doi: 10.1007/s10803-015-2539-x. Clear differences include schizophrenia’s psychosis which often involves hallucinations. AA and VS were involved with conceptualization of the study, participant recruitment and assessment. Developmental delays are described premorbidly in samples of children and adults with schizophrenia. J Neural Transm. Systematic studies of COS show high rates of the disorder being either preceded by or comorbid with autistic spectrum disorders (ASD).7, The first to describe the severity and frequency of prepsychotic developmental disorders in COS was Kolvin,2 who noted deficits in communication, motor development, and social relatedness. First, observing elevated score patterns across both ASD and SZ diagnostic instruments should not automatically entice clinicians to suspect dual diagnosis; instead, clinicians ought to consider whether symptoms associated with the patient’s primary disorder are leading to score inflations on measures designed for the other. 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. Dual Diagnosis of Schizophrenia and Substance Use Disorder Genome-wide studies aid investigation. Schizophr Res (2008) 99(1-3):164–75. Am Psychiatr Assoc (2010) 167(7):748–51. Yet some have not previously received a diagnosis of ASD. The specificity of the ADOS-2 was perfect in TD (100%). The key aim of this study was to examine the utility of ASD and SZ diagnostic instruments in discriminating these respective disorders. PloS One (2010) 5(5):e10887. Woodbury-Smith MR, Boyd K, Szatmari P. Autism spectrum disorders, schizophrenia and diagnostic confusion. American Psychiatric Association. Childhood-onset schizophrenia (COS), considered a rare and severe form of schizophrenia, frequently presents with premorbid developmental abnormalities. 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. USA: American Psychiatric Publishing (1980). Psychiatr Clinics North Am (1993) 16(2):217–44. 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). There are two key clinical implications of this study, both related to situations where clinicians are considering a differential diagnosis between SZ and ASD. Opposite Genetic Profiles of Autism vs. Schizophrenia. SZ features are typically clustered into positive and negative symptom domains (31–33). Schizophr Bull (1987) 13(2):261–76. Sensitivity and specificity of the ADOS were assessed using diagnostic cut-off scores. Kolvin I. 1.In that the schizophrenia sample was substantially older than the autism sample, the neuropsychological test scores were converted to corrected T scores (Heaton et al., 1991), and mean t score profiles for each of the schizophrenia … Buitelaar JK, van der Gaag RJ. 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). 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). Biol Psychiatry (2019) 86(7):557–67. • Children with autism are complex and at high risk for mental health conditions. 2004;111:891-902. 9. Table 3 shows intercorrelations between ADOS-Positive, ADOS-Negative, PANSS-Positive, and PANSS-Negative across the entire sample. 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. (2008). What are the implications for psychiatric practice? 2006;20:841-866. Van der Gaag RJ, Buitelaar J, Van den Ban E, et al. Negative Predictive Value (NPV) refers to the percentage of participants who did not meet the ADOS-2 criteria who also did not have an ASD diagnosis. 7. Table 2 Sensitivity and Specificity of ADOS-2: Algorithm Scores. 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. Atypical antipsychotics in children and adolescents with autistic and other pervasive developmental disorders. Autism spectrum disorder (ASD) and schizophrenia (SZ) are neurodevelopmental disorders with heterogeneous and sometimes, overlapping symptom presentation (1–5). Autism and Schizophrenia. The purpose of this study was to specify overlapping symptom domains and to identify symptoms that can reliably differentiate adults with ASD (n = 53), SZ (n = 39), and typical development (TD; n = 40). doi: 10.1176/ajp.148.12.1705, 12. Autism and Schizophrenia, though separate diagnostic entities, share some common clinical features. Background: Even if childhood-onset of schizophrenia is described in the literature, and there are several case reports of concomitant autism spectrum disorders (ASD) and childhood-onset schizophrenia (COS), early diagnosis remains less the rule than the exception. J Am Acad Child Adolesc Psychiatry. Bleuler E. Dementia praecox or the group of schizophrenias. It is important to remember that some individuals may have both COS and ASD, which has implications when designing appropriate biopsychosocial interventions. In spite of these limitations, this study has important findings adding to a body of literature demonstrating substantial symptom overlap between adults with ASD and SZ. 1988;29:865-878. 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. 25. 2008;9:2053-2068. Autism spectrum disorders and childhood-onset schizophrenia: clinical and biological contributions to a relation revisited. 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. We see children with ASD who have emerging psychotic symptoms. However, there were no significant group differences between the ASD and SZ groups (p = .828). The two overlap because in most cases of schizophrenia, patients are often diagnosed during late … 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. Brazo P, Delamillieure P, Morello R, Halbecq I, Marié R-M, Dollfus S. Impairments of executive/attentional functions in schizophrenia with primary and secondary negative symptoms. Los Angeles, CA: Western Psychological Corporation (2012). Sommers AA. Childhood-onset schizophrenia: the severity of premorbid course. J Autism Dev Disord (2014) 44(1):111–9. 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. J Dev Behav Pediatr. Specific deletions associated with schizophrenia include 22q11.2, 1q21.1, and 15q13.3, which have been found to be associated with autism, attention-deficit … 19. 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). 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. Autism Res (2018) 11(8):1110–9. 2010;125:e727-e735. • We like to “keep it simple”, but this may not be possible • Change in diagnoses with aging. These analyses suggest that the key findings from our analyses were unlikely to be confounded by sex or IQ. 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. 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. • Provide an autism alert card or hospital passport so it is easier for healthcare professionals to understand your needs. Lord C, Rutter M, DiLavore P, Risi S, Gotham K, Bishop S. Autism diagnostic observation schedule–2nd edition (ADOS-2). J Autism Dev Disord (2016) 46(1):342–51. 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. In contrast, positive symptoms in ASD and SZ may be more disorder-specific. The differential diagnosis between these disorders and the comorbid diagnoses of the two conditions is often a bit of a quagmire for clinicians. Walsh T, McClellan JM, McCarthy SE, et al. The relationship between psychotic illnesses (particularly schizo- phrenia) and autism spectrum disorder (ASD) is complex, with suggestions that there is substantial overlap between the two conditions.1However, they differ considerably in age at onset, with the former usually first becoming apparent in adolescence and early adulthood and the latter in early childhood. AA consults and holds equity in BlackThorn Therapeutics. These analyses were conducted to check whether the pattern of the main findings from the primary analyses was confounded by group differences in IQ and sex. 2007;37:1181-1191. Morgese G, Lombardo GP. The authors concluded that children with MCDD are at high risk for psychosis later in life. J Am Acad Child Adolesc Psychiatry. We first examined the sensitivity and specificity of the Autism Diagnostic Observation Schedule-2nd edition (ADOS-2) (38) for discriminating ASD and SZ. Am J Psychiatry (1991) 148(12):1705–7. By 1980, the “Diagnostic and Statistical Manual of Mental Disorders” (DSM) listed autism and schizophrenia as distinct diagnoses. Meta-Analysis of Cognitive Performance in Neurodevelopmental Disorders during Adulthood: Comparisons between Autism Spectrum Disorder and Schizophrenia on the Wechsler Adult Intelligence Scales. 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. 2010;5:e12233. Neuropsychological function and dysfunction in schizophrenia and psychotic affective disorders. Cogn Neurosci Schizophrenia Annu Rev Clin Psychol (2005) 1:321–53. Atypical antipsychotics are the mainstay of pharmacotherapy for schizophrenia at any age, and they have also been used to manage certain symptoms, particularly irritability, associated with ASD.26-28. Kumar RA, KaraMohamed S, Sudi J, et al. Although the disorders are distinct, they have shared clinical features. doi: 10.1177/0952695113484320. 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. Diagnostic and statistical manual of mental disorders (4th Text Revision ed.). For negative SZ symptoms, the SZ group scored higher than the TD group (p < .001), and the ASD group also scored higher than the TD group (p < .001). 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. Treatment of early-onset schizophrenia spectrum disorders (TEOSS): demographic and clinical characteristics. doi: 10.1016/S0001-2998(78)80014-2, 43. 2008;99:38-47. ASD, Autism Spectrum Disorder; SZ. Lam KS, Bodfish JW, Piven J. 2008;17:628-638. 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. Happé F, Ronald A, Plomin R. Time to give up on a single explanation for autism. However, recent reports have suggested that individuals with autism may be at greater risk for schizophrenia and that the conditions may … 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). Clinical genetic testing for patients with autism spectrum disorders. 1. Some mildly affected individuals may exhibit only slight delays in language and greater challenges with social interactions. Insel TR, Cuthbert B, Garvey M, Heinssen R, Pine DS, Quinn K, et al. Table 3 Intercorrelations Among ADOS and PANSS Symptom Domains. doi: 10.1146/annurev.clinpsy.1.102803.143959, 33. 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. doi: 10.1016/j.biopsych.2019.07.030, 47. 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. Diagnoses were confirmed by clinicians with extensive experience with both ASD and schizophrenia patients. Rutter M. Childhood schizophrenia reconsidered. doi: 10.1038/nn1770, 26. Such measurement issues are not unique to the ADOS-2; in unpublished work from our group, we have found that both direct assessment and caregiver/self-report measures of ASD symptoms suffer from similar lack of specificity. We then examined the ROC curves of the positive and negative scales we created to examine their functioning in discriminating diagnostic groups. His comorbid diagnosis was changed to schizoaffective disorder and, more recently, to schizophrenia. 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. 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. Researchers have long suspected that autism and schizophrenia are related. 24. Those who worked with him had difficulty in getting him off of these disturbing topics. 3rd edition. 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. Second, we examined Receiver Operating Characteristic (ROC) curves using ADOS scores. Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes. Initially, these friends were humming to him or saying hello. 1995;34:1096-1106. Lord C, Risi S, Lambrecht L, Cook EH, Leventhal BL, DiLavore PC, et al. All participants provided their written informed consent to participate in this study in accordance with the Declaration of Helsinki. Genetic overlap between autism, schizophrenia and bipolar disorder. History Hum Sci (2013) 26(3):3–31. Finally, care must be provided in an integrative manner-using a biopsychosocial model-for these multicomplex patients and their families. PLoS One. Results: Approximately half of the study group fulfilled criteria for a personality disorder, all belonging to cluster A or C. Unstrange minds: Remapping the world of autism. JF-F helped design and conceptualize the study, assessed participants, and wrote and edited sections of the manuscript. doi: 10.1016/j.psychres.2004.10.001. Unique features included lower gray matter volume in the amygdala, caudate, and frontal and medial gyrus for schizophrenia, and lower gray matter volume in the putamen for autism. doi: 10.1007/s10803-008-0674-3, 41. 38. 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. However, the rating on the ADOS-2 item as currently written is identical. It is noteworthy, however, that children who have childhood-onset schizophrenia (COS) show fairly high premorbid rates of early developmental abnormalities.2,4-7. Schizophrenia, but not bipolar disorder and unipolar depression, was greatly overrepresented among individuals with a dual diagnosis: depending on birth cohort, 3.7–5.2% of those with intellectual disability had co-occurring schizophrenia. Konstantareas MM, Hewitt T. Autistic disorder and schizophrenia: Diagnostic overlaps. Autism and schizophrenia both involve challenges with processing language and understanding other people’s thoughts and feelings. Using this model, they extracted 313 foci from 25 voxel-based studies comprising 660 patients (308 ASD, 352 first-episode schizophrenia) and 801 controls. Eack SM, Bahorik AL, McKnight SA, Hogarty SS, Greenwald DP, Newhill CE, et al. I. Hum Mol Genet. 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). 1991;148:1705-1707. 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. 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. Psychiatric comorbidities and schizophrenia. 2009;1:102. “She” was particularly disturbing to him and he wanted her to go away. 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. J Child Psychol Psychiatry (2008) 49(11):1193–200. This has significant implications for clinicians given that correct diagnosis is critical for treatment. Arora M, Praharaj SK, Sarkhel S, Sinha VK. 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. doi: 10.1016/j.ridd.2010.06.002, 30. 14. 10. The patients/participants provided their written informed consent to participate in this study. 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. 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). Evidence for three subtypes of repetitive behavior in autism that differ in familiality and association with other symptoms. 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. Kuo SS, Eack SM. doi: 10.1093/schbul/11.3.364, 49. 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. J Am Acad Child Adolesc Psychiatry (2009) 48(1):10–8. This prepsychotic developmental disorder includes deficits in communication, social relatedness, and motor development, similar to those seen in autism spectrum disorders (ASD). 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. One-hundred and thirty-two individuals participated in this study. TD controls (n = 40) were recruited from the local community and from research databases. Genetic overlap between autism, schizophrenia and bipolar disorder. Diagnostic criteria and classification. Higher scores on the PANSS represent greater severity of SZ traits. Comorbid association of autism and schizophrenia. Funding for this study was provided by NIMH R01 MH107426 (JM, VS) and NIMH R01 MH119172 (JF-F). Recurrent 16p11.2 microdeletions in autism. Expert Opin Pharmacother. 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. 2009;48:10-18. 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). 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. ‘Dementia praecocissima’: the Sante De Sanctis model of mental disorder in child psychiatry in the 20th century. 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. USA: American Psychiatric Publishing (1968). Posey DJ, Kem DL, Swiezy NB, et al. Sensitivity and specificity analyses were only conducted for the ADOS because there are no diagnostic cut-off scores for the PANSS. Reichenberg A, Harvey PD, Bowie CR, Mojtabai R, Rabinowitz J, Heaton RK, et al. Neural bases for impaired social cognition in schizophrenia and autism spectrum disorders. A pilot study of D-cycloserine in subjects with autistic disorder. doi: 10.1016/j.schres.2013.05.013, 25. doi: 10.1097/CHI.0b013e31818b1c63, 11. 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. 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). For both analyses, tests for homogeneity of variances were violated. 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. All analyses on diagnostic accuracy are based on the ADOS-2 algorithm cut-off scores and the subset of items that comprise this algorithm. J Am Acad Child Adolesc Psychiatry. JM consults with BlackThorn Therapeutics and has received research funding from Janssen Research and Development. doi: 10.1093/schbul/13.2.261, 42. Similarly, negative symptoms of ASD largely represent deficits in social–emotional reciprocity and engagement, such as reduced sharing of emotion or lack of social initiation, deficits in nonverbal communication (e.g., reduced eye contact, limited use of gesture, limited range of facial expressions), and reduced spontaneous communication and conversation flow (34). 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. American Psychiatric Association. + and − symbols refer to positive and negative symptoms, respectively. What is already known about autism and schizophrenia? 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. Table 1 Sex Distributions and Means and Standard Deviations of Age and Intelligence (IQ). Alcohol and drug problem tend to occur with depression, anxiety disorders, schizophrenia, personality disorders, etc. 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. Asperger disorder in adults. Ebert A, Bar K-J. 1993;32:775-782. Next, we examined several Receiver Operating Characteristic (ROC) curves using ADOS scores. . 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 Autism Child Schizophr. – Considerable confusion surrounds the overlapping of autism and schizophrenia. SZ symptoms were quantified with the Positive and Negative Syndrome Scale (PANSS) (41) after administering the SCI-PANSS interview (35). 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). doi: 10.1016/j.brainres.2010.11.031, 46. Not surprisingly, these disorders frequently co-occur. Psychiatry, 11 June 2020 The challenge is to distinguish symptoms of a mood disturbance from those of autism or attention deficit hyperactivity disorder (ADHD). The goal of the RDoC initiative is not to eliminate clinically useful diagnostic categories in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (1) but rather to introduce an interrelated classification system that links validated clinical presentations of psychopathology to underlying pathophysiology (6–8). J Autism Dev Disord (2011) 41(9):1256–66. Barch DM. Autism … The purpose of this study was to specify overlapping symptom domains and to identify symptoms that can reliably differentiate adults with ASD (n = 53), SZ (n = 39), and typical development (TD; n = 40). ASD symptoms were measured using the ADOS-2 (38). 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. In Canada, the term dual diagnosis is used to describe an individual’s diagnosis of a developmental disability (e.g., ASD) and a mental health problem. Schizophrenia; TD, Typical Development. 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. J Autism Dev Disord (2001) 31(1):19–28. New research at Swinburne has revealed a significant overlap in the traits associated with autism and schizophrenia. 1995;245:70-79. 50. ASD and SZ share a long history of diagnostic confusion (9, 10) cf (11). 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. doi: 10.1203/PDR.0b013e318212c196, 27. Volkmar FR, Cohen DJ. Mandy W. The Research Domain Criteria: A new dawn for neurodiversity research? 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). Nature (2010) 468(7321):187–93. doi: 10.1016/j.biopsych.2019.05.016, 48. 14. Science. Meyer U, Feldon J, Dammann O. Schizophrenia and autism: both shared and disorder-specific pathogenesis via perinatal inflammation? This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). And, perhaps, some schizophrenic kids … J Am Acad Child Adolesc Psychiatry. Also, the disorders are treated differently.2,3 Schizophrenia is thought to develop at a chance rate in individuals with autism. Many items on existing ASD measures do not clearly differentiate between positive and negative symptomology. In these children, the hallucinations or delusional preoccupations may initially be attributed to the developmental disorder. 39. The developmental disorders include communication deficiency, motor development delays and social difficulties that have a similarity to those seen in autism-related disorders. 2. 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. The TD group also had higher IQ than the ASD group (p = .018). 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. Multiple complex developmental disorder delineated from PDD-NOS. South Med J (2011) 104(4):264–8. doi: 10.1002/aur.1977, 29. 1972;2:315-337. Firstly, the overlap between symptoms means that the underlying autism often gets missed. 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. 2008;320:539-543. 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. Siever LJ, Kalus OF, Keefe RS. J Child Psychol Psychiatry. 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. 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. 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. Arch Gen Psychiatry (1982) 39(7):789–94. Am J Psychiatry. Sporn AL, Addington AM, Gogtay N, et al. Genome Med. Front. On the other hand, positive symptoms related to odd or excessive emotional gestures, echolalia, stereotyped speech patterns, unusual mannerisms, or circumscribed interests may be most indicative of an ASD diagnosis. A controlled multivariate chart review of multiple complex developmental disorder. 2006;45:1104-1113. 29. ASD, SZ, and TD groups were then compared on positive and negative ASD symptom dimensions. 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%). Limitations of this study include the small sample size and unequal sex and IQ among the different diagnosis groups. 35. Indeed, despite similar deficits in facial emotion recognition in ASD and SZ, there are markedly different patterns of EEG- and fMRI-measured neurological dysfunction associated with these deficits (46, 47). Overall, the findings suggest that positive symptoms from both the ADOS and PANSS better discriminate ASD and SZ groups than negative symptoms (see also Figure 2). His thoughts are more linear, he rarely talks about “she,” and he is much more able to engage in his schoolwork. 2005;15:465-476. Am J Psychiatry. 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. Abstract OBJECTIVE: In the last several decades, considerable evidence has suggested that autism and schizophrenia are unrelated. George is a 14-year-old boy who first presented to Dr Frazier at age 8 with a diagnosis of ASD. Schizophr Res (2013) 148(1-3):24–8. Thus, it is likely that negative social and communicative symptoms in both ASD and SZ have common neural origins that impact social cognition (37). Brain Res (2011) 1380:34–41. The patient’s age at the onset of symptoms and the clinical presentation distinguish autism from early-onset schizophrenia. These symptoms, present since early childhood, predated his symptoms of psychosis and continue to require the support of autism-specific services. 6. Berney TP. Error bars represent standard error of the means. The phenomenology of childhood psychoses. 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. Br J Psychiatry. doi: 10.1097/SMJ.0b013e31820c015d, 22. 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. These deficits were found in 28% to 55% of children with ASD, and these observations have been replicated in multiple studies.6-8. Kolvin I, Ounsted C, Humphrey M, McNay A. We ran two separate univariate ANOVAs with diagnosis (ASD, SZ or TD) as the independent variables in both models and ASD symptom type (positive or negative) as the respective dependent variables in either model. Although autism has long been recognized as a separate diagnostic entity from schizophrenia, both disorders share clinical features. 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. Shared shyness: Social difficulties in children with autism and schizophrenia dual diagnosis. The ADOS-2 is a gold-standard assessment tool used to assist clinician judgment in making decisions about a possible ASD diagnosis. J Autism Dev Disord (2009) 39(5):693–705. Semin Nucl Med (1978) 8(4):283–98. 23. History Psychiatry (2019) 30(3):300–13. Instruments better designed to capture symptoms along these dimensions would move this goal forward. 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. J Psychiatry Neurosci: Jpn (2010) 35(5):360. doi: 10.1503/jpm.100130, 23. Gillberg C. The ESSENCE in child psychiatry: early symptomatic syndromes eliciting neurodevelopmental clinical examinations. 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. The boundaries of schizophrenia. In that study, 78% of the MCDD group met criteria for at-risk mental state. Tamminga C, Holcomb H. Phenotype of schizophrenia: a review and formulation. 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. 15. 30. J Am Acad Child Adolesc Psychiatry. 13. doi: 10.1017/S003329170999078X. Nervous Child. Nat Neurosci (2006) 9(10):1218–20. doi: 10.1038/sj.mp.4001563, 6. Buckley PF, Miller BJ, Lehrer DS, Castle DJ. In addition, sex ratios between groups were unequal, χ2 (2, N = 132) = 10.04, p = .007. © 2020 MJH Life Sciences and Psychiatric Times. Figure 2 *p < .05, ***p < .001 (two-tailed). Diagnostic and statistical manual of mental disorders (DSM-5®). A final limitation is that, paralleling clinical activity in ASD and SZ, this study was not supported by neuroimaging, electroencephalography, or genetic data. 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. 1995;16(3 suppl):S7-S11. Specificity refers to the percentage of participants without ASD who did not meet the ADOS-2 criteria. 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. 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. Symptom development in childhood onset schizophrenia. 18. de Bruin EI, de Nijs PF, Verheij F, et al. doi: 10.1038/sj.mp.4001857, 4. DT analyzed the data and wrote the bulk of the manuscript. Klin A, Mayes LC, Volkmar FR, Cohen DJ. We then examined ROC curves predicting diagnostic status, this time using PANSS-Negative and PANSS-Positive scores (Figure 1C). 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. 2. Carroll LS, Owen MJ. American Psychiatric Association. 3. McDougle CJ, Stigler KA, Erickson CA, Posey DJ. 1995;34:1273-1283. Washington, DC: American Psychiatric Publishing (2000). Studies in the childhood psychoses. Vorstman JA, Morcus ME, Duijff SN, et al. The reviewer MK declared a shared affiliation, though no other collaboration, with one of the authors, JF, to the handling editor. 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). The ROC curve for the ASD + SZ samples was also statistically significant, indicating that the ADOS-2 is able to correctly classify ASD and SZ samples; however, by Metz’s (42) standard, the AUC suggests the ADOS-2 algorithm would only be considered a “fair” test for discriminating these two populations, AUC = .73, p < .001. Masi G, Mucci M, Pari C. Children with schizophrenia: clinical picture and pharmacological treatment. Front Psychiatry (2020) 11:1–16. The Autism Diagnostic Observation Schedule—Generic: A standard measure of social and communication deficits associated with the spectrum of autism. Future research is needed to determine the biological systems that distinguish positive and negative symptom domains across ASD and SZ. Rethinking schizophrenia. 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). 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. Compared with patients with schizophrenia patients with comorbid ASDs and schizophrenia were more often men, of younger age, and more frequently developed motor side effects to antipsychotics. Copyright © 2020 Trevisan, Foss-Feig, Naples, Srihari, Anticevic and McPartland. 36. This study was approved by the Yale University School of Medicine Human Subject Investigation Committee. London, England: SAGE Publications Sage UK (2018). Finally, intercorrelations between negative and positive dimensions of the PANSS and ADOS were explored to examine possible content overlap among the scales. 20. 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. Emerging study results suggest that there are both clinical and biological links between autism and schizophrenia. Additional work exploring the biological overlap between ASD and SZ, as well distinguishing positive symptoms of each disorder is clearly warranted. 20. Mol Psychiatry (2005) 10(1):27–39. Towbin KE, Dykens EM, Pearson GS, Cohen DJ. The AUC for TD + ASD was statistically significant and indicated that continuous ADOS-2 algorithm scores are an excellent tool for discriminating ASD and TD populations, AUC = .94, p < .001. JM oversaw all aspects of the study from study conceptualization, data collection, data analysis, and manuscript writing. The key take-away point is that there are some individuals who may have both COS and ASD. Diagnosing autism spectrum disorders in adults: the use of Autism Diagnostic Observation Schedule (ADOS) module 4. Comorbid association of autism and schizophrenia. North Tonawanda, NY: Multi-Health Systems (1999). Couture S, Penn D, Losh M, Adolphs R, Hurley R, Piven J. 17. van der Gaag R, Caplan R, van Engeland H, et al. Looking under the hood of convergent behavioral deficits in schizophrenia and autism. San Antonio, TX: PsychCorp ( 2011 ) VS were involved with conceptualization of the relationship autism. Scholar, 3 autism and schizophrenia dual diagnosis, we constrained the sample to just the ASD and SZ, yielding a of., van den Ban E, et al scientific understanding of Psychiatry and.! 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