Investigation of the serum levels of anterior pituitary hormones in male children with autism

<p>Abstract</p> <p>Background</p> <p>The neurobiological basis of autism remains poorly understood. The diagnosis of autism is based solely on behavioural characteristics because there are currently no reliable biological markers. To test whether the anterior pituitary hormones and cortisol could be useful as biological markers for autism, we assessed the basal serum levels of these hormones in subjects with autism and normal controls.</p> <p>Findings</p> <p>Using a suspension array system, we determined the serum levels of six anterior pituitary hormones, including adrenocorticotropic hormone and growth hormone, in 32 drug-naive subjects (aged 6 to 18 years, all boys) with autism, and 34 healthy controls matched for age and gender. We also determined cortisol levels in these subjects by enzyme-linked immunosorbent assay. Serum levels of adrenocorticotropic hormone, growth hormone and cortisol were significantly higher in subjects with autism than in controls. In addition, there was a significantly positive correlation between cortisol and adrenocorticotropic hormone levels in autism.</p> <p>Conclusion</p> <p>Our results suggest that increased basal serum levels of adrenocorticotropic hormone accompanied by increased cortisol and growth hormone may be useful biological markers for autism.</p

Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism

<p>Abstract</p> <p>Background</p> <p>Axon-guidance proteins play a crucial role in brain development. As the dysfunction of axon-guidance signaling is thought to underlie the microstructural abnormalities of the brain in people with autism, we examined the postmortem brains of people with autism to identify any changes in the expression of axon-guidance proteins.</p> <p>Results</p> <p>The mRNA and protein expression of axon-guidance proteins, including ephrin (EFN)A4, eEFNB3, plexin (PLXN)A4, roundabout 2 (ROBO)2 and ROBO3, were examined in the anterior cingulate cortex and primary motor cortex of autistic brains (n = 8 and n = 7, respectively) and control brains (n = 13 and n = 8, respectively) using real-time reverse-transcriptase PCR (RT-PCR) and western blotting. Real-time RT-PCR revealed that the relative expression levels of EFNB3, PLXNA4A and ROBO2 were significantly lower in the autistic group than in the control group. The protein levels of these three genes were further analyzed by western blotting, which showed that the immunoreactive values for PLXNA4 and ROBO2, but not for EFNB3, were significantly reduced in the ACC of the autistic brains compared with control brains.</p> <p>Conclusions</p> <p>In this study, we found decreased expression of axon-guidance proteins such as PLXNA4 and ROBO2 in the brains of people with autism, and suggest that dysfunctional axon-guidance protein expression may play an important role in the pathophysiology of autism.</p

Alteration of Plasma Glutamate and Glutamine Levels in Children with High-Functioning Autism

浜松医科大学学位論文　医博第624号（平成24年3月19日

Plasma Cytokine Profiles in Subjects with High-Functioning Autism Spectrum Disorders

Accumulating evidence suggests that dysregulation of the immune system is involved in the pathophysiology of autism spectrum disorders (ASD). The aim of the study was to explore immunological markers in peripheral plasma samples from non-medicated subjects with high-functioning ASD.A multiplex assay for cytokines and chemokines was applied to plasma samples from male subjects with high-functioning ASD (n = 28) and matched controls (n = 28). Among a total of 48 analytes examined, the plasma concentrations of IL-1β, IL-1RA, IL-5, IL-8, IL-12(p70), IL-13, IL-17 and GRO-α were significantly higher in subjects with ASD compared with the corresponding values of matched controls after correction for multiple comparisons.The results suggest that abnormal immune responses as assessed by multiplex analysis of cytokines may serve as one of the biological trait markers for ASD

Vldlr overexpression causes hyperactivity in rats

Abstract Background Reelin regulates neuronal positioning in cortical brain structures and neuronal migration via binding to the lipoprotein receptors Vldlr and Lrp8. Reeler mutant mice display severe brain morphological defects and behavioral abnormalities. Several reports have implicated reelin signaling in the etiology of neurodevelopmental and psychiatric disorders, including autism, schizophrenia, bipolar disorder, and depression. Moreover, it has been reported that VLDLR mRNA levels are increased in the post-mortem brain of autistic patients. Methods We generated transgenic (Tg) rats overexpressing Vldlr, and examined their histological and behavioral features. Results Spontaneous locomotor activity was significantly increased in Tg rats, without detectable changes in brain histology. Additionally, Tg rats tended to show performance deficits in the radial maze task, suggesting that their spatial working memory was slightly impaired. Thus, Vldlr levels may be involved in determining locomotor activity and memory function. Conclusions Unlike reeler mice, patients with neurodevelopmental or psychiatric disorders do not show striking neuroanatomical aberrations. Therefore, it is notable, from a clinical point of view, that we observed behavioral phenotypes in Vldlr-Tg rats in the absence of neuroanatomical abnormalities.</p

Clinical Characteristics of Control Subjects and Individuals with HFA.

<p>BMI: body mass index.</p><p>ADIR: Autism Diagnostic Interview-Revised.</p><p>HFA: High-Functioning Autism.</p><p>Values are expressed as the mean ± SD.</p><p>Two-tailed unpaired <i>t</i>-test.</p

Plasma Levels of Glutamate and Glutamine in Control Subjects and Individuals with HFA.

<p>Fig. 1-a: Glutamate Levels; Fig. 1-b: Glutamine Levels. Plasma levels of glutamate and glutamine were determined using HPLC. Control subjects, N = 22; individuals with HFA, N = 23. <i>Left to right: t</i> = 3.77, <i>df</i> = 43, <i>p</i><0.002; <i>t</i> = −4.55, <i>df</i> = 43, <i>p</i><0.0004. The plasma glutamate level was significantly higher (<i>p</i><0.002), and the plasma glutamine level was significantly lower (<i>p</i><0.0004) in the HFA group than in the control group. When two autistic cases with extreme values were eliminated from the glutamate data, the results changed only negligibly; <i>p</i><0.002.</p

Plasma Levels of Amino Acids and related compounds in Control Subjects and Individuals with HFA.

<p>HFA: High-Functioning Autism.</p><p>Values are expressed as the mean ± SD.</p><p>Two-tailed unpaired <i>t</i>-test with the Bonferroni correction,</p><p>*<i>p</i><0.002,</p><p>**<i>p</i><0.0004.</p