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.

The relationship between brain abnormalities and autistic psychopathology in pervasive developmental disorders.

The aim of the present research has been to determine whether there is a relationship between brain abnormalities found on magnetic resonance imaging (MRI) and autistic psychopathology. A retrospective analysis covering a period between 1998 and 2015 included 489 children with autism (404 boys, 85 girls; average age 8.0 ± 4.2 years) who underwent an MRI of the brain. For clinical diagnosis of autism, the International Classification of Diseases, 10th revision (ICD-10), was used. Autistic psychopathology was evaluated by means of the Autism Diagnostic Interview - Revised. The Spearman nonparametric correlation analysis and chi-square test were used to examine the possible relationships between variables. The group of autistic children did not manifest a statistically significant correlation between the parameters examined on MRI and autistic psychopathology. A correlation between other cysts and repetitive behavior was significant only at trend level (P = 0.054). Gliosis of the brain was significantly more frequent in autistic children with mental retardation than in children without mental retardation (14.1% vs. 7.4%; P = 0.028). Nonmyelinated areas in the brain were significantly more frequent in autistic children with autistic regression than in children without autistic regression (29.9% vs. 15.7%; P = 0.008). Mental retardation was significantly more frequent in autistic children with autistic regression than in children without regression (73.2% vs. 52.5%; P = 0.002). Our research study did not reveal a statistically significant correlation of brain abnormalities on MRI with autistic psychopathology.

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.

Bulimia symptoms in Czech youth: prevalence and association with internalizing problems.

OBJECTIVE: Although clinical studies suggest that bulimia symptoms are common in youth, research on the prevalence of such symptoms and of their association with comorbid internalizing problems in the general population has been limited. This study aimed to evaluate the gender-specific prevalence of bulimia symptoms in Czech youth and explored the association between a clinical level of self-reported bulimia symptoms (CLBS) and internalizing problems by gender, controlling for age, socio-economic status and puberty status. METHOD: The study was conducted on a representative national sample of Czech youth (N = 4430, 57.0% female) using self-report scales. Multivariate analysis of covariance (MANCOVA) was used to examine the associations. RESULTS: The 3-month CLBS prevalence was higher in girls (11.4%) than in boys (3.8%) and in both genders a CLBS was associated with higher levels of comorbid internalizing problems. DISCUSSION: Timely recognition of bulimia symptoms and associated risk factors is important for early prevention and intervention strategies. LEVEL OF EVIDENCE: V, cross-sectional descriptive study (according to Oxford (UK) CEBM Levels of Evidence, 2011).

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.

Maintenance electroconvulsive therapy in schizophrenia.

BACKGROUND: The aim of our retrospective naturalistic observational study was to describe the use of maintenance electroconvulsive therapy (M-ECT) in chronic pharmacoresistant schizophrenia. SUBJECTS AND METHODS: We delineated 19 cases of chronic pharmacoresistant schizophrenia (females N=12) recently treated with maintenance electroconvulsive therapy at the Havlickuv Brod Psychiatric Hospital in the Czech Republic. Demographic, clinical and treatment variables were recorded. RESULTS: M-ECT, when applied weekly to monthly mostly over a period of several years, was of no benefit in the treatment of chronic hallucinations and/or delusions. However, it did prove beneficial (p<0.001) in removing chronic serious symptoms like suicidal or violent behavior, automutilation, refusal of food or liquids, stupor or catatonia. Even though almost all of our patients remained hospitalized, we were nonetheless able to transfer them to an unlocked psychiatric ward and let them out for walks or occupational therapy with almost no need for using restraint. No serious adverse side effects of M-ECT were found. CONCLUSIONS: Our study is limited by using only one simple standardized measurement (Clinical Global Impression - Severity) that was retrospective. Another limitation of our retrospective study was that the subjects had not been regularly tested for their cognitive functions. According to our results, M-ECT mitigates the impact of the disease and improves social functioning of the patients. M-ECT does not treat chronic schizophrenia but does make the lives of patients more tolerable. We suggest further research into M-ECT and its clinical application in chronic pharmacoresistant schizophrenia.

The yield of structural magnetic resonance imaging in autism spectrum disorders.

AIMS: The aim of our study was to assess the yield of routine brain magnetic resonance imaging (MRI) performed at our hospital as part of the diagnostic procedures focused on autism. METHODS: Our retrospective study involved children who had attended a diagnostic examination focused on autism and underwent brain MRIs between 1998-2015. The International Classification of Diseases, 10th edition was used to make clinical diagnoses. In 489 children (404 boys, 85 girls; mean age 8.0±4.2 years), a diagnosis of a pervasive developmental disorder was confirmed. Forty-five children, where the autism diagnosis was ruled out (but other psychiatric diagnoses found), served as a control group (36 boys, 9 girls; mean age 7.0±2.4 years). We can assume that in such a control group, brain abnormalities might occur at a higher frequency than in truly healthy children which would have the effect of reducing the difference between the groups. RESULTS: MRI pathologies were more common in the autistic (45.4 %) compared to the control group (31.8%) but the difference was significant only at the trend level (P=0.085). Hypoplasia of the corpus callosum (CC) was significantly more common in the autistic vs. the control group (13.7 vs. 0%; P=0.009). In contrast, nonmyelinated areas of white matter were significantly more common in controls (31.8 vs.17.3%; P=0.018). Differences in other parameters were not significant. CONCLUSION: The occurrence of CC hypoplasia on routine MRI scans could represent a "red flag" for suspicion of autism.

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.

Somatic symptoms and internalizing problems in urban youth: a cross-cultural comparison of Czech and Russian adolescents.

Background: Although the association between somatic complaints and internalizing problems (anxiety, somatic anxiety and depression) is well established, it remains unclear whether the pattern of this relationship differs by gender and in different cultures. The aim of this study was to examine cross-cultural and gender-specific differences in the association between somatic complaints and internalizing problems in youth from the Czech Republic and Russia. Methods: The Social and Health Assessment, a self-report survey, was completed by representative community samples of adolescents, age 12-17 years, from the Czech Republic (N = 4770) and Russia (N = 2728). Results: A strong association was observed between somatic complaints and internalizing psychopathology. Although the levels of internalizing problems differed by country and gender, they increased together with and largely in a similar way to somatic complaints for boys and girls in both countries. Conclusion: The association between somatic symptoms and internalizing problems seems to be similar for boys and girls across cultures.

Community violence exposure and substance use: cross-cultural and gender perspectives.

The negative effects of community violence exposure on child and adolescent mental health are well documented and exposure to community violence has been linked both to a number of internalizing and externalizing symptoms. Our aim was, therefore, to investigate cross-cultural and gender differences in the relationship between community violence exposure and substance abuse. A self-report survey was conducted among 10,575, 12-18 year old adolescents in three different countries, Czech Republic (N = 4537), Russia (N = 2377) and US (N = 3661). We found that in all three countries both substance use and problem behavior associated with it increased similarly along with severity of violence exposure and this association was not gender-specific. It was concluded that in spite of the differences in the levels of violence exposure and substance use cross-culturally and by gender, the pattern of their association is neither culturally nor gender bound.

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.

Expanded DMPK repeats in dizygotic twins referred for diagnosis of autism versus absence of expanded DMPK repeats at screening of 330 children with autism.

Myotonic dystrophy type 1 (DM1) belongs to the broad spectrum of genetic disorders associated with autism spectrum disorders (ASD). ASD were reported predominantly in congenital and early childhood forms of DM1. We describe dizygotic twin boys with ASD who were referred for routine laboratory genetic testing and in whom karyotyping, FMR1 gene testing, and single nucleotide polymorphism array analysis yielded negative results. The father of the boys was later diagnosed with suspected DM1, and testing revealed characteristic DMPK gene expansions in his genome as well as in the genomes of both twins and their elder brother, who also suffered from ASD. In accord with previous reports on childhood forms of DM1, our patients showed prominent neuropsychiatric phenotypes characterized especially by hypotonia, developmental and language delay, emotional and affective lability, lowered adaptability, and social withdrawal. The experience with this family and multiple literature reports of ASD in DM1 on the one side but the lack of literature data on the frequency of DMPK gene expansions in ASD patients on the other side prompted us to screen the DMPK gene in a sample of 330 patients with ASD who were first seen by a geneticist before they were 10 years of age, before the muscular weakness, which may signal DM1, usually becomes obvious. The absence of any DMPK gene expansions in this cohort indicates that targeted DMPK gene testing can be recommended only in ASD patients with specific symptoms or family history suggestive of DM1.

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.

Loneliness and its association with psychological and somatic health problems among Czech, Russian and U.S. adolescents.

BACKGROUND: Loneliness is common in adolescence and has been linked to various negative outcomes. Until now, however, there has been little cross-country research on this phenomenon. The aim of the present study was to examine which factors are associated with adolescent loneliness in three countries that differ historically and culturally-the Czech Republic, Russia and the United States, and to determine whether adolescent loneliness is associated with poorer psychological and somatic health. METHODS: Data from a school survey, the Social and Health Assessment (SAHA), were used to examine these relations among 2205 Czech, 1995 Russian, and 2050 U.S. male and female adolescents aged 13 to 15 years old. Logistic regression analysis was performed to examine if specific demographic, parenting, personal or school-based factors were linked to feeling lonely and whether lonely adolescents were more likely to report psychological (depression and anxiety) or somatic symptoms (e.g. headaches, pain). RESULTS: Inconsistent parenting, shyness, and peer victimisation were associated with higher odds for loneliness in at least 4 of the 6 country- and sex-wise subgroups (i.e. Czech, Russian, U.S. boys and girls). Parental warmth was a protective factor against feeling lonely among Czech and U.S. girls. Adolescents who were lonely had higher odds for reporting headaches, anxiety and depressive symptoms across all subgroups. Loneliness was associated with other somatic symptoms in at least half of the adolescent subgroups. CONCLUSION: Loneliness is associated with worse adolescent health across countries. The finding that variables from different domains are important for loneliness highlights the necessity of interventions in different settings in order to reduce loneliness and its detrimental effects on adolescent health.

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.

Correlates of weapon carrying in school among adolescents in three countries.

OBJECTIVES: To determine the factors associated with weapon carrying in school among Czech, Russian, and US adolescents. METHODS: Logistic regression was used to analyze data drawn from the Social and Health Assessment (SAHA). RESULTS: Violent behavior (perpetration / victimization) was linked to adolescent weapon carrying in all countries. Substance use was associated with weapon carrying among boys in all countries. Greater parental warmth reduced the odds for weapon carrying among Czech and Russian adolescents. Associating with delinquent peers was important for weapon carrying only among US adolescents. CONCLUSIONS: Factors associated with weapon carrying in school vary among countries although violent behavior and substance use may be associated with weapon carrying across countries.

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.