Modulation of atypical brain activation during executive functioning in autism: a pharmacological MRI study of tianeptine
Background: Autism spectrum disorder (ASD) is associated with deficits in executive functioning (EF), and these have been suggested to contribute to core as well as co-occuring psychiatric symptoms. The biological basis of these deficits is unknown but may include the serotonergic system, which is involved in both regulating EF in neurotypical populations and in the pathophysiology of ASD. We previously demonstrated that reducing serotonin by acute tryptophan depletion (ATD) shifts differences in brain function during performance of EF tasks towards control levels. However, ATD cannot be easily used in the clinic, and we therefore need to adopt alternative approaches to challenge the serotonin system. Hence, we investigated the role of the serotonergic modulator tianeptine on EF networks in ASD.
Method: We conducted a pharmacological magnetic resonance imaging (phMRI) study, using a randomised double-blind crossover design, to compare the effect of an acute dosage of 12.5 mg tianeptine and placebo on brain activation during during two EF tasks (of response inhibition and sustained attention) in 38 adult males; 19 with ASD and 19 matched controls.
Results: Under placebo, compared to controls, individuals with ASD had atypical brain activation in response inhibtion regions including the inferior frontal cortex, premotor regions and cerebellum. During sustained attention, individuals with ASD had decreased brain activation in the right middle temporal cortex, right cuneus and left precuneus. Most of the case-control differences in brain function observed under placebo conditions were abolished by tianeptine administration. Also, within ASD individuals, brain functional differences were shifted significantly towards control levels during response inhibition in the inferior frontal and premotor cortices.
Limitations: We conducted a pilot study using a single dose of tianeptine and therefore we cannot comment on long-term outcome.
Conclusions: Our findings provide the first evidence that tianeptine can shift atypical brain activation during EF in adults with ASD towards control levels. Future studies should investigate whether this shift in the biology of ASD is maintained after prolonged treatment with tianeptine, and if it improves clinical symptoms.
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Posted 07 Jan, 2021
Received 29 Dec, 2020
On 29 Dec, 2020
Received 25 Dec, 2020
On 14 Dec, 2020
On 13 Dec, 2020
Invitations sent on 13 Dec, 2020
On 13 Dec, 2020
On 13 Dec, 2020
On 13 Dec, 2020
Received 11 Nov, 2020
On 11 Nov, 2020
On 05 Nov, 2020
Received 20 Oct, 2020
Invitations sent on 05 Oct, 2020
On 05 Oct, 2020
On 28 Aug, 2020
On 27 Aug, 2020
On 24 Aug, 2020
On 18 Aug, 2020
Modulation of atypical brain activation during executive functioning in autism: a pharmacological MRI study of tianeptine
Posted 07 Jan, 2021
Received 29 Dec, 2020
On 29 Dec, 2020
Received 25 Dec, 2020
On 14 Dec, 2020
On 13 Dec, 2020
Invitations sent on 13 Dec, 2020
On 13 Dec, 2020
On 13 Dec, 2020
On 13 Dec, 2020
Received 11 Nov, 2020
On 11 Nov, 2020
On 05 Nov, 2020
Received 20 Oct, 2020
Invitations sent on 05 Oct, 2020
On 05 Oct, 2020
On 28 Aug, 2020
On 27 Aug, 2020
On 24 Aug, 2020
On 18 Aug, 2020
Background: Autism spectrum disorder (ASD) is associated with deficits in executive functioning (EF), and these have been suggested to contribute to core as well as co-occuring psychiatric symptoms. The biological basis of these deficits is unknown but may include the serotonergic system, which is involved in both regulating EF in neurotypical populations and in the pathophysiology of ASD. We previously demonstrated that reducing serotonin by acute tryptophan depletion (ATD) shifts differences in brain function during performance of EF tasks towards control levels. However, ATD cannot be easily used in the clinic, and we therefore need to adopt alternative approaches to challenge the serotonin system. Hence, we investigated the role of the serotonergic modulator tianeptine on EF networks in ASD.
Method: We conducted a pharmacological magnetic resonance imaging (phMRI) study, using a randomised double-blind crossover design, to compare the effect of an acute dosage of 12.5 mg tianeptine and placebo on brain activation during during two EF tasks (of response inhibition and sustained attention) in 38 adult males; 19 with ASD and 19 matched controls.
Results: Under placebo, compared to controls, individuals with ASD had atypical brain activation in response inhibtion regions including the inferior frontal cortex, premotor regions and cerebellum. During sustained attention, individuals with ASD had decreased brain activation in the right middle temporal cortex, right cuneus and left precuneus. Most of the case-control differences in brain function observed under placebo conditions were abolished by tianeptine administration. Also, within ASD individuals, brain functional differences were shifted significantly towards control levels during response inhibition in the inferior frontal and premotor cortices.
Limitations: We conducted a pilot study using a single dose of tianeptine and therefore we cannot comment on long-term outcome.
Conclusions: Our findings provide the first evidence that tianeptine can shift atypical brain activation during EF in adults with ASD towards control levels. Future studies should investigate whether this shift in the biology of ASD is maintained after prolonged treatment with tianeptine, and if it improves clinical symptoms.
Figure 1
Figure 2
Figure 3