BackgroundAutism 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) ‘normalizes’ differences in brain function during performance of EF tasks. 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. MethodWe conducted a pharmacological magnetic resonance imaging (phMRI) study 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. ResultsUnder placebo, compared to controls, individuals with ASD had atypical brain activation in response inhibtion regions including inferior frontal cortex, premotor regions and cerebellum. During sustained attention, individuals with ASD had decreased brain activation in 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 ‘normalized’ during response inhibition in inferior frontal and premotor cortices.LimitationsOur sample only consisted of high functioning male adults. Therefore, our findings may not be generalizable to other autistic subgroups (e.g. children or women). ConclusionsOur findings provide the first evidence that tianeptine can ‘normalize’ atypical brain activation during EF in adults with ASD. 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.
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.
On 17 January 1526 the Zurich reformer Ulrich Zwingli wrote a letter to the medical doctor Johannes Vadianus, congratulating him on his recent appointment as mayor of the Swiss city of St Gallen. He also asked him for more detailed information concerning the terrible events which were reputed to have taken place in the vicinity of St Gallen, especially in nearby Appenzell. The Anabaptists in that area were reported to have intercourse with each other’s women, with the approval of the women themselves. A woman of previously unimpeachable conduct was said to have taken to the streets naked, offering herself to all she met, with the words, ‘I have died in the flesh and live only in the spirit; everyone may now use me as he wishes’. And this was said to be but a sample of the incidents which demonstrated how severely the Anabaptists were guilty of misconduct.
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