Annelies de Bildt

A normed study of face recognition in autism and related disorders.

Although the interpretation of studies of face recognition in older children, adolescents, and adults with autism is complicated by the fact that participating samples and adopted methodologies vary significantly, there is nevertheless strong evidence indicating processing peculiarities even when task performance is not deficient. Much less is known about face recognition abilities in younger children with autism. This study employed a well-normed task of face recognition to measure this ability in 102 young children with autism, pervasive developmental disorder not otherwise specified (PDDNOS), and non-PDD disorders (mental retardation and language disorders) matched on chronological age and nonverbal mental age, and in a subsample of 51 children divided equally in the same three groups matched on chronological age and verbal mental age. There were pronounced deficits of face recognition in the autistic group relative to the other nonverbally matched and verbally matched groups. Performance on two comparison tasks did not reveal significant differences when verbal ability was adequately controlled. We concluded that young children with autism have face recognition deficits that cannot be attributed to overall cognitive abilities or task demands. In contrast to controls, there was a lower correlation between performance on face recognition and nonverbal intelligence, suggesting that in autism face recognition is less correlated with general cognitive capacity. Contrary to our expectation, children with PDDNOS did not show face recognition deficits.

Cohort Profile: The Dutch ‘TRacking Adolescents’ Individual Lives’ Survey’; TRAILS

Mental disorders account for one-fifth of the total burden of disease in the Western world, 1 and, as such, should require due attention from the international epidemiological research community. Good quality research on the aetiology and course of psychopathology in the population is impossible without reliable and valid data from long-term longitudinal cohort studies. Research on psychopathology in adolescence is important both from a scientific point of view and from the point of view of prevention and public health policy. Adolescence is characterized by major biological, psychological and social challenges and opportunities, where interaction between the individual and environment is intense, and developmental pathways are set in motion or become established. 2–4 Furthermore, adolescent psychopathology can have important consequences for education, relationships and socioeconomic achievement in later life. 5–7 These characteristics of adolescence do not only set high demands for cohort studies aiming to capture the most salient aspects of developmental pathways, they also ensure a great gain in empirical knowledge and an invaluable source of information for public health policy from such studies. In order to fully benefit from this potential, a multidisciplinary approach is essential.

Platelet Serotonin Levels in Pervasive Developmental Disorders and Mental Retardation: Diagnostic Group Differences, Within-Group Distribution, and Behavioral Correlates

OBJECTIVE To investigate group differences, the within-group distributions, and the clinical correlates of platelet serotonin (5-HT) levels in pervasive developmental disorders (PDD). METHOD Platelet 5-HT levels were measured in Dutch children and young adults, recruited from 2001 through 2003, with PDD (autism, Aspergers, and PDD-not otherwise specified [PDD-NOS]; n = 81) or with mental retardation (MR; n = 54) but without PDD, and in normal controls (n = 60). The distribution of platelet 5-HT levels was assessed using mixture-modeling analyses. Relationships between platelet 5-HT levels and a full range of demographic, clinical, and behavioral variables were examined. RESULTS Group mean (+/- SD) platelet 5-HT levels (nmol/10 platelets) were significantly higher in the autistic (4.51 +/- 1.61, n = 33) and PDD-NOS (4.90 +/- 1.54, n = 43) groups compared to the MR (3.48 +/- 1.33, n = 54) or the normal control (3.58 +/- 1.08, n = 60) groups (F4,190 = 9.35, p <.001). Platelet 5-HT values in the combined PDD group showed a bimodal distribution, and an empirical cutpoint for hyperserotonemia was determined. None of the behavioral variables examined was significantly associated with platelet 5-HT levels. CONCLUSIONS The platelet hyperserotonemia of autism was replicated in Dutch subjects. Platelet 5-HT levels were also increased in PDD-NOS, while no elevation was seen in MR. Platelet 5-HT levels appeared to be bimodally distributed in the PDD group, with an apparent hyperserotonemic subgroup.

Diagnosing Autism Spectrum Disorders in Adults: the Use of Autism Diagnostic Observation Schedule (ADOS) Module 4

Autism Diagnostic Observation Schedule (ADOS) module 4 was investigated in an independent sample of high-functioning adult males with an autism spectrum disorder (ASD) compared to three specific diagnostic groups: schizophrenia, psychopathy, and typical development. ADOS module 4 proves to be a reliable instrument with good predictive value. It can adequately discriminate ASD from psychopathy and typical development, but is less specific with respect to schizophrenia due to behavioral overlap between autistic and negative symptoms. However, these groups differ on some core items and explorative analyses indicate that a revision of the algorithm in line with Gotham et al. (J Autism Dev Disord 37: 613–627, 2007) could be beneficial for discriminating ASD from schizophrenia.

Macrophage migration inhibitory factor and autism spectrum disorders

OBJECTIVE. Autistic spectrum disorders are childhood neurodevelopmental disorders characterized by social and communicative impairment and repetitive and stereotypical behavior. Macrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity that promotes monocyte/macrophage-activation responses by increasing the expression of Toll-like receptors and inhibiting activation-induced apoptosis. On the basis of results of previous genetic linkage studies and reported altered innate immune response in autism spectrum disorder, we hypothesized that MIF could represent a candidate gene for autism spectrum disorder or its diagnostic components. METHODS. Genetic association between autism spectrum disorder and MIF was investigated in 2 independent sets of families of probands with autism spectrum disorder, from the United States (527 participants from 152 families) and Holland (532 participants from 183 families). Probands and their siblings, when available, were evaluated with clinical instruments used for autism spectrum disorder diagnoses. Genotyping was performed for 2 polymorphisms in the promoter region of the MIF gene in both samples sequentially. In addition, MIF plasma analyses were conducted in a subset of Dutch patients from whom plasma was available. RESULTS. There were genetic associations between known functional polymorphisms in the promoter for MIF and autism spectrum disorder–related behaviors. Also, probands with autism spectrum disorder exhibited higher circulating MIF levels than did their unaffected siblings, and plasma MIF concentrations correlated with the severity of multiple autism spectrum disorder symptoms. CONCLUSIONS. These results identify MIF as a possible susceptibility gene for autism spectrum disorder. Additional research is warranted on the precise relationship between MIF and the behavioral components of autism spectrum disorder, the mechanism by which MIF contributes to autism spectrum disorder pathogenesis, and the clinical use of MIF genotyping.

Serotonin transporter intron 2 polymorphism associated with rigid-compulsive behaviors in Dutch individuals with pervasive developmental disorder

Two putatively functional polymorphisms of the serotonin transporter gene (HTT, SLC6A4) were examined for associations with risk for pervasive developmental disorders (PDDs) and specific autism phenotypes. Dutch patients diagnosed with PDD (N = 125, age range 5–20 years, DSM‐IV‐TR based criteria, ADI‐R and ADOS behavioral assessments) and their parents (N = 230) were genotyped for promoter ins/del (5‐HTTLPR) and intron 2 variable number of tandem repeats (VNTR) alleles. Using the transmission disequilibrium test (TDT), no disorder‐specific preferential transmission of promoter (long and short) or intron 2 (10‐ and 12‐repeat) alleles was observed. However, multivariate analysis of continuous autism‐related behavioral measures revealed that subjects with intron 2 12/12 genotype were significantly more impaired in the rigid‐compulsive domain (P = 0.008). Quantitative TDT (QTDT) analysis also showed significant association of the intron 2 VNTR 12‐repeat allele with rigid‐compulsive behavior (P = 0.015). These results suggest that intron 2 VNTR alleles or nearby polymorphisms in linkage disequilibrium may play a role in specific aspects of the behavioral phenotype of autism.

Evaluation of the ADOS Revised Algorithm: The Applicability in 558 Dutch Children and Adolescents

The revised ADOS algorithms, proposed by Gotham et al. (J Autism Dev Disord 37:613–627, 2007), were investigated in an independent sample of 558 Dutch children (modules 1, 2 and 3). The revised algorithms lead to better balanced sensitivity and specificity for modules 2 and 3, without losing efficiency of the classification. Including the restricted repetitive behaviour domain in the algorithm contributes to a clinical ASD classification in modules 2 and 3. For module 1, the results indicate less improvement, probably due to the low-functioning population. In most groups, the advantages of the revised algorithms are achieved without losing the strength of the original algorithm.

Validity of the Children’s Social Behavior Questionnaire (CSBQ) in Children with Intellectual Disability: Comparing the CSBQ with ADI-R, ADOS, and Clinical DSM-IV-TR Classification

The Children’s Social Behavior Questionnaire (CSBQ) was compared with the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS), and clinical classification in children with mild and moderate intellectual disability (ID), to investigate its criterion related validity. The contribution of the CSBQ to a classification of Autism Spectrum Disorder (ASD) was most specific for the subscales ‘contact’ and ‘stereotyped’, with high coherence with all three classification methods. The CSBQ may be used as a signaling, screening, or describing instrument for children with ASD and ID, as it complements other methods by adding unique information about the clinical presentation.

Standardized ADOS Scores: Measuring Severity of Autism Spectrum Disorders in a Dutch Sample

The validity of the calibrated severity scores on the ADOS as reported by Gotham et al. (J Autism Dev Disord 39: 693–705, 2009), was investigated in an independent sample of 1248 Dutch children with 1455 ADOS administrations (modules 1, 2 and 3). The greater comparability between ADOS administrations at different times, ages and in different modules, as reached by Gotham et al. with the calibrated severity measures, seems to be corroborated by the current study for module 1 and to a lesser extent for module 3. For module 2, the calibrated severity scores need to be further investigated within a sample that resembles Gotham’s sample in age and level of verbal functioning.

Increased seroreactivity in tic disorder patients to a 60 kDa protein band from a neuronal cell line.

In tic disorders, increased seroreactivity against neuronal antigens has been demonstrated, without performing molecular characterization of antigens. Here, unselected patients with a tic disorder were compared with healthy controls, autistic disorder (AD), and obsessive-compulsive disorder (OCD) patients. Seroreactivity against neuroblastoma cells was analyzed by Western blot. Anti-60 kDa binding occurred significantly more frequently in tic disorder patients (67.1%) than in AD (40.0%), OCD (40.0%) and healthy controls (41.9%). Sequence analysis of the 60 kDa protein band identified this as a ubiquitous heat shock protein. However, the involvement of other autoantigens with a molecular weight of 60 kDa cannot be excluded.