Peter J. Snyder

Cognitive effects of immediate-release methylphenidate in children with attention-deficit/hyperactivity disorder

A growing body of literature has examined the cognitive effects of immediate-release methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD). However, a clear understanding of the types and magnitude of such effects are difficult to discern from such a large and varied collection of published reports. This review evaluated a total of 40 relevant placebo-controlled studies published since Rapport and Kellys [1993. Psychostimulant effects on learning and cognitive function. In: Matson, J.L. (Ed.), Handbook of Hyperactivity in Children. Allyn & Bacon, Boston, pp. 97-136] original review of cognitive effects of methylphenidate in children with ADHD. Of these published studies, 63.5% identified some improvement in cognitive function following methylphenidate treatment. Methylphenidate improved performance on saccadic eye movement, planning/cognitive flexibility, attention/vigilance, and inhibitory control tasks in 83.3%, 71.4%, 70.6%, and 69.7% of studies, respectively. A total 58.3% and 50% of studies that evaluated the effect of methylphenidate on tasks of memory and working memory/divided attention, respectively, noted improvement. Variability of findings across studies may be explained by differential effects of methylphenidate on brain function, intra- and inter-individual variability in medication response, methodological limitations, and problems associated with repeated neuropsychological assessment and metric properties of commonly utilised neuropsychological instruments.

Changes in Human In vivo Serotonin and Dopamine Transporter Availabilities during Chronic Antidepressant Administration

Few studies have demonstrated in vivo alterations of human serotonin and dopamine transporters (SERTS and DATS) during antidepressant treatment. The current study measured these transporter availabilities with [123I]β-CIT single photon emission computed tomography (SPECT) during administration of selective serotonin reuptake inhibitors (SSRIs) or a non-SSRI, bupropion. A total of 17 healthy human subjects were randomly assigned to two different treatment protocols: (1) citalopram (40u2009mg/day) followed by augmentation with bupropion (100u2009mg/day) or (2) bupropion (100–200u2009mg/day) for 16 days. Citalopram significantly inhibited [123I]β-CIT binding to SERT in brainstem (51.4%) and diencephalon (39.4%) after 8 days of administration, which was similarly observed after 16 days. In contrast, citalopram significantly increased striatal DAT binding by 15–17% after 8 and 16 days of administration. Bupropion and its augmentation to citalopram did not have a significant effect on DAT or SERT. In 10 depressed patients who were treated with paroxetine (20u2009mg/day), a similar increase in DAT and inhibition of SERT were observed during 6 weeks treatment. The results demonstrated the inhibition of SERT by SSRI in human in vivo during the chronic treatment and, unexpectedly, an elevation of DAT. This apparent SSRI-induced modulation of the dopamine system may be associated with the side effects of these agents, including sexual dysfunction.

Electroencephalography and event-related potentials as biomarkers of mild cognitive impairment and mild Alzheimer’s disease

Successful early detection of mild cognitive impairment (MCI) and Alzheimers disease demands the identification of biomarkers capable of distinguishing individuals with prodromal or early cognitive impairment from healthy aging adults. Many laboratories are engaged in the discovery and validation of a wide array of potential genetic, proteomic, cognitive, and other types of biomarkers.

Reversal of scopolamine-induced deficits with a single dose of donepezil, an acetylcholinesterase inhibitor

To develop a more rapid screening paradigm for novel cognitive enhancers, the authors sought to determine the utility of a well‐known pharmacologic model of induced dementia (scopolamine challenge), paired with a sensitive neuropsychological test, for assessing the ability of a single oral dose of a current treatment for Alzheimers disease (donepezil) to improve cognitive performance in healthy elderly subjects.

Voice Acoustical Measurement of the Severity of Major Depression.

A number of empirical studies have documented the relationship between quantifiable and objective acoustical measures of voice and speech, and clinical subjective ratings of severity of Major Depression. To further explore this relationship, speech samples were extracted from videotape recordings of structured interviews made during the administration of the 17-item Hamilton Depression Rating Scale (HDRS; ). Pilot data were obtained from seven subjects (five males, two females) from videotapes that have been used to train expert raters on the administration and scoring of the HDRS. Several speech samples were isolated for each subject and processed to obtain the acoustic measurements. Acoustic measures were selected on the basis that they were correlated with HDRS ratings of symptom severity as seen under ideal voice recording conditions in previous studies. Our findings corroborate earlier reports that speaking rate is well correlated (negatively) with HDRS scores, with a strong correlation and nearly significant trend seen for the measure of pitch variability. A moderate pairwise correlation between percent pause time and HDRS score was also revealed, although this relationship was not statistically significant. The results from this cross-sectional study further demonstrate the ability of voice and speech signal analyses to objectively track severity of depression. In the present case, it is suggested that this relationship is robust enough to be found despite the less than ideal recording conditions and equipment used during the original videotape recording. Voice acoustical analyses may provide a powerful compliment to the standard clinical interview for depression. Use of such measures increases the range of techniques that are available to explore the neurobiological substrates of Major Depression, its treatment, and the dynamic interplay of the systems that govern the motor, cognitive, and emotional aspects of speech production.

Cerebellar volume asymmetries are related to handedness: A quantitative MRI study

Four cerebellar subregions were delineated (left, right; anterior, posterior), and their volumes measured on contiguous 3.1 mm coronal MR images in 15 dextral and 8 nondextral healthy control subjects. (1) Left and right cerebellar hemisphere volume asymmetries interacted with anterior-posterior level (anterior: right > left; posterior: left > right), following a pattern commonly found in the neocortex; (2) A significant handedness effect was found (P < or =0.01) on a composite index of cerebellar asymmetry, such that dextrals showed more asymmetry than nondextrals. These data suggest that the same pattern of asymmetries observed at the neocortical level is also present in the metencephalon. These asymmetries, possibly resulting from multiple developmental growth gradients acting on the metencephalon early in gestation, are associated with handedness differences in adulthood.

An examination of the construct validity and factor structure of the Groton Maze Learning Test, a new measure of spatial working memory, learning efficiency, and error monitoring.

This study examined the construct validity of the Groton Maze Learning Test (GMLT) in assessing processing speed, working memory, and aspects of executive function in healthy adults. Performance on GMLT outcome measures was compared to performance on tests of psychomotor speed, working memory, and learning from the CogState computerized cognitive test battery (CGS; http://www.cogstate.com/). The factor structure of the GMLT was evaluated using exploratory factor analysis. The stability of this factor structure was examined in a large sample of patients undergoing parathyroidectomy or thyroidectomy. Results of this study suggest that the GMLT measures of spatial learning efficiency and error monitoring correlate with CogState measures of attention, working memory, and learning. Exploratory factor analysis yielded a two-factor solution of error monitoring and learning efficiency, which was stable across repeated assessments.

A factor analysis of the Klein sexual orientation grid in two disparate samples

Many researchers interested in sexual orientation can be separated into two camps: The “lumpers,” who try to reduce sexual classifications to as small a number of categories as possible, and the “splitters,” who try to show differences among groups and individuals that make classification schemes increasingly difficult and/or intricate. We report factor analyses of the Klein Grid (a questionnaire with 21 sexual orientation items) to see how many factors emerge in two samples of strikingly different origins. In both samples, the first factor to emerge loaded substantially on all of the Klein Grids 21 items. This factor accounted for a majority of the variance. In both samples, a second, correlated factor emerged which indexed a separation between most of the items and those having to do with social and/or emotional preferences. In both samples, a third correlated factor also emerged, but this factor differed between the two populations: one refined the social/emotional distinction and the other distinguished ideal behavior from past and current behavior. We conclude on the basis of our analysis that both the lumpers and the splitters are correct.

The use of effect sizes to characterize the nature of cognitive change in psychopharmacological studies : an example with scopolamine

Drug induced cognitive change is generally investigated using small sample sizes. In terms of null hypothesis significance testing (NHST) this can render a meaningful change non‐significant, as a result of insufficient power in the statistical model. NHST leads to ‘all or none’ thinking, where a non‐significant result is interpreted as an absence of change. An effect size calculation indicates the magnitude of change which has occurred post‐intervention, and therefore whether a significant result is meaningful. We used a scopolamine challenge to demonstrate the usefulness of effect sizes. The aim of the study was to determine how effect sizes could describe the cognitive changes that occur following administration of subcutaneous scopolamine (s.c. scopolamine). Twenty four healthy young males (Mu2009=u200932.6, sdu2009=u20094.5 years) were administered placebo and 0.2u2009mg, 0.4u2009mg & 0.6u2009mg of s.c. scopolamine using a 4‐way crossover design. Memory, learning, psychomotor function, attention and executive function were assessed. Scopolamine significantly impaired performance on all tasks in a dose and time related manner. These results demonstrate the functionality of change scores to draw comparisons between different times and doses. This methodology overcomes the limitations of comparisons between studies using different tasks, doses and time at which cognitive functions are measured. Copyright

Impaired performance of children exposed in utero to cocaine on a novel test of visuospatial working memory.

The present study examines the potentially harmful effects of prenatal cocaine exposure on later visuospatial memory functions. A novel neuropsychological measure of immediate- and short-term memory for visuospatial information was administered to 40 children, who were identified as cocaine-exposed, and 11 age and socioeconomic status matched controls (all children were 8-9 years old). The Groton Maze Learning Test is a computer-based hidden maze learning test that consists of a timed chase test (a simple measure of visuomotor speed), 5 learning trials on a hidden maze, followed by a delayed recall trial after an 8 min delay. The specific test parameters are chosen based on the age cohort of the subjects. The cocaine-exposed group performed significantly slower on the timed chase test, the last 3 learning trials, and the delayed recall trial (p < or = .05 for all comparisons). Although there was a modest trend for the cocaine-exposed group to make more errors throughout the learning trials, there were no significant group differences. These results suggest that children who were exposed in utero to cocaine exhibit slowed visuomotor speed, a possible impairment in procedural learning, and diminished efficiency in accessing and using the internal spatial map that subjects create to master the maze.