Thomas Lempp

Phenotypic and measurement influences on heritability estimates in childhood ADHD

Twin studies described a strongly heritable component of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. However, findings varied considerably between studies. In addition, ADHD presents with a high rate of comorbid disorders and associated psychopathology. Therefore, this literature review reports findings from population-based twin studies regarding the influence of subtypes, assessment instruments, rater effects, sex differences, and comorbidity rates on ADHD heritability estimates. In addition, genetic effects on the persistence of ADHD are discussed. By reviewing relevant factors influencing heritability estimates more homogeneous subtypes relevant for molecular genetic studies can be elicited. A systematic search of population-based twin studies in ADHD was performed, using the databases PubMed and PsycInfo. Results of family studies were added in case insufficient or contradictory findings were obtained in twin studies. Heritability estimates were strongly influenced by rater effects and assessment instruments. Inattentive and hyperactive–impulsive symptoms were likely influenced by common as well as specific genetic risk factors. Besides persistent ADHD, ADHD accompanied by symptoms of conduct or antisocial personality disorder might be another strongly genetically determined subtype, however, family environmental risk factors have also been established for this pattern of comorbidity.

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.

Antipsychotic prescription in children and adolescents: an analysis of data from a German statutory health insurance company from 2005 to 2012.

BACKGROUND Despite sparse documentation of their long-term therapeutic effects and side effects, antipsychotic drugs have come to be prescribed more frequently for children and adolescents in recent years, both in the USA and in Europe. No current data are available about antipsychotic prescriptions for this age group in Germany. METHODS Data from the largest statutory health insurance fund in Germany (BARMER GEK) were studied to identify antipsychotic prescriptions for children and adolescents (age 0-19 years) from 2005 to 2012 and analyze them with respect to age, sex, drug prescribed, prescribing medical specialty, and any observable secular trends. RESULTS The percentage of children and adolescents receiving a prescription for an antipsychotic drug rose from 0.23% in 2005 to 0.32% in 2012. In particular, atypical antipsychotic drugs were prescribed more frequently over time (from 0.10% in 2005 to 0.24% in 2012). The rise in antipsychotic prescriptions was particularly marked among 10- to 14-year-olds (from 0.24% to 0.43%) and among 15- to 19-year-olds (from 0.34% to 0.54%). The prescribing physicians were mostly either child and adolescent psychiatrists or pediatricians; the most commonly prescribed drugs were risperidone and pipamperone. Risperidone was most commonly prescribed for patients with hyperkinetic disorders and conduct disorders. CONCLUSION In Germany as in other industrialized countries, antipsychotic drugs have come to be prescribed more frequently for children and adolescents in ecent years. The German figures, while still lower than those from North America, are in the middle range of figures from European countries. The causes of the increase should be critically examined; if appropriate, the introduction of prescribing guidelines of a more restrictive nature could be considered.

Altered gene expression in the prefrontal cortex of young rats induced by the ADHD drug atomoxetine

Atomoxetine (ATX), a selective norepinephrine reuptake inhibitor, is a non-stimulant approved for the treatment of attention deficit/hyperactivity disorder (ADHD). Little is known about the molecular basis for its therapeutic effect. The objective of this animal study was to determine alterations in gene expression patterns in the prefrontal cortex after long-term administration of atomoxetine. Rats were treated for 21 days during childhood and early adolescent stages of development with a once-daily oral application of 0.05 g/kg atomoxetine, which resulted in plasma levels similar to those described in children. A whole genome RNA-microarray of rat prefrontal cortical gene expression after administration of atomoxetine versus sterile water revealed an mRNA increase in 114 genes (≥2-fold) while 11 genes were down-regulated (≤0.5-fold). By applying quantitative real-time PCR (qRT-PCR) and Western Blot we confirmed a significant increase in the expression of GABA A receptor subunits as well as ubiquinol-cytochrome c reductase complex core protein 2 (Uqcrc2). SNAP-25 (synaptosomal-associated protein of 25 kDa), which is an ADHD candidate gene and an important vesicle protein involved in axonal growth, synaptic plasticity and regulation of neurotransmitter release was also significantly upregulated on RNA- and protein level after atomoxetine treatment. In summary, we could show that long-term treatment with the ADHD drug atomoxetine induces the regulation of several genes in the prefrontal cortex of young rats. Especially the increased expression of SNAP-25 and GABA-A receptor subunits may indicate additional active therapeutic mechanisms for atomoxetine.

Who Wants to Become a Child Psychiatrist? Lessons for Future Recruitment Strategies From a Student Survey at Seven German Medical Schools

ObjectiveThe objective of this survey was to investigate undergraduate German medical students’ attitudes toward child and adolescent psychiatry (CAP) and to describe the characteristics of students considering CAP as a possible career choice.MethodsThe authors conducted a cross-sectional, multicenter survey of medical students (at the time of their first CAP lecture) at seven German medical schools. The students completed an anonymous self-report questionnaire, asking about their attitude toward CAP and their view of CAP as a possible career choice.ResultsOf the 574 students, 42.9% had “high” or “very high” interest in CAP, and 59.4% rated CAP basic knowledge as “highly” or “very highly” relevant for their prospective work as physicians. CAP was a possible career choice for 25.4%. The most frequently mentioned reasons for choosing CAP were interesting clinical cases (65.8%), helping ill children (52.1%), and close patient—physician contact (50.7%). The most frequently mentioned reasons against this decision were a definite decision for another subspecialty (54.8%), expected difficulties in working with parents and family members (35.3%), and an expected high emotional burden (29.6%). In addition to the highly significant correlation with general interest in CAP, students with previous experience in general psychiatry and CAP clinical courses, as well as female students and students with relatives or acquaintances with CAP-related disorders, showed the highest interest in CAP as a possible career choice.ConclusionThe majority of the students surveyed showed a positive attitude toward CAP and considered CAP basic knowledge to be relevant for their future work. When designing recruitment strategies, it may be helpful to consider that CAP exposure early in the curriculum might be decisive and that students with previous clinical courses in this field, as well as female students, showed the highest interest in CAP as a possible career choice.

Suicide in children and adolescents - a 13-year study with 78 cases

OBJECTIVE Updated and regional data about the circumstances of death and the psychosocial backgrounds of suicides can be helpful for improving suicide-preventive strategies in childhood and adolescence. METHOD All known cases of completed suicide in the period from 1996 to 2008 in persons ≤ 21 years of age from the Institute of Forensic Medicine, Frankfurt/Main were analysed in a retrospective study. We included 78 cases and matched them with a comparative sample of 1,797 adult suicides of persons > 21 years of age. RESULTS Within the chosen period there was a 44 % decrease in incidence of suicide in the group of ≤ 21-year-olds. The fraction of incarcerated persons in this group was 8.0 % compared to 2.56 % in the adult group. Differences from suicide in adulthood were also demonstrated in terms of suicide-related substance abuse (less detection of alcohol, more frequent detection of illicit drugs) and choice of methods (more deaths by being hit by a train). CONCLUSIONS Incarcerated adolescents are an important risk group for suicidal tendency and need increased, well-directed preventive measures. Clinical adolescent psychiatry should pay special attention to the indications in this study of an age-dependent association of drug use in suicide.

Suizide im Kindes- und Jugendalter

OBJECTIVE Updated and regional data about the circumstances of death and the psychosocial backgrounds of suicides can be helpful for improving suicide-preventive strategies in childhood and adolescence. METHOD All known cases of completed suicide in the period from 1996 to 2008 in persons ≤ 21 years of age from the Institute of Forensic Medicine, Frankfurt/Main were analysed in a retrospective study. We included 78 cases and matched them with a comparative sample of 1,797 adult suicides of persons > 21 years of age. RESULTS Within the chosen period there was a 44 % decrease in incidence of suicide in the group of ≤ 21-year-olds. The fraction of incarcerated persons in this group was 8.0 % compared to 2.56 % in the adult group. Differences from suicide in adulthood were also demonstrated in terms of suicide-related substance abuse (less detection of alcohol, more frequent detection of illicit drugs) and choice of methods (more deaths by being hit by a train). CONCLUSIONS Incarcerated adolescents are an important risk group for suicidal tendency and need increased, well-directed preventive measures. Clinical adolescent psychiatry should pay special attention to the indications in this study of an age-dependent association of drug use in suicide.

Male suicide rates in German prisons and the role of citizenship

Purpose Prisoners are at a particularly high risk of suicide. In contrast to other psychosocial risk factors it remains unclear to what degree the risk of suicide differs between prisoners with local citizenship and foreigners. In order to provide more detailed information for suicide prevention in prisons, this study aims to compare suicide rates (SR) between these populations in German criminal custody. Methods Based on a German national database of completed suicide in custody, suicides by prisoners were analysed and compared with epidemiological data of the prison population and the general population, stratified for German and foreign citizenship. Data analysis was adjusted for differences in the age distribution of both populations by calculating standard mortality ratios (SMR) for suicide. Results SR were higher in prisoners with German citizenship than those with foreign citizenship (SR = 76.5 vs. SR = 42.8, P<0.01). This association was not specific to the prison population, as the higher SR in citizens compared to non-citizens (SR = 19.3 vs. SR = 9.0, P<0.01) were also found in the general population. The association between prison suicide and citizenship was comparable in juvenile and adult prisoners, indicating its relevance to both the juvenile and adult detention systems. Conclusion Imprisonment is associated with a substantially increased risk of suicide in both German and non-German citizens, a finding which needs to be taken into consideration by the justice system. The lower suicide risk in non-German citizens is independent of whether or not they are in custody.

Suizid und Suizidalität unter adoleszenten Häftlingen

Following accidents, suicide is the second leading cause of death in adolescence. This stage of life has the most suicide attempts of all age groups. In addition to mentally ill juveniles, adolescent delinquents represent a high-risk group for suicidal behavior and completed suicide. In particular, the population of detainees, an extreme form of juvenile delinquency, have a 16- to 18-fold higher risk of suicidal behavior and suicide compared to the general population. Because the composition of juvenile detainees differs greatly from that of detained adults, age-specific scientific approaches and prevention programs are needed. This task cannot be addressed by juvenile detention staff alone, but rather demands close cooperation between adolescent psychiatrists, psychologists, prison medical staff, legal experts and prison officers to use the opportunity for suicide prevention in juvenile detention facilities.

Was erwarten Medizinstudierende von Vorlesungen in der Kinder- und Jugendpsychiatrie?

OBJECTIVE In child and adolescent psychiatry (CAP) lectures are the most common teaching format for medical students. Besides conveying basic knowledge and skills related to the medical management of children and adolescents with mental health problems, lectures also play a decisive role in the recruitment of future residents for this discipline. Thus, knowledge of the expectations of medical students of lectures is a crucial factor. METHOD 1,029 medical students at ten German medical schools were surveyed with a questionnaire in a cross-sectional design. RESULTS Items perceived as most important were knowledge of disorders (73 %), medical skills in handling children and adolescents (61 %), and differential diagnosis of normal and abnormal child behaviour in children and adolescents (59 %). 71 % set a high value on patient presentation, while 41 % expressed ethical concerns about presenting mentally ill minors in lectures. CONCLUSIONS The expectations of medical students toward CAP lectures are mainly related to the transfer of specialty-related knowledge and generic skills. The important area of teaching attitudes could best be covered via patient presentations, which are desired by most students. However, ethical concerns over patient presentation also need to be discussed with students.