
| DEPRESSION |

| original Article Neuropsychopharmacology advance online publication 19 September 2007; doi: 10.1038/sj. npp.1301560 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: matthaeus.willeit@meduniwien.ac.at; 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: harald.sitte@meduniwien.ac.at 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. http://www.nature.com/npp/journal/vaop/ncurrent/pdf/1301560a.pdf CIRCADIAN RHYTHMS > DEPRESSION Related Pages: 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 stabilizers. SSRI’s 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. © 2003-2007 geciconseils Health, Inc. Terms of Use Privacy Policy Contact Us contactos@yourvida.com |

