Effects of Intravenous (IV) Citalopram on Emotional Brain Activity in Healthy Young and Elderly Adults

Rotman Research Institute at Baycrest29 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Enrollment

Conditions

Healthy Young and Elderly Volunteers

Interventions

Eligibility

Sex: MALEMin age: 20 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

BOLD fMRI Response

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.

Time frame: Visit 1, Visit 2

Secondary Outcomes

Genetics and Cognitive/Emotional Change

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.