Oxidative stress and psychological functioning among medical students.

BACKGROUND: Oxidative stress has gained attention recently in behavioral medicine and has been reported to be associated with various psychological disturbances and their prognoses.
OBJECTIVES: Study aims to evaluate the oxidative stress (malonylaldehyde (MDA) levels) and its relation with psychological factors (dimensions of personality, levels of anxiety, stress, and depression) among medical/paramedical students of 1(st) and 3(rd) year).
MATERIALS AND METHODS: A total of 150 students; 75 from 1(st) year (2010-2011) and75 from 3(rd) year (2009-2010); of medical and paramedical background were assessed on level of MDA (oxidative stress) and personality variables, that is, level of anxiety, stress, and depression. These psychological variables were correlated with the level of their oxidative stress.
RESULTS: Findings revealed that both groups are influenced by oxidative stress and their psychological variables are also compatible in order to confirm their vulnerabilities to stress.
CONCLUSIONS: Stress in 3(rd) year students was significantly higher and it was noted that it adversely affects the psychological parameters. Hence, special attention on mental health aspect in these students may be given.

Medical students are continuously exposed to psychosocial stressors during their training, if persistent, can lead to variety of pathologies in terms of biological, physiological, and psychological imbalances. Researchers like; Matsushita et al.,[1] concluded that neurotic and anxious students tend to be exposed to oxidative stress more. Matsushita et al.,[1] concluded that neurotic and anxious students tend to be exposed to oxidative stress more. Aguiar et al.,[2] and Benevides and Goncalves[3] have described stressful moments in the academic life of medical students and medical training are considered to carry high psychobiological toxicity factors that contribute to significant stress among students in medical schools, oxidative stress is one of them. Now the question is what is oxidative stress? Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive normal redox state can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and nucleic acids. In humans, oxidative stress is involved in many diseases, such as atherosclerosis, Parkinsonism, myocardial infarction (MI), Alzheimer´ sdisease, fragile Xsyndrome, and chronic fatigue syndrome; but short-term oxidative stress may also be important in prevention of aging. Oxidative stress contains large numbers of free radicals that are capable of initiating or promoting oxidative injury. Oxidative stress have higher lipid peroxidation products (malonylaldehyde (MDA)) in their blood than do normal person and hypertension increases the concentration of serum MDA levels; Jeeyar et al.[4] It is suggested that oxidative injury may play a major role in mediating the health risks associated with oxidative stress. On the contrary, psychological stressors like anxiety, depression, adjustment difficulties, and various psychological conditions are found to be directly correlated with oxidative stress which means these are encouraging agent for said stress. If these psychological stressors are coordinating with oxidative stress, an individual reflects major risk factors for cardiovascular disease, obesity, diabetes mellitus, and hyperlipidemia. Hence, MDA was selected as marker for oxidative stress in this work, as in many studies psychological stressors were positively linked to oxidative stress and the subjects were showing a high correlation with cardiovascular diseases; Wilhelm et al.[5]

As we know that oxidative stress has gained attention recently in psychiatric medicine and is reported to be associated with various diseases. The determinants of oxidative stress are regulated by an individual's unique hereditary factors, as well as his/her environment and characteristic lifestyle. Unfortunately, under the present day lifestyle conditions many people run an abnormally high level of oxidative stress that could increase their probability of early incidence of decline in optimum body functions.

Its effects include adaptation difficulties at the beginning of coursework due to competitive entrance examinations, leaving school for the realities of greater autonomy and responsibility, and the frustration caused by various expectations are to be desired in specific medical disciplines. In addition to this earning of better marks; peer pressure, popularity, domination in group specially who come from very high strata and are able to dominate over others, increased materialism, friendship and emotional bonding with opposite sex friends, parties-late night, and drug abuse and alcoholism.

Psychological stress is associated with increased oxidative stress, pro-inflammatory state, increased rate of infection, and cardiovascular disease. Oxidative stress increases the imbalances in overall way and it is assumed that oxidative stress due to dysfunction of oxidative and antioxidative systems might cause various disorders and diseases, including psychiatric illness, like anxiety, neuroticism (N), and various adjustment disorders. The toxic effects of reactive oxygen species, resulting in oxidative stress has been associated with psychological stress. In a cross-sectional study by Alan Rozanski et al.,[6] in nonsmoking college students revealed that oxidative stress was positively associated with the level of anxiety in female students and provided preliminary evidence that anxiety may play a role in vulnerability to oxidative damage among female adolescents. College students often experience negative emotions, such as depressive moods or feelings of anxiety, which could lead to poor health or absenteeism from the classroom. In addition to these aspects, personality traits inherent to medical students include obsessions, perfectionism, and self-exigency; Tarnowski and Carlotto.[7] These factors are potentially responsible for the high prevalence of suicide, depression, use of psychoactive substances, adjustment problems, stress, burnout, and professional dysfunction in doctors and medical students; Dyrbye et al.,[8] and Voltmer et al.[9]

In addition to negative emotions, the manner of coping with difficulties that are encountered might be defined by specific personality traits. Their results showed a significant and positive association between the personality trait of N and oxidative damage in the different medical female students. In contrast, there has been a positive correlation between the antioxidant potential and the level of anxiety in male subjects. Among the female participants, there was a significant association between anxiety and oxidants. Their results suggest that anxious or neurotic female students tend to be exposed to oxidative damage. From a long-range viewpoint it was also suggested that these traits might carry a substantial health risk.

In a study “Oxidative stress and psychological function in non-psychiatric patients with metabolic syndrome” by Mimoglou et al.,[10] concluded that oxidative stress was correlated with alexithymic features in patients with metabolic syndrome. Recent studies provide clear and convincing evidence that psychosocial factors contribute significantly to the pathogenesis and expression of coronary artery disease (CAD). This evidence is composed largely of data relating CAD risk to five specific psychosocial domains: (i) Depression, (ii) anxiety, (iii) personality factors and character traits, (iv) social isolation, and (v) chronic life stress.

Pathophysiological mechanisms underlying the relationship between these entities and CAD can be divided into behavioral mechanisms, whereby psychosocial conditions contribute to a higher frequency of adverse health behaviors, such as poor diet and smoking, and direct pathophysiological mechanisms, such as neuroendocrine and platelet activation.

Rozhanets et al.,[11] in their study titled “Psychological correlates of different arterial pressure levels” have showed a relationship between the blood pressure levels and different degree of sociopsychological maladjustment. In subjects with elevated pressure, there was a higher occurrence of conflicts in fundamental life spheres, the presence of emotional tension, and intrapersonal problems. Hapuarachchi et al.,[12] found psychological stress is associated with increased oxidative stress. Conversely, positive or low stress parameters, indicating good life skill mechanisms. Psychological well-being and stress are correlated with biochemical parameters both positively and negatively in relation to immunity and cardiovascular disease processes. Even ego stress tolerance can be protective for the cells. Oxidative stress contains large numbers of free radicals that are capable of initiating or promoting oxidative injury. Oxidative stress have higher lipid peroxidation products in their blood than do normal person and hypertension increases the concentration of serum MDA levels; Jeeyar et al.[4] It is suggested that oxidative injury may play a major role in mediating the health risks associated with oxidative stress. There is a positive relationship between work-related factors including physiological, psychological stress, and the formation of oxidative stress. In order to examine their possible risk factors for occupational hazards, they studied the entire routine of male and female participant in terms of working hour, work load, fatigue, sleep patterns, and psychological stress; and they concluded that psychological stress and perceived over work were related to psychopathology; Masahiro Kawahara et al.[13] Psychological stress was positively linked to oxidative stress and the subjects were showing a high correlation with cardiovascular disease; Wilhelm et al.[5] In present project, we have taken medical and paramedical students from 1st and 3rd year in order to study stress and personality dimensions in relation to oxidative stress.

The transition from the introductory clinical cycle to the clerkship cycle presents another occasion for intense anxiety, uncertainty, expectations, and fears caused by: Their feeling of limitations regarding the scientific knowledge, their changes from one stage to another, and direct contact with seriously ill people who have hopeless prognoses (may be they start identifying with such patients).

The excessive workload and educational content, combined with high level of educational demands, a lack of time for leisure, family and friends, studying for residency exams, choice of a specialty, and delayed income also contribute to stress among medical students. That is why an effort has been made to correlate personality variables with MAD, a marker of oxidant levels, in order to check their well-being.

MATERIALS AND METHODS

Present study comprised of medical and paramedical students of 1st and 3rd year batches in order to study various personality variables and their level of oxidative stress (serum MDA levels) as it is a tested assumption that medical science is very stressing biologically as well psychologically. Besides it was also assumed that there can be some personality structure might be working either as contributory for psychological disturbances or to coping mechanism.

The present study was undertaken in Santosh Medical College (Santosh Deemed University), Ghaziabad, UP and it was approved by institutional ethics committee. Study participants signed an informed consent. This study is a collaborative effort of Department of Clinical Psychology and Biochemistry during the period 2008–2011.

Total sample size for study comprised of 150 students, of medical (Bachelor of Medicine and Bachelor of Surgery (MBBS)) and paramedical group (General Nursing Midwife (GNM)) (75 from 1st* year and 75 from 3rd** year) of medical college. Each batch had 100 students from which either 37/38 students aged between 18 and 24 years were selected. But sex-wise matching was not possible as number of students in each batch was not equal; therefore, it was a random procedure to select the students considering the policy of unbiased selection [Table 1].

Table 1

Group Distribution Of Medical & aramedical Students Of 1St Year & 3Rd Year Students.

Tools

This study has followed two types of investigations:

Biochemical

Psychological.

Biochemical investigations

Estimation of lipid peroxidation

The levels of byproduct of lipid peroxidation, MDA were estimated by the modified method of Satoh.[14] This assay is based up on their action of thiobarbituricacid (TBA) with MDA, one of the aldehyde products of lipid peroxidation.

0.5 ml of serum was mixed with a reagent containing 20% TCA centrifuged at 3,500 rpm for 10 min. The precipitate was washed with 2 ml of 0.05 M H2SO4 and centrifuged at 3,500 rpm for 10 min. Three milliliter of TBA was added and the tubes were kept in boiling water bath for 30 min and cooled under tap water. Four milliliter n-butanol was mixed by vigorous shaking or vortex for 5–10 min. Centrifuged at 3,000 rpm for 10 min. The supernatant fluid was taken and measured for optical density at 532 nm in the spectrophotometer. The serum values were calculated from standard graph.

Psychological assessment

Eysenck's personality questionnaire (EPQ)

Sinha anxiety scale (SAS)

Stress reaction checklist (SRC)

Beck Depression Inventory (BDI).

Inclusion criteria

Students of both gender who was nonalcoholic, nonsmoker, nonhypertensive in the age group between 18 and 25 years, were included for the purpose of the study.

Exclusion criteria

Students excluded were above the age of 25 years, with diabetes, smoking habits, and alcoholism. Besides if they were not agreed for investigation (whether biochemical/psychological) were not taken for study. It was also inquired at the time of testing that they had no complaints of biochemical/psychological illnesses.

RESULTS

Analysis of the data has been done on the basis of calculations of means, standard deviations, t-tests for the comparisons of means (between and within groups) and correlations by Karl Pearson's method to compare the data of 1st and 3rd year students.

A comparison of oxidative stress and personality variables between 1st and 3rd year students shows that in 1st year students’ profile, the mean value of MDA is (M = 3.10 nmol ± 0.26). Regarding the level of oxidative stress, students of 3rd year are carrying high level of MDA which is a significant difference as is observed statistically by t-test [Table 2].

Table 2

Study groups and its relations of oxidative stress with various psychological variables (dimensions of personality, anxiety, and level of stress and depression)

On dimensions of personality, the mean values [Table 2] of 1st year students reveal mild indications towards extraversion (E; 12.61 ± 3.72). As far as their level of anxiety is concerned they are moderately anxious (35.43 ± 18.65). Their level of stress shows that sometimes there are certain moments when they feel stressed. Regarding depression they are free from depression at present.

In case of 3rd year students’ profile, the mean value of MDA is (M = 4.26 ± 0.55nmol). Its level is significantly higher in 3rd year students. Findings related to the dimensions of personality, the mean values [Table 2] revealed significantly higher on the dimensions of psychoticism (P) (M = 14.20 ± 3.13). Besides mild tendencies towards E (M = 13.83 ± 2.85), N (M = 14.34 ± 3.17), and Lie Scale (L) (14.09 ± 3.13) are also noticed. As far as their other psychological factors are concerned, there is a significant difference between the level of anxiety (M = 64.33 ± 7.13), level of stress (M = 38.54 ± 4.82), and depression (M = 24.30 ± 7.64) of both the groups.

t-test reveals a significant difference between the means of MDA, P, SAS, SRC, and BDI (7.72, 9.59, 1.84, 1.27, and 2.76, respectively). Besides, 3rd year group is intended to be more extraverted, neurotic, and high on Lie-scale; but these differences are not statistically significant. As far as their level of anxiety, stress, and depression is concerned; senior group is more anxious, stressed, and significantly sad.

The results related to the comparison of oxidative stress and personality variables between 1st year (male and female students) and 3rd year (male and female students) show a significant difference between MDA, P, E, N, L, and anxiety level of male and female student of 1st year [Table 3], which indicate that males have higher oxidative stress, P, and depression; while female of same batch are emotionally unstable, tended to be neurotic, anxious, and stressed. Now if we concentrate on patterns of male and female 3rd year [Table 4] batch regarding oxidative stress and personality variables, males have significantly high level of oxidative stress. On different psychological variables, females are emotionally (E-13.71 ± 2.91) vulnerable, but do not show the symptoms; on the other hand, males are intended to be neurotic, anxious, stressed, and sad which is statistically significant (MDA = 4.22 ± 0.53N (14.19 ± 2.97), anxiety (64.7 ± 7.00), level of stress (38.67 ± 3.90), depression (25.48 ± 7.46), respectively). The same was confirmed by t-test [Table 4].

Table 3

Comparison of oxidative stress and personality variables between 1st year male and female students

Table 4

Comparison of oxidative stress and personality variables between 3rd year male and female students

A comparison of medical and paramedical students (within group) [Table 5] reveals MBBS-males have raised level of stress in comparison to paramedical students (18.9 ± 8.06). While the difference between within 3rd year students (medical and paramedical students), we found that paramedical males are more anxious (63.63 ± 6.75) and depressed (24.42 ± 7.89).

Table 5

Comparison of medical and paramedical students (within group)

Besides, correlations between oxidative stress and various personality variables revealed no significant correlation between oxidative stress and different personality variables [Table 2]. High positive correlations between MDA and anxiety in both groups, more with 3rd year batch were highlighted.

DISCUSSION

Above findings support that both groups are influenced by oxidative stress and their psychological variables are compatible. A comparative analysis of the biological and psychological variables reflect that senior group is more stressed as their level of oxidative stress, dimensions of P, level of stress, and depression are significantly higher. It shows a comparison between 1st and 3rd year students in relation to MDA levels that were found to be significantly raised (P < 0.05) in 3rd year students. From the above observation, it is clear that the MDA levels of 3rd year are higher than that of the 1st year students indicating a higher oxidative stress levels in 3rd year students. Earlier studies by Kumar et al.,[15] show a direct relationship between MDA and psychological factors. It shows that those people trait wise are prone to meet with thinking and perceptual distortion, out spoken, emotionally vulnerable, and unstable; are at a risk of facing adjustment difficulties, prone to catch stress, and have social naivety and desirability. In comparison to the students of 1st year who do not carry the cut of scores high on these said dimensions rather they are controlled and carry normal personality profile, as their exposure to stress is not chronic.

On anxiety level, the finding reveal that students of 3rd year are highly anxious in comparison to the students of 1st year who are carrying normal level of anxiety. It means to some extent anxiety is desirable among the achievers, but very high level of anxiety is not at all desirable as far as achievement in profession is concerned. Students of 3rd year are found to be moderately stressed in comparison to students of 1st year who carry mild level of stress. Again it is a confirmation that achievers must carry a required level of stress, but it should not be elevated after a certain level; Chapman et al.[16]

The aim of the present study was to prove the effect of long-term oxidative stress on medical and paramedical students by estimating their lipid peroxidation (MDA levels). We have been able to conclusively prove that there is in fact, a raise of MDA levels in our results. There was an increased rate of lipid peroxidation that may be due to high oxidative stress levels as indicated by higher level of serum MDA; Millan et al.[17] It has been found after a regular exposure to stress, people get anxious and depressed. Therefore, the level of depression is also checked and low level of depression is noticed among students of 3rd year. Basically, 3rd year student are found to be highly stressed because of neurotic traits and lie behavior; Eysenck.[18] It was found to be positively reflected in terms of correlation with MDA, for example, N, anxiety, and depression (0.45, 0.90, and 0.44, respectively) are positively correlated. Even 1st year is also carrying positive correlation of MDA with N, anxiety, and depression; but intensity is more in 3rd year students which reveal that N, anxiety, and depressive personality profiles make senior students more susceptible towards increased oxidative stress (MDA).

This further suggests and strengthens the already existing reports in literature that there is higher risk of progression of atherosclerosis in individuals who are under stress and have both the risk factors, that is, hypertension and other cardiovascular disturbances. Further studies on this subject will substantiate the findings of our study.

The present study revealed that stress has a direct effect on MDA, as its levels in 3rd year student were found to be significantly high; Srivastava et al.[19] It is suggested that this study indicates that those students who are high on stress due to high study burden, if detected at the earliest, can be saved them in advance to these expected health disorders like MI. Further mild-to-moderate levels of anxiety and depression can easily be treated by counseling and at time-to-time we may keep checking their various biochemical parameters like mean arterial pressure, body mass index (BMI), serum glucose, and lipid profile in relation to MDA (oxidative stress).

It is also suggested by Moller et al.,[20] that regular exercise and carbohydrate rich diet seem to increase the resistance against oxidative stress. On the contrary, psychological stressors like anxiety, depression, adjustment difficulties, and various psychological conditions are found to be directly correlated with oxidative stress; which means these are encouraging agent for said stress. These psychological stressors if by chance are coordinating with oxidative stress, an individual reflects major risk factors for cardiovascular disease, obesity, diabetes mellitus, and hyperlipidemia. Hence, AI was selected as marker for oxidative stress in this group. There is a positive relationship between work-related factors including physiological, psychological stress, and the formation of oxidative stress.

CONCLUSIONS

The level of oxidative stress is high in both groups, but senior group is significantly more stressed. As far as their other psychological factors are concerned, there is a significant difference between the group as 3rd year students are higher on level of anxiety, stress, and depression. Gender-wise comparison within group shows no significant difference in any of the factors between male and females, neither in 1st year nor in 3rd year.

Correlations between oxidative stress and various personality variables show no significant correlation between oxidative stress and different personality variables; N, anxiety, and depression. But if we do not ignore even the smaller values, it is found that 1st year students are intended to have positive correlations between P and E, which means more the level of P more will be the oxidative stress and 3rd students are showing positive correlations of oxidative stress with N means there is significant possibilities of more oxidative stress if N is increased in personality. Even both groups are intended to be positively correlated to anxiety and depression, which is more significant in 3rd year students.

From the above observation it is indicated that the MDA levels of 3rd year are higher than that of the 1st year students, indicating a higher oxidative stress level in 3rd year students. Hence, the further work on enhancement of health can be undertaken in this group.