original Article
Neuropsychopharmacology advance online publication 19 September 2007; doi: 10.1038/sj.

Enhanced Serotonin Transporter Function during Depression in Seasonal Affective Disorder
Matthäus Willeit1,6, Harald H Sitte2,6, Nikolaus Thierry1, Klaus Michalek2, Nicole Praschak-
Rieder1, Peter Zill3, Dietmar Winkler1, Werner Brannath4, Michael B Fischer5, Brigitta
Bondy3, Siegfried Kasper1 and Ernst A Singer2

1Department of Biological Psychiatry, Medical University of Vienna, Vienna, Austria
2Center for Biomolecular Medicine and Pharmacology, Institute of Pharmacology, Medical
University of Vienna, Vienna, Austria
3Department of Neurochemistry, Ludwig Maximilians University, Munich, Germany
4Department for Medical Statistics, Medical University of Vienna, Vienna, Austria;
5Department of Transfusion Medicine, Medical University of Vienna, Vienna, Austria
Correspondence: Dr M Willeit, Department of Biological Psychiatry, Vienna General Hospital,
Medical University of Vienna, Währinger Gürtel 18-20, Vienna A-1090, Austria. Tel: +43 1 40
400 3543; Fax: +43 1 40 400 3099; E-mail:; Dr HH Sitte,
Center for Biomolecular Medicine and Pharmacology, Institute of Pharmacology, Medical
University of Vienna, Währinger Strasse 13a, Vienna A-1090, Austria. Tel: +43 1 4277
64123; Fax: +43 1 4277 9641; E-mail:

6These authors contributed equally to this work.

Received 2 March 2007; Revised 20 June 2007; Accepted 6 August 2007; Published online
19 September 2007.

Top of pageAbstract
Decreased synaptic serotonin during depressive episodes is a central element of the
monoamine hypothesis of depression. The serotonin transporter (5-HTT, SERT) is a key
molecule for the control of synaptic serotonin levels. Here we aimed to detect state-related
alterations in the efficiency of 5-HTT-mediated inward and outward transport in platelets of
drug-free depressed patients suffering from seasonal affective disorder (SAD). 5-HTT
turnover rate, a measure for the number of inward transport events per minute, and tyramine-
induced, 5-HTT-mediated outward transport were assessed at baseline, after 4 weeks of
bright light therapy, and in summer using a case–control design in a consecutive sample of
73 drug-free depressed patients with SAD and 70 nonseasonal healthy controls. Patients
were drug-naive or medication-free for at least 6 months prior to study inclusion, females
patients were studied in the follicular phase of the menstrual cycle. All participants were
genotyped for a 5-HTT-promoter polymorphism (5-HTTLPR) to assess the influence of this
polymorphism on 5-HTT parameters. Efficiency of 5-HTT-mediated inward (p=0.014) and
outward (p=0.003) transport was enhanced in depressed patients. Both measures
normalized toward control levels after therapy and in natural summer remission. Changes in
outward transport showed a clear correlation with treatment response (=0.421, p=0.001).
Changes in inward transport were mediated by changes in 5-HTT transport efficiency rather
than affinity or density. 5-HTTLPR was not associated with any of the 5-HTT parameters. In
sum, we conclude that the 5-HTT is in a hyperfunctional state during depression in SAD and
normalizes after light therapy and in natural summer remission.


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Bipolar Disorders

This information is not intended to diagnose or treat bipolar disorders, but to provide a better
understanding of this condition as well as information on new effective treatments. However,
if you recognize any of these symptoms, you should consult with your physician when
considering treatment.

Bipolar Disorder

Bipolar disorder is also known as manic depression because of extreme swings in mood,
thought and behavior. Bipolar is different than major depression in that it is marked by
episodes of euphoria or mania. These episodes commonly last from hours to days, but can
also last for months.

Bipolar Disorder afflicts 2 million adults, and possibly another 1 million plus children. It usually
starts in adolescence, with males first experiencing a manic episode and females
experiencing a depressive one.

There are two types of bipolar illnesses, bipolar 1 and bipolar 2. Bipolar 1 is more severe
than bipolar 2, and is marked by one or more manic swings followed by one or more major
depressive episodes. Bipolar 2 generally starts with one or more depressive episodes,
followed by a milder (hypomanic) episode.

Bipolar Symptoms

The depressive symptoms are similar to major depression. Mania symptoms may include
some of the following:

Heightened mood
Excited behavior, increased energy or activity
Aggressive behavior and/or irritability
Lack of desire for sleep
Impulsiveness or poor judgment, reckless behavior
Racing speech, thoughts, etc.
Overly optimistic, egoistic, delusions of grandeur
Hallucinations (extreme mania)
Bipolar Disease
“I have been diagnosed recently with manic depression (bipolar disorder), but I really think it
should be called ‘Bipolar Disease,’ because it’s something I’ll struggle with my whole life. I
think I was a bipolar child too, because I would go off in uncontrollable fits & cause a lot of
damage. Afterwards, I would feel terrible guilt for what ‘happened,’ but I would still think, ‘That’
s not me.’
I started losing friends and then I didn’t get new ones because I knew they would leave… It
has affected my schooling and career choices… Now I think my bipolar disease is under
control, and for the first time, I don’t feel ‘drugged up’ with medications anymore. I’m still on
some [medications] and light therapy has helped a great deal to keep me out of my
depression swings.”

Bipolar Disorders in Children

Bipolar disorders generally develop during adolescence, although symptoms can appear
earlier. Symptoms may be different in children than in adults. When manic, children tend to
become aggressive, irritable or prone to destructive outbursts. In a depressive episode, they
may also complain of tiredness, headaches, stomachaches, become emotional and may feel
persecuted, rejected or a failure.

Bipolar Treatment
Bipolar Medicines
Bipolar medications are generally divided into two categories: Mood stabilizers and anti
depressants. The following bipolar medicines are described as well as other effective
supplemental therapies.

Mood Stabilizers

Researchers have noticed the similarity between people who suffer from temporal lobe
seizures and bipolar I. During a seizure, the temporal lobe’s neurons fire wildly, causing many
similar reactions that bipolar I patients experience during manic episodes. These anti-seizure
medications (Lithium, Tegretol, Depakote, Neurontin, etc.) work effectively as mood


Most anti-depressants are categorized as Selective Serotonin Re-uptake Inhibitors because
they act to keep serotonin in the synaptic system longer, thus helping the brain to function
properly. SSRI’s are used to combat the depressive cycles in bipolar depression. Depression
sufferers are believed to have low levels of serotonin.

Light Therapy

The medical journal The Lancet reports that the lack of bright light like sunlight may be a
cause of depression. Bright light produces serotonin in our brains, and scientists believe that
low levels of serotonin contribute to depression. As light produces serotonin, our natural
balance returns, and we’re productive again. Clinical studies at Yale, UCSD and others, have
shown dramatic results using bright environmental light (10,000 lux intensity).

Light does what anti-depressants can’t

The discovery that light produces serotonin is significant, because it may be the only way to
increase serotonin levels in the brain. Pharmaceutical companies have never been able to
replicate this process. Anti-depressant medications are designed to keep serotonin in the
system, but they cannot produce it. For those who already have low levels of serotonin, SSRI’
s are not as effective as they otherwise might be. This is why light may be a beneficial
supplement. Recent studies suggest depression may be more effectively treated with light
and medication rather than medication alone.

Light Therapy Treatment for Bipolar Disorder
Specialized bright light is known as an effective antidepressant. Because most bipolar
patients suffer from depressive episodes during the winter and in overcast conditions,
researchers feel that light therapy should be an obvious choice for manic depression.
Several studies have demonstrated the success of light therapy in averting depressive
episodes in manic depression. In January 2004, the Cochrane Medical Review recommended
light therapy for treating Bipolar Disorders.

Light appears to be successful for two reasons: First, bipolar patients suffer from low
serotonin levels during depressive lows, and second, they are also supersensitive to
melatonin fluctuations. Since light effectively regulates melatonin and serotonin, bipolar
patients respond almost immediately.

Light Therapy & Bipolar Children
Because light therapy poses no long-term negative side effects, it is also recommended for
children. One of the more accurate works on childhood bipolar disorder, The Bipolar Child,
recommends light therapy as a first line treatment.

Cautions With Light Therapy and Bipolar Disorder
Researchers have noted that manic depression sufferers (bipolar 1) should be on an
effective mood stabilizer before using light therapy. Because light produces serotonin, it may
precipitate a manic reaction. Light has been found to be safe when used for less than an
hour at a time, but physician supervision is always recommended.

Omega-3 Fatty Acids

Omega-3 Fatty Acids (DHA and EPA) are fish oil compounds. Researchers discovered the
anti-depressant effect of fish oil by studying the low depression rates of populations that
consumed large amounts of fish. One Harvard study demonstrated that omega-3 fatty acids
were helpful in stabilizing bipolar depression.

How it works

Omega-3 fatty acids are thought to work by nourishing the brain’s nerve cell membranes,
which are made up mostly of DHE fatty acids. Depressed people have low DHE levels. Fish
oil also lowers the risk of heart attacks and strokes, and aids in building dense bones.

Caution: Higher levels of these oils may also produce free radicals. One should consider
taking vitamins C and E as natural anti oxidants. Fish oil may also interfere with anti-clotting
medications, so consult your doctor.

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