Development of subtype selective GABAA modulators

Drugs modulating gamma-aminobutyric acid (GABA) transmission via the benzodiazepine (BZ) site on the gamma-aminobutyric acid type A (GABAA) receptor have been in widespread use for more than 40 years to treat anxiety, epilepsy, and sleep disorders. These drugs have been shown to be safe, well tolerated, and effective although the mechanism by they produce a myriad of pharmacologic effects remains elusive. In recent years it has been discovered that, although the GABAA receptor is widely distributed in the brain, the substructure and composition of the receptor differs from between brain regions. Termed "GABAA receptor subtypes" their discovery leads to speculation that different subtypes may mediate specific effects of BZs such as anxiety or sedation. The phenotypic analysis of transgenic knock-in and knock-out mice in which particular GABAA receptors were rendered insensitive to the effects of BZ while others were unaffected confirmed this speculation. Subsequently, subtype-specific GABAA ligands were developed that, for example, retained the anxiolytic effects of BZs but were devoid of their sedative effects. Therefore, it may be possible to develop effective anxiolytic compounds that have a much reduced side-effect profile compared with existing drugs.     

Theory of mind and moral cognition: exploring the connections

It is widely recognized that people sometimes use theory-of-mind judgments in moral cognition. A series of recent studies shows that the connection can also work in the opposite direction: moral judgments can sometimes be used in theory-of-mind cognition. Thus, there appear to be cases in which people's moral judgments actually serve as input to the process underlying their application of theory-of-mind concepts.     

The ups and downs of attributional ambiguity: stereotype vulnerability and the academic self-knowledge of African American college students

This research examined whether stereotype vulnerability-the tendency to expect, perceive, and be influenced by negative stereotypes about one's social category-is associated with uncertainty about one's academic self-knowledge in two important ways. We predicted that stereotype-vulnerable African American students would (a) know less about how much they know than less vulnerable students do and (b) have unstable academic efficacy. In Study 1, Black and White participants took a verbal test and indicated the probability that each of their answers was correct. As expected, stereotype-vulnerable Black participants were more miscalibrated than other participants. In Study 2, participants completed measures of self-efficacy twice daily for 8 days. Also as expected, the academic efficacy of stereotype-vulnerable Blacks fluctuated more-and more extremely-than that of other participants. The results suggest that, in addition to undermining intellectual performance, stigma interferes with academic self-knowledge.     

Saccadic output is influenced by limb kinetics during eye-hand coordination

In several recent studies, saccadic eye movements were found to be influenced by concurrent reaching movements. The authors investigated whether that influence originates in limb kinematic or kinetic signals. To dissociate those 2 possibilities, the authors required participants (N = 6) to generate pointing movements with a mass that either resisted or assisted limb motion. With practice, participants were able to generate pointing responses with very similar kinematics but whose kinetics varied in a systematic manner. The results showed that saccadic output was altered by the amount of force required to move the arm, consistent with an influence from limb kinetic signals. Because the interaction occurred before the pointing response began, the authors conclude that a predictive signal related to limb kinetics modulates saccadic output during tasks requiring eye-hand coordination.     

Secure and defensive high self-esteem

Long-standing theories have suggested high self-esteem (SE) can assume qualitatively different forms that are related to defensiveness. The authors explored whether some high-SE individuals are particularly defensive because they harbor negative self-feelings at less conscious levels, indicated by low implicit SE. In Study 1, participants high in explicit SE but low in implicit SE showed the highest levels of narcissism--an indicator of defensiveness. In Studies 2 and 3, the correspondence between implicit and explicit SE predicted defensive behavior (in-group bias in Study 2 and dissonance reduction in Study 3), such that for high explicit-SE participants, those with relatively low implicit SE behaved more defensively. These results are consistent with the idea that high SE can be relatively secure or defensive.     

Tooth color: effects on judgments of attractiveness and age

Tooth whitening has become a very popular procedure. Advertisements for whitening products imply that whiter teeth are more attractive than yellower teeth. We tested this idea empirically by manipulating the tooth color of pictures of male and female targets. Participants' ratings of attractiveness were not influenced by tooth color. Exp. 2 yielded a negative correlation between attractiveness and age ratings: targets judged to be older were rated as less attractive. Unless whiter teeth help in some other way, e.g., improved self-esteem or confidence, it seems that tooth whitening procedures or products are not associated with increased attractiveness to others.     

The Association Between Sluggish Cognitive Tempo and Academic Functioning in Youth with Attention-Deficit/Hyperactivity Disorder (ADHD)

The purpose of the study was to evaluate the relation between Sluggish Cognitive Tempo (SCT) and academic functioning in a sample of 52 adolescents (40 males, 12 females) with Attention-Deficit/Hyperactivity Disorder (ADHD; M _age?=?13.75). This study builds on prior work by utilizing an empirically-based and psychometrically validated measure of SCT, collecting ratings of SCT from both parents and teachers, and examining associations with multiple domains of academic functioning from both the parent and teacher perspective as well as grade point average (GPA). Both SCT and DSM-IV symptoms of inattention were significantly correlated with domains of academic functioning. Multiple regression analyses demonstrated that the parent-rated SCT Slow subscale predicted overall academic functioning, organizational skills impairment, and homework problems above and beyond ADHD symptoms and child and demographic characteristics known to be associated with academics, including intelligence, academic achievement, and family income. The teacher-rated SCT Low Initiation/Persistence subscale also predicted homework problems and was the only SCT variable to predict school grades above and beyond ADHD symptoms and relevant covariates. Both the SCT Slow and Low Initiation/Persistence subscales include items related to youth seeming apathetic, unmotivated, and lacking initiative, behaviors that are strongly related to ADHD symptoms of inattention but not currently captured by the DSM-IV. Implications of these findings towards supporting the external validity of the SCT construct are discussed along with potential implications for intervention.     

Performance on ratio and interval schedules with matched reinforcement rates

In the first study, rats were trained to pull a chain on a schedule (RPI) that regulates the probability of reinforcement to maintain a constant average reinforcement rate without differentially reinforcing long inter-response times (IRTs). Although the response rate was sensitive to the overall rate of reinforcement, performance was unaffected by variations between 1 and 50 in the IRT memory size used in programming the schedule. In the second study, two groups of animals performed on either a random-interval (RI) schedule or a RPI schedule, with reinforcement rates determined by those generated by a third group performing on a random ratio (RR) 20 schedule. The RI group responded at a lower rate than the RPI group, which, in turn, responded at a lower rate than the RR group, even though the three groups experienced comparable rates of reinforcement. The fact that the RPI group responded at a lower rate than the RR group suggests that the standard response rate difference observed between ratio and interval schedules, which have been matched for reinforcement rate, cannot be attributed solely to the fact that conventional interval schedules differentially reinforce long IRTs.