'It's the way that you look at it'--a cognitive neuropsychological account of SSRI action in depression - PubMed (original) (raw)

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'It's the way that you look at it'--a cognitive neuropsychological account of SSRI action in depression

Catherine J Harmer et al. Philos Trans R Soc Lond B Biol Sci. 2013.

Abstract

The fact that selective serotonin reuptake inhibitors (SSRIs) have antidepressant effects in some patients supports the notion that serotonin plays a role in the mode of action of antidepressant drugs. However, neither the way in which serotonin may alleviate depressed mood nor the reason why several weeks needs to elapse before the full antidepressant effect of treatment is expressed is known. Here, we propose a neuropsychological theory of SSRI antidepressant action based on the ability of SSRIs to produce positive biases in the processing of emotional information. Both behavioural and neuroimaging studies show that SSRI administration produces positive biases in attention, appraisal and memory from the earliest stages of treatment, well before the time that clinical improvement in mood becomes apparent. We suggest that the delay in the clinical effect of SSRIs can be explained by the time needed for this positive bias in implicit emotional processing to become apparent at a subjective, conscious level. This process is likely to involve the re-learning of emotional associations in a new, more positive emotional environment. This suggests intriguing links between the effect of SSRIs to promote synaptic plasticity and neurogenesis, and their ability to remediate negative emotional biases in depressed patients.

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Figures

Figure 1.

Figure 1.

Effect of acute citalopram (20 mg orally) on amygdala response to emotional faces. Increased right amygdala activation in the placebo group associated with the contrast between unmasked fear and unmasked neutral faces and plot of mean percentage blood oxygen level-dependent (BOLD) signal change in this right amygdala cluster after acute oral treatment with citalopram and placebo. Image is thresholded at Z = 2.3, p = 0.05, corrected. Bars show the mean; error bars show the s.e.m. Asterisks represent significant level of difference from placebo (**p < 0.01). Adapted from Murphy et al. [30] with permission.

Figure 2.

Figure 2.

Effect of acute mirtazapine administration (15 mg orally) on amygdala response to emotional faces. (a) Axial, coronal and sagittal images depicting significantly increased activation in placebos for the contrast fear versus happy facial expressions (images thresholded at Z = 2.0, p = 0.05, corrected) in the right temporal cortex, extending to hippocampus and amygdala (peak voxel 28, −18, −18). (b) BOLD percent signal change extracted from the significant cluster in the right temporal cortex to fear and happy faces. Error bars show s.e.m. **p < 0.01. Adapted from Rawlings et al. [32] with permission.

Figure 3.

Figure 3.

(a) Effect of 7 days of treatment with citalopram (20 mg daily) on the medial temporal lobe response to fearful facial expressions. Mixed effects whole-brain analysis, FMRIB Software Library (Oxford); clusters determined by Z > 2.3 and (corrected) cluster significance threshold of p < 0.01. (b) Extracted signal change from amygdala regions of interest showing decreased response to fear in both right and left sides in participants taking citalopram. Adapted from Harmer et al. [37] with permission.

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