Brain scans have revealed why some people get so depressed in winter


Scientists have uncovered a biological cause that explains why some people develop seasonal affective disorder in winter, while others love the colder months.

Scientists from the University of Copenhagan in Denmark may have identified an underlying biological cause of seasonal affective disorder (SAD), and helped explain why the “winter blues” can be so severe for some people.

Brain scans have revealed that people who develop SAD have less access to serotonin, the brain signalling compound associated with feelings of wellbeing and happiness, as the days get shorter in the winter months.

This is because their brains ramp up the production of a transporter protein called serotonin transporter (SERT), which transports serotonin into the nerve cells where it’s not active.

“We believe that we have found the dial the brain turns when it has to adjust serotonin to the changing seasons,” lead researcher Brenda Mc Mahon, a neurobiologist at the University of Copenhagan, told the BBC. “The serotonin transporter (SERT) carries serotonin back into the nerve cells where it is not active – so the higher the SERT activity, the lower the activity of serotonin.”

The researchers performed positron emission tomography (PET) brain scans on 11 people with SAD and 23 healthy volunteers in both summer and winter in order to examine the differences in their brains.

They found that the volunteers with SAD had more SERT in their brains in winter compared to healthy volunteers. However, both groups had a similar amount of SERT in the summer.

“Sunlight keeps this setting naturally low, but when the nights grow longer during the autumn, the SERT levels increase, resulting in diminishing active serotonin levels,” Mc Mahon told BBC. 

“Many individuals are not really affected by SAD, and we have found that these people don’t have this increase in SERT activity, so their active serotonin levels remain high throughout the winter.”

Scientists have suspected for a while that SERT fluctuations were responsible for SAD, but this is the first study to show the difference between the levels in patients between winter and summer. The results will be presented at the annual congress of the European College of Neuropsychophar­macology this week.

But while the results are pretty exciting, it’s important to note that this is still a small-scale study and further research is needed to confirm the link between SERT and SAD, as well as the role that sunlight plays on serotonin.

The next step will be to find out more about why some people increase SERT production as the days get shorter, and why some people are unaffected. It’s estimated SAD affects more than 12 million people across northern Europe.

Sam Challis, an information manager at British mental health charity Mind, told the BBC: “We don’t yet know enough about how serotonin levels can be affected by light levels so this is quite an interesting, albeit small, study. We would welcome more research.”

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How Serotonin Reuptake Inhibitors Work: Understanding More Fundamental Mechanisms of Action.


By stimulating microRNA miR-16 in the midline serotonergic raphe, fluoxetine initiates signaling cascades that lead to hippocampal neurogenesis.

Several lines of evidence suggest that in adults, antidepressant therapies enhance neurogenesis in the hippocampus, but how this process occurs has been unclear. These researchers studied the effects of fluoxetine in mice and in humans. They worked out several pathways that begin with the stimulation by fluoxetine of the microRNA miR-16 in serotonergic neurons in raphe and ultimately result in hippocampal neurogenesis.

In a series of experiments in mice, fluoxetine activated raphe miR-16, which decreased raphe levels of the serotonin reuptake transporter (SERT). In turn, these events directly caused brain-derived neurotropic factor (BDNF) and two other signaling molecules to act on the hippocampus. Indirectly, the same events resulted in release of another protein from the raphe nuclei, S100β, which in turn stimulated the locus coeruleus to induce SERT and secrete serotonin. Both the direct and indirect pathways caused decreases in hippocampal miR-16, which sequentially led to increases in both hippocampal SERT and the bcl-2 protein (which promotes neurotrophic function), which in turn stimulated neurogenesis. In nine patients with major depression, 12-week fluoxetine treatment increased levels of the three signaling molecules in cerebrospinal fluid. The interventions were accompanied by improvements in several mouse models of depression, as well as in the patients. See accompanying figure.

Comment: These findings draw together several seemingly unconnected lines of research. The authors identify miR-16 as a “missing link” between serotonin reuptake inhibitor treatment and hippocampal neurogenesis and as a “micromanager” of the intervening changes in the raphe nucleus, locus coeruleus, serotonin receptor transporter, serotonin secretion, and hippocampal neurogenesis. The processes appear to work through the cooperative and integrated activities of several signaling molecules. Further clarification of these pathways may help refine therapeutic strategies for depressive disorders.

Source: Journal Watch Psychiatry