Association study of polymorphisms in leptin and leptin receptor genes with antipsychotic-induced body weight gain.

BACKGROUND: Antipsychotic-induced weight gain (AIWG) is a serious side-effect of antipsychotic medication leading to metabolic syndrome and increased cardiovascular morbidity. Unfortunately, there are still no valid predictors to assess an individual's risk to gain weight. Previous studies have indicated an impact of genetic variation in the genes encoding leptin, LEP, and leptin receptor, LEPR, on AIWG, but results have not been conclusive. Thus, we investigated polymorphisms in both genes for an association with AIWG. METHODS: A total of 181 schizophrenic and schizoaffective patients treated with various antipsychotics were included. In a small subset of patients, leptin plasma levels were additionally obtained. Five polymorphisms in LEP and LEPR (LEP: rs7799039 (-2548G/A polymorphism), rs10954173, rs3828942; LEPR: rs1327120, rs1137101 (Q223R polymorphism) were genotyped using TaqMan assays. Statistical association with % weight change from baseline weight was performed using ANCOVA with baseline weight as covariate. RESULTS: ANCOVA showed a non-significant trend for genotype association of the rs7799039 marker (p=.068). No significant association of the other LEP and LEPR SNPs with AIWG was detected. However, we found a significant association between a haplotype of LEP rs7799039G-rs10954173G-rs3828942G (p=.035) and AIWG. The rs7799039 G-allele (p=.042) and G-allele of rs3828942 (p=.032) were associated with higher weight gain. CONCLUSION: Our study supports the hypothesis of an impact of LEP gene variation on AIWG. Limitations of our study include heterogeneous samples, short treatment duration and multiple comparisons. Our findings were compared to previous studies in detail in order to provide the readers with a more conclusive picture. However, further studies are warranted including more gene variants and interaction analyses with other genes of the leptin-melanocortin pathway.

Synergistic effects of the dopaminergic and glutamatergic system on hippocampal volume in alcohol-dependent patients.

Several genes of the dopaminergic and glutamatergic neurotransmitter systems have been found to be associated with alcohol disease and related intermediate phenotypes. Here, we evaluated genetic variants of the catechol-O-methyltransferase (COMT) and the metabotropic glutamate receptor 3 (mGluR3) genes in alcohol-dependent patients and their association with volumetric measurements of brain structures. By combined analysis of imaging data and genotyping results, large numbers of variables are produced that overstrain conventional statistical methods based on tests for group differences. Limitations in assessment of epistatic effects and multiple testing problems are encountered. Therefore, we introduce a novel method for detecting associations between a set of genetic markers and phenotypical measurements based on machine learning techniques. Hippocampal volume was found to be associated with epistatic effects of the COMT-mGluR3 genes in alcohol-dependent patients but not in controls. These data are in line with prior studies supporting a role for dopamine-glutamate interaction in modulation of alcohol disease.

Serotonergic platelet variables in unmedicated patients suffering from major depression and healthy subjects: relationship between 5HT content and 5HT uptake.

The dependence of platelet-5HT content on apparent kinetic parameters of 5HT uptake was analyzed in 56 healthy subjects and 47 depressed patients, who had not been taking psychotropic medication for several months. There were no significant relationships between apparent Vmax or Km and platelet-5HT content in both groups. However, the ratio of Vmax to Km, as a measure of apparent 5HT uptake efficiency, significantly correlated with the platelet-5HT concentration in healthy subjects (r=0.627 p<0.001). Female controls showed a higher correlation coefficient (r=0.723) than male controls (r=0.457). A marked deviation from the linear relationship between 5HT content and the ratio Vmax/K was observed in female depressed patients (r=0.250 n.s.). In male depressed patients the correlation coefficient (r=0.485 p<0.05) was similar to male healthy subjects, but the regression equations differed significantly in slope and intercept. Dividing controls and patients in subgroups with low, median and high net uptake rates, it was found that the frequencies of these uptake rate classes were 24.6%, 33.3%, 42.1% in controls and 38.3%, 44.7%, 17.0% in patients respectively. Patients and controls with low net uptake rate showed very similar uptake kinetics and uptake efficiencies, but the lack of a significant correlation between 5HT content and the ratio Vmax/Km differentiated patients from controls. The status of the serotonergic system, expressed as relationship between 5HT content and uptake efficiency, was very similar in patients and controls in the range of medium net uptake rate. A trend toward higher values of uptake efficiency was apparent in patients with high net uptake rate but the platelet-5HT content was similar to corresponding controls. Mean scores on the HAMD scale (total score and psychic anxiety item) were significantly higher in the low net uptake rate group of patients than in those with a high net uptake rate.

[Tryptophan-loading in schizophrenia and endogenous depression]. / Tryptophanbelastung bei Schizophrenien und endogenen Depressionen.

In 95 schizophrenic patients, 20 endogenous depressed patients and 39 control subjects the level of plasma tryptophan was determined after oral load of L-tryptophan (50 mg/kg) in range of 3 hours. Among the groups quantitative and specially qualitative differences were observed in course of tryptophan. In the group of schizophrenic patients it is possible to exactly differentiate a subgroup with similar psycho-pathological symptomatic by means the course of tryptophan.

Possible role played by monoamines in the control of puberty onset in female rats.

The effect of pargyline on 5 HT concentration in a combined forebrain and midbrain section ( FMB ) have been investigated in female rats which were temporarily deprived from their dams in postnatal life and daily injected with the monoamine oxidase inhibitor. Two hours after the last pargyline injection a marked increase in 5 HT concentration could be observed both in 12 and 30 days-old rats. The question is raised whether 5 HT may be involved in neuroendocrine mechanisms which are responsible for controlling the onset of puberty, since a significant advance of puberty could be achieved by this pargyline treatment in normal and deprived female rats.

[Extraction of serotonin, bufotenin, 5-methoxytryptamine and 5-methoxy-N,N-dimethyltryptamine and their fluorometric determination with o-phthaldialdehyde]. / Extraktion von Serotonin, Bufotenin, 5-Methoxytryptamin und 5-Methoxy-N,N-Dimethyltryptamin und ihre fluorimetrische Bestimmung mit o-Phthaldialdehyd.

For the investigated indolamines, the recovery following extraction with n-butanol and acetic acid ethyl ester from alkaline solution amounted to 80-90%. Using benzene only the two 5-methoxyindolamines were transferred from the alkaline medium into the organic phase. The reaction of the o-phthaldialdehyde with substituted indolamines was optimized in regard to higher fluorimetric detection sensitivity. The lower limit of determination was 2.0 ng for 5HT and 5OHDMT, and 1.0 ng for 5MeOT and 5MeODMT.