Autism clinical trials: biological and medical issues in patient selection and treatment response

Biomedical measures are critical in the initial patient-screening and -selection phases of a clinical trial in autism and related disorders. These measures can also play an important role in the assessment and characterization of response and can provide an opportunity to study underlying etiologic and pathophysiologic processes. Thus, biomedical measures, including clinical laboratory analyses, metabolic screening, and chromosomal analysis, are used to screen for potential safety-related problems, to decrease biological and genetic heterogeneity, and to define subgroups. Neurobiological measures can be examined as possible predictors, modifiers or surrogates of therapeutic response, and adverse effects. Neurobiological research measures can also be used to study mechanisms and extent of drug action and to perform baseline and longitudinal investigations of possible pathophysiologic alterations. The potential utility and desirability of specific measures are considered and the general approach to choosing measures for incorporation is discussed.     

Transcranial direct-current stimulation enhances implicit motor sequence learning in persons with Parkinson's disease with mild cognitive impairment

Implicit motor sequence learning (IMSL) is affected in Parkinson's disease (PD). Research in healthy young participants shows the potential for transcranial direct-current stimulation (tDCS) over the primary motor cortex (M1) to enhance IMSL. In PD, only null effects have been reported to date. We determined concurrent, short-term, and long-term effects of anodal tDCS over M1 on IMSL, as measured by the serial reaction time (SRT) task, in persons with PD with mild cognitive impairment (MCI). Concurrent (anodal/sham tDCS intervention during the SRT task), short-term (5 min post-intervention), and long-term (1 week post-intervention) effects on IMSL were evaluated in persons with idiopathic PD (Hoehn and Yahr stage II-III) with MCI. Results of 11 persons with PD (8 men and 3 women; mean age = 77.1 years; mean disease duration = 7.7 years) showed significant IMSL in the anodal (p = .016), but not in the sham tDCS condition (p = .937). Post-hoc analyses showed that IMSL reached statistical significance at 1 week post-intervention (p < .001). Anodal tDCS over M1 exerted beneficial effects on IMSL in persons with PD with MCI, in particular one week post-intervention. Our study is the first to report a positive effect of tDCS on IMSL in PD. Further research should include a larger, more cognitively diverse sample and additional follow-up periods.     

Prospective Pilot Study of the Mastering Each New Direction Psychosocial Family Systems Program for Pediatric Chronic Illness

Psychosocial interventions for pediatric chronic illness (CI) have been shown to support health management. Interventions that include a family systems approach offer potentially stronger and more sustainable improvements. This study explores the biopsychosocial benefits of a novel family systems psychosocial intervention (MEND: Mastering Each New Direction). Forty‐five families participated in a 21‐session intensive outpatient family systems‐based program for pediatric CI. Within this single arm design, families were measured on five domains of Health‐Related Quality of Life (HRQL) self‐report measures; Stress, Cognitive Functioning, Mental Health, Child HRQL, Family Functioning. Both survey and biological measures (stress: catecholamine) were used in the study. Results from multivariate general linear models showed positive pre‐, post‐, and 3‐month posteffects in all five domains. The program effects ranged from small to moderate (η² = .07–.64). The largest program effects were seen in the domains of cognitive functioning (η² = .64) and stress (η² = .27). Also, between disease groups, differences are noted and future implications for research and clinical practice are discussed. Conclusions suggest that the MEND program may be useful in helping families manage pediatric chronic illnesses. Study results also add to the growing body of literature suggesting that psychosocial interventions for pediatric chronic illness benefit from a family systems level of intervention.     

Does implicit learning in non-demented Parkinson’s disease depend on the level of cognitive functioning?

We investigated the influence of the level of cognitive functioning on sequence-specific learning in Parkinson's disease (PD). This was done by examining the relationship between the scales for outcomes in Parkinson's disease-cognition [SCOPA-COG, Marinus, J., Visser, M., Verwey, N. A., Verhey, F. R. J., Middelkoop, H. A. M.,Stiggelbout, A., et al. (2003). Assessment of cognition in Parkinson's disease. Neurology, 61, 1222-1228] and the serial reaction time (SRT) task [Nissen, M. J., & Bullemer, P. T. (1987). Attentional requirements for learning: Evidence from performance measures. Cognitive Psychology, 19, 1-32] in a homogeneous sample, consisting of 25 PD patients diagnosed in Stage 3 of the Hoehn and Yahr [Hoehn, M. M., & Yahr, M. D. (1967). Parkinsonism: onset, progression, and mortality. Neurology, 17, 427-442] scale. Six patients in the low scoring cognitive group, 11 patients in the average scoring and eight patients in the high scoring group, conducted a SRT task with a deterministic sequence. Sequence-specific learning was assessed by inserting a random block to determine whether the acquisition of sequence movements differed between groups. Our results indicate an association between cognitive functioning in PD patients and sequence learning. These findings emphasize the use of assessing cognition in addition to the well-known motor aspects in PD.     

Conscious, but not unconscious, logo priming of brands and related words

This study assessed whether real-life stimulus material can elicit conscious and unconscious priming. A typical masked priming paradigm was used, with brand logo primes. We used a rigorous method to assess participants' awareness of the subliminal information. Our results show that shortly presented and masked brand logos (e.g., logo of McDonald's) have the power to prime their brand names (e.g., "McDonald's") and, remarkably, words associated to the brand (e.g., "hamburger"). However, this only occurred when the logos could be categorized clearly above the consciousness threshold. Once the primes were presented close to the consciousness threshold, no subliminal influences on behavior were observed.     

Treating Multitraumatized,Socially Marginalized Children: Results of a Naturalistic Treatment Outcome Study

Although early-onset, repeated trauma is relatively common in socially marginalized populations and related to numerous negative outcomes, most empirically validated interventions are not especially well tailored to meet the complex and individualized needs of child and adolescent trauma survivors in such contexts. Integrative treatment of complex trauma (ITCT) was developed as a specialized treatment that is empirically informed, culturally sensitive, extendable beyond the short term, and customized to the specific social and psychological issues of each child. This article examines the potential effectiveness of ITCT in assisting 151 traumatized children living in an economically deprived environment. Results indicate significant reductions in anxiety, depression, posttraumatic stress, anger, dissociation, and sexual concerns as a function of time in treatment.     

Worrying and rumination are both associated with reduced cognitive control

Persistent negative thought is a hallmark feature of both major depressive disorder and generalized anxiety disorder. Despite its clinical significance, little is known about the underlying mechanisms of persistent negative thought. Recent studies suggest that reduced cognitive control might be an explanatory factor. We investigated the association between persistent negative thought and switching between internal representations in working memory, using the internal shift task (IST). The IST was administered to a group of undergraduates, classified as high-ruminators versus low-ruminators, or high-worriers versus low-worriers. Results showed that high-ruminators and high-worriers have more difficulties to switch between internal representations in working memory as opposed to low-ruminators and low-worriers. Importantly, results were only significant when the negative stimuli used in the IST reflected personally relevant worry themes for the participants. The results of this study indicate that rumination and worrying are both associated with reduced cognitive control for verbal information that is personally relevant.     

Spatial processing and perceptual sequence learning in SRT tasks

We investigated the influence of processing relevant spatial information on learning a probabilistic sequence of irrelevant locations. Using the SRT design of Remillard (2003), we found that spatial perceptual learning occurs with paired but not with single targets. The pairs of targets consisted of the same stimuli, but in a different order, so that responses could have been based on the left-right location of an element, relative to the other element of the pair. The prerequisite of spatial pairs of targets suggests that spatial processing of relevant information plays a crucial role in perceptual location learning. In addition, spatial perceptual learning only took place when the target pair was presented together with other stimuli, but was absent when the target pair was presented in a blank field. Since in the latter case attention is automatically captured, this suggests that sequence learning requires endogenous attention.     

Dissonance reduction and causal explanation in a forced compliance situation

In a free choice forced compliance situation, subjects had to perform a tedious task. Then, just before having to evaluate the task's interest, certain subjects were provided an arbitrary positive feedback regarding their performance, others a negative feedback and others no information at all concerning their performance. Afterwards, all subjects were administered a questionnaire concerning their theories of causal explanations, which enabled us to compute an externalization score. Evaluation of the task was affected by the feedback's nature: Subjects who received the negative feedback found the task more interesting. Causal theories, however, were only affected by actual performance: the most efficient subjects were those who presented the more external orientation of causal theories. These results are in agreement with the radical conception of dissonance theory.