Seasonal affective disorder (SAD) is a mood disorder which is common in temperate climates. It consists of recurrent major depressive episodes mainly during the winter season when the levels of light are reduced. Otherwise known as the winter depression or winter blues, SAD can lead to major clinical depression (Welberg 2007). It is characterised by typical and atypical symptoms, which include lowered mood and hypersomnia, respectively (Michalak, et al., 2001). Depression in the winter is usually followed by remission through spring and summer, with SAD said to be more popular amongst females than males with a ratio of 3.5:1, and even 9:1 in some samples (Monteleone & Maj 2008) (Winkler et al., 2002). A range of aetiologies for SAD have been suggested including a link to serotonin and melatonin. In this essay I will explore these mechanisms, and treatments they have inspired.
Humans have a circadian rhythm which applies to most physiological and behavioural functions, a system which is adapted to deal with variations in the environment. For that reason, it is sensitive to changes in the endogenous circuitry that monitors circadian oscillations, which could affect the mental and physical state.
Malformation of circadian rhythms in sufferers of SAD can cause sleep disorder, and phase delays in the patterns of melatonin and cortisol secretion (Monteleone & Maj 2008).
The exact cause of SAD still remains vague; however, one theory implicates melatonin. Melatonin is a hormone that is involved in the regulation of the internal body clock, which induces the feeling of sleep when it is dark and the feeling of alertness when it is light. This internal body clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus (Monteleone & Maj 2008). Melatonin production predominates during the night and is synthesised in many organs and tissues of the body including the lymphoid organs, pineal gland and bone marrow (Srinivasan, et al 2008). Production of melatonin in response to light by way of the pineal gland is directly connected (via the retinohypothalamic tract and the suprachiasmatic nucleus) to the retina.
Administration of melatonin acts to reset the internal body clock. Since sufferers become depressed as a result of limited levels of light which upsets their circadian rhythm, therefore treatment with this hormone is practical. It has been predicted that photoperiod-related changes in the release of melatonin may play a role in the seasonal mood cycles of the disorder. Thus, suggesting that artificial bright light would be effective in treating SAD (Howland 2009). Bright-light therapy (BLT) is the medication of preference for SAD sufferers (Monteleone & Maj 2008); while patients who do not respond to this form of treatment have the option of antidepressant drug therapy as an alternative (Pjerk et al 2009). BLT is a non-pharmacological treatment method which has proven to be effective, with elimination of symptoms during the summer. The mechanism of action involving the 5-HT transporter (Monteleone & Maj 2008) (Winkler et al., 2002).
Exposure to the sun during the summer means exposure to ultraviolet (UV) light and internal synthesis of vitamin D, unlike BLT which has the UV light filtered out. In addition to low levels of vitamin D during the winter season this may also worsen the condition (Young 2009). Vitamin D is well-known for its effects on maintaining normal levels of calcium, over and above its affect on hormone synthesising tissues involved in mood, and its affect on the brain and spinal cord.
Treatment of SAD has conventionally been light therapy. On the other hand, not all sufferers respond to this kind of treatment. While treatment with melatonin has proven to be promising, other forms of treatment have also been sought.
Serotonin (or 5-Hydroxytryptamine) is a chemical mediator which has a slow onset that suggests it functions as a neuromodulator. The activity of serotonergic neurons is at its lowest or lacking during slumber, and is at its peak during states of alert wakefulness. Serotonin plays a significant role in the pathogenesis of SAD. The levels of this neurotransmitter in the neuronal synapse are controlled by the 5-HT transporter (Welberg 2007). Willeit, et al (2007) compared SAD sufferers and healthy volunteers and measured the function of the 5-HT transporter in winter, post BLT treatment (4 weeks) and in the summer season. They assessed the inward and outward transport of 5-HT in blood platelets by way of the 5-HT transporter (Welberg 2007). This transporter is a member of the Na+/Cl- dependent membrane transporters and directs the extent of the serotonergic signal by reuptake of 5-HT from the synaptic cleft directly following its discharge (Willeit, et al., 2003). They also found that both inward and outward rate of transport in platelets was improved in sufferers compared to healthy controls during the winter season. They also reported that changes in the function of platelet 5-HT transporter were eliminated after 4 weeks of treatment with bright-light, and during the summer season. What is interesting is that the levels of the transporter and its affinity for serotonin were no different in the BLT group compared to the winter and summer conditioned groups. Thus indicating that the enhanced inward transport of 5-HT found in the sufferers was due to greater efficiency of the transporter (Welberg 2007). Moreover, they assessed the genotypes of the SAD sufferers and the healthy controls to see if there were any differences in the ‘promoter region of the gene that encodes the 5-HT transporter’ (Welberg 2007) which could account for the differences observed. They found no differences between the patients and the controls and concluded that genotype does not affect the increased efficiency of the serotonin transporter seen in the SAD patients (Welberg 2007).
Expression of the 5-HT transporter is under the control of an ‘insertion/deletion polymorphism in the serotonin transporter gene promoter region (5-HTTLPR)’ (Willeit, et al., 2003). In addition, the 5-HTTLPR short allele(s) have been linked to depression, and one investigation also found that there was a connection between the allele and SAD (Willeit, et al., 2003).
Selective serotonin reuptake inhibitors (SSRI) are in use as anti-depressants and have been shown to be useful in the treatment of SAD; these include fluoxetine and sertraline. Finally, noradrenaline has also been related to the pathogenesis of SAD. But the differential beneficial value of SSRI and selective noradrenaline reuptake inhibitors (NARI) in SAD is yet to be confirmed (Pjerk, et al., 2009)
Conclusion In conclusion, SAD is cyclic disorder, and therefore signs and symptoms come and go according to seasonal changes. It occurs regularly at a certain time in the year but it is unknown how seasonal variations cause depression. Nonetheless, research into the mechanisms and treatments of SAD has shown there to be changes in the levels of circulating brain chemicals: serotonin and melatonin (in response to differing exposures to light and dark). Treatment for SAD includes both non-pharmacological (BLT) and pharmacological (SSRI and melatonin) methods.