Autism beyond diagnostic categories: characterization of autistic phenotypes in schizophrenia

BMC Psychiatry

Hannelore Ehrenreich²  Matthias Dose⁵  Tobias Banaschewski³  Joachim Becker¹  Luise Poustka³  Christiane Bach³  Beata Stepniak¹  Sarah Everts¹  Tanja Maria Michel⁴  Martin Begemann²  Anne Kästner¹ 

[1] Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str.3, Göttingen, 37075, Germany;DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany;Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany;Department of Psychiatry, Institute for Clinical Research, University of Southern Denmark, Odense, Denmark;kbo-Isar-Amper-Klinikum Taufkirchen, Taufkirchen (Vils), Germany

关键词: Adults;    Empathy quotient;    Autism quotient;    Diagnostics;    Autism diagnostic observation schedule;    Positive and negative syndrome scale;    Autism spectrum disorders;   

Others  :  1210181
DOI  :  10.1186/s12888-015-0494-x

 received in 2015-02-27, accepted in 2015-04-29,  发布年份 2015

【 摘 要 】

Background

Behavioral phenotypical continua from health to disease suggest common underlying mechanisms with quantitative rather than qualitative differences. Until recently, autism spectrum disorders and schizophrenia were considered distinct nosologic entities. However, emerging evidence contributes to the blurring of symptomatic and genetic boundaries between these conditions. The present study aimed at quantifying behavioral phenotypes shared by autism spectrum disorders and schizophrenia to prepare the ground for biological pathway analyses.

Methods

Specific items of the Positive and Negative Syndrome Scale were employed and summed up to form a dimensional autism severity score (PAUSS). The score was created in a schizophrenia sample (N = 1156) and validated in adult high-functioning autism spectrum disorder (ASD) patients (N = 165). To this end, the Autism Diagnostic Observation Schedule (ADOS), the Autism (AQ) and Empathy Quotient (EQ) self-rating questionnaires were applied back to back with the newly developed PAUSS.

Results

PAUSS differentiated between ASD, schizophrenia and a disease-control sample and substantially correlated with the Autism Diagnostic Observation Schedule. Patients with ADOS scores ≥12 obtained highest, those with scores <7 lowest PAUSS values. AQ and EQ were not found to vary dependent on ADOS diagnosis. ROC curves for ADOS and PAUSS resulted in AuC values of 0.9 and 0.8, whereas AQ and EQ performed at chance level in the prediction of ASD.

Conclusions

This work underscores the convergence of schizophrenia negative symptoms and autistic phenotypes. PAUSS evolved as a measure capturing the continuous nature of autistic behaviors. The definition of extreme-groups based on the dimensional PAUSS may permit future investigations of genetic constellations modulating autistic phenotypes.

【 授权许可】

   
2015 Kästner et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Fig. 2.

【 参考文献 】

• [1]Baron-Cohen S, Wheelwright S, Skinner R, Martin J, Clubley E: The autism-spectrum quotient (AQ): evidence from Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians. J Autism Dev Disord 2001, 31(1):5-17.
• [2]Jones RM, Cadby G, Melton PE, Abraham LJ, Whitehouse AJ, Moses EK: Genome-wide association study of autistic-like traits in a general population study of young adults. Front Hum Neurosci 2013, 7:658.
• [3]Ronald A, Happe F, Price TS, Baron-Cohen S, Plomin R: Phenotypic and genetic overlap between autistic traits at the extremes of the general population. J Am Acad Child Adolesc Psychiatry 2006, 45(10):1206-14.
• [4]Ronald A, Hoekstra RA: Autism spectrum disorders and autistic traits: a decade of new twin studies. Am J Med Genet B Neuropsychiatr Genet 2011, 156B(3):255-74.
• [5]Courty A, Maria AS, Lalanne C, Ringuenet D, Vindreau C, Chevallier C, et al.: Levels of autistic traits in anorexia nervosa: a comparative psychometric study. BMC Psychiatry 2013, 13:222. BioMed Central Full Text
• [6]Bleuler E: Dementia Precox oder Gruppe der Schizophrenien. In Handbuch der Psychiatrie. Deuticke, Leipzig, Germany; 1911.
• [7]Crespi BJ: Revisiting Bleuler: relationship between autism and schizophrenia. Br J Psychiatry 2010, 196(6):495.
• [8]Kanner L: Autistic disturbances of affective contact. Acta Paedopsychiatr 1968, 35(4):100-36.
• [9]Parnas J, Bovet P: Autism in schizophrenia revisited. Compr Psychiatry 1991, 32(1):7-21.
• [10]Konstantareas MM, Hewitt T: Autistic disorder and schizophrenia: diagnostic overlaps. J Autism Dev Disord 2001, 31(1):19-28.
• [11]APA: Diagnostic and statistical manual of mental disorders. 4th edition. American Psychiatric Association, Washington, DC; 2000.
• [12]Borsboom D, Cramer AO, Schmittmann VD, Epskamp S, Waldorp LJ: The small world of psychopathology. PLoS One 2011., 6(11) Article ID e27407
• [13]Cross-Disorder Group of the Psychiatric Genomics C: Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis Lancet 2013, 381(9875):1371-9.
• [14]Doherty JL, Owen MJ: Genomic insights into the overlap between psychiatric disorders: implications for research and clinical practice. Genome Med 2014, 6(4):29. BioMed Central Full Text
• [15]Waltereit R, Banaschewski T, Meyer-Lindenberg A, Poustka L: Interaction of neurodevelopmental pathways and synaptic plasticity in mental retardation, autism spectrum disorder and schizophrenia: implications for psychiatry. World J Biol Psychiatry 2014, 15(7):507-516.
• [16]Bevan Jones R, Thapar A, Lewis G, Zammit S: The association between early autistic traits and psychotic experiences in adolescence. Schizophr Res 2012, 135(1-3):164-9.
• [17]Stahlberg O, Soderstrom H, Rastam M, Gillberg C: Bipolar disorder, schizophrenia, and other psychotic disorders in adults with childhood onset AD/HD and/or autism spectrum disorders. J Neural Transm 2004, 111(7):891-902.
• [18]Waris P, Lindberg N, Kettunen K, Tani P: The relationship between Asperger’s syndrome and schizophrenia in adolescence. Eur Child Adolesc Psychiatry 2013, 22(4):217-23.
• [19]de Haan L, Bakker JM: Overview of neuropathological theories of schizophrenia: from degeneration to progressive developmental disorder. Psychopathology 2004, 37(1):1-7.
• [20]Murray RM, Lewis SW: Is schizophrenia a neurodevelopmental disorder? Br Med J 1987, 295(6600):681-2.
• [21]Owen MJ, O’Donovan MC, Thapar A, Craddock N: Neurodevelopmental hypothesis of schizophrenia. Br J Psychiatry 2011, 198(3):173-5.
• [22]Burbach JP, van der Zwaag B: Contact in the genetics of autism and schizophrenia. Trends Neurosci 2009, 32(2):69-72.
• [23]Carroll LS, Owen MJ: Genetic overlap between autism, schizophrenia and bipolar disorder. Genome Med 2009, 1(10):102. BioMed Central Full Text
• [24]Gauthier J, Siddiqui TJ, Huashan P, Yokomaku D, Hamdan FF, Champagne N, et al.: Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia. Hum Genet 2011, 130(4):563-73.
• [25]Rapoport J, Chavez A, Greenstein D, Addington A, Gogtay N: Autism spectrum disorders and childhood-onset schizophrenia: clinical and biological contributions to a relation revisited. J Am Acad Child Adolesc Psychiatry 2009, 48(1):10-8.
• [26]Bastiaansen JA, Meffert H, Hein S, Huizinga P, Ketelaars C, Pijnenborg M, et al.: Diagnosing autism spectrum disorders in adults: the use of Autism Diagnostic Observation Schedule (ADOS) module 4. J Autism Dev Disord 2011, 41(9):1256-66.
• [27]King BH, Lord C: Is schizophrenia on the autism spectrum? Brain Res 2011, 1380:34-41.
• [28]Cheung C, Yu K, Fung G, Leung M, Wong C, Li Q, et al.: Autistic disorders and schizophrenia: related or remote? An anatomical likelihood estimation. PLoS One 2010., 5(8) Article ID e12233
• [29]Begemann M, Grube S, Papiol S, Malzahn D, Krampe H, Ribbe K, et al.: Modification of cognitive performance in schizophrenia by complexin 2 gene polymorphisms. Arch Gen Psychiatry 2010, 67(9):879-88.
• [30]Ribbe K, Friedrichs H, Begemann M, Grube S, Papiol S, Kästner A, et al.: The cross-sectional GRAS sample: a comprehensive phenotypical data collection of schizophrenic patients. BMC Psychiatry 2010, 10:91. BioMed Central Full Text
• [31]Kästner A, Grube S, El-Kordi A, Stepniak B, Friedrichs H, Sargin D, et al.: Common variants of the genes encoding erythropoietin and its receptor modulate cognitive performance in schizophrenia. Mol Med 2012, 18:1029-40.
• [32]Kay SR, Fiszbein A, Opler LA: The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987, 13(2):261-76.
• [33]Lord C, Risi S, Lambrecht L, Cook EH Jr, Leventhal BL, DiLavore PC, et al.: The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord 2000, 30(3):205-23.
• [34]Lord C, Rutter M, Goode S, Heemsbergen J, Jordan H, Mawhood L, et al.: Autism diagnostic observation schedule: a standardized observation of communicative and social behavior. J Autism Dev Disord 1989, 19(2):185-212.
• [35]Hus V, Lord C: The autism diagnostic observation schedule, module 4: revised algorithm and standardized severity scores. J Autism Dev Disord 2014, 44(8):1996-2012.
• [36]Baron-Cohen S, Wheelwright S: The empathy quotient: an investigation of adults with Asperger syndrome or high functioning autism, and normal sex differences. J Autism Dev Disord 2004, 34(2):163-75.
• [37]Baron-Cohen S, Wheelwright S, Robinson J, Woodbury-Smith M: The Adult Asperger Assessment (AAA): a diagnostic method. J Autism Dev Disord 2005, 35(6):807-19.
• [38]Tewes U: Hamburger-Wechsler-Intelligenztest fuer Erwachsene (HAWIE-R). Huber, Bern; 1991.
• [39]Ehrenreich H, Nave KA: Phenotype-Based Genetic Association Studies (PGAS)-Towards Understanding the Contribution of Common Genetic Variants to Schizophrenia Subphenotypes. Genes 2014, 5(1):97-105.
• [40]Lehnhardt FG, Gawronski A, Pfeiffer K, Kockler H, Schilbach L, Vogeley K: The investigation and differential diagnosis of Asperger syndrome in adults. Dtsch Arztebl Int 2013, 110(45):755-63.
• [41]Michel TM, Sheldrick AJ, Frentzel TG, Herpertz-Dahlmann B, Herpertz S, Habel U, et al.: [Evaluation of diagnostic and therapeutic services in German university hospitals for adults with autism spectrum disorder (ASD)]. Fortschr Neurol Psychiatr 2010, 78(7):402-13.
• [42]Autism, Developmental Disabilities Monitoring Network Surveillance Year Principal I, Centers for Disease C, Prevention: Prevalence of autism spectrum disorders--Autism and Developmental Disabilities Monitoring Network, 14 sites, United States 2008 Morb Mortal Wkly Rep Surveill Summ 2012, 61(3):1-19.
• [43]Geschwind DH: Advances in autism. Annu Rev Med 2009, 60:367-80.
• [44]Neggers YH: Increasing prevalence, changes in diagnostic criteria, and nutritional risk factors for autism spectrum disorders. ISRN Nutrition 2014, 2014:514026.
• [45]Henderson HA, Zahka NE, Kojkowski NM, Inge AP, Schwartz CB, Hileman CM, et al.: Self-referenced memory, social cognition, and symptom presentation in autism. J Child Psychol Psychiatry 2009, 50(7):853-61.
• [46]Lombardo MV, Barnes JL, Wheelwright SJ, Baron-Cohen S: Self-referential cognition and empathy in autism. PLoS One 2007., 2(9) Article ID e883
• [47]Sheitman BB, Kraus JE, Bodfish JW, Carmel H: Are the negative symptoms of schizophrenia consistent with an autistic spectrum illness? Schizophr Res 2004, 69(1):119-20.
• [48]Reichelt AC, Rodgers RJ, Clapcote SJ: The role of neurexins in schizophrenia and autistic spectrum disorder. Neuropharmacology 2012, 62(3):1519-26.
• [49]Voineskos AN, Lett TA, Lerch JP, Tiwari AK, Ameis SH, Rajji TK, et al.: Neurexin-1 and frontal lobe white matter: an overlapping intermediate phenotype for schizophrenia and autism spectrum disorders. PLoS One 2011., 6(6) Article ID e20982
• [50]Jenkins A, Apud JA, Zhang F, Decot H, Weinberger DR, Law AJ: Identification of Candidate Single-Nucleotide Polymorphisms in NRXN1 Related to Antipsychotic Treatment Response in Patients with Schizophrenia. Neuropsychopharmacology 2014, 39(9):2170-8.
• [51]Lett TA, Tiwari AK, Meltzer HY, Lieberman JA, Potkin SG, Voineskos AN, et al.: The putative functional rs1045881 marker of neurexin-1 in schizophrenia and clozapine response. Schizophr Res 2011, 132(2-3):121-4.
• [52]Souza RP, Meltzer HY, Lieberman JA, Le Foll B, Kennedy JL: Influence of neurexin 1 (NRXN1) polymorphisms in clozapine response. Hum Psychopharmacololgy 2010, 25(7-8):582-5.