How autism became autism: The radical transformation of a central concept of child development in Britain. A controlled multivariate chart review of multiple complex developmental disorder. Recently, a large-scale meta-analysis aggregating close to 2,000,000 million participants found that individuals with ASD are 3.55 times more likely to have a concurrent diagnosis of SZ than controls (28). J Am Acad Child Adolesc Psychiatry. JM also receives royalties from Guilford Press, Lambert, and Springer. The differential diagnosis between these disorders and the comorbid diagnoses of the two conditions is often a bit of a quagmire for clinicians. Autism and Schizophrenia, though separate diagnostic entities, share some common clinical features. Central to the RDoC framework, these negative symptoms that overlap in their clinical manifestation may well stem from similar biological mechanisms. Walsh T, McClellan JM, McCarthy SE, et al. doi: 10.1007/s10803-008-0674-3, 41. We next ran two univariate ANOVAs with diagnosis (ASD, SZ or TD) as the independent variable in both models and SZ symptom type (positive or negative) as the respective dependent variable. J Autism Dev Disord (2016) 46(1):342–51. Autistic disorders and schizophrenia: related or remote? Bleuler E. Dementia praecox or the group of schizophrenias. Abstract OBJECTIVE: In the last several decades, considerable evidence has suggested that autism and schizophrenia are unrelated. For the present study, we recruited community samples of adults with ASD, SZ, and typical development (TD) and administered gold-standard diagnostic interviews for both ASD and SZ. Although the PANSS is intended to inform clinician judgment in considering severity of current psychosis symptoms, there are no diagnostic cut-off scores. Pervasive developmental disorder and childhood-onset schizophrenia: comorbid disorder or a phenotypic variant of a very early onset illness? Because of a history of at least 1 depressive episode and what appeared to be more of a chronic euphoric state with affective lability, George was given a provisional comorbid diagnosis of bipolar disorder with psychotic features. doi: 10.1001/archpsyc.1982.04290070025006, 32. Tamminga C, Holcomb H. Phenotype of schizophrenia: a review and formulation. 9. Additional work exploring the biological overlap between ASD and SZ, as well distinguishing positive symptoms of each disorder is clearly warranted. Positive symptoms in ASD encompass symptomology related to speech abnormalities such as echolalia or unusual intonation, atypical social behaviors such as exaggerated gesture and facial expressions, inappropriate social overtures, and symptoms related to stereotyped and repetitive behaviors or insistence on sameness such as unusual sensory sensitivities, repetitive hand or body movements, rigid insistence on routinized behavior, or circumscribed interests (34). PLoS One. Figure 2 *p < .05, ***p < .001 (two-tailed). No use, distribution or reproduction is permitted which does not comply with these terms. Wechsler D. WASI-II: Wechsler abbreviated scale of intelligence. JF-F helped design and conceptualize the study, assessed participants, and wrote and edited sections of the manuscript. While the specificity of the ADOS-2 was perfect (100%) in classifying TD participants (true negatives), there was a high percentage of SZ false positives, such that 43.59% of participants with SZ met ADOS-2 criteria for autism or autism-spectrum despite not meeting clinical DSM-5 criteria for ASD. • Dual diagnosis: o DSMIV did not allow for dual diagnosis of autism and ADHD. In contrast, positive items did a good job discriminating the ASD and SZ samples, AUC = .81, p < .001. doi: 10.1016/j.brainres.2010.11.031, 46. doi: 10.1093/schbul/13.2.261, 42. Across both measures of ASD and SZ symptoms, individuals from both diagnostic categories earned elevated negative symptom scores. doi: 10.1016/j.biopsych.2019.07.030, 47. The term dual diagnosis describes a situation where a person has both a developmental disability and a mental health problem. 3rd edition. J Autism Dev Disord (2000) 30(3):205–23. Meyer U, Feldon J, Dammann O. Schizophrenia and autism: both shared and disorder-specific pathogenesis via perinatal inflammation? ROC curves offer similar sensitivity and specificity information but differ in that, instead of using algorithm cut-off scores as in Table 2, ROC curves examine the extent to which continuous ADOS scores correctly classify participants into DSM-5 diagnostic categories. As reported in Table 2, sensitivity refers to the percentage of participants with ASD who met the ADOS-2 criteria for either autism or autism-spectrum. doi: 10.1038/nn1770, 26. 1998;39:911-919. doi: 10.1016/j.schres.2013.05.013, 25. 23. Symptom development in childhood onset schizophrenia. In the early years of the autism diagnosis, autism was thought by some to be a mental illness caused by poor parenting in the form of “refrigerator mothers” rather than a developmental disability caused by a difference in neurological type. Eye contact could be rated “unusual” for two very different examinees: one who does not make any eye contact, and a second who stares unrelentingly. In contrast, the ROC curve of PANSS-Positive was significant, AUC = .64, p = .030 but would still be considered a poor test in discriminating diagnostic categories. Although George’s psychotic symptoms are well controlled by the medication, symptoms of ASD persist, including poor eye contact, ongoing failure to develop appropriate peer relationships, inability to sustain a conversation with others, encompassing preoccupation with restricted patterns of interest, stereotypies, and repetitive motor mannerisms. The findings also point to the need for supplemental diagnostic measures that could more effectively parse symptom heterogeneity in ASD and better distinguish other disorders like SZ. Comparison of social cognitive functioning in schizophrenia and high functioning autism: more convergence than divergence. Resolving the matter of whether negative symptoms have similar or distinct biological mechanisms is critical for determining whether ASD and SZ populations are likely to benefit from similar treatments. Of particular interest, there was a strong, significant correlation between ADOS-Negative and PANSS-Negative, r = 0.58, p < .001, suggesting overlapping content between the two scales. Though ASD and SZ are now distinct disorders—today’s ASD remains a childhood-onset disorder whereas frank SZ predominantly emerges during young adulthood—the two disorders still share common genetic risk factors and symptom presentations (6, 14, 23–27). We are not advocating for the use of the subscales we created for diagnostic purposes. Positive Predictive Value (PPV) refers to the percentage of participants who met the ADOS-2 criteria who had an ASD diagnosis. Nowadays, in the DSM 5, it is possible to define comorbidity between autism and schizophrenia when in a patient are present both the positive symptoms of schizophrenia (SCZ) as well as the characteristics of the autism spectrum disorder (ASD). His thoughts are more linear, he rarely talks about “she,” and he is much more able to engage in his schoolwork. Second, we examined Receiver Operating Characteristic (ROC) curves using ADOS scores. Finally, intercorrelations between negative and positive dimensions of the PANSS and ADOS were explored to examine possible content overlap among the scales. The key aim of this study was to examine the utility of ASD and SZ diagnostic instruments in discriminating these respective disorders. Schizophr Bull (1985) 11(3):364–79. Social withdrawal, communication impairment, and poor eye contact seen in ASD are similar to the negative symptoms seen in youths with schizophrenia.11 When higher-functioning individuals with autism are stressed, they become highly anxious and at times may appear thought-disordered and paranoid, particularly when they are asked to shift set (such as being asked to change a topic of conversation or to stop an activity that they are engaged in and begin a new activity).12 A subset of children (28%) in the ongoing NIMH study of COS have been reported to have comorbid COS and ASD.7, A number of researchers use different terms to describe this complex mix of psychiatric comorbidity and developmental psychopathology. USA: American Psychiatric Publishing (1980). doi: 10.1016/j.schres.2007.10.024, 37. In this example, the first individual displays the absence of a typical behavior (negative symptom), whereas the second displays the presence of an atypical behavior (positive symptom). 1988;29:865-878. doi: 10.1093/schbul/sbn044, 34. It is important to remember that some individuals may have both COS and ASD, which has implications when designing appropriate biopsychosocial interventions. Many items on existing ASD measures do not clearly differentiate between positive and negative symptomology. Psychiatry 11:548. doi: 10.3389/fpsyt.2020.00548. (2008). The Positive and Negative Syndrome Scale for Schizophrenia Autism Severity Scale (PAUSS) in young people with autism and schizophrenia. I. More recently, the notion that ASD and schizophrenia can present comorbidly in a subset of patients has received further attention in the literature.7,29 Yet our current diagnostic hierarchy implies that the two conditions are distinct. The ADOS reliably discriminated ASD and TD adults, but there was a high rate of “false positives” in SZ patients who did not meet the DSM-5 criteria for ASD. In one study, participants with either ASD or SZ showed reduced neural activation in the right amygdala, fusiform face area, and ventrolateral prefrontal cortex compared to controls while performing complex social cognitive tasks (36). While positive and negative SZ symptoms have long been discussed and measured in the schizophrenia literature, this study shows for the first time that distinguishing positive and negative SZ symptoms in ASD has unique value. Eur Arch Psychiatry Clin Neurosci. Schizophr Bull (2009) 35(2):383–402. 2009;1:102. 1995;34:1096-1106. USA: American Psychiatric Publishing (1968). 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. A final limitation is that, paralleling clinical activity in ASD and SZ, this study was not supported by neuroimaging, electroencephalography, or genetic data. Basic principles of ROC analysis. 2. Schizophrenia and autism are two completely different neuro-psychological disorders. Grinker RR. Clinical genetic testing for patients with autism spectrum disorders. Foss-Feig JH, McPartland JC, Anticevic A, Wolf J. Re-conceptualizing ASD within a dimensional framework: Positive, negative, and cognitive feature clusters. Mol Psychiatry (2006) 11(9):815–36. New research at Swinburne has revealed a significant overlap in the traits associated with autism and schizophrenia. J Dev Behav Pediatr. Arora M, Praharaj SK, Sarkhel S, Sinha VK. The diagnosis had initially been made when George was 27 months old and had been reconfirmed by numerous well-regarded autism experts over the years. A controlled study of formal thought disorder in children with autism and multiple complex developmental disorders. Table 1 Sex Distributions and Means and Standard Deviations of Age and Intelligence (IQ). doi: 10.1016/S0193-953X(18)30171-0, 28. The PANSS also has a General Psychopathology scale that measures somatic concerns, anxiety, and depression among other symptoms, but this scale was not analyzed for the purposes of the present study. The term ‘autism’ was first introduced by Bleuler (14), not as an independent disorder, but as a symptom of schizophrenia, although Bleuler’s definition of autism, the symptom, shares little resemblance to today’s conceptualization of autism, the syndrome (15). Likewise, better understanding the neural mechanisms of more distinct positive features of SZ and ASD may provide clues to disorder-specific pathology that could be helpful for understanding etiology, distinguishing between disorders, and developing targeted treatment. Participants were excluded if they met the DSM-5 criteria for both ASD and SZ diagnosis (n = 2) as this would preclude inclusion in either group for sensitivity/specificity analyses. doi: 10.1146/annurev.clinpsy.1.102803.143959, 33. Retrospective studies of children with schizophrenia reveal delays in language acquisition and visual-motor coordination during early childhood before the onset of psychotic symptoms.9 Alaghband-Rad and colleagues10 reviewed the premorbid histories of children with COS and noted language delays and transient motor stereotypies (patterned repetitive movements, postures, and utterances). Positive items from the ADOS-2 include presence of atypical behaviors such as echolalia, stereotyped/idiosyncratic use of words/phrases, compulsions or rituals, or unusual sensory interests (see Supplemental Material for a full description of how ADOS-2 items were categorized into positive and negative symptoms). To examine our hypothesis that positive ASD symptoms would more effectively distinguish ASD and SZ, authors DT and JF grouped all ADOS-2 items (both algorithm and nonalgorithm) into positive and negative symptom categories. Positive symptoms, especially hallucinations, delusions, grandiosity and suspiciousness may be most indicative of SZ. “Negative symptoms”: Conceptual and methodological problems. Van der Gaag RJ, Buitelaar J, Van den Ban E, et al. In addition, sex ratios between groups were unequal, χ2 (2, N = 132) = 10.04, p = .007. Kumar RA, KaraMohamed S, Sudi J, et al. Participants were also excluded from analysis if they had full-scale intelligence quotient (IQ) score of less than 70 on the Wechsler Abbreviated Scale of Intelligence 2nd edition (WASI-II) (39). J Autism Dev Disord (2011) 41(9):1256–66. ‘Dementia praecocissima’: the Sante De Sanctis model of mental disorder in child psychiatry in the 20th century. Goals: • To record the diagnosis of autism on our computer system so involved staff are alerted to the presence of autism. His comorbid diagnosis was changed to schizoaffective disorder and, more recently, to schizophrenia. Findings from this study also call for increased research into the shared underlying biological systems that may give rise to ASD and SZ. Future research on this topic would benefit from measures that are a priori designed to categorize ASD symptoms into positive and negative symptoms similar to what is common practice for measuring SZ symptoms on instruments like the PANSS used in the present study. 2008;17:628-638. Pediatr Res (2011) 69(8):26–33. 2006;45:1104-1113. Cheung C, Yu K, Fung G, et al. 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. Clinician judgments about diagnoses were informed by a variety of information, including clinician interactions with participants during administration of diagnostic assessments and prior psychiatric and medical histories obtained during recruitment procedures. DT analyzed the data and wrote the bulk of the manuscript. Pathways to psychosis: a comparison of the pervasive developmental disorder subtype multiple complex developmental disorder and the “at risk mental state.” Schizophr Res. Limitations of this study include the small sample size and unequal sex and IQ among the different diagnosis groups. All rights reserved. Dual diagnosis: Few specialists know how to identify and treat people who have both autism and schizophrenia. Comorbid association of autism and schizophrenia. ASD, Autism Spectrum Disorder; SZ, Schizophrenia; TD, Typical Development. Lord C, Risi S, Lambrecht L, Cook EH, Leventhal BL, DiLavore PC, et al. Author. Nat Neurosci (2006) 9(10):1218–20. The question regarding whether there is phenotypic overlap or comorbidity between autism and schizophrenia dates back to 1943, when Kanner1 first used the term “autism” to describe egocentricity. – Considerable confusion surrounds the overlapping of autism and schizophrenia. |, https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00548/full#supplementary-material, Creative Commons Attribution License (CC BY). However, our IQ range was relatively typical of SZ samples, and lesser cognitive impairment in adults with ASD compared to SZ may more accurately represent these respective populations (50). doi: 10.1177/0952695113484320. What new information does this article add? ASD, Autism Spectrum Disorder; SZ. 16. 20. doi: 10.1097/CHI.0b013e31818b1c63, 11. 9. 30. Autism spectrum disorders and childhood-onset schizophrenia: clinical and biological contributions to a relation revisited. In these children, the hallucinations or delusional preoccupations may initially be attributed to the developmental disorder. Comorbid association of autism and schizophrenia. This study was approved by the Yale University School of Medicine Human Subject Investigation Committee. For example, negative symptoms in SZ include flat or blunted affect (e.g., reduced affective sharing, eye contact, facial expressions, and use of gesture), alogia (impoverished speech, perhaps reflecting difficulties with thinking and cognition), avolition/apathy (lack of energy, drive, and interest), anhedonia (lack of social and recreational interest), and inattentiveness (35). The key take-away point is that there are some individuals who may have both COS and ASD. All analyses on diagnostic accuracy are based on the ADOS-2 algorithm cut-off scores and the subset of items that comprise this algorithm. A thorough description is beyond the scope of this article, however. George had received the usual autism-specific services, and although he made gains, he continued to present with atypical behaviors. Association between schizophrenia and autism spectrum disorder: A systematic review and meta-analysis. 2010;5:e12233. J Autism Dev Disord (2009) 39(5):693–705. When he first presented to the clinic, he was disinhibited, emotionally unstable, and talked at length about his “other world.” His thoughts were loosely connected and he spoke about the friends in his other world who were talking to him. 1995;34:1273-1283. Table 2 Sensitivity and Specificity of ADOS-2: Algorithm Scores. For negative symptoms, the ASD group scored significantly higher than the TD group (p < .001), and group differences between the SZ and TD groups approached significance as the SZ group scored marginally higher (p = .061). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Am J Psychiatry (1991) 148(12):1705–7. 25. Diagnosis had a statistically significant effect on both positive symptoms, F(2,87.49) = 57.69; p < .001 and negative symptoms, F(2,110.96) = 11.83; p < .001. Because diagnosis groups had unequal IQ and sex distributions, we ran four additional ANCOVAs with diagnosis group as the independent variable, sex and IQ as covariates, and ADOS-Positive, ADOS-Negative, PANSS-Positive, and PANSS-Negative as the respective dependent variables in each ANCOVA. Psychiatric comorbidities and schizophrenia. Genetic overlap between autism, schizophrenia and bipolar disorder. The AUC for the entire sample was .84, p < .001, suggesting ADOS algorithm scores are a good test for discriminating ASD from the combined TD and SZ groups according to Metz’s (42) standards. Participants were matched on mean age but there were statistically significant group differences in IQ (see Table 1), F(2,129) = 13.661, p < .001, such that the SZ group had significantly lower IQ than the ASD group (p = .006) and the TD group (p < .001). 2004;161:2115-2117. 1972;2:315-337. In contrast, positive symptoms in ASD and SZ may be more disorder-specific. He is currently taking a typical antipsychotic. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. WB Saunders. London, England: SAGE Publications Sage UK (2018). The boundaries of schizophrenia. Prior to the release of the DSM-III (16) when ASD was first presented as a distinct clinical diagnosis, children now considered to have ASD were commonly diagnosed with “childhood onset schizophrenia” (17)—a childhood disorder characterized by abnormal perceptions of reality in addition to deficits in social functioning (18). In 1971, Kolvin2 conducted seminal research that highlighted the distinction between autism and schizophrenia, which influenced the decision to include the disorders as 2 separate categories in DSM-III. • We like to “keep it simple”, but this may not be possible • Change in diagnoses with aging. 28. Emil Kraepelin: A pioneer of scientific understanding of psychiatry and psychopharmacology. The Cognitive Neuroscience of Schizophrenia. Post hoc comparisons revealed that the SZ group scored higher on positive SZ symptoms than both the ASD group (p = .022) and the TD group (ps < .001), and the ASD group scored higher than the TD group (p < .001). Conceptualizing “borderline syndrome of childhood” and “childhood schizophrenia” as a developmental disorder. These results suggest that, when making a differential diagnosis between ASD and SZ, clinicians may benefit from focusing on the presence or absence of positive ASD and SZ symptoms. George also had unusual behaviors and mood-regulation difficulties. Schizophr Bull (2009) 35(5):1022–9. Developmental delays are described premorbidly in samples of children and adults with schizophrenia. J Am Acad Child Adolesc Psychiatry. Over the ensuing years, despite a number of medication trials including atypical antipsychotics and mood stabilizers, he became tortured by more persistent auditory hallucinations. COS-the onset of psychosis before age 13 years-is considered a rare and severe form of schizophrenia. Initially, these friends were humming to him or saying hello. Buckley PF, Miller BJ, Lehrer DS, Castle DJ. doi: 10.1007/s10803-010-1157-x, 44. As such, there is an unfortunate missed opportunity here to dissociate potentially clinically and biologically meaningful differences in behavior (see Supplemental Material for other ADOS-2 examples). Schizophrenia and autism are two completely different neuro-psychological disorders. 14. ASD symptoms were measured using the ADOS-2 (38). Keywords: autism, schizophrenia, Autism Diagnostic Observation Schedule, Positive and Negative Syndrome Scale, positive symptoms, negative symptoms, symptom overlap, Citation: Trevisan DA, Foss-Feig JH, Naples AJ, Srihari V, Anticevic A and McPartland JC (2020) Autism Spectrum Disorder and Schizophrenia Are Better Differentiated by Positive Symptoms Than Negative Symptoms. AN helped with statistical analysis and reviewed drafts of the paper. J Autism Dev Disord (2014) 44(1):111–9. Sprong M, Becker HE, Schothorst PF, et al. These studies would benefit from the inclusion of genetics and characterization of family members to get a clearer sense of the genotype-phenotype associations and predictors of outcome. 6. Volkmar FR, Cohen DJ. As an example, item B1 of the ADOS-2 relates to “unusual eye contact,” which is coded when the examiner observes poorly modulated eye contact used to initiate or regulate social interactions. As such, though both instruments are intended to index “syndrome-specific” symptoms, due to overlapping negative symptomatology, individuals with ASD often obtain elevated scores on the PANSS and those with SZ on the ADOS-2 despite not also carrying the second diagnosis. Jänsch C, Hare DJ. Couture S, Penn D, Losh M, Adolphs R, Hurley R, Piven J. Meta-Analysis of Cognitive Performance in Neurodevelopmental Disorders during Adulthood: Comparisons between Autism Spectrum Disorder and Schizophrenia on the Wechsler Adult Intelligence Scales. The degree of symptom overlap on these measures between participant groups was analyzed using Analyses of Variance (ANOVAs), Receiver Operating Characteristic (ROC) Curves, and Analyses of Covariance (ANCOVAs) to control for group differences in IQ and sex distributions. Researchers have long suspected that autism and schizophrenia are related. Psychiatr Clinics North Am (1993) 16(2):217–44. George was referred to Dr Frazier because of an increase in the intensity and frequency of unusual and disturbing preoccupations that often had a morbid theme. If a child is socially withdrawn and does not make eye contact when communicating with others, is the diagnosis schizophrenia or autism (Dvir & Frazier, 2011)? Clear differences include schizophrenia’s psychosis which often involves hallucinations. AA consults and holds equity in BlackThorn Therapeutics. To identify the reasons for low specificity in the SZ sample, we categorized ASD and SZ symptoms into ‘positive’ (presence of atypical behaviors) and ‘negative’ (absence of typical behaviors) symptoms. Alcohol and drug problem tend to occur with depression, anxiety disorders, schizophrenia, personality disorders, etc. Vorstman JA, Morcus ME, Duijff SN, et al. Am J Psychiatry. ASD, SZ, and TD groups were then compared on positive and negative ASD symptom dimensions. Their findings suggest early developmental abnormalities of the temporal and frontal lobes as evidenced by prepsychotic language difficulties; the early transient motor stereotypies indicate developmental abnormalities of the basal ganglia. doi: 10.1093/schbul/sbn135, 31. TD participants were excluded if they had any history of a psychiatric diagnosis or if they had immediate family members with an ASD or SZ diagnosis. 38. Seventeen out of 39 participants (43.59%) with a SZ diagnosis met the ADOS-2 criteria for autism or autism-spectrum despite not meeting the DSM-5 criteria for ASD by consensus diagnosis (Table 2). We thank the clinicians who assisted in clinical assessment of the participants in the study, including Julie Wolf, Brianna Lewis, Kimberly Ellison, and Ela Jarzabek. Recent studies suggest there are deeper relations in biological and clinical links between schizophrenia and autism. Adopting this framework from the SZ literature offers a new way of conceptualizing ASD symptomology that could better capture heterogeneity and allow for a dimensional approach to studying and treating shared and distinct symptomology across overlapping diagnostic categories. Berney TP. Therefore, we ran Brown––Forsythe tests to examine equality of means and Games–Howell post hoc comparisons, which are more robust to homogeneity of variance violations. 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Ct, et al developed but represent a potentially viable clinical tool in addition, ratios..., DC: American Psychiatric Pub ( 2013 ) 148 ( 1-3 ):164–75 have yet... Key aim of this disorder really complicated and diagnostic confusion 55 % of the.! ; Accepted: 28 may 2020 ; Accepted: 28 may 2020 ; Accepted: 28 may 2020 ;:... Have a similarity to those seen in autism-related disorders created to examine possible content among... For a measure of severity in autism spectrum disorder: neurobehavioral studies edited sections of the relationship between autism disorders! Variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia and autism are complex and high! Share some common clinical features RF, Brown W, Strandburg R. children a. Continued to present with atypical behaviors ASD symptoms were measured using the ADOS-2 38...

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