[article]
| Titre : |
Modulation of atypical brain activation during executive functioning in autism: a pharmacological MRI study of tianeptine |
| Type de document : |
Texte imprimé et/ou numérique |
| Auteurs : |
R. H. WICHERS, Auteur ; J. L. FINDON, Auteur ; A. JELSMA, Auteur ; V. GIAMPIETRO, Auteur ; V. STOENCHEVA, Auteur ; D. M. ROBERTSON, Auteur ; C. M. MURPHY, Auteur ; S. BLAINEY, Auteur ; G. MCALONAN, Auteur ; C. ECKER, Auteur ; K. RUBIA, Auteur ; D. G. M. MURPHY, Auteur ; Eileen DALY, Auteur |
| Article en page(s) : |
14 p. |
| Langues : |
Anglais (eng) |
| Mots-clés : |
Adult Antidepressive Agents, Tricyclic/therapeutic use Attention/drug effects Autistic Disorder/diagnostic imaging/drug therapy/physiopathology/psychology Brain/diagnostic imaging/physiopathology Cross-Over Studies Double-Blind Method Executive Function/drug effects Humans Magnetic Resonance Imaging Male Middle Aged Pilot Projects Thiazepines/therapeutic use Young Adult Autism spectrum disorder Executive functioning Serotonin Tianeptine fMRI grants from Lilly and Shire. The other authors declare that they have no competing interests. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
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-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. METHOD: We 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. RESULTS: Under 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. 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 whether it improves clinical symptoms. |
| En ligne : |
http://dx.doi.org/10.1186/s13229-021-00422-0 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 |
in Molecular Autism > 12 (2021) . - 14 p.
[article] Modulation of atypical brain activation during executive functioning in autism: a pharmacological MRI study of tianeptine [Texte imprimé et/ou numérique] / R. H. WICHERS, Auteur ; J. L. FINDON, Auteur ; A. JELSMA, Auteur ; V. GIAMPIETRO, Auteur ; V. STOENCHEVA, Auteur ; D. M. ROBERTSON, Auteur ; C. M. MURPHY, Auteur ; S. BLAINEY, Auteur ; G. MCALONAN, Auteur ; C. ECKER, Auteur ; K. RUBIA, Auteur ; D. G. M. MURPHY, Auteur ; Eileen DALY, Auteur . - 14 p. Langues : Anglais ( eng) in Molecular Autism > 12 (2021) . - 14 p.
| Mots-clés : |
Adult Antidepressive Agents, Tricyclic/therapeutic use Attention/drug effects Autistic Disorder/diagnostic imaging/drug therapy/physiopathology/psychology Brain/diagnostic imaging/physiopathology Cross-Over Studies Double-Blind Method Executive Function/drug effects Humans Magnetic Resonance Imaging Male Middle Aged Pilot Projects Thiazepines/therapeutic use Young Adult Autism spectrum disorder Executive functioning Serotonin Tianeptine fMRI grants from Lilly and Shire. The other authors declare that they have no competing interests. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
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-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. METHOD: We 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. RESULTS: Under 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. 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 whether it improves clinical symptoms. |
| En ligne : |
http://dx.doi.org/10.1186/s13229-021-00422-0 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 |
|
Modulation of atypical brain activation during executive functioning in autism: a pharmacological MRI study of tianeptine in Molecular Autism, 12 (2021)
