A novel germline mutation in the TSH receptor gene causes non-autoimmune autosomal dominant hyperthyroidism

OBJECTIVE: Clinical and genetic investigations were undertaken in a case of familial hyperthyroidism, with onset of thyrotoxic symptoms varying between childhood/adolescence. METHODS: Automatic sequence analysis was carried out of the TSH receptor (TSHR) gene. Functional studies were undertaken of mutant TSHR in transient expression experiments in COS-7 cells including the evaluation of cAMP accumulation and of protein expression by flow cytometry, as well as the calculation of specific constitutive activity (SCA). RESULTS: In four affected cases, the age of onset of thyrotoxic manifestations of non-autoimmune origin varied between 5 and 18 years. The disease transmission was typically autosomal dominant. TSHR gene sequence revealed the presence of a germline heterozygous substitution at codon 597 leading to the novel mutation V597F. This residue is located in the 5th transmembrane domain of the receptor protein in a critical region for membrane targeting and signal transduction. Functional studies of the V597F mutant indicate an 11-fold increase in SCA, associated with a reduction in receptor protein expression on the cytoplasmic membrane. CONCLUSIONS: Description was made of a family with non-autoimmune autosomal dominant hyperthyroidism carrying a novel mutation of TSHR leading to the increment in specific constitutive activity. Factors that may influence the clinical expression of TSHR germline mutations are discussed

A large-scale study on the effects of sex on gray matter asymmetry

Research on sex-related brain asymmetries has not yielded consistent results. Despite its importance to further understanding of normal brain development and mental disorders, the field remains relatively unexplored. Here we employ a recently developed asymmetry measure, based on the Dice coefficient, to detect sex-related gray matter asymmetries in a sample of 457 healthy participants (266 men and 191 women) obtained from 5 independent databases. Results show that women’s brains are more globally symmetric than men’s (p < 0.001). Although the new measure accounts for asymmetries distributed all over the brain, several specific structures were identified as systematically more symmetric in women, such as the thalamus and the cerebellum, among other structures, some of which are typically involved in language production. These sex-related asymmetry differences may be defined at the neurodevelopmental stage and could be associated with functional and cognitive sex differences, as well as with proneness to develop a mental disorder

The developmental pattern of stimulus and response interference in a color-object Stroop task: an ERP study

<p>Abstract</p> <p>Background</p> <p>Several studies have shown that Stroop interference is stronger in children than in adults. However, in a standard Stroop paradigm, stimulus interference and response interference are confounded. The purpose of the present study was to determine whether interference at the stimulus level and the response level are subject to distinct maturational patterns across childhood. Three groups of children (6–7 year-olds, 8–9 year-olds, and 10–12 year-olds) and a group of adults performed a manual Color-Object Stroop designed to disentangle stimulus interference and response interference. This was accomplished by comparing three trial types. In congruent (C) trials there was no interference. In stimulus incongruent (SI) trials there was only stimulus interference. In response incongruent (RI) trials there was stimulus interference and response interference. Stimulus interference and response interference were measured by a comparison of SI with C, and RI with SI trials, respectively. Event-related potentials (ERPs) were measured to study the temporal dynamics of these processes of interference.</p> <p>Results</p> <p>There was no behavioral evidence for stimulus interference in any of the groups, but in 6–7 year-old children ERPs in the SI condition in comparison with the C condition showed an occipital P1-reduction (80–140 ms) and a widely distributed amplitude enhancement of a negative component followed by an amplitude reduction of a positive component (400–560 ms). For response interference, all groups showed a comparable reaction time (RT) delay, but children made more errors than adults. ERPs in the RI condition in comparison with the SI condition showed an amplitude reduction of a positive component over lateral parietal (-occipital) sites in 10–12 year-olds and adults (300–540 ms), and a widely distributed amplitude enhancement of a positive component in all age groups (680–960 ms). The size of the enhancement correlated positively with the RT response interference effect.</p> <p>Conclusion</p> <p>Although processes of stimulus interference control as measured with the color-object Stroop task seem to reach mature levels relatively early in childhood (6–7 years), development of response interference control appears to continue into late adolescence as 10–12 year-olds were still more susceptible to errors of response interference than adults.</p

Mindful Aging: The Effects of Regular Brief Mindfulness Practice on Electrophysiological Markers of Cognitive and Affective Processing in Older Adults

There is growing interest in the potential benefits of mindfulness meditation practices in terms of counteracting some of the cognitive effects associated with aging. Pursuing this question, the aim of the present study was to investigate the influence of mindfulness training on executive control and emotion regulation in older adults, by means of studying behavioral and electrophysiological changes. Participants, 55 to 75 years of age, were randomly allocated to an 8-week mindful breath awareness training group or an active control group engaging in brain training exercises. Before and after the training period, participants completed an emotional-counting Stroop task, designed to measure attentional control and emotion regulation processes. Concurrently, their brain activity was measured by means of 64-channel electroencephalography. The results show that engaging in just over 10 min of mindfulness practice five times per week resulted in significant improvements in behavioral (response latency) and electrophysiological (N2 event-related potential) measures related to general task performance. Analyses of the underlying cortical sources (Variable Resolution Electromagnetic Tomography, VARETA) indicate that this N2-related effect is primarily associated with changes in the right angular gyrus and other areas of the dorsal attention network. However, the study did not find the expected specific improvements in executive control and emotion regulation, which may be due to the training instructions or the relative brevity of the intervention. Overall, the results indicate that engaging in mindfulness meditation training improves the maintenance of goal-directed visuospatial attention and may be a useful strategy for counteracting cognitive decline associated with aging

Processing of Body Odor Signals by the Human Brain

Brain development in mammals has been proposed to be promoted by successful adaptations to the social complexity as well as to the social and non-social chemical environment. Therefore, the communication via chemosensory signals might have been and might still be a phylogenetically ancient communication channel transmitting evolutionary significant information. In humans, the neuronal underpinnings of the processing of social chemosignals have been investigated in relation to kin recognition, mate choice, the reproductive state and emotional contagion. These studies reveal that human chemosignals are probably not processed within olfactory brain areas but through neuronal relays responsible for the processing of social information. It is concluded that the processing of human social chemosignals resembles the processing of social signals originating from other modalities, except that human social chemosignals are usually communicated without the allocation of attentional resources, that is below the threshold of consciousness. Deviances in the processing of human social chemosignals might be related to the development and maintenance of mental disorders

Genetic analysis of italian patients with congenital hyperinsulinism of infancy.

Background/Aims: Congenital hyperinsulinism of infancy is a rare disease that needs prompt treatment to avoid brain damage. There are currently no data regarding the clinical and molecular features of Italian patients. Methods: Thirty-three patients with HI and their parents were included. Consanguinity was reported in six patients. Half of patients were macrosomic at birth. None had raised 3-hydroxybutyrylcarnitine or hyperammonemia. Molecular analysis of ABCC8 and KCNJ11 genes was performed in all patients, and subjects with no mutation underwent analysis of HNF4A and GCK. GLUD1 and HADH genes were analyzed in a patient with leucine sensitivity. Results: Mutations in the ABCC8 and KCNJ11 genes were found in 45% of the patients (6 novel). No mutations in HNF4A, GLUD1 and GCK genes were found. Recessive mode of inheritance was found in 21% of patients. A single heterozygous mutation was identified in 24% of probands. 72% of the patients were responsive to medical treatment, and 44% of the 17 patients with no identified mutation achieved spontaneous remission. Nine children, unresponsive to medical therapy, underwent pancreatectomy. Conclusion: This is the first report on hyperinsulinism of infancy in Italy, confirming the complexity of the clinical forms and the heterogeneity of the genetic causes of the disease