1. Braat S, Kooy RF. {{Insights into GABAergic System Deficits in Fragile X Syndrome Lead to Clinical Trials}}. {Neuropharmacology};2014 (Jul 9)
An increasing number of studies implicate the GABAAergic system in the pathophysiology of the fragile X syndrome, a frequent cause of intellectual disability and autism. Animal models have proven invaluable in unravelling the molecular mechanisms underlying the disorder. Multiple defects in this inhibitory system have been identified in Fmr1 knockout mice, including altered expression of various components, aberrant GABAA receptor-mediated signalling, altered GABA concentrations and anatomical defects in GABAergic neurons. Aberrations compatible with those described in the mouse model were detected in dfmr1 deficient Drosophila melanogaster, a validated fly model for the fragile X syndrome. Treatment with drugs that ameliorate the GABAAergic deficiency in both animal models have demonstrated that the GABAA receptor is a promising target for the treatment of fragile X patients. Based on these preclinical studies, clinical trials in patients have been initiated.
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2. Heard TT, Ramgopal S, Picker J, Lincoln SA, Rotenberg A, Kothare SV. {{EEG abnormalities and seizures in genetically diagnosed Fragile X syndrome}}. {Int J Dev Neurosci};2014 (Jul 9)
We describe the seizure and EEG characteristics in a population of children with known Fragile X. The medical records of 135 genetically confirmed FXS patients receiving care in a Fragile X clinic and their available EEG reports were reviewed. The mean age was 5.94 years old including 18 males and 1 female. The mean age was 4-9 years old with an age range of 15 months to 13 years old. Twenty-two patients (16.3%) in the series had parent-reported behavior suspicious of seizures. Sixteen patients (14.1%, 1 female) had at least one EEG recorded for evaluation of clinical events suspicious for seizure, and three patients (2.2%) had an EEG in the context of a polysomnography for diagnosing sleep apnea. The mean age at EEG evaluation was 6.0 years (standard deviation 3.8 years). EEG findings included slowing of background rhythm (n=9) and epileptiform discharges (n=7). Four patients had normal EEGs (n=4). Six patients (4.4% of the sample population) were diagnosed with epilepsy by both clinical seizure semiology and documented EEG abnormalities. Thirteen patients (68.4% of total) had episodes of staring and behavioral arrest with no EEG correlate, indicating non-epileptic events. Of the eight patients who underwent a repeat EEG, five patients had showed normalization in the posterior dominant rhythm over time, two patients had unchanged findings and one patient had worsening of his EEG. Our data warrant further prospective validation.
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3. Pasalich DS, Dadds MR, Hawes DJ. {{Cognitive and affective empathy in children with conduct problems: Additive and interactive effects of callous-unemotional traits and autism spectrum disorders symptoms}}. {Psychiatry Res};2014 (Jun 24)
Callous-unemotional (CU) traits and autism spectrum disorders (ASD) symptoms are characterized by problems in empathy; however, these behavioral features are rarely examined together in children with conduct problems. This study investigated additive and interactive effects of CU traits and ASD symptoms in relation to cognitive and affective empathy in a non-ASD clinic-referred sample. Participants were 134 children aged 3 to 9 years (M=5.60; 79% boys) with oppositional defiant/conduct disorder, and their parents. Clinicians, teachers, and parents reported on dimensions of child behavior, and parental reports of family dysfunction and direct observations of parental warmth/responsiveness assessed quality of family relationships. Results from multiple regression analysis showed that, over and above the effects of child conduct problem severity and quality of family relationships, both ASD symptoms and CU traits were uniquely associated with deficits in cognitive empathy. Moreover, CU traits demonstrated an independent association with affective empathy, and this relationship was moderated by ASD symptoms. That is, there was a stronger negative association between CU traits and affective empathy at higher versus lower levels of ASD symptoms. These findings suggest including both CU traits and ASD-related social impairments in models delineating the atypical development of empathy in children with conduct problems.
