Martin Holtmann

Autism spectrum disorders: sex differences in autistic behaviour domains and coexisting psychopathology

The purpose of the present study was to examine possible differences between high‐functioning males and females with autism spectrum disorder (ASD) regarding the core symptoms of autism and coexisting psychopathology. A total of 23 females and 23 males matched for age, IQ, and ASD diagnoses were recruited(mean age 11y 9mo [SD 4y 5mo], range 5y‐20y 2mo) with an IQ above the range of learning disability (mean IQ 88.8 [SD 18.5], range 70–128). They were compared using the Autism Diagnostic Interview‐Revised, the Autism Diagnostic Observation Schedule, and the Child Behavior Checklist/4–18. We did not identify striking differences between males and females for the triad of autism core dysfunctions (deficits in reciprocal social interaction, communication, and repetitive, stereotyped behaviours) as assessed by expert ratings. However, with regard to several domains of coexisting psychopathology, parent reports revealed significantly more symptoms in females than males, particularly social problems (t=4.47, p<0.01, d=1.20), attention problems (t=3.39, p<0.01, d=0.80), and thought problems (t=3.24, p<0.01, d=0.84). These results are discussed with possible interpreting bias by parents who may expect more socially desired behaviour from daughters than from sons. The severity of social and attention problems in high‐functioning females with autism emphasizes the need for thorough assessments and interventions in these domains. Future research should compare the cognitive phenotype of autism between sexes.

Attention deficit hyperactivity disorder symptoms in pervasive developmental disorders : Association with autistic behavior domains and coexisting psychopathology

Background: Symptoms as in attention deficit hyperactivity disorder (ADHD) are frequent among individuals with pervasive developmental disorders (PDD). The aim of the present study was to examine the impact of inattention, hyperactivity and impulsivity on the clinical phenotype of children and adolescents with PDD. Sampling and Methods: A total of 182 subjects (41 females) diagnosed as having PDD were split into a high (PDD+) and a lower (PDD) attention problem group using the median of the Child Behavior Checklist (CBCL) syndrome scale ‘attention problems’ (median T score = 75). The groups were compared with regard to the degree of coexisting psychopathology, as measured by the remaining 7 CBCL subscales, and autistic core features assessed by the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule using a multivariate analysis of covariance adjusted for age, IQ and socioeconomic status. Results: The PDD+ subjects exhibited a significantly higher degree of general psychopathology than the subjects in the PDD subgroup, regarding both internalizing and externalizing symptoms. In addition, the PDD+ subgroup tended to exhibit more impairments on the social interaction scale of the ADI-R. Conclusions: Clinicians should adjust treatment plans to ensure comprehensive and effective treatment for both PDD and associated ADHD. A dual diagnosis may be essential to the implementation of effective treatments.

Autistic Traits and Autism Spectrum Disorders: The Clinical Validity of Two Measures Presuming a Continuum of Social Communication Skills

Research indicates that autism is the extreme end of a continuously distributed trait. The Social Responsiveness Scale (SRS) and the Social and Communication Disorders Checklist (SCDC) aim to assess autistic traits. The objective of this study was to compare their clinical validity. The SRS showed sensitivities of .74 to .80 and specificities of .69 to 1.00 for autism. Sensitivities were .85 to .90 and specificities .28 to.82 for the SCDC. Correlations with the ADI-R, ADOS and SCQ were higher for the SRS than for the SCDC. The SCDC seems superior to the SRS to screen for unspecific social and communicative deficits including autism. The SRS appears more suitable than the SCDC in clinical settings and for specific autism screening.

Sex differences in cognitive domains and their clinical correlates in higher-functioning autism spectrum disorders

Despite the skewed sex ratio, few studies have addressed possible cognitive sex differences in autism spectrum disorders (ASDs). This study compared visual attention to detail (ATTD) and selected executive functions (EF) in 35 males and 21 females with higher-functioning ASD and unaffected sibling controls. Females with ASD outperformed males on EF as assessed by the Trail Making Test B-A. Males with ASD showed superior performance for ATTD as measured by the Block Design Test (BD) when compared with females. EF difficulties in males were correlated with more stereotypic behaviours and interests on the Autism Diagnostic Interview-Revised or the Autism Diagnostic Observation Schedule. The results indicated clinically meaningful cognitive sex differences in ASD, particularly an association between EF and stereotypic behaviours and interests. ATTD as a potential basis for specific cognitive strengths (e.g. scientific/savant skills) might be more pronounced in males with ASD.

CBCL-pediatric bipolar disorder phenotype: severe ADHD or bipolar disorder?

SummaryBackground. In children with pediatric bipolar disorder (PBD), a consistent pattern of elevations in hyperactivity, depression/anxiety, and aggression has been identified on the child behavior checklist (CBCL-PBD profile). The aim of the present study was to estimate the prevalence of the CBCL-PBD profile in a child psychiatric sample, and to determine ICD-10 diagnoses in CBCL-PBD patients.Methods. We studied a sample of 939 consecutively referred children and adolescents, aged 4–18 years. ICD-10 discharge diagnoses were established in consensus conferences. The CBCL 4–18 was completed by parents as part of the diagnostic routine.Results. A total of 62 subjects (6.6%; 95% CI=5.2–8.4) met criteria for the CBCL-PBD phenotype. More than 75% of CBCL-PBD subjects were clinically diagnosed with disruptive behavior disorders (ADHD, ODD, and CD). Two patients (0.2% of the total sample) received a formal diagnosis of bipolar disorder, but did not show the CBCL-PBD phenotype.Conclusions. A considerable number of children in Germany are referred to psychiatric care with a mixed phenotype of aggression, anxiety, depression and attention problems. Our study demonstrated a comparable prevalence and similar clinical characteristics as reported from other countries using different diagnostic approaches. However, the CBCL-PBD phenotype does not correspond with clinical consensus diagnoses of bipolar disorder, but with severe disruptive behavior disorders.

Diminished Serotonergic Functioning in Hostile Children with ADHD: Tryptophan Depletion Increases Behavioural Inhibition

INTRODUCTIONnSerotonergic (5-HT) functioning has been shown to account for a variety of behavioural characteristics, in particular aggressive and impulsive behaviour. This study explored the effects of rapid tryptophan depletion (RTD) and the ensuing reduction of brain 5-HT synthesis on behavioural inhibition in passive avoidance learning assessed in a computerized go/no-go task.nnnMETHODSn22 male patients with an ICD-10 diagnosis of ADHD were administered RTD within an amino acid drink lacking tryptophan, the natural precursor of 5-HT, thus lowering the central nervous 5-HT synthesis rate in a placebo-controlled double-blind within-subject crossover-design. 4 hours after RTD/placebo intake the patients were subjected to a go/no-go task for assessment of behavioural inhibition.nnnRESULTSnHighly hostile aggressive patients showed increased inhibition errors under RTD compared to placebo. Low hostile aggressive patients showed lower rates of inhibition errors and thus better performance under RTD compared to placebo.nnnDISCUSSIONnThe data suggest that in ADHD levels of trait-aggressive characteristics influence the susceptibility to changed behavioural inhibition after an acute 5-HT dysfunction. The detected influence of 5-HT could also be relevant as regards behavioural inhibition being subject to a developmental change in 5-HT functioning.

Rolandic spikes increase impulsivity in ADHD – A neuropsychological pilot study

The present study was designed to examine the association of Rolandic spikes with the neuropsychological profile of children with ADHD. A total of 48 children (mean age 9.4 +/- 1.6 years, range 6.7-14.9 years; 16 ADHD children with Rolandic spikes, 16 ADHD children without epileptiform discharges and 16 healthy controls) matched for age, gender, and IQ were examined with a neuropsychological assessment battery focussing on attentional processing, cognitive efficiency, response inhibition, visuospatial and auditory-verbal short-term memory and language function (CPT-AX, Stroop, digit span, Complex Figure of Rey, Heidelberg Language Development Test). ADHD children with Rolandic spikes performed worse than ADHD children without epileptiform discharges and healthy controls in a variety of CPT and Stroop test measures. In particular, they made significantly more commission errors, reflecting impaired inhibition of an ongoing response. In addition, they had pronounced difficulties in the color word condition of the Stroop test and exhibited lower interference scores, indicating poorer interference control. Results of this pilot study suggest that in some ADHD children Rolandic spikes or an associated dysfunction aggravate the course of ADHD and predispose to increased impulsivity, evidenced in deficient inhibition of an ongoing response, and decreased interference control.

Diminished 5-HT functioning in CBCL pediatric bipolar disorder-profiled ADHD patients versus normal ADHD: susceptibility to rapid tryptophan depletion influences reaction time performance†‡

There is a current debate on characterizing children with pediatric bipolar disorder (PBD) through a profile within the child behaviour checklist (CBCL), and on the involvement of the 5‐HT system in the underlying neurobiological processes of PBD. The aim of the present paper was to investigate reaction time performance in patients with CBCL‐PBD and to discriminate ADHD from ADHD with CBCL‐PBD with respect to diminished 5‐HT functioning and reaction time.

An fMRI-study of locally oriented perception in autism: altered early visual processing of the block design test

Summary.Autism has been associated with enhanced local processing on visual tasks. Originally, this was based on findings that individuals with autism exhibited peak performance on the block design test (BDT) from the Wechsler Intelligence Scales. In autism, the neurofunctional correlates of local bias on this test have not yet been established, although there is evidence of alterations in the early visual cortex. Functional MRI was used to analyze hemodynamic responses in the striate and extrastriate visual cortex during BDT performance and a color counting control task in subjects with autism compared to healthy controls. In autism, BDT processing was accompanied by low blood oxygenation level-dependent signal changes in the right ventral quadrant of V2. Findings indicate that, in autism, locally oriented processing of the BDT is associated with altered responses of angle and grating-selective neurons, that contribute to shape representation, figure-ground, and gestalt organization. The findings favor a low-level explanation of BDT performance in autism.

Severe affective and behavioral dysregulation in youth is associated with increased serum TSH

BACKGROUNDnThe relationship of bipolar disorder (BD) and altered thyroid function is increasingly recognized. Recently, a behavioral phenotype of co-occurring deviance on the Anxious/Depressed (A/D), Attention Problems (AP), and Aggressive Behavior (AB) syndrome scales has been identified as the Child Behavior Checklist Dysregulation Profile (CBCL-DP), which itself has been linked to BD. This study tested for differences in thyroid function within a sample of n=114 psychiatric children and adolescents with and without the CBCL-DP.nnnMETHODnA CBCL-DP score was generated based on the composite of the crucial CBCL syndrome scales (A/D, AP, AB). Participants with a CBCL-DP score >or=2.5 SDs above average constituted the CBCL-DP subgroup (n=53). Those with CBCL-DP scores of 1 SD or less above average percentile were regarded as controls (n=61). Groups were compared regarding serum levels of TSH, fT3 and fT4.nnnRESULTSnIn participants showing the CBCL-DP, basal serum TSH was elevated compared to controls. More CBCL-DP subjects than controls showed subclinical hypothyroidism. No differences were observed for serum fT3 and fT4 levels.nnnCONCLUSIONSnThis is the first study to demonstrate associations between CBCL-DP and subclinical hypothyroidism. Future research should address the long-term outcome of CBCL-DP with coexisting hypothyroidism, the potential benefits of supplementation with thyroid hormone, and the association between severe dysregulation and the bipolar spectrum.