Hemispheric Dominance and Neurodevelopmental Disorders: Global Effects for Intensive Motor Training on White Matter Plasticity.

Cerebral maturation is characterized by different age-dependent molecular and cellular processes and follows a different course for grey matter (GM) and white matter (WM). During brain development, a crucial point seems to be represented by the establishment of a hemispheric specialization with the left hemisphere dominant for language and motor control and the right hemisphere dominant for visuospatial processing and attention. Therefore, motor and cognitive development are strongly connected. Atypical motor development and lateralization can be associated with neurodevelopmental disorders, such as Language Disorder, Learning Disorders (Dysgraphia and Dyslexia), Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder. The aim of our research was to investigate the possible effects of intensive motor training on WM plasticity and writing skills in children with Developmental Dysgraphia through a tractography study of the main WM tracts. Considering the effect of training for the Mean Diffusivity (MD) over 18 WM tracts, in 6 collaborating dysgraphic patient MD decrease (-4.3%) and in 3 not. Intensive motor training affects both stimulated and not stimulated WM tracts and showed a double not-specificity: for not stimulated hemilate and for not directly stimulated WM tracts. Intensive motor training improves both some lateralized brain functions and intra- and inter-hemispheric connectivity in our patients with good compliance with motor treatment. Moreover, our findings have shown that WM plasticity improvement concerned cortical areas responsible for both motor and cognitive functions.

Presence of neurologic signs in children with neurofibromatosis type 1.

BACKGROUND: Neurofibromatosis type 1 is a common neurogenetic disorder affecting nervous system, caused by germiline mutations of the NF1 gene. Although the clinical diagnosis of NF1 is defined by presence of cafe-au-laits spots, freckling and benign tumors (neurofibromatosis), neurocognitive impairment and neuropsychiatric disorders are reported in comorbidity. Children with NF1 show higher incidence of executive deficits, such attention, response inhibition, executive planning and problem solving, working memory, and learning impairment. In this study we examine the presence of neurological soft signs and planning function in subjects with NF1. The NSS are minor motor and sensory abnormalities without focal brain damage. METHODS: Eleven drug naïve children between 7-15 years with clinical and molecular diagnosis of NF are matched to 11 healthy controls to ass the presence of neurological soft signs and planning executive functions. NSS were assessed using Physical and Neurological Examination for Subtle Signs and the Tower of London task is performance test to assess the capacity of planning, organization and execution of a work. RESULTS: Our results revealed highest rate of NSS and planning deficit in children with NF1 compared to healthy controls. CONCLUSIONS: The motor abnormalities and planning deficit are possible markers to confirm that NF1 could be considering a neurodevelopmental disorder.

Attention Deficits Influence the Development of Motor Abnormalities in High Functioning Autism.

Early attentional dysfunction is one of the most consistent findings in autism spectrum disorder (ASD), including the high functioning autism (HFA). There are no studies that assess how the atypical attentional processes affect the motor functioning in HFA. In this study, we evaluated attentional and motor functioning in a sample of 15 drug-naive patients with HFA and 15 healthy children (HC), and possible link between attentional dysfunction and motor impairment in HFA. Compared to HC, HFA group was seriously impaired in a considerable number of attentional processes and showed a greater number of motor abnormalities. Significant correlations between attention deficits and motor abnormalities were observed in HFA group. These preliminary findings suggest that deficit of attentional processes can be implied in motor abnormalities in HFA.

Facet joint degeneration in patients with lumbar disc herniation and probable determining factors / Degeneração facetária em pacientes com hérnia de disco lombar e prováveis fatores determinantes / Degeneración facetaria en pacientes con hernia de disco lumbar y probables factores determinantes

ABSTRACT Objective To evaluate facet joint degeneration following surgical treatment in patients with lumbar disc herniation, seeking to correlate it with possible determining factors. Methods Cross-sectional observational study, which analyzed medical records, radiographs and magnetic resonance images of 287 patients with lumbar disc herniation treated surgically at the Spine Surgery Service of the Hospital Ortopédico de Passo Fundo. Information about age and sex was collected. In the imaging exams, the following variables were evaluated: facet joint angulation and its tropism, measured by the Karacan method, sacral slope and lumbar lordosis, measured by the Cobb method, arthrosis of the interfacetary joints, measured by the Weishaupt classification, and intervertebral disc degeneration, measured by the Pfirrmann classification. Results A statistically significant relationship was observed between facet joint degeneration and age (p = 0.002), and also between facet joint degeneration and sacral slope (p = 0.038). No correlation was found between facet joint degeneration and lumbar lordosis (p = 0.934). It was found that the most degenerated facet joints were those that had the greatest facet joint asymmetry (tropism). However, the mean degree of facet tropism did not increase homogeneously with the progression of the joint degeneration score (p = 0.380). Conclusion It was verified that there are, in fact, a multiplicity of factors related to the degree of facet joint degeneration in the low lumbar spine. Additional studies, correlated with the asymmetry of the facet joints, would be important to elucidate better preventive management of this degeneration, aiming to avert secondary low back pain and sciatica with advancing age. Level of evidence II; Retrospective study.

RESUMO Objetivo Avaliar a degeneração facetária em pacientes com hérnia de disco lombar tratados cirurgicamente, procurando correlacioná-la com possíveis fatores determinantes. Métodos Estudo observacional do tipo transversal, que analisou prontuários, radiografias e ressonâncias magnéticas de 287 pacientes com hérnia de disco lombar, tratados cirurgicamente no Serviço de Cirurgia da Coluna do Hospital Ortopédico de Passo Fundo. Foram coletadas informações sobre idade e sexo. Nos exames de imagem, foram avaliadas as seguintes variáveis: angulação facetária e seu tropismo, mensurada pelo método de Karacan, inclinação sacral e lordose lombar, medidas pelo método de Cobb, artrose das articulações interfacetárias, pela classificação de Weishaupt e degeneração do disco intervertebral, pela classificação de Pfirrmann. Resultados Foi verificada relação estatisticamente significativa entre degeneração facetária e idade (p = 0,002), assim como entre degeneração facetária e inclinação sacral (p = 0,038). Não foi encontrada correlação entre degeneração facetária e lordose lombar (p = 0,934). Constatou-se que as articulações facetárias mais degeneradas eram as que tinham maior assimetria facetária (tropismo). Porém, a média do grau de tropismo facetário não aumentou de forma homogênea com a progressão do escore de degeneração da articulação (p = 0,380). Conclusões Verificou-se que há, de fato, uma multiplicidade de fatores relacionados com o grau de degeneração facetária da coluna lombar baixa. Estudos adicionais correlacionados com a assimetria das referidas articulações seriam importantes para elucidarmos uma conduta preventiva melhor para a referida degeneração, objetivando evitar lombalgia e ciatalgia secundárias à medida que a idade avança. Nível de evidência II; Estudo retrospectivo .

RESUMEN Objetivo Evaluar la degeneración facetaria en pacientes con hernia de disco lumbar tratados quirúrgicamente, buscando correlacionarla con posibles factores determinantes. Métodos Estudio observacional del tipo transversal, que analizó historiales, radiografías y resonancias magnéticas de 287 pacientes con hernia de disco lumbar, tratados quirúrgicamente en el Servicio de Cirugía de la Columna del Hospital Ortopédico de Passo Fundo. Fueron colectadas informaciones sobre edad y sexo. En los exámenes de imagen, se evaluaron las siguientes variables: angulación facetaria y su tropismo, medida por el método de Karacan, inclinación sacral y lordosis lumbar, medidas por el método de Cobb, artrosis de las articulaciones interfacetarias, por la clasificación de Weishaupt, y degeneración del disco intervertebral, por medio de la clasificación de Pfirrmann. Resultados Se verificó relación estadísticamente significativa entre degeneración facetaria y edad (p = 0,002), así como entre degeneración facetaria e inclinación sacral (p = 0,038). No se encontró correlación entre degeneración facetaria y lordosis lumbar (p = 0,934). Se constató que las articulaciones facetarias más degeneradas eran las que tenían mayor asimetría facetaria (tropismo). Sin embargo, el promedio del grado de tropismo facetario no aumentó de forma homogénea con la progresión del score de degeneración de la articulación (p = 0,380). Conclusiones Se verificó que hay, de hecho, una multiplicidad de factores relacionados con el grado de degeneración facetaria de la columna lumbar baja. Estudios adicionales correlacionados con la asimetría de las referidas articulaciones serían importantes para que elucidemos una mejor conducta preventiva para la referida degeneración, con el objetivo de evitar lumbalgia e ciatalgia secundarias, a medida que la edad avanza. Nivel de evidencia II; Estudio retrospectivo.

New Insights on the Effects of Methylphenidate in Attention Deficit Hyperactivity Disorder.

This narrative review describes an overview of the multiple effects of methylphenidate (MPH) in attention-deficit/hyperactivity disorder (ADHD) and its potential neurobiological targets. It addressed the following aspects: 1) MPH effects on attention and executive functions in ADHD; 2) the relation between MPH efficacy and dopamine transporter gene (DAT) polymorphism; and 3) the role of MPH as an epigenetic modulator in ADHD. Literature analysis showed that MPH, the most commonly used psychostimulant in the therapy of ADHD, acts on multiple components of the disorder. Marked improvements in attentional and executive dysfunction have been observed in children with ADHD during treatment with MPH, as well as reductions in neurological soft signs. MPH efficacy may be influenced by polymorphisms in the DAT, and better responses to treatment were associated with the 10/10 genotype. Innovative lines of research have suggested that ADHD etiopathogenesis and its neuropsychological phenotypes also depend on the expression levels of human endogenous retrovirus (HERV). In particular, several studies have revealed that ADHD is associated with HERV-H over-expression and that MPH administration results in decreased expression levels of this retroviral family and a reduction in the main symptoms of the disorder. In conclusion, there is a confirmed role for MPH as an elective drug in the therapy of ADHD alone or in association with behavioral therapy. Its effectiveness can vary based on DAT polymorphisms and can act as a modulator of HERV-H gene expression, pointing to targets for a precision medicine approach.

Rett Syndrome in Males: The Different Clinical Course in Two Brothers with the Same Microduplication MECP2 Xq28.

Rett syndrome (RTT) is a neurodevelopmental disorder with a genetic basis that is associated with the mutation of the X-linked methyl-CpG binding protein 2 (MECP2) gene in approximately 90% of patients. RTT is characterized by a brief period of normal development followed by loss of acquired skills and evolution towards impairment of brain and motor functions and multi-organ dysfunction. Originally, RTT was considered lethal in males as it has an X-linked dominant inheritance. However, although this syndrome has a higher incidence in females, rare cases are also documented in males. Here, we describe the case of an 11-year-old male patient with a microduplication MECP2 Xq28. Our patient is currently living, while his older brother with the same mutation died at the age of 9 years. We showed that the role of MECP2 as an epigenetic modulator and the X-chromosome inactivation pattern can explain the lethal clinical form of the older brother with the same microduplication MECP2 Xq28 presented by our patient who is still alive. Given the limited case history of RTT in males, further studies are needed to better characterize this syndrome in males and consequently improve the currently available therapeutic strategies.

Antipsychotics Do Not Influence Neurological Soft Signs in Children and Adolescents at Ultra-High Risk for Psychosis: A Pilot Study.

OBJECTIVE: Ultra-high risk for psychosis (UHR) is considered as the condition that temporally precedes the onset of psychotic symptoms. In addition to the core symptoms, patients with schizophrenia show motor abnormalities, also known as neurological soft signs (NSS), that are considered an endophenotype for psychotic disorders and particularly for schizophrenia. Antipsychotic medications do not appear to influence NSS in individuals with schizophrenia. However, NSS in UHR subjects have been poorly studied and, to date, we do not know what effects antipsychotics have in early treated UHR subjects. Therefore, we evaluated NSS in treated UHR subjects in comparison with drug-naive UHR subjects and a group of healthy control subjects and the effect of pharmacological treatment on early treated UHR children and adolescents. PATIENTS AND METHODS: Fifteen UHR subjects receiving pharmacological treatment, 15 drug-naive UHR subjects, and 25 healthy control subjects were evaluated for NSS to analyze any differences between clinical subjects and healthy controls and to evaluate the effect of antipsychotic medications in early treated UHR subjects. RESULTS: Both clinical groups showed a greater number of NSS compared with the healthy control subjects. However, no significant differences in NSS were found between treated and drug-naive UHR subjects. CONCLUSIONS: Consistent with what has been observed in the population of patients with a first psychotic episode and/or with schizophrenia, our results support the conclusion that antipsychotic medications do not influence NSS in children and adolescents who are at high risk for psychosis.

22q11 microdeletion syndrome and ultra-high risk for psychosis: The role of neurological soft signs as an independent marker of vulnerability for psychosis.

AIM: 22q11 microdeletion syndrome has an increased risk for psychosis, similar to subjects at ultra-high risk for psychosis. Neurological soft signs are considered an endophenotype of psychotic disorders and a marker of vulnerability to Schizophrenia, consisting of overflow movements, dysrhythmia and speed of timed activities. To date, there are no studies that have evaluated the presence of the neurological soft signs in subjects with 22q11 microdeletion syndrome and there are a few studies that have analysed this issue in subjects at ultra-high risk. METHODS: We sought to measure neurological soft signs in these two conditions, compared to healthy controls and to analyse the possible correlation between neurological soft signs and positive/negative symptoms both in 22q11 microdeletion syndrome and ultra-high-risk groups. 54 drug-naive patients (29 with 22q11 microdeletion syndrome and 25 at ultra-high risk for psychosis) and 25 healthy controls were evaluated for neurological soft signs. RESULTS: Both clinical groups showed a greater number of neurological soft signs compared to healthy control, although the two clinical groups did not differ for the number of neurological soft signs. Positive correlation between speed of timed activities and negative symptoms was found in subjects at ultra-high risk. CONCLUSION: Neurological soft signs could represent a marker of atypical neurodevelopment in the two populations examined. Since we did not found a strong correlation between neurological soft signs and positive/negative symptoms, we suggest that neurological soft signs could be indicators of vulnerability to psychosis independent from the psychopathology.

Scientific Evidence for the Evaluation of Neurological Soft Signs as Atypical Neurodevelopment Markers in Childhood Neuropsychiatric Disorders.

Motor dysfunction is commonly present in children with neurodevelopmental disorders. Developmental changes in voluntary control of motor skills include improvements in speed and motor coordination as well as reduced frequency of neurological soft signs (NSS) that are commonly observed in typically developing younger children. NSS are motor and sensory conditions that cannot be linked to specific cerebral lesions. The persistence of NSS into later childhood and adolescence is linked with an increased risk of psychiatric disorders. This finding gives support to the neurodevelopmental model of NSS in which minor neurological impairments may be viewed as potential signs of deviant brain development and might represent trait markers of vulnerability for neurodevelopmental disorders. Given that NSS are easily detectable, it is important that clinicians increase their knowledge of the clinical presentation and research implications of the relationship between NSS and childhood neurodevelopmental disorders. To the best of our knowledge, this is the first review article to give an updated overview of the current knowledge of NSS in the most common neuropsychiatric disorders of childhood/adolescence, such as attention-deficit/hyperactivity disorder, autism spectrum disorder, obsessive-compulsive disorder, bipolar disorder, and first episode of psychosis. The article also presents key points for future research studies on this topic.

The Decrease in Human Endogenous Retrovirus-H Activity Runs in Parallel with Improvement in ADHD Symptoms in Patients Undergoing Methylphenidate Therapy.

Increasing scientific evidence demonstrated the deregulation of human endogenous retroviruses (HERVs) expression in complex diseases, such as cancer, autoimmune, psychiatric, and neurological disorders. The dynamic regulation of HERV activity and their responsiveness to a variety of environmental stimuli designate HERVs as genetic elements that could be modulated by drugs. Methylphenidate (MPH) is widely used in the treatment of attention deficit hyperactivity disorder (ADHD). The aim of this study was to evaluate the time course of human endogenous retrovirus H (HERV-H) expression in peripheral blood mononuclear cells (PBMCs) with respect to clinical response in ADHD patients undergoing MPH therapy. A fast reduction in HERV-H activity in ADHD patients undergoing MPH therapy was observed in parallel with an improvement in clinical symptoms. Moreover, when PBMCs from drug-naïve patients were cultured in vitro, HERV-H expression increased, while no changes in the expression levels were found in ADHD patients undergoing therapy. This suggests that MPH could affect the HERV-H activity and supports the hypothesis that high expression levels of HERV-H could be considered a distinctive trait of ADHD patients.

A Child with a c.6923_6928dup (p.Arg2308_Met2309dup) SPTAN1 Mutation Associated with a Severe Early Infantile Epileptic Encephalopathy.

Early infantile epileptic encephalopathies (EIEEs) are a group of neurological disorders characterized by early-onset refractory seizures, severe electroencephalographic abnormalities, and developmental delay or intellectual disability. Recently, genetic studies have indicated that a significant portion of previously cryptogenic EIEEs are single-gene disorders. SPTAN1 is among the genes whose mutations are associated with EIEE development (OMIM# 613477). Here, a case of the c.6923_6928dup (p.Arg2308_Met2309dup) SPTAN1 mutation associated with a severe EIEE is reported. This case shows that mutations in the α20 repeat in the C-terminal of αII spectrin can be associated with EIEE. Duplication seems essential to cause EIEE. This causation is not demonstrated for amino acid deletions in the same spectrin residues. Reportedly, children with p.(Asp2303_Leu2305del) and p.(Gln2304_Gly2306del) deletions have childhood-onset epilepsy and no or marginal magnetic resonance imaging abnormalities, suggesting that not only the location but also the type of mutation plays a role in conditioning nervous system damage. Further studies are needed for a better understanding of the phenotype/genotype correlation in SPTAN1-related encephalopathies.

Recurrent Renal Colic in a Patient with Munchausen Syndrome.

BACKGROUND: In most of the cases regarding children, factitious disorders (FDs) are intentionally produced by parents. Less attention is paid to FDs in which a child or adolescent intentionally induces or falsifies the disease to attain a patient's role. CASE PRESENTATION: A 13-year-old immigrated and adopted boy previously underwent an operation for renal joint syndrome and was affected by recurrent episodes of renal colic. The boy was admitted reporting acute left flank pain with scars on the mucous face of his prepuce and had a recent previous hospitalization for the same reason. Laboratory tests and radiological findings did not reveal any morphological or functional alterations. Self-induced FD was suspected, and a psychiatric consultation was performed. After psychiatric consultation and remission of the symptoms with a placebo, a diagnosis of Munchausen syndrome was suspected. The patient's uncle was not initially convinced of the diagnosis. Some videos clearly showed that the boy was handling his prepuce to excrete stones, explaining the scars. A therapeutic plan with psychiatrist support was later accepted with a positive outcome. No further signs and symptoms of renal colic were reported. CONCLUSIONS: It is recommended that paediatricians include FD in the differential diagnosis of a persistent and unexplained medical condition. If suspicion arises, confirmation and long-term therapy by a group of qualified specialists, including psychiatrists, should be planned.

Influence of facet tropism on the location of lumbar disc herniation / A influência do tropismo facetário sobre a localização da hérnia discal lombar / Influencia del tropismo facetario en la ubicación de la hernia de disco lumbar

ABSTRACT Objective: To correlate facet tropism with the side and location of the intervertebral disc in which the lumbar disc herniation occurred. Methods: A retrospective descriptive study that evaluated Magnetic Resonance Imaging of 255 patients with lumbar disc herniation undergoing surgical treatment with the Spine Group of the Hospital Ortopédico de Passo Fundo between 2002 and 2014. The total patient number was stratified according to the side affected by the herniated disc (right or left), location of the hernia in the intervertebral disc (central, centrolateral, foraminal and extraforaminal) and demographic data, such as age, gender etc. The degree of facet joint tropism was measured by the Karakan method and classified as mild (difference less than 7º); moderate (between 7º and 15º) and severe (difference greater than 15º). Results: A statistical significant relationship (p= 0.023) was observed between the facet joint tropism and the side where the lumbar disc herniation occurred. No correlation was found between facet joint tropism and location of the herniation on the intervertebral disc. Conclusions: The degree of facet tropism presents a statistical significant correlation with the side of the intervertebral disc in which the lumbar disc herniation will develop. Level of Evidence: II. Type of study: Retrospective study.

RESUMO Objetivo: Correlacionar o tropismo facetário com o lado e local do disco intervertebral no qual ocorreu a hérnia discal lombar. Métodos: Estudo retrospectivo descritivo, no qual foram avaliados exames de Ressonância Nuclear Magnética de 255 pacientes com hérnia discal lombar submetidos a tratamento cirúrgico pelo Grupo de Coluna do Hospital Ortopédico de Passo Fundo, entre os anos de 2002 e 2014. Estratificou-se o total de pacientes pelo lado acometido pela hérnia discal (direito ou esquerdo), localização da hérnia no disco intervertebral (central, centro-lateral, foraminal e extra-foraminal) e por dados epidemiológicos, como idade, sexo etc. O grau de tropismo facetário foi mensurado pelo método de Karakan e classificado entre leve (diferença menor que 7º), moderado (entre 7º e 15º) e grave (diferença maior que 15º). Resultados: Foi verificada relação estatisticamente significativa (p= 0,023) entre o tropismo facetário e o lado em que ocorreu a hérnia discal lombar. Não foi encontrada correlação entre tropismo facetário e localização da hérnia discal no disco intervertebral. Conclusão: O grau de tropismo facetário apresenta correlação estatisticamente significativa com o lado do disco intervertebral no qual irá se desenvolver a hérnia discal. Nível de Evidência: II. Tipo de Estudo: Estudo retrospectivo.

RESUMEN Objetivo: Correlacionar el tropismo facetario con el lado y local del disco intervertebral en el cual ocurrió la hernia del disco lumbar. Métodos: Estudio retrospectivo descriptivo, en el fueron evaluados exámenes de resonancia magnética nuclear de 255 pacientes con hernia discal lumbar sometidos a tratamiento quirúrgico por el Grupo de Columna Vertebral del Hospital Ortopédico de Passo Fundo, entre los años 2002 y 2014. El número total de pacientes fue estratificado de acuerdo con el lado acometido por la hernia discal (izquierda o derecha), localización de la hernia en el disco intervertebral (central, centro-lateral, foraminal o extra-foraminal) y datos epidemiológicos como edad, sexo etc. El grado de tropismo facetario fue medido por el método de Karakan y clasificado como leve (diferencia menor que 7º), moderado (entre 7º y 15º) y grave (diferencia mayor que 15º). Resultados: Se verificó una relación estadísticamente significativa (p = 0,023) entre el tropismo facetario y el lado en que ocurrió la hernia discal lumbar. No se encontró correlación entre el tropismo facetario y la localización de la hernia en el disco intervertebral. Conclusiones: El grado de tropismo facetario presenta correlación estadísticamente significativa con el lado del disco intervertebral en el cual se desarrollará la hernia discal lumbar. Nivel de evidencia: II. Tipo de Estudio: Estudio retrospectivo.

A Small Supernumerary Marker Derived from the Pericentromeric Region of Chromosome 5: Case Report and Delineation of Partial Trisomy 5p Phenotype.

A 17-year-old girl presented with a distinct phenotype mainly featuring craniofacial dysmorphism, including a disproportioned large, round, elongated face; hypertelorism; deep-set eyes with short palpebral fissures; obesity (BMI 37), and a neuropsychiatric disorder with high-functioning autism. Postnatal conventional cytogenetic analyses from peripheral blood revealed a mosaic small supernumerary marker chromosome (sSMC) with a mos 47,XX,+mar[7]/46,XX[43] karyotype. By cenM-FISH technique, the sSMC was identified as a ring derivative of chromosome 5. Metaphase FISH analysis with a set of dedicated probes defined its origin from the pericentromeric region of chromosome 5, including the NIPBL gene at 5p13.2. Such sSMCs, exceedingly rare in the literature, underlie proximal trisomy 5p. In order to delineate a core phenotype of proximal trisomy 5p, we compared our patient's features with those of 6 patients found in the literature with similar der(5) chromosomes. Furthermore, a dozen individuals with 5p13 (micro)duplication syndrome was compared and discussed. We identified highly distinctive craniofacial dysmorphism, obesity, and intellectual disability and/or autism spectrum disorder as typical features of proximal 5p trisomy. In the critical region (band 5p13), the NIPBL gene is likely to be a major determinant of the neurobehavioral phenotype, and its presence at the sSMC level may be relevant to predict clinical outcome.

Neurological soft signs, but not theory of mind and emotion recognition deficit distinguished children with ADHD from healthy control.

Attention Deficit Hyperactivity Disorder (ADHD) is associated with social cognition impairment, executive dysfunction and motor abnormalities, consisting in the persistence of neurological soft signs (NSS). Theory of mind (ToM) and emotion recognition (ER) deficit of children with ADHD have been interpreted as a consequence of their executive dysfunction, particularly inhibitory control deficit. To our knowledge, there are not studies that evaluate the possible correlation between the ToM and ER deficit and NSS in the population with ADHD, while this association has been studied in other psychiatric disorders, such as schizophrenia. Therefore, the aim of this study was to evaluate ToM and ER and NSS in a sample of 23 drug-naïve children with ADHD and a sample of 20 healthy children and the possible correlation between social cognition dysfunction and NSS in ADHD. Our findings suggest that ToM and ER dysfunction is not a constant feature in the population with ADHD, while NSS confirmed as a markers of atypical neurodevelopment and predictors of the severity of functional impairment in children with ADHD.

Dysfunctional personality traits in adolescence: effects on alerting, orienting and executive control of attention.

The present study examined attentional networks performance in 39 adolescents with dysfunctional personality traits, split into two group, Group < 10 and Group ≥ 10, according to the number of criteria they met at the Structured Clinical Interview for DSM-IV Axis II Personality Disorders. The attentional performance has been tested by means of a modified version of the Attentional Network Test (ANTI-V) which allows testing both phasic and tonic components of the alerting system, the exogenous aspect of the orienting system, the executive network and their interactions. Results showed that the orienting costs of having an invalid spatial cue were reduced in the Group ≥ 10 criteria compared to the Group < 10. Moreover, adolescents included in the Group ≥ 10 showed lower conflict when attention was cued to the target location (valid trials) but showed normal interference when there was no overpowering focus of attention (invalid trials). The results found with ANOVA after splitting the sample into two categorical groups were also observed in a complementary correlation analysis keeping intact the continuous nature of such variables. These findings are consistent with the notion that dysfunctional features of personality disorders may represent the psychological manifestations of a neuropsychological abnormality in attention and executive functioning. Finally, we discuss the implications of this attentional anomaly for dysfunctional personality traits and behaviour.

Controlling attention to gaze and arrows in attention deficit hyperactivity disorder.

The aim of this research was to assess implicit processing of social and non-social distracting cues in children with ADHD. Young people with ADHD and matched controls were asked to classify target words (LEFT/RIGHT) which were accompanied by a distracter eye-gaze or arrow. Typically developing participants showed evidence of interference effects from both eye-gaze and arrow distracters. In contrast, the ADHD group showed evidence of interference effects from arrow but failed to show interference from eye-gaze. This absence of interference effects from eye-gaze observed in the participants with ADHD may reflect an attentional impairment in attending to socially relevant information.

Neurological soft signs are associated with attentional dysfunction in children with attention deficit hyperactivity disorder.

INTRODUCTION: Inattention is one of the core symptoms of Attention Deficit Hyperactivity Disorder (ADHD). Most of patients with ADHD show motor impairment, consisting in the persistence of neurological soft signs (NSS). Our aim was to evaluate attentional and motor functioning in an ADHD sample and healthy children (HC) and possible link between attentional dysfunction and motor impairment in ADHD. METHOD: Twenty-seven drug-naive patients with ADHD and 23 HC were tested with a test battery, measuring different aspects of attention. Motor evaluation has provided three primary variables: overflow movements (OM), dysrhythmia and total speed of timed activities. RESULTS: Compared to HC, patients were impaired in a considerable number of attentional processes and showed a greater number of NSS. Significant correlations between disturbances of attention and motor abnormalities were observed in ADHD group. CONCLUSION: Our findings suggest that attentional processes could be involved in the pathophysiology of the NSS and add scientific evidence to the predictive value of NSS as indicators of the severity of functional impairment in ADHD. Given the marked improvement or complete resolution of NSS following treatment with methylphenidate, we suggest that evaluation of NSS is useful to monitor the effectiveness of pharmacological treatment with MPH in ADHD.

First evidence of HERV-H transcriptional activity reduction after methylphenidate treatment in a young boy with ADHD.

Human endogenous retroviruses (HERVs) have been associated with many complex diseases including neuropsychiatric diseases, such as attention deficit hyperactivity disorder (ADHD). In ADHD an over-expression of HERV-H family in peripheral blood mononuclear cells has been documented. It has been hypothesized that HERVs may represent the link between genetic and environmental risk factors, contributing to the clinical onset and/or to the progression of the neurodevelopmental disease. The effect of pharmacological treatment on HERV transcriptional activity in psychiatric disorders has been attracting attention. Using a real-time RT-PCR we investigated the influence of methylphenidate on HERV transcription in peripheral blood mononuclear cells of a young patient with ADHD. In this clinical case we describe for the first time the reduction of HERV-H expression and the significant improvement of ADHD symptoms after 6 months of methylphenidate treatment.

Dopamine dysfunction in 22q11 deletion syndrome: possible cause of motor symptoms.

22q11 Deletion syndrome (22q11DS) is a neurogenetic disorder, resulting from a hemizygous microdeletion on the long arm of chromosome 22. In 22q11DS, the phenotypic expression is highly variable. Approximately one-third of all individuals with 22q11DS develop schizophrenia-like psychotic disorder. Among the genes in the deleted region, catechol-O-methyltransferase (COMT) has a particular relevance for psychiatric disorders: lower COMT enzymatic activity decreases the clearance of dopamine (DA), yielding higher levels of catecholamines in the central nervous system. Deficits in myelinogenesis and dysfunctions in the DA system could justify the white matter abnormalities in motor/premotor circuits described in 22q11DS. The alterations in DA could determine the high incidence of psychiatric disorders and the presence of neurological soft signs in 22q11DS. Neurological soft signs are defined as non-normative performance on an examination of motor and sensory tasks without focal neurological deficits. COMT haploinsufficiency, DA dysfunction, and white matter abnormalities may contribute toward the presence of neurological soft signs in 22q11DS.