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Biomedical subjects

G Lehmkuhl

Publications and source records attributed to G Lehmkuhl.

At least 37 records · Page 2Linked to original sources

[From the prevention to the annihilation of "unworthy life"].

Starting from race hygienic and eugenic ideas at the end of 19th and at the beginning of the 20th century the development and the execution of the "euthanasia of children" by the Nazis is described. Particularly the carrying out of the killing action is so-called "special children's departments" is dealt with in detail by the use of available investigations. Finally questions about the perpetrator profile and regarding the significance of ethical principles in child and adolescent psychiatry are raised.

Child↗

Cognitive and behavioral profile of fragile X boys: correlations to molecular data.

Fragile X syndrome (FXS) is the most common form of inherited mental retardation after Down syndrome. The expansion of a CGG repeat, located in the 5'-untranslated region (5'-UTR) of the FMR1 (fragile X mental retardation) gene, leads to the hypermethylation of the repeat and the upstream CpG island. Methylation is associated with transcriptional silencing of the FMR1 gene. The lack of FMR1 protein is believed to be responsible for the typical physical and mental characteristics of the syndrome. To analyze the specific phenotype of that syndrome as well as possible associations between the phenotype and the genotype, we examined a group of 49 fragile X boys and a control group of 16 patients with tuberous sclerosis. To determine the cognitive and behavioral phenotype, the Kaufman Assessment Battery for Children (K-ABC), the Child Behavior Checklist (4/18), and a structured psychiatric interview (Kinder DIPS) were used. The genotype was analyzed by the Southern blot method. The phenotype of boys with FXS is characterized by a specific cognitive profile with strengths in acquired knowledge and in simultaneous processing. The psychiatric comorbidity is high and ADHD (attention deficit hyperactivity disorder), oppositional defiant disorder, enuresis, and encopresis predominate. In a group of 24 fragile X boys, no significant correlations between the specific aspects of the phenotype and the genotype were found.

5' Untranslated Regions↗

Complex segregation analysis of families ascertained through Gilles de la Tourette syndrome.

Although family and twin studies suggest that genetic factors are involved in the etiology of Tourette syndrome and other related tic disorders, further evidence is needed to demonstrate that the familial transmission is consistent with known genetic factors. We performed a complex segregation analysis that allowed for a variable age of onset of Gilles de la Tourette, other tic disorders and obsessive compulsive phenotype information on 108 extended families, each ascertained through one Tourette proband by using regressive models that are able to incorporate additional explanatory variables and major gene effects. A special version of the S.A.G.E. program, REGTLhunt, was used to explore the likelihood surface of all examined models. Results indicated that the pattern of Tourette and other related tic disorders in our data sample is not consistent with Mendelian inheritance even after modelling explanatory variables such as obsessive compulsive symptomatology.

Adolescent↗

[Neuropsychological testing in childhood and adolescence].

Among a number of issues and disorder pictures neuropsychological diagnostics should occupy a solid position, both in the initial assessment, as well as in that of the course. With an eye towards its use in child and adolescent psychiatry, a descriptive definition of this area of psychological diagnostics must be provided. In so doing, several essentially different approaches arise, whose effects on psychometrics and interpretation must be examined. Regardless of the fact that the current availability of standardized neuropsychological diagnostics is satisfactory only in certain areas, the methods used in clinical practice and/or research are presented. In addition to the individual test batteries, individual test methods for the areas of visual and auditory memory functions, attention functions, functions associated with speech, and executive functions are discussed. The current status of neuropsychological diagnostics generates essential tasks towards its further development. This is true with regard to goals attainable in the short term, such as adaptation or standardization of available instruments, as well as for long-term research tasks.

Adolescent↗

No evidence for involvement of polymorphisms of the dopamine D4 receptor gene in anorexia nervosa, underweight, and obesity.

Family and twin studies suggest a genetic contribution to the etiology of anorexia nervosa (AN) and obesity. Genes involved in weight regulation can be considered as candidate genes for AN. The dopaminergic system has been implicated in weight regulation; previous results had suggested a possible involvement of the dopamine D4 receptor gene (DRD4). We screened for alleles of two different polymorphisms (13-bp deletion, 48-bp repeat) in the DRD4. For association tests, allele frequencies were compared between 109 inpatients with AN, 82 underweight students, and 327 extremely obese children and adolescents. For application of transmission disequlibrium tests (TDT) we additionally genotyped 57 and 137 trios comprising a patient with AN or an extremely obese child or adolescent, respectively, and both parents. All genotyping was performed with polymerase chain reaction fragment length polymorphism analyses. None of the association tests or TDT rendered nominal P values below 0.1. An influence of alleles of the DRD4 on the development of AN, underweight, or extreme early onset obesity was not detected. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:594-597, 1999.

Adolescent↗

Tourette syndrome and the norepinephrine transporter gene: results of a systematic mutation screening.

Tourette syndrome (TS) is a complex inherited neuropsychiatric disorder characterized by multiple motor and phonic tics. Involvement of central norepinephrine mechanisms is suggested by central norepinephrinic hyperactivity in patients with TS and by the therapeutic effects of the presynaptic alpha2-adrenergic agonist clonidine. The norepinephrine transporter gene (NET) was systematically screened by single-strand conformation analysis for genetic variants, including the whole coding region and adjacent exon-intron boundaries in 43 patients with TS and 46 healthy controls. We detected 12 DNA sequence variants, among them four missense mutations (Val69Ile, Thr99Ile, Va1245Ile, and Gly478Ser). The observed missense mutations may alter conformational rearrangements during gating of the transporter, assembly of subunits, and norepinephrine-specific uptake affinity. Allele frequency and genotype distribution of the genetic variants showed no differences between TS patients and controls. No mutation of likely functional significance was found that distinguished TS patients from healthy controls, indicating that genetic variants of the NET gene are not causally related to Tourette syndrome.

Adolescent↗

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

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.

Child↗

Somatic correlates of functional enuresis.

Functional enuresis is a heterogeneous group of syndromes with different aetiology and pathophysiology. The aim was to identify specific somatic correlates of enuresis non-invasively in child psychiatric patients after exclusion of neurologic and structural forms of incontinence. One hundred sixty-seven consecutive children, aged 5 to 10 years with day and/or night wetting were examined prospectively with: urinalysis and bacteriology; ultrasonography, including bladder wall thickness and residual volume; uroflowmetry and pelvic-floor-EMG; EEG; and a complete paediatric-neurologic examination. Day wetting children had a significantly higher rate of previous antibiotic prophylaxis, larger residual volume, thicker bladder walls; the uroflow curves were significantly less bell- and more staccato-shaped, the EMG less relaxed. Voiding postponers showed a tendency towards more uroflow anomalies than urge incontinent children. Primary and secondary enuretics did not differ on most parameters, but primary nocturnal enuretics with micturition problems had significantly less relaxed EMGs than monosymptomatic enuretics. Although day wetters had more pathological EEGs and neurological signs, these differences did not reach significance. The overall rate of urogenital anomalies was 10%. In conclusion, enuresis has a high rate functional somatic correlates with clinical and theoretical, classificatory implications.

Child↗

[Urodynamics in diagnosis and therapy of "enuresis"--relevance for child and adolescent psychiatry].

Enuresis and functional urinary incontinence are clinically and pathophysiologically heterogeneous disorders. They differ with regard to their urodynamics, i.e. with regard to the function or dysfunction of the urinary tract. In addition to general measures such as history, physical examination, urinalysis, questionnaires and flow charts, noninvasive sonography and uroflowmetry with pelvic-floor EMG play an important role in diagnosis and therapy. Rates of pathological findings are especially high among day-wetting children and nocturnal enuretics with micturition problems. This group requires a detailed diagnosis, especially children with detrusor-sphincter discoordination, which can be treated effectively by means of uroflow-biofeedback. The relevance of these methods in child and adolescent psychiatry are discussed in detail and practical recommendations are made.

Adolescent↗

No evidence for an involvement of alleles of polymorphisms in the serotonin1Dbeta and 7 receptor genes in obesity, underweight or anorexia nervosa.

The serotonergic (5-hydroxytryptamine, 5-HT) system has been implicated in body weight regulation and in the etiology of anorexia nervosa (AN). Here we describe the screening of the known Phe-124-Cys polymorphism in the 5-HT1Dbeta receptor gene and of the known Pro-279-Leu polymorphism in the 5-HT7 receptor gene. For association tests allele frequencies were compared between up to 393 extremely obese children and adolescents, 142 underweight students and 84 patients with AN. None of the association tests revealed nominal P-values below 0.3. We conclude that a major role of the investigated polymorphisms in body weight regulation or AN appears unlikely.

Adolescent↗

[Drug therapy of hyperkinetic diseases in adults].

Attention deficit hyperactivity disorder (ADHD) is often diagnosed in children. Some major studies proved that symptoms can persist until the patients are grown up and that the prevalence of adult ADHD is underestimated. The classification systems ICD-10 and DSM-IV allow a diagnosis for adults, they differ, however, from childhood regarding symptoms. The diagnostic procedure requires extensive exploration and information from parents and school. Diagnostic interview procedures and questionnaires for self and expert rating are available to date only for English speaking countries. Apart from counselling and psychotherapeutic intervention pharmacotherapy is a third option. Especially stimulants proved to be an efficient treatment. Alternatively tricyclic antidepressants can be considered, other agents play only a minor role. Clinical trials trying to evaluate the efficacy of different pharmacotherapeutic agents are lacking.

Adult↗

Molecular genetics of nocturnal enuresis: linkage to a locus on chromosome 22.

The aim of this study was to investigate linkage of nocturnal enuresis to a locus on chromosome 22 in 35 German families and to analyse associations with the clinical phenotype. One hundred and sixty-seven enuretic children aged 5-11 years were examined using a somatic, psychiatric and psychological diagnostic protocol; a detailed pedigree over three generations was also compiled. Forty-two children (mean age: 8.11 years) were selected for further molecular genetic examination. EDTA blood samples were taken from the patients and 130 relatives, and polymorphisms of the microsatellite markers D22S446, D22S156 and D22S257 on chromosome 22 were analysed. Positive linkage was found in 11 families of 14 children, indicating that 39.3% of families were compatible with linkage to the markers on chromosome 22. The phenotype included primary nocturnal enuresis and combined day and night wetting. The results for chromosome 22, as with previous loci for nocturnal enuresis on chromosomes 8, 12 and 13, support the hypothesis for genetic and clinical heterogeneity.

Child↗

[Abbreviated Psychopathological Scale in basic documentation in child and adolescent psychiatry--results of a multicenter study].

The short form of the Clinical Assessment Scale of Child and Adolescent Psychopathology (CASCAP) assesses psychopathological features only on the level of symptom domains and not on the level of single symptoms. The instrument is part of the basic documentation of child and adolescent psychiatry. Based on the multicenter study sample of CASCAP the ratings of the symptom domains in the different centers were analysed. Inpatients receive higher ratings than outpatients on nearly all symptom domains. Only minor differences could be found between the centres. Advantages and disadvantages of this short version are discussed.

Adolescent↗

[Institutional handling of sexual abuse: experiences, evaluations, and desires of nonabusing parents of sexually abused children].

This article describes experiences of parents of sexual abused children and their evaluations of institutional interventions on sexual child abuse. Results are presented of a study investigating 'individual and institutional reactions on sexual child abuse'. The number of contacted institutions, personnel experiences with these institutions and resulting requirements are described. The results are based on a sample of 47 (82.5%) girls and 10 (17.5%) boys (range 6-18 years) and interviews with their 'non-abusing' parents. 28 (49.1%) of these children were abused by a member of the family, 29 (50.9%) children by non-familiar persons. It could be shown that 70.2% of the children had contacted four or more different institutions soon after the sexual abuse had been revealed. In cases of sexual abuse by a family member the first contacted institution was the Youth-and-Health-Care-System whereas in cases of sexual abuse by non-familiar persons mostly the police was contacted. Nevertheless in most cases both judicial and supporting approach were chosen. Additionally to concrete advices and professional competences the interviewed parents reported that emotional warmth was a very helpful aspect of the professional intervention. Generally the perspective of the parents seems to give some interesting informations about 'consumer satisfaction'.

Adolescent↗

Screening for mutations in the neuropeptide Y Y5 receptor gene in cohorts belonging to different weight extremes.

OBJECTIVE: The neuropeptide Y (NPY) Y5 receptor is presumed to be involved in the regulation of food intake. DESIGN: To investigate the possible role of this receptor in weight regulation, the whole coding region of the NPY Y5 receptor gene was screened for mutations using temperature gradient gel electrophoresis (TGGE). Detected mutations were screened in extended cohorts. STUDY COHORTS AND METHODS: Cohorts of 87 extremely obese children and adolescents, 15 underweight subjects and 25 patients with anorexia nervosa (AN) were initially screened by TGGE. Extended samples of these cohorts (160 obese children and adolescents; mean body mass index (BMI) 33.5 +/- 6.4 kg/m2, 128 underweight subjects; mean BMI 18.4 +/- 1.0 kg/m2 and 58 patients with AN; mean BMI 14.6 +/- 1.7 kg/m2) were screened to determine the frequencies of a detected mutation and a detected polymorphism in the NPY Y5 receptor gene. In addition, a previously described polymorphism in the first intron of the NPY Y1 receptor gene was analysed. RESULTS: The coding region of the NPY Y5 receptor gene encompasses one exon. A single mutation, which results in a non-conservative amino acid substitution in the first extracellular domain of the receptor (Glu-4-Ala), and one silent polymorphism (Gly-426-Gly-Gly) at nucleotide position 1278 (G-->A) were detected by TGGE. Both tests for association and linkage to the NPY Y1 and NPY Y5 receptor polymorphisms were negative among all cohorts. The Glu-4-Ala mutation was found only in a single patient with AN and her mother. CONCLUSION: The results do not support a major role of the NPY Y5 receptor gene in the variability of body weight in children and adolescents.

Adolescent↗

No evidence for involvement of the leptin gene in anorexia nervosa, bulimia nervosa, underweight or early onset extreme obesity: identification of two novel mutations in the coding sequence and a novel polymorphism in the leptin gene linked upstream region.

Mutations in the leptin gene can result in profound obesity in both rodents and humans. In humans, serum leptin levels correlate with body mass index (BMI: kg m(-2)). However, in patients with anorexia nervosa (AN) leptin levels are lower than in BMI-matched healthy controls. We had previously argued that genes involved in weight regulation should be considered as candidate genes for AN. To investigate this hypothesis we screened the coding region of the leptin gene and part of the leptin gene linked upstream region (LEGLUR) in 49 patients with AN and 315 children and adolescents with extreme obesity. Two novel mutations in the coding region (Ser-91-Ser; Glu-126-Gln), each found in a single proband, and a novel polymorphism in the LEGLUR (position -1387 G/A; frequency of both alleles approximately 0.50) were identified. Tests for association of LEGLUR polymorphism alleles were negative by comparing allele frequencies between 115 AN patients, 71 bulimia nervosa patients, 315 extremely obese children and adolescents, 141 healthy underweights and 50 controls that were not selected for body weight. Tests for transmission disequilibrium were also negative. Hence, an influence of variations in the leptin gene on eating disorders or extreme early onset obesity could not be detected.

Adolescent↗