A missense variant (P10L) of the melanopsin (OPN4) gene in seasonal affective disorder

Abstract

Background Melanopsin, a non-visual photopigment, may play a role in aberrant responses to low winter light levels in Seasonal Affective Disorder (SAD). We hypothesized that functional sequence variation in the melanopsin gene (Opn4) could contribute to increasing the light needed for normal functioning during winter in SAD. Methods Associations between alleles, genotypes, and haplotypes of Opn4 in SAD participants (n = 130) were performed relative to controls with no history of psychopathology (n = 90). Results SAD participants had a higher frequency of the homozygous minor genotype (T/T) for the missense variant rs2675703 (P10L) than controls, compared to the combined frequencies of C/C and C/T. Individuals with the T/T genotype were 5.6 times more likely to be in the SAD group than the control group. Limitations The study examined only one molecular component of the non-visual light input pathway, and recruitment methods for the comparison groups differed. Conclusion These findings support the hypothesis that melanopsin variants may predispose some individuals to SAD. Characterizing the genetic basis for deficits in the non-visual light input pathway has the potential to define mechanisms underlying the pathological response to light in SAD, which may improve treatment.

Intrinsically photosensitive retinal ganglion cells

“…Recently Provencio and colleagues described a missense variant of the melanopsin gene in SAD patients (Roecklein et al 2009). It is likely that many factors contribute to the etiology of SAD, and these may well include reduced sensitivity to light that may result from abnormalities in phototransduction in ipRGCs (Roecklein et al 2009) and/or abnormalities in 5-HT neurotransmission in the SCN (Sollars et al 2006).…”

“…Moreover, 5-HT 1B receptor knockout mice maintained under short-day (winterlike) conditions exhibit a delayed phase relationship to the day/night cycle (Sollars et al 2006) resembling the phase delay demonstrated by people suffering from recurrent winter depression or seasonal affective disorder (SAD) (Lewy et al 1987;Terman and Terman 2005). Recently Provencio and colleagues described a missense variant of the melanopsin gene in SAD patients (Roecklein et al 2009). It is likely that many factors contribute to the etiology of SAD, and these may well include reduced sensitivity to light that may result from abnormalities in phototransduction in ipRGCs (Roecklein et al 2009) and/or abnormalities in 5-HT neurotransmission in the SCN (Sollars et al 2006).…”

“…Recently Provencio and colleagues described a missense variant of the melanopsin gene in SAD patients (Roecklein et al 2009). It is likely that many factors contribute to the etiology of SAD, and these may well include reduced sensitivity to light that may result from abnormalities in phototransduction in ipRGCs (Roecklein et al 2009) and/or abnormalities in 5-HT neurotransmission in the SCN (Sollars et al 2006).Alterations in the phase angle of entrainment to the day/night cycle are associated with alterations in the amplitude of the diurnal rhythm of plasma corticosterone secreted from the adrenal cortex; a blunted cortisol rhythm has been reported in SAD patients (Avery et al 1997). The reduction in corticosterone secretion may result from an altered phase relationship between the adrenal gland's innate circadian rhythm in steroid biosynthesis to the day/night cycle (Oster et al 2006;Son et al 2008).…”

Alpha Rhythms Response to 10 Hz Flicker Is Wavelength Dependent

“…The involvement of alpha rhythms may promote a deeper understanding of haw phase synchronization support the flexibility of interaction between memory systems and may yield new insight into the function of phase synchronization in general [12,23]. Whereas the stimulation at the hypothalamic level, offer the possibility to interfere with many regulatory disfunction as insomnia, jet lag, (desynchronization of the biological clock), reproductive function, metabolism and seasonal affective disorder (SAD) [3,27,28].…”

Image and Non-Image Forming Melanopsin Function in Age-Related Macular Degeneration

“…In a human study, the PIPR to blue light stimuli in persons with seasonal affective disorder (SAD) was significantly reduced compared to a control group, indicating reduced ipRGC sensitivity (Roecklein et al 2013). Further, persons with gene variants (rs2675703, P10L, TT allele) in the melanopsin (opn4) photopigment had a 5.6 times higher risk of developing SAD (Roecklein et al 2009). This suggests an association between ipRGC dysfunction and the increased prevalence of depression; however, the link between depression and ipRGC dysfunction in AMD is still to be determined.…”