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Autism is a pervasive developmental disorder diagnosed in early childhood. Abnormalities of serotonergic neurotransmission have been reported in autism. Serotonin transporter (5-HTT), which modulates serotonin levels, is a major therapeutic target in autism. Therefore, factors that regulate 5-HTT expression might be implicated in autism. One candidate 5-HTT-regulatory protein is the presynaptic protein, syntaxin 1A (STX1A). We examined the association of STX1A with autism in a trio association study using DNA samples from Japanese trios with autistic probands. In TDT analysis, rs69510130 (p=0.027) showed nominal associations with autism; modest haplotype association was also observed. We further compared STX1A mRNA expression between the autistic and control groups in the postmortem brain. In the anterior cingulate gyrus region, STX1A expression in the autism group was found to be significantly lower than that of the control group. Thus, we suggest a possible role of STX1A in the pathogenesis of autism., (Copyright © 2010 Elsevier Inc. All rights reserved.)

We measured the mRNA levels of apolipoprotein E receptor type 2 (ApoER2) and very low-density lipoprotein receptor (VLDLR) in peripheral blood lymphocytes from 43 patients with major depressive disorder (27 drug-free patients and 16 medicated patients) and 43 age-matched healthy controls using a quantitative real-time RT-PCR method. The correlations between mRNA levels of both receptors and clinical variables in patients were also examined. The expression of ApoER2 mRNA, but not VLDLR, was significantly lower in patients as compared to controls, irrespective of the medication status. There was no statistically significant correlation between the reduction of ApoER2 mRNA levels and any of the clinical variables measured in patients. Results from this preliminary study suggest that the expression of ApoER2 may serve as a trait marker for major depressive disorder., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

The neurobiological basis for autism remains poorly understood. We hypothesized that adipokines, such as adiponectin, may play a role in the pathophysiology of autism. In this study, we examined whether serum levels of adiponectin are altered in subjects with autism. We measured serum levels of adiponectin in male subjects with autism (n=31) and age-matched healthy male subjects (n=31). The serum levels of adiponectin in the subjects with autism were significantly lower than that of normal control subjects. The serum adiponectin levels in the subjects with autism were negatively correlated with their domain A scores in the Autism Diagnostic Interview-Revised, which reflects their impairments in social interaction. This study suggests that decreased levels of serum adiponectin might be implicated in the pathophysiology of autism., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: The neurobiological basis of autism remains poorly understood. To examine the role played by serum cytokines in brain development, we hypothesized that Platelet-Derived Growth Factor (PDGF) and Vascular Endothelial Growth Factor (VEGF) may be associated with pathophysiology of autism. In this study, we screened serum levels of these growth factors in young male subjects with autism., Methods: We measured serum levels of PDGF subtypes and VEGF in the 31 male children with autism (6-19 years old) and 31 healthy age- and gender-matched subjects., Results: The serum levels of PDGF-BB in male children with autism (N=31, 5624.5+/-1651.8 pg/mL [mean+/-SD]) were significantly higher (two-tailed Student's t-test: p=0.0188) than those of normal control subjects (N=31, 4758.2+/-1521.5 pg/mL [mean+/-SD]). There was a significant and positive correlation (Pearson's r=0.5320, p=0.0010) between the serum levels of PDGF-BB and the Autism Diagnostic Interview-Revised (ADI-R) domain C scores, which represent stereotyped patterns of behavior in the children with autism. However, there were no marked or significant correlations between serum PDGF-BB levels and clinical variables, including the other ADI-R scores and Intellectual Quotient (IQ) scores by WAIS-R. There were no significant change and correlations with clinical variables in serum PDGF-AA, PDGF-AB, and VEGF levels in the children with autism., Conclusions: Increased levels of serum PDGF-BB homodimers might be implicated in the pathophysiology of autism., (Copyright 2009 Elsevier Inc. All rights reserved.)

Background: The mechanisms underlying the pathophysiology of autism are currently unknown. Given the role of hepatocyte growth factor (HGF) in brain development, we hypothesized that HGF plays a role in the pathophysiology of autism. In this study, we studied whether serum HGF levels are altered in subjects with high-functioning autism., Methods: Using an enzyme-linked immunosorbent assay (ELISA), we measured serum levels of HGF in 17 male adults with high-functioning autism and age-matched 18 male healthy subjects., Results: The serum levels (503.5+/-160.5 pg/mL (mean+/-SD)) of HGF in the subjects with high-functioning autism were significantly (Mann-Whitney U=34.0, p<0.001) lower than those (817.6+/-232.4 pg/mL (mean+/-SD)) of control subjects. However, there were no correlations between serum HGF levels and clinical variables in the patients., Conclusions: This study suggests that reduced HGF levels may play a role in the pathophysiology of high-functioning autism.

Background: The neurobiological basis for autism remains poorly understood. Given the key role of transforming growth factor-beta1 (TGF-beta1) in brain development, we hypothesized that TGF-beta1 plays a role in the pathophysiology of autism. In this study, we studied whether serum levels of TGF-beta1 are altered in patients with autism., Methods: We measured serum levels of TGF-beta1 in 19 male adult patients with autism and 21 age-matched male healthy subjects using enzyme-linked immunosorbent assay (ELISA)., Results: The serum levels (7.34+/-5.21 ng/mL (mean+/-S.D.)) of TGF-beta1 in the patients with autism were significantly (z=-5.106, p<0.001) lower than those (14.48+/-1.64 ng/mL (mean+/-S.D.)) of normal controls. However, there were no marked or significant correlations between serum TGF-beta1 levels and other clinical variables, including Autism Diagnostic Interview-Revised (ADI-R) scores, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), aggression, Theory of Mind, and Intellectual Quotient (IQ) in patients., Conclusions: These findings suggest that decreased levels of TGF-beta1 may be implicated in the pathophysiology of autism.

Background: Precise mechanisms underlying the pathophysiology of autism are currently unknown. Given the major role of glutamate in brain development, we have hypothesized that glutamatergic neurotransmission plays a role in the pathophysiology of autism. In this study, we studied whether amino acids (glutamate, glutamine, glycine, D-serine, and L-serine) related to glutamatergic neurotransmission are altered in serum of adult patients with autism., Methods: We measured serum levels of amino acids in 18 male adult patients with autism and age-matched 19 male healthy subjects using high-performance liquid chromatography., Results: Serum levels (mean = 89.2 microM, S.D. = 21.5) of glutamate in the patients with autism were significantly (t = -4.48, df = 35, p < 0.001) higher than those (mean = 61.1 microM, S.D. = 16.5) of normal controls. In contrast, serum levels of other amino acids (glutamine, glycine, d-serine, l-serine) in the patients with autism did not differ from those of normal controls. There was a positive correlation (r = 0.523, p = 0.026) between serum glutamate levels and Autism Diagnostic Interview-Revised (ADI-R) social scores in patients., Conclusions: The present study suggests that an abnormality in glutamatergic neurotransmission may play a role in the pathophysiology of autism.