The Effect of Citalopram Pretreatment on Neuronal Responses to Neuropsychological Tasks in Normal Volunteers: An fMRI Study

Abstract

Changes in serotonin neurotransmission have also been implicated in the etiology and treatment of impulse control disorders, depression, and anxiety. We have investigated the effect of enhancing serotonin function on fundamental brain processes that we have proposed are abnormal in these disorders. In all, 12 male volunteers received citalopram (7.5 mg intravenously) and placebo pretreatment in a single-blind crossover design before undertaking Go/No-go, Loss/No-loss, and covert (aversive) face emotion recognition tasks during functional magnetic resonance imaging (fMRI). Blood oxygenation level dependent responses were analyzed using Statistical Parametric Mapping (SPM2). The tasks activated prefrontal and subcortical regions generally consistent with literature with lateral orbitofrontal cortex (BA47) common to the three tasks. Citalopram pretreatment enhanced the right BA47 responses to the No-go condition, but attenuated this response to aversive faces. Attenuations were seen following citalopram in the medial orbitofrontal (BA11) responses to the No-go and No-loss (ie relative reward compared with Loss) conditions. The right amygdala response to aversive faces was attenuated by citalopram. These results support the involvement of serotonin in modulating basic processes involved in psychiatric disorders but argue for a process-specific, rather than general effect. The technique of combining drug challenge with fMRI (pharmacoMRI) has promise for investigating human psychiatric disorders.

Effects of Acute Tryptophan Depletion on Mood and Facial Emotion Perception Related Brain Activation and Performance in Healthy Women with and without a Family History of Depression

“…This finding was explained in terms of a stronger sensitivity of brain areas involved in the processing of fear stimuli in individuals with a high BIS score, which is possibly mediated by the 5-HT system. The finding that especially the amygdala is responsive to serotonergic manipulations is in line with a number of previous studies reporting modified amygdala responses as a result of 5-HT manipulations (eg Sheline et al, 2001;Fu et al, 2004;Del-Ben et al, 2005).…”

“…ATD generally increased right amygdala activation in the contrast comparing all stimulus events of the TRPÀ condition with all stimulus events in the TRP + condition. The effects of ATD on amygdala activation are in line with findings of several other studies reporting sensitivity of the amygdala to serotonergic manipulations (eg Sheline et al, 2001;Fu et al, 2004;Del-Ben et al, 2005). These findings are also in line with studies reporting an enhanced amygdala response to fearful stimuli in carriers of the short allele variant of a polymorphism in the promoter region of the 5-HT transporter gene (eg Hariri et al, 2002), who are characterized by a lowered 5-HT metabolism.…”

Acute Serotonin and Dopamine Depletion Improves Attentional Control: Findings from the Stroop Task

“…A relationship between serotonin and attentional control is also supported by studies in rats using the 5 choice serial reaction time task (5-CSRTT) in which enhanced premature responses (a measure of failure of behavioral inhibition) have been noted under conditions of increased serotonin neurotransmission (Dalley et al, 2002;Koskinen et al, 2003;Koskinen and Sirvio, 2001), particularly in the infralimbic/prelimbic regions of the medial prefrontal cortex (Dalley et al, 2002). Similarly, it has been found that increased serotonergic function can increase premature responses in a behavioral inhibition task in healthy humans (Del-Ben et al, 2005). Together these findings suggest that the serotonergic system within specific areas of the cortex may play an important role in attentional control, with reduced serotonergic transmission associated with greater attentional control or behavioral inhibition.…”

Does neuroimaging research examining the pathophysiology of posttraumatic stress disorder require medication-free patients?

“…In contrast, citalopram attenuated right BA 47 responses but attenuated right amygdala response to aversive faces. 29 Recently, this finding has been replicated in a randomized, placebo-controlled study. 30 Healthy volunteers were given either a single oral dose of citalopram (20 mg) or placebo.…”