Seasonal Affective Disorder and Visual Impairment

The Neurobiology of Seasonal Affective Disorder: Exploring the High Prevalence in Severe Visual Impairment

As a subtype of major depressive disorder, seasonal affective disorder (SAD) or winter depression causes severe reductions in both quality of life and productivity and results in high morbidity and frequent sick leave (1). SAD is a prevalent disorder with rates as high as 3-5% in central European countries and 8-10% in Scandinavian countries. In our recent screening survey among persons with severe visual impairment or blindness (visual acuity < 6/60), we found a strikingly high prevalence of SAD of 17 % compared to 8% in the fully sighted control group. Persons with maintained light perception had a highly increased SAD prevalence of 18 % whereas no light perception (NLP) respondents had an SAD prevalence of 13 %. Light is unquestionably of great importance in the development and treatment of SAD. It is suggested that a reduced retinal sensitivity to light leads to sub-threshold light input to the brain and consequently to the development of SAD. The novel retinal non-visual photoreceptors, the intrinsically photosensitive retinal ganglion cells (ipRGCs), are involved in the regulation of circadian rhythm and mood and their function are in part independent of the function of the classical rod and cone photoreceptors which form the basis of conscious visual perception. Function of the ipRGCs can be assessed by chromatic pupillometry where the sustained pupillary contractions following blue light stimulation (PIPR) is the main outcome. In persons with SAD without eye disorder the function of the ipRGCs is reduced. We here wish to investigate associations between ipRGC function and SAD symptoms, circadian profile and treatment response to light therapy in persons with visual impairment.

Persons with visual impairment (SAD and non-SAD) are assessed for ipRGC function with chromatic pupillometry, for seasonal mood variation by interview and questionnaire and for diurnal melatonin secretion by saliva analysis summer and winter. In winter SAD participants are treated with daily morning bright light for 6 weeks. Reduction in depression scores and tolerability is recorded.

Study Overview

• Status: Completed
• Conditions: Seasonal Affective Disorder; Visual Impairment
• Intervention / Treatment: Device: light therapy

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen Ø, Denmark, 2100
    • Mental Health Center Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Seasonal affective disorder. Visual impairment (Snellen visual acuity < 6/18) or visual field reduction (MD<10).

Exclusion Criteria:

Alcohol or drug abuse. Current or planned pregnancy. Other neuropsychiatric disorder. Antidepressant medication. Regular use of melatonin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAD; Persons with visual impairment and SAD are assessed by clinical interview, depression rating, diurnal saliva melatonin and cortisol and chromatic pupillometry during symptomatic winter phase and asymptomatic summer phase. Winter assessment is followed by a 6 week light therapy protocol ending with assessment of depression severity and repeated pupillometry.	Device: light therapy; 6 weeks morning treatment with bright light therapy in own home.
No Intervention: non-SAD; Control participants with similar visual impairment but without SAD/sSAD are assessed by clinical interview, depression rating, diurnal saliva melatonin and cortisol and chromatic pupillometry in winter and summer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
treatment response	Reduction in depression severity on the Structured interview guide for the Hamilton Depression Rating Scale - Seasonal affective disorder version (25 items version total score with range 0-78. Results from Hamilton Rating Scale for Depression 17 items (range 0-52) and the 8 item atypical symptom subscale (range 0-26) are reported. Higher scores indicate higher severity.	6 weeks
saliva melatonin concentration	Differences in melatonin secretion as indicated by area under curve (AUC) between SAD and non-SAD (summer and winter).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PIPR - light therapy	Correlation between treatment response and ipRGC function as measured by the sustained (10-20 seconds) post-illumination pupillary contraction following blue light stimulation	6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
feasibility of light therapy	side effects and tolerability of light therapy	6 weeks
Late sustained post-illumination pupillary response to blue light	Difference in late PIPR (10-30 seconds post-illumination) following high intensity blue light between SAD and non-SAD and between seasons	6 months

Collaborators and Investigators

• Sponsor: Psychiatric Centre Rigshospitalet
• Collaborators: Glostrup University Hospital, Copenhagen
• Investigators: Principal Investigator: Helle Ø Madsen, MD, Mental Health Center Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2017
• Primary Completion (Actual): March 12, 2020
• Study Completion (Actual): March 12, 2020

Study Registration Dates

• First Submitted: January 11, 2018
• First Submitted That Met QC Criteria: January 18, 2018
• First Posted (Actual): January 19, 2018

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: September 15, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: melatonin; visual impairment; pupillometry; light therapy; ipRGC
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Sensation Disorders; Depressive Disorder; Mood Disorders; Seasonal Affective Disorder; Vision, Low; Vision Disorders
• Other Study ID Numbers: BlindSAD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No