RESUMO
Robert Walser (1878-1956) is among the most prominent German-speaking writers born in Switzerland. His early writings are fascinating due to his intensive affectivity and oneiric experiences; his late work impresses through his idiosyncratic use of language and his micrographs. Due to a psychotic disease he stayed in Swiss Mental State Hospitals (Waldau and Herisau) throughout the final 27 years of his life. According to his case records Robert Walser suffered from a schizophrenic disorder (ICD-10) and from a combined sluggish/manneristic catatonia according to K. Leonhard. Walser's psychotic disorder was characterized by a chronic course with sharp-cut symptomatology with stiff postures, repetitive behaviour, movement mannerisms and omissions (manneristic component) complemented by loss of incentive, severe autism and persistent verbal hallucinations (speech-sluggish component). In the late stages his psychopathology affected the process of thinking and writing in a specific manner: his handwriting became illegibly small, and his train of thoughts did not get to the point. At age 54 he stopped writing when transferred from Waldau to Herisau, and subsequently, due to manneristic omission, he was never again able to restart literary writing. The analysis of Robert Walser's psychotic disease may contribute to a deeper understanding of his literary production, which influenced such classical German authors like Franz Kafka, Hermann Hesse and Robert Musil.
Assuntos
Literatura/história , Transtornos Mentais/história , Redação/história , História do Século XIX , História do Século XX , Humanos , SuíçaRESUMO
In the genome-wide association study (GWAS) on schizophrenia [O'Donovan et al. (2008); Nat Genet 40:10531055] a UK-sample of 479 cases with DSM-IV schizophrenia was genotyped in comparison to control subjects with follow up of 12 putative loci in international replication sets of approximately 15,000 cases and controls. In these cohorts and a combined bipolar and schizophrenia UK-sample, six single nucleotide polymorphisms (SNPs) supported association, with the strongest evidence for SNP-marker rs1344706 at the zinc finger ZNF804A locus on chromosome 2q32.1 (P = 1.61 × 10−7). We attempted replication of these findings in a German population of 2,154 individuals (632 with affective disorders, 937 with schizophrenia, and 585 controls), but found none of the GWAS risk alleles significantly associated with psychosis. Particularly rs1344706, initially surpassing the genome-wide significance level in an extended phenotype of schizophrenia and affective disorder, produced consistently negative results. At the ZNF804A locus estimated Odds ratios reached 1.08 (0.931.26 95% CI) for the schizophrenia sample and 1.04 (0.901.20 95% CI) for the combined set of cases with schizophrenia and affective disorder. The main limitation of our study may be the reduced power of the sample size, but our data may be useful for future meta-analysis of GWA data sets. Although GWAS have proven extraordinary successful in identifying susceptibility genes for complex genetic disorders, the hypothesis of common genetic variants in the complex group of the schizophrenic psychoses with small effect size but relatively high frequency is still put to further scrutiny.
Assuntos
Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Esquizofrenia/genética , Adulto , Alelos , Estudos de Casos e Controles , Estudos de Coortes , Bases de Dados Genéticas , Manual Diagnóstico e Estatístico de Transtornos Mentais , Etnicidade/genética , Etnicidade/estatística & dados numéricos , Feminino , Genoma , Genótipo , Alemanha , Humanos , Masculino , Fenótipo , Transtornos Psicóticos/genética , Medição de RiscoRESUMO
We investigated a patient with severe catatonic schizophrenia (manneristic catatonia according to Karl Leonhard) treated with electroconvulsive therapy (ECT) after pharmacological approaches did not result in any clinical improvement. Before and after nine ECT sessions a double-pulse transcranial magnetic stimulation (TMS) paradigm was used to measure intracortical inhibition (ICI) which has been shown to be reduced in a significant proportion of patients with schizophrenia. Although the patient showed no remission regarding some psychomotor aspects after ECT, we found an increase in ICI and a remarkable clinical improvement of catatonic omissions which might be due to changes in the GABAergic system.
Assuntos
Catatonia/fisiopatologia , Catatonia/psicologia , Córtex Cerebral/fisiopatologia , Eletroconvulsoterapia/métodos , Inibição Neural/fisiologia , Adulto , Catatonia/terapia , Córtex Cerebral/efeitos dos fármacos , Humanos , Masculino , Inibição Neural/efeitos dos fármacos , Testes Neuropsicológicos/normas , Resultado do TratamentoRESUMO
The human norepinephrine transporter (hNET) gene has five sequence polymorphisms that predict amino acid substitutions in the transporter protein: Val69Ile, Thr99Ile, Val245Ile, Val449Ile, and Gly478Ser. In order to functionally characterize the naturally occurring transporter variants, we used site-directed mutagenesis to establish the hNET variants and compared some basic pharmacological properties (uptake of norepinephrine and its inhibition by the tricyclic antidepressant desipramine) in COS-7 cells transiently expressing variant hNETs and wild-type hNET. None of the hNET variants displayed changes in the potency (Ki) of desipramine for inhibition of norepinephrine uptake. Furthermore, variants Val69Ile, Thr99Ile, ValZ45Ile, and Val449Ile did not affect kinetic constants (Km, Vmax) of norepinephrine uptake. However, COS-7 cells expressing the hNET variant Gly478Ser displayed an approximately four-fold increase in the Km for norepinephrine, while the Vmax was unaffected. The increase in the Km, which is equivalent to a four-fold reduction in the affinity of the variant hNET for its natural substrate norepinephrine, indicates that the glycine in position 478 is part of a substrate recognition domain. The reduced clearance of released norepinephrine by reuptake through the Gly478Ser variant might cause an increase in the synaptic and the circulating concentration of norepinephrine. Elevated norepinephrine concentrations have been associated with human diseases and it will be interesting to explore a possible contribution by the Gly478Ser variant to certain disease states.
Assuntos
Proteínas de Transporte/genética , Proteínas de Transporte/farmacocinética , Norepinefrina/farmacocinética , Simportadores , Substituição de Aminoácidos/genética , Animais , Células COS , Proteínas de Transporte/química , Desipramina/farmacologia , Humanos , Mutagênese Sítio-Dirigida , Proteínas da Membrana Plasmática de Transporte de Norepinefrina , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/farmacocinética , Transfecção , Trítio/metabolismoRESUMO
Low P300 amplitudes and topographical asymmetries have been reported in schizophrenic patients, but reference-independent amplitude assessment failed to replicate reduced amplitudes. P300 amplitude is conventially assessed at midline electrodes (Pz), and asymmetric topography as reported in schizophrenics, may confound this measurement. We investigated the possible interaction between P300 topography and assessments of amplitudes. In 41 clinically stable schizophrenics and 31 normal controls, the general finding of reduced amplitudes at the Pz-electrode and topographical asymmetries in the patient group were replicated. In both groups, asymmetries of the P300 field (lateralized peaks) reduced the standard amplitude assessment at the midline parietal electrode, but did not affect the reference-independent, global amplitude assessment. This shows that asymmetry per se does not imply reduced field strength. In addition, in schizophrenics, but not in controls, there was a significant effect of the direction of asymmetry on both amplitude measures, amplitudes being lower with increasing shift of the P300 peak to the right side. Considering also the slightly left-lateralized peaks in the normal controls, this suggests that only right-lateralized P300 peaks express functional deficits in schizophrenics, whereas left-lateralized peaks fall within the physiological variability of the P300 field. The reference-independent amplitude assessment is proposed for unambiguous amplitude assessment in order to better define the clinical, psychological and physiopathological meaning of the P300 alterations in schizophrenics.
Assuntos
Nível de Alerta/fisiologia , Atenção/fisiologia , Eletroencefalografia , Potenciais Evocados Auditivos/fisiologia , Discriminação da Altura Tonal/fisiologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Adulto , Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Dominância Cerebral/fisiologia , Eletroencefalografia/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Reação/fisiologiaRESUMO
Twenty-eight psychiatric patients with computerized tomography (CT) findings of ventricular abnormality most likely to result from prenatal/perinatal lesions (VA group) were compared to 28 sex- and age-matched psychiatric patients with normal neuroradiological findings (NCT group). The neuroradiological rater was blind to clinical psychiatric diagnoses and, vice versa, clinical diagnoses were established without knowledge of neuroradiological findings. A polydiagnostic approach (DSM-III-R, ICD-10, Leonhard Classification) was used for psychiatric diagnostic workup. Significantly more patients with cycloid psychoses (according to Leonhard's original description) were found in VA as compared to NCT patients. According to DSM-III-R and ICD-10, VA and NCT groups did not differ significantly regarding diagnostic distribution. Ventricular abnormalities that may reflect sequels of birth complications and/or adverse events during pregnancy may constitute one of the risk factors for developing cycloid psychosis as originally described by Leonhard.
Assuntos
Transtornos Psicóticos/diagnóstico por imagem , Adulto , Ansiedade/psicologia , Ventriculografia Cerebral , Confusão/psicologia , Método Duplo-Cego , Feminino , Felicidade , Humanos , Hipercinese/psicologia , Masculino , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/psicologia , Recidiva , Fatores de Risco , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Early differentiation of the nervous system and adult CNS neuroplasticity is modulated by PAX-6. We have shown previously that a highly polymorphic, functional AC/AG repeat in the 5' regulatory region of the gene showed significantly increased promoter activity, if containing > or = 29 repeats, and that the heterozygous genotype (< or = 28/> or = 29) revealed increased mRNA PAX-6 levels in human brain tissue compared to the homozygous short variant. METHODS: In a case-control study of 655 unrelated individuals, allele frequencies and genotype distributions of the functional PAX-6 promoter polymorphism were investigated comprising patients with DSM-IV schizophrenia, patients with affective disorders, and population controls. RESULTS: No allelic or genotypic association of the PAX-6 promoter polymorphism to affective disorder or to schizophrenia as one disease entity was observed. After subtyping schizophrenia into paranoid and nonparanoid forms, potential evidence was found for a genotypic association of the high-activity variant with the paranoid subtype of schizophrenia (p = .02). The estimated odds ratio was 1.7 (95% CI .98 to 2.95) for those heterozygous and 1.4 (95% CI .82 to 2.42) for those heterozygous or homozygous for the high-activity variant compared to the homozygous low-activity variant. CONCLUSIONS: Our finding indicates that early developmental genes may be involved in the etiopathogenesis of schizophrenia subtypes via variable transcriptional regulation in the developing and adult human brain.
Assuntos
Encéfalo/citologia , Genes Reguladores/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Esquizofrenia Paranoide/genética , Adulto , Alelos , Transtorno Bipolar/genética , Estudos de Casos e Controles , Técnicas de Cultura , Feminino , Ligação Genética/genética , Variação Genética/genética , Genótipo , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Plasticidade Neuronal/genética , Mutação Puntual/genética , RNA Mensageiro/genética , Transcrição Gênica/genéticaRESUMO
OBJECTIVE: An excess of obstetric complications in the histories of schizophrenic patients is a well-replicated finding, but less consistent results have been found concerning the relationships between obstetric complications and family history of schizophrenia, age at onset of schizophrenia, and gender. Small sample size limited the power of previous studies that attempted to assess such relationships. The aim of this study was to use data on individual patients from all available studies to examine the links between a history of obstetric complications and family history of schizophrenia, age at onset, and gender. METHOD: Raw data from 854 schizophrenic patients concerning history of obstetric complications rated according to the Lewis and Murray scale were obtained from 11 different research groups. Weighted average estimates were calculated with the use of regression techniques. RESULTS: A significant association was found between age at onset of schizophrenia and obstetric complications: the earlier the age at onset, the more likely the history of obstetric complications. Subjects with onset of schizophrenia before age 22 were 2.7 times more likely than those with onset at a later age to have had a history of abnormal presentation at birth and 10 times more likely to have had a history of complicated Cesarean birth. No association was found between obstetric complications and family history of schizophrenia or gender. CONCLUSIONS: The association between obstetric complications and early age at onset of schizophrenia indicates that the pathophysiology of early-onset schizophrenia involves neurodevelopmental impairment.
Assuntos
Família , Complicações na Gravidez/epidemiologia , Esquizofrenia/epidemiologia , Adolescente , Adulto , Fatores Etários , Idade de Início , Cesárea/estatística & dados numéricos , Criança , Feminino , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Complicações do Trabalho de Parto/epidemiologia , Gravidez , Análise de Regressão , Esquizofrenia/genética , Fatores SexuaisRESUMO
In family study concentrating on 139 probands with chronic DSM-III-R schizophrenia, catatonic type, 83 probands (41 women, 42 men) met the criteria for periodic catatonia and 56 probands (14 women, 42 men) for systematic catatonia according to the Leonhard classification. The reliability and stability of this subclassification were tested by 2 experienced psychiatrists working independently of each other. Both diagnosticians were kept blind as to the probands' family history. The 139 probands had a total of 543 first-degree relatives. Only those hospitalized for schizophrenia were allocated to the group of afflicted family members. Diagnostic reliability was kappa statistic 0.93 and diagnostic stability during catamnesis reached 97% and kappa of 0.93. Life-table analyses revealed that the age-corrected risks were significantly different in periodic and systematic catatonia. In systematic catatonia mothers had a risk of 6.8%, fathers 2%, and randomly selected sibs 3%. IN periodic catatonia an excess of homologous psychoses was apparent: There was a risk of 33.7% for mothers, 15.4% for fathers, and 24.4% for sibs. The quota of afflicted parents (33 of 161) was higher than that of sibs (26 of 162). In periodic catatonia, 59% of the families were multiple afflicted with pronounced unilineal vertical transmission. In 10% of the families 3 successive generations suffered from the disease and were treated in hospital. The results of the study led to the following hypotheses: Periodic and systematic catatonia are valid subgroups of DSM-III-R schizophrenia. In systematic catatonia heritability is very low. Periodic catatonia is a familial disorder. Homogeneity of familial psychoses and unilineal vertical transmission with anticipation are consistent with a major gene effect. Periodic catatonia seems to be a promising candidate for molecular genetic evaluation.
Assuntos
Heterogeneidade Genética , Esquizofrenia Catatônica/genética , Adulto , Fatores Etários , Família , Feminino , Humanos , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Morbidade , Análise Multivariada , Pais , Linhagem , Reprodutibilidade dos Testes , Risco , Esquizofrenia Catatônica/diagnósticoRESUMO
The human synapsin III gene (synapsin III) is a member of a neuron-specific phosphoprotein gene family involved in short-term neurotransmitter release. We mapped synapsin III to chromosomal region 22q13 (13.1-13.31) by fluorescence in situ hybridization, a region that has been identified as a potential schizophrenia susceptibility locus. The dinucleotide repeat marker D22S280 located in intron 5 of synapsin III was genotyped in a linkage and family-based association study to assess the role of the synapsin III locus in the etiology of schizophrenia. In 12 pedigrees with periodic catatonia comprising 135 individuals, we found exclusion of linkage of marker D22S280 using lod score analysis with autosomal dominant/recessive models as well as affected only LOD score methods with dominant/recessive models. In a family-based association study of 61 unrelated parent-offspring trios with schizophrenia (according to the the Diagnostic and Statistical Manual of Mental Disorders, fourth edition [DSM-IV, American Psychiatric Association, 1994]), we found no association of individual D22S280 alleles to disease. Results of a multiallelic transmission/disequilibrium test (TDT(max) = 3.00; P = 0.55) challenged the possibility that D22S280 alleles appear with DSM-IV schizophrenia more frequently than expected. In addition, no evidence for gender differences or parent-of-origin effects were found. Thus, the synapsin III locus at chromosome 22q13 is not likely to contain a schizophrenia susceptibility gene.
Assuntos
Aberrações Cromossômicas/genética , Cromossomos Humanos Par 22/genética , Esquizofrenia/genética , Sinapsinas/genética , Adulto , Bandeamento Cromossômico , Transtornos Cromossômicos , Saúde da Família , Feminino , Humanos , Hibridização in Situ Fluorescente , Desequilíbrio de Ligação , Escore Lod , Masculino , Pessoa de Meia-Idade , Mapeamento Físico do CromossomoRESUMO
Functional characterization studies revealed that transcriptional activity of the human monoamine oxidase A (MAOA) gene is modulated by a polymorphic repetitive sequence located approximately 1.2 kb upstream of the ATG codon. To investigate the possible influence of the allelic variants of the MAOA gene-linked polymorphic region (MAOA-LPR) on the genetic predisposition to psychiatric disorders, we have performed a case-control association study. 174 patients with affective disorders and 258 patients with schizophrenia according to DSM-IV, as well as 229 population controls were tested. Statistical analysis showed no significant differences in allele or genotype frequencies between control and patient groups. Our results suggest that there is no association between MAOA-LPR genotype and susceptibility to recurrent major depression, bipolar disorder, and schizophrenia in our population.
Assuntos
Transtornos Mentais/genética , Monoaminoxidase/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Adulto , Idade de Início , Alelos , Transtorno Bipolar/genética , Estudos de Casos e Controles , Códon , Depressão/genética , Feminino , Genótipo , Humanos , Íntrons , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/genética , Esquizofrenia/genéticaRESUMO
The complete coding region of the norepinephrine transporter (NET) gene was systematically screened for genetic variants in 137 unrelated individuals (including 46 probands with bipolar affective disorder and 45 schizophrenic probands, as well as 46 blood donors) using single-strand conformation analysis. We identified 13 DNA sequence variants, among them five missense substitutions. The missense substitutions Val69Ile, Thr99Ile, Val245Ile, Val449Ile, and Gly478Ser are located at putative transmembrane domains (TMD) 1, 2, 4, 9, and 10, respectively. The Thr99Ile substitution is at the 5th position of the putative leucine-zipper in TMD2. In a case-control study distribution of missense substitutions was found to be similar in 103 patients with bipolar affective disorder, in 228 schizophrenia patients and in 187 controls, indicating that presence of these variants is not causally related to major psychiatric diseases. The detection of a highly polymorphic silent 1287G/A polymorphism was utilized to demonstrate biallelic expression of the NET in adult human brain.
Assuntos
Proteínas de Transporte/genética , Norepinefrina/metabolismo , Simportadores , Adulto , Alelos , Clonagem Molecular , Análise Mutacional de DNA , Humanos , Íntrons , Modelos Moleculares , Proteínas da Membrana Plasmática de Transporte de Norepinefrina , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Mapeamento por RestriçãoRESUMO
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.
Assuntos
Proteínas de Transporte/genética , Simportadores , Síndrome de Tourette/genética , Adolescente , Adulto , Alelos , Análise Mutacional de DNA , Primers do DNA , Feminino , Humanos , Masculino , Proteínas da Membrana Plasmática de Transporte de Norepinefrina , Mutação Puntual , Polimorfismo de Fragmento de RestriçãoRESUMO
A possible dysregulation of dopaminergic neurotransmission has been implicated in a variety of neuropsychiatric diseases. In the present study we systematically searched for the presence of mutations in the 5'-flanking region of the dopamine D1 receptor (DRD1) gene. This region has previously been shown to contain a functional promoter [Minowa et al., 1992: Proc Natl Acad Sci 89:3045-3049; Minowa et al., 1993: J Biol Chem 268:23544-23551]. We investigated 119 unrelated individuals (including 36 schizophrenic patients, 38 bipolar affective patients, and 45 healthy controls) using single-strand conformation analysis (SSCA). Eleven overlapping PCR fragments covered 2,189 bp of DNA sequence. We identified six single base substitutions: -2218T/C, -2102C/A, -2030T/C, -1992G/A, -1251G/C, and -800T/C. None of the mutations was found to be located in regions which have important influence on the level of transcriptional activity. Allele frequencies were similar in patients and controls, indicating that genetic variation in the 5'-regulatory region of the DRD1 gene is unlikely to play a frequent, major role in the genetic predisposition to either schizophrenia or bipolar affective disorder.
Assuntos
Transtorno Bipolar/genética , Receptores de Dopamina D1/genética , Sequências Reguladoras de Ácido Nucleico , Esquizofrenia/genética , Alelos , Sequência de Bases , Primers do DNA , Frequência do Gene , Humanos , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Valores de Referência , Mapeamento por RestriçãoRESUMO
Serotonin (5-HT) is a prime candidate for studies of the interaction between the nervous and immune systems, since it is both an important neurotransmitter and released at high concentrations at sites of inflammation. Serotonergic neurotransmission is regulated by the 5-HT transporter (5-HTT), which determines the magnitude and duration of serotonergic responses. Since tumor necrosis factor alpha (TNF-alpha) and interleukin-6 are two inflammatory mediators that are central to the initiation of inflammation, we studied the impact of these cytokines on the 5-HTT. As model system we used a cell line which constitutively expresses the 5-HTT, namely the choriocarcinoma cell line JAR. We found that TNF-alpha enhances 5-HT uptake, with a doubling of the maximal velocity of uptake. Interleukin-6, on the other hand, had no effect. We thus show for the first time that the cytokine TNF-alpha modulates 5-HTT function. Furthermore, we propose a molecular mechanism for this effect. Since both 5-HT and TNF-alpha are elevated at sites of inflammation, TNF-alpha may act to renormalize 5-HT levels by way of its effect on the 5-HTT. This is especially important for the central nervous system, where the TNF-alpha effect shown here can aid in preventing disturbances of serotonergic neurotransmission.
Assuntos
Proteínas de Transporte/fisiologia , Interleucina-6/farmacologia , Glicoproteínas de Membrana/fisiologia , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Fator de Necrose Tumoral alfa/farmacologia , Divisão Celular , Coriocarcinoma , Humanos , Cinética , Serotonina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina , Células Tumorais CultivadasRESUMO
In a family study involving 83 probands with periodic catatonia a subtype of DSM IIIR schizophrenia, we reported an age-specific morbidity risk of 26.9% in first-degree relatives with homotypical psychoses and genetic anticipation indicating a possible major gene effect. Paternal transmission was associated with a trend for a younger age at onset in probands compared to that observed in the case of maternal transmission (P = 0.099). If this can be confirmed in a larger sample and then replicated, there would be evidence for the occurrence of a parent-of-origin effect. Such an observation may indicate that a paternally imprinted locus acts on periodic catatonia. Among the non-genetic mechanisms that may modify the penetrance of the disease, paternal affection did lead to a decrease in male offspring (P = 0.007) and maternal affection showed an increased frequency of non-affected male offspring (P = 0.021). We therefore propose that parent-of-origin effects as well as prenatal mortality and psychosocial factors need further investigation in the periodic catatonia subtype of schizophrenia.
Assuntos
Impressão Genômica , Esquizofrenia Catatônica/genética , Adolescente , Adulto , Idade de Início , Idoso , Características da Família , Feminino , Alemanha/epidemiologia , Humanos , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Núcleo Familiar/psicologia , Pais/psicologia , Psicologia , Transtornos Psicóticos/genética , Esquizofrenia Catatônica/epidemiologiaRESUMO
The enhancement of GABAergic neurotransmission has been closely linked to antipanic drug efficacy. This is the first study to investigate a putative association of exonic sequence variants of the human GABA(B) receptor 1 (GABA(B)R1) gene and susceptibility to panic disorder. Three DNA sequence variants in exons 1a1, 7 and 11 were assessed by polymerase chain reaction-based restriction fragment length polymorphism in a case-control study among patients with panic disorder with and without agoraphobia (DSM III-R criteria) and blood donors. There was no indication of an increased vulnerability to panic disorder or agoraphobia with respect to the allelic variants under study.
Assuntos
Agorafobia/genética , Éxons , Variação Genética , Transtorno de Pânico/genética , Receptores de GABA-B/genética , Agorafobia/complicações , Alelos , Substituição de Aminoácidos , Estudos de Casos e Controles , DNA/sangue , DNA/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Alemanha , Humanos , Masculino , Transtorno de Pânico/complicações , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNA , População Branca/genéticaRESUMO
In a family-based association study we investigated transmission of a multiallelic CAG repeat in a novel neuronal potassium channel gene, hSKCa3, in 59 parent/ offspring trios. In contrast to recent reports of an association of moderately large repeats with schizophrenia in case-control studies, our findings indicate that short CAG repeats (< or=19 repeats) are transmitted at an increased frequency to schizophrenic offspring (p=0.014), particularly among familial cases (p=0.007). No evidence for a parent-of-origin effect was found. Multiallelic TDT procedure showed no association of individual CAG repeats to schizophrenia. Further studies using family-based designs should clarify whether hSKCa3 is a susceptibility factor to schizophrenia or co-segregates with a major disease gene in tight linkage.
Assuntos
Saúde da Família , Neuropeptídeos/genética , Canais de Potássio/genética , Esquizofrenia/genética , Repetições de Trinucleotídeos , Adolescente , Adulto , Alelos , Análise Mutacional de DNA , Feminino , Ligação Genética , Genótipo , Humanos , Masculino , Linhagem , Polimorfismo Genético , Canais de Potássio Ativados por Cálcio de Condutância BaixaRESUMO
Several epidemiological studies have reported an association between complications of pregnancy and delivery and schizophrenia, but none have had sufficient power to examine specific complications that, individually, are of low prevalence. We, therefore, performed an individual patient meta-analysis using the raw data from case control studies that used the Lewis-Murray scale. Data were obtained from 12 studies on 700 schizophrenia subjects and 835 controls. There were significant associations between schizophrenia and premature rupture of membranes, gestational age shorter than 37 weeks, and use of resuscitation or incubator. There were associations of borderline significance between schizophrenia and birthweight lower than 2,500 g and forceps delivery. There was no significant interaction between these complications and sex. We conclude that some abnormalities of pregnancy and delivery may be associated with development of schizophrenia. The pathophysiology may involve hypoxia and so future studies should focus on the accurate measurement of this exposure.
Assuntos
Complicações na Gravidez , Esquizofrenia/etiologia , Estudos de Casos e Controles , Extração Obstétrica/efeitos adversos , Extração Obstétrica/estatística & dados numéricos , Feminino , Humanos , Masculino , Trabalho de Parto Prematuro/complicações , Trabalho de Parto Prematuro/epidemiologia , Gravidez , Complicações na Gravidez/epidemiologia , Projetos de Pesquisa , Esquizofrenia/epidemiologia , Estatística como AssuntoRESUMO
The 5'-flanking region of the human dopamine transporter (hDAT) was systematically screened for variants by single strand conformation analysis (SSCA) between -1586 and +97 basepair (bp) relative to the transcription start site. Five diallelic polymorphisms were found, which were shown to be due to single base substitutions: T-67A, G-660C, C-839T, C-1169G, T-1476G. In a population sample of 119 unrelated Caucasians, allele frequencies of the rarer allele were 47% for -67T, 3% for -660C, 45% for -839T, 50% for -1169G, and 8% for -1476G, respectively. Among 15 observed haplotypes, seven haplotypes collected a frequency of about 96% in our sample. T-67A, C-839T, C-1169G, T-1476G were related to potential transcriptional recognition sites. These findings and the occurrence of distinct haplotypes at the hDAT promoter locus in a Caucasian population sample make this region a promising target in the context of linkage and association studies in certain diseases.