Mood disorders often have a seasonal onset or exacerbation, although the mechanism behind such seasonal triggers for psychopathology is still unknown. Many other disorders may also have such seasonal patterns of exacerbation. We hypothesize that abnormal responses to diminished levels of environmental light in winter may account for the regular winter timing of episodes of depression, seasonal changes in biology, and the benefit of light therapy in disorders like seasonal affective disorder, bipolar disorder, nonseasonal depression, eating disorders, and cognitive decline in aging, for example. Abnormal responses to environmental light levels may be mediated by abnormal retinal signaling.
The aim of the present study is to determine if a specific pathway, the melanopsin pathway, originating in the retina and projecting to central brain areas, is involved in dysphoric mood, over eating, over sleeping, and fatigue in winter. A measure of the sensitivity of this neural pathway, the post-illumination pupil response (PIPR), will be tested for association with genetic variations in the melanopsin gene, seasonal changes in mood and behavior, and psychopathology (i.e., dysphoric mood, hypersomnia, hyperphagia, and fatigue). If diminished melanopsin photosensitivity is associated with seasonal decrements in mood, the PIPR may constitute a biomarker for this type of psychopathology, leading to a new way to classify psychopathology based on the pathway of origin, or the etiology. In the future, we may be able to use the PIPR test to identify those vulnerable to specific light-related exacerbation of psychopathology, and potentially to predict the best treatment for a given individual, reducing the trial-and-error of treatment, and reducing the time to recovery.

Public Health Relevance

Disorders characterized by dysphoric mood, hypersomnia, hyperphagia, and fatigue, such as mood disorders, are prevalent, chronic, and debilitating mental health problems with significant social costs that pose a tremendous economic burden to our society. About 10-20% of individuals with a unipolar course and 15-22% with a bipolar mood disorder in outpatient treatment have a Seasonal Pattern (SAD; Roecklein, Rohan & Postolache, 2010; APA, 2013), for a U.S. prevalence of around 2-5% (Magnusson, 2010; Lam & Levitt, 1999) or 14.5 million Americans suffering from SAD (Rohan, Roecklein & Haaga, 2009). Those with SAD have an average of 13.4 previous major depressive episodes, higher than the 10.8 episodes seen in nonseasonal depression (Roecklein et al., 2010). Combined with the average length of a SAD episode, we predict that individuals with SAD experience symptoms 40% of the year, which affect the family and workplace starting in young adulthood (Rohan et al., 2009). SAD is associated with impaired physical health, emotional well-being, daily activities, social activity level, and the experience of physical pain (Schlager et al., 1995), indicating a similar level of increased all-cause mortality and morbidity as is seen in nonseasonal depression. Empirically validated treatments exist for SAD (i.e., cognitive-behavioral therapy for SAD, bright light therapy, antidepressant medication), but not all patients respond fully to these treatments (Roecklein et al., 2013). Leveraging recent advances in melanopsin neurophysiology has the potential to improve our understanding of SAD by linking genes, biomarkers (i.e., the PIPR), and risk for dysphoric mood, and to suggest ways to improve treatments and/or predict treatment response (Roecklein et al., 2013). This proposal aims to study the role of the melanopsin photosensitivity pathway in the hopes of identifying a biomarker associated with these negative health outcomes. A biomarker for seasonal worsening of mood and behavioral problems could lead to clearer diagnosis and characterization of mental health problems, as well as a way to identify treatments that are likely to be effective for a given individual.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Adult Psychopathology and Disorders of Aging Study Section (APDA)
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Meinecke, Douglas L
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University of Pittsburgh
Schools of Arts and Sciences
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Smagula, Stephen F; DuPont, Caitlin M; Miller, Megan A et al. (2018) Rest-activity rhythms characteristics and seasonal changes in seasonal affective disorder. Chronobiol Int 35:1553-1559