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Is the dark really making me sad? | Ars Technica

the leading theory is the ‘phase-shift hypothesis’: the idea that shortened days cause the timing of our circadian rhythms to fall out of sync with the actual time of day, because of a delay in the release of melatonin. Levels of this hormone usually rise at night in response to darkness, helping us to feel sleepy, and are suppressed by the bright light of morning. “If someone’s biological clock is running slow and that melatonin rhythm hasn’t fallen, then their clock is telling them to keep on sleeping even though their alarm may be going off and life is demanding that they wake up,” says Kelly Rohan, a professor of psychology at the University of Vermont. Precisely why this should trigger feelings of depression is still unclear. One idea is that this tiredness could then have unhealthy knock-on effects. If you’re having negative thoughts about how tired you are, this could trigger a sad mood, loss of interest in food, and other symptoms that could cascade on top of that. However, recent insights into how birds and small mammals respond to changes in day length have prompted an alternative explanation. According to Daniel Kripke, an emeritus professor of psychiatry at the University of California, San Diego, when melatonin strikes a region of the brain called the hypothalamus, this alters the synthesis of another hormone—active thyroid hormone—that regulates all sorts of behaviours and bodily processes. When dawn comes later in the winter, the end of melatonin secretion drifts later, says Kripke. From animal studies, it appears that high melatonin levels just after the time an animal wakes up strongly suppress the making of active thyroid hormone—and lowering thyroid levels in the brain can cause changes in mood, appetite, and energy. For instance, thyroid hormone is known to influence serotonin, a neurotransmitter that regulates mood. Several studies have shown that levels of brain serotonin in humans are at their lowest in the winter and highest in the summer. In 2016, scientists in Canada discovered that people with severe SAD show greater seasonal changes in a protein that terminates the action of serotonin than others with no or less severe symptoms, suggesting that the condition and the neurotransmitter are linked.

Exercise boosts tryptophan, a mild hypnotic and serotonin precursor

The largest body of work in humans looking at the effect of exercise on tryptophan availability to the brain is concerned with the hypothesis that fatigue during exercise is associated with elevated brain tryptophan and serotonin synthesis. A large body of evidence supports the idea that exercise, including exercise to fatigue, is associated with an increase in plasma tryptophan and a decrease in the plasma level of the branched chain amino acids (BCAAs) leucine, isoleucine and valine (see64,65 for reviews). The BCAAs inhibit tryptophan transport into the brain.66 Because of the increase in plasma tryptophan and decrease in BCAA, there is a substantial increase in tryptophan availability to the brain. Tryptophan is an effective mild hypnotic,67 a fact that stimulated the hypothesis that it may be involved in fatigue. A full discussion of this topic is not within the scope of this editorial; however, it is notable that several clinical trials of BCAA investigated whether it was possible to counter fatigue by lowering brain tryptophan, with results that provided little support for the hypothesis. Further, exercise results in an increase in the plasma ratio of tryptophan to the BCAAs before the onset of fatigue.64,65

Overview of exercise and serotonin

A third strategy that may raise brain serotonin is exercise. A comprehensive review of the relation between exercise and mood concluded that antidepressant and anxiolytic effects have been clearly demonstrated.53 In the United Kingdom the National Institute for Health and Clinical Excellence, which works on behalf of the National Health Service and makes recommendations on treatments according to the best available evidence, has published a guide on the treatment of depression.54 The guide recommends treating mild clinical depression with various strategies, including exercise rather than antidepressants, because the risk–benefit ratio is poor for antidepressant use in patients with mild depression. Exercise improves mood in subclinical populations as well as in patients. The most consistent effect is seen when regular exercisers undertake aerobic exercise at a level with which they are familiar.53 However, some skepticism remains about the antidepressant effect of exercise, and the National Institute of Mental Health in the United States is currently funding a clinical trial of the antidepressant effect of exercise that is designed to overcome sources of potential bias and threats to internal and external validity that have limited previous research.55

Light boosts serotonin

Exposure to bright light is a second possible approach to increasing serotonin without drugs. Bright light is, of course, a standard treatment for seasonal depression, but a few studies also suggest that it is an effective treatment for nonseasonal depression38 and also reduces depressed mood in women with premenstrual dysphoric disorder39 and in pregnant women suffering from depression.40 The evidence relating these effects to serotonin is indirect. In human postmortem brain, serotonin levels are higher in those who died in summer than in those who died in winter.41 A similar conclusion came from a study on healthy volunteers, in which serotonin synthesis was assessed by measurements of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the venous outflow from the brain.42 There was also a positive correlation between serotonin synthesis and the hours of sunlight on the day the measurements were made, independent of season. In rats, serotonin is highest during the light part of the light–dark cycle, and this state is driven by the photic cycle rather than the circadian rhythm.43,44 The existence of a retinoraphe tract may help explain why, in experimental animals, neuronal firing rates, c-fos expression and the serotonin content in the raphe nuclei are responsive to retinal light exposure.44–48 In humans, there is certainly an interaction between bright light and the serotonin system. The mood-lowering effect of acute tryptophan depletion in healthy women is completely blocked by carrying out the study in bright light (3000 lux) instead of dim light.49

The Serotonin Surprise | DiscoverMagazine.com

Glenmullen has long suspected that drugs that alter serotonin metabolism cause profound changes in the brain. He bases his suspicion on a body of research during the last 20 years by scientists investigating another class of drugs that includes MDMA (Ecstasy) as well as fenfluramine, the diet drug recently removed from the market because of its association with heart valve problems. These drugs do more than just block serotonin reuptake; they primarily stimulate the release of large quantities of serotonin from nerve endings into the brain. The resulting flood is thought to cause the mind-altering effects of MDMA. And that flood, some scientists argue, leaves brain damage in its wake. When monkeys and rats are given high doses of serotonin releasers--up to 40 times the dose that people generally take--the microscopic architecture of their brains looks different from normal brains. The nerve fibers (axons) that carry serotonin to the target cells seem to change their shape and diminish in number--effects some scientists claim are properly understood as brain damage.