Biomarker Commons

Hyperhomocysteinemia among Omani autistic children: a case-control study.

Acta Biochim Pol. 2011;58(4):547-51

Authors: Ali A, Waly MI, Al-Farsi YM, Essa MM, Al-Sharbati MM, Deth RC

Abstract
High serum homocysteine (Hcy) level is regarded as an indicator for impairment of folate-dependent methionine cycle and is associated with oxidative stress. In a case control study, we evaluated eighty 3-5 years old Omani children (40 diagnosed with Autism Spectrum Disorder and 40 their age and gender matched controls) for their fasting serum homocysteine levels as a biomarker of Autism Spectrum Disorder (ASD). Serum folate and vitamin B(12) status were also evaluated. The serum homocysteine was measured using an enzyme immunoassay (EIA) technique whereas folate and vitamin B(12) were measured using an automated random access immune-assay system. The results indicated that mean serum Hcy levels were significantly (P < 0.05) higher in autistic children (20.1 ± 3.3 µmol/L) as compared to controls (9.64 ± 2.1 µmol/L). Significantly (P < 0.05) lower serum folate (1.8 ± 0.4 µg/L) and vitamin B(12) (191.1 ± 0.9 pg/mL) levels were observed in autistic children as compared to controls (6.1 ± 0.6 µg/L and 288.9 ± 1.3 pg/mL, respectively). The levels of homocysteine in autistic children were also much higher as compared to normal reference values (5-15 µmol/L). The results suggest that high fasting serum homocysteine and low folate and vitamin B(12) levels could be used as clinical biomarkers for an early diagnosis and management of ASD.

PMID: 22187679 [PubMed - indexed for MEDLINE]

A failure of left temporal cortex to specialize for language is an early emerging and fundamental property of autism.

Brain. 2012 Mar;135(Pt 3):949-60

Authors: Eyler LT, Pierce K, Courchesne E

Abstract
Failure to develop normal language comprehension is an early warning sign of autism, but the neural mechanisms underlying this signature deficit are unknown. This is because of an almost complete absence of functional studies of the autistic brain during early development. Using functional magnetic resonance imaging, we previously observed a trend for abnormally lateralized temporal responses to language (i.e. greater activation on the right, rather than the expected left) in a small sample (n = 12) of sleeping 2-3 year olds with autism in contrast to typically developing children, a finding also reported in autistic adults and adolescents. It was unclear, however, if findings of atypical laterality would be observed in a larger sample, and at even earlier ages in autism, such as around the first birthday. Answers to these questions would provide the foundation for understanding how neurofunctional defects of autism unfold, and provide a foundation for studies using patterns of brain activation as a functional early biomarker of autism. To begin to examine these issues, a prospective, cross-sectional design was used in which brain activity was measured in a large sample of toddlers (n = 80) during the presentation of a bedtime story during natural sleep. Forty toddlers with autism spectrum disorder and 40 typically developing toddlers ranging in age between 12-48 months participated. Any toddler with autism who participated in the imaging experiment prior to final diagnosis was tracked and diagnoses confirmed at a later age. Results indicated that at-risk toddlers later diagnosed as autistic display deficient left hemisphere response to speech sounds and have abnormally right-lateralized temporal cortex response to language; this defect worsens with age, becoming most severe in autistic 3- and 4-year-olds. Typically developing children show opposite developmental trends with a tendency towards greater temporal cortex response with increasing age and maintenance of left-lateralized activation with age. We have now demonstrated lateralized abnormalities of temporal cortex processing of language in autism across two separate samples, including a large sample of young infants who later are diagnosed with autism, suggesting that this pattern may reflect a fundamental early neural developmental pathology in autism.

PMID: 22350062 [PubMed - indexed for MEDLINE]

Proinflammatory and proapoptotic markers in relation to mono and di-cations in plasma of autistic patients from Saudi Arabia.

J Neuroinflammation. 2011;8:142

Authors: El-Ansary AK, Ben Bacha AG, Al-Ayadhi LY

Abstract
OBJECTIVES: Autism is a developmental disorder characterized by social and emotional deficits, language impairments and stereotyped behaviors that manifest in early postnatal life. This study aims to clarify the relationship amongst absolute and relative concentrations of K+, Na+, Ca2+, Mg2+ and/or proinflammatory and proapoptotic biomarkers.
MATERIALS AND METHODS: Na+, K+, Ca2+, Mg2+, Na+/K+, Ca2+/Mg2+ together with IL6, TNFα as proinflammatory cytokines and caspase3 as proapoptotic biomarker were determined in plasma of 25 Saudi autistic male patients and compared to 16 age and gender matching control samples.
RESULTS: The obtained data recorded that Saudi autistic patients have a remarkable lower plasma caspase3, IL6, TNFα, Ca2+ and a significantly higher K+ compared to age and gender matching controls. On the other hand both Mg2+ and Na+ were non-significantly altered in autistic patients. Pearson correlations revealed that plasma concentrations of the measured cytokines and caspase-3 were positively correlated with Ca2+ and Ca2+/K+ ratio. Reciever Operating Characteristics (ROC) analysis proved that the measured parameters recorded satisfactory levels of specificity and sensitivity.
CONCLUSION: Alteration of the selected measured ions confirms that oxidative stress and defective mitochondrial energy production could be contributed in the pathogenesis of autism. Moreover, it highlights the relationship between the measured ions, IL6, TNFα and caspase3 as a set of signalling pathways that might have a role in generating this increasingly prevalent disorder. The role of ions in the possible proinflammation and proapoptic mechanisms of autistics' brains were hypothesized and explained.

PMID: 21999440 [PubMed - indexed for MEDLINE]

Early functional brain development in autism and the promise of sleep fMRI.

Brain Res. 2011 Mar 22;1380:162-74

Authors: Pierce K

Abstract
Functional magnetic resonance imaging (fMRI) is a powerful tool for examining brain function but has yet to be systematically applied to the study of brain development in autism. Recently, however, scientists have begun to apply fMRI during natural sleep as a mechanism to study function in the developing brain. When considering the study of autism, this method opens considerable doors because it eliminates biases of past studies which only sampled from high-functioning, older populations. This paper describes the application of sleep fMRI as a way to study both extrinsic and intrinsic brain functions in autism between 12 and 36 months. Preliminary studies that use sleep fMRI method show that defects in the superior temporal gyrus (STG) in response to language are early emerging in autism and can be found in as young as 14 months in age. As such indices of abnormal early development of the STG may prove useful in the search for a biomarker of autism detectable during the infancy period. From a theoretical standpoint, examining sleep fMRI studies in autism gains some clarity when placed in context of the more established literature on structural brain development of autism which suggests that autism involves early brain overgrowth. Studies of plasticity in autism have yet to be done, but it is likely that the window of opportunity for altering the course of brain development in autism begins within the first year of life. The ability to do so relies on improving and streamlining early identification and thus early treatment efforts.

PMID: 20869953 [PubMed - indexed for MEDLINE]