Autism Spectrum Disorder
Conditions
Keywords
citalopram, tianeptine, pharmacological imaging
Brief summary
This study investigates brain response to single acute dose of citalopram, tianeptine, and placebo in males with and without autism spectrum disorder.
Detailed description
There is increasing evidence that the serotonin (5-HT) system is implicated in autism spectrum disorder (ASD), with the standard treatment for depression and anxiety in both the general population and ASD includes targeting the 5-HT system with selective serotonin reuptake inhibitors (SSRIs) citalopram. Some individuals with ASD have a good treatment response but others do not. Tianeptine, which has a different mechanism of action to SSRIs, is also an effective antidepressant. As it is unlikely that all individuals with ASD will respond to the same treatment, the investigators aim to conduct a pharmacological magnetic resonance imaging (phMRI) investigation to elucidate the neural mechanisms underlying the response to citalopram and tianeptine in ASD. The investigators are inviting 50 male adults with ASD and 50 male adults without ASD. Each participant receives each drug once (20 mg citalopram, 12.5 mg tianeptine, or placebo) and MRI is used to obtain measures of brain biochemistry, activity, and connectivity. The investigators also acquire data from questionnaires, electroencephalography, neurocognitive tests and blood samples.
Interventions
DRUGPlacebo
Two oral doses of placebo.
DRUGCitalopram
Single oral dose of citalopram (20mg) and single oral dose of placebo.
DRUGTianeptine
Single oral dose of tianeptine (12.5mg) and single oral dose of placebo.
Sponsors
King's College London
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Participants and investigators are blinded to the drug condition.
Intervention model description
Repeated-measures cross-over study, where each subject receives each of three pharmacological probes once (order of drug administration was pseudorandomised).
Eligibility
Sex/Gender
MALE
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Intelligence Quotient (IQ) above 70 * Has capacity and is capable of giving written informed consent * Able to read, comprehend and record information written in English * Bodyweight of \<120 kg and BMI within the range 18.5 - 33 kg/m2 (inclusive). * Not taking medication directly affecting gamma-aminobutyric acid (GABA) neurotransmission for at least the past 4 weeks * Not taking medication directly affecting the serotonergic system for at least the past 4 weeks * ASD only: Diagnosis of Autism Spectrum Disorder (ICD 10-R criteria, confirmed using the Autism Diagnostic Interview (ADI) and/or ADOS) including atypical autism * ASD only: Being recommended drug therapy for symptoms of depression and/or anxiety * Controls only: No diagnosis of Autism Spectrum Disorder (ICD 10-R criteria, confirmed using the ADI and/or ADOS) * Controls only: No diagnosis of major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV or ICD 10.
Exclusion criteria
* Current risk of self-harm * Acute risk of suicidality (e.g., current suicidal ideations) * Age \< 18 years or \> 60 years old. * Taking medication directly affecting the serotonergic system (e.g. SSRIs, Tricyclic antidepressants) * Taking medication directly affecting GABA neurotransmission (e.g. antiepileptic drugs, and benzodiazepines) * Taking antipsychotic medication or medication for attention deficit hyperactivity disorder (ADHD) for the past 4 weeks * History of dependence to alcohol or substances of abuse (excluding nicotine) * Major mental illness (e.g. psychosis), or a learning disability (mental retardation) * Needle phobia * Medical/genetic disorder associated with ASD * Diagnosed and treated for hyperkinesis or Tourette's syndrome * Allergy to food colouring
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain excitation and inhibition response to pharmacological stimulation as assessed by magnetic resonance spectroscopy | In the months 1-2 following the last day of scanning | The measure of brain excitation and inhibition response to placebo, citalopram, and tianeptine includes the following: Assessment of the ratio of brain excitation and inhibition (measured as the balance of excitatory and inhibitory neurotransmitters) using proton magnetic resonance spectroscopy. |
| Brain activation response to pharmacological stimulation as assessed by functional magnetic resonance imaging | In the months 3-4 following the last day of scanning | The measure of brain activation response to placebo, citalopram, and tianeptine includes the following: Assessment of the blood-oxygen-level-dependent activation during tasks using functional magnetic resonance imaging. |
| Brain connectivity response to pharmacological stimulation as assessed by resting-state functional magnetic resonance imaging | In the months 5-6 following the last day of scanning | The measure of brain connectivity response to placebo, citalopram, and tianeptine includes the following: Assessment of the regional homogeneity during resting-state using functional magnetic resonance imaging. |
Countries
United Kingdom
Contacts
Primary ContactNichol Wong, PhD
Backup ContactGrainne McAlonan, PhD
Outcome results
None listed