Evaluation of total oxidative status in adult attention deficit hyperactivity disorder and its diagnostic implications

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Abstract

Adult Attention Deficit Hyperactivity Disorder (A-ADHD) is one of the psychiatric disorders which awareness is growing. The exact causes of A-ADHD are still unknown. In addition to neurochemical and neuroanatomic disorders, genetic and environmental factors are discussed in its etiology. In our study, we aimed to evaluate the oxidative status of A-ADHD patients and investigate whether oxidative metabolites can be used as diagnostic tools or not in A-ADHD. Blood samples were taken from enrolled 50 A-ADHD patients and 31 controls in appropriate way and Total Antioxidative Status (TAS), Total Oxidative Status (TOS), and Oxidative Stress Index (OSI) were studied in Harran University Biochemistry Labs. Results were compared between groups and ROC curve was drawn in order to evaluate diagnostic performances. Patients' TAS, TOS and OSI were significantly higher than controls. There was not a significant difference between comorbid cases and only A-ADHD patients in terms of measured values. A-ADHD can be predicted for TOS over 9.8575 μmol H2O2 Eqv./L level with 86% positive predictive value and %100 negative predictive value. In A-ADHD, oxidative balance is impaired. High antioxidant levels may be compensatory against the oxidant increase. Oxidative parameters may be used in A-ADHD diagnosis.

Introduction

35 years ago, preliminary studies of Adult Attention Deficit Hyperactivity Disorder (A-ADHD) were written (Wood et al., 1976). The phenomenon was well described in children but only recent studies have shown its impact across life span (Wilens et al., 2002). Debates whether it exists or not, may be justified because nomenclature of the disorder has several flaws. The diagnostic criteria were made according to the childhood and focusing rather than “attention deficit” is the major problem (Doyle, 2006). However, several improvements have been made for the description of A-ADHD (Gunay et al., 2006; Wender, 1995). It is clear that not all but some of the adults develop adaptive behaviors against symptoms and the course of the disease changes but its effect on functionality still persists (Faraone et al., 2000; Wilens and Dodson, 2004). Why some people recover after childhood and others not is another issue to be studied.

Numerous researches have been conducted regarding neurobiology of pediatric ADHD but A-ADHD studies are relatively few. Several neurochemical and genetic mechanisms are believed to be involved in A-ADHD although the etiology remains unclear (Bulut et al., 2007; Faraone, 2004).

While aerobic life depends on oxygen, sometimes it may be hazardous for living beings which is known as “oxygen paradox”(Davies, 1995). During oxygen involved oxidation–reduction reactions for life energy, several “harmful wastes” called oxidants are produced. Oxidants are removed from the body by antioxidant defense mechanisms. The imbalance of oxidative metabolism is called oxidative stress (Valko et al., 2006). The association between oxidative stress and psychiatric disorders such as schizophrenia, bipolar disorder, depression and anxiety disorders were well studied before (Andreazza et al., 2008; Herken et al., 2007; Selek et al., 2008a, Selek et al., 2008b).

Few studies focused on oxidative stress of either pediatric or adult ADHD (Bulut et al., 2007; Ceylan et al., 2010). We have previously reported that oxidant nitric oxide levels were high and antioxidant superoxide dismutase levels were low in A-ADHD (Selek et al., 2008c). However, a total status of oxidative metabolism has not been evaluated, yet. Plasma concentrations of antioxidants can already be measured separately in the laboratory, but these measurements are time-consuming, labor-intensive and costly. The number of different antioxidants in plasma, serum, urine, or other biological samples makes it difficult to measure each antioxidant separately. Since antioxidative effects of antioxidant components of plasma are additive, the measurement of total antioxidative status (TAS) and total oxidative status (TOS) can only reflect the antioxidative status of plasma whose measurement methods were developed by Harran Biochemistry Labs (Erel, 2004, Erel, 2005). On the other hand, there may be shifts in TAS and TOS. Thus, Erel also hypothesized that current oxidative status can be stated with oxidative stress index (OSI) which can be figured out by TAS/TOS (Erel, 2005). The general relation between those parameters can be seen in Fig. 1. Therefore, for exploring a specific relationship between oxidative metabolism and suggested diseases, Erel's parameters are useful.

In this study we aim to explore the total oxidative and antioxidative status of A-ADHD and investigate whether oxidative metabolites can be used as diagnostic tools or not in A-ADHD.

Section snippets

Patients and controls

54 A-ADHD patients between 18 and 45 years of age, diagnosed according to Turgay's Turkish version of Adult ADD/ADHD DSM IV – Based Diagnostic Screening and Rating Scale by two psychiatrists (H.A.S. and S.S.) in the Psychiatry Department of Gaziantep University Hospital were involved. Since the patients were initially diagnosed as A-ADHD, they were free from stimulant and A-ADHD medication. The scale is DSM IV based and it was developed by Turgay for diagnosis and severity evaluation (Gunay

Results

Some of the sociodemographic and clinical variables are tabulated in Table 1. Fig. 2 shows TAS, TOS and OSI levels of groups.

There were significant differences between two groups of all parameters and TAS was 1,3; TOS was 4,2 and OSI was 3,2 times higher in patients than controls (T = 14.087, p < 0.001; T = 7.422, p < 0.001 and T = 6.449, p < 0.001, respectively). There was not any significant difference among subtypes of ADHD (TAS: F = 0.430, p = 0.732; TOS: F = 0.210, p = 0.889 and OSİ: F

Discussion

Our first finding is higher TOS levels in patients. In our previous studies we have found elevated specific oxidants such as Nitric oxide and Malone dealdehyde (Bulut et al., 2007; Ceylan et al., 2010; Selek et al., 2008c). Our current finding is congruent with previous results. There was not difference between only A-ADHD patients and comorbid patients suggesting the oxidative impairment may be attributed to the whole disease entity. Although TOS was found to be increased in several other

Role of funding source

None.

Contributors

Author Selek and Bulut designed the study. Kalenderoglu, Bulut and Selek collected the samples. Ocak made the biochemical analysis. Selek made the statistical analysis. Savas edited the writing of the manuscript. All of the authors finally revised the paper and gave consent for publication.

Conflict of interest

The authors declare no conflict of interest.

Acknowledgments

None.

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