2013
DOI: 10.1098/rstb.2012.0192
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Identifying serotonergic mechanisms underlying the corticolimbic response to threat in humans

Abstract: A corticolimbic circuit including the amygdala and medial prefrontal cortex (mPFC) plays an important role in regulating sensitivity to threat, which is heightened in mood and anxiety disorders. Serotonin is a potent neuromodulator of this circuit; however, specific serotonergic mechanisms mediating these effects are not fully understood. Recent studies have evaluated molecular mechanisms mediating the effects of serotonin signalling on corticolimbic circuit function using a multi-modal neuroimaging strategy i… Show more

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Cited by 31 publications
(16 citation statements)
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“…As is the case with dopamine, understanding the role of serotonin in cognitive flexibility requires consideration of multiple kinds of cognitive flexibility, as well as interactions between striatal habit learning systems and frontal systems for goal-directed action selection (Gillan et al, 2011). For example, the fact that serotonin depletion appears to increase sensitive to both negative feedback (Evers et al, 2005) and threats (Hariri and Holmes, 2006, Fisher and Hariri, 2013) could have the effect of either increasing impulsive shifting in the face of misleading punishments (Harrison et al, 1997, Chamberlain et al, 2006) or indirectly driving compulsive behavior by increasing anxiety (Deakin, 1998, Stein and Stahl, 2000, Maron et al, 2012) and/or interacting with other neuromodulatory pathways, such as dopamine systems (Perani et al, 2008). By contrast, SSRIs may reduce compulsivity by reducing threat sensitivity (Fisher and Hariri, 2013, Williams et al, 2015) and/or stress-related dopamine release (Vaessen et al, 2015).…”
Section: Reversal Learning As a Paradigm Case – Difference Neural mentioning
confidence: 99%
“…As is the case with dopamine, understanding the role of serotonin in cognitive flexibility requires consideration of multiple kinds of cognitive flexibility, as well as interactions between striatal habit learning systems and frontal systems for goal-directed action selection (Gillan et al, 2011). For example, the fact that serotonin depletion appears to increase sensitive to both negative feedback (Evers et al, 2005) and threats (Hariri and Holmes, 2006, Fisher and Hariri, 2013) could have the effect of either increasing impulsive shifting in the face of misleading punishments (Harrison et al, 1997, Chamberlain et al, 2006) or indirectly driving compulsive behavior by increasing anxiety (Deakin, 1998, Stein and Stahl, 2000, Maron et al, 2012) and/or interacting with other neuromodulatory pathways, such as dopamine systems (Perani et al, 2008). By contrast, SSRIs may reduce compulsivity by reducing threat sensitivity (Fisher and Hariri, 2013, Williams et al, 2015) and/or stress-related dopamine release (Vaessen et al, 2015).…”
Section: Reversal Learning As a Paradigm Case – Difference Neural mentioning
confidence: 99%
“…Studies in post-mortem tissues from depressed subjects indicate a reduction in cortical grey matter, and reduced glial cellularity are observed in prefrontal cortex and hippocampus of depressed subjects [14]. Fisher & Hariri [15] have focused on amygdala reactivity to fearful or threatening faces or images, as detected by multi-modal PET and blood-oxygen-leveldependent (BOLD)-fMRI. Increased 5-HT1A autoreceptor levels inversely correlated with amygdala reactivity to threat, consistent with increase in 5-HT autoinhibition reducing fear responsiveness.…”
Section: Neuroimaging In Depressionmentioning
confidence: 99%
“…6873 Variants of genes that control 5-HT synaptic availability, such as the serotonin transporter (5-HTT) 7476 and the 5-HT synthesizing enzyme tryptophan hydroxylase (TPH) 77, 78 have also been associated with alterations in socioemotional behaviors, such as differential sensitivity to the rewarding properties of social cues or reactivity to unfairness. 79 Differential corticolimbic responses to these cues have also been reported in carriers of these polymorphisms. 7678 The effect of 5-HT on social behavior is likely to be mediated in part by its effects on neurons from the frontal cortex, as this area is one of the most enriched in serotonergic axons and 5-HT receptors.…”
Section: Serotonin Influences On Social Behaviorsmentioning
confidence: 98%