Winter Brain: Why Do We Feel Sad and Tired in Winter?

Seasonal changes in brain chemicals can lead to fluctuation in mood.

Posted Nov 17, 2019

Do you feel tired, moody, irritable, or depressed during winter? You're not alone. The farther north you live from the equator, the greater you will feel and be impacted by the winter blues. There are many factors that make people sad, gain weight and tired in the winter—especially biological ones.

One culprit that has been reliably shown to be related to this phenomenon is serotonin. To understand how it is involved, we need to understand what serotonin transporters are.

Brain chemicals have multiple inactivation methods. Anything that prevents their inactivation, prolongs their actions in the brain. Anything that promotes their inactivation shortens their actions in the brain. One way serotonin gets inactivated is by being recycled back through a protein called serotonin transporter. The more numerous the transporters and/or the more efficient serotonin binds to them, the faster the serotonin gets metabolized.

Serotonin is involved in eating/feeding behaviors, mood, mating, sleep, and energy. Thus, disorders that are characterized by low mood and energy are treated by medications that increase serotonin levels in the brain. For example, antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs) and tricyclics all increase levels of serotonin. The main mechanism of action for these antidepressants is slowing the inactivation of serotonin either by inhibiting the enzyme that breaks it down or blocking the transporters and its reuptake.

Serotonin metabolism fluctuates with seasonal changes. This is not surprising as serotonin, tryptophan, and melatonin belong to the same chemical class, indoleamine. Across many species, these chemicals respond to light variations intrinsic to seasonality. For example, a study showed that sunlight alters serotonin turnover in the human brain (1). Using a highly selective neuroimaging technique, researchers were able to measure serotonin transporter efficiency in healthy subjects over 4 years (2). The brain scans were grouped according to season of scan with the cutoff between fall and winter season and the spring and summer season. They found that serotonin transporter binding potential varies throughout the seasons. The serotonin transporters were more sensitive during the fall/winter compared to spring/summer in many brain areas. The findings indicate that lower serotonin transporter density with increasing duration of sunshine. In other words, in winter/fall serotonin gets quickly inactivated and has a shorter effect. In the spring/summer, transporters are less sensitive which results in a sluggish recycling/inactivation of serotonin and longer action in the brain.

The results of the above-described study and others support the seasonality effects on the chemistry of the brain and in turn its effects on mood, eating, mating and energy. In about 1-6% of the population, these effects amount to a disorder: seasonal affective disorder (SAD). A disorder that is more prevalent in geographic places with harsh winters and high altitudes (3). SAD is a subtype of clinical depression characterized by recurrent winter major depressive episodes with full remission in spring/summer.

Is there anything different in the brains of people who are severely affected by winter’s deleterious effects on the brain? A few studies found exactly that. In a study that compared people suffering from SAD and healthy volunteers, researchers found expected brain differences (4). Serotonin transporters were more efficient in winter versus summer, and the difference was more pronounced for the SAD group. Furthermore, seasonal variations in serotonin inactivation correlated with severity of SAD symptoms. The more severe the disorder, the faster serotonin got metabolized (inactivated) in their brains in the winter season. Using these advanced scanning methods, people at risk for SAD can be screened based on serotonin transporter sensitivity.

To make this even more complicated is that there are genetic predispositions making some individuals more sensitive to winter blues. The gene for the serotonin transporter comes in two flavors (alleles): short and long. People who inherit the short allele of the serotonin transporter clear serotonin twice as fast as those with the long allele (5). In a study of 479 subjects over a three-year period, seasonality effects on serotonin differed depending on genotype of serotonin transporter, short or long (6). Participants who had the short allele showed more serotonin seasonality. And serotonin seasonality correlated with depressive symptoms. In other words, subjects who inherited two short alleles from both parents were most affected by change of season, followed by those inheriting only one short allele. Subjects who inherited two long alleles were the least affected by changes in season.

Winter blues are not because we are lazier in the winter, or only reserved for people with weak character. Winter blues are a result of complicated biochemical changes in the brain that cause changes in our thoughts, emotions, and behaviors depending on the season.

References

(1) Lambert GWReid CKaye DMJennings GLEsler MD Effect of sunlight and season on serotonin turnover in the brain. Lancet 2002;360 (9348) 1840- 1842

(2) Praschak-Rieder N, Willeit M, Wilson AA, Houle S, Meyer JH. Seasonal Variation in Human Brain Serotonin Transporter Binding. Arch Gen Psychiatry. 2008;65(9):1072–1078. doi:https://doi.org/10.1001/archpsyc.65.9.1072.

(3) Magnusson A (2000). An overview of epidemiological studies on seasonal affective disorder. Acta Psychiatr Scand 101: 176–184.

(4) Tyrer A.E. Levitan, R.D. et al. (2016). Increased seasonal variation in serotonin transporter binding in seasonal affective disorder. Neuropsychopharmacology (41), 2447-2454.

(5) Barton DA, Esler MD, Dawood T, Lambert EA, Haikerwal D, Brenchley C, et al. Elevated brain serotonin turnover in patients with depression: effect of genotype and therapy. Arch Gen Psychiatry. 2008;65:38–46.

(6) Luykx, J. J., Bakker, S. C., van Geloven, N., Eijkemans, M. J., Horvath, S., Lentjes, E., … Ophoff, R. A. (2013). Seasonal variation of serotonin turnover in human cerebrospinal fluid, depressive symptoms and the role of the 5-HTTLPR. Translational psychiatry, 3(10), e311. doi:10.1038/tp.2013.84