{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:20:42Z","timestamp":1791822042526,"version":"4.3.4"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T00:00:00Z","timestamp":1557360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["3200B0-113902\/1, 32-135596"],"award-info":[{"award-number":["3200B0-113902\/1, 32-135596"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Behavioral Sciences"],"abstract":"<jats:p>Objectives: It is common nowadays to refer to autism as a spectrum. Increased evidence of the involvement of steroid metabolites has been shown by the presence of stronger alterations in Kanner\u2019s syndrome compared with Asperger syndrome. Methods: 24 h urine samples were collected from 20 boys with Asperger syndrome, 21 boys with Kanner\u2019s syndrome, and identically sized control groups, each matched for age, weight, and height for comprehensive steroid hormone metabolite analysis via gas chromatography\u2013mass spectrometry. Results: Higher levels of most steroid metabolites were detected in boys with Kanner\u2019s syndrome and Asperger syndrome compared to their matched controls. These differences were more pronounced in affected individuals with Kanner\u2019s syndrome versus Asperger syndrome. Furthermore, a specific and unique pattern of alteration of androsterone, etiocholanolone, progesterone, tetrahydrocortisone, and tetrahydrocortisol was identified in boys with Kanner\u2019s syndrome and Asperger syndrome. Interestingly, in both matched samples, only androsterone, etiocholanolone, progesterone, tetrahydrocortisone, tetrahydrocortisol, and 5a-tetrahydrocortisol groups were positively correlated. In the Asperger syndrome group, all metabolites showed a positive correlation. In the Kanner\u2019s syndrome group, 5-a tetrahydrocortisol with androsterone showed a positive correlation. Conclusions: Due to differences in the level of alteration, the premise that Asperger syndrome is on the mild side of the autism spectrum and that Kanner\u2019s syndrome is on the severe side is supported, but alteration patterns yield different phenotypic expressions.<\/jats:p>","DOI":"10.3390\/bs9050052","type":"journal-article","created":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T03:57:07Z","timestamp":1557719827000},"page":"52","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Steroid Metabolites Support Evidence of Autism as a Spectrum"],"prefix":"10.3390","volume":"9","author":[{"given":"Benedikt Andreas","family":"Gasser","sequence":"first","affiliation":[{"name":"Department of Clinical Research, University of Bern, 3010 Berne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"Kurz","sequence":"additional","affiliation":[{"name":"Intersci Research Association, Karl Morre Gasse 10, 8430 Leibnitz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Dick","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, University of Bern, 3010 Berne, Switzerland"},{"name":"Division of Nephrology\/Hypertension, University of Bern, 3010 Berne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus Georg","family":"Mohaupt","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, University of Bern, 3010 Berne, Switzerland"},{"name":"Teaching Hospital Internal Medicine, Lindenhofgruppe, 3006 Berne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gillberg, C., Fernell, E., Ko\u010dovsk\u00e1, E., Minnis, H., Bourgeron, T., Thompson, L., and Allely, C. (2017). The role of cholesterol metabolism and various steroid abnormalities in autism spectrum disorders: A hypothesis paper. Autism Res.","DOI":"10.1002\/aur.1777"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1017\/S0954579402003115","article-title":"The neurobiological basis of autism from a developmental perspective","volume":"14","author":"Akshoomoff","year":"2002","journal-title":"Dev. Psychopathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.psychres.2006.02.003","article-title":"Hypercholesterolemia in Asperger syndrome: Independence from lifestyle, obsessive-compulsive behavior, and social anxiety","volume":"149","author":"Dziobek","year":"2007","journal-title":"Psychiatry Res."},{"key":"ref_4","unstructured":"Van Elst, L.T. (2013). Patogenetische Modelle. Das Asperger-Syndrom im Erwachsenenalter, Medizinisch Wissenschaftliche Verlagsgesellschaft."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1093\/hmg\/9.6.861","article-title":"Autism: Recent molecular genetic advances","volume":"9","author":"Lamb","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_6","first-page":"443","article-title":"Genetic factors in Asperger syndrome","volume":"65","author":"Sasaki","year":"2007","journal-title":"Nihon Rinsho"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1038\/mp.2010.102","article-title":"Sex-specific serum biomarker patterns in adults with Asperger\u2019s syndrome","volume":"16","author":"Schwarz","year":"2011","journal-title":"Mol. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1046\/j.0021-9630.2003.00317.x","article-title":"Autism and pervasive developmental disorders","volume":"45","author":"Volkmar","year":"2004","journal-title":"J. Child Psychol. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1023\/A:1026012707581","article-title":"Nosological and genetic aspects of Asperger syndrome","volume":"28","author":"Volkmar","year":"1998","journal-title":"J. Autism Dev. Disord."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1038\/sj.mp.4001099","article-title":"Serotonin transporter promotor variants in autism: Functional effects and relationship to platelet hyperserotonemia","volume":"7","author":"Anderson","year":"2002","journal-title":"Mol. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1086\/342720","article-title":"A genomewide screen for autism-spectrum disorders: Evidence for a major susceptibility locus on chromosome 3q25-27","volume":"71","author":"Auranen","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lee, R.W., and Tierney, E. (2011). Hypothesis: The role of sterols in autism spectrum disorder. Autism Res. Treat., 653570.","DOI":"10.1155\/2011\/653570"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/2040-2392-2-16","article-title":"Investigation of the serum levels of anterior pituitary hormones in male children with autism","volume":"2","author":"Iwata","year":"2011","journal-title":"Mol. Autism"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.comppsych.2007.06.010","article-title":"Clinical evidence that Asperger\u2019s disorder is a mild form of autism","volume":"49","author":"Ritvo","year":"2008","journal-title":"Compr. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hu, V.W., Nguyen, A., Kim, K.S., Steinberg, M.E., Sarachana, T., Scully, M.A., Soldin, S.J., Luu, T., and Lee, N.H. (2009). Gene expression profiling of lymphoblasts from autistic and nonaffected sib pairs: Altered pathways in neuronal development and steroid biosynthesis. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005775"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.psyneuen.2014.07.015","article-title":"A review of rhythm and responsiveness of cortisol in individuals with autism spectrum disorders","volume":"49","author":"Taylor","year":"2014","journal-title":"Psychoneuroendocrinology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/jp.2012.165","article-title":"ACTH and cortisol cord plasma concentrations in preterm and term infants","volume":"33","author":"Bagnoli","year":"2013","journal-title":"J. Perinatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1824-7288-36-71","article-title":"Basal and adrenocorticotropic hormone stimulated plasma cortisol levels among Egyptian autistic children: Relation to disease severity","volume":"36","author":"Hamza","year":"2010","journal-title":"Ital. J. Pediatr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.psyneuen.2009.02.011","article-title":"Absence of a normal cortisol awakening response (CAR) in adolescent males with Asperger syndrome (AS)","volume":"34","author":"Brosnan","year":"2009","journal-title":"Psychoneuroendocrinology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00787-007-0632-1","article-title":"Slower cortisol response during ACTH stimulation test in autistic children","volume":"17","author":"Zekan","year":"2008","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.jpsychores.2004.12.004","article-title":"Higher plasma ACTH levels in adults with Asperger syndrome","volume":"58","author":"Tani","year":"2005","journal-title":"Psychosom. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1210\/jc.2005-2252","article-title":"Adrenocorticotropin preferentially up-regulates angiopoietin 2 in the human fetal adrenal gland: Implications for coordinated adrenal organ growth and angiogenesis","volume":"91","author":"Ishimoto","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1210\/jc.2007-2509","article-title":"The periphery of the human fetal adrenal gland is a site of angiogenesis: Zonal differential expression and regulation of angiogenic factors","volume":"93","author":"Ishimoto","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1210\/er.2010-0001","article-title":"Development and Function of the Human Fetal Adrenal Cortex: A Key Component in the Feto-Placental Unit","volume":"32","author":"Hitoshi","year":"2011","journal-title":"Endocr. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1016\/j.psyneuen.2011.02.007","article-title":"Increased serum androstenedione in adults with autism spectrum conditions","volume":"36","author":"Ruta","year":"2011","journal-title":"Psychoneuroendocrinology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1111\/j.1365-2265.2012.04443.x","article-title":"Pervasive developmental disorders in children of hyperandrogenic women with polycystic ovary syndrome: A longitudinal case-control study","volume":"77","author":"Palomba","year":"2012","journal-title":"Clin. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.psyneuen.2015.06.017","article-title":"Congenital adrenal hyperplasia and risk for psychiatric disorders in girls and women born between 1915 and 2010: A total population study","volume":"60","author":"Engberg","year":"2015","journal-title":"Psychoneuroendocrinology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"E554","DOI":"10.1210\/jc.2013-3707","article-title":"Increased psychiatric morbidity in men with congenital adrenal hyperplasia due to 21-hydroxylase deficiency","volume":"99","author":"Falhammar","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.physbeh.2014.09.014","article-title":"Prenatal hyperandrogenic environment induced autistic-like behavior in rat offspring","volume":"138","author":"Xu","year":"2015","journal-title":"Physiol. Behav."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.mehy.2006.10.015","article-title":"Spironolactone might be a desirable immunologic and hormonal intervention in autism spectrum disorders","volume":"68","author":"Bradstreet","year":"2006","journal-title":"Med. Hypotheses"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1210\/jc.2010-2504","article-title":"The human placenta expresses CYP17 and generates androgens de novo","volume":"96","author":"Escobar","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1093\/ije\/dyt282","article-title":"Maternal lifestyle and environmental risk factors for autism spectrum disorders","volume":"43","author":"Lyall","year":"2014","journal-title":"Int. J. Epidemiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s00787-013-0472-0","article-title":"Marked elevation of adrenal steroids, especially androgens, in saliva of prepubertal autistic children","volume":"23","author":"Majewska","year":"2014","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/mp.2014.48","article-title":"Elevated fetal steroidogenic activity in autism","volume":"20","author":"Auyeung","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.biopsycho.2013.05.011","article-title":"Postnatal testosterone levels and disorder relevant behavior in the second year of life","volume":"94","author":"Saenz","year":"2013","journal-title":"Biol. Psychol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1523\/JNEUROSCI.4389-11.2012","article-title":"Fetal testosterone influences sexually dimorphic gray matter in the human brain","volume":"32","author":"Lombardo","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_37","unstructured":"Popper, K.R. (1969). Logik der Forschung, Mohr Siebeck."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1007\/s10803-007-0428-7","article-title":"Differentiating autism and Asperger syndrome on the basis of language delay or impairment","volume":"38","author":"Bennett","year":"2008","journal-title":"J. Autism Dev. Disord."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0378-4347(00)80683-0","article-title":"Profiling steroid hormones and urinary steroids","volume":"379","author":"Shackleton","year":"1986","journal-title":"J. Chromatogr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11745-011-3605-6","article-title":"Role of a Disordered Steroid Metabolome in the Elucidation of Sterol and Steroid Biosynthesis","volume":"47","author":"Shackleton","year":"2012","journal-title":"Lipids"},{"key":"ref_41","first-page":"811","article-title":"Reduced 11B-hydroxysteroid dehydrogenase activity in patients with the nephrotic syndrome","volume":"84","author":"Vogt","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/BF01837709","article-title":"Die \u201cAutistischen Psychopathen\u201d im Kindesalter","volume":"117","author":"Asperger","year":"1944","journal-title":"Archiv f\u00fcr Psychiatrie und Nervenkrankheiten"},{"key":"ref_43","first-page":"217","article-title":"Autistic disturbances of affective contact","volume":"2","author":"Kanner","year":"1943","journal-title":"Nerv. Child"},{"key":"ref_44","first-page":"397","article-title":"Catecholamine Metabolism in Children with Asperger\u2019s and Kanner\u2019s Syndromes","volume":"5","author":"Gorinaa","year":"2011","journal-title":"Biomed. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1210\/er.2010-0013","article-title":"The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders","volume":"32","author":"Miller","year":"2011","journal-title":"Endocr. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1055\/s-2007-979158","article-title":"Serum androsterone levels in children","volume":"28","author":"Ueshiba","year":"1996","journal-title":"Horm. Metab. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1136\/bmj.3.5873.207","article-title":"Androsterone\/Etiocholanolone Ratios in Male Homosexuals","volume":"3","author":"Margolese","year":"1973","journal-title":"Br. Med. J."},{"key":"ref_48","first-page":"275","article-title":"Morphometric study of the human suprarenal gland in the first postnatal year","volume":"58","year":"2000","journal-title":"Folia Morphol. (Warsz)"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1111\/j.1365-2826.2008.01659.x","article-title":"Maternal antenatal anxiety and amniotic fluid cortisol and testosterone: Possible implications for foetal programming","volume":"20","author":"Sarkar","year":"2008","journal-title":"J. Neuroendocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/aur.80","article-title":"Genes related to sex steroids, neural growth, and social-emotional behavior are associated with autistic traits, empathy, and Asperger syndrome","volume":"2","author":"Chakrabarti","year":"2009","journal-title":"Autism Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/j.1365-2265.2007.02868.x","article-title":"Elevated levels of growth-related hormones in autism and autism spectrum disorder","volume":"67","author":"Mills","year":"2007","journal-title":"Clin. Endocrinol."}],"container-title":["Behavioral Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-328X\/9\/5\/52\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:50:29Z","timestamp":1760187029000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-328X\/9\/5\/52"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,9]]},"references-count":51,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["bs9050052"],"URL":"https:\/\/doi.org\/10.3390\/bs9050052","relation":{},"ISSN":["2076-328X"],"issn-type":[{"value":"2076-328X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,9]]}}}