Serotonin transporter availability, neurocognitive function and their correlation in abstinent 3,4-methylenedioxymethamphetamine users.

RATIONALE: MDMA or Ecstasy has made a resurgence in popularity and the majority of users consist of teenagers and adolescents. Therefore, it is important to determine whether MDMA causes long-term damage and what this damage entails. There is an ongoing debate about possible neurocognitive changes in 3,4-methylenedioxymethamphetamine (MDMA) users related to MDMA's neurotoxic potential. Multiple neuroimaging studies have shown that Ecstasy use leads to lower serotonin transporter (SERT) availability in multiple brain regions. This may express itself in a loss of cognitive functions like memory, attention and executive function. However, there is increasing evidence reporting that MDMA's induced serotonergic adaptations are reversible over time. The question we thus address is whether the recovery of SERT function predicts a recovery of cognitive function. OBJECTIVES: This review aims to investigate MDMA's long-term effects on SERT availability and cognitive functioning. METHODS: A literature search was performed in PubMed. Studies that investigated the effects of MDMA on both SERT availability and cognitive performance were eligible for inclusion. RESULTS: SERT availability positively correlated with time of abstinence, whereas memory performance did not show this correlation, but remained impaired in MDMA users. No significant correlation between SERT availability and memory function was found (r = 0.232, p = 0.581; r = 0.176, p = 0.677). CONCLUSIONS: The main findings of this review are that MDMA-use leads to an acute decrease in SERT availability and causes an impairment in cognitive functions, mostly memory. However, SERT availability recovers with sustained abstinence while memory function does not. This suggests that SERT availability is not a biomarker for MDMA-induced cognitive impairment and likely also not for MDMA-induced neurotoxicity.

[Oxytocin for the treatment of PTSD?] / Oxytocine voor de behandeling van PTSS?

Oxytocin is mostly known for its pro-social effects and may increase positive emotions, and as such may be a relevant treatment option for PTSD. Although oxytocin indeed showed some alleviating effects on PTSD in the study by Koch et al., effects were small and the clinical significance of these findings remains to be determined.

Digging deeper in the differential effects of inflammatory and psychosocial stressors in remitted depression: Effects on cognitive functioning.

BACKGROUND: Major Depressive Disorder (MDD) covers a wide spectrum of symptoms, including cognitive dysfunction, which can persist during remission. Both inflammatory states and psychosocial stress play a role in MDD pathogenesis. METHODS: The effects of inflammatory (i.e., Salmonella typhi vaccine) and psychosocial stressor (i.e., Trier Social Stress Test), as well as their combination were investigated on cognition in women (aged 25-45 years, n = 21) with (partially) remitted MDD and healthy controls (n = 18) in a single-blind placebo-controlled study. In a crossover design, patients received on the first day one of the aforementioned interventions and on the other day a placebo, or vice versa, with a washout period of 7-14 days. Short-term and verbal memory, working memory, attention, verbal fluency, information processing speed, psychomotor function, and measures of attentional bias to emotions were measured. Exploratory analyses were performed to assess the correlation between biomarkers of inflammation and the Hypothalamic-Pituitary-Adrenal axis and cognitive functioning. RESULTS: In patients, inflammatory stress decreased information processing speed and verbal memory, and increased working memory; after psychosocial stress, there was an increase in attention. There was also an increased negative attentional bias in patients after inflammatory stress. Neither stressor had any effect in controls. LIMITIATIONS: Limitations are the relatively small sample size and antidepressant use by a part of the participants. The effects of the stressors were also measured a relatively short period after administration. CONCULSION: Patients were sensitive to the cognitive effects of inflammation and psychosocial stress on cognition, while controls were not.

Differential Effects of Inflammatory and Psychosocial Stress on Mood, Hypothalamic-Pituitary-Adrenal Axis, and Inflammation in Remitted Depression.

BACKGROUND/AIMS: Major depressive disorder (MDD) is highly recurrent. This may be due to increased stress sensitivity after remission. Both inflammatory and psychosocial stressors are implicated in the pathogenesis of MDD, but the additive or differential effect is unclear. METHODS: We conducted a single-blind placebo-controlled study to investigate the effects of inflammatory stress (i.e., typhoid vaccination), psychosocial stress (i.e., Trier Social Stress Test [TSST]), or a combination of both in women (25-45 years old) with (partially) remitted recurrent MDD (n = 21) and healthy female controls (n = 18). We evaluated the effect on mood measured by the Profile of Mood States, markers of the hypothalamic-pituitary-adrenal (HPA) axis activity, and inflammatory system activation. The study was performed during 2 testing days, separated by a washout of 7-14 days. In a crossover design, subjects received one of the interventions on one day and placebo on the other. RESULTS: A lowering of mood was seen in patients (ß [95% CI] = -4.79 [-6.82 to -2.75], p < 0.001) only after vaccination, but not after the TSST or the combination; this effect was not observed in controls. Controls experienced a significantly different response on adrenocorticotropic hormone (ACTH) after vaccination, with a general rise in ACTH not observed in patients. In both groups, the TSST activated the HPA axis and suppressed the inflammatory parameters. CONCLUSIONS: There is a differential effect of inflammatory and psychosocial stress on mood and HPA axis activation in patients with remitted recurrent MDD. This may be an interesting treatment target in MDD.

The effects of nicotine on cognition are dependent on baseline performance.

Since cholinergic neurotransmission plays a major role in cognition, stimulation of the nicotinic acetylcholine receptor may be a target for cognitive enhancement. While nicotine improves performance on several cognitive domains, results of individual studies vary. A possible explanation for these findings is that the effect of nicotine administration may be dependent on baseline cognitive function, where subjects with a suboptimal cognitive performance may benefit from nicotine, while subjects who already perform optimally may show a decline in performance after nicotinic stimulation. We conducted a double-blind randomised placebo-controlled crossover trial, examining the effects of placebo, 1, and 2mg of nicotine on cognition in young (n=16, age 18-30 years) and healthy elderly (n=16, age 60-75 years) subjects. We hypothesised that the elderly would benefit more from nicotine compared to young subjects, as normal ageing is associated with decreases in cognitive function. Attention, working memory, visual memory, information-processing speed, psychomotor function, stereotypy, and emotion recognition were assessed. Compared to the young volunteers, the elderly performed significantly worse on psychomotor function and emotion recognition in the placebo condition. Nicotine had no effect in the young volunteers and decreased performance on working memory and visual memory in the elderly. Contrary to our hypothesis, the effect of nicotine was dependent on baseline performance in both the groups, with subjects with lower baseline performance benefiting from nicotine administration, while those with higher baseline performance performed worse after nicotine administration. This suggests that subjects with lower cognitive performance, irrespective of age, may benefit from nicotine.

Bupropion for the treatment of seasonal affective disorder.

INTRODUCTION: Seasonal affective disorder (SAD) is a psychiatric illness with recurring depressive episodes during particular seasons, mostly winter. Bupropion is effective in the preventive treatment of SAD and is probably also effective in the acute treatment of SAD. AREAS COVERED: This review covers the pharmacokinetics and pharmacodynamics of bupropion. The authors also evaluate bupropion's clinical efficacy as well as its safety and tolerability. EXPERT OPINION: Bupropion is available in an immediate release formulation, as well as a sustained release formulation and an extended release (XR) formulation. The XR formulation is recommended for SAD due to its ease of use and is the only formulation currently used as a therapy. Due to the predictable nature of SAD, the use of bupropion XR is considered a relevant treatment option. Bupropion's efficacy is shown in three trials that started in autumn at a time when SAD symptoms were not yet present although treatment effects were relatively small compared with a placebo. Bupropion was also shown to have efficacy in an open-label study. That being said, in order to reach definitive conclusions about its efficacy with acute treatment of SAD, more placebo-controlled trials are needed.

Acute effects of delta-9-tetrahydrocannabinol on performance monitoring in healthy volunteers.

RATIONALE: The error-related negativity (ERN) is a negative event-related potential that occurs immediately after an erroneous response and is thought to reflect human performance monitoring. Delta-9-Tetrahydrocannabinol (THC) administration in healthy volunteers has been linked to impaired performance monitoring in behavioral studies, but to date no studies have examined the effects of cannabinoids on the ERN. METHODS: EEG data from 10 healthy volunteers was recorded during execution of a speeded choice-reaction-time task (Flankers task) after administration of THC or placebo vapor in a double-blind randomized crossover design. RESULTS: The findings of this study show that the ERN was significantly reduced after administration of THC. The behavioral outcomes on the Flankers task showed no indications of drug-induced impairments. DISCUSSION: The diminished ERN reflects impairments in the process of performance monitoring. The task design was not optimized to find behavioral effects. The study shows that cannabinoids impair performance monitoring.

Acute effects of MDMA (3,4-methylenedioxymethamphetamine) on EEG oscillations: alone and in combination with ethanol or THC (delta-9-tetrahydrocannabinol).

RATIONALE: Typical users of 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") are polydrug users, combining MDMA with alcohol or cannabis [most active compound: delta-9-tetrahydrocannabinol (THC)]. OBJECTIVES: The aim of the present study was to investigate whether co-administration of alcohol or THC with MDMA differentially affects ongoing electroencephalogram (EEG) oscillations compared to the administration of each drug alone. METHODS: In two separate experiments, 16 volunteers received four different drug conditions: (1) MDMA (100 mg); (2) alcohol clamp (blood alcohol concentration = 0.6‰) or THC (inhalation of 4, 6 and 6 mg, interval of 1.5 h); (3) MDMA in combination with alcohol or THC; and (4) placebo. Before and after drug administration, electroencephalography was recorded during an eyes closed resting state. RESULTS: Theta and alpha power increased after alcohol intake compared to placebo and reduced after MDMA intake. No interaction between alcohol and MDMA was found. Significant MDMA x THC effects for theta and lower-1-alpha power indicated that the power attenuation after the combined intake of MDMA and THC was less than the sum of each drug alone. For the lower-2-alpha band, the intake of MDMA or THC alone did not significantly affect power, but the intake of combined MDMA and THC significantly decreased lower-2-alpha power. CONCLUSIONS: The present findings indicate that the combined intake of MDMA and THC, but not of MDMA and alcohol, affects ongoing EEG oscillations differently than the sum of either one drug alone. Changes in ongoing EEG oscillations may be related to the impaired task performance that has often been reported after drug intake.

A comparative study of two methods for attaining constant alcohol levels.

AIMS: Alcohol effects or drug-alcohol interactions are preferably studied at constant blood levels. To achieve pseudo-steady state levels, various methods are used, which usually produce adequate averages but variable individual concentration profiles. The aim was to compare two modes of alcohol administration: a 'two-step prekinetic procedure' and a 'clamping method'. METHODS: The two-step prekinetic procedure started with determination of individual pharmacokinetic (PK) parameters, during a prestudy occasion. Individual infusion regimens were calculated afterwards, based on a pseudo-steady state breath alcohol concentration (BrAC) of 0.65 g l(-1) and applied on a separate occasion. For the clamping procedure, a spreadsheet-based paradigm was developed using BrAC-guided adjustments of infusion rates, to maintain stable BrAC levels of 0.6 g l(-1). RESULTS: The mean BrAC during clamping [0.61 g l(-1), 95% confidence interval (CI) 0.58, 0.63] did not differ from its intended level of 0.6 g l(-1) (1.0% on average). In contrast, the mean BrAC during the prekinetic procedure was significantly lower than the 0.65 g l(-1) set-point (0.59 g l(-1), 95% CI 0.54, 0.63) and deviated from this target by 9.7% on average. The clamping method also showed less variation between subjects [coefficient of variation (CV) 6.2%] compared with the prekinetic procedure (CV 14.6%). CONCLUSIONS: Although the two methods differ considerably in their approach, clamping of BrAC resulted in more accurate alcohol levels than infusion based on PK modelling and does not require an extra prestudy occasion. The novel alcohol clamping paradigm can be of value in future studies of alcohol interactions or the pharmacodynamics of acute alcohol administration.

Biphasic injection for femoral and aorto-femoral arteriography utilizing a standard pressure injector.

A simple method of obtaining a biphasic injection of contrast material with a standard pressure injector was developed for aorto-femoral and unilateral iliac-femoral arteriograms. An improvement in the degree of arterial filling, the quality of visualization,and the almost complete elimination of repeat injections was noted.

Abdominal aorta catheterization via the left axillary artery.

A simple technique is described for catheterization of the abdominal aorta via the left axillary artery. A commercially available pigtail catheter is used to direct the guide wire toward the descending aorta, and the contrast material may be injected through this catheter. This method works well, even in elderly patients with elongated, tortuous aortas.