Healthy Young and Elderly Volunteers
Conditions
Keywords
Citalopram, Functional Magnetic Resonance Imaging, fMRI, Pharmacokinetics, Pharmacodynamics, Amygdala, Elderly
Brief summary
Antidepressant medications known as selective serotonin reuptake inhibitors (SSRIs) are most commonly prescribed to treat depression and anxiety. How antidepressants work on the brain to alter mood and behaviour is not well understood. This study will use a brain scanning technique (functional magnetic resonance imaging) to examine how aging impacts brain activation during emotional tasks after the administration of intravenous (IV) citalopram (this is the only SSRI available in this form, and is well tolerated and safe in young and old adults). The investigators will further determine what role genetic differences play in this relationship. The investigators expect to see an increase in brain signal as the concentration of IV citalopram increases. However, the investigators propose that the brain signal in older adults will not be as strong as in younger adults. Furthermore, the investigators expect that participants genetically predisposed to have fewer serotonin transporters (the site of action of SSRIs) will show greater decreases in brain activation with citalopram.
Interventions
DRUGIntravenous Citalopram
Single dose of 20mg parenteral citalopram diluted in 250mL of 0.9% sodium chloride solution, infused over 30 minutes
DRUGNormal Saline
Single dose of 250mL of 0.9% sodium chloride solution, infused over 30 minutes
Sponsors
Centre for Addiction and Mental Health
University of Toronto
Rotman Research Institute at Baycrest
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
20 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male aged 60 or older (elderly group) * Male aged 20-40 (younger adult group) * English speaking * Right-handed * Non-smoker * Score of 27 or greater on the Mini Mental State Exam
Exclusion criteria
* Unstable medical, cardiac, or neurological illness (including stroke, brain tumour, epilepsy, significant head injury, Alzheimer's, Parkinson's or Huntington's disease) * Laboratory results indicating unanticipated illness or intolerability of blood drawing procedures or of study drug * Current or lifetime Axis-I psychiatric diagnosis on the DSM-IV/SCID (i.e., Module A: Mood, Module F: Anxiety, Module B & C: Psychosis) * History of drug or alcohol abuse within one year, or lifetime history of alcohol or drug dependence (i.e., SCID Module E: Substance Abuse, or clinically significant urine toxicology screen) * History of non-tolerance to SSRI therapy; including history of SSRI-related syndrome of inappropriate antidiuretic hormone secretion (SIADH) or sinus bradycardia on ECG (less than 50 beats per minute) * Contraindication to MRI (as per MRI Contraindication Screening Form)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BOLD fMRI Response | Visit 1, Visit 2 | Changes in affect-related neuronal activation as measured by blood oxygenation level-dependent (BOLD) fMRI response to IV citalopram are the primary outcome measures. Imaging data will be compared between IV citalopram and placebo administration and young and old adults. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Genetics and Cognitive/Emotional Change | Visit 1, Visit 2 | Secondary measures include analysis of the relationship between 5HTT polymorphism and neuronal activation, and changes in cognitive and emotional assessments between IV citalopram and placebo. |
Countries
Canada
Outcome results
None listed