Brain Response to Serotonergic Medications in ASD

Can Brain Activation and Connectivity Predict Treatment Response to Two Serotonergic Medications (Citalopram and Tianeptine) in Subjects With Autism Spectrum Disorders (ASD)?

This study investigates brain response to single acute dose of citalopram, tianeptine, and placebo in males with and without autism spectrum disorder.

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.

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