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Author: Zhenxiang Zang (3)


The serotonin transporter-linked polymorphic region 5-HTTLPR is a key genetic regulator of 5-HTT expression in the human brain where the short allele S has been implicated in emotion dysregulation. However, the neural mechanism underlying the association between this variant and emotion processing is still unclear. Earlier studies suggested an effect of 5-HTTLPR on amygdala activation during emotional face processing.

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Convergent evidence implicates regional neural responses to reward anticipation in the pathogenesis of several psychiatric disorders, such as schizophrenia, where blunted ventral striatal responses to positive reward are observed in patients and at-risk populations. In vivo oxygen amperometry measurements in the ventral striatum in awake, behaving rats reveal reward-related tissue oxygen changes that closely parallel blood oxygen level dependent (BOLD) signal changes observed in human functional magnetic resonance imaging (fMRI), suggesting that a cross-species approach targeting this mechanism might be feasible in psychopharmacology. The present study explored modulatory effects of acute, subanaesthetic doses of ketamine-a pharmacological model widely used in psychopharmacological research, both preclinically and clinically-on ventral striatum activity during performance of a reward anticipation task in both species, using fMRI in humans and in vivo oxygen amperometry in rats.

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Aberrant prefrontal-hippocampal (PFC-HC) connectivity is disrupted in several psychiatric and at-risk conditions. Advances in rodent functional imaging have opened the possibility that this phenotype could serve as a translational imaging marker for psychiatric research. Recent evidence from functional magnetic resonance imaging (fMRI) studies has indicated an increase in PFC-HC coupling during working-memory tasks in both schizophrenic patients and at-risk populations, in contrast to a decrease in resting-state PFC-HC connectivity.

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