In recent blog entries, we've discussed research that's linked gene variations with medications in order to determine if they'll be safe and effective for individuals with depression.

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The study of these relationships is referred to as psychiatric pharmacogenomics. These aren't tests to determine whether someone is depressed or not. As some of you pointed out, after years of suffering, the diagnosis of depression is not the issue.

The important new development is trying to find an effective treatment. While single genes such as the serotonin transporter gene provide us with some clues, there are still other genes that need to be discovered in order to be able to make better predictions than we can today.

In the past year, three large studies have been conducted to explore possible new genes associated with a better outcome. They include a study in England that found a gene called interleukin-2 was associated with a response to Celexa. However, studies in Germany and the United States didn't confirm this finding.

At Mayo Clinic, we're conducting a similar study to try to identify more gene variants so that we can make better predictions of response to treatment. Another goal is to find new genes that are associated with adverse effects. While many adverse effects are associated with antidepressant medications, one of the most serious is "activating" an episode of mania in someone who's previously not experienced mania.

Another major concern is that sometimes antidepressant medication seems to aggravate suicidal thoughts.  Progress is being made in using genomic testing to be able to identify who may be more likely to develop these problems.

One of the greatest motivations for finding new genes associated with medication response is that gene variation may give us new clues to help us develop new medications for depression — given that at least one in five of you with depression don't respond to any of the drugs currently available.

Helping you if you have treatment resistant depression is a critically important priority for research. Please share your thoughts.

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For some, the holidays are an especially difficult time. For others, this is a joyous time of year. National Suicide Prevention Lifeline
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1-800-950-NAMI (6264)Holiday depression — and depression in general — challenges even the most optimistic people. Although it may be difficult, promise yourself that you will commit to having a positive attitude. If you're feeling depressed during the holidays, do the following for yourself: (this will take practice)

Do the best you can. (perfection is not attainable)Give yourself the gift of positive self talk (don't repeat negative message from the past that are not true)Truly believe in yourself, including your goodness and self-worthAccept that life is not perfect. Injustices and suffering occur. It is normal at times to feel angry and to grieve. Get help on how to manage these feelings.

Depression can literally strip away self-esteem and the hope that things can get better. Depression can cause you to think in a very negative manner. But don't get discouraged. Get the help you deserve today. Share with us any tips you use on getting through holiday depression.

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We've known for awhile that some people will have a worsening of their mood in the winter. National Suicide Prevention Lifeline
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1-800-950-NAMI (6264)This is referred to as Seasonal Affective Disorder or SAD. SAD can be treated effectively with medication and/or light therapy.

A specific type of light, a full-spectrum light, is sometimes used to treat SAD. Insurance may or may not pay for the light. Not all people with depression have a seasonal worsening of mood.

Some things to keep in mind about SAD and light therapy:

The benefits of light therapy have clearly been shown in multiple studies over many yearsMost people with a diagnosis of SAD show improvement in depressive symptoms one week after starting light therapyLight therapy typically causes few side effects Light therapy requires 15 to 30 minutes per dayUse of light therapy in patients with bipolar affective disorder may destabilize the mood

Currently, researchers are looking at using light therapy to treat major depressive disorder as well as other psychiatric illnesses. Time will tell if light therapy can be used alone to treat depression or other psychiatric illnesses. As always, don't self-diagnose or self- treat; talk to your provider about your symptoms.

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We've all heard that doing things "in moderation" is acceptable. National Suicide Prevention Lifeline
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1-800-950-NAMI (6264)So can you drink a moderate amount of alcohol if you have depression? I don't advise it. In most cases, one should steer clear of alcohol for a number of reasons:

Potentially dangerous interactions with medications. Not just psychiatric medications and not just prescription medications, remember over-the-counter medications, too!Alcohol itself is a depressant and can make depression (and anxiety) worse.Alcohol affects one's judgment and decreases inhibitions.Alcohol has a negative impact on the quality of sleep overall.Alcohol can worsen other health problems.

Have a discussion with your health care provider regarding alcohol and depression. Certainly if you have a history of alcohol abuse, dependence, and/or have had treatment for alcohol or other drugs, please be honest with your provider. Your provider will be able to best help you when they have all the facts.

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Privacy policy (Updated Aug. 2, 2011) Terms and conditions of use policy (Updated Aug. 2, 2011)

LEGAL CONDITIONS AND TERMS OF USE APPLICABLE TO ALL USERS OF THIS SITE. ANY USE OF THIS SITE CONSTITUTES YOUR AGREEMENT TO THESE TERMS AND CONDITIONS OF USE.

© 1998-2011 Mayo Foundation for Medical Education and Research. All rights reserved.

This blog has sensitized me to how hard it is for so many of you with severe depression to find help. National Suicide Prevention Lifeline
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1-800-950-NAMI (6264)It's very clear that there's a wide range of severity of symptoms. Perhaps more importantly, there are wide variations in the responses you have to the currently available treatments.

If you begin to experience severe depression for the first time as a young adult, the prognosis is generally quite good. There's an almost 50 percent remission rate with the selection of the first medication — if it's taken properly and for a sufficient period of time. Ultimately, more than 80 percent of you will respond to one of the many available medications. However, the fact that some of you don't respond is a huge problem.

There's no simple solution for treatment resistant patients. Your best hope is to be persistent. However, it's difficult to be persistent when you're seriously depressed. It's a cruel "Catch 22."

Electroconvulsive therapy (ECT) is available for treatment resistant patients and many do respond to it. While there continues to be controversy about it, and there's no question that it can result in the loss of memory, ECT has saved the lives of many. Newer treatments, such as transcranial magnetic stimulation (TMS), offer hope. However, those who are resistant to medications may also be resistant to TMS.

Over the years, I've seen our treatments improve. I remember a world without serotonin transporter inhibitors. It was a world where our best drugs had considerable toxicity. It was also a time when we had fewer options if you were seriously depressed.

We treat thousands of people who have mood disorders. Clearly, most if them get better and many have a complete remission of their symptoms. However, it would be wrong to suggest that even in 2010 there's an effective treatment for everyone. Nevertheless, we're committed to finding new ways to try to help everyone.

There's no major medical specialty that has the ability to cure everyone they try to treat. Some people with asthma don't respond to even the newest asthma medications and have crippling wheezing which dramatically restricts their activity. Some people with diabetes can't control their glucose despite the huge advances in our understanding of the biological basis of diabetes. Perhaps most frustrating of all, many cancers continue to take the lives of our loved ones despite billions of dollars of medical research and the hard work of many medical professionals.

I don't want to suggest there's an easy answer for those of you who suffer from treatment resistant depression. However, I do want to underscore that many of you can improve with modern treatments. For those who don't, it's critical to maintain your determination to "fight the battle" even when it seems hopeless. Having friends, a family that cares, and a doctor you can trust are still among the most powerful weapons to fight depression.

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Dear friends of the depression blog,

Thank you for continuing the conversation even though there's been a gap in postings from us. National Suicide Prevention Lifeline
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1-800-950-NAMI (6264)Dr. Melin's been drawn into some other responsibilities of late and that's why we've had a break in our expert postings.

We don't intend to leave this blog without an expert for long. Please stay with us during this delay. We hope MayoClinic.com will continue to be a place where you can share your thoughts about the trials of living with depression.

- Medical editor-in-chief Roger W. Harms, M.D.

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It seems to be common sense that hard times are associated with developing depressive symptoms. When a personal crisis occurs, many people who had been coping pretty well become clinically depressed.

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The two classic examples are losing a relationship or losing a job. However, if a company terminates 100 employees, most of them don't develop a depressive illness. An important question is why one employee manages to cope while another develops a mood disorder.

Seven years ago, an important paper published in one of our most respected scientific journals reported that people with a genetic variant of the serotonin transporter gene were more likely to become depressed when they had experienced stressful situations.

If a person had this genetic variant and wasn't exposed to very stressful situations, they weren't any more vulnerable to depression than if they had the more protective form of the gene. It was only when they had experienced severe personal distress that their depressive symptoms occurred. People without this genetic variant were often able to tolerate quite severe stress and not develop symptoms.

There has been much discussion of this finding. Many studies were done that measured stressful experiences in a variety of different ways. About a year ago, a paper reviewed only 14 of these studies and concluded that people with this genetic variant weren't very much more vulnerable to stress. There were problems with this analysis, but it was published in a good journal and it made some doctors a bit skeptical about the finding.

This week, a new analysis of 56 studies concluded that there was a strong relationship. They demonstrated that people with the less active form of the serotonin transporter gene were more vulnerable to developing depression when they experienced severe stress.

The analysis found:

The strongest relationship was between severe stresses during childhood that then seemed to haunt the person for the rest of their life. This finding supports the view that young children are particularly vulnerable and that early abusive experiences can have a long lasting impact. The next most difficult type of stress was serious medical problems. This also makes sense as we have known for many years that some people become very depressed when faced with the prospect of having to deal with a serious medical illness.The least dangerous kind of stress was the hassles of everyday living that we're all familiar with and that sometimes get out of hand. However, even this kind of stress was associated with an increased risk of depression if a person had this genetic variant.

The bottom line is that this new analysis provides strong evidence that stress can trigger depression and that the onset of depression is far more likely in people who are genetically vulnerable to developing a mood disorder.

Does this mean that if you have the variant, you are doomed to become depressed? Absolutely not. It just means that you're more vulnerable to developing symptoms.

Does the study prove that if you don't have the variant, you won't develop a depression if you're exposed to intense stress? Again, absolutely not. It just means that the risk is lower.

Perhaps the most important point that this analysis makes is that there is a biological vulnerability to depression just like there is a biological vulnerability to diabetes, asthma, or cancer.

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It's all too clear that while many of you experience a dramatic positive response to antidepressant medications, others are frustrated and angry with the ineffectiveness of the treatment you've received.

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It's long been recognized that electroconvulsive therapy is an effective treatment, but the cost is high and problems with memory following treatment are not uncommon. For many years, treatment resistant patients have been waiting for an alternative treatment. In 2009, the FDA approved transcranial magnetic stimulation (TMS) as an alternative form of treatment for these individuals.

While transcranial magnetic stimulation has its own limitations, it can be quite effective for those of you who don't tolerate treatment with medications and aren't willing to consider electroconvulsive therapy. Since the FDA approval, the treatment has become much more widely available. While new strategies for providing TMS are being developed, the basic strategy is to provide daily treatments that last for approximately 40 minutes and don't require anesthesia.

A real advantage of transcranial magnetic stimulation is that it has a very low incidence of side effects. While some patients can begin to feel better during the first week, others require as many as six weeks before their depression resolves. While we are only beginning to understand the factors that increase the risk for relapse following a full course of treatment, some evidence suggests that a relatively modest number of ongoing treatments will maintain a positive effect.

The biggest barrier to obtaining transcranial magnetic stimulation at this point in time is concern about insurance coverage. However, as the efficacy of TMS becomes more firmly established, it's likely that insurance coverage will become more universal. The bottom line if you've struggled with antidepressant medications is that there's now an effective and safe alternative treatment.

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It's well known that depression symptoms can be caused or worsened by many medical illnesses. National Suicide Prevention Lifeline
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1-800-950-NAMI (6264)One of these is thyroid disease.

Your thyroid gland is important in controlling metabolism. If it's not functioning properly, it can affect your mood. Your thyroid can be underactive or overactive, as well as normal.

Interestingly, there is a thyroid hormone produced by your brain that travels through your bloodstream to the thyroid gland in your neck. The thyroid gland, in turn, produces other hormones that regulate metabolism.

Your health care provider may check your thyroid with a blood test. Additionally, thyroid hormone is sometimes added to the antidepressant you are currently on to give it a boost.

Some medical conditions preclude the use of oral thyroid hormone. Talk with your health care provider about options as not everyone is a candidate for this.

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Pharmacogenomics is a new field of study in medicine. It involves the identification of genetic variations that predict the response of a patient to a medication. Pharmacogenomics is relevant for all types of drugs such as medications for asthma or hypertension. It's now possible to use pharmacogenomic testing to help select an antidepressant.

In a previous blog, I discussed the relationship between a variant of the serotonin transporter gene and vulnerability to developing depression when faced with severe stress. If you have the more active form of this gene, you're less likely to develop depression even if you find yourself in a stressful situation. However, if you have the more active form of this gene and do become depressed, you're more likely to get better if you take a selective serotonin reuptake inhibitor (SSRI) antidepressant like Prozac (fluoxetine), Paxil (paroxetine), or Celexa (citalopram).

The probability of a good response to an SSRI is particularly high if you identify yourself as being "white." This suggests that other gene variations that are more common in patients of European ancestry may also influence the response of these patients to SSRI's.

For several years, it's been known that patients with the more active form of the serotonin transporter gene are more likely to respond to SSRI treatment. However, it's only been possible to test patients to see whether they have a more or less active form of this gene for the past three years. Based on the results of this pharmacogenomic testing, a psychiatrist is now able to develop a better understanding of what the probability will be for a specific patient achieving a good clinical outcome. The primary goal of testing is simply to be able to avoid side effects and identify an effective antidepressant medication more quickly.

To be able to get an even more accurate prediction of response, it will ultimately be necessary to test more than any one single gene as many genes influence the probability of responding to treatment. As testing becomes more sophisticated, there's every reason to believe that treatment outcomes will continue to improve. For many of you struggling with depression, the fact that there are now many researchers working to better understand antidepressant medication response should provide some hope.

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We talk about depression as if it were a single entity. National Suicide Prevention Lifeline
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1-800-950-NAMI (6264)This is clearly not the case. What we refer to as depression is actually many illnesses that are characterized by profound sadness. No one wants to be sick, but it's less disastrous to be sick if there's a treatment that that can effectively treat your condition.

For many of you with depression, when you take an antidepressant medication, you'll feel better. I conducted a study supported by the National Institutes of Health, rather than a pharmaceutical company, to try to identify which patients will respond to escitalopram, known as Lexapro, and which ones will not. We treated more than 600 patients with moderately severe depression. Half of the patients who took the antidepressant were feeling well within two months, and another 20 percent were feeling a lot better. Unfortunately, 30 percent were not much better.

If depression is a new problem, you have every reason to be optimistic you'll be among the 70 percent of patients who have a good response to antidepressant treatment. When an antidepressant does work, both you and your doctor are grateful.

However, a dangerous situation can evolve if a series of antidepressant medications don't work. If no medication provides relief after a reasonable number have been tried, it becomes clear that you're suffering from treatment-resistant depression and that another form of treatment needs to be tried. However, you should have the opportunity to try all of the classes of antidepressant medications before coming to the conclusion that medications won't help.

A really critical problem for many of you is that you can't get access to appropriate medical care. This is what healthcare reform should be about. Everyone should have access to effective treatments. Unfortunately, many still don't.

A final thought is that making a persistent effort to find an effective treatment usually results in success. For those of you who can't find help, this isn't comforting. However, for those who do have access to care, the odds of being able to feel well again are good.

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Depression can zap your confidence. National Suicide Prevention Lifeline
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1-800-950-NAMI (6264)Some days you may feel like you can't even follow through with the smallest of tasks. Being grateful can do wonders for your mood.

This doesn't have to be elaborate or detailed. I suggest that you write down three things each day that you're thankful for. This can be three sentences or three words, the simpler the better. Keep paper or a journal by your bedside and jot in it daily. This can be at bedtime or in the morning, whichever works best for you.

What's so nice about jotting down why you're being grateful is that it doesn't take a lot of effort and is very powerful. Looking back over what you've written can help you to evaluate and learn where you've been and who you have become. This is a simple, reasonable goal that you can accomplish. This will build up your sense of positive self worth. You can do it, and you deserve to invest in yourself.

Please share your thoughts.

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