Concordance Between Measures of Anxiety and Physiological Arousal Following Treatment of Panic Disorder in Adolescence

This study examined the concordance (or synchrony/desynchrony) between adolescents' self-reports of anxiety and physiological measures of arousal (heart rate) both prior to and after treatment for panic disorder. Results indicated a decline in reported subjective units of distress (SUDS) for the treatment group only at the post-treatment measurement for two of three tasks. Within the treatment group, heart rate changes during the Behavioral Approach Test (BAT) were observed following treatment for one task only. Implications of this apparent desynchrony between self-report and physiological measures in adolescent panic disorder are discussed, with cognitive changes in participants' perception of anxiety after treatment suggested as an important factor in recovery

Cognitive-Behavioral Treatment of Panic Disorder in Adolescence

This investigation represents the first randomized controlled trial to evaluate the feasibility and efficacy of Panic Control Treatment for Adolescents (PCT-A). Thirteen adolescents, ages 14 to 17, were randomized to 11 weekly sessions of PCT-A treatment, whereas 13 were randomized to a self-monitoring control group. Results indicate that adolescents receiving immediate PCT-A showed a significant reduction in clinician-rated severity of panic disorder and in self-reported anxiety, anxiety sensitivity, and depression, in comparison to control group participants. These treatment gains were maintained at 3- and 6-month follow-up. Clinical severity of panic continued to improve from posttreatment to 3-month follow-up and then remained stable at 6-month follow-up. In light of study limitations, these findings suggest that cognitive-behavioral treatment for panic disorder in adolescence is a feasible and potentially efficacious intervention for this debilitating condition in youth

Identifying Efficacious Treatment Components of Panic Control Treatment for Adolescents: A Preliminary Examination

Panic Control Treatment for Adolescents (PCT-A) is a developmentally sensitive and efficacious treatment for adolescents with panic disorder. The present study is a preliminary examination of the relative efficacy of individual treatment components in PCT-A in a sample of treatment completers; the study identified when rapid improvements in panic symptoms occurred over the course of treatment and which treatment components preceded these gains. Twenty-one adolescents (ages 13-17) completed weekly measures of panic-relevant symptoms, which were examined for between-session gains. Results indicate that psychoeducation may precede notable decreases in panic attacks while cognitive restructuring may contribute to rapid declines in overall anxiety and cognitive errors. The authors discuss the importance of future controlled dismantling studies to examine the relative contribution of PCT-A treatment components

Developmental alterations in Huntington's disease neural cells and pharmacological rescue in cells and mice

Neural cultures derived from Huntington’s disease (HD) patient-derived induced pluripotent stem cells were used for ‘omics’ analyses to identify mechanisms underlying neurodegeneration. RNA-seq analysis identified genes in glutamate and GABA signaling, axonal guidance and calcium influx whose expression was decreased in HD cultures. One-third of gene changes were in pathways regulating neuronal development and maturation. When mapped to stages of mouse striatal development, the profiles aligned with earlier embryonic stages of neuronal differentiation. We observed a strong correlation between HD-related histone marks, gene expression and unique peak profiles associated with dysregulated genes, suggesting a coordinated epigenetic program. Treatment with isoxazole-9, which targets key dysregulated pathways, led to amelioration of expanded polyglutamine repeat-associated phenotypes in neural cells and of cognitive impairment and synaptic pathology in HD model R6/2 mice. These data suggest that mutant huntingtin impairs neurodevelopmental pathways that could disrupt synaptic homeostasis and increase vulnerability to the pathologic consequence of expanded polyglutamine repeats over time

Modular organization of the brainstem noradrenaline system coordinates opposing learning states

International audienceNoradrenaline modulates global brain states and diverse behaviors through what is traditionally believed to be a homogeneous cell population in the brainstem locus coeruleus (LC). However, it is unclear how LC coordinates disparate behavioral functions. We report a modular LC organization in rats, endowed with distinct neural projection patterns and coding properties for flexible specification of opposing behavioral learning states. LC projection mapping revealed functionally distinct cell modules with specific anatomical connectivity. An amygdala-projecting ensemble promoted aversive learning, while an independent medial prefrontal cortex-projecting ensemble extinguished aversive responses to enable flexible behavior. LC neurons displayed context-dependent inter-relationships, with moderate, discrete activation of distinct cell populations by fear or safety cues and robust, global recruitment of most cells by strong aversive stimuli. These results demonstrate a modular organization in LC in which combinatorial activation modes are coordinated with projection- and behavior-specific cell populations, enabling adaptive tuning of emotional responding and behavioral flexibility

Creation of an Open-Access, Mutation-Defined Fibroblast Resource for Neurological Disease Research

Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community