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Despite the high prevalence of neurodevelopmental disorders, there is a notable gap in clinical studies exploring the impact of maternal diet during pregnancy on child neurodevelopment. This observational clinical study examined the association between pregnancy dietary patterns and neurodevelopmental disorders, as well as their symptoms, in a prospective cohort of 10-year-old children (n=508). Data-driven dietary patterns were derived from self-reported food frequency questionnaires. A Western dietary pattern in pregnancy (per SD change) was significantly associated with attention-deficit / hyperactivity disorder (ADHD) (OR 1.66 [1.21 - 2.27], p=0.002) and autism diagnosis (OR 2.22 [1.33 - 3.74], p=0.002) and associated symptoms (p<0.001). Findings for ADHD were validated in three large (n=59725, n=656, n=348), independent mother-child cohorts. Objective blood metabolome modelling at 24 weeks gestation identified 15 causally mediating metabolites which significantly improved ADHD prediction in external validation. Temporal analyses across five blood metabolome timepoints in two independent mother-child cohorts revealed that the association of Western dietary pattern metabolite scores with neurodevelopmental outcomes was consistently significant in early to mid-pregnancy, independent of later child timepoints. These findings underscore the importance of early intervention and provide robust evidence for targeted prenatal dietary interventions to prevent neurodevelopmental disorders in children.
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BACKGROUND: Sex differences in brain structure and neurodevelopment occur in non-clinical populations. We investigated whether sex had a similar effect on developmental domains amongst boys and girls with a familial risk of schizophrenia (FHR-SZ), bipolar disorder (FHR-BP), and controls. METHODS: Through Danish registries, we identified 522 7-year-old children (242 girls) with FHR-SZ, FHR-BP, and controls. We assessed their performance within the domains of neurocognition, motor function, language, social cognition, social behavior, psychopathology, and home environment. RESULTS: FHR-SZ boys compared with FHR-SZ girls had a higher proportion of disruptive behavior and attention-deficit hyperactivity disorder (ADHD) and exhibited lower performance in manual dexterity, balance, and emotion recognition. No sex differences were found between boys and girls within FHR-BP group. Compared with controls, both FHR-SZ boys and FHR-SZ girls showed impaired processing speed and working memory, had lower levels of global functioning, and were more likely to live in an inadequate home environment. Compared with control boys, FHR-SZ boys showed impaired manual dexterity, social behavior, and social responsiveness, and had a higher proportion of ADHD and disruptive behavior disorder diagnoses. Stress and adjustment disorders were more common in FHR-BP boys compared with control boys. We found no differences between FHR-BP girls and control girls. CONCLUSIONS: Impairment within neurodevelopmental domains associated within FHR-SZ boys v. FHR-SZ girls was most evident among boys, whereas no sex differences were found within the FHR-BP group (FHR-BP boys v. FHR-BP girls). FHR-SZ boys exhibited the highest proportion of early developmental impairments.
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Trastorno por Déficit de Atención con Hiperactividad , Trastorno Bipolar , Esquizofrenia , Masculino , Femenino , Humanos , Niño , Predisposición Genética a la Enfermedad , Trastorno Bipolar/epidemiología , Trastorno Bipolar/psicología , Esquizofrenia/epidemiología , Conducta Social , Trastorno por Déficit de Atención con Hiperactividad/epidemiologíaRESUMEN
Many psychiatric and neurodevelopmental disorders are known to be heritable, but studies trying to elucidate the genetic architecture of such traits often lag behind studies of somatic traits and diseases. The reasons as to why relatively few genome-wide significant associations have been reported for such traits have to do with the sample sizes needed for the detection of small effects, the difficulty in defining and characterizing the phenotypes, partially due to overlaps in affected underlying domains (which is especially true for cognitive phenotypes), and the complex genetic architectures of the phenotypes, which are not wholly captured in traditional case-control GWAS designs. We aimed to tackle the last two issues by performing GWASs of eight quantitative neurocognitive, motor, social-cognitive and social-behavioral traits, which may be considered endophenotypes for a variety of psychiatric and neurodevelopmental conditions, and for which we employed models capturing both general genetic association and parent-of-origin effects, in a family-based sample comprising 402 children and their parents (mostly family trios). We identified 48 genome-wide significant associations across several traits, of which 3 also survived our strict study-wide quality criteria. We additionally performed a functional annotation of implicated genes, as most of the 48 associations were with variants within protein-coding genes. In total, our study highlighted associations with five genes (TGM3, CACNB4, ANKS1B, CSMD1 and SYNE1) associated with measures of working memory, processing speed and social behavior. Our results thus identify novel associations, including previously unreported parent-of-origin associations with relevant genes, and our top results illustrate new potential gene â endophenotype â disorder pathways.
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Epigenómica , Genes Reguladores , Endofenotipos , Cognición , Epigénesis GenéticaRESUMEN
BACKGROUND: Psychiatric disorders are highly polygenic and show patterns of partner resemblance. Partner resemblance has direct population-level genetic implications if it is caused by assortative mating, but not if it is caused by convergence or social homogamy. Using genetics may help distinguish these different mechanisms. Here, we investigated whether partner resemblance for schizophrenia and bipolar disorder is influenced by assortative mating using polygenic risk scores (PRSs). METHODS: PRSs from The Danish High-Risk and Resilience Study-VIA 7 were compared between parents in three subsamples: population-based control parent pairs (N=198), parent pairs where at least one parent had schizophrenia (N=193), and parent pairs where at least one parent had bipolar disorder (N=115). RESULTS: The PRS for schizophrenia was predictive of schizophrenia in the full sample and showed a significant correlation between parent pairs (r=0.121, p=0.0440), indicative of assortative mating. The PRS for bipolar disorder was also correlated between parent pairs (r=0.162, p=0.0067), but it was not predictive of bipolar disorder in the full sample, limiting the interpretation. CONCLUSIONS: Our study provides genetic evidence for assortative mating for schizophrenia, with important implications for our understanding of the genetics of schizophrenia.
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Trastorno Bipolar , Esquizofrenia , Trastorno Bipolar/genética , Humanos , Padres , Esquizofrenia/genéticaRESUMEN
The cognitive control system matures gradually with age and shows age-related sex differences. To gain knowledge concerning error adaptation in familial high-risk groups, investigating error adaptation among the offspring of parents with severe mental disorders is important and may contribute to the understanding of cognitive functioning in at-risk individuals. We identified an observational cohort through Danish registries and measured error adaptation using an Eriksen flanker paradigm. We tested 497 7-year-old children with a familial high risk of schizophrenia (N = 192) or bipolar disorder (N = 116) for deficits in error adaptation compared with a control group (N = 189). We investigated whether error adaptation differed between high-risk groups compared with controls and sex differences in the adaptation to errors, irrespective of high-risk status. Overall, children exhibited post-error slowing (PES), but the slowing of responses did not translate to significant improvements in accuracy. No differences were detected between either high-risk group compared with the controls. Boys showed less PES and PES after incongruent trials than girls. Our results suggest that familial high risk of severe mental disorders does not influence error adaptation at this early stage of cognitive control development. Error adaptation behavior at age 7 years shows specific sex differences.
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Impaired cognitive test performance is well-documented in subjects at ultra-high risk (UHR) for psychosis. However, assessment of cognitive deficits as manifested in real life is a neglected area of UHR research that may add to the understanding of cognitive impairment and its relationship with psychosocial functioning and positive symptomatology. This study applied the interview-based Schizophrenia Cognition Rating Scale (SCoRS) and the questionnaire-based Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) in a cross-sectional sample of 39 UHR subjects and 50 healthy controls. Cognitive test performance, psychosocial functioning, and positive symptoms were also assessed. The UHR subjects demonstrated significant cognitive impairment, with large effect sizes for the SCoRS and BRIEF-A composite outcome variables (rs = -0.67 to -0.80) and a neurocognitive composite score (d = -0.97). Within the UHR group, several significant associations between worse cognitive ratings and worse cognitive test performance (rs = -0.210 to -0.343), poorer psychosocial functioning (rs = -0.058 to -0.728), and worse positive symptoms (rs= 0.415 to 0.478) were found. Worse cognitive test performance showed significant associations with more pronounced positive symptoms (rs = -0.299 to -0.457). Interview and questionnaire assessment may hold promise for supplementing traditional performance-based cognitive assessment in identifying treatment targets in the UHR population.
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Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Escalas de Valoración Psiquiátrica , Funcionamiento Psicosocial , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/psicología , Encuestas y Cuestionarios , Adolescente , Adulto , Disfunción Cognitiva/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Trastornos Psicóticos/epidemiología , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Individuals at ultra-high risk for psychosis (UHR) present with subtle alterations in cerebral white matter (WM), which appear to be associated with clinical and functional outcome. The effect of cognitive remediation on WM organization in UHR individuals has not been investigated previously. METHODS: In a randomized, clinical trial, UHR individuals aged 18 to 40 years were assigned to treatment as usual (TAU) or TAU plus cognitive remediation for 20 weeks. Cognitive remediation comprised 20 x 2-h sessions of neurocognitive and social-cognitive training. Primary outcome was whole brain fractional anisotropy derived from diffusion weighted imaging, statistically tested as an interaction between timepoint and treatment group. Secondary outcomes were restricted to five predefined region of interest (ROI) analyses on fractional anisotropy, axial diffusivity, radial diffusivity and mean diffusivity. For significant timepoint and treatment group interactions within these five ROIs, we explored associations between longitudinal changes in WM and cognitive functions/clinical symptoms. Finally, we explored dose-response effects of cognitive remediation on WM. RESULTS: A total of 111 UHR individuals were included. Attrition-rate was 26%. The cognitive remediation group completed on average 12 h of neurocognitive training, which was considerably lower than per protocol. We found no effect of cognitive remediation on whole-brain FA when compared to treatment as usual. Secondary ROI analyses revealed a nominal significant interaction between timepoint*treatment of AD in left medial lemniscus (P=0.016) which did not survive control for multiple comparisons. The exploratory test showed that this change in AD correlated to improvements of mental flexibility in the cognitive remediation group (p=0.001). We found no dose-response effect of neurocognitive training on WM. CONCLUSIONS: Cognitive remediation comprising 12 h of neurocognitive training on average did not improve global or regional WM organization in UHR individuals. Further investigations of duration and intensity of cognitive training as necessary prerequisites of neuroplasticity-based changes are warranted. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT02098408.
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BACKGROUND: One of the most basic human traits is language. Linguistic ability, and disability, have been shown to have a strong genetic component in family and twin studies, but molecular genetic studies of language phenotypes are scarce, relative to studies of other cognitive traits and neurodevelopmental phenotypes. Moreover, most genetic studies examining such phenotypes do not incorporate parent-of-origin effects, which could account for some of the heritability of the investigated trait. We performed a genome-wide association study of receptive language, examining both child genetic effects and parent-of-origin effects. RESULTS: Using a family-based cohort with 400 children with receptive language scores, we found a genome-wide significant paternal parent-of-origin effect with a SNP, rs11787922, on chromosome 9q21.31, whereby the T allele reduced the mean receptive language score by ~ 23, constituting a reduction of more than 1.5 times the population SD (P = 1.04 × 10-8). We further confirmed that this association was not driven by broader neurodevelopmental diagnoses in the child or a family history of psychiatric diagnoses by incorporating covariates for the above and repeating the analysis. CONCLUSIONS: Our study reports a genome-wide significant association for receptive language skills; to our knowledge, this is the first documented genome-wide significant association for this phenotype. Furthermore, our study illustrates the importance of considering parent-of-origin effects in association studies, particularly in the case of cognitive or neurodevelopmental traits, in which parental genetic data are not always incorporated.
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Predisposición Genética a la Enfermedad/genética , Genotipo , Lenguaje , Polimorfismo de Nucleótido Simple/genética , Alelos , Niño , Preescolar , Estudios de Cohortes , Dinamarca , Femenino , Humanos , Masculino , FenotipoRESUMEN
The nature of facial affect recognition (FAR) deficits in subjects at ultra-high risk (UHR) for psychosis remains unclear. In schizophrenia, associations between FAR impairment and poor neurocognition have been demonstrated meta-analytically, but this potential link is understudied in the UHR population. Our study investigated a cross-sectional sample of UHR subjects (n = 22) and healthy controls (n = 50), with the Degraded Facial Affect Recognition (DFAR) Task and a neurocognitive test battery. Our primary aims were 1. to examine associations between FAR and neurocognition in UHR subjects and 2. to examine if associations differed between cases and controls. The secondary aim was to examine group differences in FAR and neurocognitive performance. In UHR subjects, FAR was significantly associated with working memory, a neurocognitive composite score and intelligence, and at trend level with most other assessed neurocognitive domains, with moderate to large effect sizes. There were no significant associations in controls. Associations between FAR and working memory and the neurocognitive composite score differed significantly between cases and controls. UHR subjects did not differ from controls on DFAR Task performance but showed significant deficits in three of six neurocognitive domains. Results may suggest that FAR is associated with working memory in UHR subjects, possibly reflecting a neurocognitive compensatory mechanism.
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Expresión Facial , Reconocimiento Facial , Inteligencia , Trastornos Psicóticos/diagnóstico , Adolescente , Adulto , Estudios de Casos y Controles , Cognición/fisiología , Estudios Transversales , Femenino , Humanos , Masculino , Memoria a Corto Plazo , Pruebas de Estado Mental y Demencia , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/psicología , Factores de Riesgo , Esquizofrenia/complicacionesRESUMEN
Language is one of the cognitive domains often impaired across many neurodevelopmental disorders. While for some disorders the linguistic deficit is the primary impairment (e.g., specific language impairment, SLI), for others it may accompany broader behavioral problems (e.g., autism). The precise nature of this phenotypic overlap has been the subject of debate. Moreover, several studies have found genetic overlaps across neurodevelopmental disorders. This raises the question of whether these genetic overlaps may correlate with phenotypic overlaps and, if so, in what manner. Here, we apply a genome-wide approach to the study of the linguistic deficit in SLI, autism spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). Using a discovery genome-wide association study of SLI, we generate polygenic risk scores (PRS) in an independent sample which includes children with language impairment, SLI, ASD or ADHD and age-matched controls and perform regression analyses across groups. The SLI-trained PRS significantly predicted risk in the SLI case-control group (adjusted R2 = 6.24%; P = 0.024) but not in the ASD or ADHD case-control groups (adjusted R2 = 0.0004%, 0.01%; P = 0.984, 0.889, respectively) nor for height, used as a negative control (R2 = 0.2%; P = 0.452). Additionally, there was a significant difference in the normalized PRS between children with SLI and children with ASD (common language effect size = 0.66; P = 0.044). Our study suggests no additive common-variant genetic overlap between SLI and ASD and ADHD. This is discussed in the context of phenotypic studies of SLI and related disorders. Autism Res 2020, 13: 369-381. © 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: Language deficits are characteristic of specific language impairment (SLI), but may also be found in other neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Many studies examined the overlaps and differences across the language deficits in these disorders, but few studies have examined the genetic aspect thereof. In this study, we use a genome-wide approach to evaluate whether common genetic variants increasing risk of SLI may also be associated with ASD and ADHD in the same manner. Our results suggest that this is not the case, and we discuss this finding in the context of theories concerning the etiologies of these disorders.
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Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno del Espectro Autista/complicaciones , Estudio de Asociación del Genoma Completo/métodos , Trastorno Específico del Lenguaje/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno del Espectro Autista/genética , Niño , Dinamarca , Femenino , Humanos , Masculino , Trastorno Específico del Lenguaje/genéticaRESUMEN
In schizophrenia patients, cognitive functions appear linked to widespread alterations in cerebral white matter microstructure. Here we examine patterns of associations between regional white matter and cognitive functions in individuals at ultra-high risk for psychosis. One hundred and sixteen individuals at ultra-high risk for psychosis and 49 matched healthy controls underwent 3 T magnetic resonance diffusion-weighted imaging and cognitive assessments. Group differences on fractional anisotropy were tested using tract-based spatial statistics. Group differences in cognitive functions, voxel-wise as well as regional fractional anisotropy were tested using univariate general linear modeling. Multivariate partial least squares correlation analyses tested for associations between patterns of regional fractional anisotropy and cognitive functions. Univariate analyses revealed significant impairments on cognitive functions and lower fractional anisotropy in superior longitudinal fasciculus and cingulate gyrus in individuals at ultra-high risk for psychosis. Partial least squares correlation analysis revealed different associations between patterns of regional fractional anisotropy and cognitive functions in individuals at ultra-high risk for psychosis compared to healthy controls. Widespread higher fractional anisotropy was associated with better cognitive functioning for individuals at ultra-high risk for psychosis, but not for the healthy controls. Furthermore, patterns of cognitive functions were associated with an interaction-effect on regional fractional anisotropy in fornix, medial lemniscus, uncinate fasciculus, and superior cerebellar peduncle. Aberrant associations between patterns of cognitive functions to white matter may be explained by dysmyelination.
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Encéfalo/diagnóstico por imagen , Cognición/fisiología , Imagen de Difusión por Resonancia Magnética/métodos , Trastornos Psicóticos/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adulto , Anisotropía , Encéfalo/fisiopatología , Femenino , Humanos , Masculino , Trastornos Psicóticos/fisiopatología , Trastornos Psicóticos/psicología , Factores de Riesgo , Sustancia Blanca/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: Head-to-head trials to guide antipsychotic treatment choices for paediatric psychosis are urgently needed because extrapolations from adult studies might not be implementable. In this superiority trial with two-sided significance testing, we aimed to compare the efficacy and safety of quetiapine-extended release (quetiapine-ER) versus aripiprazole in children and adolescents with first-episode psychosis, to determine whether differences between the two treatments were sufficient to guide clinicians in their choice of one drug over the other. METHODS: In this multicentre, double-blind, randomised trial in seven Danish university clinics, we recruited children and adolescents aged 12-17 years with a diagnosis of ICD-10 schizophrenia-spectrum disorder, delusional disorder, or affective-spectrum psychotic disorder, and psychotic symptoms scoring at least 4 on at least one of the following Positive and Negative Syndrome Scale (PANSS) items: P1 (delusions), P2 (conceptual disorganisation), P3 (hallucinations), P5 (grandiosity), P6 (suspiciousness/persecution), and G9 (unusual thought content), and a total PANSS score greater than 60. Patients were randomly assigned (1:1) to 12 weeks of treatment with target doses of 600 mg/day of quetiapine-ER (starting from 50 mg/day) or 20 mg/day of aripiprazole (starting from 2·5 mg/day). The assigned drug was titrated over five levels, with 2 days at each dose, and the final dose achieved on day 9. Randomisation was done using a computer-generated concealed sequence with a block size of 8, and stratified by baseline PANSS positive score (≤20 points or >20 points) and age (12-14 years or 15-17 years). Study drugs were administered in identical capsules, and interventions, assessments, and data analysis were done masked. The primary outcome was PANSS positive score. Key adverse outcomes were bodyweight, homoeostatic model of insulin resistance (HOMA-IR), akathisia, and sedation. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01119014. FINDINGS: Between June 10, 2010, and Jan 29, 2014, 231 participants were assessed for elegibility, of whom 113 were randomly assigned to quetiapine-ER (n=55) or aripiprazole (n=58). PANSS positive score did not differ between groups after 12 weeks (adjusted mean change -5·05 [5·46] for quetiapine-ER, -6·21 [5·42] for aripiprazole; p=0·98), but decreased over time in both groups (p<0·0001). Weight gain was more rapid with quetiapine-ER (p=0·0008), with an adjusted mean weight group difference at week 12 of 3·33 kg (SD 7·23; effect size 0·64; p<0·0001). The HOMA-IR group difference at week 12 favoured aripiprazole (adjusted mean log-transformed group difference 0·259 [SD 0·906]; effect size 0·35; p=0·0060). Akathisia was more common with aripiprazole at week 2 (observed in 34 [60%] of 57 patients; estimated 63·5%) than with quetiapine-ER (15 [30%] of 50; estimated 31·3%; p=0·0021), but not at other timepoints. Sedation proportions did not change significantly over time with either intervention (observed at weeks 2, 4, and 12, respectively, for quetiapine-ER in 43 [83%] of 52, 40 [83%] of 48, and 34 [72%] of 47 patients and for aripiprazole in 49 [89%] of 55, 52 [96%] of 54, and 44 [92%] of 48 patients), and the overall estimated probability combining all timepoints was significantly higher for aripiprazole (97·1%) than for quetiapine-ER (89·2%; p=0·012). In addition to sedation and akathisia, the most common adverse events were tremor (42 [79%] patients in the quetiapine-ER group vs 52 [91%] patients in the aripiprazole group), increased duration of sleep (47 [92%] vs 39 [71%]), orthostatic dizziness (42 [78%] vs 46 [81%]), depression (43 [80%] vs 44 [77%]), tension/inner unrest (37 [69%] vs 50 [88%]), failing memory (41 [76%] vs 44 [77%]), and weight gain (46 [87%] vs 38 [68%]). INTERPRETATION: This first head-to-head comparison of quetiapine-ER versus aripiprazole in early-onset psychosis showed no significant group differences in severity of psychopathology after 12 weeks of treatment. Quetiapine-ER was associated with more metabolic adverse events and aripiprazole with more initial akathisia and, unexpectedly, more sedation. The limited antipsychotic efficacy and high level of adverse events were noticeable. This trial provides novel information for the treatment of early-onset psychosis and highlights the importance of adverse event profiles when choosing among antipsychotics for children and adolescents who often require chronic treatment. FUNDING: The National Research Council for Health and Disease Foundation for Health Promotion, AP Møller Foundation, Rosalie Petersens Foundation, Stevn and Rindom Foundation, Foundation for the Promotion of Medical Science, The Capital Region Psychiatric Research Foundation, Tryg Foundation, Region of Southern Denmark Research Foundation, Danish Psychiatric Research Educational Fund, Psychiatry Foundation, Foundation of 17-12-1981, Psychiatric Research Foundation Region Zealand, Capital Region Strategic Research Foundation, Knud og Dagny Andresens Foundation, Psychiatric Research Foundation of 1967, The Capital Region Research Foundation, Dr Sofus Carl Emil Friis and Hustru Olga Friis Scholarship, Tømrerhandler Johannes Fogs Foundation, Brdr Hartmanns Foundation DKK, Aase and Ejnar Danielsens Foundation, Jacob Madsen and wife Olga Madsens Foundation, CC Klestrup and wife Scholarship, Lundbeck Foundation Scholarship, and Tømrermester Jørgen Holm and wife Elisas Scholarship.
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Antipsicóticos/administración & dosificación , Aripiprazol/administración & dosificación , Trastornos Psicóticos/tratamiento farmacológico , Fumarato de Quetiapina/administración & dosificación , Adolescente , Antipsicóticos/efectos adversos , Aripiprazol/efectos adversos , Niño , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/efectos adversos , Dinamarca , Método Doble Ciego , Femenino , Humanos , Masculino , Escalas de Valoración Psiquiátrica , Fumarato de Quetiapina/efectos adversos , Análisis de Regresión , Resultado del Tratamiento , Aumento de PesoRESUMEN
BACKGROUND: The evidence for choices between antipsychotics for children and adolescents with schizophrenia and other psychotic disorders is limited. The main objective of the Tolerability and Efficacy of Antipsychotics (TEA) trial is to compare the benefits and harms of quetiapine versus aripiprazole in children and adolescents with psychosis in order to inform rational, effective and safe treatment selections. METHODS/DESIGN: The TEA trial is a Danish investigator-initiated, independently funded, multi-centre, randomised, blinded clinical trial. Based on sample size estimation, 112 patients aged 12-17 years with psychosis, antipsychotic-naïve or treated for a limited period are, 1:1 randomised to a 12- week, double-blind intervention with quetiapine versus aripiprazole. Effects on psychopathology, cognition, health-related quality of life, and adverse events are assessed 2, 4, and 12 weeks after randomisation. The primary outcome is change in the positive symptom score of the Positive and Negative Syndrome Scale. The recruitment period is 2010-2014. DISCUSSION: Antipsychotics are currently the only available pharmacologic treatments for psychotic disorders. However, information about head-to-head differences in efficacy and tolerability of antipsychotics are scarce in children and adolescents. The TEA trial aims at expanding the evidence base for the use of antipsychotics in early onset psychosis in order to inform more rational treatment decisions in this vulnerable population. Here, we account for the trial design, address methodological challenges, and discuss the estimation of sample size. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01119014.
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Antipsicóticos/uso terapéutico , Dibenzotiazepinas/uso terapéutico , Piperazinas/uso terapéutico , Trastornos Psicóticos/tratamiento farmacológico , Quinolonas/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Adolescente , Aripiprazol , Niño , Método Doble Ciego , Femenino , Humanos , Masculino , Selección de Paciente , Calidad de Vida , Fumarato de Quetiapina , Tamaño de la MuestraRESUMEN
The few existing long-term, neuropsychological follow-up studies of early onset schizophrenia (EOS) patients have reported relative stability in some cognitive functions but abnormal developmental trajectories in verbal memory, set shifting, aspects of attention, and speed of information processing throughout late adolescence into early adulthood. The current 5-year follow-up study compared the development of specific cognitive functions in EOS patients (N = 17) from the time of first-episode to chronic phase with that of healthy controls (N = 38) and secondarily to patients with other early onset, non-organic, non-affective psychoses (EOP) (N = 11). Speed of processing of executive functions, set shifting, and attention improved significantly in the healthy controls and reflected continuous functional maturation during late adolescence and early adulthood. The developmental progression of attention and set shifting but not speed of processing of executive functions was significantly subnormal in EOS patients. Other specific cognitive functions that had attained functional maturity in the healthy controls before or around the time of the baseline assessment showed normal development in EOS patients during the follow-up period, indicating stable cognitive deficits. These results suggest post-onset developmental deficits in two out of the three aspects of attention and executive functions that have protracted maturational trajectories and that overlap the age of onset of EOS. No significant difference in the development of any specific cognitive function was found between the EOS and EOP group.
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Atención , Función Ejecutiva , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Adolescente , Edad de Inicio , Estudios de Seguimiento , Humanos , Masculino , Pruebas Neuropsicológicas , Esquizofrenia/fisiopatologíaRESUMEN
OBJECTIVE: To characterize the relationship between IQ and attention deficits in children with ADHD and to estimate the inattention-related mean influence on IQ when children are tested before stimulant drug treatment has been initiated. METHOD: Studies of various methodologies are reviewed. RESULTS: Correlation studies show mostly weak associations between IQ scores and attention deficits. Meta-analyses report the average short-term stimulant treatment effect on IQ in children with ADHD to be 2 to 7 IQ points. CONCLUSION: The associations between IQ and attention deficits in ADHD are generally modest, with the mean influence on IQ probably amounting to 2 to 5 IQ points. This may serve as a benchmark when clinicians interpret the validity of IQ in this clinical population.
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Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Atención , Trastornos del Conocimiento/diagnóstico , Pruebas Neuropsicológicas/estadística & datos numéricos , Escalas de Wechsler/estadística & datos numéricos , Adolescente , Atención/fisiología , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/psicología , Estimulantes del Sistema Nervioso Central/uso terapéutico , Niño , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Masculino , Metaanálisis como Asunto , Escalas de Valoración Psiquiátrica , Psicometría , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
The Five to Fifteen parent questionnaire (FTF) was developed to offer a neuropsychological dimension to the assessment of children with Attention Deficit/Hyperactivity Disorder and other child psychiatric disorders. The domains included in the FTF were motor skills, executive functions, perception, memory, language, social skills and learning, in addition to a domain for emotional and behavioural problems. The aim of the present study was to test the clinical validity and utility of the FTF with a main focus on discriminant and criterion validity. The clinical sample consisted of 155 clinically diagnosed children (ICD-10 criteria), 102 were tested with WISC-III. The parents rated their children independent of the diagnostic evaluation. The results were presented as profiles. These clinical profiles were compared to those of a Swedish norm sample consisting of 854 children from the age of five to fifteen. Results demonstrated that the profiles for the clinical groups were similar in forms and levels to those of the upper 10 percent of the norm sample (those with most difficulties). Five out of eight FTF domains discriminated significantly between diagnostic groups in the clinical sample. Influence of IQ, gender and age on the results were low. Three out of four relevant FTF domains correlated significantly with corresponding WISC-III indexes/measures. The clinical utility of individual children's profiles were demonstrated. On the whole, the findings supported the clinical validity and utility of the FTF.