Serotonin deficiency may not be linked to depression

Depression strikes some 35 million people worldwide, according to the World Health Organization, contributing to lowered quality of life as well as an increased risk of heart disease and suicide. Treatments typically include psychotherapy, support groups and education as well as psychiatric medications. SSRIs, or selective serotonin reuptake inhibitors, currently are the most commonly prescribed category of antidepressant drugs in the U.S., and have become a household name in treating depression.feelings-54.jpg

The action of these compounds is fairly familiar. SSRIs increase available levels of serotonin, sometimes referred to as the feel-good neurotransmitter, in our brains. Neurons communicate via neurotransmitters, chemicals which pass from one nerve cell to another. A transporter molecule recycles unused transmitter and carries it back to the pre-synaptic cell. For serotonin, that shuttle is called SERT (short for “serotonin transporter”). An SSRI binds to SERT and blocks its activity, allowing more serotonin to remain in the spaces between neurons. Yet, exactly how this biochemistry then works against depression remains a scientific mystery.

In fact, SSRIs fail to work for mild cases of depression, suggesting that regulating serotonin might be an indirect treatment only. “There’s really no evidence that depression is a serotonin-deficiency syndrome,” says Alan Gelenberg, a depression and psychiatric researcher at The Pennsylvania State University. “It’s like saying that a headache is an aspirin-deficiency syndrome.” SSRIs work insofar as they reduce the symptoms of depression, but “they’re pretty nonspecific,” he adds.

Now, research headed up by neuroscientists David Gurwitz and Noam Shomron of Tel Aviv University in Israel supports recent thinking that rather than a shortage of serotonin, a lack of synaptogenesis (the growth of new synapses, or nerve contacts) and neurogenesis (the generation and migration of new neurons) could cause depression. In this model lower serotonin levels would merely result when cells stopped making new connections among neurons or the brain stopped making new neurons. So, directly treating the cause of this diminished neuronal activity could prove to be a more effective therapy for depression than simply relying on drugs to increase serotonin levels.

Evidence for this line of thought came when their team found that cells in culture exposed to a 21-day course of the common SSRI paroxetine (Paxil is one of the brand names) expressed significantly more of the gene for an integrin protein called ITGB3 (integrin beta-3). Integrins are known to play a role in cell adhesion and connectivity and therefore are essential for synaptogenesis. The scientists think SSRIs might promote synaptogenesis and neurogenesis by turning on genes that make ITGB3 as well as other proteins that are involved in these processes. A microarray, which can house an entire genome on one laboratory slide, was used to pinpoint the involved genes. Of the 14 genes that showed increased activity in the paroxetine-treated cells, the gene that expresses ITGB3 showed the greatest increase in activity. That gene,ITGB3, is also crucial for the activity of SERT. Intriguingly, none of the 14 genes are related to serotonin signaling or metabolism, and, ITGB3 has never before been implicated in depression or an SSRI mode of action.

These results, published October 15 2013 in Translational Psychiatry, suggest that SSRIs do indeed work by blocking SERT. But, the bigger picture lies in the fact that in order to make up for the lull in SERT, more ITGB3 is produced, which then goes to work in bolstering synaptogenesis and neurogenesis, the true culprits behind depression. “There are many studies proposing that antidepressants act by promoting synaptogenesis and neurogenesis,” Gurwitz says. “Our work takes one big step on the road for validating such suggestions.”

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The research is weakened by its reliance on observations of cells in culture rather than in actual patients. The SSRI dose typically delivered to a patient’s brain is actually a fraction of what is swallowed in a pill. “Obvious next steps are showing that what we found here is indeed viewed in patients as well,” Shomron says.

The study turned up additional drug targets for treating depression—two microRNA molecules, miR-221 and miR-222. Essentially, microRNAs are small molecules that can turn a gene off by binding to it. The microarray results showed a significant decrease in the expression of miR-221 and miR-222, both of which are predicted to target ITGB3, when cells were exposed to paroxetine. So, a drug that could prevent those molecules from inhibiting the production of the ITGB3 protein would arguably enable the growth of more new neurons and synapses. And, if the neurogenesis and synaptogenesis hypothesis holds, a drug that specifically targeted miR-221 or miR-222 could bring sunnier days to those suffering from depression.

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it’s the courage

 

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Success is not final, failure is not fatal, it’s the courage to continue that counts. Winston Churchil

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Types of Depression

Whether you’re a college student in the middle of a major slump, a new mom who can’t pinpoint why she’s feeling so glum, or a retiree grieving over the loss of a loved one, that question isn’t an easy one to answer.21789-113979.jpg

But there’s one thing for sure: “It is much more than just a sad mood,” said Angelos Halaris, MD, a professor of psychiatry and medical director of adult psychiatry at the Loyola University Medical Center in Chicago. Symptoms may include everything from hopelessness and fatigue to physical pain. And just as symptoms vary from person to person, so do the actual diagnoses. The word depression is actually just an umbrella term for a number of different forms, from major depression to atypical depression to dysthymia.

The most common form of depression? Major depression. In fact, about 7 percent of the adult U.S. population has this debilitating mental health condition at any given time, according to the National Institute of Mental Health (NIMH).

If you’re experiencing major depression, you may feel and see symptoms of extreme sadness, hopelessness, lack of energy, irritability, trouble concentrating, changes in sleep or eating habits, feelings of guilt, physical pain, and thoughts of death or suicide — and for an official diagnosis, your symptoms must last for more than two weeks. In some instances, a person might only experience one episode of major depression, but the condition tends to recur throughout a person’s life.

The best treatment is usually with antidepressant medications, explained Dr. Halaris, but talk therapy may also be used to treat depression. And there’s good news: An estimated 80 to 90 percent of people with major depression respond well to treatment.

About 2 percent of the American population has a form of depression that’s less severe than major depression, but is still very real — dysthymia.

Dysthymia is a type of depression that causes a low mood over a long period of time — perhaps for a year or more, explained Halaris. “People can function adequately, but not optimally.” Symptoms include sadness, trouble concentrating, fatigue, and changes in sleep habits and appetite.

This depression usually responds better to talk therapy than to medications, though some studies suggest that combining medication with talk therapy may lead to the greatest improvement. People with dysthymia may also be at risk for episodes of major depression.

A whopping 85 percent of new moms feel some sadness after their baby is born — but for up to 16 percent of women, that sadness is serious enough to be diagnosable.5241352878_f53a343088.jpg

Postpartum depression is characterized by feelings of extreme sadness, fatigue, loneliness, hopelessness, suicidal thoughts, fears about hurting the baby, and feelings of disconnect from the child. It can occur anywhere from weeks to months after childbirth, and Halaris explained it most always develops within a year after a woman has given birth.

“It needs prompt and experienced medical care,” he said — and that may include a combination of talk and drug therapy.

Would you prefer to hibernate during the winter than face those cold, dreary days? Do you tend to gain weight, feel blue, and withdraw socially during the season?

You could be one of 4 to 6 percent of people in the United States estimated to have seasonal affective disorder, or SAD. Though many people find themselves in winter funks, SAD is characterized by symptoms of anxiety, increased irritability, daytime fatigue, and weight gain. This form of depression typically occurs in winter climates, likely due to the lessening of natural sunlight. “We don’t really know why some people are more sensitive to this reduction in light,” said Halaris. “But symptoms are usually mild, though they can be severe.”

This depression usually starts in early winter and lifts in the spring, and it can be treated with light therapy or artificial light treatment.

Despite its name, atypical depression is not unusual. In fact, it may be one of the most common types of depression — and some doctors even believe it is underdiagnosed.

“This type of depression is less well understood than major depression,” explained Halaris. Unlike major depression, a common sign of atypical depression is a sense of heaviness in the arms and legs — like a form of paralysis. However, a study published in the Archives of General Psychiatry (now known as JAMA Psychiatry) found that oversleeping and overeating are the two most important symptoms for diagnosing atypical depression. People with the condition may also gain weight, be irritable, and have relationship problems.

Some studies show that talk therapy works well to treat this kind of depression.

Psychosis — a mental state characterized by false beliefs, known as delusions, or false sights or sounds, known as hallucinations — doesn’t typically get associated with depression. But according to the National Alliance on Mental Illness, about 20 percent of people with depression have episodes so severe that they see or hear things that are not really there.

“People with this psychotic depression may become catatonic, not speak, or not leave their bed,” explained Halaris. Treatment may require a combination of antidepressant and antipsychotic medications. A review of 10 studies concluded that it may be best to start with an antidepressant drug alone and then add an antipsychotic drug if needed. Another review, however, found the combination of medications was more effective than either drug alone in treating psychotic depression.

If your periods of extreme lows are followed by periods of extreme highs, you could have bipolar disorder (sometimes called manic depressive disorder because symptoms can alternate between mania and depression).

Symptoms of mania include high energy, excitement, racing thoughts, and poor judgment. “Symptoms may cycle between depression and mania a few times per year or much more rapidly,” Halaris said. “This disorder affects about 2 to 3 percent of the population and has one of the highest risks for suicide.” Bipolar disorder has four basic subtypes: bipolar I (characterized by at least one manic episode); bipolar II (characterized by hypomanic episodes — which are milder — along with depression); cyclothymic disorder; and other specified bipolar and related disorder.

People with bipolar disorder are typically treated with drugs called mood stabilizers.

Premenstrual dysphoric disorder, or PMDD, is a type of depression that affects women during the second half of their menstrual cycles. Symptoms include depression, anxiety, and mood swings. Unlike premenstrual syndrome (PMS), which affects up to 85 percent of women and has milder symptoms, PMDD affects about 5 percent of women and is much more severe.

“PMDD can be severe enough to affect a woman’s relationships and her ability to function normally when symptoms are active,” said Halaris. Treatment may include a combination of depression drugs as well as talk and nutrition therapies.

Also called adjustment disorder, situational depression is triggered by a stressful or life-changing event, such as job loss, the death of a loved one, trauma — even a bad breakup.

Situational depression is about three times more common than major depression, and medications are rarely needed — that’s because it tends to clear up over time once the event has ended. However, that doesn’t mean it should be ignored: Symptoms of situational depression may include excessive sadness, worry, or nervousness, and if they don’t go away, they may become warning signs of major depression.

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Movement therapy helps young kids

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Researchers pinpoint brain’s happiness region

creativity1.jpg Happiness is the meaning and the purpose of life, the whole aim and end of human existence,” the ancient Greek philosopher Aristotle once said. But how does one reach this goal? According to a new study by researchers from Japan, a person’s happiness may depend on the size of a specific brain region.

Researchers found people who were happier had larger gray matter volume in the precuneus region of the brain.

Study leader Dr. Wataru Sato, of Kyoto University in Japan, and colleagues publish their findings in the journal Scientific Reports.

The definition of happiness has been debated for centuries. In recent years, psychologists have suggested that happiness is a combination of life satisfaction and the experience of more positive than negative emotions – collectively deemed “subjective well-being.”

But according to Dr. Sato and his colleagues, the neurological mechanisms behind a person’s happiness were unclear.

“To date, no structural magnetic resonance imaging (MRI) investigation of the construct has been conducted,” they note.

“Identification of the neural substrates underlying subjective happiness may provide a complementary objective measure for this subjective construct and insight into its information-processing mechanism.”

 

Meditation may boost happiness by targeting precuneus brain region

To address this research gap, the team used MRI to scan the brains of 51 study participants.

After the scans, subjects were asked to complete three short questionnaires that asked them how satisfied they are with their lives, how happy they are and how intensely they feel positive and negative emotions.

The researchers found that individuals who had higher happiness scores had larger gray matter volume in the precuneus of the brain – a region in the medial parietal lobe that plays a role in self-reflection and certain aspects of consciousness – than their unhappy counterparts.YMen.jpg

What is more, the researchers found that one’s happiness may be driven by a combination of greater life satisfaction and intensity of positive emotion – supporting the theory of subjective well-being.

“These results indicate that the widely accepted psychological model postulating emotional and cognitive components of subjective happiness may be applicable at the level of neural structure,” they add.

These findings, the researchers say, indicate that individuals may be able to boost their happiness through practices that target the precuneus, such as meditation:

“Previous structural neuroimaging studies have shown that training in psychological activities, such as meditation, changed the structure of the precuneus gray matter.

Together with these findings, our results suggest that psychological training that effectively increases gray matter volume in the precuneus may enhance subjective happiness.”

Dr. Sato adds that, while further research is required, these current findings may be useful for developing psychological programs that boost a person’s happiness.

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It takes two

It takes two to lie. One to lie and one to listen. Homer Simpson

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Different Cultures Enhances Creativity

Creativity can be enhanced by experiencing cultures different from one’s own, according to a study in Personality and Social Psychology Bulletin (published by SAGE).

Three studies looked at students who had lived abroad and those who hadn’t, testing them on different aspects of creativity. Relative to a control group, which hadn’t experienced a different culture, participants in the different culture group provided more evidence of creativity in various standard tests of the trait. Those results suggest that multicultural learning is a critical component of the adaptation process, acting as a creativity catalyst.

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The researchers believe that the key to the enhanced creativity was related to the students’ open-minded approach in adapting to the new culture. In a global world, where more people are able to acquire multicultural experiences than ever before, this research indicates that living abroad can be even more beneficial than previously thought.

“Given the literature on structural changes in the brain that occur during intensive learning experiences, it would be worthwhile to explore whether neurological changes occur within the creative process during intensive foreign culture experiences,” write the authors, William W. Maddux, Hajo Adam, and Adam D. Galinsky. “That can help paint a more nuanced picture of how foreign culture experiences may not only enhance creativity but also, perhaps literally, as well as figuratively, broaden the mind.

The article “When in Rome… Learn Why the Romans Do What They Do: How Multicultural Learning Experiences Facilitate Creativity” in the June 2010 issue of Personality and Social Psychology Bulletin.

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