Investigation of Seasonal Variations of Brain Structure and Connectivity in SAD

• Sponsor: Sunnybrook Health Sciences Centre (Other)
• Overall Status: Completed
• CT.gov ID: NCT03313674
• Collaborator: (none)
• Enrollment: 23
• Location: 1
• Arms: 3
• Actual Duration (Months): 23.1
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

Seasonal Affective Disorder (SAD) is a subtype of Major Depressive Disorder, characterized by a recurrent temporal relationship between the season of year, the onset and the remission of a major depressive episode. Estimates of the annual prevalence state that 1-6% of the population will develop SAD with the larger prevalences found at greater extremes in latitude. SAD is most likely triggered by the shortening photoperiod experienced in the winter months leading to a deterioration of mood. Recent cross-sectional neuroimaging studies have found cellular and neurotransmitter changes in response to seasonality, ultimately having an impact on the affect of patients. Conversly, this study aims to investigate the changes in neurocircuitry related to depression and euthymic states. Patients with SAD offer a unique ability to study these changes since they have predictable triggers for the onset of depression (i.e. the winter months) and remission (i.e. the summer months).

Condition or Disease	Intervention/Treatment	Phase
Seasonal Affective Disorder; Major Depressive Disorder; Neuroimaging	Device: Bright Light Therapy	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Seasonal Affective Disorder: Exploratory Investigation of Seasonal Variations in Brain Structure and Connectivity as a Predictor for Depressive Severity
• Actual Study Start Date: Nov 1, 2017
• Actual Primary Completion Date: Oct 5, 2019
• Actual Study Completion Date: Oct 5, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Seasonal Affective Disorder The primary objective is to use neuroimaging paradigms to identify perturbations in neural circuits of SAD patients when they are clinically depressed in the winter, after bright light therapy treatment, and when they are healthy in the summer	Device: Bright Light Therapy; Light box that emits light at 10,000 lux or higher and has been demonstrated to regulate circadian rhythm that is aberrant in the SAD population
No Intervention: Major Depressive Disorder SAD patients will be compared to unipolar depressed patient cohort, who will be imaged in the winter and the summer.
No Intervention: Healthy Controls SAD patients will be compared to healthy controls, who will be imaged in the winter and the summer.

Outcome Measures

Primary Outcome Measures

1. Changes in neural function [12 months]

   Functional MRI Scan

2. Changes in connectivity [12 months]

   Diffusion Tensor Imaging Scan

Secondary Outcome Measures

1. Executive Function [12 months]

   Trail Makers Test B will be used to measure executive function. Test is scored based on time to complete.Average time is 75 seconds, deficient time is >273 seconds

2. Concentration [12 months]

   Digit Symbol Substitute Test will be used to measure concentration. Survey score is determined by the number of correct and incorrect responses

3. Memory [12 months]

   California Verbal Learning Test. Score is conducted based on a propriety software based on the number of correctly recalled words after a list is administrated.

4. Blood Serum Metabolomic seasonal variation [12 months]

   Blood will be drawn to assess different serum metabolites depending on the season. One blood draw will be taken in Winter, one in the summer. Over 3300 metabolites will be acquired from a single sample.

5. Depressive severity measured through the • Structured Interview Guide for the Hamilton Depression Rating Scale-SAD version [12 months]

   Sigh-SAD measures Depressive Severity specifically in SAD patients. It contains 29 items, with the total score ranging from 0 to 29. Higher values in the scale indicate worse depression severity. Of the 29 items, 21 question (adapted from the Hamilton Depression scale) are used to determine typical depression severity, with an additional eight items for the "atypical" symptoms which are presented in seasonal affective disorder. The final score is summed, with equal weighting, to give the total score.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria for SAD Cohort

1. Male or female between the ages of 18 to 65 years, inclusive

2. Patients who are able and willing to give consent and able to attend study visits

3. Agreement to use light therapy for four weeks

4. DSM-V diagnosis of seasonal affective disorder, at least 2 year history of the illness with a Structured Interview Guide for the Hamilton Depression Rating Scale-SAD version (SIGH-SAD) score ≥ 25 at screening

Exclusion Criteria for SAD Cohort

1. Current alcohol and/or substance use disorder

2. Use of cigarettes

3. Past or present psychiatric disorders (axis I and II) other than SAD

4. Taken medications approved and/or employed off-label for depression

5. Previous use of light therapy

6. Use of photosensitive medications

7. Montreal Cognitive Assessment score < 24

8. Patients with standard contraindications for MR imaging. For example, non-MRI compatible metallic implants including cardiac pacemaker, size limitations etc.

9. Known intolerance or allergies to MRI contrast agent (Gadolinium or Magnevist) including advanced kidney disease

10. Severely impaired renal function (estimated glomerular filtration rate <30ml/min/1.73m2)

11. Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment

12. Pregnant and/or breastfeeding

13. Travelled to another a more southern latitude within 6 months of scan

14. Night shift workers

15. Are participating or have participated in clinical trial or research study in the last 30 days

16. Unable to communicate with investigator and/or staff

17. Diagnosis of a reading disability, dyslexia or significant learning disorder

Inclusion Criteria for Unipolar Depression Cohort contraindications

1. Male or female between the ages of 18 to 65 years, inclusive

2. Patients who are able and willing to give consent and able to attend study visits

3. DSM-V diagnosis of major depressive disorder, with a Hamilton Depression Rating Scale score ≥ 22 at screening

Exclusion Criteria for Unipolar Depression Cohort

1. Current alcohol and/or substance use disorder

2. Past or present psychiatric disorders (axis I and II) other than SAD

3. Montreal Cognitive Assessment score < 24

4. Patients with standard contraindications for MR imaging. For example, non-MRI compatible metallic implants including cardiac pacemaker, size limitations etc.

5. Known intolerance or allergies to MRI contrast agent (Gadolinium or Magnevist) including advanced kidney disease

6. Severely impaired renal function (estimated glomerular filtration rate <30ml/min/1.73m2)

7. Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment

8. Pregnant and/or breastfeeding

9. Are participating or have participated in clinical trial or research study in the last 30 days

10. Unable to communicate with investigator and/or staff

11. Diagnosis of a reading disability, dyslexia or significant learning disorder

Inclusion Criteria for Healthy Controls

1. Male or female between the ages of 18 to 65 years, inclusive

2. Patients who are able and willing to give consent and able to attend study visits

3. No current or past history of mental disorder

4. No unstable medical disorders

Exclusion Criteria for Healthy Controls

1. Use of any medication for a general medical disorder and/or condition that, in the opinion of the investigator, may affect neural structure

2. Alcohol or drug-use within 24 hours of MRI

3. Pregnant and/or breastfeeding

4. Montreal Cognitive Assessment score < 24

5. Patients with standard contraindications for MR imaging. For example, non-MRI compatible metallic implants including cardiac pacemaker, size limitations etc.

6. Known intolerance or allergies to MRI contrast agent (Gadolinium or Magnevist)

7. Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment

8. Are participating or have participated in clinical trial or research study in the last 30 days

9. Unable to communicate with investigator and/or staff

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sunnybrook Health Science Centre	Toronto	Ontario	Canada	M4N 3M5

Sponsors and Collaborators

• Sunnybrook Health Sciences Centre

Investigators

• Principal Investigator: Nir Lipsman, MD PhD, Sunnybrook Health Sciences Centre

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dr. Nir Lipsman, Neurosurgeon, Scientist, Sunnybrook Health Sciences Centre
• ClinicalTrials.gov Identifier: NCT03313674
• Other Study ID Numbers: 281-2017
• First Posted: Oct 18, 2017
• Last Update Posted: Mar 16, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depressive Disorder, Major; Mood Disorders; Seasonal Affective Disorder

Study Results

No Results Posted as of Mar 16, 2021