Emotional Processing and Antidepressant Action

Abstract

Negative affective schema and associated biases in information processing have long been associated with clinical depression. Such an approach has guided the development of successful psychological therapies for this and other emotional disorders. However, until quite recently, there has been a large chasm between the practitioners and scientists working with this approach and those working on the neurobiological basis of depression and its treatment. Recent research, however, has started to bridge this gap and our understanding of the neural processes underpinning these cognitive processes has progressed markedly over the past decade. Moreover, rather than representing separate targets for psychological and biological treatments, novel findings suggest that pharmacological interventions for depression also modify these psychological maintaining factors early in treatment and may be involved in the later emergence of clinically relevant change. Such findings offer the possibility of greater integration between psychological and pharmacological conceptualisations of psychiatric illness and provide an experimental medicine model to generate and test specific predictions. Such a model could be applied to improve treatment development, stratification and combination approaches for patients with depression and provide a framework for considering and overcoming treatment nonresponse.

Mouse chronic social stress increases blood and brain kynurenine pathway activity and fear behaviour: Both effects are reversed by inhibition of indoleamine 2,3-dioxygenase

“…Repeated escitalopram reversed the increased fear expression, specifically, in CSD mice, indicating that the model has predictive validity. Indeed, in healthy humans and MDD patients, acute and repeated escitalopram reduced amygdala reactivity to fearful facial stimuli (Godlewska et al, 2012;Harmer, 2013). Whilst it was not the aim of the current study to investigate SSRI effects on kynurenines, it is noteworthy that the SSRI sertraline did not affect blood kynurenines in MDD patients (Zhu et al, 2013) and there was no effect of citalopram on CSF kynurenines in rat (Toghi et al, 1995).…”

“…Now the current study provides some of the first evidence for the reversal of behavioural effects of stress-induced IDO1-KYN pathway activation. Given the importance of amygdala and hippocampus in fear conditioning (Duvarci and Pare, 2014;LeDoux, 2000;Maren et al, 2013;Wolff et al, 2014) and stress-related psychiatric disorders (Harmer, 2013;Phelps and LeDoux, 2005;Price and Drevets, 2010; 31 Sheline et al, 2001), it is noteworthy that amygdala and vHIPP, together with other brain regions, exhibited increased levels of kynurenines. In healthy humans, LPS induced increased amygdala reactivity to fearful faces (Inagaki et al, 2012).…”

Facilitation of emotion regulation with a single dose of escitalopram: A randomized fMRI study

“…Nevertheless, the findings of the present study-that treatment facilitates emotion regulation-need to be replicated in clinical samples. While neurophysiological measures of the acute effects of antidepressants hold promise for the prediction of their clinical efficacy (Kemp et al, 2008;Pizzagalli, 2011), the predictive ability of cognitive neuropsychological models of antidepressant action remains to be tested (Harmer, 2012). A number of limitations are also noted.…”

Impact of acute administration of escitalopram on the processing of emotional and neutral images: a randomized crossover fMRI study of healthy women

“…While neurophysiological measures of the acute effects of antidepressants hold promise for the prediction of their clinical efficacy, 5,34 the predictive ability of cognitive neuropsychological models of antidepressant action remains to be tested. 63 …”