Glutathione pathway gene variation and risk of autism spectrum disorders

Despite evidence that autism is highly heritable with estimates of 15 or more genes involved, few studies have directly examined associations of multiple gene interactions. Since inability to effectively combat oxidative stress has been suggested as a mechanism of autism, we examined genetic variation 42 genes (308 single-nucleotide polymorphisms (SNPs)) related to glutathione, the most important antioxidant in the brain, for both marginal association and multi-gene interaction among 318 case–parent trios from The Autism Genetic Resource Exchange. Models of multi-SNP interactions were estimated using the trio Logic Regression method. A three-SNP joint effect was observed for genotype combinations of SNPs in glutaredoxin, glutaredoxin 3 (GLRX3), and cystathione gamma lyase (CTH); OR = 3.78, 95% CI: 2.36, 6.04. Marginal associations were observed for four genes including two involved in the three-way interaction: CTH, alcohol dehydrogenase 5, gamma-glutamylcysteine synthetase, catalytic subunit and GLRX3. These results suggest that variation in genes involved in counterbalancing oxidative stress may contribute to autism, though replication is necessary

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

Infantile zinc deficiency: Association with autism spectrum disorders

Elucidation of the pathogenesis and effective treatment of autism spectrum disorders is one of the challenges today. In this study, we examine hair zinc concentrations for 1,967 children with autistic disorders (1,553 males and 414 females), and show considerable association with zinc deficiency. Histogram of hair zinc concentration was non-symmetric with tailing in lower range, and 584 subjects were found to have lower zinc concentrations than −2 standard deviation level of its reference range (86.3–193ppm). The incidence rate of zinc deficiency in infant group aged 0–3 year-old was estimated 43.5 % in male and 52.5 % in female. The lowest zinc concentration of 10.7 ppm was detected in a 2-year-old boy, corresponding to about 1/12 of the control mean level. These findings suggest that infantile zinc deficiency may epigenetically contribute to the pathogenesis of autism and nutritional approach may yield a novel hope for its treatment and prevention

Dikkat eksikliği hiperaktivite bozukluğu tanılı çocuklarda doğum sırası

Amaç: Dikkat Eksikliği Hiperaktivite Bozukluğu (DEHB)’nun etiyopatogenezi net olarak aydınlatılamamıştır. Çevresel ve genetik nedenlerin rol oynadığı düşünülmektedir. Perinatal fetal örselenmeler minimal beyin hasarına neden olabilmektedir. İlk çocuk olmak doğum travmalarına maruziyet açısından risk faktörüdür. DEHB’de doğum sırasının etkisine ilişkin az sayıda araştırmaya rastlanmıştır. Bu çalışmada DEHB tanılı çocuklarda doğum sıra özelliklerini araştırmak amaçlanmıştır. Yöntem: DEHB tanısı konmuş 49 erkek, 16 kız çocuğun kardeşleri arasındaki doğum sırası tespit edilmiştir. Doğum sıra tespitinde Slater indeksi kullanılmıştır. Veriler kontrol grubu ile karşılaştırılmıştır. Sonuçlar: DEHB tanılı kız ve erkek çocukların doğum sıra indeksleri kontrol grubuna göre iststistiksel olarak anlamlı düzeyde düşük bulunmuştur. Bu sonuçlar, DEHB tanılı çocukların kardeşleri arasında ilk ya da önce doğmuş çocuk (büyük kardeş) olduğunu göstermektedir. Tartışma: Araştırma sonuçları, ilk ya da önce doğmuş çocukların perinatal örselenmelere daha çok maruz kaldığı, bu nedenle DEHB etiyopatogenezinde minimal beyin hasarının önemli rol oynadığı yönünde yorumlanmıştır

Possible negative effects of snoring and increased sleep fragmentation on developmental status of preschool children

Limited studies have investigated the effects of snoring although harmful neurocognitive effects of obstructive sleep apnea syndrome are relatively well known. The aim of the present study was to investigate the effects of snoring and fragmented sleep on mental development in preschool children. The study population consisted of 212 healthy preschool children (age range 3.1-6 years; mean = 5.4 +/- 0.6 years; 112 boys, 100 girls). The developmental status of the children was investigated by using the Ankara Developmental Screening Inventory (ADSI) and Peabody Picture Vocabulary Test (PBT). Children's sleep and snoring frequency were assessed by using parent completed Children's Sleep Habits Questionnaire (CSHQ). Snoring children had lower scores of language/cognitive skills, social/activities of daily living skills, and general development compared to controls (P 0.05). Children with fragmented sleep had lower scores of language/cognitive skills, fine motor skills, social/activities of daily living skills, and general development compared to controls (P 0.05). Present study suggested that healthy preschool children who have habitual snoring or sleep fragmentation may have reduced scores of various mental development compared to controls. Uninterrupted sleep may be more important than sleep duration for the development of the various mental abilities in healthy preschool children. More studies investigating snoring and sleep fragmentation on mental development in children are warranted for a definite conclusion