Impact of recent findings on study design of future autism clinical trials

There are specific challenges to studying the design of pharmacologic trials in child/adolescent and adult autism, such as subject stratification and parallel versus crossover designs. This article describes how optimal study design is influenced by subject selection and outcome measures chosen. Lessons learned in study design from the Research Units on Pediatric Psychopharmacology Autism Network trial with risperidone, Seaver Center trials with fluoxetine and valproate, Dartmouth trials with amantadine, and National Institutes of Health secretin trials are highlighted. The Internet System for Assessing Autistic Children system for managing multicenter clinical trials in autism and statistical issues in autism research are also described.     

FOXP2 and the mirror system

An inherited deficit in spoken language has been associated with a mutation in the forkhead box P2 (FOXP2) gene on chromosome 7. A recent functional magnetic resonance imaging study has linked the deficit to underactivity in Broca's area during word generation, which in turn suggests a possible link between FOXP2 and the mirror-neuron system observed in the primate homologue of Broca's area. This link might have implications for the evolution of Broca's area and its role in speech.     

Functional connectivity during working memory maintenance

Neurophysiological experiments with monkeys have demonstrated that working memory (WM) is associated with persistent neural activity in multiple brain regions, such as the prefrontal cortex (PFC), the parietal cortex, and posterior unimodal association areas. WM maintenance is believed to require the coordination of these brain regions, which do not function in isolation but, rather, interact to maintain visual percepts that are no longer present in the environment. However, single-unit physiology studies and traditional univariate analyses of functional brain imaging data cannot evaluate interactions between distant brain regions, and so evidence of regional integration during WM maintenance is largely indirect. In this study, we utilized a recently developed multivariate analysis method that allows us to explore functional connectivity between brain regions during the distinct stages of a delayed face recognition task. To characterize the neural network mediating the on-line maintenance of faces, the fusiform face area (FFA) was defined as a seed and was then used to generate whole-brain correlation maps. A random effects analysis of the correlation data revealed a network of brain regions exhibiting significant correlations with the FFA seed during the WM delay period. This maintenance network included the dorsolateral and ventrolateral PFC, the premotor cortex, the intraparietal sulcus, the caudate nucleus, the thalamus, the hippocampus, and occipitotemporal regions. These findings support the notion that the coordinated functional interaction between nodes of a widely distributed network underlies the active maintenance of a perceptual representation.     

Coping with threat and memory for ambiguous information: testing the repressive discontinuity hypothesis

Two studies examined the influence of coping dispositions (repression, sensitization, and nondefensiveness) and anxiety on the encoding and memory representation of ambiguous threat-related stimuli. In Study 1, memory was tested shortly after encoding. Study 2 contrasted immediate and delayed testing. Repressers showed evidence of "mixed" affective reactions to ambiguous stimuli at encoding, accompanied by weak memory representation of potentially threatening implications of these stimuli. In contrast, sensitizers and anxious individuals manifested a processing bias in favor of threatening implications of ambiguous stimuli. Influences of coping on memory were most pronounced for delayed testing. Anxiety influences on memory were weak. An expectancy-based account of individual differences in processing ambiguous stimuli is discussed.     

Cognitive defusion and self-relevant negative thoughts: examining the impact of a ninety year old technique

Cognitive defusion techniques are designed to reduce the functions of thoughts by altering the context in which they occur, rather than the attempting to alter the form, frequency, or situational sensitivity of the thoughts themselves. Applied technologies designed to produce cognitive defusion seem to lead to reductions in the believability of negative thoughts, but defusion techniques are generally only parts of complex packages and the role of defusion techniques per se is note yet known. The present study examined the impact of a cognitive defusion technique first described by Titchener nearly 90 years ago: rapidly repeating a single word. In series of eight single-case alternating treatment designs, this defusion technique was compared to a distraction task, and to a thought control task on reductions in the discomfort and believability of self-relevant negative thoughts. The cognitive defusion technique reduced both discomfort and believability more so than the comparison approaches. Control studies showed that the effect was probably not due to demand characteristics.     

Applications of computer-based instruction: using specialized software to aid letter-name and letter-sound recognition

We evaluated computerized training and testing programs with children who were having difficulties learning prereading skills. The programs were derived from equivalence research and were written in authoring software designed for educators. After learning to match uppercase and lowercase printed letters to the corresponding letter names (Tasks 1 and 2), the children matched the letters to one another (Tasks 4 and 5). Then, after learning to match uppercase letters to sounds (Task 3), they also matched lowercase letters to sounds (Task 6) and matched printed to spoken words (Tasks 7 and 8). The results recommend equivalence-based protocols and user-friendly software in further development of prereading instruction.     

Relational measures in psychotherapy research on process and outcome: a commentary on the studies

Using Benjamin's (2000) Structural Analysis of Social Behavior, we evaluated change in "self-directed" affiliation and autonomy and prediction of treatment response and relapse/recurrence among adult outpatients with recurrent major depressive disorder consenting to acute phase cognitive therapy (A-CT; Beck, Rush, Shaw, & Emery, 1979; N=156); A-CT responders randomized (N=84) to 8 months of continuation phase cognitive therapy (C-CT; Jarrett, 1989; Jarrett et al., 1998; Jarrett & Kraft, 1997) or assessment-only control; and C-CT and control patients entering a 16-month, assessment-only follow-up (N=74). Self-directed affiliation and autonomy increased after A-CT, and C-CT further increased affiliation and autonomy. Affiliation and autonomy did not predict A-CT response, but lower affiliation and higher autonomy pre-A-CT predicted relapse/recurrence post-A-CT. We discuss potential clinical implications of these results and present case examples to illustrate patterns of change.     

A comparison of the MCMI-III personality disorder and modifier indices with the MMPI-2 clinical and validity scales

In this study, we examined the relationship of the MCMI-III (Millon, Davis, & Millon, 1997; Millon, Millon, & Davis, 1994) modifier indices and personality disorder scales to the validity and basic clinical scales of the MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989). The MCMI-III modifier indices highly correlated with all of the MMPI-2 validity scales except for the F(p) scale. Similarly, the MCMI-III personality disorder scales strongly covaried with the MMPI-2 validity and clinical scales except for the F(p) and 5 (Mf) scales. A factor analysis with Promax rotation revealed substantial relationships between the MMPI-2 and MCMI-III. However, the MMPI-2 F(p) scale did not tend to correlate with MMPI-2 or MCMI-III scales, indicating that F(p) scale variance was largely independent of other scales. The results suggest that clinicians should consider the interrelationship between personality characteristics and dissimulation.