Melanopsin Gene Variations Interact With Season to Predict Sleep Onset and Chronotype

Abstract

The human melanopsin gene has been reported to mediate risk for seasonal affective disorder (SAD), which is hypothesized to be caused by decreased photic input during winter when light levels fall below threshold, resulting in differences in circadian phase and/or sleep. However, it is unclear if melanopsin increases risk of SAD by causing differences in sleep or circadian phase, or if those differences are symptoms of the mood disorder. To determine if melanopsin sequence variations are associated with differences in sleep-wake behavior among those not suffering from a mood disorder, the authors tested associations between melanopsin gene polymorphisms and self-reported sleep timing (sleep onset and wake time) in a community sample (N = 234) of non-Hispanic Caucasian participants (age 30–54 yrs) with no history of psychological, neurological, or sleep disorders. The authors also tested the effect of melanopsin variations on differences in preferred sleep and activity timing (i.e., chronotype), which may reflect differences in circadian phase, sleep homeostasis, or both. Daylength on the day of assessment was measured and included in analyses. DNA samples were genotyped for melanopsin gene polymorphisms using fluorescence polarization. P10L genotype interacted with daylength to predict self-reported sleep onset (interaction p < .05). Specifically, sleep onset among those with the TT genotype was later in the day when individuals were assessed on longer days and earlier in the day on shorter days, whereas individuals in the other genotype groups (i.e., CC and CT) did not show this interaction effect. P10L genotype also interacted in an analogous way with daylength to predict self-reported morningness (interaction p < .05). These results suggest that the P10L TT genotype interacts with daylength to predispose individuals to vary in sleep onset and chronotype as a function of daylength, whereas other genotypes at P10L do not seem to have effects that vary by daylength. A better understanding of how melanopsin confers heightened responsivity to daylength may improve our understanding of a broad range of behavioral responses to light (i.e., circadian, sleep, mood) as well as the etiology of disorders with seasonal patterns of recurrence or exacerbation.

Pupillary response abnormalities in depressive disorders

“…Studies of melanopsin gene variation and seasonal affective disorder suggest a potential relationship between melanopsin-mediated retinohypothalamic tract pathways and SAD (Roecklein et al, 2012, 2013b). The retinal circuitry for transmitting environmental light signals used in chronobiological functions has recently been found to involve melanopsin, a photopigment found in intrinsically photosensitive retinal ganglion cells (ipRGCs) (Guler et al, 2008; Kawasaki and Kardon, 2007).…”

“…When the retina is exposed to 485 nm wavelength light, the melanopsin-mediated pathway is activated causing signals to travel to the suprachiasmatic nucleus via the retinohypothalamic tract and also to the midbrain resulting in the PIPR. Due to the proposed relationship between the melanopsin-mediated retinohypothalamic tract pathway and SAD (Roecklein et al, 2012, 2013b), we were interested in how the melanopsin-mediated PIPR may vary based on a person's diagnosis with seasonal depression and hours of daylight at different seasons. We suspected that those vulnerable to seasonal depressive episodes would show decreased ability to transmit light signals to the brain, which could be quantifiable by comparing pupillary light reflexes.…”

Melanopsin, photosensitive ganglion cells, and seasonal affective disorder

“…Some SAD patients differ from controls based on sequence variation in the melanopsin gene (Roecklein et al, 2009). Additionally, those variations are associated with seasonal changes in sleep timing and chronotype (Roecklein et al, 2012). Although melanopsin variations may hypothetically be the physiological basis underlying the retinal subsensitivity hypothesis, other possibilities are discussed as well.…”

“…This association was retested in a healthy sample to remove the effect of mood disorder symptoms. In 268 healthy individuals, the effects of P10L TT genotype and day length interacted to predict earlier bedtime when individuals were assessed on shorter days, and later bedtime when individuals were assessed on longer days (Roecklein et al, 2012). If replicated, and found in SAD as well, these data may indicate a specific etiological relationship between P10L, changes in sleep timing, and SAD.…”

Schizophrenia: the role of sleep and circadian rhythms in regulating dopamine and psychosis

“…Photosensitive retinal ganglion cells are the cells in the retina, which contain the photopigment melanopsin that project to the SCN and regulate circadian rhythms. While melanopsin polymorphisms have as yet been associated with schizophrenia, they are associated with chronotype ( Roecklein et al, 2012) and risks for seasonal affective disorder (Roecklein et al, 2009), indicating that melanopsin has both circadian and psychological effects. In the retina, dopamine levels modulate mRNA levels of melanopsin, which is likely mediated by D2 receptors (Sakamoto et al, 2005).…”