The online version of this article (doi:10.1186/2040-2392-5-4) contains supplementary material, which is available to authorized users.
SB and JDC are consultants for Myriad-RBM. This does not affect policies regarding sharing of data and materials specified by this journal.
HS, JMR, PS and JDC carried out the molecular profiling data analyses. PCG, SB and SB-C interpreted the results, prepared the figures and tables, and wrote the manuscript. LR, SB, HR and SB-C designed the clinical studies and edited the manuscript. EI, LR, and BA coordinated clinical data collection. SB and SB-C conceived the study, interpreted the results and edited the manuscript. All authors read and approved the final manuscript.
The higher prevalence of Asperger Syndrome (AS) and other autism spectrum conditions in males has been known for many years. However, recent multiplex immunoassay profiling studies have shown that males and females with AS have distinct proteomic changes in serum.
Here, we analysed sera from adults diagnosed with AS (males = 14, females = 16) and controls (males = 13, females = 16) not on medication at the time of sample collection, using a combination of multiplex immunoassay and shotgun label-free liquid chromatography mass spectrometry (LC-MSE). The main objective was to identify sex-specific serum protein changes associated with AS.
Multiplex immunoassay profiling led to identification of 16 proteins that were significantly altered in AS individuals in a sex-specific manner. Three of these proteins were altered in females (ADIPO, IgA, APOA1), seven were changed in males (BMP6, CTGF, ICAM1, IL-12p70, IL-16, TF, TNF-alpha) and six were changed in both sexes but in opposite directions (CHGA, EPO, IL-3, TENA, PAP, SHBG). Shotgun LC-MSE profiling led to identification of 13 serum proteins which had significant sex-specific changes in the AS group and, of these, 12 were altered in females (APOC2, APOE, ARMC3, CLC4K, FETUB, GLCE, MRRP1, PTPA, RN149, TLE1, TRIPB, ZC3HE) and one protein was altered in males (RGPD4). The free androgen index in females with AS showed an increased ratio of 1.63 compared to controls.
Taken together, the serum multiplex immunoassay and shotgun LC-MSE profiling results indicate that adult females with AS had alterations in proteins involved mostly in lipid transport and metabolism pathways, while adult males with AS showed changes predominantly in inflammation signalling. These results provide further evidence that the search for biomarkers or novel drug targets in AS may require stratification into male and female subgroups, and could lead to the development of novel targeted treatment approaches.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders IV. 1994, Washington DC: American Psychiatric Press Inc, ISBN-10: 0890420262
Schwarz E, Guest PC, Rahmoune H, Harris LW, Wang L, Leweke FM, Rothermundt M, Bogerts B, Koethe D, Kranaster L, Ohrmann P, Suslow T, McAllister G, Spain M, Barnes A, van Beveren NJ, Baron-Cohen S, Steiner J, Torrey FE, Yolken RH, Bahn S: Identification of a biological signature for schizophrenia in serum. Mol Psychiatry. 2012, 17: 494-502. 10.1038/mp.2011.42. CrossRefPubMed
Martins-de-Souza D, Alsaif M, Ernst A, Harris LW, Aerts N, Lenaerts I, Peeters PJ, Amess B, Rahmoune H, Bahn S, Guest PC: The application of selective reaction monitoring confirms dysregulation of glycolysis in a preclinical model of schizophrenia. BMC research notes. 2012, 5: 146-10.1186/1756-0500-5-146. PubMedCentralCrossRefPubMed
Suzuki K, Matsuzaki H, Iwata K, Kameno Y, Shimmura C, Kawai S, Yoshihara Y, Wakuda T, Takebayashi K, Takagai S, Matsumoto K, Tsuchiya KJ, Iwata Y, Nakamura K, Tsujii M, Sugiyama T, Mori N: Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders. PLoS One. 2011, 6: e20470-10.1371/journal.pone.0020470. PubMedCentralCrossRefPubMed
Iwata K, Matsuzaki H, Miyachi T, Shimmura C, Suda S, Tsuchiya KJ, Matsumoto K, Suzuki K, Iwata Y, Nakamura K, Tsujii M, Sugiyama T, Sato K, Mori N: Investigation of the serum levels of anterior pituitary hormones in male children with autism. Mol Autism. 2011, 2: 16-10.1186/2040-2392-2-16. doi:10.1186/2040-2392-2-16 PubMedCentralCrossRefPubMed
Moses L, Katz N, Weizman A: Metabolic profiles in adults with autism spectrum disorder and intellectual disabilities. Eur Psychiatry. 2013, 10.1016/j.eurpsy.2013.05.005. [Epub ahead of print]
Palomba S, Marotta R, Di Cello A, Russo T, Falbo A, Orio F, Tolino A, Zullo F, Esposito R, La Sala GB: Pervasive developmental disorders in children of hyperandrogenic women with polycystic ovary syndrome: a longitudinal case-control study. Clin Endocrinol (Oxf). 2012, 77: 898-904. 10.1111/j.1365-2265.2012.04443.x. CrossRef
Bonnet F, Cephise FL, Gautier A, Dubois S, Massart C, Camara A, Larifla L, Balkau B, Ducluzeau PH: Role of sex steroids, intrahepatic fat and liver enzymes in the association between SHBG and metabolic features. Clin Endocrinol (Oxf). 2012, 79: 517-522. [Epub ahead of print] CrossRef
Chromogranin A, Duque M, Modlin IM, Gupta A, Saif MW: Biomarkers in neuroendocrine tumors. JOP. 2013, 14: 372-376.
Chu TM: Prostate cancer-associated markers. Immunol Ser. 1990, 53: 339-356. PubMed
Hong SW, Jin DH, Shin JS, Moon JH, Na YS, Jung KA, Kim SM, Kim JC, Kim KP, Hong YS, Lee JL, Choi EK, Lee JS, Kim TW: Ring finger protein 149 is an E3 ubiquitin ligase active on wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF). J Biol Chem. 2012, 287: 24017-24025. 10.1074/jbc.M111.319822. PubMedCentralCrossRefPubMed
Smits P, Bolton AD, Funari V, Hong M, Boyden ED, Lu L, Manning DK, Dwyer ND, Moran JL, Prysak M, Merriman B, Nelson SF, Bonafé L, Superti-Furga A, Ikegawa S, Krakow D, Cohn DH, Kirchhausen T, Warman ML, Beier DR: Lethal skeletal dysplasia in mice and humans lacking the golgin GMAP-210. N Engl J Med. 2010, 362: 206-216. 10.1056/NEJMoa0900158. PubMedCentralCrossRefPubMed
Li X, Liu B, Ji CN, Kang Y, Mao Y: Cloning and expression of ARMC3_v2, a novel splicing variant of the human ARMC3 gene. Genetika. 2006, 42: 999-1003. PubMed
Kameno Y, Iwata K, Matsuzaki H, Miyachi T, Tsuchiya KJ, Matsumoto K, Iwata Y, Suzuki K, Nakamura K, Maekawa M, Tsujii M, Sugiyama T, Mori N: Serum levels of soluble platelet endothelial cell adhesion molecule-1 and vascular cell adhesion molecule-1 are decreased in subjects with autism spectrum disorder. Mol Autism. 2013, 4: 19-10.1186/2040-2392-4-19. PubMedCentralCrossRefPubMed
van den Hengel LG, Versteeg HH: Tissue factor signalling: a multi-faceted function in biological processes. Front Biosci (Schol Ed). 2011, 3: 1500-1510. CrossRef
Asadabadi M, Mohammadi MR, Ghanizadeh A, Modabbernia A, Ashrafi M, Hassanzadeh E, Forghani S, Akhondzadeh S: Celecoxib as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial. Psychopharmacology (Berl). 2013, 225: 51-59. 10.1007/s00213-012-2796-8. CrossRef
Lai MC, Lombardo MV, Pasco G, Ruigrok AN, Wheelwright SJ, Sadek SA, Chakrabarti B, Baron-Cohen S, MRC AIMS Consortium: A behavioural comparison of male and female adults with high functioning autism spectrum conditions. PLoS One. 2011, 6: e20835-10.1371/journal.pone.0020835. PubMedCentralCrossRefPubMed
- Serum proteomic analysis identifies sex-specific differences in lipid metabolism and inflammation profiles in adults diagnosed with Asperger syndrome
Jordan M Ramsey
Paul C Guest
Jason D Cooper
- BioMed Central
Neu in den Fachgebieten Neurologie und Psychiatrie
Meistgelesene Bücher in der Neurologie & Psychiatrie