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Original Article |

Serotonin and the Neural Processing of Facial Emotions in Adults With Autism:  An fMRI Study Using Acute Tryptophan Depletion

Eileen M. Daly, BA; Quinton Deeley, PhD; Christine Ecker, MSc, PhD; Michael Craig, PhD; Brian Hallahan, MRCPsych; Clodagh Murphy, MRCPsych; Patrick Johnston, PhD; Debbie Spain, MSc; Nicola Gillan, MSc; Michael Brammer, PhD; Vincent Giampietro, PhD; Melissa Lamar, PhD; Lisa Page, MRCPsych; Fiona Toal, MRCPsych; Anthony Cleare, PhD; Simon Surguladze, MD, PhD; Declan G. M. Murphy, FRCPsych
Arch Gen Psychiatry. 2012;69(10):1003-1013. doi:10.1001/archgenpsychiatry.2012.513.
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Context  People with autism spectrum disorders (ASDs) have lifelong deficits in social behavior and differences in behavioral as well as neural responses to facial expressions of emotion. The biological basis to this is incompletely understood, but it may include differences in the role of neurotransmitters such as serotonin, which modulate facial emotion processing in health. While some individuals with ASD have significant differences in the serotonin system, to our knowledge, no one has investigated its role during facial emotion processing in adults with ASD and control subjects using acute tryptophan depletion (ATD) and functional magnetic resonance imaging.

Objective  To compare the effects of ATD on brain responses to primary facial expressions of emotion in men with ASD and healthy control subjects.

Design  Double-blind, placebo-controlled, crossover trial of ATD and functional magnetic resonance imaging to measure brain activity during incidental processing of disgust, fearful, happy, and sad facial expressions.

Setting  Institute of Psychiatry, King's College London, and South London and Maudsley National Health Service Foundation Trust, England.

Participants  Fourteen men of normal intelligence with autism and 14 control subjects who did not significantly differ in sex, age, or overall intelligence.

Main Outcome Measures  Blood oxygenation level–dependent response to facial expressions of emotion.

Results  Brain activation was differentially modulated by ATD depending on diagnostic group and emotion type within regions of the social brain network. For example, processing of disgust faces was associated with interactions in medial frontal and lingual gyri, whereas processing of happy faces was associated with interactions in middle frontal gyrus and putamen.

Conclusions  Modulation of the processing of facial expressions of emotion by serotonin significantly differs in people with ASD compared with control subjects. The differences vary with emotion type and occur in social brain regions that have been shown to be associated with group differences in serotonin synthesis/receptor or transporter density.

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Figures

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Figure 1. Disgust facial expression experiment. A, Maps of interaction of serotonin status (placebo vs acute tryptophan depletion [ATD]) by group (control vs autism spectrum disorder [ASD]) from the disgust experiment. B, Plot of mean blood oxygenation level–dependent signal (sum of squares [SSQ]) extracted from each disgust interaction cluster: (1) Left medial frontal gyrus Brodman area 11; (2) Left medial frontal gyrus Brodman area 6; and (3) Left lingual gyrus. Error bars = 95% confidence intervals. Right side of figure is left side of brain.

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Figure 2. Happy facial expression experiment. A, Map of interaction of serotonin status (placebo vs acute tryptophan depletion [ATD]) and group (control vs autism spectrum disorder [ASD]) from the happy experiment. B, Plot of mean blood oxygenation level–dependent signal (sum of squares [SSQ]) extracted from the happy interaction cluster: left medial frontal gyrus Brodman area 9. Error bars = 95% confidence intervals. Right side of figure is left side of the brain.

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Figure 3. Sad facial expression experiment. A, Maps of interaction of serotonin status (placebo vs acute tryptophan depletion [ATD]) and group (control vs autism spectrum disorder [ASD]) from the sad experiment. B, Plot of mean blood oxygenation level–dependent signal (sum of squares [SSQ]) extracted from each sad interaction cluster: (1) Right middle frontal gyrus Brodman area 8 and (2) Right putamen. Error bars = 95% confidence intervals. Right side of figure is left side of the brain.

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Figure 4. Fear facial expression experiment. A, Maps of main effect group (control vs autism spectrum disorder [ASD]) analysis of variance from the fear experiment. B, Plot of mean blood oxygenation level–dependent signal (sum of squares [SSQ]) extracted from the fear main effect of group cluster: left lingual gyrus Brodman area 18. Error bars = 95% confidence intervals. Right side of figure is left side of the brain.

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