European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
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Eur Neuropsychopharmacol · Nov 2013
Randomized Controlled Trial Comparative StudyImpact of 5-HTTLPR and BDNF polymorphisms on response to sertraline versus transcranial direct current stimulation: implications for the serotonergic system.
Transcranial direct current stimulation (tDCS) has been intensively investigated as a non-pharmacological treatment for major depressive disorder (MDD). While many studies have examined the genetic predictors of antidepressant medications, this issue remains to be investigated for tDCS. In the current study, we evaluated whether the BDNF Val66Met and the 5-HTT (5-HTTLPR) polymorphisms were associated with tDCS antidepressant response. ⋯ A dose-response relationship between active-sham differences with the long allele was also suggested. These results strengthen the role of the serotonergic system in the tDCS antidepressant effects and expand previous findings that reported that tDCS mechanisms of action partially involve serotonergic receptors. Therefore, we hypothesize that tDCS is a neuromodulation technique that acts over depression through the modulation of serotonergic system and that tDCS "top-down" antidepressant effects might not be optimal in brain networks with a hyperactive amygdala inducing bottom-up effects, such as occurs in short-carriers.
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Eur Neuropsychopharmacol · Nov 2013
Paraventricular nucleus of the hypothalamus glutamate neurotransmission modulates autonomic, neuroendocrine and behavioral responses to acute restraint stress in rats.
In the present study, the involvement of paraventricular nucleus of the hypothalamus (PVN) glutamate receptors in the modulation of autonomic (arterial blood pressure, heart rate and tail skin temperature) and neuroendocrine (plasma corticosterone) responses and behavioral consequences evoked by the acute restraint stress in rats was investigated. The bilateral microinjection of the selective non-NMDA glutamate receptor antagonist NBQX (2 nmol/ 100 nL) into the PVN reduced the arterial pressure increase as well as the fall in the tail cutaneous temperature induced by the restraint stress, without affecting the stress-induced tachycardiac response. On the other hand, the pretreatment of the PVN with the selective NMDA glutamate receptor antagonist LY235959 (2 nmol/100 nL) was able to increase the stress-evoked pressor and tachycardiac response, without affecting the fall in the cutaneous tail temperature. ⋯ The PVN glutamate neurotransmission, via non-NMDA receptors, has a facilitatory influence on stress-evoked autonomic responses. On the other hand, the present data point to an inhibitory role of PVN NMDA receptors on the cardiovascular responses to stress. Moreover, our findings also indicate an involvement of PVN NMDA glutamate receptors in the mediation of the plasma corticosterone response as well as in the delayed emotional consequences induced by the restraint stress.
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Eur Neuropsychopharmacol · Nov 2013
Randomized Controlled TrialA randomised, double-blind, placebo-controlled, efficacy study of nalmefene, as-needed use, in patients with alcohol dependence.
This study evaluated the efficacy of as-needed use of the opioid system modulator nalmefene in reducing alcohol consumption in patients with alcohol dependence. Seven hundred and eighteen patients (placebo=360; nalmefene=358), ≥ 18 years of age, with a diagnosis of alcohol dependence, ≥ 6 heavy drinking days and an average alcohol consumption ≥ WHO medium drinking risk level in the 4 weeks preceding screening, were randomised (1:1) to 24 weeks of as-needed placebo or nalmefene 18 mg/day. The co- primary efficacy analyses showed a significantly superior effect of nalmefene compared to placebo in the change from baseline to month 6 in heavy drinking days (group difference: -1.7 days/month [95% CI -3.1; -0.4]; p=0.012) and a better but not significant effect in reducing total alcohol consumption (group difference: -5.0 g/day last month [95% CI -10.6; 0.7]; p=0.088). ⋯ Improvements in Clinical Global Impression and reductions in liver enzymes were greater in the nalmefene group than in the placebo group. Adverse events were more common with nalmefene; the incidence of adverse events leading to dropout was similar in both groups. This study provides evidence for the efficacy of nalmefene, which constitutes a new pharmacological treatment paradigm in terms of treatment goal (reduced drinking) and dosing regimen (as-needed), in alcohol dependent patients unable to reduce alcohol consumption on their own.
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Eur Neuropsychopharmacol · Nov 2013
Comparative Study Controlled Clinical TrialComparable seizure characteristics in magnetic seizure therapy and electroconvulsive therapy for major depression.
Electroconvulsive therapy (ECT) is highly effective for treatment-resistant depression (TRD); however, its use for less severe forms of depression is somewhat limited by a lack of control over current spreading to medial temporal lobe memory structures, resulting in various cognitive side effects. In contrast, magnetic seizure therapy (MST), which uses high frequency repetitive transcranial magnetic stimulation (rTMS) for local seizure induction, has been associated with reduced cognitive side effects. To assess whether different characteristics of seizures induced by both methods are responsible for the differences in neuropsychological side-effect profile, we studied seven TRD-patients undergoing both MST and ECT in an open-label, within subject, controlled crossover pilot study. ⋯ Our results showed no differences in motor activity or EMG and EEG characteristics, thus implicating similar electrophysiological processes in seizure induction with MST and ECT. In line with previous studies, we observed shorter postictal recovery and reorientation times following MST. The ictal characteristics of induced seizures were found similar with ECT and MST suggesting that the more focal seizure induction associated with MST may account for the more beneficial neuropsychological side effect profile of MST.