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Seasonal Affective Disorder and HPA axis function: A Systematic Review.

BRUNO AGUSTINI1*, Maria Bocharova1, Allan Young1 and Mario F. Juruena1
  • 1 King's College London, Centre for Affective Disorders/Dept of Psychological Medicine, United Kingdom

Background: Life on earth is dictated by constant, yet predictable, changes in environment, a consequence of earth’s movements and the seasons that derive from it. For virtually all animals, the environment will vary markedly according to these changes. Different seasons require special strategies and different behavioural, energetic, metabolic and immunological priorities. These changes are clearly demonstrated in animal models, but there is still insufficient data to characterize robust seasonal changes in humans. One condition, Seasonal Affective Disorder (SAD), may provide the best example, in an extreme form, of this variability. SAD is known as a form of depression that usually occurs in the winter, and is typically characterized by atypical symptoms, with fatigue, hyperphagia, craving for carbohydrate-rich foods and weight gain observed in these depressive episodes, frequently preceding the functional impairments seen afterwards. Based on the energy-conserving nature of these core symptoms of SAD, various evolutionary theories have been proposed, suggesting a shift in metabolic strategies. Nevertheless, the etiology and pathophysiology of the condition remains unclear. So far, evidence points to external, environmental factors, especially related to perceived day light and day length and/or internal, molecular and genetic clocks with chronobiological functions. Another common finding related to SAD are disturbances in serotonin genes, production and transportation. All these different pathways will, ultimately, have some of their actions via bidirectional inputs in the hypothalamus. So, it seems logical that we may find alterations in hypothalamic outputs in this condition, especially in the Hypothalamic-Pituitary-Adrenal (HPA) axis. Although anecdotal reports characterize SAD as a hypocortisolemic condition (together with Chronic Fatigue Syndrome and Depression with atypical features), there are no systematic reviews on SAD and HPA axis function. This review intends to summarize these findings and improve our understanding of this highly prevalent, often predictable, yet little understood, mood disorder. Methods: Using the PRISMA (2009) guideline recommendations and the PRISMA NMA checklist (2015), we searched for relevant articles indexed in databases including MEDLINE, EMBASE, PsycINFO, and PsychArticles, using the Ovid platform. The following keywords were used: "Seasonal affective disorder", OR "Winter Depression", OR "Seasonal depression" associated with: “HPA Axis” OR “cortisol” OR “atypical depression” OR “melancholic depression”. We included full text articles, in humans, written in English language, with no temporal limits. Animal studies and review articles were excluded. Results: A total of 151 articles were found. After thorough screening and selection, a total of 14 articles were included in the qualitative analysis. We divided these studies in 4 groups: 1) Baseline and variation: Just one study (2011) measured baseline cortisol levels in saliva, and found that the cortisol awakening response was lower in patients with SAD compared with healthy controls. Diurnal variation was the same between groups; 2) Studies with Dexamethasone suppression test (DST) (n=2): these showed conflicting results, with one study finding normal DST, while other, comparing with Schizophrenic patients, found lower baseline cortisol levels and less suppression after DST, in winter, for SAD patients; 3) Studies using Serotonin agonists (n=6): these also showed discrepant results, with 4 of the studies finding no significant difference between SAD patients and controls, and 2 studies indicating lower cortisol levels in SAD patients after challenge with 5HT agonists; 4) Studies with light therapy (n=5): showed normal baseline cortisol levels for patients with SAD compared to healthy controls. One of this studies found delayed circadian rhythm in patients with SAD in the winter, and that light therapy advances these rhythms in SAD patients, bringing them closer to healthy controls; another study found that "natural light” (walk in the street) was more effective, and reduced salivary cortisol, compared to patients undergoing artificial light treatment (this study has the obvious confounder of physical activity). Conclusion: There is some evidence for lower basal cortisol levels in patients with SAD, and symptomatic improvement (with light therapy or serotonin agonists) may be correlated with alterations in HPA axis function, but this is far from consolidated. All the studies were conducted with heterogeneous populations and methods, leading to discrepant results. The common association of SAD and low cortisol levels still needs to be confirmed by larger samples and more homogeneous methods. The use of salivary cortisol, present in only 2 studies, can help in that task, providing a non-invasive and reliable procedure to monitor these subjects. No study tried to correlate cortisol levels with specific vegetative symptoms, what may also lead to more robust results. Another interesting finding is that the number of studies with SAD tended to decrease with time (which partially explains the small use of salivary cortisol as measure). This might be explained by controversies around its diagnostic validity. If we look beyond diagnostic criteria, with its inherent limitations and artificial boundaries (if it is a separate condition, a type of bipolar disorder or even a type of depression), SAD appears to be an important window of opportunity to understand the intrinsic connection of mood disorders and circadian rhythms. We suggest that more studies, temporally synchronized and homogeneously designed, with more modern and available techniques, may provide key insights to our understanding of mood disorders and circadian rhythms as a whole, being of the utmost importance.

References

1. Oginska H, Oginska-Bruchal K. Chronotype and personality factors of predisposition to seasonal affective disorder. Chronobiol Int [Internet]. 2014;31(4):523–31. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24397301
2. McClung CA, Kasof J, Leppämäki S, Partonen T, Vakkuri O, Lönnqvist J, et al. Circadian profiles of cortisol, prolactin, and thyrotropin in seasonal affective disorder. Psychoneuroendocrinology [Internet]. Elsevier Ltd; 2000 [cited 2016 Nov 13];37(3):87–91.
3. James SP, Wehr TA, Sack DA, Parry BL, Rogers S, Rosenthal NE. The dexamethasone suppression test in seasonal affective disorder. Compr Psychiatry. 1986;27(3):224–6.
4. Lam RW, Levitan RD. Pathophysiology of seasonal affective disorder: A review. J Psychiatry Neurosci. 2000;25(5):469–80.
5. Wirz-Justice A, Graw P, Kräuchi K, Sarrafzadeh A, English J, Arendt J, et al. “Natural” light treatment of seasonal affective disorder. J Affect Disord. 1996;37(2–3):109–20.
6. Radua J, Pertusa A, Cardoner N. Climatic relationships with specific clinical subtypes of depression. Psychiatry Res [Internet]. Elsevier Ireland Ltd; 2010;175(3):217–20. Available from: http://dx.doi.org/10.1016/j.psychres.2008.10.025
7. Nawab SS, Miller CS, Dale JK, Greenberg BD, Friedman TC, Chrousos GP, et al. Self-reported sensitivity to chemical exposures in five clinical populations and healthy controls. Psychiatry Res. 2000;95(1):67–74.
8. Leppämäki S, Partonen T, Vakkuri O, Lönnqvist J, Partinen M, Laudon M. Effect of controlled-release melatonin on sleep quality, mood, and quality of life in subjects with seasonal or weather-associated changes in mood and behaviour. Eur Neuropsychopharmacol. 2003;13(3):137–45.
9. Joseph-Vanderpool JR, Rosenthal NE, Chrousos GP, Wehr TA, Skwerer R, Kasper S, et al. Abnormal pituitary-adrenal responses to corticotropin-releasing hormone in patients with seasonal affective disorder: clinical and pathophysiological implications. J Clin Endocrinol Metab [Internet]. 1991;72(6):1382–7.
10. Thorn L, Hucklebridge F, Evans P, Clow A. The cortisol awakening response, seasonality, stress and arousal: A study of trait and state influences. Psychoneuroendocrinology. 2009;34(3):299–306.
11. Sher L, Oquendo MA, Galfalvy HC, Zalsman G, Cooper TB, Mann JJ. Higher cortisol levels in spring and fall in patients with major depression. Prog Neuro-Psychopharmacology Biol Psychiatry. 2005;29(4):529–34.
12. Avery DH, Dahl K, Savage M V., Brengelmann GL, Larsen LH, Kenny MA, et al. Circadian temperature and cortisol rhythms during a constant routine are phase-delayed in hypersomnic winter depression. Biol Psychiatry. 1997;41(11):1109–23.
13. Roecklein KA, Wong PM, Miller MA, Donofry SD, Kamarck ML, Brainard GC. Melanopsin, photosensitive ganglion cells, and seasonal affective disorder. Neurosci Biobehav Rev [Internet]. Elsevier Ltd; 2013;37(3):229–39. Available from: http://dx.doi.org/10.1016/j.neubiorev.2012.12.009
14. Jackson PR, Pr J, Ej W, Le R, Jönsson B. Genetics of seasonal affective disorder. The Lancet Publishing Group . 2002;359:2001–2.
15. Thorn L, Evans P, Cannon A, Hucklebridge F, Evans P, Clow A. Seasonal differences in the diurnal pattern of cortisol secretion in healthy participants and those with self-assessed seasonal affective disorder. Psychoneuroendocrinology. 2011;36(6):816–23.
16. McClung CA. Mind your rhythms: An important role for circadian genes in neuroprotection. J Clin Invest. 2013;123(12):4994–6.
17. Kasof J. Cultural variation in seasonal depression: Cross-national differences in winter versus summer patterns of seasonal affective disorder. J Affect Disord [Internet]. Elsevier B.V.; 2009;115(1–2):79–86. Available from: http://dx.doi.org/10.1016/j.jad.2008.09.004
18. Oren DA, Levendosky AA, Kasper S, Duncan CC, Rosenthal NE. Circadian profiles of cortisol, prolactin, and thyrotropin in seasonal affective disorder. Biol Psychiatry. 1996;39(3):157–70.

Keywords: Seasonal Affective Disorder, HPA axis, cortisol, winter depression, Seasonal variation

Conference: ISAD LONDON 2017: Perspectives on Mood and Anxiety Disorders: Looking to the future, London, United Kingdom, 6 Jul - 7 Jul, 2017.

Presentation Type: Poster

Topic: Other (specify):

Citation: AGUSTINI B, Bocharova M, Young A and Juruena MF (2019). Seasonal Affective Disorder and HPA axis function: A Systematic Review.. Front. Psychiatry. Conference Abstract: ISAD LONDON 2017: Perspectives on Mood and Anxiety Disorders: Looking to the future. doi: 10.3389/conf.fpsyt.2017.48.00036

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Received: 26 May 2017; Published Online: 25 Jan 2019.

* Correspondence: Dr. BRUNO AGUSTINI, King's College London, Centre for Affective Disorders/Dept of Psychological Medicine, London, SE5 8AF, United Kingdom, brunoagustini23@gmail.com