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Introduction Rupatadine fumarate is a potent, selective, histamine HI-receptor antagonist and PAF inhibitor with demonstrated efficacy for the relief of allergic rhinitis. Rupatadine does not easily cross the blood-brain barrier and is believed to be non-sedating at therapeutic doses. Consequently, rupatadine should show no impairment on car driving. Objective This study compared the acute effects of rupatadine, relative to placebo and hydroxyzine (as an active control), on healthy subjects' driving performance. Methods Twenty subjects received a single dose of rupatadine 10 mg, hydroxyzine 50 mg, or placebo in each period of this randomized, double-blind, three-way crossover study. Two hours postdosing, subjects operated a specially instrumented vehicle in tests designed to measure their driving ability. Before and after the driving tests ratings of sedation were recorded. Results There was no significant difference between rupatadine and placebo in the primary outcome variable: standard deviation of lateral position (SDLP); however, hydroxyzine treatment significantly increased SDLP (p <0.001 for both comparisons). Objective (Stanford sleepiness scale) and subjective sedation ratings (Visual Analogue Scales) showed similar results: subjects reported negative effects after hydroxyzine but not after rupatadine. Conclusion Rupatadine 10 mg is not sedating and does not impair driving performance.

Objectives: To investigate neurophysiological parameters which possibly distinguish subtypes I and II of patients with a bipolar disorder, and contrast the findings with observations from a group of schizophrenic patients and a group of healthy controls. Methods: Sixty-six volunteers underwent a MRI scan to determine the number and location of white matter lesions (WSL). A electrophysiological registration was made while all volunteers performed a auditory 'oddball' task, and the amplitude of the resulting P300 wave was compared. Results: Earlier reports of higher numbers of WSL in bipolar disorder were not replicated in this study. Subtypes I and II showed a different P300 amplitude and subtype I resembled the results of the schizophrenia group. Conclusion: Bipolar patients in remission have a functional brain disorder that is expressed by a change in physiological response to external stimuli.

Methylphenidate (MPH), a stimulant drug with dopamine and noradrenaline reuptake inhibition properties, is mainly prescribed in attention deficit hyperactivity disorder, is increasingly used by the general population, intending to enhance their cognitive function. In this literature review, we aim to answer whether this is effective. We present a novel way to determine the extent to which MPH enhances cognitive performance in a certain domain. Namely, we quantify this by a percentage that reflects the number of studies showing performance enhancing effects of MPH. To evaluate whether the dose-response relationship follows an inverted-U-shaped curve, MPH effects on cognition are also quantified for low, medium and high doses, respectively. The studies reviewed here show that single doses of MPH improve cognitive performance in the healthy population in the domains of working memory (65% of included studies) and speed of processing (48%), and to a lesser extent may also improve verbal learning and memory (31%), attention and vigilance (29%) and reasoning and problem solving (18%), but does not have an effect on visual learning and memory. MPH effects are dose-dependent and the dose-response relationship differs between cognitive domains. MPH use is associated with side effects and other adverse consequences, such as potential abuse. Future studies should focus on MPH specifically to adequately asses its benefits in relation to the risks specific to this drug.

BACKGROUND: Pregnancy has often been associated with cognitive deficits, but results are equivocal and little is known about how these deficits progress with time. METHOD: In the present study, the cognitive performance of 57 pregnant women was compared with that of 50 non-pregnant women matched for age and education, using a well-validated neurocognitive test battery at weeks 14, 17, 29, and 36 of pregnancy, and 32 weeks postpartum in the pregnant group and at comparable times in the non-pregnant group. RESULTS: Memory encoding and retrieval, as assessed with a word learning task, were significantly lower in the pregnant group than in the control group. This difference was still present at 32 weeks after delivery. The two groups did not differ in complex speed of information processing at any of the test moments; however, general speed of information processing was significantly compromised during early motherhood (week 32 postpartum). CONCLUSION: Thus, memory performance is poorer during pregnancy and early motherhood, and general speed of information processing is slower during early motherhood. AD - Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, The Netherlands. RHM.deGroot@NP.unimaas.nl FAU - de Groot, R H M AU - de Groot RH FAU - Vuurman, E F P M AU - Vuurman EF FAU - Hornstra, G AU - Hornstra G FAU - Jolles, J AU - Jolles J LA - eng PT - Journal Article PT - Multicenter Study DEP - 20060306 PL - England TA - Psychol Med JT - Psychological medicine JID - 1254142 SB - IM MH - Adult MH - *Cognition MH - Comparative Study MH - Delivery, Obstetric/psychology MH - Female MH - Humans MH - Learning MH - Memory MH - Mothers/*psychology MH - Netherlands MH - Postpartum Period/*psychology MH - Pregnancy/*psychology MH - Reference Values

There is evidence for a specific impairment of human vigilance following enhancement of serotonergic activity by antidepressant drugs. In the present study, we investigated the putative role of serotonergic-dopaminergic interactions in diminished vigilance by comparing the attentional effects of sertraline, a selective serotonin reuptake inhibitor (SSRI) with additional mild dopamine stimulating effects, with those of paroxetine, a SSRI without dopamine activity, using a placebo-controlled, double-blind, three-way cross-over design. Twenty-one (of 24) healthy middle-aged subjects completed the three treatment periods of 2 weeks in which sertraline (50 mg, days 1-7; 100 mg, days 8-14), paroxetine (20 mg, days 1-7; 40 mg, days 8-14) and placebo were administered. Vigilance (Mackworth Clock Test), selective (Stroop, Dichotic Listening) and divided attention (Dichotic Listening) were assessed at baseline and on days 7 and 14 of each treatment period. Selective and divided attention were unaffected by SSRI treatment. Subchronic administration of paroxetine impaired vigilance performance at each investigated dose. Sertraline did not produce a significant decline in vigilance performance, presumably due to its concomitant effects on dopamine activity, counteracting the negative effects of serotonin on dopamine neurotransmission. It is concluded that a serotonergically mediated reduction of dopamine activity plays an important role in the reduction of human vigilance following SSRI administration.

Rationale: Serotonin reuptake inhibitors (SSRIs) have been attributed CNS-activating properties based on their ability to elevate the Critical Flicker Fusion (CFF) threshold. However, such an interpretation may be questioned since CFF elevations may also be due to SSRI-induced increases in pupil diameter. Objectives: The effect of pupillary changes on CFF assessment following SSRI administration was investigated in a double blind, crossover study. Methods: During three periods of 15 days, 21 healthy men and women (30-50 years) received sertraline (50 mg on days 1-8, 100 mg on days 9-15), citalopram (20 mg on days 1-8, 40 mg on days 9-15) and placebo. Assessments were done on days 1, 8 and 15 and consisted of pupillary measurements and CFF assessments with and without pupillary control (a 2-mm artificial pupil) using the Leeds Psychomotor Tester. Results: Both SSRIs induced an acute and steady increase in pupil diameters. CFF thresholds were depressed following acute administration of sertraline and citalopram, but this was only apparent when a control was made for the pupillary changes. No CFF effects were seen at day 8, but CFF was again reduced at day 15, with and without control for pupil size. Conclusions: Mydriasis masked the detrimental effects of both SSRIs on CFF during the acute assessments. Our results raise questions regarding the validity of the assessment of the behavioural toxicity of SSRIs based on CFF measurements without ample control for pupil size, especially when these concern acute measurements.

Brain activation differences of reading-related processes between dyslexic and normal reading children were localized with functional magnetic resonance imaging (MRI). The children performed tasks that varied in visuospatial, orthographic, phonologic, and semantic processing demands. Enhanced activation of the left extrastriate cortex was found during all tasks in the dyslexic group. During orthographic processing, dyslexic children predominantly showed activation in the right prefrontal cortex, as also occurred during the visuo-spatial task. Normal readers also showed activation in the left prefrontal cortex. Dyslexic readers showed less activation of both the temporal and the prefrontal cortex during phonologic processing. The results suggest that dyslexic readers fail to use brain areas that are normally specialized in language processing, but rather use areas that underlie visuospatial processing.

Recent studies have indicated a role for the thalamus in attention, arousal and the capacity to perform tasks of speeded information processing. The present study evaluated the role of the thalamus in age-related cognitive decline by investigating the correlations between thalamic volume, cognition and age. This was done in 57 healthy subjects ranging from 21 to 82 years of age. All subjects underwent neurocognitive testing with information processing tests and structural magnetic resonance imaging. A significant decrease in volume of the thalamus with increasing age was found, relatively stronger than and independent of the decrease of total brain volume. The decrease of thalamic volume was apparent before the onset of loss of volume of the total brain. Over the age-span studied, the thalamic decrease in volume correlated with the diminished performance on tests of cognitive speed. Additionally, in young and middle-aged, but not in old subjects, the size of the thalamus predicted performance on tasks that require cognitive speed.

Krabbendam l, honig a, wiersma j, vuurman efpm, hofman pam, derix mma, nolen wa, jolles j. Cognitive dysfunctions and white matter lesions in patients with bipolar disorder in remission. Acta psychiatr scand 2000: 101: 274–280. Objective: to compare cognitive functioning in relation to white matter lesions in bipolar disorder in remission and schizophrenia. Method: cognitive performance and the occurrence of white matter lesions on mri images of the brain were assessed in 22 patients with bipolar disorder in remission, 22 patients with schizophrenia and 22 healthy volunteers. Results: performance of tests of memory, speed and cognitive flexibility was significantly impaired in both patient groups. The frequency of white matter lesions did not differ significantly between the three groups. No differences in cognitive performance were found between patients with white matter lesions and patients without such lesions. Conclusion: white matter lesions apparently do not underlie cognitive deficits that are found in patients with bipolar disorder in remission and in patients with schizophrenia.

Recent studies of cerebral pathology in patients with schizophrenia have focused on symptomatological and electrophysiological correlates of reduced temporal lobe structure volumes. Volume deficits of the left superior temporal gyrus have been correlated with auditory hallucinations as well as to left-sided P300 amplitude reduction. However, caution is needed to interpret correlational data as evidence of a specific relationship. Therefore, a controlled study was undertaken on schizophrenic patients with and without auditory hallucinations. MRI-defined volumes of the left superior temporal gyrus and other temporal lobe structures were quantified from 3-mm coronal slices in 15 schizophrenic patients with chronic auditory hallucinations (hallucinators), 15 schizophrenic patients without auditory hallucinations (nonhallucinators) and 17 healthy controls. In all subjects a simple oddball paradigm was used to elicit P300 responses at temporal and centro-parietal electrode sites. No evidence was found for volume reductions of temporal lobe structures in the combined patient group compared with controls, or in the hallucinators compared with the nonhallucinators. The patients did show left P300 amplitude reduction compared with controls, particularly in the hallucinator group. Correlations between volumes of left temporal lobe structures and left P300 amplitudes were low and not significant. The results of the present study do not indicate that auditory hallucinations and associated abnormal electrophysiological activity are the consequence of atrophy of localized temporal lobe structures. However, replication in a larger sample of subjects is needed before firm conclusions can be drawn.