Effects of Escitalopram Administration on Face Processing in Intermittent Explosive Disorder: An fMRI Study

Disruptions in the cortico-limbic emotion regulation networks have been linked to depression, anxiety, impulsivity, and aggression. Altered transmission of the central nervous serotonin (5-HT) contributes to dysfunctions in the cognitive control of emotions. To date, studies relating to pharmaco-fMRI challenging of the 5-HT system have focused on emotion processing for facial expressions. We investigated effects of a single-dose selective 5-HT reuptake inhibitor (escitalopram) on emotion regulation during virtual violence. For this purpose, 38 male participants played a violent video game during fMRI scanning. The SSRI reduced neural responses to violent actions in right-hemispheric inferior frontal gyrus and medial prefrontal cortex encompassing the anterior cingulate cortex (ACC), but not to non-violent actions. Within the ACC, the drug effect differentiated areas with high inhibitory 5-HT1A receptor density (subgenual s25) from those with a lower density (pregenual p32, p24). This finding links functional responses during virtual violent actions with 5-HT neurotransmission in emotion regulation networks, underpinning the ecological validity of the 5-HT model in aggressive behavior. Available 5-HT receptor density data suggest that this SSRI effect is only observable when inhibitory and excitatory 5-HT receptors are balanced. The observed early functional changes may impact patient groups receiving SSRI treatment.

HighlightsSelf- and other-reflection in schizophrenia were studied with fMRI.Patients failed to activate the right temporo-parietal junction in other-reflection.They also hyperactivated lateral prefrontal cortex for self and other-reflection.These findings might be linked to altered self/other processing in schizophrenia.

The temporo-parietal junction (TPJ) is implicated in a variety of processes including multisensory integration, social cognition, sense of agency and stimulus-driven attention functions. Furthermore, manipulation of cortical excitation in this region can influence a diverse range of personal and interpersonal perceptions, from those involved in moral decision making to judgments about the location of the self in space. Synthesis of existing studies places the TPJ at the neural interface between mind and matter, where information about both mental and physical states is processed and integrated, contributing to self-other differentiation. After first summarising the functions of the TPJ according to existing literature, this narrative review aims to offer insight into the potential role of TPJ dysfunction in neuropsychiatric disorders, with a focus on the involvement of the right TPJ in controlling representations relating to the self and other. Problems with self-other distinctions may reflect or pose a vulnerability to the symptoms associated with Tourette syndrome, Schizophrenia, Autistic Spectrum Disorder and Obsessive Compulsive Disorder. Further study of this most fascinating neural region will therefore make a substantial contribution to our understanding of neuropsychiatric symptomatology and highlight significant opportunities for therapeutic impact.