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Byline: Marcus R. Munafo (Department of Experimental Psychology, University of Bristol, Bristol, UK, marcus.munafo@bristol.ac.uk); Zola N. Mannie (Department of Psychiatry, University of Oxford, Oxford, UK); Philip J. Cowen (Department of [...]

Abstract The synthesis of serotonin (5-HT) in the central nervous system is dependent on the availability to the brain of its precursor amino acid, tryptophan (TRP). Recent studies suggest that [...]

Background: The neurocognitive model of antidepressant treatment in depression states that antidepressants work by producing relatively immediate positive shifts in emotional processing, which translate into clinical improvement with time. St John's Wort has shown antidepressant potential in randomised controlled trials; however, its pharmacological actions are broad and it is unknown whether treatment also produces changes in emotional processing.Aims: We investigated whether short-term treatment with St John's wort has similar effects on emotional processing to those reported with other antidepressants such as selective serotonergic reuptake inhibitors.Methods: Forty-eight healthy participants were given St John's wort or placebo treatment for seven days. On day 7 they completed a battery of tasks to measure emotional processing and other elements of cognition.Results: St John's wort treatment produced similar changes to other antidepressants, for example reducing recognition of disgusted faces and attention to fearful faces, while increasing memory for positive words. We failed to find evidence for an effect of St John's wort on other aspects of cognition including working memory.Conclusions: These findings lend support to the theory that the production of early positive biases in emotional processing may be a common feature of all clinically effective antidepressants with diverse pharmacological mechanisms. [ABSTRACT FROM AUTHOR]

There has been increasing interest in the antidepressant effects of the muscarinic cholinergic receptor antagonist scopolamine. Here we assess, for the first time, whether a transdermal scopolamine patch is sufficient to induce changes in cognition that are consistent with the reported cognitive and antidepressant effects of scopolamine. A scopolamine or placebo patch was administered to healthy volunteers ( n=33) for 17 h in a double-blind, between-subject procedure. There was no clear effect of scopolamine patch on emotional cognition, verbal or working memory, suggesting that the effective dose of scopolamine available through the patch is too low to represent a viable antidepressant mechanism. [ABSTRACT FROM AUTHOR]

Ketamine is a N-methyl-D-aspartic acid (NMDA) antagonist that has been associated with temporary clinical improvement in patients with depression. Studies using magnetic resonance spectroscopy (MRS) have shown that major depression is associated with decreased levels of glutamate and glutamine (Glx) in the anterior cingulate cortex, which normalize with clinical recovery. The present study aimed to test whether a ketamine infusion would increase cortical Glx levels in healthy volunteers. Healthy volunteers received an intravenous infusion of ketamine (0.5 mg kg−1, n = 8) or saline (n = 9) over 40 minutes. MRS measurements were obtained at baseline, during, and at the end of the infusion. The infusion of ketamine had significant effects on mental state but there was no effect of ketamine on the levels of Glx (F3,39 = 1.70, p = 0.18) or glutamate (F3,39 = 48, p = 0.70). This study suggests that the gradual infusion of low-dose ketamine in antidepressant doses not cause changes in cortical glutamate or glutamine in healthy volunteers that are visible by proton MRS. [ABSTRACT FROM PUBLISHER]

Rimonabant is a cannabinoid type 1 receptor (CB1) antagonist formerly used to treat obesity, but which was withdrawn from the market in late 2008 because of its association with psychiatric adverse effects such as depression and anxiety. Previously, we showed that a single dose of rimonabant produced a negative bias on an emotional word memory task, in the absence of subjective mood effects. The present study investigated whether a similar effect on emotional processing could be seen after 7 days’ daily treatment with rimonabant 20 mg, using a randomized, placebo-controlled, between-subjects design in healthy volunteers (final n = 21). In comparison with placebo, rimonabant induced a negative bias on a memory recognition task without producing a change in subjective mood. This raises the possibility that the depressogenic effects of rimonabant may be linked to emotional memory biases, and that such biases may be detectable in the absence of subjective mood changes. Investigating such effects could be useful in detecting adverse psychiatric effects of novel treatments. [ABSTRACT FROM PUBLISHER]

Current antidepressant agents are similar in efficacy to the original drugs discovered in the 1950s. The development of new treatments for depression is, however, limited by the absence of validated human biomarker models to predict efficacy, clinical profile and dosing. Such models need to meet key criteria for biomarkers including sensitivity, specificity and relevance to depression. Here we review studies exploring whether early changes in emotional processing with antidepressant drug administration meet these criteria. A large body of evidence suggests that changes in emotional memory are particularly relevant to depression and to antidepressant drug action whereas changes in attentional processing are sensitive to anxiolytic drugs. These tasks are not consistently affected by agents which have failed in clinical trials in depression, but do show changes in the predicted direction with agents associated either with amelioration or induction of symptoms. Hence, early assessment of novel drugs on emotional processing may predict likely clinical effects and dosing prior to randomized controlled trials. Greater validation is required to assess whether these effects are an obligatory component of effective treatment of depression and whether use of these models can improve the accuracy of go/no-go decisions in drug development. [ABSTRACT FROM PUBLISHER]

Agomelatine is a new antidepressant with a novel profile of pharmacological action. The clinical efficacy of agomelatine has been established in major depression, but its actions on emotional bias are unknown. Consequently, the current experimental study assessed the effect of agomelatine on emotional processing in healthy volunteers using an Emotional Test Battery shown to be sensitive to serotonin and noradrenaline reuptake inhibitors. Volunteers were randomized to receive placebo, 25 mg or 50 mg of agomelatine over a 7-day period in a double-blind parallel groups design. Emotional processing (n = 48) was assessed on the morning of day 8 using the Emotional Test Battery which included facial expression recognition, emotional memory, attentional visual probe and emotion-potentiated startle. Mood and subjective state were monitored before and during treatment. Agomelatine (25 mg) decreased subjective ratings of sadness, reduced recognition of sad facial expressions, improved positive affective memory and reduced the emotion-potentiated startle response. The results show that agomelatine has more selective effects on the processing of social facial cues than conventional antidepressants, which could contribute to less blunting of emotional experience. The study highlights the potential value of volunteer models in drug development for screening and profiling of novel antidepressants. [ABSTRACT FROM PUBLISHER]

The synthesis of serotonin (5-HT) in the central nervous system is dependent on the availability to the brain of its precursor amino acid, tryptophan (TRP). Recent studies suggest that alpha-lactalbumin, a whey-derived protein with a relatively high TRP content, increases plasma TRP and produces endocrine and cognitive changes consistent with facilitation of brain 5-HT function. In the present study we assessed the biochemical and cognitive effects of alpha-lactalbumin (40 g) in 28 healthy female subjects in a parallel group, placebo-controlled design. Relative to a casein-derived control protein, alpha-lactalbumin increased plasma TRP and the ratio of TRP to neutral amino acids. However, there was no effect on salivary cortisol secretion or tasks of emotional processing shown previously to be sensitive to pharmacological manipulation of 5-HT in healthy volunteers. The results suggest that alpha-lactalbumin produces a relatively modest increase in TRP availability which may not be sufficient to produce the changes in emotional processing seen with administration of pure TRP in healthy subjects. Further studies in subjects more vulnerable to stress are needed to assess the potential therapeutic effects of alpha-lactalbumin in clinical populations. [ABSTRACT FROM AUTHOR]