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.

The study combines two models: a case/control study with observational outcomes where all cases are consequently included in a non-randomized interventional study

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.

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.

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.

Differences in melatonin secretion as indicated by area under curve (AUC) between SAD and non-SAD (summer and winter).

Correlation between treatment response and ipRGC function as measured by the sustained (10-20 seconds) post-illumination pupillary contraction following blue light stimulation

Difference in late PIPR (10-30 seconds post-illumination) following high intensity blue light between SAD and non-SAD and between seasons

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.