Natasja D. J. van Lang

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.

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.

Adult Attachment Interview differentiates adolescents with Childhood Sexual Abuse from those with clinical depression and non-clinical controls.

Although attachment representation is considered to be disturbed in traumatized adolescents, it is not known whether this is specific for trauma, as comparative studies with other clinical groups are lacking. Therefore, attachment representation was studied by means of the Adult Attachment Interview in adolescents with Childhood Sexual Abuse (CSA) (N = 21), clinical depression (N = 28) and non-clinical controls (N = 28). Coherence of mind and unresolved loss or trauma, as well as the disorganized attachment classification differentiated the CSA group from the clinical depression group and controls, over and above age, IQ, and psychiatric symptomatology. In the current era of sustained criticism on criteria-based classification, this may well carry substantial clinical relevance. If attachment is a general risk or vulnerability factor underlying specific psychopathology, this may guide diagnostic assessment as well as treatment.

Anterior cingulate cortex grey matter volume abnormalities in adolescents with PTSD after childhood sexual abuse

Adverse childhood experiences (ACE) substantially increase the risk of later psychiatric and somatic pathology. While neurobiological factors are likely to play a mediating role, specific insights are lacking. The scarce neuroimaging studies in traumatised pediatric populations have provided inconsistent results, potentially due to the inclusion of different types of trauma. To further improve our understanding of the neurobiology of pediatric psychotrauma, this study seeks to investigate abnormalities in grey matter volume (GMV) in a homogeneous group of adolescents with posttraumatic stress disorder (PTSD) due to childhood sexual abuse (CSA) and the relationship between GMV and symptom severity. We performed a voxel based morphometry (VBM) analysis in 21 adolescents with CSA-related PTSD and 25 matched non-traumatised, non-clinical adolescents. Hippocampus, amygdala, anterior cingulate cortex (ACC), medial PFC (mPFC) and superior temporal gyrus (STG) were chosen as regions of interest (ROIs). Trauma symptomatology was measured with the Trauma Symptom Checklist for Children (TSCC) and dissociation symptoms with the Adolescent Dissociative Experiences Scale (A-DES). The ROI analysis showed that the CSA-related PTSD group had significant smaller volumes of the dorsal ACC as compared to healthy controls. However, no correlations were found between GMV and scores on the TSCC and A-DES. The smaller ACC volume is partly in line with previous studies in traumatised youth and is a consistent finding in traumatised adults. Taken together our results suggest that the dorsal ACC is implicated in the neurobiological sequelae of CSA, potentially associated with an altered evaluative processing of emotion, but not directly with PTSD severity.

The visual rooting reflex in individuals with autism spectrum disorders and co-occurring intellectual disability

The rooting reflex has long been studied by neurologists and developmentalists and is defined as an orientation toward tactile stimulation in the perioral region or visual stimulation near the face. Nearly, all previous reports of the visual rooting reflex (VRR) concern its presence in adults with neurological dysfunction. Previously, the VRR was reported to be present in a majority of individuals with autism and absent in control subjects. In the present larger study, we examined the presence of the VRR in 155 individuals with ASD and co‐occurring Intellectual Disability (ASD + ID: autism, N = 60; Pervasive Developmental Disorder‐Not Otherwise Specified (PDD_NOS), N = 95) and in a contrast group of 65 individuals with ID only. The VRR was present significantly more often in the ASD + ID (43.9%) group than in the ID‐only group (24.6%; = 7.19; P = 0.007). Individuals with autism displayed a VRR more often (55.0%) than individuals with PDD‐NOS (36.8%; = 4.92; P = 0.026) and individuals with ID only (24.6%; = 12.09; P = 0.001). A positive VRR was associated with lower IQ and adaptive functioning; in the ASD + ID group, ADI‐R/ADOS domain scores were significantly higher in the VRR‐positive subgroup. The results replicate and extend the finding of an increased occurrence of the VRR in autism. Although some association with IQ was observed, the VRR occurred substantially more often in the autism group compared with an intellectually disabled group, indicating some degree of specificity. Additional studies of infants and children with typical development, ASD and ID are needed to determine the utility of the VRR in ASD risk assessment and to elucidate possible specific behavioral associations. Autism Res 2012,5:67–72.

Differential Fairness Decisions and Brain Responses After Expressed Emotions of Others in Boys with Autism Spectrum Disorders

Little is known about how emotions expressed by others influence social decisions and associated brain responses in autism spectrum disorders (ASD). We investigated the neural mechanisms underlying fairness decisions in response to explicitly expressed emotions of others in boys with ASD and typically developing (TD) boys. Participants with ASD adjusted their allocation behavior in response to the emotions but reacted less unfair than TD controls in response to happiness. We also found reduced brain responses in the precental gyrus in the ASD versus TD group when receiving happy versus angry reactions and autistic traits were positively associated with activity in the postcentral gyrus. These results provide indications for a role of precentral and postcentral gyrus in social-affective difficulties in ASD.