Kv7 potassium channel activation with ICA-105665 reduces photoparoxysmal EEG responses in patients with epilepsy.

PURPOSE: To assess the effects of ICA-105665, an agonist of neuronal Kv7 potassium channels, on epileptiform EEG discharges, evoked by intermittent photic stimulation (IPS), the so-called photoparoxysmal responses (PPRs) in patients with epilepsy. METHODS: Male and female patients aged 18-60 years with reproducible PPRs were eligible for enrollment. The study was conducted as a single-blind, single-dose, multiple-cohort study. Four patients were enrolled in each of the first three cohorts. Six patients were enrolled in the fourth cohort and one patient was enrolled in the fifth cohort. PPR responses to 14 IPS frequencies (steps) were used to determine the standard photosensitivity range (SPR) following placebo on day 1 and ICA-105665 on day 2. The SPR was quantified for three eye conditions (eyes closing, eyes closed, and eyes open), and the most sensitive condition was used for assessment of efficacy. A partial response was defined as a reduction in the SPR of at least three units at three separate time points following ICA-105665 compared to the same time points following placebo with no time points with more than three units of increase. Complete suppression was defined by no PPRs in any eye condition at one or more time points. KEY FINDINGS: Six individual patients participated in the first three cohorts (100, 200, and 400 mg). Six patients participated in the fourth cohort (500 mg), and one patient participated in the fifth cohort (600 mg). Decreases in SPR occurred in one patient at 100 mg, two patients receiving 400 mg ICA-105665 (complete abolishment of SPR occurred in one patient at 400 mg), and in four of six patients receiving 500 mg. The most common adverse events (AEs) were those related to the nervous system, and dizziness appeared to be the first emerging AE. The single patient in the 600 mg cohort developed a brief generalized seizure within 1 h of dosing, leading to the discontinuation of additional patients at this dose, per the predefined protocol stopping rules. SIGNIFICANCE: ICA-105665 reduced the SPR in patients at single doses of 100 (one of four), 400 (two of four), and 500 mg (four of six). This is the first assessment of the effects of activation of Kv7 potassium channels in the photosensitivity proof of concept model. The reduction of SPR in this patient population provides evidence of central nervous system (CNS) penetration by ICA-105665, and preliminary evidence that engagement with neuronal Kv7 potassium channels has antiseizure effects.

Self-help cognitive-behavioral therapy with minimal therapist contact for social phobia: a controlled trial.

Due to treatment accessibility and cost issues, interest in self-help programs (e.g., bibliotherapy, telehealth) for common psychological disorders is growing. Research supporting the efficacy of such a program for social anxiety, however, is limited. The present study examined the efficacy of an 8-week self-directed cognitive behavioral treatment with minimal therapist involvement for social phobia based on a widely available self-help book. Twenty-one adults with social phobia initially received either treatment (i.e. assigned readings in the workbook with limited therapist contact) or were wait-listed. Wait-listed patients eventually received the same self-directed treatment. Results revealed that the self-help/minimal therapist contact treatment was superior to wait-list on most outcome measures. Across the entire sample, reductions in social anxiety, global severity, general anxiety, and depression were observed at posttest and 3-month follow-up. These findings provide preliminary support for using this self-help workbook for individuals with mild to moderate social anxiety in conjunction with infrequent therapist visits to reinforce the treatment principles. Study limitations and future directions are discussed.

Parents' Use of Internal State Language with Toddlers at High and Low Genetic Risk for Autism Spectrum Disorder.

Parents of toddlers with an older sibling with autism spectrum disorder (ASD; high risk, HR) and parents of low risk (LR) toddlers with typically-developing older siblings read a wordless picture book to their child at 22 and 28 months. Parents' and toddlers' internal state language (ISL) was coded; parents reported on toddlers' use of ISL. Diagnostic assessments conducted at 36 months identified three groups: ASD, HR-noASD, LR. Parents did not differ in overall ISL, but parents of toddlers with later ASD attempted to elicit ISL from their children less than parents of LR toddlers. Toddlers increased their use of ISL with age, but those with ASD had lower scores and less age-related improvement than children in the other two groups.

Developmental Changes in Pretend Play from 22- to 34-Months in Younger Siblings of Children with Autism Spectrum Disorder.

Developmental trajectories of children's pretend play and social engagement, as well as parent sensitivity and stimulation, were examined in toddlers with an older sibling with autism spectrum disorder (ASD, high risk; HR) and toddlers with typically-developing older siblings (low risk; LR). Children (N = 168, 97 boys, 71 girls) were observed at 22, 28, and 34 months during free play with a parent and elicited pretend play with an examiner. At 28 and 34 months, children were asked to imagine the consequences of actions pantomimed by the examiner on a pretend transformation task. At 36 months children were assessed for ASD, yielding 3 groups for comparison: HR children with ASD, HR children without ASD (HR-noASD), and LR children. Children in all 3 groups showed developmental changes, engaging in more bouts of pretend play and obtaining higher scores on the elicited pretend and transformation tasks with age, but children with ASD lagged behind the other 2 groups on most measures. Children with ASD were also less engaged with their parents or the examiner during play interactions than either LR or HR-noASD children, with minimal developmental change evident. Parents, regardless of group, were highly engaged with their children, but parents of HR-noASD children received somewhat higher ratings on stimulation than parents of LR children. Most group differences were not accounted for by cognitive functioning. Instead, lower social engagement appears to be an important correlate of less advanced pretend skills, with implications for understanding the early development of children with ASD and for early intervention.

The cognitive mediation of thought-control strategies.

Research suggests that people use various strategies to control their normally occurring intrusive thoughts. Strategies that involve worrying about the thought and self punishment appear to be associated with certain forms of psychopathology, such as obsessive-compulsive (OC) symptoms. The present study sought to examine whether dysfunctional beliefs associated with OC symptoms (e.g., beliefs that intrusive thoughts are highly significant) underlie the use of such thought control strategies. Ninety-three non-clinical participants completed self-report questionnaires measuring cognitive variables, thought-control strategies, and OC symptoms. Analyses revealed that overestimates of threat and responsibility, beliefs about the significance and need to control intrusions, the need for perfection and certainty, and scrupulosity were associated with the use of punishment, but not worry thought control strategies. These cognitive phenomena also mediated the relationship between OC symptoms and the use of punishment as a thought-control strategy. Results are discussed in terms of cognitive models of OC symptoms and their implications for cognitive-behavioral therapy.

An experimental analysis of hypochondriasis.

Hypochondriasis (HC) involves preoccupation with fears of having a serious medical illness based on the misinterpretation of benign bodily perturbations. Individuals with HC also perform behaviors such as checking and reassurance-seeking presumably to reduce health-related fears. Experimental behavioral analyses of HC symptoms, however, are lacking. In the present study, 27 patients with HC were exposed to personally relevant health-related stimuli under one of two conditions: (a) subsequently performing safety-seeking behaviors (e.g., checking) (n=14) or (b) subsequently being instructed not to perform such behaviors (n=13). In both groups, subjective anxiety and urges to perform safety behaviors were monitored for 1h. Results indicated that exposure to the personally relevant health trigger provoked anxiety and urges to perform safety behaviors. For patients who performed such behaviors, these feelings were reduced. For patients who did not, a more gradual reduction of anxiety and urges was observed. Findings are discussed in terms of the conceptualization and treatment of HC behavior, and are relevant to HC's possible relationship to panic and obsessive-compulsive disorder.

Developmental Changes in Empathic Concern and Self-Understanding in Toddlers at Genetic Risk for Autism Spectrum Disorder.

Toddlers with an older sibling with autism spectrum disorder (ASD) and low risk (LR) toddlers were observed at 22, 28, and 34 months during two empathy probes: a crying baby and an adult who pretended to hurt her finger. Toddlers with a later ASD diagnosis showed less empathic concern and self-distress at each age on both empathy probes than LR toddlers. HR toddlers with no diagnosis showed growth in empathic concern between 22 and 34 months in response to the adult's pain, differing from the children with ASD, but not the LR children, by 34 months. Developmental changes in parent-rated self-understanding showed a similar pattern. Results highlight individual differences in the social development of HR toddlers.

Pretend Play and Social Engagement in Toddlers at High and Low Genetic Risk for Autism Spectrum Disorder.

Toddlers with an older sibling with autism spectrum disorder (ASD) and low risk (LR) toddlers with typically-developing older siblings were observed during free play with a parent and elicited pretend with an examiner at 22-months. Functional and pretend play, children's social engagement, and parent sensitivity were assessed during free play. Complexity of play was assessed during the elicited pretend task. Toddlers with an ASD diagnosis showed less pretend play across contexts and less social engagement with parents or the examiner than either LR toddlers or high risk toddlers without a diagnosis (HR-noASD). Lower levels of pretend play and social engagement were associated with symptom severity within the high risk group, reflecting emerging ASD in toddlerhood.

Mild traumatic brain injury and anxiety sequelae: a review of the literature.

There is scattered but significant psychological and neuropsychological evidence to suggest that mild traumatic brain injury (mild TBI) plays a notable role in the emergence and expression of anxiety. Conversely, there is also empirical evidence to indicate that anxiety may exert a pronounced impact on the prognosis and course of recovery of an individual who has sustained a mild TBI. Although the relationship between mild TBI and anxiety remains unclear, the present body of research attempts to elucidate a number of aspects regarding this topic. Overall, the mild TBI research is rife with inconsistencies concerning prevalence rates, the magnitude and implications of this issue and, in the case of PTSD, even whether certain diagnoses can exist at all. This review obviates the need for greater consistencies across studies, especially between varying disciplines, and calls for a shift from studies overly focused on categorical classification to those concerned with dimensional conceptualization.