Genetic links to the seasonal clock
Have trouble with changing seasons? Maybe your genetics are to blame. -
Over the past decade, the role of rhythms—whether daily or seasonal—in disease has received a tremendous amount of attention in research and clinical applications. There is growing interest in how rhythms govern our sleep-wake cycles, metabolism and food consumption, along with our mood. Recent efforts to discover the genetics underlying natural variation in these physiological and behavioral processes may uncover how altered or disrupted rhythms may contribute to psychiatric disorders and other diseases. One such disorder, seasonal affective disorder (SAD), is characterized by seasonal mood changes which is typically seen as autumn or winter depression that spontaneously remits during spring and summer.
A recent study from Korea recruited a community-based sample of healthy young adults who were asked to respond to a series of questionnaires retrospectively assessing seasonal variation in sleep, social activity, mood, weight, appetite, and energy level, in addition to their own perceived ‘difficulty’ with seasonal changes.I Based on these ratings, participants were categorized into SAD winter or summer types (feeling ‘worse’ during those months), subsyndromal SAD, and non-seasonals. Of these participants, 22.3% were considered seasonals (12% winter or summer type and 10.3% subsyndromal). However, those of the summer-type were excluded from further analyses because of the possibility that the biological bases underlying winter and summer subtypes are quite different1.
In addition, leukocytes were collected from each participant for genotyping analyses of specific single nucleotide polymorphisms (SNPs) in the following circadian genes: CLOCK, ARNTL (or BMAL1), and NPAS2. These genes encode for the core set of transcription factors that drive rhythmic gene transcription throughout almost every cell of the body. ARNTL or NPAS2 polymorphisms were only associated with body weight and appetite subscales, respectively, which do differ from previous studies reporting significant associations with winter depression.4,5 Interestingly, the CLOCK (rs1801260) SNP was related to seasonal variation, body weight, and appetite, and the T-allele carriers were more frequent among the seasonals, suggesting a possible susceptibility genotype. Moreover, an interaction between CLOCK (rs1801260) and ARNTL (rs2278749) polymorphisms predicted seasonality, suggesting the interaction of these genes may further contribute to SAD susceptibility.
CLOCK and ARNTL polymorphisms have also been associated with bipolar disorder,2,3 antidepressant treatment response.4 and metabolic syndromes5,6 in clinical populations. In a sample of healthy subjects, this study suggests these polymorphisms may resemble susceptibility loci to SAD and metabolic phenotypes associated with seasonal variations, providing further evidence for the involvement of circadian genes in disease. We are finding that rhythms, from genes to behavior, are becoming more and more important to our understanding of how we, as humans, adapt to changing environments and how these systems may go awry and lead to maladaptive behavior.
- I. Kim HI, Lee HJ, Cho CH, Kang SG, Yoon HK, Park YM, Lee SH, Moon JH, Song HM, Lee E, Kim L (2015) Association of CLOCK, ARNTL, and NPAS2 gene polymorphisms and seasonal variations in mood and behavior. Chronobiol Int 32:785-791. 10.3109/07420528.2015.1049613
- 1. Levitan RD (2007) The chronobiology and neurobiology of winter seasonal affective disorder. Dialogues Clin Neurosci 9:315-324.
- 2. Benedetti F, Serretti A, Colombo C, Barbini B, Lorenzi C, Campori E, Smeraldi E (2003) Influence of CLOCK gene polymorphism on circadian mood fluctuation and illness recurrence in bipolar depression. Am J Med Genet B Neuropsychiatr Genet 123B:23-26. 10.1002/ajmg.b.20038
- 3. Nievergelt CM, Kripke DF, Barrett TB, Burg E, Remick RA, Sadovnick AD, McElroy SL, Keck PE, Jr., Schork NJ, Kelsoe JR (2006) Suggestive evidence for association of the circadian genes PERIOD3 and ARNTL with bipolar disorder. Am J Med Genet B Neuropsychiatr Genet 141B:234-241. 10.1002/ajmg.b.3025
- 4. Serretti A, Cusin C, Benedetti F, Mandelli L, Pirovano A, Zanardi R, Colombo C, Smeraldi E (2005) Insomnia improvement during antidepressant treatment and CLOCK gene polymorphism. Am J Med Genet B Neuropsychiatr Genet 137B:36-39. 10.1002/ajmg.b.30130
- 5. Scott EM, Carter AM, Grant PJ (2008) Diabetes and cardiovascular disease: related disorders created by disturbances in the endogenous clock. J Indian Med Assoc 106:736-738, 740.
- 6. Woon PY, Kaisaki PJ, Braganca J, Bihoreau MT, Levy JC, Farrall M, Gauguier D (2007) Aryl hydrocarbon receptor nuclear translocator-like (BMAL1) is associated with susceptibility to hypertension and type 2 diabetes. Proc Natl Acad Sci U S A 104:14412-14417. 10.1073/pnas.0703247104
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