Juvenile onset Huntington's disease--clinical and research perspectives

Huntington's disease (HD) is an inherited neurodegenerative disorder. The mutation which causes the disease is an expansion in the number of repetitions of three nucleotides, C, A, and G in exon 1 of the huntingtin gene. The gene normally has 15 to 30 repeats and an expansion to 40 or more is associated with HD. HD usually has a mid-life onset, but a juvenile form, defined by onset of symptoms before the age of 21 years, is present in about 7% of HD cases. Juvenile HD is characterized by (1) transmission from an HD affected father, (2) an unusually large repeat size, usually of 60 or more units, and (3) unique clinical features, including rigidity and seizure disorder. Although juvenile onset is associated with a more severe neuropathological involvement, the neuropathological characteristics of juvenile HD are similar to those seen in the adult form in that the striatum bears the brunt of the illness. Clumps of protein, termed inclusion bodies, which stain positive for huntingtin and ubiquitin, are found primarily in the nucleus but also in the cytoplasm and axons in HD neurons. Research suggests that these inclusion bodies sequester a deleterious protein fragment and prolong cell life during the degenerative process of the disease.     

Counseling Women in Midlife: An Integrative Approach to Menopause

Menopause is a normative life transition that is experienced by virtually all women, yet remains poorly understood. The dominance of the biomedical model results in a unidimensional definition of menopause as a biological event, ignoring the influence of cultural and psychosocial factors. Counselors who use an integrative approach can not only provide accurate biomedical information but also conceptualize menopause as a normative midlife transition. The purpose of this article is to provide a foundation in biomedical issues and to consider how these independently, and in interaction with cultural and psychosocial factors, influence the experience of menopause.     

Metacognitive therapy in treatment-resistant depression: a platform trial

Patients with treatment-resistant depression received up to 8 sessions of metacognitive therapy (MCT) targeting attentional control, rumination, worry, and metacognitive beliefs. A baseline period was followed by weekly sessions with follow-up assessments at 6 and 12 months post treatment. Large and statistically significant improvements occurred in all symptom measures at post treatment and were maintained over follow-up. Two out of 3 process measures significantly improved at post treatment and all of these measures were improved at follow-up. Treatment was associated with similar response rates on the BDI and Hamilton rating scale. Using liberal criteria 80% of completers were classified as recovered at post treatment and 70% at follow-up on the BDI. In the intention to treat sample 66.6% were recovered at post treatment and 58.3% at follow-up. More stringent criteria showed 60% recovery rates at post treatment and at 12 m. The results suggest that MCT could be a brief and effective treatment and they provide a precedent for more definitive randomized controlled trials.     

I know you're me, but who am I? Perspective taking and seeing the other in the self

Research examining the consequences of perspective-taking on cognition suggests that through perceiver–target overlap, perspective-taking can lead to greater valuing of targets, greater helping of targets, and a reduction in stereotyping of targets and the groups to which they belong. Research has also begun to focus more closely on the ways perceivers come to think and act like targets. This research, however evocative, is not conclusive. The current studies set out to provide firmer support. Reported here, two studies found that perspective-taking influences perceiver–target overlap, which mediates changes in self-concept (ratings of the self on researcher-related attributes and beliefs after taking the perspective of a researcher in Study 1 and attitudes toward African Americans after taking the perspective of a racist in Study 2). In the same studies, overlap simultaneously mediated valuing of the targets (target ratings on positive attributes in Study 1 and liking for the target in Study 2).     

The role of thought-content and mood in the preparative benefits of upward counterfactual thinking

Upward counterfactual thoughts identify how a prior outcome could have been better and have been shown to improve subsequent performance. Both the identification of corrective actions (content-specific effects) and the more general mobilization of effort as a result of negative affect (content-neutral effects) have been suggested to underlie performance benefits. The results of three experiments presented here indicate that counterfactual thoughts have broad benefits for performance, independent of their content and beyond the effects of planning. These benefits were consistently dependent upon the experience of negative affect, but were eliminated when negative affect could be (mis)attributed to an intervening task. This misattribution effect is consistent with the operation of a mood-as-input process in which affect informs judgments of goal progress. Overall, the findings suggest that the benefits of upward counterfactual thinking reflect more broad attempts to improve following a subjectively unsatisfactory performance.     

Perspective taking instructions and self-other overlap: Different motives for helping

In two studies (N’s = 57 and 115), we demonstrate that type of perspective-taking instruction (“imagine self” vs. “imagine other”) differentially affects two motives for helping: self-other overlap and empathic concern. Imagine-self instructions produce greater self-other overlap than imagine-target and objective instructions, while both types of perspective-taking instruction promote empathic concern relative to an objective condition. In Study 2, imagine-self instructions indirectly increased the likelihood of helping via empathic concern and self-other overlap, while imagine-target instructions led indirectly to greater helping only through empathic concern. We discuss how different perspective-taking instructions may implicate different emotional and motivational paths to increasing helping.     

SAwSu: An Integrated Model of Associative and Reinforcement Learning

Successfully explaining and replicating the complexity and generality of human and animal learning will require the integration of a variety of learning mechanisms. Here, we introduce a computational model which integrates associative learning (AL) and reinforcement learning (RL). We contrast the integrated model with standalone AL and RL models in three simulation studies. First, a synthetic grid‐navigation task is employed to highlight performance advantages for the integrated model in an environment where the reward structure is both diverse and dynamic. The second and third simulations contrast the performances of the three models in behavioral experiments, demonstrating advantages for the integrated model in accounting for behavioral data.     

Augmenting treatment efficiency in exposure therapy for PTSD: a randomized double-blind placebo-controlled trial of yohimbine HCl

The alpha-2 adrenergic receptor antagonist, yohimbine, can facilitate fear extinction in animals and humans. One potential mechanism is increased noradrenergic activity and associated arousal in the presence of conditioned stimuli. Accordingly, yohimbine might augment prolonged exposure (PE) therapy for posttraumatic stress disorder (PTSD), where heightened exposure-oriented arousal is a theorized driver and empirical predictor of treatment success. A double-blind placebo-controlled randomized trial (NCT 01031979) piloted yohimbine augmentation in 26 males with combat-related PTSD. Participants were given one-time dose of yohimbine or placebo prior to the first imaginal exposure. Subsequently, both arms completed standard PE. The primary outcome was trauma-cued heart-rate reactivity a week after the drug/exposure visit, a highly specified, objective measure sensitive to incremental change. Secondary outcomes included arousal during the drug/exposure visit and slope of distress, PTSD, and depression over the course of PE. Consistent with hypothesis, yohimbine led to higher objective and subjective arousal during the drug/exposure visit and to lower trauma-cued heart-rate reactivity one-week later. One dose of yohimbine also led to greater between-session habituation and more rapid improvement on depression, but not PTSD, over the course of care. Results of this controlled pilot indicate support for continued investigation of yohimbine-augmented exposure therapy for PTSD.     

Acceptability,Feasibility, and Effectiveness of Internet-Based Cognitive-Behavioral Therapy for Obsessive-Compulsive Disorder in New York

Cognitive-behavioral therapy (CBT), consisting of exposure and response prevention (EX/RP), is both efficacious and preferred by patients with obsessive–compulsive disorder (OCD), yet few receive this treatment in practice. This study describes the implementation of an Internet-based CBT program (ICBT) developed in Sweden in individuals seeking OCD treatment in New York. After translating and adapting the Swedish ICBT for OCD, we conducted an open trial with 40 adults with OCD. Using the RE-AIM implementation science framework, we assessed the acceptability, feasibility, and effectiveness of ICBT. The Yale–Brown Obsessive Compulsive Scale (Y-BOCS) was the primary outcome measure. Of 40 enrolled, 28 participants completed the 10-week ICBT. In the intent-to-treat sample (N = 40), Y-BOCS scores decreased significantly over time (F = 28.12, df = 2, 49, p < . 001). Depressive severity (F = 5.87, df = 2, 48, p < . 001), and quality of life (F = 12.34, df = 2, 48, p < . 001) also improved. Sensitivity analyses among treatment completers (N = 28) confirmed the intent-to-treat results, with a large effect size for Y-BOCS change (Cohen’s d = 1.38). ICBT took less time to implement than face-to face EX/RP and participants were very to mostly satisfied with ICBT. On a par with results in Sweden, the adapted ICBT program reduced OCD and depressive symptoms and improved quality of life among individuals with moderate to severe OCD. Given its acceptability and feasibility, ICBT deserves further study as a way to increase access to CBT for OCD in the United States.     

Strategies in probabilistic categorization: results from a new way of analyzing performance

The "Weather Prediction" task is a widely used task for investigating probabilistic category learning, in which various cues are probabilistically (but not perfectly) predictive of class membership. This means that a given combination of cues sometimes belongs to one class and sometimes to another. Prior studies showed that subjects can improve their performance with training, and that there is considerable individual variation in the strategies subjects use to approach this task. Here, we discuss a recently introduced analysis of probabilistic categorization, which attempts to identify the strategy followed by a participant. Monte Carlo simulations show that the analysis can, indeed, reliably identify such a strategy if it is used, and can identify switches from one strategy to another. Analysis of data from normal young adults shows that the fitted strategy can predict subsequent responses. Moreover, learning is shown to be highly nonlinear in probabilistic categorization. Analysis of performance of patients with dense memory impairments due to hippocampal damage shows that although these patients can change strategies, they are as likely to fall back to an inferior strategy as to move to more optimal ones.