Abstract
This selective review aims to summarize the recent advances in understanding the neuromolecular underpinnings of biased cognition in depressive disorder. We begin by considering the cognitive correlates of depressed mood and the key brain systems implicated in its development. We then review the core findings across two domains of biased cognitive function in depression: pessimistic judgment bias and abnormal response to negative feedback. In considering their underlying substrates, we focus on the neurochemical mechanisms identified by genetic, molecular and pharmacological challenge studies. We conclude by discussing experimental approaches to the treatment of depression, which are derived largely from an improved understanding of its cognitive substrates.
Highlights
Depression is the leading cause of disability in the 21st century, affecting an estimated 350 million people worldwide [1]
Thanks to the introduction of the ambiguouscue interpretation (ACI) paradigm [33,34], a test allowing for measurement of cognitive judgment bias in animals, Rygula and colleagues demonstrated in 2014 that acute administration of the dopaminergic booster d-amphetamine produces optimism in rats [35]
Because similar effects were observed following treatment with a serotonergic compound, the selective serotonin reuptake inhibitor (SSRI) escitalopram [38], it has been suggested that the effects of acute dopaminergic and serotonergic manipulations on pessimistic/optimistic interpretation of ambiguous cues may, at least in animals, depend on the basal valence of cognitive judgment bias [38]
Summary
Depression is the leading cause of disability in the 21st century, affecting an estimated 350 million people worldwide [1]. The insula has been suggested to be involved in the evaluation of negative outcomes and in the processing of changes in previously learned actions [16], while the anterior and posterior cingulate cortices are involved in post-feedback performance adjustments [17]. This selective minireview aims to summarize recent advances in understanding the neuromolecular underpinnings of biased cognition in depressive disorder. We begin by reviewing the core findings across two domains of biased cognitive function in depression: pessimistic judgment bias and abnormal response to negative feedback In considering their underlying substrates, we focus on the neurochemical mechanisms identified by genetic, molecular and pharmacological challenge studies. We conclude by discussing potential experimental approaches to the treatment of depression, which are derived largely from an improved understanding of its cognitive substrates
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