Dopamine impacts your willingness to work

Everyone knows that people vary substantially in how hard they are willing to work, but the origin of these individual differences in the brain remains a mystery.

High levels of dopamine activity, shown in orange and yellow, were found in the striatum (center) and ventromedial prefrontal cortex (right) in the brains of "go getters" [Credit: Zald Lab, Vanderbilt University]

Now the veil has been pushed back by a new brain imaging study that has found an individual's willingness to work hard to earn money is strongly influenced by the chemistry in three specific areas of the brain. In addition to shedding new light on how the brain works, the research could have important implications for the treatment of attention-deficit disorder, depression, schizophrenia and other forms of mental illness characterized by decreased motivation.

The study was published May 2 in the Journal of Neuroscience and was performed by a team of Vanderbilt scientists including post-doctoral student Michael Treadway and Professor of Psychology David Zald.

Using a brain mapping technique called positron emission tomography (PETscan), the researchers found that "go-getters" who are willing to work hard for rewards had higher release of the neurotransmitter dopamine in areas of the brain known to play an important role in reward and motivation, the striatum and ventromedial prefrontal cortex. On the other hand, "slackers" who are less willing to work hard for a reward had high dopamine levels in another brain area that plays a role in emotion and risk perception, the anterior insula.

"Past studies in rats have shown that dopamine is crucial for reward motivation," said Treadway, "but this study provides new information about how dopamine determines individual differences in the behavior of human reward-seekers."

The role of dopamine in the anterior insula came as a complete surprise to the researchers. The finding was unexpected because it suggests that more dopamine in the insula is associated with a reduced desire to work, even when it means earning less money. The fact that dopamine can have opposing effects in different parts of the brain complicates the picture regarding the use of psychotropic medications that affect dopamine levels for the treatment of attention-deficit disorder, depression and schizophrenia because it calls into question the general assumption that these dopaminergic drugs have the same effect throughout the brain.

The study was conducted with 25 healthy volunteers (52 percent female) ranging in age from 18 to 29. To determine their willingness to work for a monetary reward, the participants were asked to perform a button-pushing task. First, they were asked to select either an easy or a hard button-pushing task. Easy tasks earned $1 while the reward for hard tasks ranged up to $4. Once they made their selection, they were told they had a high, medium or low probability of getting the reward. Individual tasks lasted for about 30 seconds and participants were asked to perform them repeatedly for about 20 minutes.

"At this point, we don't have any data proving that this 20-minute snippet of behavior corresponds to an individual's long-term achievement," said Zald, "but if it does measure a trait variable such as an individual's willingness to expend effort to obtain long-term goals, it will be extremely valuable."

The research is part of a larger project designed to search for objective measures for depression and other psychological disorders where motivation is reduced. "Right now our diagnoses for these disorders is often fuzzy and based on subjective self-report of symptoms," said Zald. "Imagine how valuable it would be if we had an objective test that could tell whether a patient was suffering from a deficit or abnormality in an underlying neural system. With objective measures we could treat the underlying conditions instead of the symptoms."

Further research is needed to examine whether similar individual differences in dopamine levels help explain the altered motivation seen in forms of mental illness such as depression and addiction. Additional research is under way to examine how medications specifically impact these motivational systems. 

Source: Vanderbilt University [May 01, 2012]

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The bright side of death: Awareness of mortality can result in positive behaviors

Contemplating death doesn't necessarily lead to morose despondency, fear, aggression or other negative behaviors, as previous research has suggested. Following a review of dozens of studies, University of Missouri researchers found that thoughts of mortality can lead to decreased militaristic attitudes, better health decisions, increased altruism and helpfulness, and reduced divorce rates.

"According to terror management theory, people deal with their awareness of mortality by upholding cultural beliefs and seeking to become part of something larger and more enduring than themselves, such as nations or religions," said Jamie Arndt, study co-author and professor of psychological sciences. "Depending on how that manifests itself, positive outcomes can be the result."

For example, in one study American test subjects were reminded of death or a control topic and then either imagined a local catastrophe or were reminded of the global threat of climate change. Their militaristic attitudes toward Iran were then evaluated. After being reminded of death, people who were reminded of climate change were more likely to express lower levels of militarism than those who imagined a local disaster.

"The differences seen in this study resulted from the size of the group with which the test subjects identified," said Ken Vail, lead author and psychology doctoral student. "In both cases, they responded to the awareness of mortality by seeking to protect the relevant groups. When the threat was localized, subjects aggressively defended their local group; but when the threat was globalized, subjects associated themselves with humanity as a whole and became more peaceful and cooperative."

After real catastrophes, such as the terrorist attacks of 9/11 and the Oklahoma City bombing, people's heightened fear and awareness of death had both positive and negative effects.

"Both the news media and researchers tended to focus on the negative reaction to these acts of terrorism, such as violence and discrimination against Muslims, but studies also found that people expressed higher degrees of gratitude, hope, kindness and leadership after 9/11." Vail said. "In another example, after the Oklahoma City bombing, divorce rates went down in surrounding counties. After some stimuli escalates one's awareness of death, the positive reaction is to try to reaffirm that the world has positive aspects as well."

In their personal lives, people also were influenced to make positive choices after their awareness of death was increased. Studies found that conscious thoughts of death can inspire intentions to exercise more. Other studies found that keeping mortality in mind can reduce smoking and increase sunscreen use.

Even subconscious awareness of death can more influenced behavior. In one experiment, passers-by who had recently overheard conversations mentioning the value of helping were more likely to help strangers if they were walking within sight of cemeteries.

"Once we started developing this study we were surprised how much research showed positive outcomes from awareness of mortality," said Arndt. "It seems that people may be just as capable of doing the opposite and 'looking on the bright side of death,' as the Monty Python song says."

Source: University of Missouri-Columbia [April 30, 2012]

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Happiness is not in the jeans

You may throw on an outfit without much thought in the morning, but your choice is strongly affected by your mood. And the item of casual wear in almost everyone's wardrobe -- denim jeans -- is what most people wear when depressed, new research from psychologists at the University of Hertfordshire reveals. 

Denim jeans is what most people wear when feeling depressed [Credit: © art_zzz / Fotolia]

A study conducted by Professor Karen Pine, co-author of "Flex: Do Something Different, found that what a woman chooses to wear is heavily dependent upon her emotional state."* One hundred women were asked what they wore when feeling depressed and more than half of them said jeans. Only a third would wear jeans when feeling happy. In a low mood a woman is also much more likely to wear a baggy top; 57% of the women said they would wear a baggy top when depressed, yet a mere 2% would wear one when feeling happy. Women also revealed they would be ten times more likely to put on a favorite dress when happy (62%) than when depressed (6%). 

The psychologists conclude that the strong link between clothing and mood state suggests we should put on clothes that we associate with happiness, even when feeling low. 

Professor Pine said: "This finding shows that clothing doesn't just influence others, it reflects and influences the wearer's mood too. Many of the women in this study felt they could alter their mood by changing what they wore. This demonstrates the psychological power of clothing and how the right choices could influence a person's happiness." 

Accessories can make a difference too. The study found that: 

• Twice as many women said they would wear a hat when happy than when depressed. 

• Five times as many women said they would wear their favorite shoes when happy (31%) than when depressed (6%). 

The study found that 'happy' clothes -- ones that made women feel good -- were well-cut, figure enhancing, and made from bright and beautiful fabrics. Professor Pine pointed out that these are exactly the features that jeans lack: "Jeans don't look great on everyone. They are often poorly cut and badly fitting. Jeans can signal that the wearer hasn't bothered with their appearance. People who are depressed often lose interest in how they look and don't wish to stand out, so the correlation between depression and wearing jeans is understandable. Most importantly, this research suggests that we can dress for happiness, but that might mean ditching the jeans." 

*FLEX: Do Something Different. How to use the other 9/10ths of your personality, by psychologists Professor Ben (C) Fletcher and Professor Karen Pine, published January 2012 by University of Hertfordshire Press. 

Source: University of Hertfordshire [March 08, 2012]

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A gene for depression localized

Psychiatric disorders can be described on many levels, the most traditional of which are subjective descriptions of the experience of being depressed and the use of rating scales that quantify depressive symptoms. Over the past two decades, research has developed other strategies for describing the biological underpinnings of depression, including volumetric brain measurements using magnetic resonance imaging (MRI) and the patterns of gene expression in white blood cells. 

During this period, a great deal of research has attempted to characterize the genes that cause depression as reflected in rating scales of mood states, alterations in brain structure and function as measured by MRI, and gene expression patterns in post-mortem brain tissue from people who had depression. 

So what would happen if one tried to find the gene or genes that explained the "whole picture" by combining all of the different types of information that one could collect? This is exactly what was attempted by Dr. David Glahn, of Yale University and Hartford Hospital's Institute of Living, and his colleagues. 

"They have provided a very exciting strategy for uniting the various types of data that we collect in clinical research in studies attempting to identify risk genes," said Dr. John Krystal, Editor of Biological Psychiatry. 

Their work localized a gene, called RNF123, which may play a role in major depression. 

They set out with two clear goals: to describe a new method for ranking measures of brain structure and function on their genetic 'importance' for an illness, and then to localize a candidate gene for major depression. 

"We were trying to come up with a way that could generally be used to link biological measurements to (psychiatric) disease risk," said Dr. John Blangero, director of the AT&T Genomics Computing Center at the Texas Biomedical Research Institute. "And in our first application of this, in relation to major depressive disorder, we've actually come up with something quite exciting." 

While RNF123 hasn't previously been linked to depression, it has been shown to affect a part of the brain called the hippocampus, which is altered in people with major depression. 

"We assume that the biological measures are closer mechanistically to the underlying disease processes in the brain. Yet, ultimately we are interested in the subjective experiences and functional impairment associated with mental illness," added Krystal. "The approach employed in this study may help to make use of all of this information, hopefully increasing our ability to identify genes that cause depression or might be targeted for its treatment." 

Glahn said, "We still have more work before we truly believe this is a home-run gene, but we've got a really good candidate. Even that has been tough to do in depression." 

Source: Elsevier [January 04, 2012]

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Deep brain stimulation shows promising results for unipolar and bipolar depression

A new study shows that deep brain stimulation (DBS) is a safe and effective intervention for treatment-resistant depression in patients with either unipolar major depressive disorder (MDD) or bipolar ll disorder (BP). The study was published Online First by Archives of General Psychiatry, one of the JAMA/Archives journals. 

The study was led by Helen S. Mayberg, MD, professor in the Departments of Psychiatry and Behavioral Sciences and Neurology at Emory University School of Medicine, with co-investigators Paul E. Holtzheimer, MD, lead psychiatrist and now associate professor and director of the Mood Disorders Service, Dartmouth Medical School, and neurosurgeon Robert E. Gross, MD, PhD, associate professor in the Departments of Neurosurgery and Neurology at Emory. Gross served as chief neurosurgeon for the study. 

"Depression is a serious and debilitating medical illness," says Mayberg. "When we found that the potential for effective and sustained antidepressant response with DBS for patients with otherwise treatment resistant major depressive disorder was high, the next step was to determine if patients with intractable bipolar depression could also be successfully treated." 

An earlier study by Mayberg done in Toronto in collaboration with scientists at Toronto Western Hospital, University Health Network and Emory, was the first to show such results for patients with treatment-resistant major depressive disorder. Mayberg conducted this new expanded trial at Emory to include patients with bipolar ll disorder. 

Bipolar spectrum disorder, sometimes referred to as manic-depression, is characterized by bouts of mania or hypomania alternating between episodes of depression. Although people with bipolar ll disorder do not have full manic episodes, depressive episodes are frequent and intense, and there is a high risk of suicide. A major challenge in treating bipolar depression is that many antidepressant medications may cause patients to "switch" into a hypomanic or manic episode. 

DBS uses high-frequency electrical stimulation targeted to a predefined area of the brain specific to the particular neuropsychiatric disorder. Here, each study participant was implanted with two thin wire electrodes, one on each side of the brain. The other end of each wire was connected under the skin of the patient's neck to a pulse generator implanted in the chest – similar to a pacemaker – that directs the electrical current. 

Study participants received single-blind stimulation for four weeks (patients did not know if the DBS system was on or off), followed by active stimulation for 24 weeks. Patients were evaluated for up to two years following onset of active stimulation. Seventeen patients were enrolled in the study. 

A significant decrease in depression and increase in function were associated with continuing stimulation. Remission and response rates were 18 percent and 41 percent after 24 weeks; 36 percent and 36 percent after one year and 58 percent and 92 percent after two years of active stimulation. Patients who achieved remission did not experience a spontaneous relapse. Efficacy was similar for Major Depressive Disorder and Bi-Polar patients, and no participant experienced a manic or hypomanic episode. 

Mayberg and her colleagues continue to refine this intervention. Current studies include demographic, clinical and imaging predictors of response and remission, and introduction of psychotherapeutic rehabilitation. Why and how this treatment works is the primary focus of ongoing research. 

"Most of these patients have been in a depressed state for many years and are disabled and isolated," says Holtzheimer. "As their depression improves, they need a process to help them achieve full recovery that includes integration back into society. 

"We hope to optimize the rate of improvement for these patients by using a model of care that provides psychotherapeutic rehabilitation built on evidence-based psychotherapy but tailored to the specific individual's situation."  

Source: Emory University [January 02, 2012]

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A novel mechanism regulating stress is identified

Neuroscience researchers from Tufts have demonstrated, for the first time, that the physiological response to stress depends on neurosteroids acting on specific receptors in the brain, and they have been able to block that response in mice. This breakthrough suggests that these critical receptors may be drug therapy targets for control of the stress-response pathway. This finding may pave the way for new approaches to manage a wide range of neurological disorders involving stress. 

The stress-control pathway, more technically known as the Hypothalamus-Pituitary-Adrenal (HPA) axis, determines the levels of cortisol and other stress hormones in the human body. In addition to being implicated in the types of emotional and psychological stress that can lead to major depression, disorders of the stress-control pathway are also associated with obesity, premenstrual syndrome, postpartum depression, Cushing's syndrome (hypercortisolism) and diseases including epilepsy and osteoporosis. 

"We have identified a novel mechanism regulating the body's response to stress by determining that neurosteroids are required to mount the physiological response to stress. Moreover, we were able to completely block the physiological response to stress as well as prevent stress-induced anxiety," said author Jamie Maguire, PhD, assistant professor in the department of neuroscience at Tufts University School of Medicine and a member of the Neuroscience and Pharmacology & Experimental Therapeutics program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts. 

Using the brain tissues of adult mice, the research team identified mechanisms controlling the activity of Corticotrophin Releasing Hormone (CRH) neurons involved in the control of the stress pathway. By monitoring the activity of CRH neurons following stress and measuring levels of corticosterone in the blood, they found that the production of stress hormones required the action of neurosteroids on specific receptors on CRH neurons. 

Apart from the finding that stress causes a neurosteroid-induced increase in blood corticosterone levels, the researchers also found that blocking the synthesis of neurosteroids is sufficient to block the stress-induced elevations in corticosterone and prevent stress-induced, anxiety-like behavior in mice. Previous research had identified the presence of specialized CRH-nerve-cell receptors in the HPA axis, but the findings had been controversial because of limited studies showing any connection between these receptors and the regulation of the CRH nerve cells. 

"We have found a definite role of neurosteroids on the receptors regulating CRH nerve cells and the stress response. The data suggest that these receptors may be novel targets for control of the stress-control pathway. Our next work will focus on modulating these receptors to treat disorders associated with stress, including epilepsy and depression-like behaviors," said Maguire. 

Source: Tufts University, Health Sciences Campus [December 13, 2011]

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Mental Illness: Probing the causes of schizophrenia, depression and anxiety

New research identifies the brain chemicals and circuits involved in mental illnesses like schizophrenia, depression, and anxiety, giving potential new directions to their treatment. In addition, research with children shows that early-life depression and anxiety changes the structure of the developing brain. The findings were presented at Neuroscience 2011, the Society for Neuroscience’s annual meeting and the world’s largest source of emerging news about brain science and health. 

One in 17 Americans suffer from a serious mental illness, such as schizophrenia, major depression, or bipolar disorder, making it one of the leading causes of disability. Yet science is only beginning to understand the underlying physical causes of these diseases. 

Today’s new findings show: 

• Childhood anxiety and depression alter the way the amygdala connects to other regions of the brain. This finding may help explain how early life stress can lead to future emotional and behavioral issues (Shaozheng Qin, PhD, abstract 927.06, see attached summary). 

• In animal studies, a link between two factors associated with schizophrenia, prenatal infection and impaired function of a molecule important in memory (Melissa Burt, abstract 763.11, see attached summary). 

• Researchers have identified a brain chemical important to antidepressant response in mice. The findings may help in the design of therapies for major depression (Maha Elsayed, abstract 904.10, see attached summary). 

• The connections between two specific areas of the brain — the prefrontal cortex and the dorsal raphe nucleus — may contribute to depression. Stimulating these circuits in rats had an antidepressant effect (Melissa Warden, PhD, abstract 306.15, see attached summary). 

• An enzyme called STEP is elevated in the brains of people with schizophrenia. Mice lacking this chemical did not develop schizophrenia-like behaviors (Nikisha Carty, PhD, abstract 238.03, see attached summary). 

"If we can fully understand the roots of mental illness in brain circuitry and systems, we may be able to develop better treatment targets for the millions suffering from these diseases," said press conference moderator Carol Tamminga, MD, of the University of Texas Southwestern, who is an expert on schizophrenia. 

This research was supported by national funding agencies, such as the National Institutes of Health, as well as private and philanthropic organizations. 

Source: Society for Neuroscience [November 15, 2011]

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Obesity and depression independently increase health costs

Obesity and depression both dramatically increase health care costs, but they mainly act separately, according to a study published in the November 2011 Journal of General Internal Medicine by Group Health Research Institute scientists. Gregory Simon, MD, MPH, a Group Health psychiatrist and Group Health Research Institute senior investigator, led the research. 

“Previous research shows that both depression and obesity are associated with higher health care costs,” he said. “But depression and obesity often occur together, so it was important to know if the relationship between obesity and cost is really due to depression—or vice versa.” 

Simon and his colleagues tested whether depression confounds the increase in health care use that is associated with obesity. Confounding means an apparent connection—such as the link between increased health care costs and obesity—is influenced or even caused by a third factor. In this study, the authors tested if depression confounds the increase in health care seen in obese patients. 

The study used telephone interviews to determine obesity and depression, and Group Health’s extensive medical records to calculate health care costs for 4,462 women aged 40–65. All were enrolled in Group Health Cooperative, a nonprofit health care system in Washington and northern Idaho. Obesity was measured as body mass index (BMI), a standard obesity measure that is calculated from height and weight. A BMI below 25 is considered normal weight, 25-30 considered overweight, and over 30 is considered obese. Depression was measured with a 9-item American Psychiatric Association questionnaire. 

The researchers found: 

• In middle-aged women, health care costs increased with obesity. Specifically, costs increased 65 percent in women with a BMI of 30-35, and 157 percent in women with a BMI higher than 35, compared to women of normal weight. 

• The trend was similar for all types of health care that the researchers examined: primary care, outpatient prescriptions, specialist visits, inpatient care, and mental health care. 

• Health care costs increased with higher depression scores, but depression was a not a major confounder of the obesity results. 

• Even accounting for depression, health costs increased with every rise in BMI category. 

The study concluded that in this population of women, obesity is associated with higher health care costs, but not because of co-occurring depression. Similarly, depression is associated with higher costs, but not because of co-occurring obesity. These higher costs have an economic impact. Increased costs associated with depression were spread across all types of health care, not just mental health care. 

“Obesity and depression are both very common,” Dr. Simon said, “so the increased costs we find add up to a very large amount in the general population.” The relationships among obesity, depression, and chronic illness related to obesity are complex, as are the effects of depression on behavior and health. But one thing is clear, the study’s authors said: Effective obesity prevention is a crucial factor in tackling our rising health care costs. 

Source: Group Health Research Institute [October 31, 2011]

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