Parent and self-report health-related quality of life measures in young patients with Tourette syndrome

Tourette syndrome is a neurodevelopmental disorder characterized by tics and comorbid behavioral problems. This study compared child- and parent-reported quality of life and everyday functioning. We assessed 75 children with Tourette syndrome, of which 42 (56%) had comorbid conditions (obsessive-compulsive disorder = 25; attention-deficit hyperactivity disorder = 6; both comorbidities = 4). All patients completed psychometric instruments, including the Gilles de la Tourette Syndrome-Quality of Life Scale for Children and Adolescents (child report) and the Child Tourette's Syndrome Impairment Scale (parent report). Data were compared for patients with pure Tourette syndrome, Tourette syndrome + obsessive-compulsive disorder, Tourette syndrome + attention-deficit hyperactivity disorder, and Tourette syndrome + both comorbidities. There were no group differences in quality of life. However, there were differences for total, school, and home activities impairment scores. Children and parents may not share similar views about the impact of Tourette syndrome on functioning. The measurement of health-related quality of life in Tourette syndrome is more complex in children than adults

Sex-Specific Effects of Prenatal Stress on Bdnf Expression in Response to an Acute Challenge in Rats : a Role for Gadd45β

Exposure to early adversities represents a major risk factor for psychiatric disorders. We have previously shown that exposure to prenatal stress (PNS) in rats alters the developmental expression of brain-derived neurotrophic factor (Bdnf) with a specific temporal profile. However, exposure to early-life stress is known to alter the ability to cope with challenging events later in life, which may contribute to the enhanced vulnerability to stress-related disorders. Since Bdnf is also an important player for activity-dependent plasticity, we investigated whether the exposure to PNS in rats could alter Bdnf responsiveness to an acute challenge at adulthood. We found that exposure to PNS produces significant changes in Bdnf responsiveness with brain region- and gender-specific selectivity. Indeed, exposure to an acute stress upregulates Bdnf expression in the prefrontal cortex, but not in the hippocampus, of control animals. Moreover, such modulatory activity is selectively impaired in PNS female rats, an effect that was associated with changes in the modulation of the DNA demethylase Gadd45\u3b2. Our results suggest that exposure to PNS may reprogram gene transcription through epigenetic mechanisms reducing the ability to cope under adverse conditions, a trait that is disrupted in psychiatric diseases

Modulation of BDNF expression by repeated treatment with the novel antipsychotic lurasidone under basal condition and in response to acute stress

It is known that long-term treatment with antipsychotic drugs (APDs) produces neuroadaptive changes through the modulation of different proteins that, by enhancing neuronal plasticity and cellular resiliency, may improve core disease symptoms. The aim of this study was to investigate the ability of chronic treatment with the novel antipsychotic lurasidone to modulate BDNF expression in hippocampus and prefrontal cortex, under basal conditions or in response to an acute stress, a major precipitating element in psychiatric disorders. By means of real-time PCR, we found that (1) chronic lurasidone treatment increases total BDNF mRNA levels in rat prefrontal cortex and, to less extent, in hippocampus; (2) the modulation of BDNF mRNA levels in response to acute swim stress in lurasidone-treated rats was markedly potentiated in hippocampus, and to less extent in prefrontal cortex, through the selective regulation of different neurotrophin isoforms. The increase of BDNF mRNA levels in prefrontal cortex was paralleled by an enhancement of mature BDNF protein levels. In conclusion, repeated exposure to lurasidone regulates BDNF expression, through a finely tuned modulation of its transcripts. This effect may contribute to the amelioration of functions, such as cognition, closely associated with neuronal plasticity, which are deteriorated in schizophrenia patients

Morc1 knockout evokes a depression-like phenotype in mice

Morc1 gene has recently been identified by a DNA methylation and genome-wide association study as a candidate gene for major depressive disorder related to early life stress in rodents, primates and humans. So far, no transgenic animal model has been established to validate these findings on a behavioral level. In the present study, we examined the effects of a Morc1 loss of function mutation in female C57BL/6N mice on behavioral correlates of mood disorders like the Forced Swim Test, the Learned Helplessness Paradigm, O-Maze and Dark-Light-Box. We could show that Morc1(-/-) mice display increased depressive-like behavior whereas no behavioral abnormalities regarding locomotor activity or anxiety-like behavior were detectable. CORT plasma levels did not differ significantly between Morc1(-/-) mice and their wildtype littermates, yet - surprisingly - total Bdnf mRNA-levels in the hippocampus were up-regulated in Morc1(-/-) animals. Although further work would be clarifying, Morc1(-/-) mice seem to be a promising epigenetically validated mouse model for depression associated with early life stress

Long-term chromospheric activity in southern M dwarfs: Gl 229 A and Gl 752 A

Several late-type stars present activity cycles similar to that of the Sun. However, these cycles have been mostly studied in F to K stars. Due to their small intrinsic brightness, M dwarfs are not usually the targets of long-term observational studies of stellar activity, and their long-term variability is generally not known. In this work, we study the long-term activity of two M dwarf stars: Gl 229 A (M1/2) and Gl 752 A (M2.5). We employ medium resolution echelle spectra obtained at the 2.15 m telescope at the Argentinian observatory CASLEO between the years 2000 and 2010 and photometric observations obtained from the ASAS database. We analyzed Ca \II K line-core fluxes and the mean V magnitude with the Lomb-Scargle periodogram, and we obtain possible activity cycles of $\sim$4 yr and $\sim$7 yr for Gl 229 A and Gl 752 A respectively.Comment: Accepted for publication by Astronomical Journal (AJ

Blood Chemistry, Acid- Base, Electrolyte, Blood Lactate Metabolism and Sleep at 3480 m in Mountain Marathon Runners

Altered blood chemistry, acid-base and electrolyte are suggested determinants of sleep disturbance, with frequent arousal at high altitude even in well and long-trained altitude marathon runners. In this sample of experienced altitude marathon runners with maximal aerobic power at sea level of 61.4 \ub1 2.7 ml/kg 121\u387min 121 we found that pO2 and percent of oxygen saturation (%SO2) were lower at 2050 m and 3480 m than at sea level; pO2 was higher after 38 - 41 hours than after 30 - 31 hours of acclimatization at 3480 m (P < 0.05). After ascent to 3480 m %SO2 decreased (P < 0.003). Compared to sea level values, pH increased at high altitude (P < 0.05) consistent with changes in pCO2 and [HCO3-] (P < 0.05). Nocturnal %SpaO2 at a sleeping altitude of 3480 m was lower (P < 0.05) than at sea level. At high altitude, the percent of wake (W) time and delay falling asleep (DFA) increased, whereas non-rapid eye movement sleep (N-REM), REM sleep and total sleep time (TST) decreased (P < 0.05). Simple regression analysis disclosed a significant correlation between the changes in TST and the percent of REM sleep and the changes in %SpaO2 recorded during sleep (P < 0.05). Simple regression analysis showed a positive correlation between the changes in pO2 at higher altitude and the percent of W and of TST (P < 0.05). The changes in pO2, tCO2 and [HCO3-] correlated negatively and significantly with the percent of REM sleep changes at high altitude (P < 0.05). The TST changes at high altitude correlated positively with the changes in pO2 and pH and correlated negatively with the changes in %SO2, pCO2, tCO2, and [HCO3-] (P < 0.05). The changes in the percent of W at high altitude correlated significantly and positively with the changes in bases excess [BE] at high altitude (P < 0.05). The changes in the percent of REM sleep correlated significantly and positively with the changes in [iCa++] and [BE] and negatively with the changes in buffered bases [BB] and [BEeffective] (P < 0.05). The change in the percent of NREM + REM sleep at high altitude correlated significantly and positively with the changes in [BE] and [BB] concentration (P < 0.05). The increase in DFA at high altitude correlated significantly and negatively with the changes in pCO2 and significantly and negatively with the changes in [K+] (P < 0.05). Simple regression analysis demonstrated that the changes in pH at high altitude correlated positively and significantly with the percent of W and the DFA and negatively with the percent of changes in NREM sleep, REM sleep, NREM + REM sleep (P < 0.05). The decrease in the TST at high altitude correlated significantly and negatively with the changes in pCO2, tCO2, [HCO3-]and [K+] (P < 0.05). Our data demonstrate that the arterialized ear lobe techniques we used for evaluating most of the changes in blood chemistry, acid-base, electrolyte and blood lactate metabolism are suitable for clinical and laboratory assessment and are important predictors of the quality and quantity of acclimatization and sleep at high altitude

Scn1a gene reactivation after symptom onset rescues pathological phenotypes in a mouse model of Dravet syndrome

Dravet syndrome is a severe epileptic encephalopathy caused primarily by haploinsufficiency of the SCN1A gene. Repetitive seizures can lead to endurable and untreatable neurological deficits. Whether this severe pathology is reversible after symptom onset remains unknown. To address this question, we generated a Scn1a conditional knock-in mouse model (Scn1a Stop/+) in which Scn1a expression can be re-activated on-demand during the mouse lifetime. Scn1a gene disruption leads to the development of seizures, often associated with sudden unexpected death in epilepsy (SUDEP) and behavioral alterations including hyperactivity, social interaction deficits and cognitive impairment starting from the second/third week of age. However, we showed that Scn1a gene re-activation when symptoms were already manifested (P30) led to a complete rescue of both spontaneous and thermic inducible seizures, marked amelioration of behavioral abnormalities and normalization of hippocampal fast-spiking interneuron firing. We also identified dramatic gene expression alterations, including those associated with astrogliosis in Dravet syndrome mice, that, accordingly, were rescued by Scn1a gene expression normalization at P30. Interestingly, regaining of Nav1.1 physiological level rescued seizures also in adult Dravet syndrome mice (P90) after months of repetitive attacks. Overall, these findings represent a solid proof-of-concept highlighting that disease phenotype reversibility can be achieved when Scn1a gene activity is efficiently reconstituted in brain cells

Long-term sex-dependent vulnerability to metabolic challenges in prenatally stressed rats

Prenatal stress (PNS) might affect the developmental programming of adult chronic diseases such as metabolic and mood disorders. The molecular mechanisms underlying such regulations may rely upon long-term changes in stress-responsive effectors such as Brain-Derived Neurotrophic Factor (BDNF) that can affect neuronal plasticity underlying mood disorders and may also play a role in metabolic regulation. Based upon previous data, we hypothesized that PNS might lead to greater vulnerability to an obesogenic challenge experienced at adulthood. In order to investigate our hypothesis, pregnant Sprague-Dawley female rats underwent a chronic procedure of restraint stress during the last week of gestation. The adult offspring were then challenged with a high fat diet (HFD) over 8 weeks and tested for metabolic and emotional endpoints. Moreover, brain specific changes in Bdnf expression levels were also assessed. Overall, HFD resulted in increased caloric intake, insulin resistance, impaired glucose tolerance and higher circulating levels of leptin, while PNS increased the leptin/adiponectin ratio, an index of metabolic risk in adult male subjects. Interestingly, HFD consumption increased anxiety-like behaviors in the Elevated Plus Maze, particularly in males, and this effect was buffered by PNS. Levels of Bdnf were finely modulated by PNS and HFD in a region- and sex-dependent fashion: female offspring overall showed greater plasticity, possibly mediated through increased total Bdnf mRNA expression both in the hippocampus and in the hypothalamus. In conclusion, while the experience of maternal stress during intrauterine life promotes metabolic dysfunction induced by a HFD at adulthood, the interaction between PNS and HFD is positive in male subjects, and in agreement with the match-mismatch hypothesis, resulting in a reduction of anxious behaviors