Effects of 5-HT on memory and the hippocampus: model and data.

5-Hydroxytryptamine (5-HT) transmission has been implicated in memory and in depression. Both 5-HT depletion and specific 5-HT agonists lower memory performance, while depression is also associated with memory deficits. The precise neuropharmacology and neural mechanisms underlying these effects are unknown. We used neural network simulations to elucidate the neuropharmacology and network mechanisms underlying 5-HT effects on memory. The model predicts that these effects are largely dependent on transmission over the 5-H

Acute tryptophan depletion improves performance and modulates the BOLD response during a Stroop task in healthy females

To gain more insight into the effect of low brain serotonin (5-HT) on brain activation related to conflict, the present study examined the effect of acute tryptophan depletion (ATD) on performance and the blood oxygen level dependent (BOLD) response during a combined cognitive and emotional Stroop task. Fifteen healthy female volunteers were tested during a placebo and tryptophan depletion session in an event-related fMRI design. ATD improved performance during Stroop interference. Two effects of ATD on the BOLD response were found. Firstly, ATD increased the BOLD response in the anterior cingulate cortex (ACC) (BA 32) when incongruent color words were compared with congruent color words in the first Stroop block the participants performed. Secondly, ATD increased the BOLD response in the left precuneus (BA 31) and cuneus (BA 18) during congruent color words. ATD did not affect the BOLD response accompanying emotional stimuli. However, we showed that ATD increased the interference of negative words on color naming. This finding was explained in terms of an emotional processing bias in favor of negative words, which leads to stronger interference of these words. In line with previous studies, the present study showed that a temporary reduction of 5-HT improved Stroop performance and changed the underlying brain activation pattern in healthy female participants. Moreover, we replicated our previous finding that ATD modulated the BOLD response in the dorsomedial prefrontal cortex during tasks that require cognitive control

Driving impairment in depressed patients receiving long-term antidepressant treatment

Background Depression is a common mental disorder with cognitive deficits, but little information is available on the effects of antidepressant treatment on driving performance in depressed patients. Aims Assessing actual driving performance and cognition of depressed patients receiving long-term antidepressant treatment. Materials and methods Performance was assessed in depressed patients receiving selective serotonin reuptake inhibitor (SSRI) or serotonin and noradrenalin reuptake inhibitor (SNRI) treatment for 6-52 weeks and in matched healthy controls by means of two standardised on-the-road driving tests and laboratory tests of cognition. Results Data showed poorer driving performance as indicated by a higher standard deviation of lateral position or 'weaving motion' in medicated patients relative to controls. Time to speed adaptation and critical flicker fusion threshold were also impaired in medicated patients. The Hamilton Depression Rating Scale scores in medicated patients were significantly higher as compared to that of controls. No other significant results between the two groups were demonstrated on the variables of the driving tests and laboratory tests of cognition. Conclusions The depressed patients receiving long-term treatment with SSRI- and SNRI-type antidepressants show impaired driving performance. This impairment in driving performance can probably be attributed to residual depressive symptoms instead of the antidepressant treatment

Specific serotonergic reuptake inhibition impairs vigilance performance acutely and after subchronic treatment.

Subchronic treatment with the selective serotonergic reuptake inhibitors (SSRIs) fluoxetine, venlafaxine and paroxetine, but not sertraline, were previously shown to specifically impair vigilance performance. The current study was designed to compare the vigilance effects of subchronic treatment with the SSRIs sertraline and citalopram in healthy volunteers, according to a placebo-controlled, double-blind, three-way cross-over design. Twenty-four healthy subjects, aged 30-50 years, of whom 21 completed the study, underwent three treatment periods of 2 weeks in which they received sertrahne (50 mg on days 1-8, 100 mg on days 8-15), citalopram (20 mg on days 1-8, 40 mg on days 8-15) and placebo. Treatment periods were separated by 14 days washout periods. Vigilance performance was assessed through a 45-min Mackworth Clock Test at days 1, 8 and 15 of each treatment period. It was found that citalopram impaired vigilance performance acutely after the first 20 mg dose and subchronically after 40 mg daily doses. By contrast, no vigilance impairment was found during sertraline treatment. Sertraline is the only SSRI studied so far with no detrimental effects on vigilance. This may be due to the affinity of sertraline for the dopamine reuptake site. Because citalopram is the most specific SSRI showing this effect, it is concluded that the SSRI-induced decrement of vigilance performance is specifically associated with serotonergic reuptake inhibition

Cafeine improves memory performance during distraction in middle-aged, but not in young or old subjects

The present study evaluated the effect of caffeine (225 mg) on cognitive performance in young, middle‐aged, and old subjects in a placebo‐controlled parallel groups design (n=60). Groups were matched for level of education and sex. Positive effects of caffeine, as compared to placebo, were found in middle‐aged subjects in the first trial of the word learning test. In contrast, caffeine had negative effects on the speed of searching short‐term memory in young subjects. Caffeine had no effect on the intercept, which is an indicator for sensorimotor speed, of a memory scanning task. The middle‐aged subjects appeared to regularly consume twice as much caffeine as the young and old subjects. These results were similar to earlier findings in a large population study. Although statistical analyses with habitual caffeine consumption as a covariate did not yield different results, a caffeine withdrawal effect was hypothesized to be responsible for the reduced cognitive performance of middle‐aged subjects receiving placebo. The habitual use of large amounts of caffeine by middle‐aged subjects may be a means to overcome the age‐related decrease in cognitive functioning that is caused by changes in information processing

The effects of habitual caffeine use on cognitive change: a longitudinal perspective.

The efficiency of higher cortical functions, such as memory and speed of complex information processing, tends to decrease with advancing age in normal healthy individuals. Recently, a high habitual intake of caffeine was found associated with better verbal memory performance and psychomotor speed in several cross-sectional population studies. We tested the hypothesis that habitual caffeine intake can reduce or postpone age-related cognitive decline in healthy adults. For this purpose, the cognitive performance of all participants in the maastricht aging study (maas), aged between 24 and 81 years, was reassessed after 6 years. Information on the intake of caffeine-containing beverages was available from the baseline questionnaire. After 6 years, 1376 (75.6%) individuals were available for reassessment. After correction for demographic characteristics, baseline performance and health status, there were small albeit significant associations between the overall estimated caffeine intake at baseline and the 6-year change in complex motor speed (motor choice reaction time). The earlier found association between caffeine intake and verbal memory performance was not apparent in this longitudinal study. These results imply that the longitudinal effect of habitual caffeine intake is limited and will not promote a substantial reduction in age-related cognitive decline at a population level

Modulation of the critical flicker fusion effects of serotonin reuptake inhibitors by concomitant pupillary changes.

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