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Update on the Biology of Seasonal Affective Disorder

Published online by Cambridge University Press:  07 November 2014

Chang-Ho Sohn  and
Raymond W. Lam
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Abstract

The etiology and pathophysiology of seasonal affective disorder (SAD) has been linked to the seasons and to light since its first conceptualization. Aspects of SAD that make it particularly amenable to biological investigation include the predictable recurrent episodes, the rapid response to a nonpharmacologic treatment, the specific neurovegetative features, and the availability of rich animal models of seasonality. This paper reviews new findings for the major biological hypotheses for SAD, focusing on circadian rhythms, neurotransmitters, and molecular genetics. Integrative issues and future directions for the study of SAD, including the heuristic value of a dualvulnerability hypothesis that conceptualizes seasonality as a dimensional construct and the importance of studying endophenotypes, will be discussed.

Type
Review Article
Information
CNS Spectrums , Volume 10 , Issue 8 , August 2005 , pp. 635 - 646
Copyright
Copyright © Cambridge University Press 2005

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References

REFERENCES

1.Kasper, S, Wehr, TA, Bartko, JJ, Gaist, PA, Rosenthal, NE. Epidemiological findings of seasonal changes in mood and behavior. A telephone survey of Montgomery County, Maryland. Arch Gen Psychiatry. 1989;46:823–833.Google Scholar
2.Rosenthal, NE, Sack, DA, Gillin, JC, et al.Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy. Arch Gen Psychiatry. 1984;41:72–80.Google Scholar
3.Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.Google Scholar
4.Blazer, DG, Kessler, RC, Swartz, MS. Epidemiology of recurrent major and minor depression with a seasonal pattern. The National Comorbidity Survey. Br J Psychiatry. 1998;172:164–167.CrossRefGoogle ScholarPubMed
5.Levitt, AJ, Boyle, MH, Joffe, RT, Baumal, Z. Estimated prevalence of the seasonal subtype of major depression in a Canadian community sample. Can J Psychiatry. 2000;45:650–654.Google Scholar
6.Magnusson, A. An overview of epidemiological studies on seasonal affective disorder. Acta Psychiatr Scand. 2000;101:176–184.CrossRefGoogle ScholarPubMed
7.Rosenthal, NE, Genhart, M, Jacobsen, FM, Skwerer, RG, Wehr, TA. Disturbances of appetite and weight regulation in seasonal affective disorder. Ann N Y Acad Sci. 1987;499:216–230.Google Scholar
8.Lam, RW, Levitan, RD. Pathophysiology of seasonal affective disorder: a review. J Psychiatry Neurosci. 2000;25:469–480.Google ScholarPubMed
9.Schwartz, PJ, Rosenthal, NE, Kajimura, N, et al.Ultradian oscillations in cranial thermoregulation and electroencephalographic slow-wave activity during sleep are abnormal in humans with annual winter depression. Brain Res. 2000;866:152–167.Google Scholar
10.Schwartz, PJ, Rosenthal, NE, Wehr, TA. Band-specific electroencephalogram and brain cooling abnormalities during NREM sleep in patients with winter depression. Biol Psychiatry. 2001;50:627–632.Google Scholar
11.Levitt, AJ, Boyle, MH. The impact of latitude on the prevalence of seasonal depression. Can J Psychiatry. 2002;47:361–367.Google Scholar
12.Michalak, EE, Lam, RW. Seasonal affective disorder: the latitude hypothesis revisited. Can J Psychiatry. 2002;47:787–788.Google Scholar
13.Wehr, TA. Photoperiodism in humans and other primates: evidence and implications. J Biol Rhythms. 2001;16:348–364.Google Scholar
14.Wehr, TA, Duncan, WC Jr, Sher, L, et al.A circadian signal of change of season in patients with seasonal affective disorder. Arch Gen Psychiatry. 2001;58:1108–1114.Google Scholar
15.Oren, DA, Moul, DE, Schwartz, PJ, Brown, C, Yamada, EM, Rosenthal, NE. Exposure to ambient light in patients with winter seasonal affective disorder. Am J Psychiatry. 1994;151:591–593.Google Scholar
16.Graw, P, Recker, S, Sand, L, Krauchi, K, Wirz-Justice, A. Winter and summer outdoor light exposure in women with and without seasonal affective disorder. J Affect Disord. 1999;56:163–169.Google Scholar
17.Terman, JS, Terman, M. Photopic and scotopic light detection in patients with seasonal affective disorder and control subjects. Biol Psychiatry. 1999;46:1642–1648.Google Scholar
18.Szabo, Z, Antal, A, Tokaji, Z, et al.Light therapy increases visual contrast sensitivity in seasonal affective disorder. Psychiatry Res. 2004;126:15–21.CrossRefGoogle ScholarPubMed
19.Hebert, M, Beattie, CW, Tam, EM, Yatham, LN, Lam, RW. Electroretinography in patients with winter seasonal affective disorder. Psychiatry Res. 2004;127:27–34.CrossRefGoogle ScholarPubMed
20.Lee, TM, Blashko, CA, Janzen, HL, Paterson, JG, Chan, CC. Pathophysiological mechanism of seasonal affective disorder. J Affect Disord. 1997;46:25–38.CrossRefGoogle ScholarPubMed
21.Terman, M, Terman, JS, Quitkin, FM, McGrath, PJ, Stewart, JW, Rafferty, B. Light therapy for seasonal affective disorder. A review of efficacy. Neuropsychopharmacology. 1989;2:1–22.Google Scholar
22.Thompson, C. Evidence-based treatment. In: Partonen, T, Magnusson, A, eds. Seasonal Affective Disorder. Practice and Research. London, England: Oxford University Press; 2001;151–158.Google Scholar
23.Gaynes, BN, Ekstrom, D, Hamer, RM, et al.The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence. Am J Psychiatry. 2005;162:656–662.Google Scholar
24.Lewy, AJ, Sack, RL, Miller, LS, Hoban, TM. Antidepressant and circadian phaseshifting effects of light. Science. 1987;235:352–354.Google Scholar
25.Checkley, SA, Murphy, DG, Abbas, M, et al.Melatonin rhythms in seasonal affective disorder. Br J Psychiatry. 1993;163:332–337.Google Scholar
26.Eastman, CI, Gallo, LC, Lahmeyer, HW, Fogg LE The circadian rhythm of temperature during light treatment for winter depression. Biol Psychiatry. 1993;34:210–220.Google Scholar
27.Oren, DA, Levendosky, AA, Kasper, S, Duncan, CC, Rosenthal, NE. Circadian profiles of cortisol, prolactin, and thyrotropin in seasonal affective disorder. Biol Psychiatry. 1996;39:157–170.CrossRefGoogle ScholarPubMed
28.Lewy, AJ. The dim light melatonin onset, melatonin assays and biological rhythm research in humans. Biol Signals Recept. 1999;8:79–83.CrossRefGoogle ScholarPubMed
29.Lewy, AJ, Bauer, VK, Cutler, NL, Sack, RL, Ahmed, S, Thomas, KH, Blood, ML, Jackson, JM. Morning vs evening light treatment of patients with winter depression. Arch Gen Psychiatry. 1998;55:890–896.CrossRefGoogle ScholarPubMed
30.Dahl, K, Avery, DH, Lewy, AJ, et al.Dim light melatonin onset and circadian temperature during a constant routine in hypersomnic winter depression. Acta Psychiatr Scand. 1993;88:60–66.Google Scholar
31.Lewy, AJ, Sack, RL, Singer, CM, White, DM, Hoban, TM. Winter depression and the phase-shift hypothesis for bright light's therapeutic effects: history, theory, and experimental evidence. J Biol Rhythms. 1988;3:121–134.CrossRefGoogle ScholarPubMed
32.Avery, DH, Dahl, K, Savage, MV, et al.Circadian temperature and cortisol rhythms during a constant routine are phase-delayed in hypersomnic winter depression. Biol Psychiatry. 1997;41:1109–1123.Google Scholar
33.Wirz-Justice, A, Krauchi, K, Brunner, DP, et al.Circadian rhythms and sleep regulation in seasonal affective disorder. Acta Neuropsychiatrica. 1995;7:41–43.Google Scholar
34.Koorengevel, KM, Beersma, DG, den Boer, JA, Van den Hoofdakker, RH. A forced desynchrony study of circadian pacemaker characteristics in seasonal affective disorder. J Biol Rhythms. 2002;17:463–475.Google Scholar
35.Koorengevel, KM, Beersma, DG, den Boer, JA, Van den Hoofdakker, RH. Mood regulation in seasonal affective disorder patients and healthy controls studied in forced desynchrony. Psychiatry Res. 2003;117:57–74.Google Scholar
36.Koorengevel, KM, Beersma, DG, Gordijn, MC, den Boer, JA, Van den Hoofdakker, RH. Body temperature and mood variations during forced desynchronization in winter depression: a preliminary report. Biol Psychiatry. 2000;47:355–358.Google Scholar
37.Wirz-Justice, A, Graw, P, Krauchi, K, et al.Light therapy in seasonal affective disorder is independent of time of day or circadian phase. Arch Gen Psychiatry. 1993;50:929–937.CrossRefGoogle ScholarPubMed
38.Rosenthal, NE, Levendosky, AA, Skwerer, RG, et al.Effects of light treatment on core body temperature in seasonal affective disorder. Biol Psychiatry. 1990;27:39–50.Google Scholar
39.Terman, JS, Terman, M, Lo, ES, Cooper, TB. Circadian time of morning light administration and therapeutic response in winter depression. Arch Gen Psychiatry. 2001; 58:69–75.Google Scholar
40.Burgess, HJ, Fogg, LF, Young, MA, Eastman, CI. Bright light therapy for winter depression—is phase advancing beneficial? Chronobiol Int. 2004;21:759–775.Google Scholar
41.Lewy, AJ, Bauer, VK, Cutler, NL, Sack, RL. Melatonin treatment of winter depression: a pilot study. Psychiatry Res. 1998;77:57–61.CrossRefGoogle ScholarPubMed
42.Lewy, AJ, Lefler, BJ, Hasler, BP, Bauer, VK, Bernert, RA, Emens, JS. Plasma DLMO10 Zeitgeber time 14: The therapeutic window for phase-delayed winter depressives treated with melatonin. Chronobiol Int. 2003;20:1215–1216.Google Scholar
43.Lambert, GW, Reid, C, Kaye, DM, Jennings, GL, Esler, MD. Effect of sunlight and season on serotonin turnover in the brain. Lancet. 2002;360:1840–1842.Google Scholar
44.Neumeister, A, Pirker, W, Willeit, M, et al.Seasonal variation of availability of serotonin transporter binding sites in healthy female subjects as measured by [1231]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and single photon emission computed tomography. Biol Psychiatry. 2000;47:158–160.CrossRefGoogle ScholarPubMed
45.Neumeister, A, Konstantinidis, A, Praschak-Rieder, N, et al.Monoaminergic function in the pathogenesis of seasonal affective disorder. Int J Neuropsychopharmacol. 2001;4:409–420.Google Scholar
46.Booij, L, Van der Does, AJ, Riedel, WJ. Monoamine depletion in psychiatric and healthy populations: review. Mol Psychiatry. 2003;8:951–973.Google Scholar
47.Young, SN, Smith, SE, Pihl, RO, Ervin, FR. Tryptophan depletion causes a rapid lowering of mood in normal males. Psychopharmacology. 1985;87:173–177.CrossRefGoogle ScholarPubMed
48.Nishizawa, S, Benkelfat, C, Young, SN, et al.Differences between males and females in rates of serotonin synthesis in human brain. Proc Natl Acad Sci U S A. 1997;94:5308–5313.Google Scholar
49.Neumeister, A. Tryptophan depletion, serotonin, and depression: where do we stand? Psychopharmacol Bull. 2003; 37:99–115.Google Scholar
50.Booij, L, Van der Does, W, Benkelfat, C, et al.Predictors of mood response to acute tryptophan depletion. A reanalysis. Neuropsychopharmacology. 2002;27:852–861.Google Scholar
51.Neumeister, A, Praschak-Rieder, N, Hesselmann, B, et al.Rapid tryptophan depletion in drug-free depressed patients with seasonal affective disorder. Am J Psychiatry. 1997;154:1153–1155.Google Scholar
52.Lam, RW, Zis, AP, Grewal, A, Delgado, PL, Charney, DS, Krystal, JH. Effects of rapid tryptophan depletion in patients with seasonal affective disorder in remission after light therapy. Arch Gen Psychiatry. 1996;53:41–44.CrossRefGoogle ScholarPubMed
53.Neumeister, A, Praschak-Rieder, N, Besselmann, B, Rao, ML, Gluck, J, Kasper, S. Effects of tryptophan depletion on drug-free patients with seasonal affective disorder during a stable response to bright light therapy. Arch Gen Psychiatry. 1997;54:133–138.CrossRefGoogle ScholarPubMed
54.Neumeister, A, Turner, EH, Matthews, JR, et al.Effects of tryptophan depletion vs catecholamine depletion in patients with seasonal affective disorder in remission with light therapy. Arch Gen Psychiatry. 1998;55:524–530.Google Scholar
55.Neumeister, A, Praschak-Rieder, N, Hesselmann, B, Vitouch, O, Rauh, M, Barocka, A, Kasper, S. Effects of tryptophan depletion in fully remitted patients with seasonal affective disorder during summer. Psychol Med. 1998;28:257–264.Google Scholar
56.Leyton, M, Ghadirian, AM, Young, SN, et al.Depressive relapse following acute tryptophan depletion in patients with major depressive disorder. J Psychopharmacol. 2000;14:284–287.CrossRefGoogle ScholarPubMed
57.Lam, RW, Bowering, TA, Tam, EM, et al.Effects of rapid tryptophan depletion in patients with seasonal affective disorder in natural summer remission. Psychol Med. 2000;30:79–87.CrossRefGoogle ScholarPubMed
58.Neumeister, A, Habeler, A, Praschak-Rieder, N, Willeit, M, Kasper, S. Tryptophan depletion: a predictor of future depressive episodes in seasonal affective disorder? Int Clin Psychopharmacol. 1999;14:313–315.CrossRefGoogle ScholarPubMed
59.Bremner, JD, Vythilingam, M, Ng, CK, et al.Regional brain metabolic correlates of alpha-methylparatyrosine-induced depressive symptoms: implications for the neural circuitry of depression. JAMA. 2003;289:3125–3134.Google Scholar
60.Berman, RM, Narasimhan, M, Miller, HL, et al.Transient depressive relapse induced by catecholamine depletion: potential phenotypic vulnerability marker? Arch Gen Psychiatry. 1999;56:395–403.Google Scholar
61.Lam, RW, Tam, EM, Grewal, A, Yatham, LN. Effects of alpha-methyl-paratyrosine-induced catecholamine depletion in patients with seasonal affective disorder in summer remission. Neuropsychopharmacology. 2001;25(5 suppl):S97–S101.CrossRefGoogle Scholar
62.Hilger, E, Willeit, M, Praschak-Rieder, N, Stastny, J, Neumeister, A, Kasper, S. Reboxetine in seasonal affective disorder: an open trial. Eur Neuropsychopharmacol. 2001;11:1–5.CrossRefGoogle ScholarPubMed
63.Dilsaver, SC, Qamar, AB, Del Medico, VJ. The efficacy of bupropion in winter depression: results of an open trial. J Clin Psychiatry. 1992;53:252–255.Google Scholar
64.Neumeister, A, Willeit, M, Praschak-Rieder, N, et al.Dopamine transporter availability in symptomatic depressed patients with seasonal affective disorder and healthy controls. Psychol Med. 2001;31:1467–1473.Google Scholar
65.Willeit, M, Praschak-Rieder, N, Neumeister, A, et al.[1231]-beta-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder. Biol Psychiatry. 2000;47:482–489.Google Scholar
66.Allen, JM, Lam, RW, Remick, RA, Sadovnick, AD. Depressive symptoms and family history in seasonal and nonseasonal mood disorders. Am J Psychiatry. 1993;150:443–448.Google Scholar
67.Wirz-Justice, A, Bucheli, C, Graw, P, Kielholz, P, Fisch, HU, Woggon, B. Light treatment of seasonal affective disorder in Switzerland. Acta Psychiatr Scand. 1986;74:193–204.CrossRefGoogle ScholarPubMed
68.Lam, RW, Buchanan, A, Remick, RA. Seasonal affective disorder—a Canadian sample. Ann Clin Psychiatry. 1989;1:241–245.Google Scholar
69.White, DM, Lewy, AJ, Sack, RL, Blood, ML, Wesche, DL. Is winter depression a bipolar disorder? Compr Psychiatry. 1990;31:196–204.Google Scholar
70.Thompson, C, Isaacs, G. Seasonal affective disorder—a British sample. Symptomatology in reference to mode of referral and diagnostic subtype. J Affect Disord. 1988;14:1–11.Google Scholar
71.Sher, L, Goldman, D, Ozaki, N, Rosenthal, NE. The role of genetic factors in the etiology of seasonal affective disorder and seasonality. J Affect Disord. 1999;53:203–210.Google Scholar
72.Stamenkovic, M, Aschauer, HN, Riederer, F, et al.Study of family history in seasonal affective disorder. Neuropsychobiology. 2001; 44:65–69.Google Scholar
73.Madden, PA, Heath, AC, Rosenthal, NE, Martin, NG. Seasonal changes in mood and behavior. The role of genetic factors. Arch Gen Psychiatry. 1996; 53:47–55.Google Scholar
74.Jang, KL, Lam, RW, Livesley, WJ, Vernon, PA. Gender differences in the heritability of seasonal mood change. Psychiatry Res. 1997;70:145–154.Google Scholar
75.Rosenthal, NE, Carpenter, CJ, James, SP, Parry, BL, Rogers, SL, Wehr, TA. Seasonal affective disorder in children and adolescents. Am J Psychiatry. 1986;143:356–358.Google Scholar
76.Sasaki, T, Sakamoto, K, Akaho, R, Nakajima, T, Takahashi, K. Familial transmission of seasonal changes in sleep and eating function in the general population. Psychiatry Res. 1998;81:211–217.Google Scholar
77.Rosenthal, NE, Mazzanti, CM, Barnett, RL, et al.Role of serotonin transporter promoter repeat length polymorphism (5-HTTLPR) in seasonality and seasonal affective disorder. Mol Psychiatry. 1998;3:175–177.Google Scholar
78.Sher, L, Hardin, TA, Greenberg, BD, Murphy, DL, Li, Q, Rosenthal, NE. Seasonality associated with the serotonin transporter promoter repeat length polymorphism [letter]. Am J Psychiatry. 1999; 156:1837.Google Scholar
79.Johansson, C, Smedh, C, Partonen, T, et al.Seasonal affective disorder and serotonin-related polymorphisms. Neurobiol Dis. 2001;8:351–357.Google Scholar
80.Willeit, M, Praschak-Rieder, N, Neumeister, A, 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;8:942–946.Google Scholar
81.Johansson, C, Willeit, M, Levitan, R, et al.The serotonin transporter promoter repeat length polymorphism, seasonal affective disorder and seasonality. Psychol Med. 2003;33:785–792.Google Scholar
82.Arias, B, Gutierrez, B, Pintor, L, Gasto, C, Fananas, L. Variability in the 5-HT(2A) receptor gene is associated with seasonal pattern in major depression. Mol Psychiatry. 2001;6:239–242.Google Scholar
83.Enoch, MA, Goldman, D, Barnett, R, Sher, L, Mazzanti, CM, Rosenthal, NE. Association between seasonal affective disorder and the 5-HT2A promoter polymorphism, -1438G/A. Mol Psychiatry. 1999; 4:89–92.Google Scholar
84.Levitan, RD, Masellis, M, Basile, VS, et al.Polymorphism of the serotonin-2A receptor gene (HTR2A) associated with childhood attention deficit hyperactivity disorder (ADHD) in adult women with seasonal affective disorder. J Affect Disord. 2002;71:229–233.Google Scholar
85.Ozaki, N, Rosenthal, NE, Pesonen, U, et al.Two naturally occurring amino acid substitutions of the 5-HT2A receptor: similar prevalence in patients with seasonal affective disorder and controls. Biol Psychiatry. 1996;40:1267–1272.CrossRefGoogle ScholarPubMed
86.Hasler, G, Drevets, WC, Manji, HK, Charney, DS. Discovering endophenotypes for major depression. Neuropsychopharmacology. 2004;29:1765–1781.CrossRefGoogle ScholarPubMed
87.Praschak-Rieder, N, Willeit, M, Winkler, D, et al.Role of family history and 5-HTTLPR polymorphism in female seasonal affective disorder patients with and without premenstrual dysphoric disorder. Eur Neuropsychopharmacol. 2002;12:129–134.Google Scholar
88.Thierry, N, Willeit, M, Praschak-Rieder, N, et al.Serotonin transporter promoter gene polymorphic region (5-HTTLPR) and personality in female patients with seasonal affective disorder and in healthy controls. Eur Neuropsychopharmacol. 2004;14:53–58.Google Scholar
89.Levitan, RD, Masellis, M, Lam, RW, et al.Childhood inattention and dysphoria and adult obesity associated with the dopamine D4 receptor gene in overeating women with seasonal affective disorder. Neuropsychopharmacology. 2004;29:179–186.CrossRefGoogle ScholarPubMed
90.Levitan, RD, Masellis, M, Basile, VS, et al.The dopamine-4 receptor gene associated with binge eating and weight gain in women with seasonal affective disorder: an evolutionary perspective. Biol Psychiatry. 2004;56:665–669.Google Scholar
91.Gould, TD, Manji, HK. Signaling networks in the pathophysiology and treatment of mood disorders. J Psychosom Res. 2002;53:687–697.Google Scholar
92.Avissar, S, Schreiber, G, Nechamkin, Y, et al.The effects of seasons and light therapy on G protein levels in mononuclear leukocytes of patients with seasonal affective disorder. Arch Gen Psychiatry. 1999;56:178–183.Google Scholar
93.Siffert, W, Rosskopf, D, Siffert, G, et al.Association of a human G-protein beta3 subunit variant with hypertension. Nat Genet. 1998;18:45–48.Google Scholar
94.Zill, P, Baghai, TC, Zwanzger, P, et al.Evidence for an association between a G-protein beta3-gene variant with depression and response to antidepressant treatment. Neuroreport. 2000;11:1893–1897.Google Scholar
95.Willeit, M, Praschak-Rieder, N, Zill, P, Neumeister, A, Ackenheil, M, Kasper, S, Bondy, B. C825T polymorphism in the G protein beta3-subunit gene is associated with seasonal affective disorder. Biol Psychiatry. 2003; 54:682–686.Google Scholar
96.Johansson, C, Willeit, M, Aron, L, et al.Seasonal affective disorder and the G-protein beta-3-subunit C825T polymorphism. Biol Psychiatry. 2004;55:317–319.Google Scholar
97.Zheng, B, Albrecht, U, Kaasik, K, et al.Nonredundant roles of the mPer1 and mPer2 genes in the mammalian circadian clock. Cell. 2001;105:683–694.Google Scholar
98.Steinlechner, S, Jacobmeier, B, Scherbarth, F, Dernbach, H, Kruse, F, Albrecht, U. Robust circadian rhythmicity of Per1 and Per2 mutant mice in constant light, and dynamics of Perl and Per2 gene expression under long and short photoperiods. J Biol Rhythms. 2002;17:202–209.Google Scholar
99.King, DP, Zhao, Y, Sangoram, AM, et al.Positional cloning of the mouse circadian clock gene. Cell. 1997;89:641–653.Google Scholar
100.Johansson, C, Willeit, M, Smedh, C, et al.Circadian clock-related polymorphisms in seasonal affective disorder and their relevance to diurnal preference. Neuropsychopharmacology. 2003;28:734–739.Google Scholar
101.Young, MA, Watel, LG, Lahmeyer, HW, Eastman, CI. The temporal onset of individual symptoms in winter depression: differentiating underlying mechanisms. J Affect Disord. 1991;22:191–197.Google Scholar
102.Lam, RW, Tam, EM, Yatham, LN, Shiah, IS, Zis, AP. Seasonal depression: the dual vulnerability hypothesis revisited. J Affect Disord. 2001;63:123–132.Google Scholar
103.Han, L, Nielsen, DA, Rosenthal, NE, et al.No coding variant of the tryptophan hydroxylase gene detected in seasonal affective disorder, obsessive-compulsive disorder, anorexia nervosa, and alcoholism. Biol Psychiatry. 1999;45:615–619.Google Scholar
104.Lenzinger, E, Neumeister, A, Praschak-Rieder, N, et al.Behavioral effects of tryptophan depletion in seasonal affective disorder associated with the serotonin transporter gene? Psychiatry Res. 1999;85:241–246.Google Scholar
105.Murray, G, Allen, NB, Trinder, J. Seasonality and circadian phase delay: prospective evidence that winter lowering of mood is associated with a shift towards Eveningness. J Affect Disord. 2003;76:15–22.CrossRefGoogle ScholarPubMed
106.Hebert, M, Dumont, M, Lachapelle, P. Electrophysiological evidence suggesting a seasonal modulation of retinal sensitivity in subsyndromal winter depression. J Affect Disord. 2002;68:191–202.Google Scholar
107.Nelson, RJ, Drazen, DL. Melatonin mediates seasonal changes in immune function. Ann N Y Acad Sci. 2000;917:404–415.Google Scholar
108.Maes, M, Stevens, W, Scharpe, S, et al.Seasonal variation in peripheral blood leukocyte subsets and in serum interleukin-6, and soluble interleukin-2 and -6 receptor concentrations in normal volunteers. Experientia. 1994;50:821–829.Google Scholar
109.Katila, H, Cantell, K, Appelberg, B, Rimon, R. Is there a seasonal variation in the interferon-producing capacity of healthy subjects? J Interferon Res. 1993;13:233–234.CrossRefGoogle Scholar
110.Connor, TJ, Leonard, BE. Depression, stress and immunological activation: the role of cytokines in depressive disorders. Life Sci. 1998;62:583–606.Google Scholar
111.Lam, RW, Song, C, Yatham, LN. Does neuroimmune dysfunction mediate seasonal mood changes in winter depression? Med Hypotheses. 2004;63:567–573.Google Scholar
112.Leu, SJ, Shiah, IS, Yatham, LN, Cheu, YM, Lam, RW. Immune-inflammatory markers in patients with seasonal affective disorder: effects of light therapy. J Affect Disord. 2001;63:27–34.Google Scholar
113.Stastny, J, Konstantinidis, A, Schwarz, MJ, et al.Effects of tryptophan depletion and catecholamine depletion on immune parameters in patients with seasonal affective disorder in remission with light therapy. Biol Psychiatry. 2003;53:332–337.Google Scholar
114.Terman, JS, Terman, M. Photopic and scotopic light detection in patients with seasonal affective disorder and control subjects. Biol Psychiatry. 1999;46:1642–1648.Google Scholar
115.Provencio, I, Rollag, MD, Castrucci, AM. Photoreceptive net in the mammalian retina. This mesh of cells may explain how some blind mice can still tell day from night. Nature. 2002;415:493.CrossRefGoogle ScholarPubMed
116.van der Horst, GT, Muijtjens, M, Kobayashi, K, et al.Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms. Nature. 1999;98:627–630.Google Scholar
117.Berson, DM, Dunn, FA, Takao, M. Phototransduction by retinal ganglion cells that set the circadian clock. Science. 2002;295:1070–1073.Google Scholar