Gerd Lehmkuhl

Inhibition, flexibility, working memory and planning in autism spectrum disorders with and without comorbid ADHD-symptoms

BackgroundRecent studies have not paid a great deal of attention to comorbid attention-deficit/hyperactivity disorder (ADHD) symptoms in autistic children even though it is well known that almost half of children with autism spectrum disorder (ASD) suffer from hyperactivity, inattention and impulsivity. The goal of this study was to evaluate and compare executive functioning (EF) profiles in children with ADHD and in children with ASD with and without comorbid ADHD.MethodsChildren aged 6 to 18 years old with ADHD (n = 20) or ASD (High-Functioning autism or Asperger syndrome) with (n = 20) and without (n = 20) comorbid ADHD and a typically developing group (n = 20) were compared on a battery of EF tasks comprising inhibition, flexibility, working memory and planning tasks. A MANOVA, effect sizes as well as correlations between ADHD-symptomatology and EF performance were calculated. Age- and IQ-corrected z scores were used.ResultsThere was a significant effect for the factor group (F = 1.55; dF = 42; p = .02). Post-hoc analysis revealed significant differences between the ADHD and the TD group on the inhibition task for false alarms (p = .01) and between the ADHD group, the ASD+ group (p = .03), the ASD- group (p = .02) and the TD group (p = .01) for omissions. Effect sizes showed clear deficits of ADHD children in inhibition and working memory tasks. Participants with ASD were impaired in planning and flexibility abilities. The ASD+ group showed compared to the ASD- group more problems in inhibitory performance but not in the working memory task.ConclusionOur findings replicate previous results reporting impairment of ADHD children in inhibition and working memory tasks and of ASD children in planning and flexibility abilities. The ASD + group showed similarities to the ADHD group with regard to inhibitory but not to working memory deficits. Nevertheless the heterogeneity of these and previous results shows that EF assessment is not useful for differential diagnosis between ADHD and ASD. It might be useful for evaluating strengths and weaknesses in individual children.

Rates for tic disorders and obsessive compulsive symptomatology in families of children and adolescents with Gilles de la Tourette syndrome

The aim of this study was to assess rates for tic disorders and obsessive compulsive psychopathology in families of children and adolescents with Gilles de la Tourette syndrome (TS). Diagnoses were based on the DSM III-R criteria. Obsessive compulsive psychopathology, that did not fulfill the criteria for obsessive compulsive disorder (OCD) was additionally assessed and termed obsessive compulsive symptoms (OCS). The authors hypothesized that comorbid OCD or OCS in TS patients predicts a higher familial loading with obsessive compulsive symptomatology. The study cohort included 87 patients with TS who were evaluated clinically and with the use of a structured psychiatric interview. All available parents (152/174; 87%), several sibs (49/93; 53%) and some second degree relatives (27/659; 4.1%) were also interviewed. For other first and second degree relatives the family history method was used. Familial rates for TS were clearly elevated. Rates for chronic tic disorders (CT) were considerably lower than in previous studies. Additionally, tic disorders not otherwise specified (TDNOS) were diagnosed in a substantial number of first degree (15/267; 5.6%) and second degree relatives (36/659; 5.5%). OCD in parents (4/174; 2.3%) did not occur in an above baseline rate. However, both OCD (14/87; 16.1%) and OCS (15/87; 17.2%) were frequently associated with TS in index patients. Interestingly, 10 of 16 fathers with OCS also had a tic disorder. Obsessive compulsive psychopathology clustered in families. It is concluded that genetic studies in TS could profit from adhering to a conservative diagnostic approach to both tic disorders and OCD. The familial clustering of OCS/OCD in conjunction with the elevated paternal rate for the co-occurrence of tic disorders and OCS might indicate heterogeneity of TS.

Serotonin transporter gene-linked polymorphic region: Allele distributions in relationship to body weight and in anorexia nervosa

Several lines of evidence implicate a role for the serotonergic system in body weight regulation and eating disorders. The magnitude and duration of postsynaptic responses to serotonin (5-HT) is directed by the transport into and release from the presynaptic neuron. Recently, a common polymorphism of a repetitive element in the region of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) was identified that results in a system of two common alleles. The activity of the 5-HTT, as measured in in vitro assays and in human lymphoblastoid cell lines, is dependent on the respective genotype. We thus hypothesized that this polymorphism is relevant for weight regulation in general and is possibly involved in the etiology of anorexia nervosa (AN). Allele frequencies and genotypes were determined in a total of 385 unrelated obese children, adolescents and adults, 112 underweight subjects and 96 patients with AN. Furthermore, both parents of 98 obese children and adolescents and of 55 patients with AN, respectively, were genotyped, thus allowing to test for both association and linkage. The comparison of allele frequencies between obese and underweight probands provided no evidence for a major role of the 5-HTTLPR in weight regulation. Patients with AN had allele frequencies not significantly different to those observed for obese and underweight individuals.

Discriminant validity of the child behaviour checklist CBCL-4/18 in German samples

Abstract This study examined the discriminant validity of the German version of CBCL in two large samples of referred and non-referred children and adolescents which were matched for age, sex and socio-economic status. The combined sample that was used for statistical analysis consists of 2,058 referred and 2,058 non-referred boys and girls between 4 and 18 years of age (mean age: referred boys=10.9 years, non-referred boys=10.9 years, referred girls=11.3 years, non-referred girls=11.1 years). Referral status was used as validity criterion. Statistical procedures included Odds Ratios, Total Predictive Values, ROC analyses and discriminant analyses. Results indicated that the discriminant validity of the German version of CBCL is comparable to the original English version. With the use of CBCL Total Problem Score as predictor (cut-off T≥ 60) 83.8 % of children and adolescents could correctly be classified (sensitivity 83.6 %, specificity 83.9 %). Symptoms of the “Attention Problems Scale” show the highest discriminative power to distinguish between disturbed and undisturbed children and adolescents.

Clinical behavioral problems in day- and night-wetting children.

Abstract In this prospective, clinical study of 167 consecutive wetting children, the associations between specific forms of day and night wetting and clinical behavioral symptoms according to a parental questionnaire (Child Behavior Checklist; CBCL), as well as ICD-10 child psychiatric diagnoses are analyzed. For the entire group, the proportion of children with at least one ICD-10 diagnosis was 40.1% and for the CBCL total problems scale 28.2% – three times higher than in the general population. Expansive disorders (21%) were twice as common as emotional disorders (12%). A significantly higher (P<0.05) proportion of day-wetting children had at least one diagnosis (52.6%) and emotional disorders (19.5%) compared with nocturnal enuretics (33.6% and 8.2%, respectively). Secondary nocturnal enuretics had significantly higher CBCL total problem scores (39.3% vs. 20.0%, P<0.05) as well as psychiatric ICD-10 diagnoses (75% vs. 19.5%, P<0.001) than primary enuretics. Children with primary monosymptomatic enuresis had the lowest rate of CBCL total behavioral symptoms (14.5%) and diagnoses (10%). Of the day-wetting children, those with voiding postponement had more expansive disorders (39.3% vs. 13.6%, P<0.05) and externalizing symptoms (37% vs. 19.%, NS) than those with urge incontinence. In summary, a third of wetting children showed clinically relevant behavioral problems with specific psychiatric comorbidity for the subtypes. A more-detailed differentiation into syndromes rather than into day/night and primary/secondary forms is needed.

Effectiveness of an adaptive multimodal treatment in children with Attention-Deficit Hyperactivity Disorder -- global outcome.

AbstractBackgroundThe meaning of different components within a multimodal treatment of ADHD remains to be further clarified.ObjectiveTo evaluate the effectiveness of behaviour therapy and drug treatment within an adaptive and individually tailored multimodal treatment for children with ADHD.MethodAfter an initial psychoeducation n = 75 school-children aged 6–10 years with a diagnosis of ADHD/HKD were assigned to either behaviour therapy (including continued psychoeducation) or medical management with methylphenidate plus psychoeducation. Depending on the effectiveness, the treatment was either terminated (if totally effective) with long–term aftercare and continuation of medication if needed, or (if partially effective) the other treatment component was added (combined treatment), or (if ineffective) the treatment components were replaced. Thus a treatment rationale was applied which resulted in an adaptive and individually tailored therapy – similar to a strategy that may be useful in clinical practice.ResultsOf the children who started with behaviour therapy after initial psychoeducation 26% received a combined treatment in later treatment stages. In most of the cases (82%) with initial medical management, behaviour therapy was added. ADHD symptoms, individually defined behaviour problems and comorbid symptoms were significantly reduced during the course of treatment. On core measures large pre–post effect sizes were found. On teacher ratings combined treatment was more effective than behaviour therapy.ConclusionsBoth, behaviour therapy and combined treatment are effective interventions within an adaptive and individually tailored multimodal treatment strategy.

Examining relations between psychopathology and psychopathy dimensions among adolescent female and male offenders.

AimThis study was performed to investigate relations between psychopathology and psychopathy in adolescent female and male detainees.MethodWe examined 91 male and 123 female adolescent detainees (aged 14–19) for psychopathology -using the Youth Self Report, the Overt Aggression Scale-Modified and a Conduct Disorder Self Report Scale- and for psychopathic dimensions using the psychopathy checklist youth version (PCL:YV). Based on a linear regression analysis we compared the specific associations between psychopathology and psychopathy in both male and female delinquent juveniles.ResultsOur results revealed higher scores for externalizing behavior and psychopathic dimensions in delinquent males, and higher internalizing problem scores in delinquent females. Furthermore, we found a positive relationship between suicidal behavior and the psychopathy total score as well as the affective, the lifestyle and the antisocial dimension only in girls. No association was found for suicidal behavior in boys. Regarding anxious-depressive behavior, we found a negative relation to the psychopathy total score and to the affective psychopathy factor for the boys.ConclusionExpectedly, the population of incarcerated adolescents exhibited a high prevalence of psychopathology. At the same time our results referred to meaningful gender-related differences with respect to associations with psychopathy. The gender-related differences in psychopathological symptoms could indicate varied subtypes of psychopathy in boys and girls.

Genome-wide association study in German patients with attention deficit/hyperactivity disorder

The heritability of attention deficit hyperactivity disorder (ADHD) is approximately 0.8. Despite several larger scale attempts, genome‐wide association studies (GWAS) have not led to the identification of significant results. We performed a GWAS based on 495 German young patients with ADHD (according to DSM‐IV criteria; Human660W‐Quadv1; Illumina, San Diego, CA) and on 1,300 population‐based adult controls (HumanHap550v3; Illumina). Some genes neighboring the single nucleotide polymorphisms (SNPs) with the lowest P‐values (best P‐value: 8.38 × 10−7) have potential relevance for ADHD (e.g., glutamate receptor, metabotropic 5 gene, GRM5). After quality control, the 30 independent SNPs with the lowest P‐values (P‐values ≤ 7.57 × 10−5) were chosen for confirmation. Genotyping of these SNPs in up to 320 independent German families comprising at least one child with ADHD revealed directionally consistent effect‐size point estimates for 19 (10 not consistent) of the SNPs. In silico analyses of the 30 SNPs in the largest meta‐analysis so far (2,064 trios, 896 cases, and 2,455 controls) revealed directionally consistent effect‐size point estimates for 16 SNPs (11 not consistent). None of the combined analyses revealed a genome‐wide significant result. SNPs in previously described autosomal candidate genes did not show significantly lower P‐values compared to SNPs within random sets of genes of the same size. We did not find genome‐wide significant results in a GWAS of German children with ADHD compared to controls. The second best SNP is located in an intron of GRM5, a gene located within a recently described region with an infrequent copy number variation in patients with ADHD.

The Changing Prevalence of Attention-Deficit/Hyperactivity Disorder and Methylphenidate Prescriptions: A Study of Data From a Random Sample of Insurees of the AOK Health Insurance Company in the German State of Hesse, 2000–2007

BACKGROUND The goal of this study is to assess changes in the prevalence of attention-deficit/hyperactivity disorder (ADHD) and methylphenidate prescriptions over the period 2000 to 2007 on the basis of data from a German statutory health insurance carrier. METHODS In a cross-sectional study, we analyzed data from a random sample of insurees of the AOK health insurance company in the German state of Hesse for the years 2000 to 2007. Per calender year, 50,000 to 63,000 children and adolescents were retrospectively observed with respect to the documentation of ADHD diagnosis (ICD-10 diagnosis F90) and the prescribing of methylphenidate (ATC: N06BA04). RESULTS In 2007, the overall prevalence of ADHD in all age groups (0-18 years) was 2.21% (95% CI: 2.09-2.34). This figure was 45% greater than the corresponding figure for the year 2000. The prevalence increased by a larger amount among girls aged 6 to 18 years than among boys in the same age group (+69% vs. +53%). In 2007, 1.06% (95% CI: 0.98-1.16) of the children/adolescents received at least one prescription for methylphenidate; this was a 96% increase over the prescription rate for 2000. A comparison of the two years 2000 and 2007 reveals a clear prevalence shift towards the older age groups, as well as an 82% increase in the average number of daily doses per recipient. Outpatient departments of child and adolescent psychiatry initiated more treatments in 2007 than in 2000. CONCLUSION The 1% prevalence of methylphenidate use among children and adolescents that was found in this study is the same as that reported in other European countries, such as Switzerland, the Netherlands, and Norway. A drawback of our study is its limitation to a single insurance carrier in a single region. Nonetheless, data of this type are useful for monitoring. The findings suggest further issues worth studying, e.g., off-label use or the indications for treatment in older age groups.

Support of the histaminergic hypothesis in Tourette Syndrome: association of the histamine decarboxylase gene in a large sample of families

Background Gilles de la Tourette Syndrome is a neurodevelopmental disorder that is caused by the interaction of environment with a complex genetic background. The genetic etiology of the disorder remains, so far, elusive, although multiple promising leads have been recently reported. The recent implication of the histamine decarboxylase (HDC) gene, the key enzyme in histamine production, raises the intriguing hypothesis of a possible role of histaminergic dysfunction leading to TS onset. Methods Following up on the finding of a nonsense mutation in a single family with TS, we investigated variation across the HDC gene for association with TS. As a result of a collaborative international effort, we studied a large sample of 520 nuclear families originating from seven European populations (Greek, Hungarian, Italian, Polish, German, Albanian, Spanish) as well as a sample collected in Canada. Results and Conclusions Interrogating 12 tagging SNPs (tSNP) across the HDC region, we find strong over-transmission of alleles at two SNPs (rs854150 and rs1894236) in the complete sample, as well as a statistically significant associated haplotypes. Analysis of individual populations also reveals signals of association in the Canadian, German and Italian samples. Our results provide strong support for the histaminergic hypothesis in TS etiology and point to a possible role of histamine pathways in neuronal development.