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Seasonal Affective Disorder (seasonal depression) – symptoms, risk factors, causes and genetics

Medicover Genetics Editorial Team |
November 16th 2022

Here in the Northern Hemisphere, winter is not far away. The days are colder and shorter. It is barely light when we put on our coats to go to work in the morning, and by late afternoon, the light is fading again. There are many people who do not like this time of year or who would rather stay at home in the evening than go out in the dark, but for some people, fewer daylight hours trigger a more serious winter depression: seasonal affective disorder.

What is seasonal affective disorder?

Seasonal affective disorder is a mental health condition that is related to the changing seasons. In most cases, there is depression with an onset in autumn and winter that resolves in spring and summer. However, in about 10% of people, the pattern is reversed and depressive symptoms are experienced in spring and summer that resolve during autumn and winter [1].

How common is seasonal affective disorder?

Seasonal affective disorder affects up to 3% of the general population [1] and is more common in women [2]. It may not recur every year and it is more likely to occur in people previously diagnosed with depression (affects 10-20%), bipolar disorder (affects 25%) or other mental health disorders (such as anxiety or eating disorders) [1].

People with bipolar disorder and seasonal affective disorder find that their periods of depression occur in the autumn and winter and mania occurs in the spring and summer.

What are the symptoms of seasonal affective disorder?

Signs and symptoms include [1, 2]

  • Depressed mood, feeling sad or down
  • Low energy
  • Difficulty concentrating
  • Loss of interest in activities
  • Carbohydrate cravings and overeating
  • Weight gain
  • Excessive sleeping (hypersomnia)

When seasonal affective disorder starts in spring, difficulty sleeping (insomnia), loss of appetite and weight loss may be seen instead.

What are the risk factors of seasonal affective disorder?

Risk factors for seasonal affective disorder include [1, 2]

  • Medical history: history of depression or other mental health disorder
  • Family history: a first-degree relative with seasonal affective disorder or relatives with another type of mental health disorder
  • Gender: females are more likely to be affected
  • Low levels of vitamin D: vitamin D is associated with mood and levels are lower when there is less skin exposed to sunlight
  • Geographical location: living further from the equator is associated with less sunlight in the winter

What causes seasonal affective disorder?

The exact cause of seasonal affective disorder is unclear, but multiple causes have been investigated. These include altered serotonin levels (a neurotransmitter involved in mood regulation), increased melatonin secretion in winter (a hormone produced by the brain in response to darkness that is involved in the circadian rhythm and sleepiness), changes to the sleep-wake cycle caused by less daylight and psychological factors [3]. There may also be an association between vitamin D levels and depression, thus vitamin D levels may play a role in seasonal affective disorder [4, 5]. Some of these suggested causes can be influenced by genetics, and genes related to serotonin metabolism, melatonin production and the circadian clock have been investigated. This is discussed in the following section.

Does seasonal affective disorder have a genetic cause?

Research into the genetics of seasonal affective disorder is inconclusive, but the idea that it is a result of a biochemical changes and therefore influenced by genetics is supported by research into the familial component of the disorder. In particular, twin studies have shown that seasonality, defined as how vulnerable someone is to seasonal changes in mood and behavior, has a genetic link [6, 7], and that genetics accounts for around 29% of the difference in seasonality between men and women [8].

Serotonin metabolism genes

Serotonin in a neurotransmitter that is thought to have a role in regulating mood. As such, it is a focus for research into many types of depression, including seasonal affective disorder. Research focused on serotonin metabolism found that a genetic variant in the serotonin transporter gene promotor region (5-HTTLPR) was associated with seasonal affective disorder and seasonality [6, 9, 10]. An insertion or deletion polymorphism in this region results in long or short repeats that can affect the expression of the serotonin transporter, 5-HTT. Called long or short alleles, the effect of the 5-HTTLPR polymorphism has been investigated in insomnia, anxiety and depression with inconclusive results. Results are also inconclusive for seasonal affective disorder: the short allele has been suggested [10] and disputed [11] as a risk factor, while both alleles have been implicated in specific depression sub-types in seasonal affective disorder [12]. This has led researchers to the conclusion that these changes are not directly causal but rather associated with the presentation of the disease [10, 12]. This aligns with the general understanding of depression as a multifactorial disease affected by the combined influence of genetic changes and the environment. Even where no relationship between 5‑HTTLPR and seasonal affective disorder was found, an association with seasonality was noted [11].

Researchers have also found that a polymorphism or variation in the serotonin receptor 5-HT2A (5-HT2A-1438G/A gene promoter polymorphism) was associated with seasonal affective disorder but not seasonality [6, 9, 13].

Circadian clock genes

The circadian clock synchronizes the body with the 24-hour light and dark cycle of the solar day. As seasonal affective disorder typically starts when there is less daylight, the involvement of the circadian clock in the development of the disorder is the subject of much research. Circadian genes have been implicated in other mood disorders [14] and have been studied in seasonal affective disorder.

A study of 159 Europeans with seasonal affective disorder and matched controls investigated single nucleotide polymorphisms in four genes involved in the circadian clock for their association with seasonal affective disorder, seasonality or diurnal preference (morning or evening). The authors reported significant findings for polymorphisms in two genes: NPAS2 471 Leu/Ser was found to have a possible association with seasonal affective disorder and Period3 647 Val/Gly was found to have a possible association with diurnal preference. It should be noted that the authors clearly state that they may not be causative [15].

An analysis of sequence variations in three genes that form a functional unit of the circadian clock (PER2, ARNTL, and NPAS2) found a single nucleotide polymorphism in each gene with a significant association with seasonal affective disorder. The authors also reported an additive effect and identified a risk genotype combination and a protective genotype combination. They reported that carriers of a risk genotype have a four‐fold risk of having seasonal affective disorder than other genotype combinations and a ten-fold risk compared to those with the protective genotype. The authors concluded that these three genes have a role in causing seasonal affective disorder, although more research is required to confirm the genotype combinations and relationship to disease presentation [16]. ARNTL and NPAS2 have also been associated with seasonality with regards to weight and appetite [17].

Two rare genetic variants in the PERIOD3 gene (PER3-P415A/H417R) have been found in a small number of people exhibiting altered sleep behavior and symptoms of seasonal affective disorder. The gene is thought to have a role in circadian clock regulation [18].

A genome-wide study of 1380 patients and 2937 controls that aimed to identify a common gene variant for seasonal affective disorder identified ZBTB20 as a candidate susceptibility gene that requires further investigation. It is interesting to note that in mice the Zbtb20 gene is important for normal circadian rhythms [19].

Melatonin genes

It has been suggested that melatonin has a role in the etiology of seasonal affective disorder [4] through changes to the time of onset or duration of melatonin secretion [20]. One theory is that genetic factors cause patients with seasonal affective disorder to generate a biological signal for season change that is unseen in healthy individuals and that results in a longer duration of active melatonin secretion [21].

Other genes

Other genes and their roles in seasonal affective disorder have also been studied [14]. They include the melanopsin gene, OPN4. Melanopsin is a photopigment important in aligning circadian rhythms. Researchers found that single missense variant (P10L) in the OPN4 gene is associated with an increased risk of seasonal affective disorder in a small number of people [22].

Can seasonal affective disorder be inherited?

Although seasonal affective disorder may run in families it has no clear pattern of inheritance and the exact nature of the familial component is not clear. It is known that seasonal affective disorder is more likely to occur where there is a first-degree relative with the condition. It is estimated that this is the case for approximately 15% of people with seasonal affective disorder. Furthermore, up to 67% of people with seasonal affective disorder have at least one relative with another type of mood disorder [1].

What is the treatment for seasonal affective disorder?

It may be possible to take steps to manage the onset or severity of seasonal affective disorder and it is important to consult a physician or healthcare provider if you have any concerns about your health and well-being. Treatment options may include light therapy, Vitamin D, antidepressant medication and counseling [3, 4]. A physician will be able to determine the correct options for you.

Conclusion

Seasonal affective disorder is a mental health condition typically characterized by the onset of depression in autumn and winter that resolves in spring and summer. It may run in families. There have been many studies looking at potential genetic changes responsible for seasonal affective disorder and it is generally accepted that it has a genetic component; however, the exact causes remain unclear. Studies investigating the genetics of seasonal affective disorder are often small, may be affected by geographical location, and the results are sometimes inconclusive, suggesting that genes such as those involved in the circadian clock and serotonin metabolism should be investigated further. It is likely that seasonal affective disorder is multifactorial, meaning that is caused by an interaction between multiple factors and/or multiple genes, although it is currently unclear exactly how genetic and environmental risk factors interact. There is much scope for further research into the etiology of seasonal affective disorder to increase our understanding and potentially benefit patients.

This article cannot replace medical advice. Please visit your healthcare provider if you have concerns about your health and well-being.

References

[1] Seasonal affective disorder. Retrieved 13 October from https://medlineplus.gov/genetics/condition/seasonal-affective-disorder

[2] Seasonal affective disorder (SAD). Mayo Clinic. Retrieved 13 October from https://www.mayoclinic.org/diseases-conditions/seasonal-affective-disorder/symptoms-causes/syc-20364651

[3] Roecklein KA, Rohan KJ. Seasonal affective disorder: an overview and update. Psychiatry (Edgmont). 2005 2(1):20-6. PMID: 21179639; PMCID: PMC3004726. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004726/

[4] Melrose S. Seasonal Affective Disorder: An Overview of Assessment and Treatment Approaches. Depress Res Treat 2015 178564. doi: 10.1155/2015/178564. Epub 2015 Nov 25. PMID: 26688752; PMCID: PMC4673349. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673349/

[5] Is a Vitamin D Deficiency Causing Your Depression? Retrieved 10 November 2022 from https://www.healthline.com/nutrition/depression-and-vitamin-d

[6] Sher L. Genetic studies of seasonal affective disorder and seasonality. Compr Psychiatry. 2001 42(2):105-10. doi: 10.1053/comp.2001.21217. PMID: 11244145. https://pubmed.ncbi.nlm.nih.gov/11244145/

[7] Sher L. Genetics of seasonal affective disorder. The Lancet 2002 359:893-894. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(02)07937-0/fulltext

[8] Madden PA et al. Seasonal changes in mood and behavior. The role of genetic factors. Arch Gen Psychiatry 1996 53(1):47-55. doi: 10.1001/archpsyc.1996.01830010049008. PMID: 8540777 https://pubmed.ncbi.nlm.nih.gov/8540777/

[9] Sher L et al. The role of genetic factors in the etiology of seasonal affective disorder and seasonality. J Affect Disord 1999 53(3):203-10. doi: 10.1016/s0165-0327(98)00194-3. PMID: 10404705. https://pubmed.ncbi.nlm.nih.gov/10404705/

[10] Rosenthal NE et al. Role of serotonin transporter promoter repeat length polymorphism (5-HTTLPR) in seasonality and seasonal affective disorder. Mol Psychiatry 1998 3(2):175-7. doi: 10.1038/sj.mp.4000360. PMID: 9577843. https://pubmed.ncbi.nlm.nih.gov/9577843/

[11] Johansson C et al. The serotonin transporter promoter repeat length polymorphism, seasonal affective disorder and seasonality. Psychol Med 2003 33(5):785-92. doi: 10.1017/s0033291703007372. PMID: 12877393. https://pubmed.ncbi.nlm.nih.gov/12877393/

[12] Willeit M et al. A polymorphism (5-HTTLPR) in the serotonin transporter promoter gene is associated with DSM-IV depression subtypes in seasonal affective disorder. Mol Psychiatry 2003 8(11):942-6. doi: 10.1038/sj.mp.4001392. PMID: 14593433. https://pubmed.ncbi.nlm.nih.gov/14593433/

[13] Enoch MA et al. Association between seasonal affective disorder and the 5-HT2A promoter polymorphism, -1438G/A. Mol Psychiatry 1999 4(1):89-92. doi: 10.1038/sj.mp.4000439. PMID: 10089016. https://pubmed.ncbi.nlm.nih.gov/10089016/

[14] Garbazza C, Benedetti F. Genetic Factors Affecting Seasonality, Mood, and the Circadian Clock. Front Endocrinol (Lausanne) 2018 9:481. doi: 10.3389/fendo.2018.00481. PMID: 30190706; PMCID: PMC6115502. https://www.frontiersin.org/articles/10.3389/fendo.2018.00481/full

[15] Johansson C et al. Circadian clock-related polymorphisms in seasonal affective disorder and their relevance to diurnal preference. Neuropsychopharmacology 2003 28(4):734-9. doi: 10.1038/sj.npp.1300121. Epub 2002 Dec 3. PMID: 12655319. https://www.nature.com/articles/1300121

[16] Partonen T et al. Three circadian clock genes Per2, Arntl, and Npas2 contribute to winter depression. Ann Med 2007 39(3):229-38. doi: 10.1080/07853890701278795. Erratum in: Ann Med. 2010 Oct;42(7):555. PMID: 17457720. https://www.tandfonline.com/doi/full/10.1080/07853890701278795

[17] Kim HI et al. Association of CLOCK, ARNTL, and NPAS2 gene polymorphisms and seasonal variations in mood and behavior. Chronobiol Int 2015 32(6):785-91. doi: 10.3109/07420528.2015.1049613. Epub 2015 Jul 2. PMID: 26134245. https://www.tandfonline.com/doi/abs/10.3109/07420528.2015.1049613?journalCode=icbi20

[18] Zhang L et al. A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait. Proc Natl Acad Sci U S A. 2016 113(11):E1536-44. doi: 10.1073/pnas.1600039113. Epub 2016 Feb 22. PMID: 26903630; PMCID: PMC4801303. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801303/

[19] Ho KWD et al. Genome-wide association study of seasonal affective disorder. Transl Psychiatry. 2018 8(1):190. doi: 10.1038/s41398-018-0246-z. PMID: 30217971; PMCID: PMC6138666. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138666/

[20] Srinivasan V, Smits M, Spence W, Lowe AD, Kayumov L, Pandi-Perumal SR, Parry B, Cardinali DP. Melatonin in mood disorders. World J Biol Psychiatry. 2006 7(3):138-51. doi: 10.1080/15622970600571822. PMID: 16861139. https://pubmed.ncbi.nlm.nih.gov/16861139/

[21] Wehr TA et al. A circadian signal of change of season in patients with seasonal affective disorder. Arch Gen Psychiatry 2001 58(12):1108-14. doi: 10.1001/archpsyc.58.12.1108. PMID: 11735838. https://pubmed.ncbi.nlm.nih.gov/11735838/

[22] Roecklein KA et al. A missense variant (P10L) of the melanopsin (OPN4) gene in seasonal affective disorder. J Affect Disord 2009 114(1-3):279-85. doi: 10.1016/j.jad.2008.08.005. Epub 2008 Sep 18. PMID: 18804284; PMCID: PMC2647333. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647333/

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