Tryptophan research in panic disorder.

A considerable body of evidence suggests the involvement of serotonin neurotransmission in the pathogenesis of panic disorder. Research on pathways and functions of tryptophan, an essential amino acid converted into serotonin, may advance our understanding of serotonergic actions in panic disorder and related phenomena. The investigative approaches in this field include manipulations of tryptophan availability as well as genetic association and functional brain imaging studies. In this review we examine the principle findings of these studies and propose further research directions

Differentiated effects of the multimodal antidepressant vortioxetine on sleep architecture: Part 1, a pharmacokinetic/pharmacodynamic comparison with paroxetine in healthy men

We compared the effect of vortioxetine, paroxetine and placebo after three days of dosing on sleep architecture. This was a randomised, double-blind, four-way crossover, placebo-controlled, multiple-dose study in 24 healthy young men. Subjects received 20mg vortioxetine, 40mg vortioxetine, 20mg paroxetine or placebo for three consecutive days in four different periods with at least three weeks between them. Polysomnography and blood sampling for pharmacokinetic analysis were performed on the pre-dose night and nights 1 and 3 of dosing in each period. Plasma concentrations of vortioxetine and paroxetine during the polysomnography measurement were used to estimate SERT occupancies using published relationships in healthy subjects. All three active treatments significantly increased REM onset latency and decreased time spent in REM sleep. In the pharmacokinetic/pharmacodynamics analysis significant relationships were found between REM onset latency and time spent in REM sleep and vortioxetine/paroxetine exposure. The relation between REM suppression parameters and SERT occupancy was significantly different between vortioxetine and paroxetine, despite the same SERT occupancy. This indicates that vortioxetine has a different clinical pharmacological profile from paroxetine, which may explain the differences in adverse effect profile of the two drugs, for instance the lower incidence of nausea, weight gain and sexual dysfunction with vortioxetine

Psychopharmacological characterisation of the successive negative contrast effect in rats

Rationale Successive negative contrast (SNC) describes a change in the behaviour of an animal following a downshift in the quantitative or qualitative value of an expected reward. This behavioural response has been hypothesised to be linked to affective state, with negative states associated with larger and/or prolonged shifts in behaviour. Objective This study has investigated whether different psychopharmacological treatments have dissociable actions on the SNC effect in rats and related these findings to their actions on different neurotransmitter systems and affective state. Methods Animals were trained to perform a nose-poke response to obtain a high-value food reward (four pellets). SNC was quantified during devalue sessions in which the reward was reduced to one pellet. Using a within-subject study design, the effects of acute treatment with anxiolytic, anxiogenic, antidepressant and dopaminergic drugs were investigated during both baseline (four pellets) or devalue sessions (one pellet). Results The indirect dopamine agonist, amphetamine, attenuated the SNC effect whilst the D1/D2 antagonist, alpha-flupenthixol, potentiated it. The antidepressant citalopram, anxiolytic buspirone and anxiogenic FG7142 had no specific effects on SNC, although FG7142 induced general impairments at higher doses. The α2-adrenoceptor antagonist, yohimbine, increased premature responding but had no specific effect on SNC. Results for the anxiolytic diazepam were mixed with one group showing an attenuation of the SNC effect whilst the other showed no effect. Conclusions These data suggest that the SNC effect is mediated, at least in part, by dopamine signalling. The SNC effect may also be attenuated by benzodiazepine anxiolytics

The development and validation of a human screening model of tobacco abstinence

INTRODUCTION: Given the low efficacy of smoking cessation methods, an experimental medicine model indicating smoking abstinence would be of great benefit to the development of new treatments. Hence the sensitivity of cognitive tasks and ambulatory craving measures to smoking abstinence were investigated. METHODS: Cognitive tasks and ambulatory ratings of craving were assessed for sensitivity to acute abstinence (experiment 1), and nicotine replacement therapy administration (NRT) (experiment 2). RESULTS: In experiment 1 go/no-go performance was improved (Mean Difference [MD] -0.99, 95% CI: -1.90 to -0.08) and craving was lower (Regression Coefficient [RC] -33.39, 95% CI: -39.96 to -26.82) in satiated compared with abstinent smokers. There was no clear evidence that N-back (MD 0.64, 95% CI: -0.42 to 2.51), delay discounting (MD 0.01, 95% CI: 0.001 to 0.005) or dot probe performance (MD 0.61, 95% CI: -0.87 to 1.54) were sensitive to acute abstinence. In experiment 2 go/no-go performance was improved (MD 1.12, 95% CI: 0.16-2.08) and craving was lower (RC -18.59, 95% CI: -24.63 to -12.55) smokers abstinent overnight receiving NRT compared with placebo. There was no clear evidence that N-back (MD -0.25, 95% CI: -1.45 to 0.94), delay discounting (MD 0.01, 95% CI: -0.002 to 0.004) or dot probe performance (MD -0.49, 95% CI: -1.61 to -0.64) were sensitive to NRT. CONCLUSIONS: Findings from two experiments converge to suggest that abstinence in smokers reliably increases ambulatory craving assessments and, to a lesser extent, decreases go/no-go task performance. These findings can be utilized in the development of an experimental medicine model to test novel treatments for smoking cessation

Behavioral tasks sensitive to acute abstinence and predictive of smoking cessation success: A systematic review and meta-analysis

BACKGROUND AND AIMS: Performance on cognitive tasks may be sensitive to acute smoking abstinence and may also predict whether quit attempts fail. Our aim was to conduct a systematic review and meta-analysis to identify cognitive tasks sensitive to acute abstinence and predictive of smoking cessation success. METHODS: Embase, Medline, PsycInfo and Web of Science were searched up to March 2016. Studies were included if they enrolled adults and assessed smoking using used a quantitative measure. Studies were combined in a random effects meta-analysis. RESULTS: We included 42 acute abstinence studies and 13 cessation studies. There was evidence for an effect of abstinence on delay discounting [d = 0.26, 95% CI 0.07 to 0.45, p = 0.005], response inhibition [d = 0.48, 95% CI 0.26 to 0.70, p < 0.001], mental arithmetic [d = 0.38, 95% CI 0.06 to 0.70, p = 0.018], and recognition memory [d = 0.46, 95% CI 0.23 to 0.70, p < 0.001]. In contrast performance on the Stroop [d =0 .17, 95% CI -0.17 to 0.51, p = 0.333] and smoking Stroop [d = 0.03, 95% CI -0.11 to 0.17, p = 0.675] task was not influenced by abstinence. We found only weak evidence for an effect of acute abstinence on dot probe task performance [d = 0.15, 95% CI -0.01 to 0.32, p = 0.072]. The design of the cessation studies was too heterogeneous to permit meta-analysis. CONCLUSIONS: Compared with satiated smokers, acutely abstinent smokers display higher delay discounting, lower response inhibition, impaired arithmetic, and recognition memory performance. However, reaction time measures of cognitive bias appear to be unaffected by acute tobacco abstinence. Conclusions about cognitive tasks that predict smoking cessation success were limited by methodological inconsistencies

Semantic activation in LSD: evidence from picture naming

Lysergic acid diethylamide (LSD) is a classic psychedelic drug that alters cognition in a characteristic way. It has been suggested that psychedelics expand the breadth of cognition via actions on the central nervous system. Previous work has shown changes in semantic processing under psilocybin (a related psychedelic to LSD) that are consistent with an increased spread of semantic activation. The present study investigates this further using a picture-naming task and the psychedelic, LSD. Ten participants completed the task under placebo and LSD. Results revealed significant effects of LSD on accuracy and error correction that were consistent with an increased spread of semantic activation under LSD. These results are consistent with a generalised “entropic” effect on the mind. We suggest incorporating direct neuroimaging measures in future studies, and to employ more naturalistic measures of semantic processing that may enhance ecological validity

Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression

RATIONALE: Depressed patients robustly exhibit affective biases in emotional processing which are altered by SSRIs and predict clinical outcome. OBJECTIVES: The objective of this study is to investigate whether psilocybin, recently shown to rapidly improve mood in treatment-resistant depression (TRD), alters patients' emotional processing biases. METHODS: Seventeen patients with treatment-resistant depression completed a dynamic emotional face recognition task at baseline and 1 month later after two doses of psilocybin with psychological support. Sixteen controls completed the emotional recognition task over the same time frame but did not receive psilocybin. RESULTS: We found evidence for a group × time interaction on speed of emotion recognition (p = .035). At baseline, patients were slower at recognising facial emotions compared with controls (p < .001). After psilocybin, this difference was remediated (p = .208). Emotion recognition was faster at follow-up compared with baseline in patients (p = .004, d = .876) but not controls (p = .263, d = .302). In patients, this change was significantly correlated with a reduction in anhedonia over the same time period (r = .640, p = .010). CONCLUSIONS: Psilocybin with psychological support appears to improve processing of emotional faces in treatment-resistant depression, and this correlates with reduced anhedonia. Placebo-controlled studies are warranted to follow up these preliminary findings

A case of PTSD presenting with psychotic symptomatology: a case report

A male patient aged 43 presented with psychotic symptomatology after a traumatic event involving accidental mutilation of the fingers. Initial presentation was uncommon although the patient responded well to pharmacotherapy. The theoretical framework, management plan and details of the treatment are presented

Significant reductions in human visual gamma frequency by the gaba reuptake inhibitor tiagabine revealed by robust peak frequency estimation

The frequency of visual gamma oscillations is determined by both the neuronal excitation-inhibition balance and the time constants of GABAergic processes. The gamma peak frequency has been linked to sensory processing, cognitive function, cortical structure, and may have a genetic contribution. To disentangle the intricate relationship among these factors, accurate and reliable estimates of peak frequency are required. Here, a bootstrapping approach that provides estimates of peak frequency reliability, thereby increasing the robustness of the inferences made on this parameter was developed. The method using both simulated data and real data from two previous pharmacological MEG studies of visual gamma with alcohol and tiagabine was validated. In particular, the study by Muthukumaraswamy et al. [] (Neuropsychopharmacology 38(6):1105-1112), in which GABAergic enhancement by tiagabine had previously demonstrated a null effect on visual gamma oscillations, contrasting with strong evidence from both animal models and very recent human studies was re-evaluated. After improved peak frequency estimation and additional exclusion of unreliably measured data, it was found that the GABA reuptake inhibitor tiagabine did produce, as predicted, a marked decrease in visual gamma oscillation frequency. This result demonstrates the potential impact of objective approaches to data quality control, and provides additional translational evidence for the mechanisms of GABAergic transmission generating gamma oscillations in humans. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc