Predictors of age at diagnosis in autism spectrum disorders: the use of multiple regression analyses and a classification tree on a clinical sample.

The increasing prevalence of autism spectrum disorders (ASD) has led to worldwide interest in factors influencing the age of ASD diagnosis. Parents or caregivers of 237 ASD children (193 boys, 44 girls) diagnosed using the Autism Diagnostic Observation Schedule (ADOS) completed a simple descriptive questionnaire. The data were analyzed using the variable-centered multiple regression analysis and the person-centered classification tree method. We believed that the concurrent use of these two methods could produce robust results. The mean age at diagnosis was 5.8 ± 2.2 years (median 5.3 years). Younger ages for ASD diagnosis were predicted (using multiple regression analysis) by higher scores in the ADOS social domain, higher scores in ADOS restrictive and repetitive behaviors and interest domain, higher maternal education, and the shared household of parents. Using the classification tree method, the subgroup with the lowest mean age at diagnosis were children, in whom the summation of ADOS communication and social domain scores was ≥ 17, and paternal age at the delivery was ≥ 29 years. In contrast, the subgroup with the oldest mean age at diagnosis included children with summed ADOS communication and social domain scores < 17 and maternal education at the elementary school level. The severity of autism and maternal education played a significant role in both types of data analysis focused on age at diagnosis.

Can Maternal Autoantibodies Play an Etiological Role in ASD Development?

Autism spectrum disorder (ASD) is a heterogeneous condition with multiple etiologies and risk factors - both genetic and environmental. Recent data demonstrate that the immune system plays an important role in prenatal brain development. Deregulation of the immune system during embryonic development can lead to neurodevelopmental changes resulting in ASD. One of the potential etiologic factors in the development of ASD has been identified as the presence of maternal autoantibodies targeting fetal brain proteins. The type of ASD associated with the presence of maternal autoantibodies has been referred to as maternal antibodies related to ASD (MAR ASD). The link between maternal autoantibodies and ASD has been demonstrated in both clinical studies and animal models, but the exact mechanism of their action in the pathogenesis of ASD has not been clarified yet. Several protein targets of ASD-related maternal autoantibodies have been identified. Here, we discuss the role of microtubule-associated proteins of the collapsin response mediator protein (CRMP) family in neurodevelopment and ASD. CRMPs have been shown to integrate multiple signaling cascades regulating neuron growth, guidance or migration. Their targeting by maternal autoantibodies could change CRMP levels or distribution in the developing nervous system, leading to defects in axon growth/guidance, cortical migration, or dendritic projection, which could play an etiological role in ASD development. In addition, we discuss the future possibilities of MAR ASD treatment.

Diffusion Tensor Imaging And Tractography In Autistic, Dysphasic, And Healthy Control Children.

BACKGROUND: Diffusion tensor imaging (DTI) is a powerful tool for investigating brain anatomical connectivity. The aim of our study was to compare brain connectivity among children with autism spectrum disorders (ASD), developmental dysphasia (DD), and healthy controls (HC) in the following tracts: the arcuate fasciculus (AF), inferior frontal occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), and uncinate fasciculus (UF). METHODS: Our sample consisted of 113 children with a mean age 8.7±2.2 years (77 boys, 36 girls), divided into three subgroups: ASD (n=39), DD (n=36), and HC (n=38). The International Classification of Diseases, 10th ed. was used to make clinical diagnoses. DTI images were collected using a 1.5 T Phillips Achieva MR imaging system. RESULTS: Detailed analyses of fractional anisotropy (FA) revealed significant differences among the ASD, DD, and HC groups in the left AF (p=0.014) and right AF (p=0.001), the left IFOF (p<0.001) and right IFOF (p<0.001), the left ILF (p<0.001) and right ILF (p<0.001), but not in the UF. Post-hoc analyses revealed three patterns of FA differences among the groups: (1) in the right AF, right IFOF, and right ILF, FA was significantly lower in the ASD group compared to the DD and HC groups; however, there was no difference in FA between DD and HC; (2) in the left AF and left IFOF, FA was significantly lower in the ASD than in the HC group, but there were no differences between DD vs HC nor DD vs ASD; and (3) in the left ILF, no difference in FA was seen between ASD and DD, but FA in both was significantly lower than in the HC. CONCLUSION: Microstructural white matter properties differed between ASD vs DD and HC subjects. The tract where FA impairment in ASD and DD subjects was the most similar was the left ILF.

Childhood narcolepsy and autism spectrum disorders: four case reports.

BACKGROUND: Childhood narcolepsy is associated with various emotional, behavioural and cognitive dysfunctions as well as with psychiatric and neurodevelopmental disorders: anxiety, depression, attention deficit hyperactivity disorder and psychosis. A relationship between these conditions is unclear - comorbidity or similar pathophysiological mechanisms can be suggested. OBJECTIVE: We reported four children with narcolepsy type 1 (NT1) and autism spectrum disorder (ASD) - Asperger syndrome (AS). RESULTS AND CONCLUSION: To the best of our knowledge co-occurrence of NT1 and AS has not been described in the literature as noted in this report.

Some children with autism have latent social skills that can be tested.

BACKGROUND: The idea of latent social skills in autism emerged as a possible interpretation of the rapid (but temporary) improvement of autistic subjects in oxytocin studies. We tested a hypothesis that a normal response to Item No 59 "Secure Base" from the third version of the Autism Diagnostic Interview - Revised (ADIR-59) could indicate the presence of latent social skills in autism. METHODS: We examined 110 autistic children (88 boys and 22 girls) with a mean age of 6.0±2.5 years (range: 2.2-14.8 years) using the Autism Diagnostic Observation Schedule (ADOS) - Generic. A diagnosis of mental retardation was established in 68 autistic children (62%). RESULTS: The difference in the ADOS social domain between children aged ≤5 years on one side and children older than 5 years on the other side was significant in subjects with normal responses to ADIR-59 (9.60 vs 6.47; P=0.031) but not in those with abnormal responses to ADIR-59 (10.62 vs 9.63; P=0.537). In a predictive model, lower ADOS social domain scores were predicted by older age (P=0.001), lower scores on the ADIR-59 (P=0.01), and the absence of mental retardation (P=0.049). CONCLUSION: The results support the hypothesis that the normal response to item ADIR-59 "Secure Base" indicates the presence of latent social skills in autism that might foretell further social growth in older autistic subjects.

A possible role of the Infant/Toddler Sensory Profile in screening for autism: a proof-of-concept study in the specific sample of prematurely born children with birth weights <1,500 g.

OBJECTIVE: The objective of this study was to explore the potential of the Infant/Toddler Sensory Profile (ITSP) as a screening tool for autism spectrum disorders (ASD) in prematurely born children. METHODS: Parents of 157 children with birth weights <1,500 g (aged 2 years, corrected for prematurity; 88 boys, 69 girls) completed a screening battery that included the ITSP, Modified Checklist for Autism in Toddlers (M-CHAT), and the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist (CSBS-DP-ITC). Children with known disabilities were excluded. All the children who were screened positive on any of the screening tools subsequently underwent clinical examination including the Autism Diagnostic Observation Schedule. RESULTS: We used classification trees to answer the question whether ITSP (or some of its subscales) could be combined with the M-CHAT and/or the CSBS-DP-ITC or its subscales into an effective ASD screening tool. Using the CSBS-DP-ITC, overall score, and the Sensation Seeking subscale of the ITSP, we obtained a screening tool that was able to identify all of the ASD children in our sample (confirmed by cross-validation). The proposed screening tool is scored as follows: 1) if the overall CSBS-DP-ITC value is <45.5, then the screening is positive; 2) if the overall CSBS-DP-ITC value is ≥45.5 and the z-score of the Sensation Seeking subscale of ITSP is ≥1.54, then the screening is positive; 3) otherwise, the screening is negative. CONCLUSION: The use of CSBS-DP-ITC in combination with the Sensation Seeking subscale of the ITSP improved the accuracy of autism screening in preterm children.

Age at diagnosis of autism spectrum disorders: is there an association with socioeconomic status and family self-education about autism?

BACKGROUND: The marked increase in autism spectrum disorders (ASD) prevalence has stimulated worldwide interest in exploring broader circumstances of care of autistic children, including the role of socioeconomic status (SES) and family information on autism. METHODS: Our sample comprised of 160 children who participated in a diagnostic examination focused on autism, and their parents who completed a simple descriptive questionnaire focusing on the family situation as well as family self-education about autism. The diagnosis of ASD was confirmed in 120 children (75% of the sample; 94 boys, 26 girls) with mean age 6.2±2.7 years (median 5.3, range 2.2-17.2 years). In 71 autistic patients (59.2%), a diagnosis of mental retardation was also established. RESULTS: The age at diagnosis of ASD correlated negatively with maternal (P=0.014) and paternal (P=0.002) ages at the time of birth of the ASD child as well as with paternal (P=0.002) and maternal (P=0.050) education. The age at diagnosis of ASD did not correlate with family SES. Mothers were significantly more active in seeking information on autism than fathers or both parents equally (80 vs 9 vs 28 cases, respectively; P<0.001). The mean number of information sources on autism was 3.5±1.8 with a range 0-9. The mean number of resources did not differ among the three SES groups (3.50 vs 3.49 vs 4.25, respectively; P=0.704). The mean number of sources did not correlate with the age at diagnosis of ASD. The most often used sources were the Internet (81.7%), followed by psychologists (48.3%), books (46.7%), and child and adolescent psychiatrists (43.3%). CONCLUSION: An earlier diagnosis of ASD is associated with higher parental age at birth and higher parental education but not with family SES or number of family information sources.

Suicidal behavior and self-harm in girls with eating disorders.

Comorbid psychopathology, including self-harm and suicidal behavior, is often found in patients with eating disorders. To better understand the reasons for high comorbid psychopathology among eating disorders, self-harm, and suicidal behavior, we examined this comorbidity in female patients hospitalized with eating disorders. In a sample of 47 girls admitted for anorexia nervosa, atypical anorexia nervosa, and bulimia nervosa, 72% had depressive symptoms, 11% had obsessive-compulsive symptoms, 9% had anxiety disorder, 23% had substance abuse, and 57% had disharmonious personality development. Suicidal behavior was present in 60% of patients and self-harm in 49%. Association was found between self-harm and suicidality. In all, 68% of girls with eating disorders had a positive score in the Children's Depression Inventory questionnaire and 62% of them in the Child Adolescent Suicidal Potential Index questionnaire. Clinical examination of girls with eating disorders should focus on identifying the risk of suicidal behavior and self-harm.

Early-onset anorexia nervosa in girls with Asperger syndrome.

Eating disorders frequently occur in conjunction with autism spectrum disorders, posing diagnostic and therapeutic difficulties. The comorbidity of anorexia nervosa and Asperger syndrome is a significant clinical complication and has been associated with a poorer prognosis. The authors are presenting the cases of an eleven-year-old girl and a five-and-a-half-year-old girl with comorbid eating disorders and Asperger syndrome.

Atypical antipsychotics in the treatment of early-onset schizophrenia.

Atypical antipsychotics (AAPs) have been successfully used in early-onset schizophrenia (EOS). This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least.

Comparison of three screening tests for autism in preterm children with birth weights less than 1,500 grams.

BACKGROUND: Preterm children seem to be at increased risk for autism spectrum disorders (ASD). METHODS: Parents of 157 children with birth weights less than 1,500 g (age 2 years, corrected for prematurity; 88 boys, 69 girls) completed screening questionnaires. The screening battery included the Modified Checklist for Autism in Toddlers (M-CHAT), Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist (CSBS-DP-ITC), and the Infant/Toddler Sensory Profile (ITSP). Children with disabilities were excluded. All children who screened positive on any of the screening tools were subsequently assessed by clinical examination including the Autism Diagnostic Observation Schedule. RESULTS: Fifty-six children (35.7%) screened positive on at least one of the parental screening questionnaires. Of the 56 children who tested positive, 33 participated in the detailed clinical follow-up assessment. A diagnosis of ASD was confirmed in 13 of the 33 children. The ASD prevalence was 9.7% of the sample. Analysis of children with and without an ASD diagnosis found significant differences relative to gestational age (26.9 weeks vs 28.3 weeks, P=0.033) and length of the stay in hospital (89.5 days vs 75.4 days, P=0.042). The screening tool with the most positive results was CSBS-DP-ITC (42 positive screens [PS]), followed by M-CHAT (28 PS), and ITSP (22 PS). Differences in the frequency of PS among the tests were significant (P=0.008). CSBS-DP-ITC had the highest sensitivity (0.846), followed by M-CHAT (0.692) and ITSP (0.462). CONCLUSION: Our results indicate a higher prevalence of autism in children with birth weights <1,500 g at 2 years of age compared to the general population prevalence. The ASD diagnosis was associated with shorter gestation times and longer hospital stays. Our findings support the simultaneous use of more than one screening tests in order to increase screening sensitivity.

Screening for autism in preterm children with extremely low and very low birth weight.

BACKGROUND: Studies of children with very low birth weight (VLBW, 1,000-1,500 g) and extremely low birth weight (ELBW, less than 1,000 g) indicate that this population seems to be at increased risk of autism spectrum disorder (ASD). METHODS: Parents of 101 VLBW and ELBW children (age 2 years, corrected for prematurity) agreed to participate in the study and signed informed consents; however, parents of only 75 children (44 boys, 31 girls) completed the screening questionnaires. The screening battery included the Modified Checklist for Autism in Toddlers (M-CHAT), Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist (CSBS-DP-ITC), and the Infant/Toddler Sensory Profile (ITSP). Children with disabilities were excluded. All children who screened positive on any of the screening tools were subsequently invited for a detailed assessment. RESULTS: Thirty-two children (42.7%) screened positive on at least one of the screening questionnaires. The screening tool with the most positive results was the CSBS-DP-ITC (26 positive screens), followed by the M-CHAT (19 positive screens) and the ITSP (11 positive screens). Of the 32 children who tested positive, 19 participated in the detailed follow-up assessment. A diagnosis of ASD was confirmed in eight of the 19 children. ASD prevalence, calculated from those 19 children and those with negative screening results (43 children), yielded a prevalence of 12.9% in the sample. The difference in frequency of positive screens between the tests was significant (P=0.011). In pair comparisons, ITSP was found to be significantly less positive than CSBS-DP-ITC (P=0.032). No significant differences were found between the M-CHAT and CSBS-DP-ITC or between the M-CHAT and ITSP. CONCLUSION: The results strongly support the hypothesis of an increased prevalence of autism in children with a birth weight less than 1,500 g.

Asperger syndrome related suicidal behavior: two case studies.

Asperger syndrome hinders adaptation to developmental challenges during childhood and adolescence, particularly with regard to interpersonal relationships. Individuals with Asperger syndrome display lack of empathy and limited ability to understand social and emotional exchanges with other people. Individuals with Asperger syndrome are significantly exposed to the risk of suicidal behavior, especially during adolescence. The authors describe cases of suicidal behavior in two adolescent boys with Asperger syndrome.

Controversies in autism: is a broader model of social disorders needed?

This article examines the most significant, contradictory evidence pertaining to autism. The first section of the article includes reports of recovery from autism, data obtained from studies involving oxytocin, early deprivation, autism in preterm children, late-onset autism, and symptom overlap among ASD, social phobias and personality disorders. In the second section of the article, we offer a model that better incorporates current findings and address controversies that continue to surround ASD. We propose an umbrella term "social inhibition disorders" which integrates autism spectrum disorders and social phobias, as well as schizoid, schizotypal, and obsessive-compulsive personality disorders. It would also include "quasi-autism," which has been found in early deprivation studies, autism in preterm children, and cases of late-onset autism presenting after herpes encephalitis infection. Finally, we discuss suggestions for further research and clinical perspectives.

Olfactory functions are not associated with autism severity in autism spectrum disorders.

BACKGROUND: Changes in olfactory functions have been found in many neurodegenerative and psychiatric disorders, including autism spectrum disorders (ASDs). The aim of the present study was to evaluate the relationship between olfactory functions (odor-detection thresholds, odor identification, and odor preference) and autism severity and sensory-related behavior in children and adolescents with ASD. SUBJECTS AND METHODS: Our sample consisted of 35 high-functioning patients with ASD (mean age 10.8±3.6 years, 31 boys). Olfactory testing (threshold and identification) used the Sniffin' Sticks test. Odor pleasantness was assessed on a 5-point scale using the Identification part of the Sniffin' Sticks test. The severity of autistic psychopathology was measured using the Childhood Autism Rating Scale (CARS). RESULTS: Using Spearman's correlation, we found no significant correlations between autism severity (as expressed by total CARS score) and odor-detection thresholds (R=0.144, P=0.409), odor identification (R=0.07, P=0.966), or odor pleasantness (R=-0.046, P=0.794). There was also no significant relationship between CARS item 9 ("Taste, smell, and touch response and use") and odor-detection thresholds (R=0.170, P=0.330), odor identification (R=0.282, P=0.100), or odor pleasantness (R=0.017, P=0.923). CONCLUSION: We did not find any significant relationship between the severity of autistic psychopathology and olfactory functions.

Onset of action of atypical and typical antipsychotics in the treatment of adolescent schizophrenic psychoses.

OBJECTIVES: The aim of our study was to assess the time to 'first improvement' associated with specific atypical (AAP) and typical (TAP) antipsychotic drugs in patients with early-onset schizophrenia and other related psychotic disorders. METHODS: This study involved a systematic chart review of all patients receiving routine clinical care in our department, with selected AAPs and TAPs, for schizophrenic psychoses, between 1997 and 2007. During this period, our review identified 296 teenage patients (141 males, 155 females; mean age 16.0 ± 1.5 years). The time to first improvement could be estimated in 258 patients; of these, 195 patients (76%) had been treated with AAPs and 63 patients (24%) with TAPs. We found that most patients were taking risperidone (N = 96), followed by olanzapine (64 patients). Other patient numbers were as follows: ziprasidone (16 patients), quetiapine (12 patients), clozapine (7 patients), haloperidol (15 patients), perphenazine (28 patients), and sulpiride (20 patients). RESULTS: The mean time to first improvement was 6.9 (± 4.2) days in the AAP group and 5.8 (± 3.5) days in the TAP group; the difference was significant at the trend level (p=0.063). With respect to individual drugs, the mean time to first improvement was 7.1 (± 4.1) days for risperidone, 6.7 (± 4.2) days for olanzapine, 6.5 (± 5.2) days for ziprasidone, 6.1 (± 4.4) days for quetiapine, 7.4 (± 3.0) days for clozapine, 5.2 (± 2.4) days for haloperidol, 5.9 (± 3.8) days for perphenazine, and 6.0 (± 3.9) days for sulpiride. Differences among drugs were not significant (p=0.680). CONCLUSIONS: Analysis revealed a significant group level trend indicating that typical antipsychotic drugs have faster onsets of action than atypical antipsychotic drugs.

Odor detection threshold, but not odor identification, is impaired in children with autism.

The aim of our study was to examine odor detection thresholds and odor identification in autistic subjects. Thirty-five patients with Asperger's syndrome and high functioning autism (mean age 10.8 ± 3.6 years; 31 boys) were compared with 35 healthy control subjects (mean age 10.4 ± 2.4 years; 28 boys). There were no significant differences between groups with regard to mean age (p = 0.598) and gender proportion (p = 0.324). Olfactory testing used the Sniffin' Sticks test (threshold and identification parts only). Participants with Asperger's syndrome and high functioning autism, in comparison with healthy controls, were significantly impaired relative to odor detection thresholds (6.3 ± 3.1 vs. 7.9 ± 2.0; p = 0.025). Autistic participants were significantly better in correctly identifying the odor of an orange (94 vs. 63%; p < 0.05) and significantly worse at correctly identifying the odor of cloves (40 vs. 74%; p < 0.05). With regard to identification of fourteen other substances, there were no significant differences. There was no significant difference between autistic and control subjects on the total score of olfactory identification (p = 0.799). Odor identification ability (as expressed by this total score) correlated significantly with age in the control group (p = 0.049), but not in the autism group (p = 0.103). We found impaired odor detection and almost normal odor identification in children with autism. Implications for further research are discussed.

Brief report: significant differences in perceived odor pleasantness found in children with ASD.

The aim of our study was to explore possible differences in estimation of odor pleasantness in children with autism spectrum disorders (ASD) compared to controls. Thirty-five patients with Asperger's syndrome and high functioning autism (mean age 10.8 ± 3.6 years; 31 boys) were compared with 35 healthy control subjects (mean age 10.4 ± 2.4 years; 28 boys). Odor pleasantness was assessed on a 5-point scale using the Sniffin' Sticks test (Identification part of the test). Patients with ASD, compared to healthy controls, perceived the smell of cinnamon and pineapple as significantly less pleasant (p < 0.05); at the trend level, the same was true of cloves (p < 0.1). The possibility of olfactory dysfunctions as an autism biomarker is discussed.