Abstract
Adults with autism spectrum disorder (ASD) are frequently prescribed selective serotonin reuptake inhibitors (SSRIs). However, there is limited evidence to support this practice. Therefore, it is crucial to understand the impact of SSRIs on brain function abnormalities in ASD. It has been suggested that some core symptoms in ASD are underpinned by deficits in executive functioning (EF). Hence, we investigated the role of the SSRI citalopram on EF networks in 19 right-handed adult males with ASD and 19 controls who did not differ in gender, age, IQ or handedness. We performed pharmacological functional magnetic resonance imaging to compare brain activity during two EF tasks (of response inhibition and sustained attention) after an acute dose of 20 mg citalopram or placebo using a randomised, double-blind, crossover design. Under placebo condition, individuals with ASD had abnormal brain activation in response inhibition regions, including inferior frontal, precentral and postcentral cortices and cerebellum. During sustained attention, individuals with ASD had abnormal brain activation in middle temporal cortex and (pre)cuneus. After citalopram administration, abnormal brain activation in inferior frontal cortex was ‘normalised’ and most of the other brain functional differences were ‘abolished’. Also, within ASD, the degree of responsivity in inferior frontal and postcentral cortices to SSRI challenge was related to plasma serotonin levels. These findings suggest that citalopram can ‘normalise’ atypical brain activation during EF in ASD. Future trials should investigate whether this shift in the biology of ASD is maintained after prolonged citalopram treatment, and if peripheral measures of serotonin predict treatment response.
Highlights
Autism spectrum disorder (ASD) is a neurodevelopmental condition that is characterised by social communication deficits and repetitive or stereotypical behaviours[1]
No correlations between functional activations and PRP 5-HT levels or symptoms were observed in the typically developed (TD) group. To our knowledge, this is the first functional Magnetic Resonance Imaging (fMRI) study to examine the effect of citalopram on brain activation during executive functioning (EF) in adults with ASD
We observed abnormal brain activation in adults with ASD compared to controls during successful inhibitory control in left inferior frontal, right precentral and postcentral cortices, and right cerebellum
Summary
Autism spectrum disorder (ASD) is a neurodevelopmental condition that is characterised by social communication deficits and repetitive or stereotypical behaviours[1]. Antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), are prescribed in 6% of people. Wichers et al Translational Psychiatry (2019)9:286 indicates that clinical trials are needed to further investigate the effectiveness of SSRIs in adults with ASD, especially as there are currently no pharmacological treatments approved by the Food & Drug Administration (FDA) for treating core symptoms. It is crucial that we first provide ‘proof of concept’ that potential treatments (e.g. SSRIs) can impact on abnormalities in brain functions associated with core symptoms. It has been proposed that core symptoms are partially underpinned by deficits in executive functioning (EF) in ASD12,13. EF networks may provide novel treatment targets and/or an early ‘read out’ of potential efficacy
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