RESUMEN
Metabolism of the monoamines dopamine, serotonin and noradrenaline, is altered in the central nervous system of people with schizophrenia, and their major metabolites homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), respectively, have been intensively studied as indirect measures of these neurotransmitters in cerebrospinal fluid (CSF). Regular tobacco smoking has been shown to alter neurotransmitter metabolism in the brain and studies have found CSF monoamine metabolite concentrations to be substantially lower in smokers. However, few studies investigating these monoamines in CSF have controlled for regular tobacco smoking. We investigated if regular tobacco smoking influences CSF HVA, 5-HIAA and MHPG concentrations in patients treated for psychotic disorders (nâ¯=â¯69) and healthy non-psychotic human volunteers (nâ¯=â¯200). After lumbar puncture CSF samples were analyzed with mass fragmentography. CSF HVA, 5-HIAA and MHPG concentrations did not significantly differ between smokers and non-smokers neither in patients, nor in healthy subjects, whereas back-length predicted HVA and 5-HIAA and antipsychotic medication MHPG concentrations. The results indicate that regular tobacco smoking has no significant effect on monoamine metabolite concentrations in CSF. This suggests that lack of controlling for regular tobacco smoking should not substantially violate the results in studies of the major monoamine metabolites in CSF.
Asunto(s)
Monoaminas Biogénicas/líquido cefalorraquídeo , Trastornos Psicóticos/líquido cefalorraquídeo , Esquizofrenia/líquido cefalorraquídeo , Fumar Tabaco/líquido cefalorraquídeo , Adolescente , Adulto , Biomarcadores/líquido cefalorraquídeo , Femenino , Ácido Homovanílico/líquido cefalorraquídeo , Humanos , Ácido Hidroxiindolacético/líquido cefalorraquídeo , Masculino , Metoxihidroxifenilglicol/líquido cefalorraquídeo , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/epidemiología , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiología , Fumar Tabaco/efectos adversos , Adulto JovenRESUMEN
Dopamine activity, mediated by the catecholaminergic neurotransmitter dopamine, is prominent in the human brain and has been implicated in schizophrenia. Dopamine targets five different receptors and is then degraded to its major metabolite homovanillic acid (HVA). We hypothesized that genes encoding dopamine receptors may be associated with cerebrospinal fluid (CSF) HVA concentrations in patients with psychotic disorder. We searched for association between 67 single nucleotide polymorphisms (SNPs) in the five dopamine receptor genes i.e., DRD1, DRD2, DRD3, DRD4 and DRD5, and the CSF HVA concentrations in 74 patients with psychotic disorder. Nominally associated SNPs were also tested in 111 healthy controls. We identified a locus, located downstream DRD1 gene, where four SNPs, rs11747728, rs11742274, rs265974 and rs11747886, showed association with CSF HVA concentrations in psychotic patients. The associations between rs11747728, which is a regulatory region variant, and rs11742274 with HVA remained significant after correction for multiple testing. These associations were restricted to psychotic patients and were absent in healthy controls. The results suggest that the DRD1 gene is implicated in the pathophysiology of psychosis and support the dopamine hypothesis of schizophrenia.
Asunto(s)
Dopamina/metabolismo , Sitios Genéticos , Ácido Homovanílico/líquido cefalorraquídeo , Trastornos Psicóticos/líquido cefalorraquídeo , Trastornos Psicóticos/genética , Receptores de Dopamina D1/genética , Adulto , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Receptores de Dopamina D2/genética , Receptores de Dopamina D3/genética , Receptores de Dopamina D4/genética , Receptores de Dopamina D5/genética , Adulto JovenRESUMEN
Glutamate-related genes have been associated with schizophrenia, but the results have been ambiguous and difficult to replicate. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are the major degradation products of the monoamines dopamine, serotonin and noradrenaline, respectively, and their concentrations in the cerebrospinal fluid (CSF), mainly HVA, have been associated with schizophrenia. In the present study, we hypothesized that CSF HVA, 5-HIAA and MHPG concentrations represent intermediate phenotypes in the association between glutamate-related genes and psychosis. To test this hypothesis, we searched for association between 238 single nucleotide polymorphisms (SNPs) in ten genes shown to be directly or indirectly implicated in glutamate transmission and CSF HVA, 5-HIAA and MHPG concentrations in 74 patients with psychotic disease. Thirty-eight nominally significant associations were found. Further analyses in 111 healthy controls showed that 87% of the nominal associations were restricted to the patients with psychosis. Some of the psychosis-only-associated SNPs found in the d-amino acid oxidase activator (DAOA) and the kynurenine 3-monooxygenase (KMO) genes have previously been reported to be associated with schizophrenia. The present results suggest that CSF monoamine metabolite concentrations may represent intermediate phenotypes in the association between glutamate-related genes and psychosis.
Asunto(s)
Monoaminas Biogénicas/líquido cefalorraquídeo , Ácido Glutámico/líquido cefalorraquídeo , Ácido Glutámico/genética , Fenotipo , Trastornos Psicóticos/líquido cefalorraquídeo , Trastornos Psicóticos/genética , Adulto , Biomarcadores/líquido cefalorraquídeo , Dopamina/líquido cefalorraquídeo , Femenino , Ácido Homovanílico/líquido cefalorraquídeo , Humanos , Ácido Hidroxiindolacético/líquido cefalorraquídeo , Quinurenina 3-Monooxigenasa/líquido cefalorraquídeo , Quinurenina 3-Monooxigenasa/genética , Masculino , Metoxihidroxifenilglicol/líquido cefalorraquídeo , Norepinefrina/líquido cefalorraquídeo , Polimorfismo de Nucleótido Simple/genética , Trastornos Psicóticos/diagnóstico , Serotonina/líquido cefalorraquídeoRESUMEN
BACKGROUND: Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are the major monoamine metabolites in the central nervous system (CNS). Their cerebrospinal fluid (CSF) concentrations, reflecting the monoamine turnover rates in CNS, are partially under genetic influence and have been associated with schizophrenia. We have hypothesized that CSF monoamine metabolite concentrations represent intermediate steps between single nucleotide polymorphisms (SNPs) in genes implicated in monoaminergic pathways and psychosis. METHODS: We have searched for association between 119 SNPs in genes implicated in monoaminergic pathways [tryptophan hydroxylase 1 (TPH1), TPH2, tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), dopamine beta-hydroxylase (DBH), catechol-O-methyltransferase (COMT), monoamine oxidase A (MAOA) and MAOB] and monoamine metabolite concentrations in CSF in 74 patients with psychotic disorder. RESULTS: There were 42 nominally significant associations between SNPs and CSF monoamine metabolite concentrations, which exceeded the expected number (20) of nominal associations given the total number of tests performed. The strongest association (p = 0.0004) was found between MAOB rs5905512, a SNP previously reported to be associated with schizophrenia in men, and MHPG concentrations in men with psychotic disorder. Further analyses in 111 healthy individuals revealed that 41 of the 42 nominal associations were restricted to patients with psychosis and were absent in healthy controls. CONCLUSIONS: The present study suggests that altered monoamine turnover rates in CNS reflect intermediate steps in the associations between SNPs and psychosis.
Asunto(s)
Dopamina/líquido cefalorraquídeo , Norepinefrina/líquido cefalorraquídeo , Trastornos Psicóticos/líquido cefalorraquídeo , Trastornos Psicóticos/genética , Serotonina/líquido cefalorraquídeo , Adulto , Monoaminas Biogénicas/líquido cefalorraquídeo , Femenino , Genotipo , Humanos , Masculino , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Free vascularized fibular graft is of the greatest importance in the orthopaedics and trauma. Bone, skeletal defects due to the trauma, infections and congenital anomalies could be successfully solved by the free vascularized fibular grafts. In this article the main anatomical data of fibular graft, surgical techniques, indications for the FVFG in the treatment of trauma caused bone defects or its complications -sequels are described.
Asunto(s)
Traumatismos del Brazo/cirugía , Trasplante Óseo/métodos , Peroné/trasplante , Traumatismos de la Pierna/cirugía , Huesos/lesiones , Huesos/cirugía , Peroné/irrigación sanguínea , Humanos , Trasplantes/irrigación sanguíneaRESUMEN
The scaphoid is vitally important for the proper mechanics of wrist function. Fracture of the scaphoid bone is the most common carpal fracture. Among all wrist injuries the incidence of scaphoid fracture is second only to fractures of the distal radius. Scaphoid fractures are significant because a delay in diagnosis can lead to a variety of adverse outcomes that include nonunion, delayed union, decreased grips strength, range of motion and osteoarthritis of the radiocarpal joint. To avoid missing this diagnosis, a high index of suspicion and a through history and physical examination are necessary, because initial radiographs are often negative. Regardless of the technique of bone grafting, there will almost always be some loss of motion even if the fracture unites.
Asunto(s)
Fracturas Óseas/diagnóstico , Fracturas Óseas/cirugía , Hueso Escafoides/lesiones , Traumatismos de la Muñeca/diagnóstico , Traumatismos de la Muñeca/cirugía , Trasplante Óseo , Moldes Quirúrgicos , Fijación Interna de Fracturas , Fracturas Óseas/clasificación , Fracturas Óseas/terapia , Humanos , Traumatismos de la Muñeca/clasificación , Traumatismos de la Muñeca/terapiaRESUMEN
The D-amino acid oxidase activator (DAOA) protein regulates the function of D-amino oxidase (DAO), an enzyme that catalyzes the oxidative deamination of D-3,4-dihydroxyphenylalanine (D-DOPA) and D-serine. D-DOPA is converted to L-3,4-DOPA, a precursor of dopamine, whereas D-serine participates in glutamatergic transmission. We hypothesized that DAOA polymorphisms are associated with dopamine, serotonin and noradrenaline turnover in the human brain. Four single-nucleotide polymorphisms, previously reported to be associated with schizophrenia, were genotyped. Cerebrospinal fluid (CSF) samples were drawn by lumbar puncture, and the concentrations of the major dopamine metabolite homovanillic acid (HVA), the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the major noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured. Two of the investigated polymorphisms, rs3918342 and rs1421292, were significantly associated with CSF HVA concentrations. Rs3918342 was found to be nominally associated with CSF 5-HIAA concentrations. None of the polymorphisms were significantly associated with MHPG concentrations. Our results indicate that DAOA gene variation affects dopamine turnover in healthy individuals, suggesting that disturbed dopamine turnover is a possible mechanism behind the observed associations between genetic variation in DAOA and behavioral phenotypes in humans.
Asunto(s)
D-Aminoácido Oxidasa/genética , Ácido Homovanílico/líquido cefalorraquídeo , Polimorfismo de Nucleótido Simple/genética , Adolescente , Adulto , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Población Blanca , Adulto JovenRESUMEN
The dystrobrevin binding protein-1 (DTNBP1) gene encodes dysbindin-1, a protein involved in neurodevelopmental and neurochemical processes related mainly to the monoamine dopamine. We investigated possible associations between eleven DTNBP1 polymorphisms and cerebrospinal fluid (CSF) concentrations of the major dopamine metabolite homovanillic acid (HVA), the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), and the major noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy human subjects (n=132). Two polymorphisms, rs2619538 and rs760666, were nominally associated with CSF HVA and 5-HIAA concentrations, whereas a third polymorphism, rs909706, showed association only with HVA. After correction for multiple testing only the associations between rs2619538 and HVA and 5-HIAA concentrations remained significant. No significant association was found between any of the investigated DTNBP1 polymorphisms and CSF MHPG concentrations. The results suggest that genetic variation in DTNBP1 gene affects the regulation of dopamine and serotonin turnover in the central nervous system of healthy volunteers.
Asunto(s)
Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Ácido Homovanílico/líquido cefalorraquídeo , Ácido Hidroxiindolacético/líquido cefalorraquídeo , Metoxihidroxifenilglicol/líquido cefalorraquídeo , Neurotransmisores/metabolismo , Dopamina/metabolismo , Disbindina , Proteínas Asociadas a la Distrofina , Femenino , Frecuencia de los Genes , Variación Genética , Genotipo , Ácido Homovanílico/metabolismo , Humanos , Ácido Hidroxiindolacético/metabolismo , Masculino , Metoxihidroxifenilglicol/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Norepinefrina/metabolismo , Polimorfismo de Nucleótido Simple , Serotonina/metabolismoRESUMEN
Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin synthesis. We investigated possible relationships between five TPH1 gene polymorphisms and cerebrospinal fluid (CSF) concentrations of the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the major dopamine metabolite homovanillic acid (HVA), and the major norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n=132). The G-allele of the TPH1 rs4537731 (A-6526G) polymorphism was associated with 5-HIAA and HVA, but not MHPG concentrations. None of the other four TPH1 polymorphisms (rs211105, rs1800532, rs1799913 and rs7933505) were significantly associated with any of the monoamine metabolite concentrations. Two (rs4537731G/rs211105T/rs1800532C/rs1799913C/rs7933505G and rs4537731A/rs211105T/rs1800532C/rs1799913C/rs7933505G) of five common TPH1 five-allele haplotypes were associated with 5-HIAA and HVA concentrations in opposite directions. None of the common haplotypes was associated with MHPG concentrations in the CSF. The results suggest that TPH1 gene variation participates in the regulation of serotonin and dopamine turnover rates in the central nervous system of healthy human subjects.
Asunto(s)
Ácido Homovanílico/líquido cefalorraquídeo , Indoles/líquido cefalorraquídeo , Polimorfismo Genético/genética , Triptófano Hidroxilasa/genética , Adolescente , Adulto , Femenino , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Adulto JovenRESUMEN
Angiotensin II has been suggested to influence central dopamine and serotonin turnover. Since the angiotensin-converting enzyme (ACE) plays a key role in angiotensin regulation by converting inactive angiotensin I to active angiotensin II, we hypothesised that the functional insertion/deletion (I/D) polymorphism in the ACE gene, which has previously been suggested to be associated with, depression and panic disorder, may influence monoamine activity. A well-established technique for assessing brain monoamine turnover in humans is to measure concentrations of monoamine metabolites in the cerebrospinal fluid (CSF). We thus investigated possible associations between the ACE I/D polymorphism and CSF monoamine metabolite concentrations in a population of healthy male subjects. After having found such an association between the ACE I/D polymorphism and CSF levels of the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindoleacetic acid in this sample, I carriers displaying lower levels, we tried to replicate this observation in a population of violent male offenders from which also both CSF and DNA were available. Also in this sample, the same associations were found. Our results suggest that the ACE I/D polymorphism may play a role in the modulation of serotonergic and dopaminergic turnover in men.
Asunto(s)
Ácido Homovanílico/líquido cefalorraquídeo , Ácido Hidroxiindolacético/líquido cefalorraquídeo , Metoxihidroxifenilglicol/líquido cefalorraquídeo , Mutagénesis Insercional/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético/genética , Adolescente , Adulto , Criminales , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Estadística como Asunto , Adulto JovenRESUMEN
BACKGROUND: The objective of this study was to determine the minimum volume of blood that should be discarded from a range of different types of central venous catheter (CVC), such that the subsequent blood sample was not diluted or contaminated by the residual intra-luminal fluid. PROCEDURE: Seventy children aged 1-19 years with central venous access inserted as part of their standard clinical treatment were recruited to this prospective study. Statistical comparison of the extent of variation in biochemical and haematological parameters observed between two blood samples taken following routine 5 ml discard blood volumes, as compared to the extent of variation between samples drawn following a 5 ml discard volume and <5 ml volumes, was carried out. RESULTS: Data indicate that the measurement error in a clinical sample obtained following a 3 ml discard volume is no different to the measurement error obtained when using a standard 5 ml discard volume. Comparable results were obtained from patients with various different types of CVC or portacath access. CONCLUSIONS: The withdrawal of a 3 ml discard volume is sufficient to ensure that the subsequent blood sample is not diluted or contaminated by residual intra-luminal fluid. This may have a significant clinical impact in paediatric oncology, where patients frequently require blood transfusions due to the haematological toxicities associated with chemotherapy. It is hoped that these results will impact on hospital policies concerning specified discard volumes taken from CVCs prior to the withdrawal of blood samples for research purposes and routine clinical analysis.
Asunto(s)
Recolección de Muestras de Sangre/métodos , Cateterismo Venoso Central/métodos , Neoplasias/sangre , Adolescente , Adulto , Análisis Químico de la Sangre/métodos , Recolección de Muestras de Sangre/instrumentación , Cateterismo Venoso Central/instrumentación , Niño , Preescolar , Estudios de Seguimiento , Humanos , Lactante , Estudios ProspectivosRESUMEN
BACKGROUND: We aimed at estimating the value of structured interviews, medical records and clinical diagnoses for assessing lifetime diagnosis of patients with schizophrenia. In addition, the validity of the Operational Criteria Checklist (OPCRIT) system was analysed. SAMPLING AND METHODS: Swedish patients (n = 73), diagnosed with schizophrenia and related disorders by their treating physician, were scrutinized. Independent research diagnoses according to the Diagnostic and Statistical Manual, ed. 3, revised (DSM-III-R) were obtained by (1) a structured interview; (2) the OPCRIT algorithm, based on record analysis only; (3) the OPCRIT algorithm, based on record and interview analysis, or (4) a separate traditional research diagnosis based on both record and interview analysis. In addition, clinical International Classification of Diseases (ICD) diagnoses, given by the treating physician, were obtained from the case notes. Concordance rates for the different psychosis diagnoses were calculated. RESULTS: Diagnoses based on interviews only showed poor to fair agreement with the other research diagnoses, but patients diagnosed with schizophrenia or schizophrenic psychoses (i.e. schizophrenia, schizophreniform or schizoaffective disorder) at the interview almost always also obtained a corresponding research diagnosis based on record or combined sources. Diagnoses based on records only showed a good to excellent agreement with diagnoses based on records and interviews. Clinical ICD diagnoses generally displayed poor agreement with the research diagnoses, but 94% of patients ever given a clinical ICD diagnosis of schizophrenic psychosis received a corresponding traditional research diagnosis. OPCRIT diagnoses and independently assigned research diagnoses, based on the same information, displayed excellent concordance. CONCLUSIONS: Structured interviews performed with Swedish long-term-treated psychosis patients during non-hospitalization are a poor source for the evaluation of psychosis diagnoses, but a good screening instrument for the detection of DSM-III-R schizophrenia. In the investigated population, medical records are a valuable source for diagnostic assessment of psychoses and may serve as a stand-alone procedure in this patient category. Swedish clinical ICD diagnoses have a high positive predictive power identifying DSM-III-R diagnoses of schizophrenic psychoses, indicating validity of register-based research focusing on these diagnoses. The OPCRIT system is a valid tool for assessing DSM-III-R psychosis diagnoses. It should be emphasized that the present conclusions are based on the investigated Swedish psychosis population and cannot be generalized to populations composed of other patient groups or sampled in other settings, with other traditions regarding the use and availability of medical records.
Asunto(s)
Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/epidemiología , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiología , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Trastornos Mentales/diagnóstico , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Relationships between cognitive deficits and brain morphological changes observed in schizophrenia are alternately explained by less gray matter in the brain cerebral cortex, by alterations in neural circuitry involving the basal ganglia, and by alteration in cerebellar structures and related neural circuitry. This work explored a model encompassing all of these possibilities to identify the strongest morphological relationships to cognitive skill in schizophrenia. METHODS: Seventy-one patients with schizophrenia and sixty-five healthy control subjects were characterized by neuropsychological tests covering six functional domains. Measures of sixteen brain morphological structures were taken using semi-automatic and fully manual tracing of MRI images, with the full set of measures completed on thirty of the patients and twenty controls. Group differences were calculated. A Bayesian decision-theoretic method identified those morphological features, which best explained neuropsychological test scores in the context of a multivariate response linear model with interactions. RESULTS: Patients performed significantly worse on all neuropsychological tests except some regarding executive function. The most prominent morphological observations were enlarged ventricles, reduced posterior superior vermis gray matter volumes, and increased putamen gray matter volumes in the patients. The Bayesian method associated putamen volumes with verbal learning, vigilance, and (to a lesser extent) executive function, while caudate volumes were associated with working memory. Vermis regions were associated with vigilance, executive function, and, less strongly, visuo-motor speed. Ventricular volume was strongly associated with visuo-motor speed, vocabulary, and executive function. Those neuropsychological tests, which were strongly associated to ventricular volume, showed only weak association to diagnosis, possibly because ventricular volume was regarded a proxy for diagnosis. Diagnosis was strongly associated with the other neuropsychological tests, implying that the morphological associations for these tasks reflected morphological effects and not merely group volumetric differences. Interaction effects were rarely associated, indicating that volumetric relationships to neuropsychological performance were similar for both patients and controls. CONCLUSION: The association of subcortical and cerebellar structures to verbal learning, vigilance, and working memory supports the importance of neural connectivity to these functions. The finding that a morphological indicator of diagnosis (ventricular volume) provided more explanatory power than diagnosis itself for visuo-motor speed, vocabulary, and executive function suggests that volumetric abnormalities in the disease are more important for cognition than non-morphological features.
Asunto(s)
Trastornos del Conocimiento/psicología , Pruebas Neuropsicológicas , Psicología del Esquizofrénico , Adulto , Concienciación , Teorema de Bayes , Encéfalo/patología , Estudios de Cohortes , Femenino , Humanos , Aprendizaje , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Trastornos Psicóticos/psicología , Valores de Referencia , Análisis de Regresión , Esquizofrenia/patologíaRESUMEN
The objective was to investigate putative associations between brain-derived neurotrophic factor gene (BDNF) polymorphisms and brain morphology in patients with schizophrenia and healthy control subjects. Four BDNF polymorphisms were genotyped and analyzed versus 39 brain volume measures in 96 patients with schizophrenia or schizoaffective disorder and 104 healthy subjects. In all subjects, quantitative data on segmented gray, white, and cerebrospinal fluid (CSF) tissue class volumes of total brain and major cerebral lobes including ventricular CSF were obtained using magnetic resonance imaging (MRI). In a randomly selected subset of this population (n = 101-122), MR volumes from cerebellar tonsil, hemispheres, and vermis subregions, striatal structures, hippocampus, and corpus callosum were also measured. The BDNF 11757 G/C polymorphism was highly significantly associated with frontal gray matter volume variation in patients alone and in patients and control subjects combined. In patients only, the 270 C/T polymorphism was associated with total caudate volume. Significant associations were demonstrated between the BDNF 11757 G/C and Val66Met polymorphisms and a global haplotype estimate of four BDNF polymorphisms and the posterior superior cerebellar vermis volume in the controls as well as in the combined group, but not in the patients. The 11757 G/C polymorphism was associated with cerebellar hemisphere white and gray matter volumes in the combined group. The BDNF -633 T/A polymorphism was associated with gray matter of the putamen in the controls. Trends for associations between several polymorphisms/haplotype estimates and MRI volumes were found. BDNF gene variation may influence brain morphology. The effects may be different in patients with schizophrenia and healthy subjects.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/genética , Encéfalo/patología , Polimorfismo Genético , Esquizofrenia/genética , Adulto , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esquizofrenia/líquido cefalorraquídeo , Esquizofrenia/patologíaRESUMEN
Polymorphisms in the brain-derived neurotrophic factor (BDNF) gene have been suggested to be associated with schizophrenia. In a replication attempt, Swedish patients with schizophrenia (n=187) and control subjects (n=275) were assessed for four BDNF gene polymorphisms. There were no significantly different allele, genotype or haplotype frequencies between cases or controls. Neither were there any differences when schizophrenic patients were sub-divided with regard to a number of different clinical variables, although a small group of psychotic patients with prominent affective features displayed higher frequencies of the less common alleles of the Val66Met and 11757 G/C polymorphisms compared to controls. The present Swedish results do not verify previous associations between putative functional BDNF gene polymorphisms and schizophrenia. However, when combined with previous studies meta-analyses indicated that the BDNF 270 T-allele and the Val66Met homozygous state were associated with the disorder. Thus, the BDNF gene may confer susceptibility to schizophrenia. Additional studies are warranted to shed further light on this possibility.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/genética , Esquizofrenia/epidemiología , Esquizofrenia/genética , Adulto , Alelos , Sustitución de Aminoácidos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Variación Genética , Genotipo , Haplotipos , Humanos , Desequilibrio de Ligamiento/genética , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Suecia/epidemiologíaRESUMEN
OBJECTIVE: Anatomical structures of the striatum were studied in 58 patients with schizophrenia and 56 healthy comparison subjects of both genders matched for age and handedness. METHOD: Magnetic resonance imaging scans were used to measure gray matter, white matter, and CSF volumes of the caudate, putamen, and nucleus accumbens in the left and the right hemispheres. RESULTS: White matter/gray matter ratios of the striatal structures were significantly lower in patients than in healthy subjects. In patients, relative white matter volumes in the caudate and nucleus accumbens were reduced, whereas gray matter in the putamen was increased. The total accumbens volume did not differ by diagnosis, but left side accumbens was larger than right in the healthy subjects. The proportion of white matter was greater in women in both the patient and healthy comparison groups. Total caudate and putamen volumes demonstrated no differences due to diagnosis or laterality, but a negative correlation was found in patients between white matter volumes and increasing age. There were no significant correlations among total striatal volumes, white matter/gray matter ratios, age at onset of illness, or illness duration. An estimate of lifetime neuroleptic consumption was positively correlated with right gray matter volume of the putamen in male schizophrenia patients who received typical neuroleptics. CONCLUSIONS: The proportion of white matter to gray matter tissue volumes of the caudate, putamen, and nucleus accumbens is altered in medicated chronic schizophrenia patients, but the total volumes are unchanged.
Asunto(s)
Cuerpo Estriado/patología , Imagen por Resonancia Magnética/estadística & datos numéricos , Esquizofrenia/patología , Adulto , Antipsicóticos/uso terapéutico , Mapeo Encefálico , Núcleo Caudado/patología , Femenino , Lateralidad Funcional , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Núcleo Accumbens/patología , Putamen/patología , Esquizofrenia/diagnóstico , Esquizofrenia/tratamiento farmacológico , Factores SexualesRESUMEN
We aimed to estimate the value of structured interviews, medical records and Swedish register diagnoses for assessing lifetime diagnosis of patients with schizophrenia. Psychiatric records and diagnostic interviews of 143 Swedish patients diagnosed by their treating physician with schizophrenia and related disorders were scrutinized. Based on record analysis only, or a combined record and interview analysis, DSM-IV diagnoses were obtained by the OPCRIT algorithm. Independent of the OPCRIT algorithm, a standard research DSM-IV diagnosis, based on both record and interview analysis, was given by the research psychiatrist. Concordance rates for the different psychosis diagnoses were calculated. DSM-IV diagnoses based on records only, showed a good to excellent agreement with diagnoses based on records and interviews. Swedish register diagnoses displayed generally poor agreement with the research diagnoses. Nevertheless, 94% of subjects sometimes registered with a diagnosis of schizophrenic psychoses (i.e. schizophrenia, schizoaffective psychosis or schizophreniform disorder) displayed a standard research DSM-IV diagnosis of these disorders. For patients in long-term treatment for schizophrenia in Sweden, psychiatric record reviews should be optimal, cost effective and sufficient for assessment of lifetime research diagnoses of schizophrenia. For these patients a research interview adds little new information. The results further indicate that a Swedish register diagnosis of schizophrenic psychoses has a high positive predictive power to a standard research DSM-IV diagnosis of the disorders. It is concluded that for future Swedish large-scale genetic studies focusing on a broad definition of schizophrenia, it would be sufficient to rely on the Swedish register diagnoses of schizophrenic psychosis.
Asunto(s)
Manual Diagnóstico y Estadístico de los Trastornos Mentales , Entrevista Psicológica , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/epidemiología , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiología , Adulto , Anciano , Algoritmos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Sistema de Registros , Suecia/epidemiologíaRESUMEN
BACKGROUND: It has been recently reported that a functional variant in the ZDHHC8 gene encoding a putative palmitoyltransferase directly confers susceptibility to schizophrenia in females (). METHODS: We investigated the putative risk allele (rs175174) in four schizophrenia association samples including a Bulgarian proband and parent sample (474 trios) and three case-control panels of European origin (1028 patients/1253 control subjects) in an attempt to replicate these findings. RESULTS: Our results do not support the hypothesis that genetic variation at rs175174 is associated with increased risk for schizophrenia nor do they suggest the presence of gender-specific differences. CONCLUSIONS: Our data suggest that the reported genetic association by either represents type I error resulting from sampling variance or that rs175174 is in linkage disequilibrium (LD) with the functional variant for schizophrenia and different LD patterns obscure the detection of association.
Asunto(s)
Aciltransferasas/genética , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple/genética , Esquizofrenia/genética , Población Blanca/genética , Alelos , Bulgaria/etnología , Niño , Cromosomas Humanos Par 22 , Femenino , Predisposición Genética a la Enfermedad/genética , Variación Genética , Humanos , Desequilibrio de Ligamiento , Masculino , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Riesgo , Esquizofrenia/enzimología , Factores Sexuales , Dedos de Zinc/genéticaRESUMEN
BACKGROUND AND PURPOSE: In MR spectroscopic imaging (MRSI), the volume-selection profiles of metabolites differ from each other. These differences cause variations in metabolite intensities, which are particularly prominent when the hippocampi are evaluated. We hypothesize that the errors arising from these effects cause notable artifact when temporal lobe epilepsy (TLE) is lateralized with MRSI. METHODS: We examined a metabolite phantom, control subjects, and patients with TLE by using MRSI. We calculated the error arising from the different volume-selection profiles of metabolites in vitro and evaluated this correction in the examination of the control subjects and in the lateralization of epilepsy in the patients. RESULTS: Without a correction, a considerable error in the metabolite content existed, even deep inside the spectroscopic volume of interest. The result was false asymmetry (P < .008) in the hippocampi of control subjects. Among the 11 patients, TLE was correctly lateralized in three only after the correction was made, and in one, TLE was incorrectly lateralized. CONCLUSION: The volume-selection profiles of N-acetylaspartate, choline, and creatine differ enough to cause a significant error, even in the metabolite ratios, when patients with TLE are examined with MRSI. We propose a simple phantom method to correct for this error without a need to modify the pulse sequence.
Asunto(s)
Epilepsia del Lóbulo Temporal/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Concentrations of monoamine metabolites in human cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. CSF monoamine metabolite concentrations are partly determined by genetic influences. METHODS: We investigated possible relationships between DNA polymorphisms in the serotonin 2C receptor (HTR2C), the serotonin 3A receptor (HTR3A), the dopamine D4 receptor (DRD4), and the dopamine beta-hydroxylase (DBH) genes and CSF concentrations of 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 90). RESULTS: The HTR3A 178 C/T variant was associated with 5-HIAA levels (p = 0.02). The DBH-1021 heterozygote genotype was associated with 5-HIAA (p = 0.0005) and HVA (p = 0.009) concentrations. Neither the HTR2C Cys23Ser variant, nor the DRD4 -521 C/T variant were significantly associated with any of the monoamine metabolites. CONCLUSIONS: The present results suggest that the HTR3A and DBH genes may participate in the regulation of dopamine and serotonin turnover rates in the central nervous system.