This has significant implications for clinicians given that correct diagnosis is critical for treatment. Lord C, Risi S, Lambrecht L, Cook EH, Leventhal BL, DiLavore PC, et al. 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. Copy number variant and rare allele studies have found a relationship between autism and point and structural mutations in neurologins, neurexins, and related genes.7, There have also been reports that implicate the neurexin family in schizophrenia. Foss-Feig JH, McPartland JC, Anticevic A, Wolf J. Re-conceptualizing ASD within a dimensional framework: Positive, negative, and cognitive feature clusters. The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. Studies in the childhood psychoses. This fits with the neurodevelopmental insult and imbalance in excitatory and inhibitory transmission hypothesis for both autism and schizophrenia.20, Specific deletions associated with schizophrenia include 22q11.2, 1q21.1, and 15q13.3, which have been found to be associated with autism, attention-deficit disorder, and mental retardation.20 In individuals with velocardiofacial syndrome (chromosome 22q11), rates of ASD and psychosis are higher.21 Similarly, 16p11.2 microdeletions or microduplications have been reported in 1% of cases of autism and in 2% of the NIMH COS cohort.22-24 These copy number variants confer a risk for a range of neurodevelopmental phenotypes that include autism and schizophrenia.20 Although there have not been systemic comparisons of genome-wide association studies for autism and schizophrenia, some functional links have been reported at voltage-gated calcium channel genes, which are integral to presynaptic function and plasticity, across phenotypes.20, Both autism and schizophrenia have accelerated trajectories of brain development around the age of symptom onset: those with autism have an acceleration or brain overgrowth during the first 3 years of life, and those with COS have an acceleration of brain development (pruning) during adolescence.7, Cheung and colleagues25 attempted to quantify brain structural similarities and differences in ASD and schizophrenia using a quantified anatomical likelihood estimation approach to synthesize existing brain imaging datasets. 14. In contrast, positive symptoms in ASD and SZ may be more disorder-specific. What new information does this article add? Kuo SS, Eack SM. Dual diagnosis or co-occurring disorders is a term for someone who experiences a mental illness because of binge drinking, or the person abusing heroin during periods of mania. Copyright © 2020 Trevisan, Foss-Feig, Naples, Srihari, Anticevic and McPartland. For both analyses, tests for homogeneity of variances were violated. Clinical genetic testing for patients with autism spectrum disorders. Br J Psychiatry. Neurologins are a family of postsynaptic proteins that bind transsynaptically to neurexins, which are presynaptic proteins that seem necessary for both excitatory and inhibitory synaptogenesis and synapse maturation. • We like to “keep it simple”, but this may not be possible • Change in diagnoses with aging. The patients/participants provided their written informed consent to participate in this study. Lord C, Rutter M, DiLavore P, Risi S, Gotham K, Bishop S. Autism diagnostic observation schedule–2nd edition (ADOS-2). 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). 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. 8. 5. The negative symptom scale assesses blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and conversation flow, and stereotyped thinking. 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. 2005;15:465-476. 24. Biol Psychiatry (2019) 86(7):557–67. Am J Psychiatry. Specific deletions associated with schizophrenia include 22q11.2, 1q21.1, and 15q13.3, which have been found to be associated with autism, attention-deficit … Specificity refers to the percentage of participants without ASD who did not meet the ADOS-2 criteria. 39. It’s particularly important for the doctor to get to know the individual and his or her family and environment before attempting such a diagnosis. Kanner L. Autistic disturbances of affective contact. Schizophr Bull (2009) 35(5):1022–9. Asarnow RF, Brown W, Strandburg R. Children with a schizophrenic disorder: neurobehavioral studies. Table 1 Sex Distributions and Means and Standard Deviations of Age and Intelligence (IQ). JM consults with BlackThorn Therapeutics and has received research funding from Janssen Research and Development. The specificity of the ADOS-2 was perfect in TD (100%). Psychiatry Res (2005) 133(1):45–55. The ADOS-2 algorithm sums across a subset of scored items in order to categorize participants into autism (representing higher severity ASD traits), autism-spectrum (representing lesser severity of ASD traits, but still enough to constitute ASD criteria), and non-spectrum. Previous research has identified parallel deficits in social cognition in ASD and SZ (37) that may have similar origins in atypical neural activation of select brain areas (36). J Am Acad Child Adolesc Psychiatry. Morgese G, Lombardo GP. J Neural Transm. The phenomenology of childhood psychoses. Childhood-onset schizophrenia (COS), considered a rare and severe form of schizophrenia, frequently presents with premorbid developmental abnormalities. doi: 10.1017/S003329170999078X. San Antonio, TX: PsychCorp (2011). (2008). Second, in order to resolve this confusion, clinicians ought to focus on the presence or absence of positive symptom domains of both ASD and SZ. All analyses on diagnostic accuracy are based on the ADOS-2 algorithm cut-off scores and the subset of items that comprise this algorithm. Schizophrenia and autism are two completely different neuro-psychological disorders. Comparisons among the schizophrenia clusters and the autism group are presented in Table 2, and the WAIS-R data are presented graphically in Fig. Another limitation is that the ADOS-2 Positive and Negative items were derived post hoc and without a separate validation study, and many ADOS-2 items describing core ASD features could not be classified as either positive or negative so are omitted from our scales. Revista de Psiquiatría y … Oxford: International Universities Press (1950). Similarly, a study by Sprong and colleagues19 that compared youths with MCDD with youths at risk for psychosis found that although the groups clearly had differing early developmental and treatment histories, there were no differences in schizotypal traits, disorganization, and general prodromal symptoms. Carroll LS, Owen MJ. Jablensky A. Subtyping schizophrenia: implications for genetic research. Recurrent 16p11.2 microdeletions in autism. How autism became autism: The radical transformation of a central concept of child development in Britain. Berney TP. Tamminga C, Holcomb H. Phenotype of schizophrenia: a review and formulation. J Am Acad Child Adolesc Psychiatry. 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 Autism Dev Disord (2014) 44(1):111–9. Lam KS, Bodfish JW, Piven J. The ADOS-2 was administered by trained, research-reliable clinicians and consists of semistructured activities and conversations meant to sample a participant’s real-world social behavior and core autistic characteristics related to language and communication, reciprocal social interaction, imagination and creativity, stereotyped behaviors and restricted interests, and other atypical behaviors. Abstract OBJECTIVE: In the last several decades, considerable evidence has suggested that autism and schizophrenia are unrelated. Barch DM. An anatomical likelihood estimation. The two diagnoses started to take on separate lives, with age of diagnosis — around 4 years in autism and between 16 and 30 in schizophrenia — becoming an important differentiator. Klin A, Mayes LC, Volkmar FR, Cohen DJ. Finally, intercorrelations between negative and positive dimensions of the PANSS and ADOS were explored to examine possible content overlap among the scales. Dual Diagnosis. 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. In these children, the hallucinations or delusional preoccupations may initially be attributed to the developmental disorder. 22. Mandy W. The Research Domain Criteria: A new dawn for neurodiversity research? Nat Neurosci (2006) 9(10):1218–20. 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. What are the implications for psychiatric practice? (B) ROC curves predicting DSM-5 ASD or SZ diagnostic status based on continuous ADOS-2 negative and positive symptoms. Rethinking schizophrenia. Symptom overlap between ASD and SZ may be most apparent in the negative symptom domain, broadly reflecting deficits in social communication and social–emotional reciprocity. 1995;245:70-79. While statistically controlling for sex and IQ did not change the overall pattern of results, it would have been more ideal if all groups were equal on these participant characteristics. ‘Dementia praecocissima’: the Sante De Sanctis model of mental disorder in child psychiatry in the 20th century. 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). Foss-Feig JH. J Autism Dev Disord (2000) 30(3):205–23. Schizophrenia; TD, Typical Development. We predicted that positive symptoms from both the ADOS and PANSS would better discriminate ASD and SZ groups than negative symptoms. • Dual diagnosis: o DSMIV did not allow for dual diagnosis of autism and ADHD. 2000;176:20-25. 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. We then examined the ROC curves of the positive and negative scales we created to examine their functioning in discriminating diagnostic groups. Few positive ASD symptoms were noted in SZ patients, suggesting that ratings of these symptoms may be most helpful in making a differential diagnosis in this context. History Psychiatry (2019) 30(3):300–13. Bastiaansen JA, Meffert H, Hein S, Huizinga P, Ketelaars C, Pijnenborg M, et al. Asperger disorder in adults. 2007;37:1181-1191. All rights reserved. Central to the RDoC framework, these negative symptoms that overlap in their clinical manifestation may well stem from similar biological mechanisms. A professor is studying the differences between the social impairments found in autism and schizophrenia to help develop better treatments for people with both disorders. Autism spectrum disorder (ASD) and schizophrenia (SZ) are heterogenous neurodevelopmental disorders that overlap in symptom presentation. In addition, sex ratios between groups were unequal, χ2 (2, N = 132) = 10.04, p = .007. In the case of childhood autism, we need to be aware that there can be a dual diagnosis, meaning an autistic kid can also be schizophrenic. Such heterogeneity and overlap in these and other disorders motivated the National Institute of Mental Health (NIMH) to propose the Research Domain Criteria (RDoC) initiative in an effort to develop new ways of conceptualizing and clustering symptoms within and across different disorders (6). Indeed, others have delineated the importance of carefully considering how IQ affects the results of ADOS-2 assessments (40). doi: 10.1023/A:1005605528309, 10. © 2020 MJH Life Sciences and Psychiatric Times. 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. The reviewer MK declared a shared affiliation, though no other collaboration, with one of the authors, JF, to the handling editor. Kay SR, Fiszbein A, Opler LA. AA and VS were involved with conceptualization of the study, participant recruitment and assessment. 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. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. No use, distribution or reproduction is permitted which does not comply with these terms. Mol Psychiatry (2006) 11(9):815–36. 19. Also, the disorders are treated differently.2,3 Schizophrenia is thought to develop at a chance rate in individuals with autism. An investigation of the “jumping to conclusions” data-gathering bias and paranoid thoughts in Asperger syndrome. 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). 1998;39:911-919. Pinkham AE, Hopfinger JB, Pelphrey KA, Piven J, Penn DL. 40. Although autism has long been recognized as a separate diagnostic entity from schizophrenia, both disorders share clinical features. PloS One (2010) 5(5):e10887. The term dual diagnosis describes a situation where a person has both a developmental disability and a mental health problem. Yet some have not previously received a diagnosis of ASD. doi: 10.1176/ajp.148.12.1705, 12. 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. – During the last few years the prevalence of autism and Autism Spectrum Disorder (ASD) has increased greatly. 1995;16(3 suppl):S7-S11. Similarly, psychotic symptoms, such as delusions and auditory hallucinations have been observed in less impaired people with ASD and in what was previously termed “Asperger syndrome” (20–22) Although these autism subtypes (CDD and Asperger syndrome) are now subsumed under “autism spectrum disorder” as of DSM-5 (1), these findings demonstrate that psychotic symptoms can be associated with the full spectrum of autism severity. doi: 10.1016/j.ridd.2010.06.002, 30. A pattern emerged such that individuals with ASD and SZ have overlap in the overt presentation of negative symptoms, such as reduced social–emotional reciprocity, blunted affect, reduced nonverbal communication, apathy, reduced affect sharing, and reduced social overture and response, resulting in elevated scores in both groups on the negative scales of both the ADOS-2 and PANSS. Comorbid association of autism and schizophrenia. The editor and reviewers' affiliations are the latest provided on their Loop research profiles and may not reflect their situation at the time of review. 2. 2. It is noteworthy, however, that children who have childhood-onset schizophrenia (COS) show fairly high premorbid rates of early developmental abnormalities.2,4-7. Positive Predictive Value (PPV) refers to the percentage of participants who met the ADOS-2 criteria who had an ASD diagnosis. Sporn AL, Addington AM, Gogtay N, et al. Indian J Psychiatry (2010) 52(2):191. doi: 10.4103/0019-5545.64591, 13. In Figure 1A, we constrained the sample to just the ASD and TD samples or just the ASD and SZ samples. There is a need for further research to understand whether the mechanisms contributing to negative symptoms in ASD and SZ are shared or distinct. George had received the usual autism-specific services, and although he made gains, he continued to present with atypical behaviors. Diagnostic and statistical manual of mental disorders (4th Text Revision ed.). doi: 10.1038/nn1770, 26. 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. doi: 10.1177/0957154X19832776. 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. The Cognitive Neuroscience of Schizophrenia. doi: 10.1093/schbul/sbn044, 34. Rapoport J, Chavez A, Greenstein D, et al. 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. Funding for this study was provided by NIMH R01 MH107426 (JM, VS) and NIMH R01 MH119172 (JF-F). Every person with autism has a unique personality and combination of characteristics which can make the diagnosis of this disorder really complicated. A professor is studying the differences between the social impairments found in autism and schizophrenia to help develop better treatments for ...Schizophrenia and autism seem to overlap at multiple levels. The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00548/full#supplementary-material. 14. 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. J Am Acad Child Adolesc Psychiatry. 7. @AnnaBWell: I actually think that the dual diagnosis of schizophrenia spectrum + autism spectrum is under-reported, for several reasons. Atypical antipsychotics in children and adolescents with autistic and other pervasive developmental disorders. ASD and SZ groups overlapped on negative symptoms largely related to the absence of typical social and communicative behaviors, whereas disorder-specific positive symptoms differentiated ASD and SZ. J Clin Psychiatry. Diagnostic and statistical manual of mental disorders (2nd edition). Basic principles of ROC analysis. As the DSM-5 categorizes disorders primarily on symptom presentation, a key objective of RDoC is to work towards a classification system that clusters disorders based on biologically meaningful mechanisms—with the ultimate goal of better targeting optimal treatments (7). Autism spectrum diagnosis was confirmed by Diagnostic Interview for Social and Communication Disorders with a collateral informant. J Dev Behav Pediatr. Next, we examined several Receiver Operating Characteristic (ROC) curves using ADOS scores. • To ensure that clinical staff are … 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. Andreasen NC, Olsen S. Negative v positive schizophrenia: Definition and validation. Alcohol and drug problem tend to occur with depression, anxiety disorders, schizophrenia, personality disorders, etc. Reichenberg A, Harvey PD, Bowie CR, Mojtabai R, Rabinowitz J, Heaton RK, et al. A recurring issue is the overlap and boundaries between Intellectual Developmental Disorder (IDD), ASD and Schizophrenia Spectrum Disorders (SSD). .This article highlights the biological and clinical links between the two disorders, reviewing shared genetics, brain changes, and similarities and differences in clinical presentations. Adult psychiatrists may benefit from additional training in the diagnosis of ASD in adults, whereas child psychiatrists may benefit from increased comfort with identifying primary psychotic symptoms in autistic youth. King BH, Lord C. Is schizophrenia on the autism spectrum? 2008;99:38-47. These respective descriptions suggest an overlap between ASD and SZ related to the absence of typical social and communicative behaviors (9). We further expected that negative symptoms, quantified on both the ADOS-2 and the Structured Clinical Interview -Positive and Negative Syndrome Scale (SCI-PANSS) (35) would be relatively similar between ASD and SZ groups, whereas positive symptoms from each assessment would be more sensitive and disorder-specific. 26. Evidence of positive symptoms from both ASD and SZ diagnostic assessments may warrant a dual diagnosis, which recent research converges in suggesting occurs with more frequency than once thought (27, 46). Data used in the preparation of this manuscript are publicly available to approved researchers as part of the NIMH Data Archive (nda.nih.gov) in collection C2312. Because the SZ group had significantly lower IQ than the other groups and because groups had unequal sex distributions, we reran all main and post hoc analyses with PANSS and ADOS-2 (positive and negative scales) as dependent variables—this time statistically controlling for IQ and sex as covariates in ANCOVAs. Differential patterns of visual sensory alteration underlying face emotion recognition impairment and motion perception deficits in schizophrenia and autism spectrum disorder. Not surprisingly, these disorders frequently co-occur. doi: 10.1203/PDR.0b013e318212c196, 27. In our analysis with the ADOS-2, there were 11 items where one or more of the codes could not be categorized as either positive or negative. Limitations of this study include the small sample size and unequal sex and IQ among the different diagnosis groups. Comorbid association of autism and schizophrenia. Insel TR. Sommers AA. By 1980, the “Diagnostic and Statistical Manual of Mental Disorders” (DSM) listed autism and schizophrenia as distinct diagnoses. Finally, care must be provided in an integrative manner-using a biopsychosocial model-for these multicomplex patients and their families. Expert Opin Pharmacother. 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. 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). Recent studies suggest there are deeper relations in biological and clinical links between schizophrenia and autism. Masi G, Mucci M, Pari C. Children with schizophrenia: clinical picture and pharmacological treatment. Los Angeles, CA: Western Psychological Corporation (2012). ASD and SZ share a long history of diagnostic confusion (9, 10) cf (11). What is already known about autism and schizophrenia? 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. Alaghband-Rad J, McKenna K, Gordon CT, et al. 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). To test our prediction that the ADOS would be more effective at discriminating the ASD and TD groups versus the ASD and SZ groups, we constrained the samples to just the ASD and TD groups in one analysis and just the ASD and SZ groups in a second analysis. Association between schizophrenia and autism spectrum disorder: A systematic review and meta-analysis. History Hum Sci (2013) 26(3):3–31. Autism and schizophrenia both involve challenges with processing language and understanding other people’s thoughts and feelings. A controlled multivariate chart review of multiple complex developmental disorder. Studies in the childhood psychoses. AA consults and holds equity in BlackThorn Therapeutics. We also examined group differences in positive and negative symptoms of SZ as measured by the PANSS. Examples of negative items include absence or diminished observation of typical behaviors such as absence of descriptive or instrumental gesture, deficient reporting of events, lack of communication of affect, or absence of social overtures. The positive symptom scale assesses the presence of delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness, and hostility. 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. Van der Gaag RJ, Buitelaar J, Van den Ban E, et al. 36. Over the ensuing years, despite a number of medication trials including atypical antipsychotics and mood stabilizers, he became tortured by more persistent auditory hallucinations. George’s affective instability continued, but his thought disorder and psychosis have been the most enduring symptoms, even in the absence of mood dysregulation. 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. J Am Acad Child Adolesc Psychiatry (2009) 48(1):10–8. Martínez A, Tobe R, Dias EC, Ardekani BA, Veenstra-VanderWeele J, Patel G, et al. Comparison of social cognitive functioning in schizophrenia and high functioning autism: more convergence than divergence. J Autism Dev Disord (2011) 41(9):1256–66. Some mildly affected individuals may exhibit only slight delays in language and greater challenges with social interactions. 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. • Provide an autism alert card or hospital passport so it is easier for healthcare professionals to understand your needs. Although the PANSS is intended to inform clinician judgment in considering severity of current psychosis symptoms, there are no diagnostic cut-off scores. 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). 13. 35. Opposite Genetic Profiles of Autism vs. Schizophrenia. 2007;46:979-988. DT analyzed the data and wrote the bulk of the manuscript. For positive symptoms, post hoc comparisons revealed that the ASD group displayed more positive symptoms than both the SZ (p < .001) and TD groups (p < .001), and the SZ group scored marginally higher on this scale than the TD group (p = .051). II. 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). Autism-an evolving concept. Emil Kraepelin: A pioneer of scientific understanding of psychiatry and psychopharmacology. It is important to remember that some individuals may have both COS and ASD, which has implications when designing appropriate biopsychosocial interventions. Opler L, Kay S, Lindenmayer J, Fiszbein A. Finally, we completed the same steps for the PANSS, which separates symptoms into positive and negative domains by design—we conducted ANOVAs to examine diagnostic group differences in positive and negative SZ symptoms followed by analysis of ROC curves. Evidence for three subtypes of repetitive behavior in autism that differ in familiality and association with other symptoms. As the pattern of main effects and post hoc comparisons for all ANCOVAs after controlling for sex and IQ was the same as the original ANOVAs reported above, we do not report these analyses in detail. + and − symbols refer to positive and negative symptoms, respectively. Adult psychiatrists and mental health professionals would benefit from further training in the diagnosis of ASD in adults, and child mental health professionals would benefit from training in the diagnosis of schizophrenia spectrum disorders in youths. Kolvin I, Ounsted C, Humphrey M, McNay A. 2004;55:989-994. doi: 10.1111/j.1469-7610.2008.01944.x, 5. Diagnostic and statistical manual of mental disorders (DSM-5®). Autistic disorders and schizophrenia: related or remote? Until recently, a rare and severe autistic disorder known as “childhood disintegrative disorder” (CDD; previously known as Heller’s syndrome) characterized by developmental regression, was frequently associated with what is presumed to be paranoia and psychosis (19). JM oversaw all aspects of the study from study conceptualization, data collection, data analysis, and manuscript writing. Positive symptoms, especially hallucinations, delusions, grandiosity and suspiciousness may be most indicative of SZ. Diagnoses were confirmed by clinicians with extensive experience with both ASD and schizophrenia patients. Systematic long-term follow-up studies that include individuals with ASD and with COS are indicated to further inform the field regarding similarities and differences between autism and schizophrenia. Rather, our clustering provides a “proof of concept” and supports the need for new measures specifically designed and validated to distinguish positive and negative ASD symptoms. COS-the onset of psychosis before age 13 years-is considered a rare and severe form of schizophrenia. A pilot study of D-cycloserine in subjects with autistic disorder. It has also discovered that people in … I. Shared shyness: Social difficulties in children with autism and schizophrenia dual diagnosis. Second, we examined Receiver Operating Characteristic (ROC) curves using ADOS scores. J Child Psychol Psychiatry. Schizophr Res (2008) 99(1-3):164–75. Zheng Z, Zheng P, Zou X. Am J Psychiatry (1991) 148(12):1705–7. Autism spectrum disorder (ASD) and schizophrenia (SZ) are heterogenous neurodevelopmental disorders that overlap in symptom presentation. Goals: • To record the diagnosis of autism on our computer system so involved staff are alerted to the presence of autism. Given the complex symptom profile in youths with schizophrenia spectrum disorders, there tends to be a delay in diagnosis, even when symptoms are present for years.30 In addition, child mental health professionals would benefit from training in more specific identification of primary psychotic disorders in youths with ASD. 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). Nervous Child. 1972;2:315-337. Schizophrenia and autism are two completely different neuro-psychological disorders. 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. Psychiatric comorbidities and schizophrenia. This was the first time that negative and positive ASD symptoms have been split apart within a clinical measure of ASD symptoms and doing so seems to improve sensitivity and specificity. |, https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00548/full#supplementary-material, Creative Commons Attribution License (CC BY). 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). 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. Researchers have long suspected that autism and schizophrenia are related. The TD group also had higher IQ than the ASD group (p = .018). 3. 16. Although the disorders are distinct, they have shared clinical features. The Autism Diagnostic Observation Schedule—Generic: A standard measure of social and communication deficits associated with the spectrum of autism. Volkmar FR, Cohen DJ. Areas under the curve (AUC) of 1 represent perfect sensitivity and specificity of a measure, whereas.5 represents a test that is completely ineffective at discriminating diagnostic status. Arora M, Praharaj SK, Sarkhel S, Sinha VK. Science. SZ symptoms were quantified with the Positive and Negative Syndrome Scale (PANSS) (41) after administering the SCI-PANSS interview (35). Sprong M, Becker HE, Schothorst PF, et al. • Children with autism are complex and at high risk for mental health conditions. South Med J (2011) 104(4):264–8. 9. New research at Swinburne has revealed a significant overlap in the traits associated with autism and schizophrenia. Appropriate identification of comorbid conditions can enhance intervention efforts (eg, autism-related services for those with comorbid ASD and/or use of antipsychotics in patients who have comorbid ASD and a psychotic disorder). doi: 10.1016/j.schres.2013.05.013, 25. A controlled study of formal thought disorder in children with autism and multiple complex developmental disorders. Grinker RR. Diagnosis had a statistically significant effect on both positive SZ symptoms, F(2,50.06) = 21.75; p < .001 and negative SZ symptoms, F(2,82.92) = 45.66; p < .001. Therefore, we ran Brown–Forsythe tests to examine quality of means and Games–Howell post hoc comparisons, which are more robust to homogeneity of variances violations. 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. This article highlights the biological and clinical links between autism and schizophrenia. doi: 10.1038/sj.mp.4001857, 4. J Am Acad Child Adolesc Psychiatry. Diagnostic criteria and classification. Cheung C, Yu K, Fung G, et al. “She” was particularly disturbing to him and he wanted her to go away. Instruments better designed to capture symptoms along these dimensions would move this goal forward. As such, divisions among diagnostic categories in the DSM-5 can be complex and sometimes arbitrary, highlighting the need for a better understanding of shared risk factors and more nuanced ways of distinguishing symptom presentation across diagnostic categories in order to advance biologically informed research and practice. 10. 1988;29:865-878. 2008;320:539-543. McDougle CJ, Stigler KA, Erickson CA, Posey DJ. The key aim of this study was to examine the utility of ASD and SZ diagnostic instruments in discriminating these respective disorders. Bleuler E. Dementia praecox or the group of schizophrenias. Symptom development in childhood onset schizophrenia. Six ADOS items that could not easily be categorized as positive or negative (e.g., “Unusual Eye Contact,” and “Overall Quality of Rapport”) were dropped from this analysis (see Discussion section). However, there were no significant group differences between the ASD and SZ groups (p = .828). A thorough description is beyond the scope of this article, however. Rutter M. Childhood schizophrenia reconsidered. Future research is needed to determine the biological systems that distinguish positive and negative symptom domains across ASD and SZ. 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. Structured clinical interview: The positive and negative syndrome scale (SCI-PANSS). Meta-Analysis of Cognitive Performance in Neurodevelopmental Disorders during Adulthood: Comparisons between Autism Spectrum Disorder and Schizophrenia on the Wechsler Adult Intelligence Scales. Washington, DC: American Psychiatric Publishing (2000). Semin Nucl Med (1978) 8(4):283–98. 1991;148:1705-1707. Wechsler D. WASI-II: Wechsler abbreviated scale of intelligence. Received: 04 April 2020; Accepted: 28 May 2020;Published: 11 June 2020. 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). Genome Med. 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). Many items on existing ASD measures do not clearly differentiate between positive and negative symptomology. New York, NY: Basic Books. The developmental disorders include communication deficiency, motor development delays and social difficulties that have a similarity to those seen in autism-related disorders. Essential Resources in the Treatment of Schizophrenia. American Psychiatric Association. Front. North Tonawanda, NY: Multi-Health Systems (1999). Sensitivity and specificity analyses were only conducted for the ADOS because there are no diagnostic cut-off scores for the PANSS. Psychiatry, 11 June 2020 The authors concluded that children with MCDD are at high risk for psychosis later in life. Conceptualizing “borderline syndrome of childhood” and “childhood schizophrenia” as a developmental disorder. In the late 1800s, Emil Kraepelin popularized the term ‘dementia praecox’ (today known as schizophrenia) to differentiate progressive neurodegenerative disease associated with irreversible loss of cognitive function, from episodic affective disorders such as ‘manic depression’ (12). Participants included community samples of adults with SZ (n = 39) or ASD (n = 53), aged 18–48, who were recruited for this study after seeking treatment, services, and/or research participation at the Yale Developmental Disabilities Clinic, the Specialized Treatment for Early Psychosis (STEP) Clinic, or the Yale Psychiatric department in New Haven, Connecticut. Looking under the hood of convergent behavioral deficits in schizophrenia and autism. ASD, Autism Spectrum Disorder; SZ. Konstantareas MM, Hewitt T. Autistic disorder and schizophrenia: Diagnostic overlaps. Volkmar FR, Cohen DJ. Couture S, Penn D, Losh M, Adolphs R, Hurley R, Piven J. The two overlap because in most cases of schizophrenia, patients are often diagnosed during late … 29. doi: 10.1097/SMJ.0b013e31820c015d, 22. All participants regardless of diagnosis were administered gold-standard diagnostic assessments of ASD and SZ characteristics including the Autism Diagnostic Observation Schedule (ADOS-2) and the Positive and Negative Syndrome Scale (PANSS). Firstly, the overlap between symptoms means that the underlying autism often gets missed. His comorbid diagnosis was changed to schizoaffective disorder and, more recently, to schizophrenia. 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. AN helped with statistical analysis and reviewed drafts of the paper. J Autism Dev Disord. We see children with ASD who have emerging psychotic symptoms. doi: 10.1038/sj.mp.4001563, 6. Happé F, Ronald A, Plomin R. Time to give up on a single explanation for autism. Eur Arch Psychiatry Clin Neurosci. In clinical practice with people with IDD, the alternative or adjunctive diagnosis of ASD or SSD is particularly challenging. CNS Drugs. Figure 1 (A) ROC curves predicting DSM-5 diagnostic status based on continuous ADOS-2 algorithm score. 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. 8. doi: 10.1093/schbul/sbn135, 31. J Psychiatry Neurosci: Jpn (2010) 35(5):360. doi: 10.1503/jpm.100130, 23. Emerging study results suggest that there are both clinical and biological links between autism and schizophrenia. The boundaries of schizophrenia. The distinction between the two disorders remained unclear for nearly 30 years, until DSM-II included children with autism under the diagnostic umbrella of schizophrenia, childhood type. Our program is frequently asked to rule out ASD, schizotypal personality disorder and/or schizophreniform disorder, and first-episode schizophrenia in youths and young adults. J Child Psychol Psychiatry. – Considerable confusion surrounds the overlapping of autism and schizophrenia. Autism and Schizophrenia. Among the 22 cases who manifested psychotic symptoms (84.6%), 16 had a concurrent diagnosis of schizophrenia (72.73%) and 6 of mood disorders (27.27%). .Autism and schizophrenia may present as 2 separate disorders that need to be differentiated, or as comorbid conditions. Similar to what is already common practice in SZ research, the distinction between positive and negative symptoms may be useful for parsing heterogeneity within the ASD population, for better understanding the biology of distinct symptom manifestations and for targeting treatment. 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. At the Yale Child Study Center, a subgroup of children with ASD was labeled as having multiplex developmental disorder.13,14 Researchers in the Netherlands used the term “multiple complex developmental disorders” (MCDD) to describe children who met criteria for ASD and also exhibited affect dysregulation and disordered thinking.15-18 Of significant interest are follow-up studies, which showed that psychosis developed by adulthood in 64% of children with MCDD.16. However, there were no statistically significant differences between the ASD and SZ groups for negative ASD symptoms (p = .087). 23. PANSS-Negative items measured continuously would be considered a “bad” tool for discriminating ASD and SZ groups according to Metz’s (42) standard, and the ROC curve was not statistically significant, AUC = .52, p = .79. This decision was made to ensure ability to accurately self-report during diagnostic assessments. Metz CE. Those with ASD and schizophrenia had lower gray matter volumes within limbic-striato-thalamic neurocircuitry than did controls. 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. USA: American Psychiatric Publishing (1980). In SZ, positive symptoms largely encompass hallucinations (e.g., hearing voices that no one else hears), delusions (e.g., feelings of grandiosity, or feelings of being controlled by outside forces), bizarre behavior (e.g., talking to oneself, unusual dress and physical appearance), and positive formal thought disorder (e.g., disorganized thinking or incoherent speech) (31, 35). Those who worked with him had difficulty in getting him off of these disturbing topics. In contrast, disorder-specific positive symptomology classified on the ADOS-2 and PANSS differentiated ASD and SZ groups more effectively. 4. J Am Acad Child Adolesc Psychiatry. doi: 10.1002/aur.1977, 29. Shortly thereafter, Sante De Sanctis extended the field of psychiatry to childhood, classifying ‘dementia praecocissima’ as a childhood condition that included psychotic and autistic symptoms by today’s definitions, such as “strangeness of character,” apathy, depressed mood, hallucinations and catatonia (13). J Child Adolesc Psychopharmacol. doi: 10.1371/journal.pone.0010887, PubMed Abstract | CrossRef Full Text | Google Scholar, 3. 27. Total scores for ADOS-2-Positive ranged from 0 to 10, and total scores for ADOS-2-Negative ranged from 0 to 16. He is currently taking a typical antipsychotic. 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. 15. doi: 10.1016/j.biopsych.2019.05.016, 48. Across both measures of ASD and SZ symptoms, individuals from both diagnostic categories earned elevated negative symptom scores. In contrast, ADOS-Positive and PANSS-Positive had a low, nonsignificant correlation, r = 0.16, p = .077, suggesting the positive symptom domains from either scale are tapping relatively distinct constructs. For example, those with ASD scored higher on restricted and repetitive behaviors and stereotyped language, whereas those with SZ scored higher on psychotic symptoms such as delusions and hallucinations. 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). 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. Multiple complex developmental disorder delineated from PDD-NOS. 18. de Bruin EI, de Nijs PF, Verheij F, et al. Genetic overlap between autism, schizophrenia and bipolar disorder. 17. To explore whether a subset of symptoms was driving high ADOS-2 scores in SZ participants, we categorized ADOS-2 items into positive and negative symptom domains and tested the extent to which these item clusters could better discriminate true ASD from SZ. 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. We first examined the utility of the ADOS-2 in classifying participants with ASD, SZ, or TD by comparing ADOS-2 cut-off scores with clinical diagnostic consensus by expert licensed clinical psychologists based on information obtained from the ADOS-2, SCID-R, developmental history, collateral information, and the expert opinion of licensed clinical psychologists. These respective positive symptoms in ASD and SZ overlap less than negative symptoms of each disorder do, suggesting an area of more phenotypic distinction and perhaps greater divergence in underlying neural substrates. Gillberg C. The ESSENCE in child psychiatry: early symptomatic syndromes eliciting neurodevelopmental clinical examinations. Schizophr Res (2013) 148(1-3):24–8. SZ features are typically clustered into positive and negative symptom domains (31–33). Table 3 shows intercorrelations between ADOS-Positive, ADOS-Negative, PANSS-Positive, and PANSS-Negative across the entire sample. 12. The researchers concluded that in terms of brain volumetrics, ASD and schizophrenia have a clear degree of overlap that may reflect shared etiological mechanisms.25, A variety of psychosocial and educational interventions that support children with COS and children with ASD exist to address core deficits in socialization, communication, and behavior and the associated developmental and medical conditions. American Psychiatric Association. Dual diagnosis: Few specialists know how to identify and treat people who have both autism and schizophrenia. doi: 10.1016/j.schres.2007.10.024, 37. Unstrange minds: Remapping the world of autism. Impact Factor 2.849 | CiteScore 3.2More on impact ›, Faculty of Medicine, University of Oslo, Norway, Centro Hospitalar Psiquiátrico de Lisboa, Portugal, University Medical Center Göttingen, Germany. 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. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. George is a 14-year-old boy who first presented to Dr Frazier at age 8 with a diagnosis of ASD. 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. Additional work exploring the biological overlap between ASD and SZ, as well distinguishing positive symptoms of each disorder is clearly warranted. 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