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Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are clinical conditions characterized by the sudden onset of obsessive-compulsive disorder and/or tics, often accompanied by other behavioral symptoms in a group of children with streptococcal infection. PANDAS-related disorders, including pediatric acute-onset neuropsychiatric syndrome (PANS), childhood acute neuropsychiatric symptoms (CANS), and pediatric infection triggered autoimmune neuropsychiatric disorders (PITANDs), have also been described. Since first defined in 1998, PANDAS has been considered a controversial diagnosis. A comprehensive review of the literature was performed on PubMed and Scopus databases, searching for diagnostic criteria and diagnostic procedures of PANDAS and related disorders. We propose a test panel to support clinicians in the workout of PANDAS/PANS patients establishing an appropriate treatment. However, further studies are needed to improve our knowledge on these acute-onset neuropsychiatric conditions.
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Mucopolysaccharidosis III (Sanfilippo syndromes) types A-D are rare lysosomal storage disorders characterized by heparan sulfate accumulation and neurodegeneration. Patients with MPS III present with developmental stagnation and/or regression, sleep disturbance, and behavioral abnormalities usually in the first years of life. Epilepsy may occur in a proportion of patients during the disease course. However, the progression of epilepsy and EEG changes in MPS III have not been systematically investigated. We report electroclinical features in a cohort of patients with MPS III over a follow-up period ranging from 6.5 to 22 years. Participants include 15 patients (11 females; aged 7-31 years) with MPS III A (n = 7, 47%), MPS III B (n = 5, 34%), MPS III C (n = 2, 13%), and MPS III D (n = 1, 6%). At the time of this study, 8 out of 15 patients (53%) had epilepsy. Epilepsy occurred in patients with advanced disease even in the first decade of life (mean age at onset: 12.1 ± 6.7 years). However, seizure onset may also be associated with abrupt worsening of the neurobehavioral phenotype. The main epilepsy types observed were generalized (four out of eight, 50%), followed by focal (three out of eight, 37%) and combined (two out of eight, 25%) epilepsy and status epilepticus (one out of eight, 12.5%). Seizures were generally controlled by one antiepileptic drug (AED) and most patients (seven out of eight, 87%) were still on therapy after a median follow-up period of 5 years (range: 1-9 years). A total of 66 EEGs were analyzed with a median EEG follow-up duration of 7 years (range: 6 months-14 years). Slowing of the background activity occurred in 7 (46%) patients aged 4-19 years. Epileptiform EEG abnormalities were observed in 10 patients at a mean age of 9.6 ± 2.9 years. EEG epileptiform discharges were not unavoidably linked to epilepsy. Early recognition and careful monitoring of electroclinical features in MPS III is necessary for appropriate care and for the detection of disease progression.
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AIM: To report on psychomotor development and outcomes in term born neonates with non-epileptic paroxysmal events (NEPEs). METHOD: From October 2017 to March 2019 we enrolled 38 consecutive term born neonates (22 males, 16 females; aged between 0-28d), born at the University Hospital San Marco in Catania, Italy, with NEPEs. We performed the Hammersmith Neonatal Neurological Examination scale (at enrolment), the Hammersmith Infant Neurological Examination (HINE) scale (at age 3, 6, 9, and 12mo), and the Griffiths scale (at age 12mo). RESULTS: The age at onset of first paroxysmal manifestations ranged from birth to 4 days. We recorded a suboptimal global score in 18 out of 38 patients at enrolment and in 10 out of 38 patients at age 3 months (>70% of these infants were male); all events disappeared within 6 months of life. At age 6, 9, and 12 months, all infants scored within normal values on the HINE and Griffiths scale. INTERPRETATION: Patients with NEPEs achieve neurodevelopment optimal scores within their first year of life. WHAT THIS PAPER ADDS: Neonates experiencing non-epileptic paroxysmal events (NEPEs) can be examined with the Hammersmith Neonatal Neurological Examination, Hammersmith Infant Neurological Examination, and Griffiths scale at follow-up. Newborn infants with NEPEs achieve optimal scores within the first year of life.
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Desarrollo Infantil/fisiología , Convulsiones/fisiopatología , Adulto , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Examen Neurológico , Estudios ProspectivosRESUMEN
Gilles de la Tourette syndrome (GTS) and autism spectrum disorder (ASD) are etiologically related neurodevelopmental disorders with an onset age before 18 years and a reported comorbidity of 2.9-20%. The aim of the present study was to identify the incidence of ASD in a large clinical sample of individuals affected by GTS and to compare our results with previously reported incidences. We retrospectively analyzed clinical data (n = 1200) from January 2010 to March 2019 obtained from the outpatient Catania Tourette Clinic, part of the Child and Adolescent Neurology and Psychiatry of the Medical and Experimental Department of Catania University. We used internationally validated evaluation tools. The neuropsychological evaluation was carried out by an expert and a certificated team of child and adolescent neurologists, supervised by two expert child neurologists (R.R. and M.G.). We investigated 975 GTS-affected individuals of various socioeconomic levels aged 5-18 years, and 8.9% (n = 87) were affected by ASD. The incidence of GTS with ASD was significantly lower (p < 0.001) in children than in adolescents. No statistically significant differences were found in the sex distribution and age of onset of tics between individuals with GTS alone and those with GTS and ASD. The incidence of GTS and ASD comorbidity in this study was high, and this has several implications in terms of treatment and prognosis.
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Pediatric cancer survivors are at increased risk for psychological distress. We sought to understand the severity and symptoms' co-occurrence among pediatric survivors compared to controls by rating both self- and parent-reported symptomatology. Forty survivors (22 males; mean age at study time: 12.9 years) participated in the study. Most survivors (85%) had a diagnosis of acute lymphoblastic leukemia. Seventy-nine healthy controls with the same age and gender distribution as the patients were included. A standardized assessment of psychological functioning was conducted by self- and parent-reported symptoms evaluations. The self-reported anxious symptom severity was significantly higher in survivors. A significantly higher proportion of survivors compared to controls had clinically significant anxiety, depression, and combined anxiety symptoms (i.e., social anxiety, separation anxiety, or physical symptoms). In both study groups, the self-reported emotional and somatic symptoms were significantly associated. The multi-informant assessments of the psychological symptoms revealed distinct associations between the child- and parent-reported symptoms in the survivors' group: the survivors' self-reports of depressive symptoms, somatic symptoms, and functional impairment were significantly correlated with the parent reports of child behavioral concerns, somatic complaints, and functional impairment, respectively. Conclusion: Self-reported symptoms showed similar comorbidity profiles in survivors and control peers. The multi-informant assessments detected differences in the association of self- and parent-reported symptoms between the survivor and control groups. The present study showed that multi-informant assessment is critical to understanding symptom profiles and to informing intervention with particular regard to parental participation and support.
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Recent evidence has demonstrated that salivary molecules, as well as bacterial populations, can be perturbed by several pathological conditions, including neuro-psychiatric diseases. This relationship between brain functionality and saliva composition could be exploited to unveil new pathological mechanisms of elusive diseases, such as Autistic Spectrum Disorder (ASD). We performed a combined approach of miRNA expression profiling by NanoString technology, followed by validation experiments in qPCR, and 16S rRNA microbiome analysis on saliva from 53 ASD and 27 neurologically unaffected control (NUC) children. MiR-29a-3p and miR-141-3p were upregulated, while miR-16-5p, let-7b-5p, and miR-451a were downregulated in ASD compared to NUCs. Microbiome analysis on the same subjects revealed that Rothia, Filifactor, Actinobacillus, Weeksellaceae, Ralstonia, Pasteurellaceae, and Aggregatibacter increased their abundance in ASD patients, while Tannerella, Moryella and TM7-3 decreased. Variations of both miRNAs and microbes were statistically associated to different neuropsychological scores related to anomalies in social interaction and communication. Among miRNA/bacteria associations, the most relevant was the negative correlation between salivary miR-141-3p expression and Tannerella abundance. MiRNA and microbiome dysregulations found in the saliva of ASD children are potentially associated with cognitive impairments of the subjects. Furthermore, a potential cross-talking between circulating miRNAs and resident bacteria could occur in saliva of ASD.
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Trastorno del Espectro Autista/psicología , Bacterias/clasificación , MicroARNs/genética , Saliva/química , Saliva/microbiología , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/microbiología , Bacterias/genética , Bacterias/aislamiento & purificación , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , MicroARNs/economía , Filogenia , ARN Ribosómico 16S/genéticaRESUMEN
Gilles de la Tourette syndrome (GTS) and autism spectrum disorder (ASD) are two neurodevelopmental disorders with male predominance, frequently comorbid, that share clinical and behavioral features. The incidence of ASD in patients affected by GTS was reported to be between 2.9% and 22.8%. We hypothesized that higher ASD rates among children affected by GTS previously reported may be due to difficulty in discriminating GTS sub-phenotypes from ASD, and the higher scores in the restrictive and repetitive behaviors in particular may represent at least a "false comorbidity". We studied a large population of 720 children and adolescents affected by GTS (n = 400) and ASD (n = 320), recruited from a single center. Patients were all assessed with The Yale Global Tic Severity Rating Scale (YGTSS), The Autism Diagnostic Observation Schedule (ADOS), The Autism Diagnostic Interview Revised (ADI-R), The Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), and The Children's Yale-Brown Obsessive-Compulsive Scale for autism spectrum disorder (CY-BOCS ASD). Our results showed statistically significant differences in ADOS scores for social aspects between GTS with comorbid attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) sub-phenotypes and ASD. No differences were present when we compared GTS with comorbid ASD sub-phenotype to ASD, while repetitive and restrictive behavior scores in ASD did not present statistical differences in the comparison with GTS and comorbid OCD and ASD sub-phenotypes. We also showed that CY-BOCS ASD could be a useful instrument to correctly identify OCD from ASD symptoms.
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Autism spectrum disorder (ASD) is associated with various molecular mechanisms including copy number variants (CNVs). We investigated possible associations between CNVs and ASD clinical correlates. We evaluated pertinent physical characteristics and phenotypic measures such as cognitive level, severity of ASD symptoms and comorbid conditions in ASD patients consecutively recruited over the study period. Children with causative (C-CNVs), non-causative (NC-CNVs) and without CNVs (W-CNVs) were compared. Out of 109 patients, 31 imbalances (16 duplications and 15 deletions) were detected in 25 subjects. Seven (6.4%) had C-CNVs and 18 (16.5%) had NC-CNVs. Paired post hoc comparisons with Bonferroni adjustment showed that dysmorphisms and microcephaly were significantly more frequent in the C-CNVs group. Patients with C-CNVs had more severe autistic core symptoms, while comorbid internalizing behavioral symptoms were more represented among participants with NC-CNVs. No significant differences were observed for distribution of macrocephaly, intellectual disability, epilepsy, isolated electroencephalogram abnormalities and studied neuroimaging characteristics among groups. Recurrent and rare C-CNVs highlighting genes relevant to neurodevelopment had a statistically higher occurrence in children with more severe ASD symptoms and further developmental abnormalities. This study documents the importance of measuring the physical and neurobehavioural correlates of ASD phenotypes to unravel the underlying molecular mechanisms in patient subgroups.
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Trastorno del Espectro Autista/genética , Variaciones en el Número de Copia de ADN/genética , Adolescente , Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno del Espectro Autista/psicología , Causalidad , Niño , Conducta Infantil , Preescolar , Cognición , Comorbilidad , Anomalías Congénitas/genética , Anomalías Congénitas/psicología , Electroencefalografía , Epilepsia/etiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Microcefalia/diagnóstico por imagen , Microcefalia/genética , Microcefalia/psicología , Pruebas Neuropsicológicas , FenotipoRESUMEN
Due to its rarity, coupled to a multifactorial and very heterogeneous nature, the molecular etiology of Arnold-Chiari (AC) syndrome remains almost totally unknown. Its relationship with other neuropsychiatric disorders such as Tourette syndrome (TS) is also undetermined. The rare comorbid status between both disorders (ACTS) complicates the framework of diagnosis and negatively affects the patients' quality of life. In this exploratory study, we aimed to identify serum microRNA expression profiles as molecular fingerprints for AC, TS, and ACTS, by using a high-throughput approach. For this aim, 10 AC patients, 11 ACTS patients, 6 TS patients, and 8 unaffected controls (NC) were recruited. Nine miRNAs resulted significantly differentially expressed (DE): let-7b-5p (upregulated in ACTS vs. TS); miR-21-5p (upregulated in ACTS vs. AC; downregulated in AC vs. TS); miR-23a-3p (upregulated in TS vs. NCs; downregulated in AC vs. TS); miR-25-3p (upregulated in AC vs. TS and NCs; downregulated in ACTS vs. AC); miR-93-5p (upregulated in AC vs. TS); miR-130a-3p (downregulated in ACTS and TS vs. NCs); miR-144-3p (downregulated in ACTS vs. AC; upregulated in AC vs. TS); miR-222-3p (upregulated in ACTS vs. NCs); miR-451a (upregulated in AC vs. TS and NCs; in ACTS vs. NCs). Altered expression of miRNAs was statistically correlated to neuroimaging and neuropsychological anomalies. Furthermore, computational analyses indicated that DE miRNAs are involved in AC and TS pathomechanisms. Finally, we propose the dysregulation of the miRNA set as a potential molecular tool for supporting the current diagnosis of AC, TS, and ACTS by using liquid biopsies, in an unbiased and non-invasive way.
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Introduction: Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder, characterized by the presence of multiple motor and, at least one, phonic tics, for more than one year, beginning before 18 years of age; its treatment is often a challenge for the clinicianAreas covered: GTS treatment requires a multidisciplinary management to treat each patient's symptom. Although individuals with GTS often have comorbid psychiatric disorders, the focus of this review will only be on the management of tics.Expert opinion: The authors summarized the steps that clinicians should follow treating GTS patient; the impact of the tics on a patients' life should be the first step; different patients could present different levels of tolerance to the symptoms. Second, comorbidities should be considered before starting a treatment for tic. Finally, clinicians must focus the attention of the patient and family, on the length of the treatment and the duration of time after which the effects of the drug will occur. Before the treatment, the potential side effects must be mentioned to the parents, and the choice of treatment must be made in the light of the patient's tolerance to these.
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Síndrome de Tourette/terapia , Humanos , Síndrome de Tourette/fisiopatologíaRESUMEN
BACKGROUND: Headache is one of the main complaints in pediatric neurology. Exogenous melatonin has been shown to be useful and safe in improving sleep-wake cycles and sleep quality in children. Tryptophan as well plays a key role in sleep regulation. So far, no studies tried to analyze the effects of a combination of both melatonin and tryptophan in treating chronic headache in children affected also by night-time awakenings. METHODS: Thirty-four children with a diagnosis of chronic headache (with or without sleep disorders) have been enrolled. The study was articulated in two steps: 1) each child was observed for one month without any intervention; 2) children have been then randomized into two groups: the "ME-group", which received the nutritional supplement melatonin for two months and the "MET-group", which received the nutritional supplements melatonin, tryptophan, and vitamin B6 for two months. RESULTS: In terms of changes in number of headache events, responders in the ME-group were 91.7% and those in the MET-group were 66.7% (P=0.113). In terms of changes in number of night awakenings, in the ME group, mean number at baseline, after 30 days, and after 60 days were 3.6±3.2, 3.2±3.5, and 2.7±3.4 (P=0.495). In the MET group, mean number of night awakenings was 7.4±8.1, 4.0±4.4, and 3.3±2.9 (P=0.041). CONCLUSIONS: Using either nutritional supplement for two months can help in decreasing the monthly number of headache episodes and night awakenings. The addition of tryptophan and vitamin B6 appears to have stronger influence on night awakenings reduction than melatonin only.
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Suplementos Dietéticos , Cefaleas Primarias/tratamiento farmacológico , Melatonina/administración & dosificación , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Triptófano/administración & dosificación , Vitamina B 6/administración & dosificación , Adolescente , Antidepresivos de Segunda Generación/administración & dosificación , Antioxidantes/administración & dosificación , Niño , Femenino , Cefaleas Primarias/complicaciones , Humanos , Italia , Masculino , Proyectos Piloto , Trastornos del Sueño-Vigilia/complicaciones , Complejo Vitamínico B/administración & dosificaciónRESUMEN
BACKGROUND: Word comprehension across semantic categories is a key area of language development. Using online automated eye-tracking technology to reduce response demands during a word comprehension test may be advantageous in children with autism spectrum disorder (ASD). OBJECTIVES: To measure online accuracy of word recognition across eleven semantic categories in preschool children with ASD and in typically developing (TD) children matched for gender and developmental age. METHODS: Using eye-tracker methodology we measured the relative number of fixations on a target image as compared to a foil of the same category shown simultaneously on screen. This online accuracy measure was considered a measure of word understanding. We tested the relationship between online accuracy and offline word recognition and the effects of clinical variables on online accuracy. Twenty-four children with ASD and 21 TD control children underwent the eye-tracking task. RESULTS: On average, children with ASD were significantly less accurate at fixating on the target image than the TD children. After multiple comparison correction, no significant differences were found across the eleven semantic categories of the experiment between preschool children with ASD and younger TD children matched for developmental age. The ASD group showed higher intragroup variability consistent with greater variation in vocabulary growth rates. Direct effects of non-verbal cognitive levels, vocabulary levels and gesture productions on online word recognition in both groups support a dimensional view of language abilities in ASD. CONCLUSIONS: Online measures of word comprehension across different semantic categories show higher interindividual variability in children with ASD and may be useful for objectively monitor gains on targeted language interventions.
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Trastorno del Espectro Autista/fisiopatología , Comprensión , Gestos , Desarrollo del Lenguaje , Diferencial Semántico , Percepción del Habla , Trastorno del Espectro Autista/psicología , Niño , Preescolar , Femenino , Humanos , Masculino , SemánticaRESUMEN
Given its prevalence and social impact, Autism Spectrum Disorder (ASD) is drawing much interest. Molecular basis of ASD is heterogeneous and only partially known. Many factors, including disorders comorbid with ASD, like TS (Tourette Syndrome), complicate ASD behavior-based diagnosis and make it vulnerable to bias. To further investigate ASD etiology and to identify potential biomarkers to support its precise diagnosis, we used TaqMan Low Density Array technology to profile serum miRNAs from ASD, TS, and TS+ASD patients, and unaffected controls (NCs). Through validation assays in 30 ASD, 24 TS, and 25 TS+ASD patients and 25 NCs, we demonstrated that miR-140-3p is upregulated in ASD vs.: NC, TS, and TS+ASD (Tukey's test, p-values = 0.03, = 0.01, < 0.0001, respectively). ΔCt values for miR-140-3p and YGTSS (Yale Global Tic Severity Scale) scores are positively correlated (Spearman r = 0.33; Benjamini-Hochberg p = 0.008) and show a linear relationship (p = 0.002). Network functional analysis showed that nodes controlled by miR-140-3p, especially CD38 and NRIP1 which are its validated targets, are involved in processes convergingly dysregulated in ASD, such as synaptic plasticity, immune response, and chromatin binding. Biomarker analysis proved that serum miR-140-3p can discriminate among: (1) ASD and NC (Area under the ROC curve, AUC: 0.70; sensitivity: 63.33%; specificity: 68%); (2) ASD and TS (AUC: 0.72; sensitivity: 66.66%; specificity: 70.83%); (3) ASD and TS+ASD (AUC: 0.78; sensitivity: 73.33%; specificity: 76%). Characterization of miR-140-3p network would contribute to further clarify ASD etiology. Serum miR-140-3p could represent a potential non-invasive biomarker for ASD, easy to test through liquid biopsy.
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OBJECTIVE: Gilles de la Tourette syndrome (GTS) and depression are both common disorders. It has been suggested that depression occurs in 13%-76% GTS patients. Despite this, there are few studies into the specific relationships and correlates between the two disorders. There is only some consensus as to the precise relationship between the two disorders. MATERIALS AND METHODS: We undertook the study to investigate the relationship between depressive symptomatology and the core clinical features of GTS in a well-characterized clinical population of youth with this disorder. Our aim was to verify the association between depression and comorbid obsessive-compulsive disorder and explore further other potential associations highlighted in some, but not all, of the studies focused on this topic. RESULTS: Our results demonstrated that (1) the GTS patients were significantly older than the controls, (2) the GTS patients were significantly more depressed than controls, (3) depression was associated with tic severity, (4) the Diagnostic Confidence Index scores were higher in GTS patients without depression, (5) anxiety, attention-deficit/hyperactivity disorder (ADHD), conduct disorder (CD), and behavioral problems were significantly associated with depression, and (6) finally, patients with GTS and depression have a positive family history of depression. However, obsessionality (CY-BOCS) did not differentiate between depressed and not depressed GTS patients. CONCLUSIONS: Depression is common in patients with GTS and occurs significantly more in GTS than in controls. Depression is significantly associated with GTS factors such as tic severity, comorbidity with ADHD, and the presence of coexistent anxiety, CDs, and behavior problems. Depression is importantly significantly associated with a positive family history of depression. Intriguingly, depression in our sample was not related to obsessionality.
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Depresión/complicaciones , Depresión/psicología , Trastorno Depresivo/complicaciones , Trastorno Depresivo/psicología , Síndrome de Tourette/complicaciones , Síndrome de Tourette/psicología , Adolescente , Ansiedad/complicaciones , Ansiedad/psicología , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/psicología , Niño , Comorbilidad , Trastorno de la Conducta/complicaciones , Trastorno de la Conducta/psicología , Familia , Femenino , Humanos , Masculino , Escalas de Valoración Psiquiátrica , Calidad de VidaRESUMEN
BACKGROUND: Nocturnal enuresis (NE) is an involuntary voiding during sleep. It is a very common disorder in school-age children. Comorbid psychopathologies are common in patients affected by enuresis. According to the ICCS, the rate of behavioral and emotional disorders in children with enuresis is doubled compared with healthy control (HC) children. OBJECTIVE: The aim of the present study was to investigate the prevalence of neuropsychiatric comorbidities in children affected by NE. STUDY DESIGN: Two hundred children with a diagnosis of enuresis were recruited from the Neuropsychiatric Unit of Catania University and 200 age-matched neurologically intact HC children were recruited from local schools. The inclusion criteria were a normal IQ and the absence of other pathological clinical conditions such as diabetes or kidney malformation. The exclusion criteria were failure to complete the initial evaluation or clinical/diagnostic procedures, inability (because of young age) to complete study questionnaires, and severe neurological or physical impairment. RESULTS: Age and gender proportions were not significantly different between the groups. In the NE group, 138 subjects (69%) had a familial history of NE, compared with 24 subjects (12%) in the HC group (p < 0.01). The NE group demonstrated significantly higher scores in the Child Behavior Check List, Conners' Multidimensional Anxiety Scale for Children, and the Child Depression Inventory compared than the HC group as well as the Yale Global Tic Severity Score and Child-Yale-Brown Obsessive Compulsive Scale scores (p < 0.01). Quality of life scores were significantly lower in the NE group than in the HCs group; specifically, between-group differences were significant in the relationship and self domains (p > 0.01 for both comparisons) (Figure). DISCUSSION: The present case-control study evaluates the prevalence of different neuropsychiatric comorbidities in children with NE as diagnosed according to the new ICCS criteria. An important finding was that neuropsychiatric conditions were more prevalent in NE patients than in age-matched HC subjects. To the best of our knowledge, this is the first study to report associations between enuresis and obsessive compulsive disorder as well as tic disorder, and is the first to describe the comparative psychopathological profiles of 200 children with enuresis and 200 matched HC children. CONCLUSION: The results suggest that clinicians should not underestimate the effects of enuresis on psychosocial development. Childhood NE should be managed carefully and comprehensively in order to prevent the development of more serious behavioral problems in the future.
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Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Depresión/epidemiología , Enuresis Nocturna/epidemiología , Calidad de Vida , Adolescente , Niño , Comorbilidad/tendencias , Femenino , Estudios de Seguimiento , Humanos , Italia/epidemiología , Masculino , Prevalencia , Estudios Prospectivos , Autoimagen , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
In this study, we have tested the effects of the dopamine D2 receptor blocker pimozide on timing performance in patients with Tourette syndrome (TS). Nine children with TS were tested off-medication and following 3 months of daily treatment with pimozide. Subjects completed a time reproduction and a time production task using supra-second temporal intervals. We show that pimozide improves motor timing performance by reducing the patients' variability in reproducing the duration of visual stimuli. On the other hand, this medication has no effect on the reproduction accuracy and on both variability and accuracy of the performance on the time production task. Our results suggest that pimozide might have improved motor timing variability as a result of its beneficial side effect on endogenous dopamine levels (i.e., normalization).
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Antipsicóticos/uso terapéutico , Pimozida/uso terapéutico , Síndrome de Tourette/tratamiento farmacológico , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Gilles de la Tourette syndrome (GTS) is a complex neuropsychiatric disorder with a strong genetic influence where copy number variations are suggested to play a role in disease pathogenesis. In a previous small-scale copy number variation study of a GTS cohort (n = 111), recurrent exon-affecting microdeletions of four genes, including the gene encoding arylacetamide deacetylase (AADAC), were observed and merited further investigations. METHODS: We screened a Danish cohort of 243 GTS patients and 1571 control subjects for submicroscopic deletions and duplications of these four genes. The most promising candidate gene, AADAC, identified in this Danish discovery sample was further investigated in cohorts from Iceland, the Netherlands, Hungary, Germany, and Italy, and a final meta-analysis, including a total of 1181 GTS patients and 118,730 control subjects from these six European countries, was performed. Subsequently, expression of the candidate gene in the central nervous system was investigated using human and mouse brain tissues. RESULTS: In the Danish cohort, we identified eight patients with overlapping deletions of AADAC. Investigation of the additional five countries showed a significant association between the AADAC deletion and GTS, and a final meta-analysis confirmed the significant association (p = 4.4 × 10(-4); odds ratio = 1.9; 95% confidence interval = 1.33-2.71). Furthermore, RNA in situ hybridization and reverse transcription-polymerase chain reaction studies revealed that AADAC is expressed in several brain regions previously implicated in GTS pathology. CONCLUSIONS: AADAC is a candidate susceptibility factor for GTS and the present findings warrant further genomic and functional studies to investigate the role of this gene in the pathogenesis of GTS.