Citalopram modulation of neuronal responses to aversive face emotions: a functional MRI study

Anderson, Ian M.; Del-Ben, Cristina Marta; McKie, Shane; Richardson, P. S.; Williams, S. R.; Elliott, Richard M.; Deakin, Bill

doi:10.1097/wnr.0b013e3282742115

Cited by 121 publications

(111 citation statements)

References 21 publications

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“…This concurs with some studies in human subjects that found acute 5-HT manipulations selectively to affect reactions to negative stimuli (Browning et al, 2007;Chamberlain et al, 2006), punishment prediction (Cools et al, 2008b), and the activation of brain areas involved in error detection and processing of aversive events (Anderson et al, 2007;Del-Ben et al, 2005;Evers et al, 2005;McKie et al, 2005).…”

Section: Discussionsupporting

confidence: 73%

Serotonin Modulates Sensitivity to Reward and Negative Feedback in a Probabilistic Reversal Learning Task in Rats

Bari

Theobald

Caprioli

et al. 2010

Neuropsychopharmacol

297

338

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Depressed patients show cognitive deficits that may depend on an abnormal reaction to positive and negative feedback. The precise neurochemical mechanisms responsible for such cognitive abnormalities have not yet been clearly characterized, although serotoninergic dysfunction is frequently associated with depression. In three experiments described here, we investigated the effects of different manipulations of central serotonin (5-hydroxytryptamine, 5-HT) levels in rats performing a probabilistic reversal learning task that measures response to feedback. Increasing or decreasing 5-HT tone differentially affected behavioral indices of cognitive flexibility (reversals completed), reward sensitivity (win-stay), and reaction to negative feedback (lose-shift). A single low dose of the selective serotonin reuptake inhibitor citalopram (1 mg/kg) resulted in fewer reversals completed and increased lose-shift behavior. By contrast, a single higher dose of citalopram (10 mg/kg) exerted the opposite effect on both measures. Repeated (5 mg/kg, daily, 7 days) and subchronic (10 mg/kg, b.i.d., 5 days) administration of citalopram increased the number of reversals completed by the animals and increased the frequency of win-stay behavior, whereas global 5-HT depletion had the opposite effect on both indices. These results show that boosting 5-HT neurotransmission decreases negative feedback sensitivity and increases reward (positive feedback) sensitivity, whereas reducing it has the opposite effect. However, these effects depend on the nature of the manipulation used: acute manipulations of the 5-HT system modulate negative feedback sensitivity, whereas long-lasting treatments specifically affect reward sensitivity. These results parallel some of the findings in humans on effects of 5-HT manipulations and are relevant to hypotheses of altered response to feedback in depression.

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Section: Discussionsupporting

confidence: 73%

Serotonin Modulates Sensitivity to Reward and Negative Feedback in a Probabilistic Reversal Learning Task in Rats

Bari

Theobald

Caprioli

et al. 2010

Neuropsychopharmacol

297

338

View full text Add to dashboard Cite

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“…Contrary to our expectations, here we did not find evidence that citalopram decreases amygdala activation in IED. Moreover, although the results in controls (escitalopram increases amygdala activation) are in line with a prior report (Bigos et al, 2008), some studies did not observe an effect of citalopram on amygdala activity (Brühl et al, 2010;Henry et al, 2013) and several other single-dose and short-term citalopram administration studies found amygdala decreases (Del-Ben et al, 2005;Harmer et al, 2006;Anderson et al, 2007;Arce et al, 2008;Murphy et al, 2009;Windischberger et al, 2010). Although it is possible that our results in controls are perhaps due to sampling error (see Limitations section), several other methodological issues in citalopram administration studies also need to be considered.…”

Section: Discussionsupporting

confidence: 70%

“…Research has mostly shown that, in controls, a single-dose or short-term administration of citalopram reduces amygdala activity (Del-Ben et al, 2005;Harmer et al, 2006;Anderson et al, 2007;Murphy et al, 2009;Windischberger et al, 2010), although increases have also been found (Bigos et al, 2008). We hypothesize that escitalopram will lower amygdala activity in IED.…”

Section: Introductionmentioning

confidence: 98%

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

Cremers

Lee

Keedy

et al. 2015

Neuropsychopharmacol

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The neurobiological underpinnings of intermittent explosive disorder (IED) are traditionally linked to deficiencies in the serotonergic system. In this study, we investigated the effects of escitalopram, a selective serotonin reuptake inhibitor (SSRI), on brain activation during face processing. We expected that escitalopram would reduce amygdala activity in IED and in addition, we explored the effect in other social-emotional-related brain regions. A total of 17 subjects with current IED and 14 healthy controls participated in a randomized, double-blind, placebo-controlled, counterbalanced fMRI face processing study. The analysis focused on the faces compared to a fixation baseline contrast, and a factorial model with Group as between-subject and Drug as within-subject factor was tested. Group × Drug interaction effects were found in the amygdala (small volume corrected) and the left temporal parietal junction (TPJ; whole-brain corrected). Escitalopram increased amygdala activation in controls, but surprisingly not in IED. However, the TPJ showed increased activity in IED on escitalopram compared with placebo. The TPJ is associated with social-cognitive processes, such as perspective taking and empathy. The TPJ findings suggest that SSRI administration may reduce aggressive tendencies towards other people by enhancing these social-cognitive processes. Future research should further elucidate the long-term effects of SSRIs on various social-emotional tasks in IED.

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“…Thalamocortical coupling is altered in depression and antidepressant therapy targets this connection [26][27][28]. HC healthy control subjects, rMD remitted depressed subjects, aMD acute depressed patients fMRI-1 functional magnetic resonance imaging session one, HAM-D 24 Hamilton Depression Rrating Scale (24 item version), HAM-A Hamilton Anxiety Rating Scale, BDI Beck Depression Index, CGI Clinical Global Impression scale, f female, m male, y years, m months, r right, l left a p-value chi-square test b p-value analysis of variance c p-value t-test d for detiailed medication see supplementary Table S5 e only one patient Antidepressant effects on the pulvinar and the thalamus are substantiated in other fMRI tasks [29][30][31]. Moreover, thalamocortical connectivity was altered upon ketamine administration [32] and transracial magnetic stimulation to the dorsolateral prefrontal cortex elevated activity in the pulvinar nuclei [33].…”

Section: Discussionmentioning

confidence: 99%

The pulvinar nucleus and antidepressant treatment: dynamic modeling of antidepressant response and remission with ultra-high field functional MRI

et al. 2018

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Functional magnetic resonance imaging (fMRI) successfully disentangled neuronal pathophysiology of major depression (MD), but only a few fMRI studies have investigated correlates and predictors of remission. Moreover, most studies have used clinical outcome parameters from two time points, which do not optimally depict differential response times. Therefore, we aimed to detect neuronal correlates of response and remission in an antidepressant treatment study with 7 T fMRI, potentially harnessing advances in detection power and spatial specificity. Moreover, we modeled outcome parameters from multiple study visits during a 12-week antidepressant fMRI study in 26 acute (aMD) patients compared to 36 stable remitted (rMD) patients and 33 healthy control subjects (HC). During an electrical painful stimulation task, significantly higher baseline activity in aMD compared to HC and rMD in the medial thalamic nuclei of the pulvinar was detected (p = 0.004, FWE-corrected), which was reduced by treatment. Moreover, clinical response followed a sigmoid function with a plateau phase in the beginning, a rapid decline and a further plateau at treatment end. By modeling the dynamic speed of response with fMRI-data, perigenual anterior cingulate activity after treatment was significantly associated with antidepressant response (p < 0.001, FWE-corrected). Temporoparietal junction (TPJ) baseline activity significantly predicted non-remission after 2 antidepressant trials (p = 0.005, FWE-corrected). The results underline the importance of the medial thalamus, attention networks in MD and antidepressant treatment. Moreover, by using a sigmoid model, this study provides a novel method to analyze the dynamic nature of response and remission for future trials.

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Citalopram modulation of neuronal responses to aversive face emotions: a functional MRI study

Cited by 121 publications

References 21 publications

Serotonin Modulates Sensitivity to Reward and Negative Feedback in a Probabilistic Reversal Learning Task in Rats

Serotonin Modulates Sensitivity to Reward and Negative Feedback in a Probabilistic Reversal Learning Task in Rats

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

The pulvinar nucleus and antidepressant treatment: dynamic modeling of antidepressant response and remission with ultra-high field functional MRI

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