RESUMEN
Autism is an etiologic heterogeneous entity caused by many different diseases occurring in the central nervous system at an early stage in life. Several metabolic defects have been associated with autistic symptoms with a rate higher than that found in the general population. Inborn errors of metabolism can probably account for less than 5% of individuals. Selective metabolic testing should be done in the presence of suggestive clinical findings, including lethargy, cyclic vomiting, early seizures, dysmorphic features, and mental retardation. In some patients, early diagnosis of the metabolic disorders and proper therapeutic interventions may significantly improve the long-term cognitive and behavioral outcome.
Asunto(s)
Trastorno Autístico/complicaciones , Encéfalo/metabolismo , Enfermedades Metabólicas/complicaciones , Errores Innatos del Metabolismo/complicaciones , Trastorno Autístico/metabolismo , Encéfalo/fisiopatología , Femenino , Humanos , Masculino , Enfermedades Metabólicas/clasificación , Errores Innatos del Metabolismo/clasificaciónRESUMEN
Some clinical studies on attention deficit hyperactivity disorder (ADHD) have been found to overlap those of studies on personality, particularly those on the Novelty Seeking trait (NS) as measured by the Junior Temperament and Character Inventory (JTCI). The aim of this study was to evaluate the potential role of NS in clinical research on ADHD. We enroled 146 ADHD children (125 boys; mean age=9.61, S.D.=2.50) and 223 age- and gender-matched control children (178 boys; mean age=9.41, S.D.=2.30). All the parents filled in the JTCI for the evaluation of personality according to Cloninger׳s model. An exploratory factor analysis differentiated the NS items that concern "Impulsivity" (NS1) from those that concern other features (NS2). Multivariate Analysis of Variance (MANOVAs) revealed significant differences between ADHD children and non-ADHD children in temperamental dimensions: the scores of ADHD children were higher than those of non-ADHD children in Total NS, NS1-Impulsivity and NS2. Our results show that the NS dimension of the JTCI in ADHD children is higher than in non-ADHD children, even when a correction is made for impulsivity items. This finding suggests that the NS trait plays a central role in ADHD diagnosis even when items referred to impulsivity are removed from the NS scale.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/psicología , Carácter , Conducta Exploratoria , Temperamento , Atención , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Investigación Biomédica , Niño , Femenino , Humanos , Conducta Impulsiva , Masculino , Personalidad , Trastornos de la Personalidad , Inventario de Personalidad/estadística & datos numéricos , FenotipoRESUMEN
Besides the crucial role of genetic susceptibility in the development of early-onset obesity, it has been shown that feeding behavior could contribute to increased body weight. A significant association between obesity/overweight and ADHD has been reported, suggesting that these two conditions, despite their heterogeneity, might share common molecular pathways. Although the co-occurrence of obesity and ADHD is increasingly supported by empirical evidence, the complex pathogenetic link between these two conditions is still unclear. Here, we focus on the relationship between MC4R gene mutations and ADHD in children with early-onset obesity. Mutations in the gene MC4R lead to the most common form of monogenic obesity. We hypothesize that dysregulated eating behavior in a subset of patients with MC4R mutation might be due to comorbid ADHD symptoms, underpinned by abnormal reward mechanisms. Therefore, we speculate that it is possible to prevent obesity in a subset of patients with MC4R mutation, even if these patients are genetically programmed to "be fat", via an appropriate treatment of ADHD symptoms. We hope that our paper will stimulate further studies testing if the early screening for ADHD symptoms and their appropriate treatment may be an effective way to prevent obesity in a subset of children with MC4R mutation.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Conducta Alimentaria/fisiología , Obesidad/etiología , Receptor de Melanocortina Tipo 4/genética , Humanos , Modelos Biológicos , Mutación/genética , RecompensaRESUMEN
UNLABELLED: Interest is rising for auto-immune contribution in neuro-psychiatry. We evaluated the auto-antibodies against dopamine transporter (DAT aAbs) in 61 children (46 ADHD who met DSM-IV-TR criteria, 15 healthy controls). METHODS: ADHD patients were assigned, according to severity, either to a non-pharmacological therapy (NPT, N=32) or to a pharmacological treatment (PT, N=14) with methylphenidate (MPH). In ADHD children, blood samples were withdrawn twice, at recruitment (T0 basal) and after 6 weeks (T1); following 16 excluded subjects, DAT genotype was characterized (9-repeat or 10-repeat alleles; N=15 each). After 18 months of NPT or PT, some patients (carrying at least one 9-repeat allele) were blood sampled again (T2), for comparison with healthy controls (final n=8) RESULTS: Compared to NPT, basal DAT aAbs titers were higher within most severe patients (then assigned to PT), specifically if carrying a DAT 10/10 genotype. DAT aAbs levels of NPT group resulted highly correlated with distinct subscales of Conners' Parent/Teacher Scales (Rs>0.34), especially within DAT 10/10 genotype (Rs>0.53). While T1 titers were elevated over T0 baseline for NPT children, such an increase was not observed in PT patients carrying at least one 9-repeat allele, who also showed behavioral response to subchronic MPH. After 12-24 months of MPH exposure, DAT aAbs titers in PT subjects were comparable to those of healthy controls, while titers remained significantly elevated in NPT patients. Data warrant further research on serum DAT aAbs, which could be used to confirm ADHD diagnosis and/or to monitor therapeutic efficacy of MPH.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Autoanticuerpos/sangre , Estimulantes del Sistema Nervioso Central/uso terapéutico , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/inmunología , Metilfenidato/uso terapéutico , Trastorno por Déficit de Atención con Hiperactividad/sangre , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/genética , Niño , Análisis Mutacional de ADN , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Masculino , Escala del Estado Mental , Repeticiones de Minisatélite/genéticaRESUMEN
We report the case of a young male with attention-deficit hyperactivity disorder, oppositional defiant disorder, eating problems and overweight, and mild mental retardation. Karyotype analysis detected an apparently balanced translocation: t(1;2)(p34.1;q21.1) de novo. Array comparative genomic hybridization analysis defined a de-novo cryptic deletion of 2q21.1-q22.2 bands. The deletion, here first associated with this complex phenotype, encompasses several genes with a putative role in different domains of behavioral control and neurocognitive functions; their deregulated expression may influence metabolic pathways and the role of dopamine in reward, explaining the complex psychiatric phenotype and the pharmacotherapy response described in our patient.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Atracón/complicaciones , Trastorno por Atracón/genética , Deleción Cromosómica , Cromosomas Humanos Par 2/genética , Adolescente , Niño , Humanos , Masculino , FenotipoRESUMEN
BACKGROUND: HOXB1 plays a major role in brainstem morphogenesis and could partly determine the cranial circumference in conjunction with HOXA1. In our sample, HOXA1 alleles significantly influence head growth rates both in autistic patients and in population controls. An initial report, suggesting that HOXB1 could confer autism vulnerability in interaction with HOXA1, was not confirmed by five small association studies. METHODS: Our sample includes 269 autistic individuals, belonging to 219 simplex and 28 multiplex families. A mutational analysis of the two exons and flanking intronic sequences of the HOXB1 gene was carried out in 84 autistic patients by denaturing high performance liquid chromatography, followed by DNA sequencing. Identified rare variants were then searched by a restriction analysis in 236 autistic patients and 325-345 controls. Case-control and family-based association studies were performed on two common variants in 169 Italian patients versus 184 Italian controls and in 247 trios. RESULTS: We identified three common polymorphisms, rs72338773 [c.82insACAGCGCCC (INS/nINS)], rs12939811 [c.309A>T (Q103H)], and rs7207109 [c.450G>A (A150A)] and three rare variants, namely IVS1+63G>A, rs35115415 [c.702G>A (V234V)] and c.872_873delinsAA (S291N). SNPs rs72338773 and rs12939811 were not associated with autism, using either a case-control (alleles, exact P = 0.13) or a family-based design [transmission/disequilibrium test (TDT)chi2 = 1.774, P = 0.183]. The rare variants, all inherited from one of the parents, were present in two Italian and in two Caucasian-American families. Autistic probands in two families surprisingly inherited a distinct rare variant from each parent. The IVS1+63A allele was present in 3/690 control chromosomes, whereas rare alleles at rs35115415 and c.872_873delinsAA (S291N) were not found in 662 and 650 control chromosomes, respectively. The INS-T309 allele influenced head size, but its effect appears more modest and shows no interaction with HOXA1 alleles. The INS-T309 allele is also associated with more severe stereotypic behaviours, according to ADI-R scores (N = 60 patients, P < 0.01). CONCLUSIONS: HOXB1 mutations do not represent a common cause of autism, nor do HOXB1 common variants play important roles in autism vulnerability. HOXB1 provides minor, albeit detectable contributions to head circumference in autistic patients, with HOXA1 displaying more prominent effects. HOXB1 variants may modulate the clinical phenotype, especially in the area of stereotypic behaviours.
RESUMEN
We describe a 7-year-old patient with autism, moderate mental retardation, secondary microcephaly, agenesis of right optic nerve, and dysmorphic features carrying a de novo cryptic deletion of chromosome 2p25.2, detected by aCGH. Pure monosomies of 2p are very rare, and are usually observed as part of more complex aberrations involving other chromosomes. To the best of our knowledge, this is the first case presenting with a severe clinical phenotype and a de novo pure deletion of 2p25.2. The phenotypic effects of this rearrangement and the role of SOX11 gene, removed in our case, are herein discussed.