Novel metabolic biomarkers related to sulfur-dependent detoxification pathways in autistic patients of Saudi Arabia

<p>Abstract</p> <p>Background</p> <p>Xenobiotics are neurotoxins that dramatically alter the health of the child. In addition, an inefficient detoxification system leads to oxidative stress, gut dysbiosis, and immune dysfunction. The consensus among physicians who treat autism with a biomedical approach is that those on the spectrum are burdened with oxidative stress and immune problems. In a trial to understand the role of detoxification in the etiology of autism, selected parameters related to sulfur-dependent detoxification mechanisms in plasma of autistic children from Saudi Arabia will be investigated compared to control subjects.</p> <p>Methods</p> <p>20 males autistic children aged 3-15 years and 20 age and gender matching healthy children as control group were included in this study. Levels of reduced glutathione (GSH), total (GSH+GSSG), glutathione status (GSH/GSSG), glutathione reductase (GR), glutathione- s-transferase (GST), thioredoxin (Trx), thioredoxin reductase (TrxR) and peroxidoxins (Prxs I and III) were determined.</p> <p>Results</p> <p>Reduced glutathione, total glutathione, GSH/GSSG and activity levels of GST were significantly lower, GR shows non-significant differences, while, Trx, TrxR and both Prx I and III recorded a remarkably higher values in autistics compared to control subjects.</p> <p>Conclusion</p> <p>The impaired glutathione status together with the elevated Trx and TrxR and the remarkable over expression of both Prx I and Prx III, could be used as diagnostic biomarkers of autism.</p

Inter-relationship of plasma markers of oxidative stress and thyroid hormones in schizophrenics

<p>Abstract</p> <p>Background</p> <p>The relationship of oxidative stress to thyroid hormones has not been studied in the schizophrenics. The present study determined the status and interrelationship of plasma markers of oxidative stress, nitric oxide and thyroid hormones in thirty (17 males and 13 females) newly diagnosed patients with acute schizophrenia before initiation of chemotherapy. Twenty five (13 males and 12 females) mentally healthy individuals served as controls. Patients and controls with history of hard drugs (including alcohol and cigarette), pre-diagnosis medications (e.g. antiparkinsonian/antipsychotic drugs), chronic infections, liver disease and diabetes mellitus were excluded from the study. Plasma levels of total antioxidant potential (TAP), total plasma peroxides (TPP), nitric oxide (NO), malondialdehyde (MDA), thyroxine (T4), tri-iodothyronine (T3) and thyroid stimulating hormone (TSH) were determined in all participants using spectrophotometric and enzyme linked immunosorbent assay (ELISA) methods respectively. Oxidative stress index (OSI) was calculated as the percent ratio of total plasma peroxides and total antioxidant potential.</p> <p>Findings</p> <p>Significantly higher plasma levels of MDA (p < 0.01), TPP (p < 0.01), OSI (p < 0.01), T3 (p < 0.01) and T4 (p < 0.05) were observed in schizophrenics when compared with the controls. The mean levels of TAP, NO and TSH were significantly lower in schizophrenics (p < 0.01) when compared with the controls. The result shows that T3 values correlate significantly with MDA (p < 0.05) and TPP (p < 0.01) in schizophrenics.</p> <p>Conclusions</p> <p>Higher level of TPP may enhance thyroid hormogenesis in schizophrenics. Adjuvant antioxidant therapy may be a novel approach in the treatment of schizophrenic patients.</p

The 5-HTTLPR polymorphism of the serotonin transporter gene and short term behavioral response to methylphenidate in children with ADHD

<p>Abstract</p> <p>Background</p> <p>Animal models of ADHD suggest that the paradoxical calming effect of methylphenidate on motor activity could be mediated through its action on serotonin transmission. In this study, we have investigated the relationship between the 5-HTTLPR polymorphism in the serotonin transporter gene (<it>SLC6A4</it>) and the response of ADHD relevant behaviors with methylphenidate treatment.</p> <p>Methods</p> <p>Patients between ages 6-12 (n = 157) were assessed with regard to their behavioral response to methylphenidate (0.5 mg/kg/day) using a 2-week prospective within-subject, placebo-controlled (crossover) trial. The children were then genotyped with regard to the triallelic 5-HTTLPR polymorphism in the <it>SLC6A4 </it>gene. Main outcome measure: Conners' Global Index for parents (CGI-Parents) and teachers (CGI-Teachers) at baseline and at the end of each week of treatment with placebo and methylphenidate. For both outcome measurements, we used a mixed model analysis of variance to determine gene, treatment and gene × treatment interaction effects.</p> <p>Results</p> <p>Mixed model analysis of variance revealed a gene × treatment interaction for CGI-Parents but not for CGI-Teachers. Children homozygous for the lower expressing alleles (<it>s+l_G= s'</it>) responded well to placebo and did not derive additional improvement with methylphenidate compared to children carrying a higher expressing allele (<it>l_A</it>). No genotype main effects on either CGI-Parents or CGI-teachers were observed.</p> <p>Conclusions</p> <p>A double blind placebo-controlled design was used to assess the behavioral effects of methylphenidate in relation to the triallelic 5-HTTLPR polymorphism of the <it>SLC6A4 </it>gene in children with ADHD. This polymorphism appears to modulate the behavioral response to methylphenidate in children with ADHD as assessed in the home environment by parents. Further investigation is needed to assess the clinical implications of this finding.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00483106</p

Development of Functional Symptoms in Children Exposed to Traumatic Events

This chapter will review the typical symptoms occurring in children after stressful traumatic exposures. Unlike other chapters in this book, no specific organ system is the most likely focus of functional symptoms in this setting. Psychological distress may exacerbate symptoms of physical illness and injury associated with the traumatic events, may be expressed as almost any seemingly unrelated symptom, may intensify the age appropriate fears typical of any child, or may predominantly be exhibited behaviorally. In most nonsevere cases, the impact is self-limited and the individual’s functioning will be back to normal within days or weeks. We will suggest simple behavioral and environmental interventions intended to help relieve children’s distress. However, when large populations are affected and individuals suffer severe loss such as in a mass casualty disaster, the scale of events requires community-wide efforts to meet the needs of children and their families. The fact that some children are more psychosocially vulnerable than others will be discussed. The chapter will conclude by highlighting warning signs warranting professional mental health care

Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis

A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (∼0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD

Psychiatric comorbidity distribution and diversities in children and adolescents with attention deficit/hyperactivity disorder: a study from Turkey

Murat Y&uuml;ce,1 S&uuml;leyman Salih Zoroglu,2 Mehmet Fatih Ceylan,3 Hasan Kandemir,4 Koray Karabekiroglu5 1Department of Child and Adolescent Psychiatry, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey; 2Department of Child and Adolescent Psychiatry, Medical Faculty of Istanbul, Istanbul University, Istanbul, Turkey; 3Department of Child and Adolescent Psychiatry, Dr Sami Ulus Children&#39;s Hospital, Ankara, Turkey; 4Department of Child and Adolescent Psychiatry, Faculty of Medicine, Harran University, Sanliurfa, Turkey; 5Department of Child and Adolescent Psychiatry, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey Objective: We aimed to determine distribution and diversities of psychiatric comorbidities in children and adolescents with attention deficit/hyperactivity disorder (ADHD) in terms of age groups, sex, and ADHD subtype. Materials and methods: The sample included 6&ndash;18 year old children and adolescents from Turkey (N=108; 83 boys, 25 girls) diagnosed with ADHD. All comorbid diagnoses were determined based on the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version assessment. Results: 96.3% of the cases were found to have at least one psychiatric comorbid diagnosis. The most frequent psychiatric comorbid disorder was oppositional defiant disorder (69.4%) followed by anxiety disorders (49%) and elimination disorders (27.8%). Disruptive behavior disorders were more common in ADHD-combined type. Depression and anxiety disorders were more common in girls. Separation anxiety disorder and elimination disorder were more common in children, whereas depression, bipolar disorder, obsessive&ndash;compulsive disorder, and social phobia were more common in the adolescents. Conclusion: According to our results, when a diagnostic tool was used to assess the presence of comorbid psychiatric disorders in children and adolescents diagnosed with ADHD, almost all cases had at least one comorbid diagnosis. Therefore, especially in the clinical sample, ADHD cases should not be solely interpreted with ADHD symptom domains, instead they should be investigated properly in terms of accompanying psychiatric disorders. Keywords: attention deficit/hyperactivity disorder, psychiatric comorbidity, child, adolescen

Increased nitric oxide and superoxide dismutase levels in euthymic bipolar patients: Impact of past episodes

Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences -- MAR 31-APR 06, 2005 -- San Diego, CAWOS: 000227610705063Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeu

Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism

There is great evidence in recent years that oxygen free radicals play an important role in the pathophysiology of many neuropsychiatric disorders. The present study was performed to assess the changes in red blood cells thiobarbituric acid-reactive substances (TBARS) levels, and superoxide dismutase (SOD), catalase (CAT), adenosine deaminase (ADA) and xanthine oxidase (XO) activities in patients with autism (n = 27) compared to age- and sex-matched normal controls (n = 26). In the autistic group, increased TBARS levels (p < 0.001) and XO (p < 0.001) and SOD (p < 0.001) activity, decreased CAT (p < 0.001) activity and unchanged ADA activity were detected. It is proposed that antioxidant status may be changed in autism and this new situation may induce lipid peroxidation. These findings indicated a possible role of increased oxidative stress and altered enzymatic antioxidants, both of which may be relevant to the pathophysiology of autism