Every winter the cycle repeats itself: we look outside our windows and despair to the sight of a cloudy winter sky, with no trace of the sunny days. But the familiar “winter blues” feelings might not be just a “phase”: for some people such periods of low light exposure represent a serious problem to face, and that’s where the term “seasonal affective disorder” (SAD) comes in place. Why does SAD start, and can a look at the neurobiology of the brain help us to understand it more?
Deconstructing SAD: definition, symptoms, epidemiology
The idea of a more serious winter blues is not a recent discover: psychiatrists started to talk about a specific seasonal depression disorder in the early 80s, but there are no definitive answers yet as to the cause of it. To clarify how SAD is understood and treated in the clinical context it is important to define it correctly: this disorder is a specific subtype of major depression disorder. Does this mean that you’re experiencing seasonal affective disorder when feeling a little “blue” in winter? Not necessarily.
Even though SAD does come in winter, it is characterized by a very strict seasonal pattern, meaning that it appears constantly (not only occasionally) during winter and remits spontaneously during the other seasons. Crucially, compared to the “occasional” winter sadness, those who suffer from SAD in winter present most of the symptoms common in depression (for more information on depression symptoms you can visit https://www.psycom.net/depression-definition-dsm-5-diagnostic-criteria/). As for the prevalence of SAD, several authors used the Seasonal Pattern Assessment Questionnaire (SPAQ) to estimate a prevalence of this disorder in a variety of populations across the world, finding percentages from 0 up to 9.7% .
An important predictor of the prevalence of SAD turned out to be light exposure, as in total hours of sunshine. Some of the processes affected by light are circadian rhythms, which provide an important contribution to our wellbeing and biological functions. In the brain their “headquarters” are located in the suprachiasmatic nucleus (SCN), a little nucleus of the hypothalamus. It shouldn’t come as a surprise then that northern countries seem to have the highest prevalence of this disorder, and that there seems to be a growing prevalence of this problem as the latitude gets higher.
Melatonin: why circadian rhythms matter in SAD
Looking at the previous paragraph it might come natural to ask ourselves if somewhere in the sunlight lies the answer to SAD development. When we go to sleep (and the sun has set) our brain is in reality still working, producing and regulating different molecules: among these we find melatonin, a hormone released by the pineal gland in the epithalamus, that maintains our sleep-wake cycle. As long as there is light, there is NO melatonin production. Viceversa, when we go to sleep, melatonin levels rise and make us feel “sleepy”. Initially scientists focused on melatonin as the possible “culprit”, as the shorter and darker winter days would induce a higher melatonin production, but many studies show varied and conflicting findings about melatonin secretion alone, making it hard to consider melatonin dysfunctions as the sole cause of SAD.
In 1988, Lewy et al. proposed a ”phase-delay hypothesis” to explain SAD: the authors had previously shown that exposing healthy volunteers to bright light at certain points during the night leads to a shift in the circadian rhythm and in the melatonin production rhythm. By unifying these viewpoints they argued that individuals ,especially in winter, might experience abnormal circadian rhythms (for example, due to reduced sunlight exposure), relative to external rhythms (e.g. sleep-wake cycle). However, only in people with SAD these abnormalities would lead to a depressive outcome (that settles back once winter has passed).
Is this theory from 1988 the key to SAD? There is no simple answer to this, but this hypothesis might not be totally valid to fully explain SAD. The dim-light melatonin onset (DLMO) is a measure indicating the starting time point at which melatonin gets secreted in controlled light conditions. In some studies the DLMO was found to be effectively delayed in SAD patients compared to control, but other studies found only tendencies to delays or even no DLMO differences between different groups. Moreover, other predictions made from the phase-delay hypothesis (such as phase delays in the body temperature circadian cycle) are not met in other studies conducted with SAD and control patients.
The “mood” neurotransmitter: serotonin’s role in SAD
Sunlight doesn’t just affect complex hormones: it also has effects on simpler, yet highly prevalent, neurotransmitters in our brain. One example linked to SAD is serotonin (5-HT): this molecule is a neurotransmitter greatly involved in mood disorders. As it was for melatonin, we find yet other seasonal changes in 5-HT levels and correlated molecules. Previous studies have shown changes in healthy participants during winter such as:
- a decrease in the binding of serotonin to its receptors
- increases in 5-HTT BPND (an index related to 5-HTT density, more on this molecule in the paragraph below)
In 2016 Tyrer et al. conducted a study that aimed to see how these changes evolved over the seasons in SAD patients. The authors compared PET and MRI scans of both SAD and healthy patients, focusing on the biomarker 5-HTT BPND. 5-HTT (also known as SERT) is a protein transporter of serotonin acting at the level of synapses: it brings the neurotransmitter from the synaptic cleft to the presynaptic neuron, thus terminating its action. The authors expected to find:
- a difference in the variation of the biomarker seasonal levels between the two groups of patients (with SAD patients having greater seasonal variations compared to healthy controls)
- a link between the magnitude of these seasonal variations and the gravity-intensity of the symptoms in SAD patients
In the end the authors found a significant difference in seasonal fluctuations of the biomarker used in the study between SAD and controls. Moreover, these fluctuations were higher in SAD patients that showed the most intense symptoms. These results point to a greater availability of 5-HTT in SAD patients during winter compared to summer, which in turn would indicate reduced serotonin levels in winter!
5-HTT BPND is not the only biomarker that has been investigated in relation to SAD. Monoamine oxidase A (MAO-A) is an enzyme involved in the recycling and disposal of serotonin: in a recent 2018 study scientists tried to assess whether SAD patients showed higher physiological fluctuations in the levels of MAO-A VT (an index of MAO-A density in the brain) compared to healthy controls. Starting from an equal MAO-A VT baseline for healthy controls and SAD patients, both groups received a therapy (Bright Light Therapy – BLT, see Conclusion) for SAD. PET imaging data (performed before and after BLT) showed that:
- Before BLT, MAO-A VT levels in SAD patients stayed at stationary levels in the passage from fall/winter to spring/summer
- Before BLT, in the healthy controls MAO-A VT levels were reduced in the passage from fall/winter to spring/summer
- After BLT, MAO-A VT levels decreased. This result shows that BLT might be an effective therapy for SAD: the decrease of MAO-A VT in the SAD group following therapy would induce a lower rate of serotonin degradation, and therefore induce overall higher serotonin levels!
A brief conclusion: how can we stop to “be SAD”?
In conclusion, there is still a long way to go to fully explain SAD. Different molecules and mechanisms seem to point to a SAD explanation revolving around circadian dysfunctions and dysregulation of cerebral neurotransmitter expression. Research is still lacking definite answers, and new hypotheses still need to be further tested. But what about the treatments of SAD? Is there a solution to the problem? The answer is yes, and it’s surprisingly intuitive: more light!
Bright Light Therapy (BLT) is a type of treatment in which a person is exposed to artificial light that resembles the spectrum of sunlight. Patients with SAD can use these light emitters for a short period of time in the morning to aid the regulation of light cycles and “trick” their brain into regular circadian cycles. A different option is the use of antidepressants in SAD treatment: since this disorder seems to influence serotonin levels, using substances such as SSRIs or MAO-A inhibitors might increase the levels of this neurotransmitter.
In the end the take-home message is: enjoy the sun as much as you can and you “won’t be SAD”!