Article

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

Graduate Program in Medical Psychology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
Journal of Affective Disorders (Impact Factor: 3.38). 10/2008; 114(1-3):279-85. DOI: 10.1016/j.jad.2008.08.005
Source: PubMed

ABSTRACT

Melanopsin, a non-visual photopigment, may play a role in aberrant responses to low winter light levels in Seasonal Affective Disorder (SAD). We hypothesize that functional sequence variation in the melanopsin gene could contribute to increasing the light needed for normal functioning during winter in SAD.
Associations between alleles, genotypes, and haplotypes of melanopsin in SAD participants (n=130) were performed relative to controls with no history of psychopathology (n=90).
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, and all 7 (5%) of individuals with the T/T genotype at P10L were in the SAD group.
The study examined only one molecular component of the non-visual light input pathway, and recruitment methods for the comparison groups differed.
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.

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    • "Preliminary studies of patients with seasonal affective disorder (SAD) found blue light treatment to be more effective than red light (Anderson et al., 2009; Glickman et al., 2006 ), and that sequence variation in the melanopsin gene may increase vulnerability to SAD (Roecklein et al., 2009). Other recent evidence supports the importance of a large monthly increase in solar insolation. "

    Full-text · Dataset · Dec 2014
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    • "Preliminary studies of patients with seasonal affective disorder (SAD) found blue light treatment to be more effective than red light (Anderson et al., 2009; Glickman et al., 2006 ), and that sequence variation in the melanopsin gene may increase vulnerability to SAD (Roecklein et al., 2009). Other recent evidence supports the importance of a large monthly increase in solar insolation. "
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    ABSTRACT: BACKGROUND: The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode. METHODS: Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations. RESULTS: There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduced by half if there was no family history. The maximum monthly increase in solar insolation occurred in springtime. The effect was one-third smaller for initial episodes of mania than depression. The largest maximum monthly increase in solar insolation occurred in northern latitudes such as Oslo, Norway, and warm and dry areas such as Los Angeles, California. LIMITATIONS: Recall bias for onset and family history data. CONCLUSIONS: A large springtime increase in sunlight may have an important influence on the onset of bipolar disorder, especially in those with a family history of mood disorders.
    Full-text · Article · May 2014 · Journal of Affective Disorders
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    • "Another example of the health risk of a short duration of sunlight is seasonal affective disorder (SAD), which is involved in the mechanism of melanopsin-containing non-visual response to light. Although it has been reported that melanopsin gene polymorphism is associated with prevalence of SAD [38], it is unknown whether natural selection has driven it or not. Further study based on population genetics, such as a statistical approach to estimate the degree of population differentiation (Wright’s Fst) [39] and to measure linkage disequilibrium as evidence of selective sweep [40], is needed. "
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    ABSTRACT: Background In our previous studies, we found that the Ile394Thr SNP in the melanopsin gene (OPN4) was functionally associated with the pupillary light reflex. This indicates the possibility that OPN4*Ile394Thr is associated with other non-image forming responses. The aim of this study was therefore to determine whether OPN4*Ile394Thr is associated with sleep/wake timing. Methods A total of 348 healthy Japanese university students participated in this study. Scalp hair was used to genotype the Ile394Thr SNP of OPN4. Sleep habits, including bedtime, wake time and sleep duration, were assessed separately for weekdays and weekends. A total of 328 samples, including 223 samples with TT genotype, 91 with TC genotype and 14 with CC genotype, were used for statistical analysis. No significant difference in age or male/female distribution was found among the three genotype groups. Results There was no significant difference in circadian preference among the genotype groups. During weekdays, bedtime, wake time and midpoint of sleep for CC subjects were significantly later than those for TT and TC subjects. However, there was no difference between TT and TC subjects in any of their sleep habits. During weekends, bedtime of CC subjects was significantly later than those of TT and TC subjects, and the midpoint of sleep of CC subjects was significantly later than that of TC subjects. Conclusions Our findings demonstrated that OPN4*Ile394Thr is associated with sleep/wake timing. We also found that the sleep/wake timing of subjects with the CC genotype was later than that of subjects with the TT or TC genotype.
    Full-text · Article · May 2014 · Journal of PHYSIOLOGICAL ANTHROPOLOGY
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