Neurodevelopmental Disorders Associated with Chromosome 15

Chromosome 15 is a focus of increasing interest to both psychiatry and neurology. Several neurodevelopmental disorders are genetically associated with this autosome, including Prader-Willi syndrome, Angelman syndrome, Dyslexia, Autism, Hyperlexia, Ring 15 Chromosome syndrome, and Trisomy 15 syndrome. This report provides a review of the molecular biology of chromosome 15 and these associated disorders

Clinical variability in individuals with ATR-X syndrome in the Netherlands

Background: The Alpha Thalassemia mental Retardation syndrome, X-linked (ATR-X syndrome, MIM: 301040) is a rare genetic disorder characterized by alpha thalassemia, intellectual disability, peculier facial characteristics and genital abnormalities. Detailed information regarding the clinical phenotype is lacking. Aims: Detailed descriptions of the clinical phenotype are rare. The aim of this study was to describe the clinical phenotype of ATR-X syndrome. Methods: Data was collected through questionnaires, interviews, physical examination and the study of medical records. Results: Twenty-two individuals, aged 2–68 years old, were included. Three individuals were deceased at the time of the study. The individuals had a variable degree of intellectual disability. Alpha thalassemia was found in 30 % and genital anomalies in 70 % of the individuals. First clinical signs of the syndrome were most frequently feeding problems, started in the neonatal period in the majority. Other main reported health problems were reflux (59 %), constipation (72 %), periods of anorexia and adipsia (45 %), heart defects (28 %), epilepsy (33 %), scoliosis/kyphosis (48 %), visual impairment (61 %) and hearing loss (38 %). Behavioral problems (86 %) and sleeping problems (64 %) also occurred frequently. Conclusion: We report on the largest cohort of clinically studied individuals with ATR-X syndrome, including the eldest individuals, reported to date. Clinical knowledge is essential to improve care and to evaluate future therapies for this group.</p

Electroconvulsive therapy mediates neuroplasticity of white matter microstructure in major depression.

Whether plasticity of white matter (WM) microstructure relates to therapeutic response in major depressive disorder (MDD) remains uncertain. We examined diffusion tensor imaging (DTI) correlates of WM structural connectivity in patients receiving electroconvulsive therapy (ECT), a rapidly acting treatment for severe MDD. Tract-Based Spatial Statistics (TBSS) applied to DTI data (61 directions, 2.5 mm(3) voxel size) targeted voxel-level changes in fractional anisotropy (FA), and radial (RD), axial (AD) and mean diffusivity (MD) in major WM pathways in MDD patients (n=20, mean age: 41.15 years, 10.32 s.d.) scanned before ECT, after their second ECT and at transition to maintenance therapy. Comparisons made at baseline with demographically similar controls (n=28, mean age: 39.42 years, 12.20 s.d.) established effects of diagnosis. Controls were imaged twice to estimate scanning-related variance. Patients showed significant increases of FA in dorsal fronto-limbic circuits encompassing the anterior cingulum, forceps minor and left superior longitudinal fasciculus between baseline and transition to maintenance therapy (P&lt;0.05, corrected). Decreases in RD and MD were observed in overlapping regions and the anterior thalamic radiation (P&lt;0.05, corrected). Changes in DTI metrics associated with therapeutic response in tracts showing significant ECT effects differed between patients and controls. All measures remained stable across time in controls. Altered WM microstructure in pathways connecting frontal and limbic areas occur in MDD, are modulated by ECT and relate to therapeutic response. Increased FA together with decreased MD and RD, which trend towards normative values with treatment, suggest increased fiber integrity in dorsal fronto-limbic pathways involved in mood regulation

Study design, baseline patient characteristics and intervention in a cross-cultural framework: results from the ADORE study

Abstract : Objective : To describe the methodology and to present the baseline findings of the Attention-deficit/hyperactivity Disorder Observational Research in Europe (ADORE) study, the primary objective of which is to describe the relationship between treatment regimen prescribed and quality of life of children with ADHD in actual practice. Methods : In this 2-year prospective observational study, data on diagnosis, prescribed treatment and outcomes of ADHD were collected at seven time points by paediatricians and child psychiatrists on 1,573 children recruited in 10 European countries. The data presented here from the 1,478 patients included in the analyses describe the baseline condition, initial treatment regimen prescribed and quality of life of families with children with ADHD. Results : Patients had a mean age of 9.0 years (SD 2.5) and 84% were male. Physicians diagnoses were made using DSM-IV (43 %), ICD-10 (32%) and both DSM-IV and ICD-10 (12 %). Mean age of awareness of a problem was 5.1 years, suggesting an average delay of approximately 4 years between awareness and diagnosis of ADHD. Baseline ADHD rating scale scores (physicianrated) indicated moderate to severe ADHD. Parent-rated SDQ scores were in agreement and suggested significant levels of co-existing problems. CGI-S, CGAS and CHIPCE scores also indicated significant impairment. Patients were offered the following treatments after the initial assessment: pharmacotherapy (25 %), psychotherapy (19 %), combination of pharmacotherapy and psychotherapy (25 %), other therapy (10 %) and no treatment (21 %). Conclusion : The ADORE study shows that ADHD is similarly recognised across 10 European countries and that the children are significantly impaired across a wide range of domains. In this respect, they resemble children described in previous ADHD sample

Age-dependence of sensorimotor and cerebral electroencephalographic asymmetry in rats subjected to unilateral cerebrovascular stroke

Background: The human population mostly affected by stroke is more than 65 years old. This study was designed to meet the recommendation that models of cerebral ischemia in aged animals are more relevant to the clinical setting than young animal models. Until now the majority of the pre-clinical studies examining age effects on stroke outcomes have used rats of old age. Considering the increasing incidence of stroke among younger than old human population, new translational approaches in animal models are needed to match the rejuvenation of stroke. A better knowledge of alterations in stroke outcomes in middle-aged rats has important preventive and management implications providing clues for future investigations on effects of various neuroprotective and neurorestorative drugs against cerebrovascular accidents that may occur before late senescence. Methods: We evaluated the impact of transient focal ischemia, induced by intracerebral unilateral infusion of endothelin-1 (Et-1) near the middle cerebral artery of conscious rats, on volume of brain damage and asymmetry in behavioral and electroencephalographic (EEG) output measures in middle-aged (11-12 month-old) rats. Results: We did not find any age-dependent difference in the volume of ischemic brain damage three days after Et-1 infusion. However, age was an important determinant of neurological and EEG outcomes after stroke. Middle-aged ischemic rats had more impaired somatosensory functions of the contralateral part of the body than young ischemic rats and thus, had greater left-right reflex/sensorimotor asymmetry. Interhemispheric EEG asymmetry was more evident in middle-aged than in young ischemic rats, and this could tentatively explain the behavioral asymmetry.Conclusions: With a multiparametric approach, we have validated the endothelin model of ischemia in middle-aged rats. The results provide clues for future studies on mechanisms underlying plasticity after brain damage and motivate investigations of novel neuroprotective strategies against cerebrovascular accidents that may occur before late senescence. © 2013 Moyanova et al.; licensee BioMed Central Ltd

Phenotypic Spectrum and Molecular Findings in 17 ATR-X Syndrome Italian Patients: Some New Insights

ATR-X syndrome is a rare X-linked congenital disorder caused by hypomorphic mutations in the ATRX gene. A typical phenotype is well defined, with cognitive impairment, characteristic facial dysmorphism, hypotonia, gastrointestinal, skeletal, urogenital, and hematological anomalies as characteristic features. With a few notable exceptions, general phenotypic differences related to specific ATRX protein domains are not well established and should not be used, at least at the present time, for prognostic purposes. The phenotypic spectrum and genotypic correlations are gradually broadening, mainly due to rapidly increasing accessibility to NGS. In this scenario, it is important to continue describing new patients, illustrating the mode and age of onset of the typical and non-typical features, the classical ones and those tentatively added more recently. This report of well-characterized and mostly unreported patients expands the ATR-X clinical spectrum and emphasizes the importance of better clinical delineation of the condition. We compare our findings to those of the largest ATR-X series reported so far, discussing possible explanations for the different drawn conclusions

MECP2 duplication syndrome: The electroclinical features of a case with long-term evolution

MECP2 duplication syndrome (MDS) is a rare and severe neurodevelopmental disorder frequently associated with epilepsy. Different seizure types and electroencephalographic (EEG) patterns were described in patients with MDS, although it lacks a specific phenotype. We report on an adult patient with long-term epilepsy showing an evolution of the EEG pattern that progressively changed into burst suppression (BS) during sleep. As BS has not been previously reported in MDS, this report expands the neurophysiological phenotype of MDS and further suggest the possible occurrence of a longitudinal spectrum of seizure types and EEG patterns in MDS