摘要:

The Fawn-Hooded (FH/Wjd) rat is an inbred strain of rat that has been reported to exhibit both high immobility in the forced swim test and high voluntary ethanol intake, measures that have been periodically linked with depression and alcoholism in humans. The present paper will first present a survey of the literature and previously unpublished findings that bear on the question of whether FH/Wjd rats should be considered genetic animal models of depression and alcoholism. Subsequently, behavioral studies of the FH/Wjd rats, the non-drinking ACI/N strain, and their F1 and F2 intercrosses will be described. Under free choice conditions, the FH/Wjd rat drinks up to 6 g/kg 10% ethanol per day. This intake was sufficient to render the rats tolerant to the hypothermic effects of injected ethanol (2.5 g/kg). Rats that had been voluntarily drinking for at least 6 weeks also exhibited withdrawal-induced anxiety in the social interaction, elevated plus maze, and ultrasonic vocalization tasks. The FH/Wjd rat exhibits a 25–30% increase in alcohol intake when the alcohol is returned after a 24-h period of deprivation. It responds to drugs that are effective in humans with a reduction in alcohol intake. Therefore, the FH/Wjd rat meets most of the criteria for an animal model of alcoholism. Chronic antidepressant treatments correct several of the abnormalities exhibited by the FH/Wjd rats, including the exaggerated immobility in the forced swim test. Therefore, the FH/Wjd rats also fulfill some of the criteria for an animal model of depression. On the contrary, inbred ACI/N rats do not drink much alcohol voluntarily and are quite active in the forced swim test. The FH/Wjd and ACI/N rats were intercrossed to obtain the F1 and F2 progenies, which were then tested for alcohol intake and immobility. Alcohol intake and immobility were distributed in different patterns in the F1 and F2 progenies. Alcohol intake was intermediate in the F1 progeny, while immobility was closer to the FH/Wjd parents. In the F2 progeny, chi-square analyses indicated that the distributions were significantly different. In addition, there were no significant litter effects, indicating that maternal effects did not appear to occur. There were also no significant differences among rats with different coat colors, suggesting that the Fawn-Hooded phenotype can be separated from the measures of alcohol intake and immobility. We conclude that the FH/Wjd rat is a genetic animal model of depression and alcoholism, but that the two measures reflective of these states are under separate genetic controls.

ISSN:0955-8829    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

It is well established that G-proteins represent essential regulatory components in transmembrane signaling. Theαsubunit of the olfactory G-protein Golf(GNAL) maps to a region on chromosome 18 where linkage to affective disorders has been reported, as well as a parent-of-origin effect in affective disorders with some markers near the locus for the α subunit of the Golfgene. We investigated whether two polymorphisms in theαsubunit of the Golfgene (A→G in intron 3, and T→G in intron 10) are associated with major depression in 176 major depressive patients compared with 145 healthy control subjects, and additionally tested for a parent-of-origin effect in separated gender groups. In the control group, we found a significant increase in the G-allele frequency of the intron 3 polymorphism in females (P=0.0036, odds ratio=2.13, 95% confidence interval=1.29–3.54, Fisher's Exact Test). In patients, we found a similar tendency for higher G-allele frequencies in females. Concerning the intron 10 polymorphism, no differences in the genotype or allele frequencies were detectable for any of the separated gender groups. Also, the total patient and control groups showed no differences in allele or genotype frequencies for any of the investigated polymorphisms. The results of this study agree with the reported parent-of-origin effects on chromosome 18, but do not support the hypothesis that the Golfgene is a major susceptibility factor for major depression.

ISSN:0955-8829    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Association studies with candidate genes may contribute towards the understanding of the etiopathogenesis of bipolar disorder. Candidate genes in bipolar disorders are those related to aminergic neurotransmission, which is the target of the effects of antipsychotics and antidepressants, as well as genes related to signal transduction pathways, reporting the target for the mood-stabilizing effects of lithium. Association with such candidate genes may provide clues towards the understanding of the biological components of bipolar disorder. An association study was performed between the 5′ regulatory region of the serotonin transporter gene (5-HTTLPR), the inositol polyphosphate 1-phosphatase gene (INPP1) and bipolar disorder using our sample of proband/parent trios. A total of 101 bipolar probands were considered eligible for the study. Since both parents had to be available, mean age at onset of bipolar disorder in probands was relatively young. However, the mean duration of illness and the number of episodes were consistent with a stable diagnosis. In our trios sample, the transmission disequilibrium test revealed no preferential transmission of alleles of the 5-HTTLPR and INPP1 from heterozygous parents to probands. Therefore, additional family-based data are warranted, possibly with a more complete subdivision of 5-HTTLPR alleles, since short and long alleles have recently been divided into four and six kinds of allelic variant, respectively, with significant ethnic differences in allele and genotype distributions.

ISSN:0955-8829    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The D2 and D4 dopamine receptors (DRD2 and DRD4) play major roles in the central effects of psychostimulants and in the reward system. Previous studies, although not all, have demonstrated associations between the DRD2TaqI and the DRD4 exon III variable number tandem repeat (VNTR) polymorphisms and substance dependence. For this study, we have investigated the associations between these two polymorphisms and methamphetamine (MAP) dependence, as manifested in a Chinese-male sample population. No significant difference was demonstrated for genotype or allele frequency when comparing MAP-dependent and control cases for the DRD2TaqI and the DRD4 gene exon III VNTR polymorphisms, suggesting that these two polymorphisms do not play major roles in MAP dependence for our sample of Chinese males.

ISSN:0955-8829    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

A locus on chromosome 2p12-16 has been implicated in dyslexia susceptibility by two independent linkage studies, including our own study of 119 nuclear twin-based families, each with at least one reading-disabled child. Nonetheless, no variant of any gene has been reported to show association with dyslexia, and no consistent clinical evidence exists to identify candidate genes with any strong a priori logic. We used 21 microsatellite markers spanning 2p12-16 to refine our 1-LOD unit linkage support interval to 12cM between D2S337 and D2S286. Then, in quantitative association analysis, two microsatellites yieldedPvalues<0.05 across a range of reading-related measures (D2S2378 and D2S2114). The exon/intron borders of two positional candidate genes within the region were characterized, and the exons were screened for polymorphisms. The genes were Semaphorin4F (SEMA4F), which encodes a protein involved in axonal growth cone guidance, andOTX1, encoding a homeodomain transcription factor involved in forebrain development. Two non-synonymous single nucleotide polymorphisms were found in SEMA4F, each with a heterozygosity of 0.03. One intronic single nucleotide polymorphism between exons 12 and 13 of SEMA4F was tested for quantitative association, but no significant association was found. Only one single nucleotide polymorphism was found in OTX1, which was exonic but silent. Our data therefore suggest that linkage with reading disability at 2p12-16 is not caused by coding variants of SEMA4F or OTX1. Our study outlines the approach necessary for the identification of genetic variants causing dyslexia susceptibility in an epidemiological population of dyslexics.

ISSN:0955-8829    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

A strong genetic association between the NOTCH4 locus on chromosome 6 and schizophrenia was recently reported. Based on the data suggesting overlapping susceptibility for schizophrenia and bipolar disorder, we genotyped the polymorphic (CTG)nencoding polyleucine repeat in exon 1 of NOTCH4 in 65 pedigrees ascertained for a genetic linkage study of bipolar disorder. In addition, we analyzed a subset of our pedigrees with psychotic features at this locus. We failed to find any association between the (CTG)nNOTCH4 polymorphism and either the bipolar or the psychotic bipolar phenotype in our 65 pedigrees.

ISSN:0955-8829    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Several lines of biochemical evidence support a role ofα2-macroglobulin (A2M) in the pathogenesis of Alzheimer's dementia (AD). A2M participates in the general defence mechanism against proteinases and it is supposed to be involved in the degradation of beta-amyloid peptide (βAP). Furthermore, A2M has been shown to reduceβAP fibril formation, and it is upregulated in the acute-phase inflammatory response like the process occurring in the AD brain. The exon 18 splice acceptor deletion polymorphism and the exon 24 (Val-1000-Ile) GG genotype were reported to be associated with AD, but the results are contradictory. Since the Hungarian population is genetically distinct from the other European ethnic groups, we examined whether the risk for developing AD is increased in the A2M GG carriers. The interaction of apolipoprotein E (apoE) and A2M polymorphisms was also examined. The distribution of A2M genotypes and alleles in the entire data set was consistent with the previous negative observations in which A and G allelic frequencies were comparable in both groups (72% and 28% in the AD population, and 72% and 28% in the control population, respectively). The GG genotype was over-represented (14%) only in the apoEϵ4 non-carrier subgroup of AD probands (7% in the control group), but the difference was not significant. Our data suggest that, although A2M has an important role in the AD-specific neurodegenerative process, its exon 24 Val-1000-Ile polymorphism is not likely to be associated with late-onset sporadic AD in the Hungarian population.

ISSN:0955-8829    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Reports have linked atypical antipsychotics (AAPs) with weight gain. The polymorphic CYP2D6 involved in metabolism has been associated with medication morbidity. Eleven subjects receiving olanzapine were genotyped for CYP2D6 to examine the relationship between 2D6 and AAP weight gain. Using a linear regression, the dependent variable was percent change in body mass index (BMI). Genotype, dose and duration of treatment were independent. Genotype was significant (P<0.0097) for those with a *1/*3 or *4 genotype experiencing a larger percent BMI change than those with a *1/*1 genotype. This may be due to increased olanzapine concentrations leading to increased exposure, which may trigger AAP weight gain.

ISSN:0955-8829    

出版商:OVID    

年代:2002

数据来源: OVID