in 2020 in all 43 medical schools in Spain, we analyze the prevalence of depression, anxiety, empathy and burnout among medical students, in the first nationwide analysis of these mental health variables in this particular population. Although previous studies in this field have reported findings from some isolated university centers [3– 6], ours is the first to offer global data from across the entire country. Moreover, the sample (5,216 participants) is large enough to endow the data presented here with a high degree of reliability, thereby enabling conclusions to be drawn. At present, the total number of university undergraduates studying medicine in Spain is close to 42,000, since around 7,000 freshmen began their studies in September 2019 [16]. This means that our sample represents around 12% of the total number of medical students in Spain. It is also important to highlight the fact that the survey, which was carried out at the beginning of the second semester, includes responses from students studying at all 43 medical schools operating at that time in Spain. We therefore believe that the number of participants may reflect the true situation of the problem in Spain medical training. In relation to depression symptoms, the data indicate an overall prevalence of 41%, with the figure for moderate and severe depression being 23.4%. These findings are similar to those reported in the local studies cited above, being slightly lower than the figure reported for 4th Table 8. Risk factors for empathy. EMPATHY P value Odds Ratio I.C. 95% for Odds Ratio Lower Upper Being woman <0.001 1.726 1.435 2.077 4th-6th year <0.001 1.503 1.306 1.730 High social support 3 <0.001 1.430 1.106 1.847 https://doi.org/10.1371/journal.pone.0260359.t008 PLOS ONE | https://doi.org/10.1371/journal.pone.0260359 December 2, 2021 11 / 16 PLOS ONE Depression, anxiety, burnout and empathy among Spanish medical students year students at Catalonian medical schools (47%) [3] and practically identical to those found at the Universities of Murcia and Valencia [4–6]. In all these studies, as in the present work, depression was found to be more prevalent among women than among men. This is consistent also with the data reported in practically all international studies carried out on this topic [1]. Our results for depression symptoms are also consistent with those published recently in rela- tion to some Italian medical schools, as well as with the findings of systematic reviews in both Europe and worldwide [17–19]. We can therefore conclude that Spanish medical students behave similarly to their counterparts in other countries, indicating a certain degree of con- stancy in terms of problems or inductive factors throughout university centers worldwide. Our findings are also consistent with previous research reporting that the prevalence of depression symptoms is higher among medical students than in the general population, and also higher among women. For instance, in Spain, according to data from the 2017 National Health Sur- vey [20], depression is more than twice as prevalent among women in the general population (9.2%) than among men (4%). In relation to the prevalence of depression symptoms among university students from disciplines other than medicine, the data are inconclusive [21], with percentages being either similar or lower [22]. Two of the most important factors associated with depression in our study were health issues and dissatisfaction with academic perfor- mance, which may well be the cause of the problem, while others such as lack of interest and participation in daily activities and consumption of psychotropic drugs may be its consequences. One important finding in relation to the study of depression is the percentage of suicidal ideation found among Spanish medical students, in relation to which our results are consistent with those published previously [1, 3–6]. As stated earlier, around 10% of medical students admit to having engaged in suicidal ideation, a figure that indicates an urgent need to establish preventive measures and improve students’ access to advice, care and treatment to help them overcome this problem. Unfortunately, there are around 3,500 suicides every year in Spain (3,539 in 2018), of which 7% are young people between the ages of 15 and 29 [23]. However, no data is available on specific suicide rates among university students [24], although higher suicide rates have been reported among physicians than among the general population (1.3% as opposed to 0.8%) [25]. Regarding burnout, our data are consistent with those found among 3rd and 6th year medi- cal students from a Spanish university [6], among which burnout risk was significantly more prevalent among 6th year students (37.5%) than among those in their 3rd year of training (14.8%), with no association being found between burnout and gender. In our study, burnout scores increased after the 1st year of the medical degree, with the highest scores being found in the 5th year. However, the means were very similar (around 35%), suggesting that the preva- lence of burnout among medical students is fairly similar to that found among medical resi- dents and practicing physicians [26, 27]. We identified several factors that may contribute to burnout among medical students, including curricular factors, personal life events, and the learning environment [14, 28, 29]; and burnout in turn may have serious consequences, lead- ing to unprofessional conduct, increased risk of suicidal ideation, and serious thoughts of dropping out of medical school. However, some authors have suggested that burnout among medical students may be reversible, with 26% of sufferers recovering within a year [28]. We therefore believe it is vital to identify and treat students suffering from this syndrome before they begin their medical residencies. In relation to empathy, the scores obtained by our sample were at the upper end of the scale [12, 15] and the mean value observed is consistent with that reported by previous studies both in Spain and abroad [15, 30–33], and even slightly higher than in some. As stated in the Results section, women scored higher than men, as did those engaging in clinical rotations and those PLOS ONE | https://doi.org/10.1371/journal.pone.0260359 December 2, 2021 12 / 16 PLOS ONE Depression, anxiety, burnout and empathy among Spanish medical students with strong social support, as indeed has been reported previously by other authors [34, 35]. It therefore appears that empathy levels increase over time and specially when students enter into contact with patients during their clinical rotations [36, 37]. The anxiety levels found in our study are consistent with the values reported previously [7, 11] among medical students, and are higher than in the general population in both categories or scales (trait and state). Furthermore, the greater prevalence of trait anxiety among women observed in our results has been also reported previously [11, 38, 39]. In relation to risk factors, the two categories were closely related to each other, and state anxiety particularly was very fre- quent among students who worked while studying, as well as among those experiencing finan- cial difficulties. Finally, although no statistical differences were observed between students on different years of the degree course, those engaging in clinical rotations did seem to be some- what protected against state anxiety, probably because they were better able to cope with medi- cal school activities. Strengths and limitations The nationwide nature of the study design is a factor that speaks to the generalizability of our results; however, although the number of responses was high, not all the results will be applica- ble to each and every university, since the response rate varied widely across centers (from 0.2% to 5.8% of the total number of responses). The use of a self-administered instrument rather than structured clinical interviews may also be a limitation, since although used in many studies, depression scores may not accurately reflect the severity of depression. However, since it was not possible to perform a clinical evaluation of all medical students in Spain, we believe that the approach adopted provides a clear picture of something that is often com- mented on by students themselves, and which may lead to stigmatization [40]. It is also possi- ble that students who were especially sensitive to these issues or were aware of having these problems were more predisposed to complete the survey than others. The moment at which surveys are launched may also be a confounding factor. We therefore decided to start the sur- vey at the beginning of the second semester (which usually commences during the last week of January in most Spanish universities), once all the first semester examinations had finished and students had no responsibilities other than attending theoretical classes or practical and hospital rotations. Also, we only captured individual constructs, whereas institutional con- structs that may also contribute were not analysed. Finally, it is important to emphasize that the instruments used in the present study are not diagnostic but of a screening nature. Finally, the sampling procedure was non probabilistic, since participation was offered to everyone but only those who wanted participated. Conclusions In the present study, we report the prevalence of depression, anxiety, burnout and empathy among students from all the medical schools in Spain. The results, which are similar to those already published in relation to other countries, provide a clear picture of the mental disorders affecting Spanish medical students. Medicine is an extremely demanding degree and it is important that universities and medical schools view this study as an opportunity to ensure conditions that help minimize mental health problems among their students. Some of the fac- tors underlying these problems can be prevented by, among other things, creating an environ- ment in which mental health is openly discussed and guidance is provided. Other factors need to be treated medically, and medical schools and universities should therefore provide support to students in need through the medical services available within their institutions. PLOS ONE | https://doi.org/10.1371/journal.pone.0260359 December 2, 2021 13 / 16 PLOS ONE Depression, anxiety, burnout and empathy among Spanish medical students Acknowledgments The authors wish to thank the following students for helping them with the survey: Sònia Ser- rabou Pradas, Universidad Autónoma de Barcelona; Jorge Monzón Moya, Universidad de Alcalá de Henares; Lucı́a Martı́n López, Universidad Autónoma de Madrid; Ignacio Coll Orduña; Universidad Alfonso X El Sabio; Alba Arbués Martı́, Universidad de Barcelona- Bell- vitge; Mar Niella Bellot, Universidad de Barcelona-Clinic; Marı́a Sası́a, Universidad de Canta- bria; Ángel Francisco Serrano Andrades, Universidad de Cádiz; Ander Santiago Gómez, Universidad CEU Cardenal Herrera–Castelló; Sara Ivars Bernal, Universidad CEU Cardenal Herrera- Valencia; Laura Sindı́n, Universidad San Pablo C.E.U.; Juan Fco Vázquez Rodrı́guez, Universidad de Castilla La Mancha-Ciudad Real; Beatriz Jarabo Tévar, Universidad de Castilla La Mancha-Albacete; Jorge Mesa Guadalupe, Universidad Complutense de Madrid; Jesús Canales Fernández, Universidad de Córdoba; Alba Marı́a Torrat Novés, Universidad Católica de Valencia S. Vicente M.; Maria Molina Guerrero, Universidad de Girona; Alysson Micolta, Universidad Europea de Madrid; Clara Hoyas Sánchez, Universidad de Extremadura; Daniela Rocca Flores, Universidad Francisco de Vitoria; Araceli Jiménez Lara, Universidad de Gra- nada; Yeray Damas Pons, Universitat de las Illes Balears; Marc Vallés Alabart, Universidad Internacional de Cataluña; Chourok Aknin, Universitat Jaume I de Castellón; Iriana Rodrı́guez Hernández, Universidad La Laguna; Rosa Maria Navarro Lopez, Universidad de Murcia; Yosef Benzaquen Aserraf, Universidad de Málaga; Laura Sánchez Sánchez, Universidad Miguel Hernández de Elche; Alberto Lorenzo Longedo, Universidad de Oviedo; Patricia Cap- devila, Universitat Pompeu Fabra; Rodrigo Guitian Montes, Universidad del Paı́s Vasco; Lucas Antigono, Universidad Rey Juan Carlos; Bruno Fernández Cuevas, Universidad de Sevilla; Gloria Corbacho Hernández, Universidad de Salamanca; Candela Fernández Reino, Universi- dad de Santiago de Compostela; Jesús Andicoberry López, Universitat de València; Mateo Jiménez Garcı́a, Universidad de Valladolid; Ana Garcı́a Blasco, Universidad de Zaragoza; Mar Garcı́a Bellas, Universidad las Palmas de Gran Canaria; Jose Carte Garcı́a, Universidad de Navarra. We also thank Diana Draper for correcting the english manuscript. Author Contributions Conceptualization: Patricia Capdevila-Gaudens, J. Miguel Garcı́a-Abajo, Mila Garcı́a-Bar- bero, Joaquı́n Garcı́a-Estañ. Data curation: Diego Flores-Funes, Joaquı́n Garcı́a-Estañ. Formal analysis: Joaquı́n Garcı́a-Estañ. Investigation: J. Miguel Garcı́a-Abajo, Diego Flores-Funes, Joaquı́n Garcı́a-Estañ. Methodology: Patricia Capdevila-Gaudens, Diego Flores-Funes, Joaquı́n Garcı́a-Estañ. Project administration: Patricia Capdevila-Gaudens, Mila Garcı́a-Barbero, Joaquı́n Garcı́a- Estañ. Resources: J. Miguel Garcı́a-Abajo, Diego Flores-Funes. Software: Diego Flores-Funes. Supervision: Patricia Capdevila-Gaudens, Mila Garcı́a-Barbero, Joaquı́n Garcı́a-Estañ. Validation: Mila Garcı́a-Barbero. Writing – review & editing: Patricia Capdevila-Gaudens, J. Miguel Garcı́a-Abajo, Diego Flo- res-Funes, Mila Garcı́a-Barbero, Joaquı́n Garcı́a-Estañ. 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