RESUMEN
Risperidone is commonly used to treat different psychiatric disorders worldwide. Knowledge on dose-concentration relationships of risperidone treatment in children and adolescents with schizophrenia or other psychotic disorders is, however, scarce and no age-specific therapeutic ranges have been established yet. Multicenter data of a therapeutic drug monitoring service were analyzed to evaluate the relationship between risperidone dose and serum concentration of the active moiety (risperidone (RIS) plus its main metabolite 9-hydroxyrisperidone (9-OH-RIS)) in children and adolescents with psychotic disorders. Patient characteristics, doses, serum concentrations and therapeutic outcomes were assessed by standardized measures. The study also aimed to evaluate whether the therapeutic reference range for adults (20-60 ng/ml) is applicable for minors. In the 64 patients (aged 11-18 years) included, a positive correlation between daily dose and the active moiety (RISam) concentration was found (rs = 0.49, p = 0.001) with variation in dose explaining 24% (rs2 = 0.240) of the variability in serum concentrations. While the RISam concentration showed no difference, RIS as well 9-OH-RIS concentrations and the parent to metabolite ratio varied significantly in patients with co-medication of a CYP2D6 inhibitor. Patients with extrapyramidal symptoms (EPS) had on average higher RISam concentrations than patients without (p = 0.05). Considering EPS, the upper threshold of the therapeutic range of RISam was determined to be 33 ng/ml. A rough estimation method also indicated a possibly decreased lower limit of the preliminary therapeutic range in minors compared to adults. These preliminary data may contribute to the definition of a therapeutic window in children and adolescents with schizophrenic disorders treated with risperidone. TDM is recommended in this vulnerable population to prevent concentration-related adverse drug reactions.
Asunto(s)
Antipsicóticos , Enfermedades de los Ganglios Basales , Trastornos Psicóticos , Esquizofrenia , Adolescente , Adulto , Antipsicóticos/efectos adversos , Enfermedades de los Ganglios Basales/inducido químicamente , Niño , Monitoreo de Drogas , Humanos , Palmitato de Paliperidona/uso terapéutico , Trastornos Psicóticos/tratamiento farmacológico , Risperidona/uso terapéutico , Esquizofrenia/tratamiento farmacológicoRESUMEN
Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelopmental disorders. To identify rare (frequency ≤1%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls (P=2.8 × 10(-4) after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients (P=1.2 × 10(-3) after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control (P=4.3 × 10(-2)). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/genética , Variaciones en el Número de Copia de ADN/genética , Predisposición Genética a la Enfermedad , Ubiquitina-Proteína Ligasas/genética , Adolescente , Adulto , Anciano , Niño , Planificación en Salud Comunitaria , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
In previous studies of a genetic isolate, we identified significant linkage of attention deficit hyperactivity disorder (ADHD) to 4q, 5q, 8q, 11q and 17p. The existence of unique large size families linked to multiple regions, and the fact that these families came from an isolated population, we hypothesized that two-locus interaction contributions to ADHD were plausible. Several analytical models converged to show significant interaction between 4q and 11q (P<1 × 10(-8)) and 11q and 17p (P<1 × 10(-6)). As we have identified that common variants of the LPHN3 gene were responsible for the 4q linkage signal, we focused on 4q-11q interaction to determine that single-nucleotide polymorphisms (SNPs) harbored in the LPHN3 gene interact with SNPs spanning the 11q region that contains DRD2 and NCAM1 genes, to double the risk of developing ADHD. This interaction not only explains genetic effects much better than taking each of these loci effects by separated but also differences in brain metabolism as depicted by proton magnetic resonance spectroscopy data and pharmacogenetic response to stimulant medication. These findings not only add information about how high order genetic interactions might be implicated in conferring susceptibility to develop ADHD but also show that future studies of the effects of genetic interactions on ADHD clinical information will help to shape predictive models of individual outcome.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/genética , Cromosomas Humanos Par 11/genética , Ligamiento Genético/genética , Predisposición Genética a la Enfermedad/genética , Receptores Acoplados a Proteínas G/genética , Receptores de Péptidos/genética , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Encéfalo/metabolismo , Estudios de Casos y Controles , Colina/metabolismo , Glutamina/metabolismo , Humanos , Inositol/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Metilfenidato/uso terapéutico , Polimorfismo de Nucleótido Simple/genética , ProtonesRESUMEN
Bipolar disorder (BD) and attention deficit/hyperactivity disorder (ADHD) may share common genetic risk factors as indicated by the high co-morbidity of BD and ADHD, their phenotypic overlap especially in pediatric populations, the high heritability of both disorders, and the co-occurrence in families. We therefore examined whether known polygenic BD risk alleles are associated with ADHD. We chose the eight best SNPs of the recent genome-wide association study (GWAS) of BD patients of German ancestry and the nine SNPs from international GWAS meeting a 'genome-wide significance' level of α = 5 × 10(-8). A GWAS was performed in 495 ADHD children and 1,300 population-based controls using HumanHap550v3 and Human660 W-Quadv1 BeadArrays. We found no significant association of childhood ADHD with single BD risk alleles surviving adjustment for multiple testing. Yet, risk alleles for BD and ADHD were directionally consistent at eight of nine loci with the strongest support for three SNPs in or near NCAN, BRE, and LMAN2L. The polygene analysis for the BP risk alleles at all 14 loci indicated a higher probability of being a BD risk allele carrier in the ADHD cases as compared to the controls. At a moderate power to detect association with ADHD, if true effects were close to estimates from GWAS for BD, our results suggest that the possible contribution of BD risk variants to childhood ADHD risk is considerably lower than for BD. Yet, our findings should encourage researchers to search for common genetic risk factors in BD and childhood ADHD in future studies.
Asunto(s)
Alelos , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno Bipolar/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno Bipolar/complicaciones , Niño , Femenino , Estudio de Asociación del Genoma Completo , Haplotipos , Humanos , Masculino , Población Blanca/genéticaRESUMEN
Dyslexia is one of the most common learning disorders affecting about 5% of all school-aged children. It has been shown that event-related potential measurements reveal differences between dyslexic children and age-matched controls. This holds particularly true for mismatch negativity (MMN), which reflects automatic speech deviance processing and is altered in dyslexic children. We performed a whole-genome association analysis in 200 dyslexic children, focusing on MMN measurements. We identified rs4234898, a marker located on chromosome 4q32.1, to be significantly associated with the late MMN component. This association could be replicated in an independent second sample of 186 dyslexic children, reaching genome-wide significance in the combined sample (P = 5.14e-08). We also found an association between the late MMN component and a two-marker haplotype of rs4234898 and rs11100040, one of its neighboring single nucleotide polymorphisms (SNPs). In the combined sample, this marker combination withstands correction for multiple testing (P = 6.71e-08). Both SNPs lie in a region devoid of any protein-coding genes; however, they both show significant association with mRNA-expression levels of SLC2A3 on chromosome 12, the predominant facilitative glucose transporter in neurons. Our results suggest a possible trans-regulation effect on SLC2A3, which might lead to glucose deficits in dyslexic children and could explain their attenuated MMN in passive listening tasks.
Asunto(s)
Cromosomas Humanos Par 4 , Dislexia/genética , Potenciales Evocados Auditivos/genética , Transportador de Glucosa de Tipo 3/genética , Percepción del Habla/genética , Adolescente , Estudios de Casos y Controles , Niño , Variación Contingente Negativa/genética , Discriminación en Psicología/fisiología , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Valores de Referencia , Adulto JovenRESUMEN
Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental syndrome characterized by hyperactivity, inattention and increased impulsivity. To detect micro-deletions and micro-duplications that may have a role in the pathogenesis of ADHD, we carried out a genome-wide screen for copy number variations (CNVs) in a cohort of 99 children and adolescents with severe ADHD. Using high-resolution array comparative genomic hybridization (aCGH), a total of 17 potentially syndrome-associated CNVs were identified. The aberrations comprise 4 deletions and 13 duplications with approximate sizes ranging from 110 kb to 3 Mb. Two CNVs occurred de novo and nine were inherited from a parent with ADHD, whereas five are transmitted by an unaffected parent. Candidates include genes expressing acetylcholine-metabolizing butyrylcholinesterase (BCHE), contained in a de novo chromosome 3q26.1 deletion, and a brain-specific pleckstrin homology domain-containing protein (PLEKHB1), with an established function in primary sensory neurons, in two siblings carrying a 11q13.4 duplication inherited from their affected mother. Other genes potentially influencing ADHD-related psychopathology and involved in aberrations inherited from affected parents are the genes for the mitochondrial NADH dehydrogenase 1 α subcomplex assembly factor 2 (NDUFAF2), the brain-specific phosphodiesterase 4D isoform 6 (PDE4D6) and the neuronal glucose transporter 3 (SLC2A3). The gene encoding neuropeptide Y (NPY) was included in a â¼3 Mb duplication on chromosome 7p15.2-15.3, and investigation of additional family members showed a nominally significant association of this 7p15 duplication with increased NPY plasma concentrations (empirical family-based association test, P=0.023). Lower activation of the left ventral striatum and left posterior insula during anticipation of large rewards or losses elicited by functional magnetic resonance imaging links gene dose-dependent increases in NPY to reward and emotion processing in duplication carriers. These findings implicate CNVs of behaviour-related genes in the pathogenesis of ADHD and are consistent with the notion that both frequent and rare variants influence the development of this common multifactorial syndrome.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/genética , Variaciones en el Número de Copia de ADN/genética , Dosificación de Gen/genética , Neuropéptido Y/genética , Linaje , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/patología , Encéfalo/irrigación sanguínea , Encéfalo/patología , Niño , Mapeo Cromosómico/métodos , Cromosomas Humanos Par 7/genética , Estudios de Cohortes , Hibridación Genómica Comparativa/métodos , Salud de la Familia , Femenino , Estudio de Asociación del Genoma Completo/métodos , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/métodos , Masculino , Neuropéptido Y/sangre , Oxígeno/sangre , FenotipoRESUMEN
Attention-Deficit/Hyperactivity Disorder (ADHD) has a very high heritability (0.8), suggesting that about 80% of phenotypic variance is due to genetic factors. We used the integration of statistical and functional approaches to discover a novel gene that contributes to ADHD. For our statistical approach, we started with a linkage study based on large multigenerational families in a population isolate, followed by fine mapping of targeted regions using a family-based design. Family- and population-based association studies in five samples from disparate regions of the world were used for replication. Brain imaging studies were performed to evaluate gene function. The linkage study discovered a genome region harbored in the Latrophilin 3 gene (LPHN3). In the world-wide samples (total n=6360, with 2627 ADHD cases and 2531 controls) statistical association of LPHN3 and ADHD was confirmed. Functional studies revealed that LPHN3 variants are expressed in key brain regions related to attention and activity, affect metabolism in neural circuits implicated in ADHD, and are associated with response to stimulant medication. Linkage and replicated association of ADHD with a novel non-candidate gene (LPHN3) provide new insights into the genetics, neurobiology, and treatment of ADHD.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/genética , Estimulantes del Sistema Nervioso Central/uso terapéutico , Predisposición Genética a la Enfermedad , Receptores Acoplados a Proteínas G/genética , Receptores de Péptidos/genética , Adolescente , Adulto , Encéfalo/metabolismo , Supervivencia Celular/genética , Niño , Preescolar , Mapeo Cromosómico , Femenino , Ligamiento Genético , Genotipo , Humanos , Espectroscopía de Resonancia Magnética/métodos , Masculino , Polimorfismo Genético , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Péptidos/metabolismoRESUMEN
Previous genome-wide linkage studies applied the affected sib-pair design; one investigated extended pedigrees of a genetic isolate. Here, results of a genome-wide high-density linkage scan of attention-deficit/hyperactivity disorder (ADHD) using an array-based genotyping of approximately 50 K single nucleotide polymorphism (SNPs) markers are presented. We investigated eight extended pedigrees of German origin that were non-related, not part of a genetic isolate and ascertained on the basis of clinical referral. Two parametric analyses maximizing LOD scores (MOD) and a non-parametric analysis for both a broad and a narrow phenotype approach were conducted. Novel linkage loci across all families were detected at 2q35, 5q13.1, 6q22-23 and 14q12, within individual families at 18q11.2-12.3. Further linkage regions at 7q21.11, 9q22 and 16q24.1 in all families, and at 1q25.1, 1q25.3, 9q31.1-33.1, 9q33, 12p13.33, 15q11.2-13.3 and 16p12.3-12.2 in individual families replicate previous findings. High-resolution linkage mapping points to several novel candidate genes characterized by dense expression in the brain and potential impact on disorder-relevant synaptic transmission. Our study provides further evidence for common gene effects throughout different populations despite the complex multifactorial etiology of ADHD.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/genética , Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 5/genética , Polimorfismo de Nucleótido Simple , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Niño , Femenino , Genotipo , Alemania/epidemiología , Humanos , Escala de Lod , Masculino , Variaciones Dependientes del Observador , Análisis de Secuencia por Matrices de Oligonucleótidos , Linaje , Índice de Severidad de la Enfermedad , Estadísticas no ParamétricasRESUMEN
UNLABELLED: Tramadol is currently one of the most frequently used opioid analgesics in the world. OBJECTIVE: The objective of this study was to investigate the rate and extent of tramadol bioavailability following evening versus morning intake of an extended-release pellet system designed for once daily administration. Moreover, the suitability of the preparation for chrono-adjusted pharmacotherapy was to be investigated. METHODS: 18 male and female volunteers were enrolled in the study and treated with 200 mg tramadol extended-release capsules, which were to be taken in the fasted state between 7:30 and 8:00 a.m. or p.m., respectively. The parent compound and its O-desmethyl-metabolite were analyzed in plasma samples using a LC-MS/MS procedure. RESULTS: Maximum exposure of tramadol (geometric means of C(max)-values) was determined as 289.3 ng/ml after morning and 283.1 ng/ml after evening administration. Extent of tramadol exposure (geometric means of AUC(0-48)-values) was calculated as 4,802.5 ng x h/ml after morning and 4,767.0 ng x h/ml after evening administration. Also tmax-values were comparable after morning and evening administration (9.00 vs. 9.50 hours). Statistical analyses, based on conventional bioequivalence approach, revealed no evidence of any impact of the time-point of administration on the biopharmaceutical performance of the dosage form investigated here. CONCLUSIONS: Bioavailability of the extended-release tramadol capsules for once daily administration is not affected by the time-point of administration. Total and maximum exposure of the product was bioequivalent after intake in the morning and at night. Thus, the time-point of administration may be adjusted to the patient's needs without any significant change in the in-vivo performance.
Asunto(s)
Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/farmacocinética , Biofarmacia/métodos , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/farmacocinética , Cronoterapia de Medicamentos , Dolor/tratamiento farmacológico , Tramadol/administración & dosificación , Tramadol/farmacocinética , Adulto , Analgésicos Opioides/efectos adversos , Disponibilidad Biológica , Preparaciones de Acción Retardada/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tramadol/efectos adversosRESUMEN
UNLABELLED: Objective of this study was to investigate the rate and extent of tramadol bioavailability following evening versus morning administration. METHODS: The study was performed following an open, randomised, cross-over study-design. 18 male and female volunteers were enrolled into the study and treated with 200 mg tramadol extended-release capsules (T-long), which were to be taken either in the morning or in the evening. RESULTS: Plasma concentration versus time profiles obtained after morning and evening administration were almost superimposable for both, tramadol and its active metabolite. Maximum exposure of tramadol and O-desmethyltramadol (geometric means of c(max)-values) as well as extent of exposure (geometric means of AUC(0-48)-values) were comparable after morning and eveningadministration. CONCLUSIONS: Time-point of administration does not have any relevant impact on the rate and extent of absorption in the investigated dosage form. Thus, time-point of administration may be adjusted to the patient's need in a chronopharmacologically optimised way for pain therapy.
Asunto(s)
Analgésicos Opioides/administración & dosificación , Dolor/tratamiento farmacológico , Tramadol/administración & dosificación , Adulto , Analgésicos Opioides/sangre , Analgésicos Opioides/farmacocinética , Artritis Reumatoide/tratamiento farmacológico , Disponibilidad Biológica , Cápsulas , Ritmo Circadiano , Intervalos de Confianza , Estudios Cruzados , Preparaciones de Acción Retardada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Selección de Paciente , Factores de Tiempo , Tramadol/sangre , Tramadol/farmacocinéticaRESUMEN
Methylphenidate (MPH) is a centrally acting (psycho)stimulant which reversibly blocks the dopamine re-uptake transporter. At present MPH is one of the most frequently prescribed drugs for the symptomatic treatment of attention deficit hyperactivity disorder (ADHD). Although MPH has been in use for about 50 years, there is no information available concerning the long-term benefits and risks of medication. Based on experiments in rats it has been suggested that MPH treatment may affect the maturation of central dopaminergic systems and may be a risk factor for the development of Parkinson's disease (PD). The aim of the present case-control study was to gain information about (1) ADHD-like symptoms that may precede PD motor symptoms, and (2) the exposure to psychostimulants in childhood. We used a German short version of the Wender Utah Rating Scale (WURS-k, Retz-Junginger et al., 2002) which is a reliable measure for the retrospective diagnosis of childhood ADHD, and another questionnaire including a rating scale for symptoms of ADHD in childhood (Q-ADHD-Child) according to DSM-IV and ICD-10 criteria. A total of 92 patients with PD and 115 control subjects were enrolled in this study. Ninety-six percentage of PD patients (N = 88) completed the two rating scales. The data of these patients and of 88 randomly selected individuals of the controls were included for analysis. In the WURS-k, the PD group showed higher total scores compared to control subjects. In addition, we found increased scores in PD patients regarding the items attention deficit, hyperactivity and anxious and depressive symptoms, but not regarding impulsivity, oppositional behaviour and deficits in social adaptation. The results of the Q-ADHD-Child also showed increased scores in PD patients regarding attention deficit and hyperactivity. However, one cannot conclude that the PD patients enrolled in this study had suffered from childhood ADHD, since the average total WURS-k score of (14.4) was far below the cut-off score of 30 or higher which is considered to identify childhood ADHD. Finally, we found no evidence that PD patients had been exposed to psychostimulants such as MPH and amphetamine.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Estimulantes del Sistema Nervioso Central/efectos adversos , Metilfenidato/efectos adversos , Enfermedad de Parkinson/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estudios de Casos y Controles , Causalidad , Estimulantes del Sistema Nervioso Central/uso terapéutico , Niño , Comorbilidad , Femenino , Humanos , Cuidados a Largo Plazo , Masculino , Metilfenidato/uso terapéutico , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , Determinación de la Personalidad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Rett syndrome, a common cause of mental retardation in females, is caused by mutations in the MECP2 gene. Most females with MECP2 mutations fulfil the established clinical criteria for Rett syndrome, but single cases of asymptomatic carriers have been described. It is therefore likely that there are individuals falling between these two extreme phenotypes. OBJECTIVE: To describe three patients showing only minor symptoms of Rett syndrome. FINDINGS: The patient with the best intellectual ability had predominantly psychiatric problems with episodes of uncontrolled aggression that have not been described previously in individuals with MECP2 mutations. All three patients had normal hand function, communicated well, and showed short spells of hyperventilation only under stress. Diagnosis in such individuals requires the identification of subtle signs of Rett syndrome in girls with a mild mental handicap. Analysis of the MECP2 gene revealed mutations that are often found in classical Rett syndrome. Skewed X inactivation was present in all three cases, which may explain the mild phenotype. CONCLUSIONS: Because of skewed X inactivation, the phenotype of Rett patients may be very mild and hardly recognisable.
Asunto(s)
Síndrome de Rett/diagnóstico , Inactivación del Cromosoma X/genética , Adolescente , Niño , Análisis Mutacional de ADN , Femenino , Humanos , Leucocitos/patología , Proteína 2 de Unión a Metil-CpG/genética , Fenotipo , Mutación Puntual , Reacción en Cadena de la Polimerasa/métodosRESUMEN
In the ICD-10 classification, the body dysmorphophobic (dysmorphic) disorder is subsumed under the code for somatoform or hypochondriacal disorders (F45.2). To the fore is an excessive preoccupation with an imagined, but not objectifiable, bodily defect, usually affecting a part of the body that is either exposed or considered to be of importance for the patient's attractiveness. In many cases, the patient insistently demands surgical correction. During the further course of the condition, depression, social phobia, obsessive-compulsive and self-destructive behavior may develop. The condition usually begins early in the patient's life, and the lifetime prevalence is estimated to be 5%. Since an involvement of the serotonergic system is assumed, selective serotonin reuptake inhibitors are considered to be the medication of first choice. Surgical interventions do not lead to remission but simply to a transference of symptoms. Referral to a psychiatric specialist with the aim of clarifying the diagnosis is indicated.
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Trastornos Somatomorfos/diagnóstico , Adolescente , Adulto , Estudios Transversales , Deluciones/diagnóstico , Deluciones/psicología , Deluciones/terapia , Diagnóstico Diferencial , Femenino , Humanos , Hipocondriasis/diagnóstico , Hipocondriasis/psicología , Hipocondriasis/terapia , Masculino , Trastornos de la Personalidad/diagnóstico , Trastornos de la Personalidad/psicología , Trastornos de la Personalidad/terapia , Psicoterapia , Derivación y Consulta , Factores Sexuales , Aislamiento Social , Trastornos Somatomorfos/psicología , Trastornos Somatomorfos/terapia , Prevención del SuicidioRESUMEN
Schizophrenic disorders in childhood are rare: 0.1-1 percent of all schizophrenic disorders manifest themselves before age 10, and 4 percent before age 15. There is, however, a remarkable increase in schizophrenia during adolescence. Age and developmental stage also influence symptoms, course, and outcome. The evidence for a male preponderance in the very early-onset group (< 14) does not apply for adolescents over age 14. The presence of positive and negative precursor symptoms can be demonstrated in child and adolescent schizophrenia before the first clinical manifestation leading to inpatient treatment. With regard to pharmacologic treatment, atypical neuroleptics such as clozapine can be used successfully. As to outcome, schizophrenic psychoses with early manifestation have a poor prognosis. The patients' premorbid personality also seems to be of great importance: A poor prognosis can be found in patients who were cognitively impaired, shy, introverted, and withdrawn before the beginning of their psychotic state.
Asunto(s)
Desarrollo de la Personalidad , Esquizofrenia Infantil/diagnóstico , Adolescente , Adulto , Antipsicóticos/uso terapéutico , Niño , Estudios Transversales , Femenino , Alemania/epidemiología , Humanos , Incidencia , Masculino , Admisión del Paciente , Pronóstico , Esquizofrenia Infantil/tratamiento farmacológico , Esquizofrenia Infantil/epidemiología , Factores Sexuales , Resultado del TratamientoRESUMEN
OBJECTIVE: The continuous performance test (CPT) is successfully applied to evaluate attentional performance in attention-deficit hyperactivity disorder (ADHD)-children. The aim of the present study was to investigate the changes of the topographic P300-features in relation to methylphenidate-medication and to different attentional processes in primer- and distractor-conditions. METHODS: Twenty-one-channel-ERPs of 17 ADHD-boys were analyzed with reference-independent methods. Four quasi stable microstates within the time frames of conventional P100, P200, P3a and P3b components were identified by means of a data-driven segmentation procedure. RESULTS: In segment 3 topographical assessment yielded a significant occipital and right-shift of the positive centroid, longer centroid distance and higher amplitudes in primer- than in distractor conditions. MPH increased the amplitude and distance in primer and distractor-condition, without changing the topography. In segment 4 the electric field strength of distractor-conditions collapsed, whereas the primer condition showed a strong fronto-parietally oriented potential-field. There was a tendency to higher amplitudes due to MPH-medication. CONCLUSIONS: These results indicate a robust neurophysiologic differentiation of cognitive processes. MPH activates an early (P3a) covert attention process indicated by increased amplitudes and centroid. No effects were seen in later processes. Based on these effects, we propose to use the amplitude- and distance-increase in microstate 3 as an indicator of MPH efficacy in ADHD-boys.
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Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/psicología , Encéfalo/fisiología , Estimulantes del Sistema Nervioso Central/uso terapéutico , Electroencefalografía , Metilfenidato/uso terapéutico , Desempeño Psicomotor/fisiología , Adulto , Potenciales Relacionados con Evento P300/efectos de los fármacos , Potenciales Relacionados con Evento P300/fisiología , Humanos , Masculino , Pruebas NeuropsicológicasRESUMEN
OBJECTIVE: Several studies presented evidence for magnocellular deficits in dyslexics both in behavioural as well as in electrophysiological data of local electrode sites. We investigated two well-known paradigms (motion-onset and random-dot-kinematogram) with regard to global electrophysiological parameters. METHODS: Twenty-one-channel event-related potentials (ERPs) of 16 dyslectic and 15 control children were analyzed with reference-independent methods. For each paradigm quasi stable microstates were identified by means of a data-driven segmentation procedure and compared between both groups. RESULTS: Differences in global ERP responses between dyslexic and control children could be found for rapid moving gratings but not for the dot coherence. CONCLUSIONS: Dyslexic children seem to have some highly specific visual deficits in processing moving stimuli. These deficits can be related to the magnocellular system.
Asunto(s)
Dislexia/fisiopatología , Percepción Visual/fisiología , Niño , Electroencefalografía , Electrofisiología , Potenciales Relacionados con Evento P300/fisiología , Femenino , Humanos , Masculino , Movimiento/fisiología , Estimulación LuminosaRESUMEN
OBJECTIVES: This case report deals with the day care treatment of two seven- and eight-year-old siblings with elective mutism. Their treatment entails a combination of psychopharmacological and intensive behavior therapy. The multimodal therapeutic process is presented together with continuing psychosocial steps. Behavioral intervention focuses on building verbal expressive capacity, reducing speech anxiety in social situations and generalization to non-therapeutic situations. The case report is discussed in the context of the current literature on elective mutism.
Asunto(s)
Terapia Conductista , Centros de Día/psicología , Mutismo/terapia , Paroxetina/administración & dosificación , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Hermanos/psicología , Aculturación , Niño , Terapia Combinada , Etnicidad/psicología , Femenino , Alemania , Humanos , Mutismo/etnología , Mutismo/psicología , Trastornos Fóbicos/etnología , Trastornos Fóbicos/psicología , Trastornos Fóbicos/terapia , Timidez , Medio Social , Aislamiento Social , Tailandia/etnologíaRESUMEN
OBJECTIVES: We present a retrospective study of 140 patients (110 with anorexia nervosa, 30 with bulimia nervosa), hospitalized between 1982-1992 at the Department of Child and Adolescent Psychiatry at the University of Wuerzburg, Germany. METHODS: All patients met the ICD-10 criteria for anorexia nervosa or bulimia nervosa. We collected data from basic documentation and the multiaxial classification (MAS), using a variety of standard instruments such as Anis 32, MMPI, BDI, HAWIK-R and HAWIE. RESULTS: Our findings show significant differences between the two populations. At the time of their first admission anorectic patients were somewhat younger than their bulimic counterparts (14.5 years vs. 16.5 years, respectively). With regard to the typical symptoms of either disorder, the two populations differ in their eating behavior on the factor bulimia described by Anis-32. A comparison of personality features reveals that anorectic patients scored lower than bulimic patients on the MMPI scales, especially on psychopathology, but higher on depression in the BDI. Other characteristics of anorectic patients include a higher-than-average IQ, more enmeshment and overprotectiveness in family relations, more separation anxiety and insufficient communication skills at school. By contrast, bulimic patients demonstrated poorer scholastic performance and more discipline problems at school, while communication among family members was impaired.