A Pharmacological MRI Study of Response Inhibition in Autism Spectrum Disorder Using Tianeptine

Background:  

Hyperserotonaemia is frequently reported in autism spectrum disorder (ASD). However, current drug treatments with selective serotonin reuptake inhibitors (SSRI's) further increase brain serotonin, and it is controversial whether they are effective. We recently demonstrated that an alternative approach – reducing brain serotonin using tryptophan depletion (ATD) - ‘normalizes’ fronto-cerebellar dysfunctions in ASD during tasks of inhibitory control that were associated with restricted, stereotyped and repetitive behaviours (Daly et al. 2014).  Hence, repurposing existing drugs that reduce brain serotonin may offer a new therapeutic opportunity that can be rapidly translated to the clinic. 

Objectives:  

This study aimed to test the effect of the selective serotonin reuptake enhancer (SSRE) tianeptine, on inhibitory control networks in ASD.  

Methods:  

We included 10 right-handed adult males with ASD and 10 age- and IQ- matched controls.  Pharmacological magnetic resonance imaging (phMRI) was used to compare brain activity during a Go/No-Go task under an acute dosage of 12.5 mg tianeptine and placebo in a randomised, double blind procedure. The fMRI data were analysed using a nonparametric approach to minimize assumptions (c.f. http://brainmap.it) and significance was defined as p <.05 corrected for multiple comparisons.

Results:  

Following tianeptine dosage, adults with ASD showed a significant increase in activation compared to placebo in key inhibitory regions including left medial prefrontal gyrus, right cerebellum and right cuneus.

Conclusions:  

We report proof of concept that tianeptine modulates abnormal brain activation during response inhibition in ASD.  Further work is required to determine if it can be repurposed to reduce repetitive behaviours.