|Year : 2018 | Volume
| Issue : 2 | Page : 78-82
Serum uric acid level in drug-naive depressed patients
Eman S Soliman1, Rehab S Mahdy2
1 Psychiatry Department, Zagazig University, Zagazig; Clinical Department, College of Medicine, Princess Nourah Bint Abdelrahman University, Riyadh, Egypt
2 Psychiatry Department, Zagazig University, Zagazig, Egypt
|Date of Submission||28-Sep-2017|
|Date of Acceptance||15-Oct-2018|
|Date of Web Publication||2-May-2018|
Eman S Soliman
Psychiatry, Psychiatry Department, Faculty of Medicine, Zagazig University
Source of Support: None, Conflict of Interest: None
Background Study of the correlation between uric acid (UA) and depression will help to establish evidence for, or against, the new hypothesis stating that the activation of inflammatory, oxidative, and nitrosative stress pathways is a key pathophysiological factor in depression, and reduced antioxidant reserve may coexist with the increased consumption of UA as a scavenger.
Objective The aim of this study was to investigate whether serum UA levels are different between drug-naive depressed patients and healthy controls and to compare UA levels in those depressed patients before and after treatment.
Materials and methods The serum UA levels and Hamilton Depression Rating Scale scores were estimated in 120 patients with major depressive disorder before and after 5 weeks of treatment with antidepressants. In addition, serum UA levels were measured in 120 healthy controls.
Results Drug-naive depressed patients had significantly lower UA levels (3.8±0.93 mg/dl) than the healthy control group (4.57±0.83 mg/dl, P<0.001). We also found that the UA levels of depressive patients increased significantly after 5 weeks of treatment with antidepressants.
Conclusion This study presents further proof of the involvement of UA in the pathogenesis and treatment of depression.
Keywords: depressed patients, drug naive, uric acid
|How to cite this article:|
Soliman ES, Mahdy RS. Serum uric acid level in drug-naive depressed patients. Egypt J Psychiatr 2018;39:78-82
| Introduction|| |
Major depressive disorder is a common mental disorder associated with a significant negative impact on quality of life, morbidity/mortality, and cognitive function (Behr et al., 2012).
Depression is a disease with a heterogeneous pathology that involves central monoamine transmitters and corresponding receptor changes; it is also associated with neuroendocrine disorders. Recently, a new hypothesis was formulated stating that the activation of inflammatory, oxidative, and nitrosative stress pathways is a key pathophysiological factor in depression (Maes, 2008).
Throughout their life span, depressed patients may be challenged with several depressive episodes associated with (sub) chronic inflammatory responses and by inference with significantly increased reactive oxygen species and reactive nitrogen species production (Leonard and Maes, 2012). Oxidative and nitrosative stress have detrimental effects on membrane fatty acids, the function and stability of proteins, and DNA damage, as well as its repair mechanisms (Yager et al., 2010). If unchecked, this may result in apoptosis and in part explain the brain volumetric changes evident in depression (Kubera et al., 2011).
Uric acid (UA) is an important antioxidant accounting for over 60% of total antioxidant capacity in the human blood and derangement of which is observed in several neurological and psychiatric disease states, such as Parkinson’s disease, multiple sclerosis, optic neuritis, Alzheimer’s disease, bipolar disorder, and depression. Treatment has shown to improve the UA levels in these patients (Bowman et al., 2010).
| Materials and methods|| |
The study was performed in the Psychiatry Department, Zagazig University Hospitals, Sharkia, Egypt, in the period between January 2015 and January 2016.
Study groups consisted of a control group of healthy participants and drug-naive depressed patients. The participants included in the study were of both sexes between the age group of 18 and 60 years. Control group have been matched for age, sex, and socioeconomic class, and they were excluded for history of any psychiatric illnesses.
Major depressive disorder was diagnosed by trained psychiatrist using Diagnostic and Statistical Manual of Mental Disorders, fifth ed. criteria and Arabic version of 17-item Hamilton Depression Rating Scale (HRSD) score to measure the severity of the disorder (Fatim, 1994). The patients had no history of other comorbid psychiatric disorder, and they were free of psychotropic medication for at least 4 weeks before the study.
Medical illnesses that are known to affect free-radical status and UA levels were excluded, for example, gout, chronic inflammatory disease, diabetes, hypertension, renal failure, liver disease, and endocrine disorders (as judged from history, clinical, and laboratory examinations).
Also, treatment with drugs that could increase or affect serum UA was among our exclusion criteria, for example, acetylsalicylic acid, thiazide diuretics, steroids, ibuprofen, vitamin E, inosine, coQ10, ethambutol, pyrazinamide, and cytotoxic chemotherapy.
Approval was obtained from the Institutional Review Board and the Department of Psychiatry, Zagazig University. Written informed consent was obtained from all patients.
Blood samples were drawn from all patients and healthy controls after an overnight fast from a peripheral vein and the serum level of the UA was detected.
The method principle was enzymatic uricase method, and the instrument name was Cobas Integra 400 plus (Roche, France). In our hospital, the normal range of serum UA values has been measured as 3.4–7 mg/dl in men and 2.4–5.7 mg/dl in women. Samples were collected from all patients and healthy participants.
The depressed patients were treated with antidepressants from different classes (mainly selective serotonin reuptake inhibitors and tricyclic antidepressants) at effective doses during the 5-week period, and then they were assessed using Arabic version of 17-item HRSD (Fatim, 1994) and their serum UA was measured again using the same instrument.
The collected data were computerized and statistically analyzed using program statistical package for the social sciences (PASW Statistics for Windows, Version 18.0. Chicago: SPSS Inc.). Qualitative data were represented as frequencies and relative percentages.
χ2-Test was used to calculate difference between qualitative variables.
Independent t-test was used to calculate difference between quantitative variables in two groups in normally distributed data.
Paired t-test was used to compare means from matched pairs or two different samples from the same individuals (before and after observations on the same patients).
One way analysis of variance (ANOVA) was used to calculate difference between quantitative variables in more than two groups in normally distributed data.
Pearson’s correlation coefficient (r) was used to calculate correlation between quantitative variables.
P value was used to indicate level of significance: values were considered significant when the P value was less than 5% (P<0.05), highly significant when the P value was less than 0.1% (P<0.001), and nonsignificant when the probability of error was more than 5% (P>0.05).
| Results|| |
The current study showed that serum UA levels of patients with depression were significantly lower (3.8±0.93 mg/dl) when compared with the healthy control group (4.57±0.83 mg/dl, P<0.001) ([Table 1]).
|Table 1 Serum uric acid levels in drug-naive depressed patients and healthy controls|
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Female patients with depression exhibited significantly lower serum UA levels compared with male patients (P<0.001) ([Table 2]). A significant positive correlation between age of the patients and serum UA level was detected ([Table 3]).
|Table 2 Serum uric acid levels of drug-naive depressed patients regarding sex|
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|Table 3 Correlation between age and serum uric acid level of drug-naive depressed patients|
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Patients with very severe depression (HRSD scores >22) had the lowest serum UA levels, but the difference was not statistically significant compared with patients with less severe depression (HRSD scores 19–22) or moderate depression (HRSD scores 14–18) ([Table 4]).
|Table 4 Serum uric acid levels of drug-naive depressed patients regarding severity of depression according to Hamilton depression rating scale scores|
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After a 5-week treatment with antidepressants, there was a statistically significant reduction in HRSD scores of patients with depression ([Table 5]) and their serum UA levels were significantly higher (4.2±0.83 mg/dl; P<0.001) when compared with those before treatment (3.8±0.93 mg/dl) ([Table 6]).
|Table 5 Comparison between Hamilton depression rating scale scores of depressed patients before and after treatment|
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|Table 6 Comparison of serum uric acid levels of depressed patients before and after treatment|
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| Discussion|| |
The results of the current study showed that serum UA levels of patients with depression were significantly lower when compared with the healthy control group. These results are in agreement with findings of Chaudhari et al. (2010) who reported that UA levels in newly diagnosed patients were significantly low (P<0.001) as compared with healthy participants. Similarly, Wen et al. (2012) found that serum UA levels of patients with depression were significantly lower when compared with patients with other mental disorders and the healthy control groups.
Bove et al. (2010), in a population-based study (the Massa Lombarda Project), selected 106 elderly patients who did not suffer from chronic or severe disabling disease and had no history of depression or anxiety disorder. They found that most of the elderly people were not depressed (65%), whereas 35% of the patients suffered from depression and serum UA levels of depressed patients were lower than those of nondepressed patients.
As Wen et al. (2012) pointed out, it is unclear whether depressed patients with low serum UA levels are more likely to be challenged with free-radical toxicity and inflammation or rather low serum UA is owing to the consumption of UA by radical interaction and damaged tissue encountered in depression.
In contrast to our results, Tao and Li (2014) compared the levels of serum UA in adolescent depressive patients and normal adolescents and they found that the serum UA level in depressed patients was significantly higher than the healthy control group. The possible cause of difference between our study and their study may be the different study group they investigated, which consisted of first episode depressive male patients and all of them were adolescents. As these patients are adolescents, their pathology may evolve into bipolar disorder or another psychiatric disorder.
In our study, we found that women had lower mean serum UA levels when compared with men, which was consistent with other previous studies (Fang and Alderman, 2000; Chaudhari et al., 2010; Wen et al., 2012; Gu et al., 2015).
Also, we found that serum UA level increased with aging. This broadly agrees with previous studies (Kuzuya et al., 2002; Richette and Bardin, 2010; Rosa et al., 2010).
In this study, patients with very severe depression had the lowest serum UA levels, but the difference was not statistically significant compared with patients with less severe depression or moderate depression. Similarly, Wen et al. (2012) revealed that UA levels were not significantly correlated with the severity of major depressive disorder. In addition, Keshavarz et al. (2016) showed that there was no significant correlation between UA levels and severity of mood disorders in both the manic and the depressed patients.
Our results showed that after 5 weeks of treatment with antidepressants, there was significant change in the HRSD scores of depressed patients. In addition, serum UA levels of patients with depression after a 5-week treatment were significantly higher when compared with those before treatment. These results are in agreement with findings of Wen et al. (2012) who showed that serum UA levels of patients with depression after a 5-week treatment were significantly higher when compared with those before treatment. In addition, Chaudhari et al. (2010) compared the pretreatment levels of UA in depressed patients with that of post-treatment levels at 6 and 12 weeks. Fluoxetine treatment significantly increased serum UA at 6 weeks when compared with before treatment concentrations. Further, the levels were significantly elevated at 12 weeks as compared with that of 6 weeks after treatment with fluoxetine (Chaudhari et al., 2010).
Although no literature is available regarding the direct effect of antidepressants on serum UA levels, the rise could be due to decreased consumption of UA required for scavenging free radicals.
Human studies and animal models of depression provide evidence that O and NS pathways are involved in the working mechanisms of antidepressant agents.
Bowman et al. (2010) found that oxidative stress is reduced with antidepressant therapy in depressed patients. Selective serotonin reuptake inhibitors are known to decrease lipid peroxidation in major depression. Similarly, they also increase plasma ascorbic acid levels and upregulate superoxide dismutase (SOD1) gene in depressive patients and produce neuroprotective effects against free-radical-induced damage in major depression (Li et al., 2000; Khanzode et al., 2003). In vitro, imipramine increased the survival rate of neural stem cells and prevented the endotoxin-induced apoptosis (Peng et al., 2008).
Our study had some limitations such as heterogeneity of the antidepressants used, relatively short duration of treatment, and the cross-sectional design, so the temporal sequence between exposure and disease may be difficult to establish.
| Conclusion|| |
Our study showed that drug-naive depressed patients had lower serum UA levels. There were some uncertainties about whether low serum UA level was a cause or consequence of the disease. In addition, this demonstrated an increase in serum UA levels with treatment, and this rising may be an indicator of an antioxidant defense increment in the course of the treatment.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]