Francesco Margari

GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak

Paroxysmal dyskinesias are episodic movement disorders that can be inherited or are sporadic in nature. The pathophysiology underlying these disorders remains largely unknown but may involve disrupted ion homeostasis due to defects in cell-surface channels or nutrient transporters. In this study, we describe a family with paroxysmal exertion-induced dyskinesia (PED) over 3 generations. Their PED was accompanied by epilepsy, mild developmental delay, reduced CSF glucose levels, hemolytic anemia with echinocytosis, and altered erythrocyte ion concentrations. Using a candidate gene approach, we identified a causative deletion of 4 highly conserved amino acids (Q282_S285del) in the pore region of the glucose transporter 1 (GLUT1). Functional studies in Xenopus oocytes and human erythrocytes revealed that this mutation decreased glucose transport and caused a cation leak that alters intracellular concentrations of sodium, potassium, and calcium. We screened 4 additional families, in which PED is combined with epilepsy, developmental delay, or migraine, but not with hemolysis or echinocytosis, and identified 2 additional GLUT1 mutations (A275T, G314S) that decreased glucose transport but did not affect cation permeability. Combining these data with brain imaging studies, we propose that the dyskinesias result from an exertion-induced energy deficit that may cause episodic dysfunction of the basal ganglia, and that the hemolysis with echinocytosis may result from alterations in intracellular electrolytes caused by a cation leak through mutant GLUT1.

A review of executive function deficits in autism spectrum disorder and attention-deficit/hyperactivity disorder

Executive dysfunction has been shown to be a promising endophenotype in neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). This article reviewed 26 studies that examined executive function comparing ASD and/or ADHD children. In light of findings from this review, the ASD + ADHD group appears to share impairment in both flexibility and planning with the ASD group, while it shares the response inhibition deficit with the ADHD group. Conversely, deficit in attention, working memory, preparatory processes, fluency, and concept formation does not appear to be distinctive in discriminating from ASD, ADHD, or ASD + ADHD group. On the basis of neurocognitive endophenotype, the common co-occurrence of executive function deficits seems to reflect an additive comorbidity, rather than a separate condition with distinct impairments.

Parents Psychopathology of Children with Attention Deficit Hyperactivity Disorder.

Attention Deficit Hyperactivity Disorder (ADHD) is a disorder with extremely complex etiology, not yet well defined but certainly multi-factorial. This study investigated the possible etiopathogenetic role of ADHD symptoms and psychopathology disorders in parents of children with ADHD. We present a case-control study of parents of 50 children affected by ADHD and of 45 healthy children, matched to age and gender. Parents of ADHD children reported higher levels of ADHD symptoms, depressive disorders and Depressive Personality Disorders than parents of healthy children. Mothers displayed greater presence of depression, while fathers showed problems concerning alcohol use. The occurrence of ADHD symptoms, psychopathology and personality disorders in parents highlights the importance to integrate the treatment programs in the ADHD children with the screening and treatment for psychopathological symptoms of the parents.

Psychiatric Symptoms and Quality of Life in Patients Affected by Epidermolysis Bullosa

The aim of our study was to provide a psychosocial and psychiatric evaluation of patients with epidermolysis bullosa (EB; a rare genetic disorder characterized by skin fragility), to assess psychological status, ascertain the presence of any psychiatric disorders and understand the impact of EB on quality of life. Twenty-five patients were assessed using a case record form and several standardized instruments. In 82% of patients, EB had a negative impact on quality of life and 80% of patients experienced psychiatric symptoms. Our findings revealed a high prevalence of psychosocial problems and psychiatric symptoms in patients with EB and suggested that a combined bio-psychosocial approach is the most appropriate therapeutic intervention.

Tolerability and safety profile of risperidone in a sample of children and adolescents.

The aim of this prospective observational study was to verify the tolerability and safety profile of risperidone in a sample of antipsychotic-naive children/adolescent patients having a different psychiatric diagnosis. Twenty-two (mean age of 12±3.2) antipsychotic-naive patients who started therapy with risperidone were recruited. The assessment involved anthropometric data (weight, height, BMI, BMI z-score and BMI percentile), cardiovascular parameters (blood pressure and QTc interval) and blood tests (levels of glucose, triglycerides, total cholesterol, glutamic oxaloacetic and pyruvic transaminases, &ggr;-glutamyl transferase, prolactin, free triiodothyronine, free thyroxine, thyroid-stimulating hormone, thyroglobulin, antithyroid peroxidase and antithyroglobulin). After an average follow-up of 6 months of risperidone therapy, a statistically significant increase in weight and body composition was observed. Furthermore, an increase in serum levels of prolactin was observed in 50% of patients. No other significant changes in metabolic and cardiovascular parameters were found. Although an increase in these parameters was detected, it remained in the normal range. This study suggests the use of specific protocols for monitoring children/adolescents treated with second-generation antipsychotics to manage the metabolic long-term complications and progression to more severe disease states.

Clinical features and therapeutic management of patients admitted to Italian acute hospital psychiatric units: the PERSEO (psychiatric emergency study and epidemiology) survey.

BackgroundThe PERSEO study (psychiatric emergency study and epidemiology) is a naturalistic, observational clinical survey in Italian acute hospital psychiatric units, called SPDCs (Servizio Psichiatrico Diagnosi e Cura; in English, the psychiatric service for diagnosis and management). The aims of this paper are: (i) to describe the epidemiological and clinical characteristics of patients, including sociodemographic features, risk factors, life habits and psychiatric diagnoses; and (ii) to assess the clinical management, subjective wellbeing and attitudes toward medications.MethodsA total of 62 SPDCs distributed throughout Italy participated in the study and 2521 patients were enrolled over the 5-month study period.ResultsAlmost half of patients (46%) showed an aggressive behaviour at admission to ward, but they engaged more commonly in verbal aggression (38%), than in aggression toward other people (20%). A total of 78% of patients had a psychiatric diagnosis at admission, most frequently schizophrenia (36%), followed by depression (16%) and personality disorders (14%), and no relevant changes in the diagnoses pattern were observed during hospital stay. Benzodiazepines were the most commonly prescribed drugs, regardless of diagnosis, at all time points. Overall, up to 83% of patients were treated with neuroleptic drugs and up to 27% received more than one neuroleptic either during hospital stay or at discharge. Atypical and conventional antipsychotics were equally prescribed for schizophrenia (59 vs 65% during stay and 59 vs 60% at discharge), while atypical drugs were preferred in schizoaffective psychoses (72 vs 49% during stay and 70 vs 46% at discharge) and depression (41 vs 32% during stay and 44 vs 25% at discharge). Atypical neuroleptics were slightly preferred to conventional ones at hospital discharge (52 vs 44%). Polypharmacy was in general widely used. Patient attitudes toward medications were on average positive and self-reported compliance increased during hospital stay.ConclusionResults confirm the widespread use of antipsychotics and the increasing trend in atypical drugs prescription, in both psychiatric in- and outpatients.

Parenting stress among parents of children with Neurodevelopmental Disorders

In recent years, studies have shown that parents of children with Neurodevelopmental Disorders (NDDs) experience more parenting stress than parents of typically developing children, but the relation between the type of disorders and parenting stress is far from clear. The purpose of this study was to compare the parenting stress experienced by parents of 239 children with Specific Learning Disorders (SpLD), Language Disorders (LD), Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD), and typical development (TD). Parents of children with NDDs experience more parenting stress than those of children who have TD. Although, parents of children with ASD or ADHD report the most high scores of parenting stress, also the parents of children with SpLD or LD report higher parental stress compared with parent of children without NDDs. Another interesting finding was that IQ level or emotional and behavioral problems are associated with the higher levels of parenting stress. This study suggest that parent, both mothers and fathers, of children with different type of NDDs should be provided with interventions and resources to empower them with the knowledge and skills to reduce their stress and to enhance their quality of life.

Psychopathology in children and adolescents with primary headaches: categorical and dimensional approaches.

Background Recurrent headache is common in childhood, but there is not a great amount of data on the associations between headaches and psychopathology in children. Objective The aim of this study is to examine the relationships between primary headaches and psychopathology in children, using both the categorical and dimensional assessment. Methods The sample consisted of 70 patients with primary headache compared to a matched sample of 50 healthy children. Psychiatric comorbidity was defined according to the diagnostic criteria of the Diagnostic and Statistical Manual of Disorders. Child psychopathology outcomes were assessed using child- and parent-reported standardized instruments. Results Internalizing and externalizing problems were significantly represented among children with headaches compared to the control group, respectively 63% and 27%, without significant differences between migraine and tension-type headache children. Moreover, a total of 26% of the children with a headache reported psychiatric comorbidity such as anxiety and mood disorders. Conclusion The dimensional approach improves accuracy in the recognition of emotional and behavioral problems compared to the categorical approach; however, the use of both of these approaches could be useful for clinical practice, treatment and research.

Aggression, impulsivity, and suicide risk in benign chronic pain patients - a cross-sectional study

Objectives The objective of this study was to investigate the role that psychopathological dimensions as overt aggression and impulsivity play in determining suicide risk in benign chronic pain patients (CPPs). Furthermore we investigated the possible protective/risk factors which promote these negative feelings, analyzing the relationship between CPPs and their caregivers. Methods We enrolled a total of 208 patients, divided into CPPs and controls affected by internistic diseases. Assessment included collection of sociodemographic and health care data, pain characteristics, administration of visual analog scale (VAS), Modified Overt Aggression Scale (MOAS), Barratt Impulsiveness Scale Version 11 (BIS), Hamilton Depression Rating Scale (HDRS), and a caregiver self-administered questionnaire. All variables were statistically analyzed. Results A significant difference of VAS, MOAS-total/verbal/auto-aggression, HDRS-total/suicide mean scores between the groups were found. BIS mean score was higher in CPPs misusing analgesics. In CPPs a correlation between MOAS-total/verbal/auto-aggression with BIS mean score, MOAS with HDRS-suicide mean score and BIS with HDRS-suicide mean scores were found. The MOAS and BIS mean scores were significantly higher when caregivers were not supportive. Conclusion In CPPs, aggression and impulsivity could increase the risk of suicide. Moreover, impulsivity, overt aggression and pain could be interrelated by a common biological core. Our study supports the importance of a multidisciplinary approach in the CPPs management and the necessity to supervise caregivers, which may become risk/protective factors for the development of feelings interfering with the treatment and rehabilitation of CPPs.

Familial liability, obstetric complications and childhood development abnormalities in early onset schizophrenia: a case control study

BackgroundGenetic and environmental risk factors and gene-environment interactions are linked to higher likelihood of developing schizophrenia in accordance with the neurodevelopmental model of disease; little is known about risk factors and early development in early-onset schizophrenia (EOS) and very early-onset schizophrenia (VEOS).MethodsWe present a case-control study of a sample of 21 patients with EOS/VEOS and a control group of 21 patients with migraine, recruited from the Child Neuropsychiatry Unit, Department of Neurologic and Psychiatric Science, University of Bari, Italy. The aim was to assess the statistical association between VEOS/EOS and family history for psychiatric disorders, obstetric complications and childhood developmental abnormalities using 2 × 2 tables and a Chi Squared or Fisher test.ResultsThe results show a statistical association between EOS/VEOS and schizophrenia and related disorders (P = 0.02) and personality disorders (P = 0.003) in relatives, and between EOS/VEOS and developmental abnormalities of early relational skills (P = 0.008) and learning (P = 0.04); there is not a statistically relevant difference between cases and controls (P > 0.05) for any obstetric complications (pre, peri and postpartum).ConclusionsThis study confirms the significant role of familial liability but not of obstetric complications in the pathogenesis of VEOS/EOS; the association between childhood developmental abnormalities and EOS/VEOS supports the neurodevelopmental model of disease.