Modulation of atypical brain activation during executive functioning in autism: a pharmacological MRI study of tianeptine

Molecular Autism

Vladimira Stoencheva¹  Katya Rubia²  Christine Ecker³  Eileen M. Daly⁴  Sarah Blainey⁴  James L. Findon⁴  Dene M. Robertson⁵  Declan G. M. Murphy⁵  Robert H. Wichers⁵  Grainne McAlonan⁵  Clodagh M. Murphy⁵  Auke Jelsma⁶  Vincent Giampietro⁷ 

[1] Behavioural and Developmental Psychiatry Clinical Academic Group, South London and Maudsley NHS Trust, London, UK;Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK;Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt am Main, Goethe-University, Frankfurt am Main, Germany;Department of Forensic and Neurodevelopmental Sciences, The Sackler Centre for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, PO50 De Crespigny Park, Denmark Hill, SE5 8AF, London, UK;Department of Forensic and Neurodevelopmental Sciences, The Sackler Centre for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, PO50 De Crespigny Park, Denmark Hill, SE5 8AF, London, UK;Behavioural and Developmental Psychiatry Clinical Academic Group, South London and Maudsley NHS Trust, London, UK;Department of Forensic and Neurodevelopmental Sciences, The Sackler Centre for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, PO50 De Crespigny Park, Denmark Hill, SE5 8AF, London, UK;VU University Medical Center, Amsterdam, The Netherlands;Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK;

关键词: Autism spectrum disorder;    Executive functioning;    Tianeptine;    Serotonin;    fMRI;   

DOI  :  10.1186/s13229-021-00422-0

来源: Springer

【 摘 要 】

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-occurring psychiatric symptoms. The biological basis of these deficits is unknown but may include the serotonergic system, which is involved both in 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.MethodWe conducted a pharmacological magnetic resonance imaging study, using a randomized double-blind crossover design, to compare the effect of an acute dosage of 12.5 mg tianeptine and placebo on brain activation 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 inhibition 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.LimitationsWe conducted a pilot study using a single dose of tianeptine, and therefore, we cannot comment on long-term outcome.ConclusionsOur 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 whether it improves clinical symptoms.

【 授权许可】

CC BY