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.

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).

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.

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.

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.

Changes of orexin A plasma levels in girls with anorexia nervosa during eight weeks of realimentation.

OBJECTIVE: Orexin A (OXA) is a hypothalamic neuropeptide involved in regulation of food intake and nutritional status. There are multiple disturbances of neuropeptide signaling described in girls with anorexia nervosa (AN), but OXA levels have not been addressed in this population to date. Therefore, we analyzed OXA levels of AN girls in this study. METHOD: OXA (radioimmunoassay/RIA/method), leptin, insulinlike growth factor-1 (IGF-1), and insulinlike growth factor-1 binding protein-3 (IGFBP-3) levels were measured before and after 8 weeks of realimentation in 36 girls with AN and in 14 healthy controls (control group: CG). RESULTS: Average weight increased significantly in AN during the study (p < .0001), while plasma levels of OXA decreased (before realimentation: 56.2 ± 2.4 pg/ml; after realimentation: 47.5 ± 1.4 pg/ml; p = .0025). OXA levels before realimentation differed from levels in the CG (47.15 ± 2.6 pg/ml, p = .034), but not afterward. We did not find any correlation between OXA and age, height, weight, BMI; or IGF-1, IGFBP-3, and leptin levels. DISCUSSION: OXA levels in untreated AN patients differ significantly from healthy subjects and decrease during realimentation. These findings indicate that OXA may be involved in the nutritional regulation of malnourished children and adolescents.

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.

Long lasting complex nocturnal hallucinations during Osmotic Release Oral System (OROS) methylphenidate treatment in a 7-year old girl.

We report a case of a girl with Attention deficit hyperactivity disorder (ADHD) and Oppositional defiant disorder (ODD) who experienced a 3-hour episode of nocturnal complex bizarre visual hallucinations when treated with 18 mg Osmotic Release Oral System (OROS) methylphenidate (MPH). Nocturnal polysomnography performed two weeks later revealed REM sleep reduction (17%) and fragmentation . Two episodes of confusional arousals were recorded. This finding is typical of parasomnia associated with NREM sleep - disorder of arousal. We hypothesize that this preexisting sleep impairment represents a factor of vulnerability to MPH sleep side effects. In our search of literature, we found no report of nocturnal hallucination alone during treatment with stimulants.

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.

Anorexia nervosa in a blind girl.

Eating disorders represent significant psychopathological spectrum, particularly in adolescent girls. One of the risk factors associated with eating disorders is a strong emphasis of western visual-oriented culture on physical appearance and slimness. However, sensory handicap leading to disability to see one's own body and bodies of others does not mean that eating disorder cannot develop in blind people. The authors believe that body image is a mental construct that is not dependent on sensory perception only. They present the case of an adolescent patient, blind from early childhood, who shows symptoms of mental anorexia, depression, suicidal behavior and self-harming.

FMR1 gene expansion, large deletion of Xp, and skewed X-inactivation in a girl with mental retardation and autism.

We describe a girl with mild facial anomalies, mild mental retardation, and atypical autism with a remarkable behavioral phenotype of persistent anger, aggression, and dysphoria. The occurrence of late-onset tremor and premature ovarian failure in the maternal branch of the family pointed to a possible defect in the FMR1 gene. Indeed, the patient carried a full FMR1 mutation. Unexpectedly, both alleles of the gene were almost completely methylated. Cytogenetic examination of the patient revealed in addition a large de novo deletion in band Xp22 on one of her X chromosomes. The deletion was fine mapped using oligonucleotide array CGH, and its breakpoints were localized using sequencing. The size of the deletion was about 17.4 Mb, and it contained more than 90 protein-coding genes. Microsatellite analysis indicated paternal origin of the aberrant chromosome. The large rearrangement was the most probable cause of the X-inactivation skewing, thus explaining the methylation of not only the expanded (maternal) but also the normal (paternal) FMR1 alleles. This pattern of skewed X-inactivation was confirmed using the analysis of methylation at the AR locus. The relatively mild phenotype of the patient resulted most likely from unmasking of the FMR1 defect. Although the deleted region contained many important genes, the phenotypic contribution of the rearranged X chromosome was probably limited by its almost complete inactivation. However, reduced dose of several genes escaping X-inactivation might also play a role in the phenotype of the patient.

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.

Self-harm in adolescence: a girl who swallowed needles.

Self-harm represents a serious and pathological behavior that occurs most notably during adolescent years and currently seems to be a problem that is on the increase. Self-harm is a self destructive behavior which most frequently takes the form of cutting and burning. Relative to suicidal behavior, self-harm, in and of itself, is not intended to be lethal and tends to be repeated and addictive. However, in cases of self-harm the risk of suicidal behavior cannot be ignored. This presentation is a case study of a girl who engaged in an unusual form of self-harm, by swallowing needles.

Suicidal behavior in children and adolescents: does a history of trauma predict less severe suicidal attempts?

OBJECTIVES: The aim of this study was to identify risk factors and possible predictors of severity of suicidal behavior of children and adolescents. METHODS: Seventy-seven patients (15 boys and 62 girls) aged 15.5+/-1.6 years on average, hospitalized due to a suicidal attempt in the department of pediatric psychiatry, were examined. Structured interviews with patients and their parents were used to clinically assess circumstances of suicidal behavior, relevant risk factors and severity of suicidal behavior. RESULTS: The results indicated that patients with any previous traumatic experience tended to have somatically less severe suicidal attempts (p=0.050). Intensity of suicidal intent was associated with a history of depression (p=0.014) and anxiety disorders (p=0.004), and the current stress from a mental disorder (p=0.014). Somatic severity of suicidal behavior was significantly associated with intensity of suicidal intent (p=0.014). A history of any trauma (previous traumatic experience predicted less severe suicidal behavior, p=0.053) and the current stress from sexual problems (p=0.067) were identified as predictors of somatic severity of suicidality. These two predictors showed only a trend level of significance. The only significant predictor of intensity of suicidal intent was the current stress from a mental illness (p=0.017). CONCLUSIONS: Several risk factors of somatic severity of suicidal behavior and intensity of suicidal intent were described. The most important finding of the study was the association between a history of psychological trauma and a tendency to have less somatically severe suicidal behavior.

Weight gain associated with atypical and typical antipsychotics during treatment of adolescent schizophrenic psychoses: A retrospective study.

OBJECTIVES: The aim of the study was to assess weight changes associated with certain atypical (AAP) and typical (TAP) antipsychotic drugs in patients with early-onset schizophrenia and other related psychotic disorders. METHODS: Our retrospective study included 109 patients (52 boys, 57 girls) with a mean age of 15.8 +/- 1.6 years. The patients were evaluated based to their medical records prior to starting therapy, and then after 1, 3, and 6 weeks of treatment. RESULTS: During the first week of treatment, the AAP group (n = 85; risperidone, olanzapine, ziprasidone, and clozapine) gained 1.5% of baseline weight whereas the TAP group (n = 24; haloperidol, perphenazine, and sulpiride) gained only 0.2% (p = 0.049). Differences in relative changes between the two groups were not significant at weeks 3 and 6. Expressed as absolute values, patients in our sample gained an average of 3.4 kg (SD 3.2) on AAP and 2.0 kg (SD 3.9) on TAP during 6 weeks of treatment (p = 0.335). Only the risperidone, olanzapine, and clozapine groups had sufficient numbers of patients to allow a comparison at the endpoint of the study (week 6). The patients gained, on average, 3.6 kg (SD 2.6) on risperidone, 4.4 kg (SD 2.5) on olanzapine, and 2.1 kg (SD 4.0) on clozapine during the six weeks of treatment (p = 0.286). CONCLUSIONS: In our study, we did not find a difference in weight gain between the AAP and TAP groups, as large as has been described in the literature. It also seems plausible that the unique and variable weight changes associated with individual AAPs in the pediatric population are different from those observed in the adult population.

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.

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.