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Biomedical subjects

H Remschmidt

Publications and source records attributed to H Remschmidt.

At least 109 records · Page 6Linked to original sources
PubMed1997

Blood biogenic amines during clozapine treatment of early-onset schizophrenia.

The aims of this investigation were to evaluate long-term and short-term effects of clozapine-treatment on plasma biogenic amines and psychopathology measures in adolescents with schizophrenia (DSM-III-R criteria). The long-term study was conducted in a study sample of 40 young patients (age 14-22 years) following a mean of 3.4 years of neuroleptic treatment. During the study, 20 patients received clozapine, and the other 20 patients were treated with standard neuroleptic medications. At the beginning of the open clinical trials, the patients had already been receiving clozapine treatment for 24 +/- 15 months. Assessment of the biochemical and psychopathological measures was performed on six occasions at consecutive 6-week intervals during maintenance treatment with clozapine or conventional neuroleptics. Blood levels of serotonin, 3-methoxy-4-hydroxy-phenylglycol (MHPG), norepinephrine, and epinephrine were significantly higher in clozapine-treated patients than in conventionally treated patients. During long-term treatment, higher serotonin levels were associated with significantly fewer negative symptoms of schizophrenia, whereas higher MHPG levels were correlated with less depression. The short-term effects of clozapine were assessed in a second and independent study sample. After failing on conventional neuroleptics in clinical trials lasting a mean of 1.6 years, 15 inpatients (aged 11-20 years) received clozapine. Weekly ratings of psychopathological symptoms using standard rating scales were performed in parallel to blood samplings for measurements of biogenic amines and serum levels of clozapine. These measures were obtained for 6 weeks during conventional neuroleptic treatment and for 6 weeks during the open-label clozapine trial. Serum levels of serotonin and plasma norepinephrine levels were significantly higher during treatment with clozapine than during pretreatment with typical neuroleptics. A comparison of plasma epinephrine levels in responders (n = 7) and nonresponders (n = 8) to clozapine revealed that response to clozapine can be predicted by epinephrine levels prior to initiation of treatment with clozapine (responders ranging from 32.2 to 90.3 pg/ml; nonresponders ranging from 92.5 to 473.5 pg/ml). Additionally, subjects who responded to clozapine showed increased mean plasma concentrations of MHPG and epinephrine during treatment with this drug in comparison to the levels measured during pretreatment with typical neuroleptic medication. Nonresponders to clozapine failed to show this increase. Finally, in responders to clozapine a negative linear relationship between negative symptoms of schizophrenia and the concentrations of plasma norepinephrine and serum serotonin were observed. In conclusion, our results demonstrate that plasma epinephrine levels prior to initiation of clozapine therapy predict response to this atypical neuroleptic. Our findings derived from short-term and maintenance treatment with clozapine suggest involvement of norepinephrine, epinephrine and serotonin in the therapeutic actions of the atypical neuroleptic clozapine.

Adolescent↗
PubMed1997

Evaluation of a Cys23Ser mutation within the human 5-HT2C receptor gene: no evidence for an association of the mutant allele with obesity or underweight in children, adolescents and young adults.

Serotonin is a neurotransmitter involved in a large number of psychophysiological processes including the regulation of mood, arousal, aggression, sleep, learning, nociceptions, nerve growth and importantly, appetitive functions. Alterations of 5-HT receptor activity have been shown to occur in many psychiatric diseases including depression, anxiety, eating disorders, schizophrenia etc. Hence, genetic variation in genes coding for serotonin receptor proteins might well be involved in the genetic predisposition to these diseases and therefore are of great pharmacogenetic relevance. Knockout mice deficient of a functional 5-HT2C receptor have implicated a potential role of this receptor subtype in the serotonergic control of appetite. A Cys23Ser mutation in the human 5-HT2C receptor gene discovered recently prompted us to investigate this mutation with regard to the development of human obesity. We have evaluated this mutation in 241 obese children and adolescents (mean BMI > or = 97th percentile), 80 normal weight children (BMI 5th-85th percentile) and 92 underweight probands (BMI < or = 15th percentile) for a possible association with obesity. The frequencies of the mutant allele in all three weight groups (obese subjects: 0.1597; normal weight: 0.168; underweight: 0.1575) were very similar. Association as well as linkage studies were negative. Therefore it is unlikely that this receptor mutation plays a direct role in the development of human obesity.

Adolescent↗
PubMed1997

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.

Adolescent↗
PubMed1997

Significant weight gains in a clinical sample of obese children and adolescents between 1985 and 1995.

OBJECTIVE: Within the past decades prevalence rates for obesity among children and adolescents have increased in different populations. The hypothesis of this study is that the degree of adiposity in clinical study cohorts of extremely obese children and adolescents increased within the past decade. DESIGN: In six different study cohorts of the time period from 1985-1995 body mass indices (BMIs) of obese children and adolescents who were treated as inpatients at a specialized children's hospital were evaluated. For this purpose body heights, body weights, ages and sex of all inpatients of three referring agencies were retrospectively assessed biannually. RESULTS: In these six cohorts a significant BMI-increase from 1985-1995 of 1.9 kg/m2 (P < 0.0001) for constant sex, age and referring agencies was found: Comparisons of the quartiles and the ninth decline in both sexes did not show any systematic increase at the first quartile. In contrast, BMI-increases at the ninth decile were approximately 5 kg/m2 for males and 2.5 kg/m2 for females. CONCLUSION: Within the decade studied a significant BMI-increase was detectable in this clinical population. This effect is especially discernible in the most extreme weight groups and in males.

Adolescent↗
PubMed1997

Beta 3-adrenergic-receptor allele distributions in children, adolescents and young adults with obesity, underweight or anorexia nervosa.

OBJECTIVE: The missense mutation (64Trp to 64Arg) in the beta 3-adrenergic-receptor has previously been described to confer a genetic predisposition to the development of obesity. DESIGN: To test the hypothesis we evaluated allele frequencies in children, adolescents and young adults who belonged to different weight groups that were delineated with percentiles for the body mass index (BMI; kg/m2). SUBJECTS: 99 underweight probands (BMI < or = 15th percentile). 80 normal weight probands (BMI: 5th-85th percentile). 238 obese children and adolescents (BMI > or = 97th percentile). 84 patients with anorexia nervosa (AN). MEASUREMENTS: The cohorts were screened by polymerase chain reaction with subsequent restriction fragment length polymorphism (PCR-RFLP) analysis. Data were statistically analysed for association. In addition to these case control studies, the transmission disequilibrium test (TDT) was applied to 80 families of obese probands and to 52 families of patients with AN. RESULTS: Both the tests for association and linkage were negative. The Trp64Arg allele frequencies in the three weight groups (obesity: 0.071; normal weight: 0.081; underweight: 0.056) and the AN patients (0.054) were similar. Extremely obese individuals showed no excess of the Trp64Arg allele. No homozygotes for the Trp64Arg allele were detected. CONCLUSION: Heterozygosity for the Trp64Arg allele is not of major importance in regulation of body weight in individuals younger than 35 y. Additionally, the extreme obese subgroup is not enriched for the polymorphism.

Adolescent↗
PubMed1997

Leptin levels in patients with anorexia nervosa are reduced in the acute stage and elevated upon short-term weight restoration.

Circulating leptin concentrations are known to be low in acute anorexia nervosa (AN), which is characterized by low weight, amenorrhea and specific psychopathological features. In this study plasma leptin concentrations were determined during inpatient treatment of 23 adolescent females with AN using a sensitive radioimmunoassay (RIA) and set into relationship to leptin levels of females matched for age, body mass index (BMI; kg m-2) and/or percent body fat. At referral patients had leptin concentrations well below the female controls. Weight gains led to steep increases of leptin levels which peaked at values well in excess of those observed in controls matched for BMI. In patients who reached the final treatment stage and who were followed-up after discharge, levels subsequently fluctuated and finally dropped into or below the control range. The low leptin levels at referral are likely to be involved in the pathogenesis of amenorrhea and the reduced metabolic state of acutely ill patients. Peak leptin levels reached after weight gain are possibly the cause of increased energy expenditure during this stage of the disorder.

Adolescent↗
PubMed1997

Low leptin levels predict amenorrhea in underweight and eating disordered females.

Evidence that leptin plays an important role in reproductive function is accumulating rapidly. We hypothesized that low leptin synthesis is associated with amenorrhea. We therefore determined serum leptin levels in 43 underweight female students, who were screened for lifetime occurrence of amenorrhea. We assessed the predictive value of leptin, body mass index (BMI), fat mass and percent body fat, respectively, for lifetime occurrence of amenorrea. Factors predicting amenorrhea were tested for their capability to predict current amenorrhea in a second cohort of 63 inpatients with anorexia nervosa (AN) or bulimia nervosa (BN). Furthermore, the relationships between serum leptin levels and of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol and progesterone, respectively, were evaluated. Only leptin predicted lifetime occurrence of amenorrhea in the student cohort. The critical leptin level was in the range of 1.85 micrograms L-1. This level served to largely separate anorectic from bulimic patients. In patients with AN mean serum log10 leptin levels over the first 4 weeks of inpatient treatment were correlated with mean FSH, LH and estradiol levels, respectively. Evidently, a critical leptin level is needed to maintain menstruation. In affluent populations eating disorders are likely to be a major cause of a low leptin synthesis.

Adolescent↗
PubMed1997

Restrained eating is associated with low leptin levels in underweight females.

Psychometrically defined restrained eaters consume fewer calories, take fewer meals, show higher preference for low calorie foods, have lower energy expenditure and a higher rate of ovarial dysfunction than unrestrained eaters. We hypothesized that restrained eaters as assessed with the factor cognitive restraint of the Three-Factor Eating Questionnaire have low leptin levels; therefore, we measured serum leptin levels in 136 underweight students and 49 overweight students, who had filled out the Three-Factor Eating Questionnaire. Body mass indexes, fat mass and percent body fat were determined. Spearman correlations revealed that log10 leptin levels of only the 67 underweight females were negatively correlated with cognitive restraint scores (r = -0.5; nominal P-value < 0.001). The restraint score explained 22% of the total variance of leptin levels in underweight females; in combination with percent body fat, 52% of the variance was accounted for. To our knowledge this is the first study to identify a relationship between a score on a psychometric scale and leptin levels. Restrained eating has a biological correlate in underweight females.

Adult↗
PubMed1997

Further support for linkage of extreme obesity to the obese gene in a study group of obese children and adolescents.

The role of the obese gene in human obesity is presently unclear. Evidence for linkage of markers flanking the gene to obesity has been found in some but not all studies. We investigated transmission disequilibrium between two highly polymorphic microsatellite markers (D7S504 and D7S1875) flanking the human obese gene (OB) and extreme obesity in a study group of German children and adolescents. Due to the early onset and severity of obesity in the ob/ob mouse we hypothesized that especially children and adolescents with extreme obesity are enriched for possible mutations in the human OB. The analysis of 88 trios (index probands and both parents) for transmission disequilibrium of a haplotype which has previously been determined to be linked to extreme obesity (Reed et al., 1996) revealed a one-sided transmission disequilibrium test (TDT) p-value of 0.039. Post hoc analyses revealed one-sided TDT p-values of 0.015 for the 214 bp allele of D7S1875 (corrected p-value = 0.03) and 0.215 for the 145 bp allele of D7S504 (corrected p-value = 0.43). These findings substantiate the evidence for linkage of extreme obesity to OB.

Adolescent↗
PubMed1997

Low body weight in male children and adolescents with schizoid personality disorder or Asperger's disorder.

This study explored the hypothesis that body weight is reduced in male children and adolescents with schizoid personality disorder or Asperger's disorder. The body weights of 33 consecutively admitted male subjects with one of these disorders were retrospectively assessed with percentiles for the body mass index (BMI). The mean percentile (+/- SD) for the BMI was 31.6 +/- 27.6 and differed significantly from the expected value of 50 (P<0.001). Ten subjects had a BMI of < or = 10th age percentile. Post hoc comparisons revealed that BMI percentiles were (a) reduced to a similar extent in patients with schizoid personality disorder and Asperger's disorder and (b) reduced to a greater extent in patients with abnormal eating behaviour. During childhood and adolescence both diagnoses are associated with an increased risk of being underweight. Population-based BMI percentiles are useful for detecting associations between specific psychopathological syndromes and body weight.

Adolescent↗
PubMed1997

Prediction of low body weight at long-term follow-up in acute anorexia nervosa by low body weight at referral.

OBJECTIVE: The authors investigated the hypothesis that in acute anorexia nervosa a low body weight predicts a poor weight prognosis for the future. METHOD: The body mass indexes at referral of 272 female patients were examined in relation to the body mass indexes of these patients after a mean follow-up of 9.5 years. RESULTS: The overall correlation between body mass indexes at referral and at follow-up was r = 0.33. Despite this low correlation, the 100 patients with body mass indexes less than 13 kg/m2 at referral had low weights at long-term follow-up. Eleven of the 12 deceased patients were among these 100 patients, as were 24 of the 46 surviving patients whose body mass indexes were 17.5 kg/m2 or less at follow-up. CONCLUSIONS: For patients with anorexia nervosa, a body mass index less than 13 kg/m2 at referral indicates a substantial risk for chronic anorexia nervosa and death related to emaciation.

Acute Disease↗
PubMed1997

[Follow-up and treatment outcome of early anorexia nervosa].

In a two-center follow-up study on the early-onset form of anorexia nervosa, we reexamined 43 (74%) of 58 former patients who had developed anorexia nervosa at the age of 13 years or younger. In addition to make a standardized assessment of the eating disorder at follow-up we assessed psychiatric comorbidity with a structured interview based on the criteria of DSM-III-R and ICD-10. After an average follow-up period of 6.8 years, 8 (18%) of our former patients had an eating disorder not otherwise specified (EDNOS) and 4 (9%) still suffered from anorexia nervosa. 5 (11%) of the subjects had developed bulimia nervosa. In 3 cases (7%) we found both syndromes. 12 (28%) of our former patients had an additional psychiatric disorder. The results of our study indicate that the quality of outcome in patients with an early-onset form of anorexia nervosa does not differ from that in individuals with a later manifestation of the eating disorder. Factors of prognostic relevance were the existence of an eating disorder during the first year of life and the duration of the follow-up period.

Adolescent↗
PubMed1997

[The Marburg parent-child spelling training].

The first results of a parent-child program for improving the children's spelling are reported. Seventeen spelling-disabled children and their mothers took part for about one year in a supervised tutoring program that was based on German spelling rules. The parents met with two therapists one evening a month and received guidance with the program. Overall there was no improvement in spelling. However, a qualitative analysis of spelling errors revealed marked improvement in those areas that had been worked on in the program. Significant predictors of spelling improvement were the spelling ability of the mother and whether the mother was working or not.

Adult↗