Autism Spectrum Disorders: The Role of Genetics in Diagnosis and Treatment spectrum disorder"(Tanguay, 2004). An assumption of the autism-spectrum model is that autism conditions lie on a continuum of social-communication skills(Baron-Cohen et al, 2001; Wakabayashi et al., 2007). A continuum view shifts us away from categorical diagnosis and towards a quantitative approach. Diagnostic agreement for PDD-NOS is generally considered to be weak (Tanguay, 2004) Walker and colleagues presented compelling evidence, both from the literature and from their study, that attempting to improve the DSM-IV criteria for PDD-NOS can be quite frustrating(Walker et al., 2004). Many of the symptoms of PDD-NOS can occur in non-PDD conditions, such as severe mental retardation or language delay, and they may present with similar developmental history(Bishop et al., 2006). Furthermore, clinical presentation of PDD-NOS may resemble presenting symptoms in high functioning autism, Aspergers disorder, reactive attachment disorder, and psychotic disorders, and the differential diagnosis may be highly complicated. Studies on the distinction between Autistic Disorder(AD)and Pervasive Developmental Disorder Not Otherwise Specified(PDD-NOS)have been inconclusive(Snow &z Lecavalier, 2011). The field is in need of more studies examining subtype differences. As the diagnostic validity of PDD-NOS is still open to question, and to explore proposed underlying factors, we have to assign cases based on a valid clinical assessment. Therefore, we still need to investigate further the clinical features of children with PDD-NOS that distinguish them from children with autism and other non -PDD conditions 2. Autism PDD-NOs and ADHD Barkley(1990)reported that it is common for children with PDD-NOS to be initially given a diagnosis of Attention Deficit/Hyperactivity Disorder(ADHD). Jensen et al. ,(199 reported that 74%of the children in their study diagnosed with PDD-NOS were originally diagnosed with ADHD. Another study showed that children with PDD-NOS and ADHD did not differ from each other with respect to total number of autistic symptoms, genera psychopathology, or attention difficulties(Lutein et al, 2000). Methods for differentiating PDD-NOS from the non-PDD disorders, such as attention deficit hyperactivity disorder (ADHD), are not well established. Several investigators concluded that it is difficult to make a distinction between ADHD and PDd by using the present diagnostic criteria in DSM-IV (Bryson et al., 2008; Gokler et al., 2004). The characteristics that differentiated children with PDD-NOS from those with autism and non- pDd disorders were also explored by Buitelaar et al.,(1999). Four criteria discriminated autism from PDD-NOS most effectively: children with autism more often demonstrated restricted patterns of interest, lacked varied make- believe play, failed to use nonverbal behavior, and had an earlier age of onset. In another study(Allen et al., 2001), the PDD-NOS group(including both high-and low-functioning children) did not differ significantly from the autism or non- PDD groups on measures of guage or adaptive functioning but did show less restricted stereotyped behaviors than the high-functioning autism group In a very recent study(Snow Lecavalier, 2011), authors examined the validity of PDD NOS by comparing it to autistic disorder(AD) and other developmental disorders(DD) on parent-reported behavior problems. Fifty-four children with PDD-NOs were individually matched on age and nonverbal iQ to 54 children with AD and 54 children
18 Autism Spectrum Disorders: The Role of Genetics in Diagnosis and Treatment “spectrum disorder” (Tanguay, 2004). An assumption of the autism-spectrum model is that autism conditions lie on a continuum of social-communication skills (Baron-Cohen et al., 2001; Wakabayashi et al., 2007). A continuum view shifts us away from categorical diagnosis and towards a quantitative approach. Diagnostic agreement for PDD-NOS is generally considered to be weak (Tanguay, 2004). Walker and colleagues presented compelling evidence, both from the literature and from their study, that attempting to improve the DSM-IV criteria for PDD-NOS can be quite frustrating (Walker et al., 2004). Many of the symptoms of PDD-NOS can occur in non-PDD conditions, such as severe mental retardation or language delay, and they may present with similar developmental history (Bishop et al., 2006). Furthermore, clinical presentation of PDD-NOS may resemble presenting symptoms in high functioning autism, Asperger’s disorder, reactive attachment disorder, and psychotic disorders, and the differential diagnosis may be highly complicated. Studies on the distinction between Autistic Disorder (AD) and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) have been inconclusive (Snow & Lecavalier, 2011). The field is in need of more studies examining subtype differences. As the diagnostic validity of PDD-NOS is still open to question, and to explore proposed underlying factors, we have to assign cases based on a valid clinical assessment. Therefore, we still need to investigate further the clinical features of children with PDD-NOS that distinguish them from children with autism and other non-PDD conditions. 2. Autism, PDD-NOS, and ADHD Barkley (1990) reported that it is common for children with PDD-NOS to be initially given a diagnosis of Attention Deficit/Hyperactivity Disorder (ADHD). Jensen et al., (1997) reported that 74% of the children in their study diagnosed with PDD-NOS were originally diagnosed with ADHD. Another study showed that children with PDD-NOS and ADHD did not differ from each other with respect to total number of autistic symptoms, general psychopathology, or attention difficulties (Luteijn et al., 2000). Methods for differentiating PDD-NOS from the non-PDD disorders, such as attention deficit hyperactivity disorder (ADHD), are not well established. Several investigators concluded that it is difficult to make a distinction between ADHD and PDD by using the present diagnostic criteria in DSM-IV (Bryson et al., 2008; Gökler et al., 2004). The characteristics that differentiated children with PDD-NOS from those with autism and non-PDD disorders were also explored by Buitelaar et al., (1999). Four criteria discriminated autism from PDD-NOS most effectively: children with autism more often demonstrated restricted patterns of interest, lacked varied makebelieve play, failed to use nonverbal behavior, and had an earlier age of onset. In another study (Allen et al., 2001), the PDD-NOS group (including both high- and low-functioning children) did not differ significantly from the autism or non-PDD groups on measures of language or adaptive functioning but did show less restricted stereotyped behaviors than the high-functioning autism group. In a very recent study (Snow & Lecavalier, 2011), authors examined the validity of PDD NOS by comparing it to autistic disorder (AD) and other developmental disorders (DD) on parent-reported behavior problems. Fifty-four children with PDD-NOS were individually matched on age and nonverbal IQ to 54 children with AD and 54 children
Pervasive Developmental Disorder- not Otherwise Specified: Specifying and Differentiating with DD. The only differen een PDD-NOS and Ad groups was higher scores in the PDD-NOS group on two neasuring Anxiety/Depression. Cognitive functioning may be a more salient va than subtype when studying psychopathology in individuals with asDs In a study(Karabekiroglu Akbas, in press) designed to explore whether PDD-NOS encompassed a distinct cluster of symptoms and clinical profile or not, we investigated differential features of PDD-NOS such as presenting symptoms, developmental history, and comorbidity with respect to autism and ADHD. The study involved 188 children(PDD-NOS n=94; ADHD n=47; autism n=47)(male n=150, female n=38)who were 5.5(+2.5) years old on average(range 2-11 yrs ) The children with Asperger Syndrome were excluded. Preliminary PDD-NOS screening scale(PPsSS)was developed based on the 'presenting symptoms of PDD-NOS that were systematically collected in a pilot group of children Table 1) The clinical diagnoses and comorbidities were based on the comprehensive mental status examination, Schedule for Affective Disorders and Schizophrenia for School Age Children- Present and Lifetime Version-Turkish Version(K-SADS-PL-D), and the consensus between two child and adolescent psychiatry specialists. The prevelance rates of the most common presenting symptoms in the PDD-NOS and autism groups showed a similar pattern of distribution from most common to the least(Figure 1), even when the results were corrected for age. However, almost all of these symptoms are reported significantly less in prevalence in the PDD-NOS group. In this study, ADHD was also explored as a co-morbid diagnosis; 38.3% of the children in the PDD-NOS group and 53.2% of the children with autism fullfilled ADHD criteria(p> 05) Compared with children in the PDD-NOS group, children in the Adhd group had significantly higher rates of co-morbid disruptive behavior disorders(27.6% vs. 9.6%) learning disorders(14.9% vS. 5.3%), elimination disorders(12.8% VS. 2.1%), tic disorders (8.5% VS. 2. 1%), social anxiety disorder(8.5% vS. 2.1%)and lower rates of co-morbid obsessive compulsive disorder(2.1%vS. 23. 4%). The rates of other co-morbid disorders, such as depression, language disorders, and sleep disorders, were found to be similar across iagnostic groups. The findings of this study reveal that the PDD-NOS group had a high number of features in common with the autism and the Adhd groups, in terms of presenting and/or reported symptoms and developmental history. Similar to previous studies( Volkmar, et al 1993), gender distribution was similar for all groups(in each group more than 75% of the patients were male). A recent study has suggested that approximately 70% of children with ASDs have at least one comorbid psychiatric disorder(Simonoff et al 2008). The most prevalent comorbid disorders were anxiety disorders (42%), oppositional or conduct disorders(30%), and ADHD (28 %) In our study(Karabekiroglu Akbas, in press), as shown in Table 1 and Figure 1, the prevelance rates of the most common presenting symptoms in the PDD-NOS and autism groups had a similar pattern of distribution from more to less common. However, almost all of these symptoms were reported significantly less in children diagnosed with PDD-NOS than children with autism the autism and the pdd-nos shared a common clinical symptom profile on the first clinical admission. On the other hand, the children with ADHD had a distinct set of symptoms. The results suggest that PDD-NOS may be assumed as a quantitative partial subtype of autism, and it represents a less severe form that lies on a continuum of social-communication skills
Pervasive Developmental Disorder- not Otherwise Specified: Specifying and Differentiating 19 with DD. The only difference between PDD-NOS and AD groups was higher scores in the PDD-NOS group on two items measuring Anxiety/Depression. Cognitive functioning may be a more salient variable than subtype when studying psychopathology in individuals with ASDs. In a study (Karabekiroglu & Akbas, in press) designed to explore whether PDD-NOS encompassed a distinct cluster of symptoms and clinical profile or not, we investigated differential features of PDD-NOS such as presenting symptoms, developmental history, and comorbidity with respect to autism and ADHD. The study involved 188 children (PDD-NOS n=94; ADHD n=47; autism n=47) (male n=150, female n=38) who were 5.5(±2.5) years old on average (range 2-11 yrs.). The children with Asperger Syndrome were excluded. Preliminary PDD-NOS screening scale (PPSSS) was developed based on the ‘presenting’ symptoms of PDD-NOS that were systematically collected in a pilot group of children (Table 1). The clinical diagnoses and comorbidities were based on the comprehensive mental status examination, Schedule for Affective Disorders and Schizophrenia for School Age ChildrenPresent and Lifetime Version-Turkish Version (K-SADS-PL-T), and the consensus between two child and adolescent psychiatry specialists. The prevelance rates of the most common presenting symptoms in the PDD-NOS and autism groups showed a similar pattern of distribution from most common to the least (Figure 1), even when the results were corrected for age. However, almost all of these symptoms are reported significantly less in prevalence in the PDD-NOS group. In this study, ADHD was also explored as a co-morbid diagnosis; 38.3% of the children in the PDD-NOS group and 53.2% of the children with autism fullfilled ADHD criteria (p>.05). Compared with children in the PDD-NOS group, children in the ADHD group had significantly higher rates of co-morbid disruptive behavior disorders (27.6% vs. 9.6%), learning disorders (14.9% vs. 5.3%), elimination disorders (12.8% vs. 2.1%), tic disorders (8.5% vs. 2.1%), social anxiety disorder (8.5% vs. 2.1%) and lower rates of co-morbid obsessive compulsive disorder (2.1% vs. 23.4%). The rates of other co-morbid disorders, such as depression, language disorders, and sleep disorders, were found to be similar across diagnostic groups. The findings of this study reveal that the PDD-NOS group had a high number of features in common with the autism and the ADHD groups, in terms of presenting and/or reported symptoms and developmental history. Similar to previous studies (Volkmar, et al 1993), gender distribution was similar for all groups (in each group more than 75% of the patients were male). A recent study has suggested that approximately 70% of children with ASDs have at least one comorbid psychiatric disorder (Simonoff et al., 2008). The most prevalent comorbid disorders were anxiety disorders (42%), oppositional or conduct disorders (30%), and ADHD (28%). In our study (Karabekiroglu & Akbas, in press), as shown in Table 1 and Figure 1, the prevelance rates of the most common presenting symptoms in the PDD-NOS and autism groups had a similar pattern of distribution from more to less common. However, almost all of these symptoms were reported significantly less in children diagnosed with PDD-NOS than children with autism. The autism and the PDD-NOS shared a common clinical symptom profile on the first clinical admission. On the other hand, the children with ADHD had a distinct set of symptoms. The results suggest that PDD-NOS may be assumed as a quantitative partial subtype of autism, and it represents a less severe form that lies on a continuum of social-communication skills
Autism Spectrum Disorders: The Role of Genetics in Diagnosis and Treatment Preliminary PDD-NOS Symptom Presence of the symptoms Screening Saale(PPsss)Items (percentages) PDD- Overall nos Autism ADHD (2) (p value) 1. poor social interaction 5969798.5<0011:2;1:3;23 2. hyperactivity <001 1:2;1:3 3. not speaking/ language retardation 53.2 00112;13;23 33.046.8617Ns. 5. stubbornness 31946.8447 6. inattentiveness 0011:2;1:3;2 7. obsessions 14.9 8. not responsive to social stimuli 25.5 95.7 40.4<.001 1:2;2:3 9. stereotypies 24.5 59.6 1:2:13;23 10. impatience and /or impulsiveness 23.4 7<0011:2;:13;23 11. fastidiousness, choosyness 10.610.6 12. echolalia 223 14.9 13. highly interested in television 20.2 46.8 17.0<.001 14. conduct problems 40.4 15. articulation and /or prosody problems 16. lack of eye contact 00112;1:3;2:3 17. multiple fears 170 NS 18. sleep problems 4910.6277 19. tactile oversensitivity 0. confusing pronouns 117 128 17.0 22. emotional lability 11.7 23. tics 4.310.6 24. poor appetite 25.521.3NS 25. inappropriate laughing 170 2.1 N S 26. persistence with sameness 2.1 12.8 NS Table 1. Preliminary PDD-NOS Symptom Screening Scale(PPsSS)item distributions of atients in each diagnosis group
20 Autism Spectrum Disorders: The Role of Genetics in Diagnosis and Treatment Preliminary PDD-NOS Symptom Screening Scale (PPSSS) Items Presence of the symptoms (percentages) PDDNOS (1) Autism (2) ADHD (3) Overall significan ce (p value) Source of significance 1. poor social interaction 59.6 97.9 8.5 <.001 1:2; 1:3; 2:3 2. hyperactivity 56.4 80.9 89.4 <.001 1:2; 1:3 3. not speaking/ language retardation 53.2 97.9 6.4 <.001 1:2; 1:3; 2:3 4. aggressiveness 33.0 46.8 61.7 N.S. 5. stubbornness 31.9 46.8 44.7 N.S. 6. inattentiveness 30.9 66.0 91.5 <.001 1:2; 1:3; 2:3 7. obsessions 29.8 27.7 14.9 N.S. 8. not responsive to social stimuli 25.5 95.7 40.4 <.001 1:2; 2:3 9. stereotypies 24.5 59.6 6.4 <.001 1:2; 1:3; 2:3 10. impatience and/or impulsiveness 23.4 48.9 78.7 <.001 1:2; 1:3; 2:3 11. fastidiousness, choosyness 23.4 10.6 10.6 N.S. 12. echolalia 22.3 14.9 - N.S. 13. highly interested in television 20.2 46.8 17.0 <.001 1:2; 2:3 14. conduct problems 21.3 36.2 40.4 N.S. 15. articulation and/or prosody problems 18.1 8.5 4.3 N.S. 16. lack of eye contact 14.9 59.6 - <.001 1:2; 1:3; 2:3 17. multiple fears 14.9 8.5 17.0 N.S. 18. sleep problems 14.9 10.6 27.7 N.S. 19. tactile oversensitivity 12.8 25.5 6.4 N.S. 20. confusing pronouns 11.7 12.8 - N.S. 21. shyness 11.7 6.4 17.0 N.S. 22. emotional lability 11.7 - 27.7 <.001 1:3; 2:3 23. tics 10.6 4.3 10.6 N.S. 24. poor appetite 7.4 25.5 21.3 N.S. 25. inappropriate laughing 4.3 17.0 2.1 N.S. 26. persistence with sameness 2.1 12.8 6.4 N.S. 27. frequent startles 1.1 10.6 8.5 N.S. Table 1. Preliminary PDD-NOS Symptom Screening Scale (PPSSS) item distributions of patients in each diagnosis group
Pervasive Developmental Disorder- not Otherwise Specified: Specifying and Differentiating 0800000000 H Autism Differential symptoms Fig. 1. The significantly discriminative symptom percentages of the diagnostic groups 3. Cluster and factor analysis To identify ASD subgroups, several investigators used cluster and factor analysis based on social functioning, intelligence, developmental milestones, and so forth. Various clusters were reported(Eaves et al, 1994; Prior et al. 1998; Sevin et al., 1995; Waterhouse et al., 1996; wing Gould, 1979). But these findings were not replicated and the clusters identified were ot adopted or replicated in later studies. Despite several studies with ASD, clinical validity and differential features of PDD-NOS are yet to be consistently established. A very recent ady(Shumway et al, 2011)examined the relationship between functioning using a recently proposed onset classification system in 272 young children with autism spectrum disorder (ASD). Participants were classified into one of the following groups, based on parent report using the Autism Diagnostic Interview-Revised: Early Onset(symptoms by 12 months, no loss), Delay and Regression(symptoms by 12 months plus loss), Plateau (no early symptoms or loss), and Regression(no early symptoms, followed by loss). Findings indicate that current functioning does not differ according to onset pattern, calling into question the use of onset categorizations for prognostic purposes in children with asD a previous study performed a factor analysis on a sample of variant categories of PDD, and two factors emerged. One factor represented autistic symptoms and another represented level of functioning (Szatmari et al., 2002). More recent studies used a factor analytic approach based on particular diagnostic in nstruments, suc ch as the Autism Diagnostic Interview-Revised(ADI-R)and the Autism Diagnostic Observation Schedule(ADOS) 2003; Tanguay, 2004). The results suggested that there is a developmental continuum from affective reciprocity to emotional joint attention to verbal joint attention and to intuitive social knowledge(Tanguay, 2004). Tadevosyan-Layfer et al (2003)found six factors: spoken language, compulsions, developmental milestones, savant kills, sensory aversion, and social intent
Pervasive Developmental Disorder- not Otherwise Specified: Specifying and Differentiating 21 0 10 20 30 40 50 60 70 80 90 100 poor social interaction hyperactivity language retardation inattentiveness not responsiveness stereotypies impulsiveness high TV interest lack of eye contact emotional lability Differential symptoms Percentage PDD-NOS Autism ADHD Fig. 1. The significantly discriminative symptom percentages of the diagnostic groups 3. Cluster and factor analysis To identify ASD subgroups, several investigators used cluster and factor analysis based on social functioning, intelligence, developmental milestones, and so forth. Various clusters were reported (Eaves et al., 1994; Prior et al., 1998; Sevin et al., 1995; Waterhouse et al., 1996; Wing & Gould, 1979). But these findings were not replicated and the clusters identified were not adopted or replicated in later studies. Despite several studies with ASD, clinical validity and differential features of PDD-NOS are yet to be consistently established. A very recent study (Shumway et al., 2011) examined the relationship between onset status and current functioning using a recently proposed onset classification system in 272 young children with autism spectrum disorder (ASD). Participants were classified into one of the following groups, based on parent report using the Autism Diagnostic Interview—Revised: Early Onset (symptoms by 12 months, no loss), Delay and Regression (symptoms by 12 months plus loss), Plateau (no early symptoms or loss), and Regression (no early symptoms, followed by loss). Findings indicate that current functioning does not differ according to onset pattern, calling into question the use of onset categorizations for prognostic purposes in children with ASD. A previous study performed a factor analysis on a sample of variant categories of PDD, and two factors emerged. One factor represented autistic symptoms and another represented level of functioning (Szatmari et al., 2002). More recent studies used a factor analytic approach based on particular diagnostic instruments, such as the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) (Tadevosyan-Layfer et al., 2003; Tanguay, 2004). The results suggested that there is a developmental continuum from affective reciprocity to emotional joint attention to verbal joint attention and to intuitive social knowledge (Tanguay, 2004). Tadevosyan-Layfer et al. (2003) found six factors: spoken language, compulsions, developmental milestones, savant skills, sensory aversion, and social intent
Autism Spectrum Disorders: The Role of Genetics in Diagnosis and Treatment In our study(Karabekiroglu Akbas, in press), including all subjects in all diagnostic groups(PDD-NOS n=94; ADHD n=47; autism n=47)(male n=150, female n=38)who were 5(+2.5) years old on average(range 2-11 yrs ) a principal axis factor analysis with Promax rotation revealed ten factors; seven were found to be discriminative(Table 2, Figure 2). We 月可R可导导阴高用同时阳与利同 需 R的图 的时可 -m+“公同后1 Note Loadings <30 are omitted. Adopted items into the factors are shown bold. Table 2. PpSSs items and factor loadings for the rotated ten factors
22 Autism Spectrum Disorders: The Role of Genetics in Diagnosis and Treatment In our study (Karabekiroglu & Akbas, in press), including all subjects in all diagnostic groups (PDD-NOS n=94; ADHD n=47; autism n=47) (male n=150, female n=38) who were 5.5(±2.5) years old on average (range 2-11 yrs.), a principal axis factor analysis with Promax rotation revealed ten factors; seven were found to be discriminative (Table 2, Figure 2). We Note. Loadings <.30 are omitted. Adopted items into the factors are shown bold. Table 2. PPSSS items and factor loadings for the rotated ten factors