Search

Background: Growing evidence from clinical trials and epidemiological studies suggests that statins can have clinically significant antidepressant effects, potentially related to anti-inflammatory action on several neurobiological structures. However, the underlying neuropsychological mechanisms of these effects remain unexplored. Aims: In this experimental medicine trial, we investigated the 7-day effects of the lipophilic statin, atorvastatin on a battery of neuropsychological tests and inflammation in healthy volunteers. Methods: Fifty healthy volunteers were randomised to either 7 days of atorvastatin 20 mg or placebo in a double-blind design. Participants were assessed with psychological questionnaires and a battery of well-validated behavioural tasks assessing emotional processing, which is sensitive to putative antidepressant effects, reward learning and verbal memory, as well as the inflammatory marker, C-reactive protein. Results: Compared to placebo, 7-day atorvastatin increased the recognition (p = 0.006), discriminability (p = 0.03) and misclassifications (p = 0.04) of fearful facial expression, independently from subjective states of mood and anxiety, and C-reactive protein levels. Otherwise, atorvastatin did not significantly affect any other psychological and behavioural measure, nor peripheral C-reactive protein. Conclusions: Our results reveal for the first time the early influence of atorvastatin on emotional cognition by increasing the processing of anxiety-related stimuli (i.e. increased recognition, discriminability and misclassifications of fearful facial expression) in healthy volunteers, in the absence of more general effects on negative affective bias. Further studies exploring the effects of statins in depressed patients, especially with raised inflammatory markers, may clarify this finding and inform future clinical trials. [ABSTRACT FROM AUTHOR]

Controversy continues with regard to antidepressants and withdrawal. Recent debates have focused on the prevalence and length of withdrawal, and some continue to state that withdrawal from these compounds constitutes 'addiction'. In this editorial we examine the evidence underlying these recent debates. We acknowledge gaps in knowledge, and make suggestions for how the field can progress. [ABSTRACT FROM AUTHOR]

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]

The antidepressant, agomelatine, has a novel pharmacological profile, with agonist properties at M1 and M2 receptors and antagonist properties at 5HT2C receptors. Whether the antidepressant effects of this treatment are mediated by the drug's effects at the M1 and M2 receptors or the 5HT2C receptor or a synergy between these actions remains unclear. In the present study, a healthy volunteer model of emotional processing, which discriminates between effective and non-effective antidepressant compounds, was used to assess the contribution of melatonin agonism to the efficacy of agomelatine. Fifty-eight healthy volunteers were randomised to receive 7 days of once daily treatment with either 1 mg melatonin, 3 mg melatonin or placebo. Seven days treatment with 3 mg melatonin resulted in earlier bedtimes consistent with a phase advance in circadian rhythm. Some marginal effects of melatonin were observed on emotional processing; however, these were neither consistent with nor comparable to those seen following conventional antidepressant treatment or with agomelatine itself. These data suggest that the antidepressant action of agomelatine cannot be accounted for solely by its action at the M1 and M2 receptors. [ABSTRACT FROM AUTHOR]