Methylphenidate significantly improves declarative memory functioning of adults with ADHD

Contains fulltext : 87790.pdf (publisher's version ) (Closed access)BACKGROUND: Declarative memory deficits are common in untreated adults with attention-deficit hyperactivity disorder (ADHD), but limited evidence exists to support improvement after treatment with methylphenidate. The objective of this study was to examine the effects of methylphenidate on memory functioning of adults with ADHD. METHODS: Eighteen adults with ADHD who were clinical responders to methylphenidate participated in this randomized crossover trial. After 3 days of no treatment, patients received in random order either their usual methylphenidate dose (mean: 14.7 mg; range: 10-30 mg) or placebo, separated by a 6-7-day washout period. Patients performed an immediate word recall test 1 h after treatment administration. Three hours after intake, patients performed the second part of the memory test (delayed word recall and a recognition test). RESULTS: Delayed recognition and immediate recall was similar on treatment and on placebo. Delayed word recall was significantly better in the methylphenidate than in the placebo condition (F (1, 17) = 7.0, p < 0.017). A significant correlation was found between prestudy CES-D depression scores and difference scores on delayed recall (r = 0.602, p < 0.008). CONCLUSION: Methylphenidate improves declarative memory functioning in patients with ADHD. New studies should further examine whether subclinical depressive symptoms mediate the effect of methylphenidate on declarative memory.1 oktober 201

Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers

Contains fulltext : 73592.pdf (publisher's version ) (Open Access)RATIONALE: In Western societies, a considerable percentage of young people expose themselves to 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"). Commonly, ecstasy is used in combination with other substances, in particular alcohol (ethanol). MDMA induces both arousing as well as hallucinogenic effects, whereas ethanol is a general central nervous system depressant. OBJECTIVE: The aim of the present study is to assess the acute effects of single and co-administration of MDMA and ethanol on executive, memory, psychomotor, visuomotor, visuospatial and attention function, as well as on subjective experience. MATERIALS AND METHODS: We performed a four-way, double-blind, randomised, crossover, placebo-controlled study in 16 healthy volunteers (nine male, seven female) between the ages of 18-29. MDMA was given orally (100 mg) and blood alcohol concentration was maintained at 0.6 per thousand by an ethanol infusion regime. RESULTS: Co-administration of MDMA and ethanol was well tolerated and did not show greater impairment of performance compared to the single-drug conditions. Impaired memory function was consistently observed after all drug conditions, whereas impairment of psychomotor function and attention was less consistent across drug conditions. CONCLUSIONS: Co-administration of MDMA and ethanol did not exacerbate the effects of either drug alone. Although the impairment of performance by all drug conditions was relatively moderate, all induced significant impairment of cognitive function

Differences between low and high trait impulsivity are not associated with differences in inhibitory motor control

Objective: The present study investigates whether there is an association between trait impulsivity in the normal population and inhibitory motor control as assessed by the stop task. Method: Low- and high-impulsive participants (as assessed by the I7questionnaire; both groups n = 31) performed the stop task. Differences in performance were analyzed by an independent samples t-test. Furthermore, a short meta-analysis was performed on this study and three previous studies with a similar aim. Results: The low- and high-impulsive groups did not differ on the speed to stop the response (SSRT). However, the meta-analysis revealed that high-impulsives are marginally slower in stopping than low-impulsives (effect size = -0.26, p = 0.06). Conclusions: There is only minor evidence that impulsivity in the common population is associated with poor inhibitory motor control

The effects of low dose ketamine on sensory gating, neuroendocrine secretion and behavior in healthy human subjects

Recently, much interest has been given to the role of glutamatergic N- methyl-D-aspartate receptors (NMDA) in sensory gating, such as prepulse inhibition (PPI) and reduction of the P50 evoked response potential (ERP). Currently, mainly animal data are available describing the role of NMDA receptors in these stimulus evaluation processes. Human data are virtually lacking and are potentially important, for instance for the understanding of sensory gating deficits observed in schizophrenia. Therefore, the effects of the NMDA antagonist ketamine, in a dose of 0.3 mg/kg IV, on concurrent assessment of PPI and P50 reduction was studied in 18 healthy male volunteers. Ketamine was administered in a pseudo-steady state model with a subacute loading dose. In addition, the effects of ketamine on behavior, vital signs, homovanillic acid (HVA) plasma levels and secretion of cortisol and luteinizing hormone (LH) were also determined. Ketamine did not significantly alter PPI or the reduction of the P50 ERE A small but significant increase in Brief Psychiatric Rating Scale (BPRS) total scores and BPRS composite scores 'thinking disorder' and 'withdrawal/retardation' was observed. Several subjects experienced visual perceptional alterations, but complex hallucinations did not occur. Ketamine induced mild analgesia and coordination problems. In addition, ketamine induced a marked rise in cortisol secretion, while LH secretion was not affected. Finally, systolic and diastolic, blood pressure and heart rate increased during ketamine infusion. Although in humans NMDA receptors may not be involved in the regulation of PPI and P50 reduction, the most likely explanation for the lack of effect of ketamine on these sensory gating paradigms is the dose used in this experiment. However, using a higher dose is hampered by the aspecificity of racemic ketamine. Future studies should use the enantiomer Sketamine, which is more specific to NMDA receptors, to evaluate the involvement of NMDA receptors in these neurophysiological processes further

The effects of a sub-anaesthetic dose of ketamine on human selective attention

A growing number of studies demonstrate that antagonists of the N- methyl-D-aspartate (NMDA) receptors can induce a broad range of psychophysiological anomalies in healthy subjects similar to those observed in schizophrenia. In this study, the effect of a sub-anaesthetic dose of the non-competitive NMDA antagonist, ketamine, on human selective attention was explored. It was hypothesized that ketamine would induce in healthy subjects psychophysiological anomalies that are commonly observed in schizophrenic patients, such as reduced P300 amplitude and a reduction of both mismatch negativity (MMN) and processing negativity (PN). In a double-blind randomized placebo-controlled design, healthy male volunteers (n = 18) were challenged with a sub-anaesthetic dose of ketamine (0.3 mg/kg iv) after which they were tested in a selective attention task. In this task, two types of stimuli were evenly presented to the left or right ear: standard tones (80%) and deviant tones (20%) of either 1000 or 1100 Hz. The duration of a stimulus (95 dB) was 50 ms, the interstimulus intervals were randomized between 1750 and 2150 ms. The volunteer was instructed to push a button as quickly as possible after hearing the deviant tone in a specified ear. Ketamine did not alter performance of the subjects: in both the placebo and drug condition their reaction times for and percentages of hits and false alarms did not differ. Ketamine did, however, reduce PN and the P300 amplitude (both in general and to deviant stimuli in particular). However, no drug effect on MMN was found. In addition, ketamine enhanced the N100 amplitude to deviant stimuli. In conclusion, ketamine induces some of the attentional deficits in healthy controls that are observed in schizophrenic patients. Consequently, reduced glutamatergic activity in the brain may be involved in some of the symptoms of schizophrenia. (C) 2000 American College of Neuropsychopharmacology

P50 suppression and prepulse inhibition of the startle reflex in humans: A correlational study

Background: Sensory gating is an important feature of the normally functioning brain. When not operating correctly, it can contribute to different kinds of psychiatric illnesses by flooding the higher brain functions with useless information. Over the years, two paradigms have evolved to quantify the amount of sensory gating: the prepulse inhibition (PPI) of the startle reflex and the suppression of the P50 evoked potential. To enable comparison across studies it is important to find out to what extent these paradigms reflect the same processes. In the present study, this relationship was explored. Methods: Thirty-one healthy male volunteers with no personal or family history of mental illness were tested on their ability to suppress the P50 wave and to inhibit the startle reflex. Results: A significant positive correlation was found between PPI and P50 suppression mainly early in testing, when habituation of the startle reflex is taking place. Furthermore, a significant negative correlation was found between P50 suppression in the second half of testing and the habituation of the startle reflex. Conclusions: PPI and P50 suppression are correlated at an early stage of testing, when the process of habituation of the startle reflex is active. The role of the habituation in the correlation between these two measures needs to be further explored