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At least 127 records · Page 7Linked to original sources
PubMed1989

Perinatal complications and genetic loading in schizophrenia: preliminary findings.

History of perinatal complications (PCs) and first degree family history (FH) of psychiatric illness were examined in groups of schizophrenic/schizoaffective (n = 21) and bipolar (n = 10) patients. PCs were significantly more frequent in the schizophrenic and schizoaffective patients than in bipolar patients. An inverse relationship was found between PCs and FH status, with FH-positive patients having significantly fewer PCs than the FH-negative group. This relationship persisted when the bipolar patients were excluded. Findings emphasize the etiological importance of genetics and perinatal events in the psychoses, and support the validity of a familial/sporadic distinction.

Brain Damage, Chronic↗
PubMed1995

Reduced genetic load revealed by slow inbreeding in Drosophila melanogaster.

The rate of decline in reproductive fitness in populations of Drosophila melanogaster inbred at an initial rate of approximately 1% per generation has been investigated under both competitive and noncompetitive conditions. Breeding population size was variable in the inbred lines with an estimated harmonic mean of 66.7 +/- 2.2. Of the 60 lines maintained without reserves, 75% survived a period of 210 generations of slow inbreeding and were then rapidly inbred by full-sib mating to near-homozygosity. The initial rate of inbreeding was estimated to be 0.96 +/- 0.16% per generation, corresponding to an effective population size of approximately 50. However, the rate of inbreeding declined significantly with time to average only 0.52 +/- 0.08% per generation over the 210 generation period, most likely due to associative overdominance built up by genetic sampling and selection in the small populations. The total inbreeding depression in fitness was estimated to be 87 +/- 3% for competitive ability and 27 +/- 5% for fitness under uncrowded conditions, corresponding to rates of decline of 2.0 +/- 0.3 and 0.32 +/- 0.07%, respectively, per 1% increase in the inbreeding coefficient. The frequency of lethal second chromosomes in the resultant near-homozygous lines was of the order of 5%, lethal free second chromosomes showed a mean viability under both crowded and uncrowded conditions of approximately 95%, and their population cage fitness was 60% that of Cy/+ heterozygotes. It can be concluded that homozygous genotypes from which deleterious genes of major effect have been eliminated during slow inbreeding may show far less depression in reproductive fitness than suggested by earlier studies of wild chromosome homozygotes. The loss in fitness due to homozygosity throughout the entire genome may be as little as 85-90% under competitive conditions, and 25-30% in an optimal environment.

Animals↗
PubMed1987

[Medico-genetical study of the population of the Kostroma Region. IV. Genetic load and diversity of hereditary pathology in 5 districts].

Data on the prevalence of hereditary diseases in five regions of the Kostroma province were obtained and analysed. 28 autosomal recessive, 25 autosomal dominant and 4 X-linked recessive disorders were found. Segregation analysis proved the rightness of the material subdivision, according to the type of inheritance. The load of hereditary diseases in five regions was: 0.86 +/- 0.09 X 10(3) for autosomal recessive, 0.97 +/- 0.1 X 10(3) for autosomal dominant and 0.36 +/- 0.09 X 10(3) for X-linked recessive disorders. The problems of prevalence of hereditary diseases connected with population structure is discussed.

Female↗
PubMed1990

[Genetic load in a rural population in the Armenian SSR].

The reproductive function of women was analysed using interviews in zones with different levels of pesticides application. Increase in frequency of abnormal pregnancies in the zone of high level of pesticides application is shown. The main part of cases with hereditary pathology constituted the children with mental retardation. On the basis of surnames differentiation analysis, the relative homogeneity of structures of populations studied was demonstrated. The cytogenetic analysis only revealed small increase in SCE levels and no changes in the levels of aberrations of chromosomes in cultures of lymphocytes of rural workers contacting pesticides.

Armenia↗
PubMed2000

Neuropsychologic functioning among the nonpsychotic relatives of schizophrenic patients: the effect of genetic loading.

BACKGROUND: We previously reported that the nonpsychotic relatives of schizophrenic patients exhibited disturbances in executive functioning, verbal and visual memory, auditory attention, mental control, and verbal ability. In a 4-year follow-up, we showed that the discriminating power of most of these tests was stable over time. METHODS: In this report we compare 41 nonpsychotic persons who have only one schizophrenic first-degree relative (simplex families) with 36 nonpsychotic persons who have two schizophrenic first-degree relatives (multiplex families). Our goal was to test a hypothesis that neuropsychologic deficits would be worse among the latter. RESULTS: Relatives from multiplex families differed significantly from controls on estimated intelligence, immediate and delayed logical memories, and immediate visual reproductions. In contrast, in comparisons with controls, relatives from simplex families only differed on immediate logical memories. Comparisons between relatives from multiplex and simplex families showed that the former group had significantly worse scores for estimated intelligence, immediate and delayed logical memories, and immediate visual reproductions. We also found group x gender interactions: the worse performance of the multiplex group was seen for females. CONCLUSIONS: These results are consistent with the idea that neuropsychologic deficits in relatives of schizophrenic patients reflect their degree of genetic predisposition to schizophrenia. They also suggest hypotheses about gender differences in the familial transmission of the disorder.

Adolescent↗
PubMed1999

Differential regulation of IGF-I, its receptor and GH receptor mRNAs in the right ventricle and caval vein in volume-loaded genetically hypertensive and normotensive rats.

It has been suggested, mainly by in vitro findings, that cardiovascular tissue in the spontaneously hypertensive rat (SHR) should be more prone to proliferate/hypertrophy than that of the Wistar-Kyoto rat (WKY). The present study tests the hypothesis that the tissue of the low-pressure compartment in SHR, being structurally similar to that of the WKY, shows an increased growth response due to activation of the GH-IGF-I system. An aortocaval fistula (ACF) was induced in 64 SHR and WKY male rats and 44 rats served as controls. They were all followed for 1, 2, 4 and 7 days after surgery. In separate groups of SHR (n=4) and WKY (n=3), central venous pressure was measured by telemetry recordings prior to opening of the fistula and for up to 16 h post-surgery. Systolic blood pressure was measured during the week post-surgery. The right ventricular (RV) and the caval vein IGF-I mRNA and RV IGF-I receptor and GH receptor mRNAs were quantitated by means of solution hybridisation assay. In rats with ACF the systolic blood pressure decreased, approximately 29% in SHR and 16% in WKY between 1 and 7 days post-surgery (P<0.05, n=5-6 in each group). SHR with ACF showed a transient elevation in central venous pressure vs WKY. Within the week following fistula induction both strains showed a similar, pronounced increase in RV hypertrophy. SHR with ACF showed a smaller, or even blunted, overall response with respect to activation of the GH-IGF-I system compared with WKY, the latter showing clear-cut elevation of gene expressions. Two days after shunt opening in SHR, RV and caval vein IGF-I mRNA increased by 57% and 108% (P<0.05 for both, n=5-6 in each group) respectively, and these expressions were then turned off, whereas RV GH receptor and IGF-I receptor mRNA expression remained unaffected compared with WKY rats. WKY rats showed on average a later and a greater response of GH-IGF-I system mRNA expression vs SHR. The present in vivo study suggests that the SHR requires less activation of the GH-IGF-I system for creating a given adaptive structural growth response.

Animals↗
PubMedDate not supplied

Platelet monoamine-oxidase activity in schizophrenia. Relation to genetic load of the illness and treatment with antipsychotic drugs.

A significant decrease of mean platelet monoamine-oxidase (MAO) activity was observed in a sample of haloperidol-treated schizophrenic patients as compared with normal control subjects. The enzyme activity was not significantly reduced in drug-free schizophrenics. No significant difference was found between drug-free schizophrenics with and without a family history of the illness and between healthy relatives of schizophrenics and normal subjects without a family history of schizophrenia. MAO activity was significantly reduced after 14 and 21 days of treatment with haloperidol, in comparison with baseline values. It is suggested that neuroleptic intake may at least in part explain low MAO values repeatedly reported in schizophrenics.

Adult↗
PubMed1994

Purging inbreeding depression and the probability of extinction: full-sib mating.

Inbreeding depression has been a topic of interest in recent years from a number of perspectives, particularly in the captive breeding of endangered species. Generally, the goal of captive breeding is to avoid the detrimental effects of inbreeding depression and to retain genetic variation for future adaptation. However, an important component of another suggested approach to captive breeding is to purge rapidly the population of its genetic load so that its long-term fitness is not compromised. I have examined the effectiveness of purging the genetic load by documenting both the reduction in inbreeding depression and the increase of the probability of extinction when there is continuous full-sib mating. When the genetic load is the result of lethals, the inbreeding depression is quickly purged without a high probability of extinction, except when the total genetic load is high. On the other hand, if the load is due to detrimentals of relatively small effect, the genetic load becomes fixed, the mean fitness is reduced, and the probability of extinction may be greatly increased. In other words, the success of such a programme to purge genetic load without an increase in the probability of extinction is highly dependent upon the genetic basis of inbreeding depression, information that is not readily available for most species.

Adaptation, Physiological↗
PubMed2005

[Consequences of nosographic and trans-nosological concepts of schizophrenia].

This essay starts with a brief remark about the -- necessary -- de-tours of the historical pathway to the concept of schizophrenia. The first part on nosographic approaches then describes the results of cross-sectional and longitudinal psychopathological symptom-assembling, subgrouping by factorial analyses, and the cross-cultural stability of the emerging disease concept: The human idiopathic syndrome of structural mental decline in its clinical variegation. The second part about de-nosological approaches provides an account of the clinical concepts of basic symptoms, spectrum disorders, neuropsychological deficits and their genetic family loading. Genetics of neuropsychological deficits demonstrate in detail that risk and protective factors to schizophrenia are genetically closely enmeshed. Higher familial loading of some neuropsychological deficits compared to the actual disease itself points at the dilemma that functional psychopathology deepens causal understanding and yet looses specificity for the disease syndrome. The concluding part of this essay emphasizes some sequelae of de-nosological approaches: Better tools for earlier recognition treatment and prevention; ego-distal concepts of basic dysfunctions rather than the previous ego-proximal concepts, hence better self-esteem, insight, and de-stigmatization for patients.

History, 20th Century↗
PubMed1995

The role of genetic factors in conduct disorder based on studies of Tourette syndrome and attention-deficit hyperactivity disorder probands and their relatives.

To examine the role of genetic factors in oppositional defiant disorder (ODD) and conduct disorder (CD), 38 variables relating to the relevant DSM-III-R criteria, as well as other angry and aggressive behaviors, were examined in 1177 Tourette syndrome (TS) and attention-deficit hyperactivity disorder (ADHD) probands, their first-degree relatives, and controls. Two techniques were used: (1) a genetic loading technique comparing the frequency of symptoms in groups with progressively less genetic loading for Gts and ADHD genes, and (2) comparison of the frequency of symptoms in relatives with, versus relatives without, TS or ADHD. When significant, the latter rules out ascertainment bias and inappropriate controls. For TS, the results were significant with most p values less than 10(-8). The same trends were seen in the smaller number of ADHD families. A polygenic model is proposed in which TS and ADHD alone represent lesser degrees of genetic loading and expression, and TS + CD not equal to ADHD represents a higher degree of genetic loading and expression of genes common to all three disorders. These studies emphasize the important role of genetic factors in ODD and CD. The therapeutic implications are discussed.

Adolescent↗
PubMed2006

Accumulation of deleterious mutations in small abiotic populations of RNA.

The accumulation of slightly deleterious mutations in populations leads to the buildup of a genetic load and can cause the extinction of populations of small size. Mutation-accumulation experiments have been used to study this process in a wide variety of organisms, yet the exact mutational underpinnings of genetic loads and their fitness consequences remain poorly characterized. Here, we use an abiotic system of RNA populations evolving continuously in vitro to examine the molecular events that can instigate a genetic load. By tracking the fitness decline of ligase ribozyme populations with bottleneck sizes between 100 and 3000 molecules, we detected the appearance and subsequent fixation of both slightly deleterious mutations and advantageous mutations. Smaller populations went extinct in significantly fewer generations than did larger ones, supporting the notion of a mutational meltdown. These data suggest that mutation accumulation was an important evolutionary force in the prebiotic RNA world and that mechanisms such as recombination to ameliorate genetic loads may have been in place early in the history of life.

Base Sequence↗
PubMedDate not supplied

[Investigation of the level of genetical safety of urban population].

As it is universally recognized, the population is a sound criteria of the environment quality. The most reliable method to evaluate genetic processes in a population under the condition of the environmental pollution is genetic monitoring, a survey of dynamic parameters of genetic load. An evaluation of genetical safety of an urbanized area of a city is represented in this article. The parameters of genetic load like congenital malformations and multifactorial diseases have been used in the models of monitoring. The analysis and comparison of disease frequencies in Kharkiv Dzerzhinsky District, in other European populations and in regional rural districts with various levels of production have been made.

Adolescent↗