Be happy! Don't be SAD; the role of light and melatonin in Seasonal Affective Disorder

Seasonal affective disorder (SAD), also known as winter depression, winter blues, or seasonal depression, is a type of depression that occurs at a certain time of the year, usually in the winter. It affects people who have normal mental health throughout most of the year

The U.S. National Library of Medicine notes that "some people experience a serious mood change when the seasons change. They may sleep too much, have little energy, and may also feel depressed. Though symptoms can be severe, they usually clear up."

Some people experience a serious mood change during the winter months, when there is less natural sunlight, with full remission in the spring.
Studies of twins, families with a SAD proband, and other relatively homogeneous groups indicate that SAD may be, in part, an inherited disorder

Syntomps and Diagnosis

The major syntomps of SAD are:

• Sad, anxious or "empty" feelings
• Feelings of hopelessness and/or pessimism
• Feelings of guilt, worthlessness or helplessness
• Irritability, restlessness
• increased sensitivity to social rejection and keeping away of social situations(hibernation)
• Loss of interest or pleasure in activities you used to enjoy
• Fatigue and decreased energy
• Difficulty concentrating, remembering details and making decisions
• Difficulty sleeping or tendency to increasing sleeping
• Changes in hunger, that results in a increased weight
• Physical problems as headaches and stomach aches
• In the most severe cases we could also notice thoughts of death or suicide

MedlinePlus Overview seasonal affective disorder,2013

The diagnosis of SAD depends on these criteria:

1. a history of depression fulfilling Research Diagnostic Criteria for major affective disorder, depression

2. a history of minimum two chronological years of fall/winter depressive episodes with remission in the spring or summer

3. the destitution of other major psychiatric disorder or psychosocial abstraction for the seasonal mood changes

The symptoms of SAD start in the second or third epoch of life.

Role of serotonin in seasonal affective disorder. Diagnosis 2013

Incidence

It appears four times more commonly in women than men, a sex-related preponderance greater than for most other psychiatric disorders. The prevalence of the SAD increases in proportion to the distance from the equator of the place where people live.
It was estimated that the prevalence of SAD approaches 10 percent in northern latitudes.In a given year, about 5 percent of the U.S. population experiences SAD, with symptoms lasting approximately 40 percent of the year.

Prevalence of seasonal affective disorder at four latitudes,1990

Etiology

SAD is probably a complex disorder resulting from a combination of factors :
there are several biologic mechanisms underlying SAD, including circadian phase delay or advance (the phase shift hypothesis), which tends to appear as the chief cause in the literature. Moreover in the etiology of SAD are involved also retinal sensitivity to light, neurotransmitter dysfunction, genetic variations affecting circadian rhythms, serotonin and melatonin levels.
Shorter days seem to be a main trigger for SAD. Reduced sunlight in fall and winter can disrupt body’s internal clock, or circadian rhythm. This 24-hour biological clock responds to cues in our surroundings, especially light and darkness. During the day, our brain sends signals to other parts of the body to help keep us awake and ready for action. At night, the epiphysis produces a chemical called melatonin, which helps people to sleep. Shortened daylight hours in winter can alter this natural rhythm and lead to SAD in certain people.

The role of Serotonin
The serotonin (5-HT), biochemically derived from tryptophan, is an important neurotransimtter.
There are 7 classes of serotonin receptors.
The serotonergic system plays an important role in regulating mood, control appetite, sleep, arousal and pain.
The serotonin concentration and activity alters across the seasons.
SAD patients show different polymorphisms of serotonin transporters promoter genes and of serotonin receptor.
The serotonin content in the hypothalamus in human post mortem samples has a considerable seasonal variation: in facts, the minimum levels were found during the winter months of December and january. The hypothalamic serotonin has an important role in indulgence and feeding regulation, this could explain the fact that SAD patients desiderate carbohydrates and increase weight during winter depressive episodes.

Role of serotonin in seasonal affective disorder,2013

The role of the light
The phase shift hypothesis
Researchers discovered that bright light could suppress melatonin production in humans. Because of that, bright light exposure was scheduled in the morning and late afternoon/evening in order to mimic a spring photoperiod. A group of physicians focused on a circadian approach to SAD,based on the phase shift hypothesis (PSH) which states that most patients with SAD become depressed in the winter, at least in part because of a phase delay in circadian rhythms relative to the sleep/wake cycle. ​The PSH further postulates that a smaller subgroup of SAD patients becomes depressed in the winter because of a phase advance.

It has been reported that bright light scheduled in the morning causes a phase advance (a shift to an earlier time) and that bright light scheduled in the evening causes a phase delay (a shift to a later time), using the dim light melatonin onset (DLMO, that is, the time of the beginning of melatonin production in dim light) as the marker for circadian phase position. Most of SAD patients preferentially responded to the antidepressant effects of morning light, whereas some patients preferentially responded to evening light.

The phase shift hypothesis for the circadian component of winter depression, 2007

The melatonin

Individuals with SAD have a longer period of melatonin synthesis at night in the winter. In addition SAD patients may have higher daytime melatonine levels than people without SAD.
Melatonin is an hormone which is produced in dim light and darkness by the pineal gland, since there are direct connections, via the retinohypothalamic tract and the suprachiasmatic nucleus, between the retina and the pineal gland. Melatonin secretion is controlled by the endogenous circadian clock, but can also be suppressed by bright light.
Melatonin onset each evening is called the dim-light melatonin onset (DLMO).
It is principally blue light, around 460 to 480 nm, that suppresses melatonin, proportional to the light intensity and length of exposure

Melatonin synthesis is triggered by darkness. Daylight blood levels are normally very low, with a nocturnal peak. The diurnal and circadian rhythm of this secretion is brought about by light entering the retina. Light/dark information reaches the suprachiasmatic nuclei (SCN) from retinal photosensitive ganglion cells, which are intrinsically photosensitive photoreceptor cells that are distinct from the rods and cones of the retina(involved in the primary image formation). These cells represent 2% of all retinal ganglion cells in humans and express the photopigment melanopsin.
Melanopsin is a 7-transmembrane opsin protein with the usual vitamin A-like cis-retinal cofactor having a peak absorption at 484 nm, in the blue light part of the visible spectrum. The photoperiod cue created by blue light (from a blue image of the sky) entrains a circadian rhythm, and thus determins resultant production of specific "dark"- and "light"-induced neural and endocrine signals that regulate behavioral and physiological circadian rhythms associated with melatonin.

So, the light stimulates the melanopsin-expressing retinal ganglion cells, then these cells through the retinohypothalamic tract stimulate the suprachiasmatic nuclei, then the paraventricular nucleus(PVN) is regulated by the hypothalamus. The signal arrives to the intermediolateral cell column. Finally, passing through the superior cervical ganglion, the stimolation arrives to the pineal gland through a noradrenergic mechanism,cAMP-dependent, to regulate the production of melatonin.
The hyphothalamus inhibits the pineal gland from converting serotonin to melatonin. With the darkness, the inhibitory mechanism isn't present, so the pineal gland begins synthesizing melatonin.

Melanopsin and ipRGCs, flipper 2010

This figure show the biochemical pathway followed by our body to produce serotonin from tryptophan, with the enzime tryptophan hydroxylase,that produce 5-HTP, and with the enzime 5-HTP decarboxylase, that gives us serotonin. Then we can obtain melatonin through two more steps: the SNAT turn serotonin into N-acetylserotonin, then transformed into melatonin with the enzime HIOMT.

Circadian mechanisms in the regulation of melatonin synthesis:

disruption with light at night and the pathophysiological

consequences,2011

There are evidences that the timing and duration of melatonin secretion is affected by the lenght of day and night. In SAD patients there is a delayed nocturnal onset of melatonin secretion. Nocturnal melatonin in women with SAD is increased in winter compared to summer. In contrast, women without SAD don't demonstrate this seasonal variance in melatonin synthesis. Elevated daytime blood melatonin levels have also been observed in SAD patients.

In the majority of patients with SAD, melatonin levels do not exhibit the normal night fluctuations. Under normal conditions, the blood level of this molecule is expected to reach a peak around 2 am, and then decrease.
It is believed that in patients with SAD, within 24 hours, melatonin levels remain high for about two hours longer than normal, before beginning to decline.

Epidemiology, Etiology, and Natural Treatment of Seasonal Affective Disorder,2005

Therapy

Different treatments for classic (winter-based) seasonal affective disorder are available, including light therapy, pharmacological therapy, ionized-air administration, cognitive-behavioral therapy(CBT) and carefully timed supplementation of the hormone melatonin.
In this article we focus on the light-therapy( also called phototherapy)

THE PHOTOTHERAPY

Photoperiod-related alterations of the duration of melatonin secretion may affect the seasonal mood cycles of SAD. This suggests that light therapy, based on the administration of light similar to the natural one, may be an effective treatment for SAD.
The intrinsically photosensitive Retinal Ganglion Cells (ipRGCs), were eventually linked directly to the production of serotonin, and the regulation of melatonin and other hormones.
These receptors are separate from those that we use for vision. In fact, they tend to be located in the lower portion of the eyeball, and are primarily sensitive to blue light. This location suggests that they tend to sample the amount of blue light in the sky, well above our normal field of view.
Blue light, positioned above the field of view, provides significantly superior light therapy results in clinical environments as compared to full spectrum light (located in any position).
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Melanopsin-Containing Retinal Ganglion Cells: Architecture, Projections, and Intrinsic Photosensitivity,2002

Light therapy uses a lightbox which emits far more lumens than a customary incandescent lamp. Light therapy is thought to affect brain chemicals linked to mood, easing SAD symptoms. Bright white "full spectrum" light at 10,000 lux, blue light at a wavelength of 480 nm at 2,500 lux or green light at a wavelength of 500 nm at 350 lux are used,
Bright light therapy is effective with the patient sitting a prescribed distance, commonly 30–60 cm, in front of the box with her/his eyes open but not staring at the light source for 30–60 minutes.

Light therapy can also consist of exposure to sunlight, either by spending more time outside.
Moreover, the SAD patient treated with pharmacological therapy, if it was associated with the light-therapy showed earlier clinical improvement.
The effectiveness of light therapy for treating SAD may be linked to the fact that light therapy makes up for lost sunlight exposure and resets the body's internal clock

Studies have shown that light therapy relieves SAD symptoms for the 70% of patients after a few weeks of treatment.

Beat the Winter Blues

A meta-analysis of the major studies confirmed the efficacy of the bright light therapy, that is comparable to the efficacy found in many antidepressant pharmacotherapy trials.

Figure:Effect Sizes in Studies of Treatment of Seasonal Affective Disorder With Bright Light

- The Can-SAD study: a randomized controlled trial of the effectiveness of light therapy and fluoxetine in patients with winter seasonal affective disorder, 2006

- The Efficacy of Light Therapy in the Treatment of Mood Disorders: A Review and Meta-Analysis of the Evidence, 2005

- Artificial Light and Melatonin Secretion, flipper 2013

Conclusions

The Seasonal Affective Disorder has an important prevalence in developed countries. Even if there are many theories about the etiology and the major biological causes, today's medicine can cope with this disease. In fact, this is one of very few disease in which the treatment of choice is natural and non-invasive(light-therapy). It is easily administered,effective in the majority of patients, and without side effects.