Depression - a disease of the mind and of the body

New View of Depression:

An Ailment of the

Entire Body

The Wall Street Journal

Scientists are increasingly finding that depression and other psychological disorders can be as much diseases of the body as of the mind.

Shirley Wang on Lunch Break discusses the impact of depression on aging and why people with a history of depression are also known to be at greater risk for cardiovascular disease, diabetes and other aging-related diseases.

People with long-term psychological stress, depression and post-traumatic stress disorder tend to develop earlier and more serious forms of physical illnesses that usually hit people in older age, such as stroke, dementia, heart disease and diabetes. Recent research points to what might be happening on the cellular level that could account for this.

Scientists are finding that the same changes to chromosomes that happen as people age can also be found in people experiencing major stress and depression.

The phenomenon, known as "accelerated aging," is beginning to reshape the field's understanding of stress and depression not merely as psychological conditions but as body-wide illnesses in which mood may be just the most obvious symptom.

"As we learn more…we will begin to think less of depression as a 'mental illness' or even a 'brain disease,' but as a systemic illness," says Owen Wolkowitz, a psychiatry professor at the University of California, San Francisco, who along with colleagues has conducted research in the field.

Gaining a better understanding of the mechanisms that link physical and mental conditions could someday prove helpful in diagnosing and treating psychological illnesses and improving cognition in people with memory problems, Dr. Wolkowitz says.

In an early look at accelerated aging, researchers at Duke University found about 20 years ago that brain scans of older people with depression showed much faster age-related loss of volume in the brain compared with people without depression. The reasons for the accelerated aging appeared to go beyond unhealthy behaviors, like smoking, diet and lack of exercise, researchers said.

Recent efforts to study what is behind accelerated aging on a cellular level have focused on telomeres, a protective covering at the ends of chromosomes that have been recognized as playing an important role in aging. Telomeres get shorter as people age, and shortened telomeres also are related to increased risk of disease and mortality.

In several studies conducted at UCSF, researchers have found shortened telomere length to be associated with depression, childhood trauma and other conditions. A study of 43 adults with chronic post-traumatic stress disorder, whose average age was about 30, and 47 healthy control subjects, found shorter telomere length in the PTSD group that equated to an estimated 4.5 years of accelerated aging, Dr. Wolkowitz says. The study was published last year in Biological Psychiatry.

In separate research, scientists in Sweden found similar results. In a study involving 91 patients with major depression and 451 healthy control subjects, researchers from Umeå University concluded that shortened telomere length was associated with depression and greater perceived life stress. The study was published in Biological Psychiatry in February.

Scientists say more work needs to be done to figure out exactly how severe a psychological experience must be to affect telomere length. Some research suggests that as few as two episodes of major depression may be sufficient to affect cell structure. Other studies indicate that the more bouts of depression a person experiences, the more impact there is on telomere length.

The "holy grail" of this area of work is to try to find the molecular mechanisms by which depression or stress take their toll on the body, says P. Murali Doraiswamy, head of the division of biological psychiatry at Duke University, who isn't involved in telomere work. Such information could help provide clues about how much of age-related disease is due to genetics versus life experience, and whether it can be reversed, he says.

Researchers also want to understand why not all stressed people develop shortened telomeres. Telomere length is thought to be affected by the body's production of certain stress hormones or inflammatory molecules, which are made in greater quantities when people are stressed or depressed. Meanwhile, an enzyme known as telomerase acts to protect against telomere shortening.

Some people appear to have innate biological protective factors, like higher antioxidant level and anti-inflammatory proteins, according to UCSF's Dr. Wolkowitz.

How individuals experience the stress, cope with it and view the world more generally also are thought to relate to telomere length. In 2009, the UCSF researchers found that a personality characteristic, pessimism, correlated with shorter telomeres and increased production of a chemical produced by the immune system related to stress.

In another study, UCSF researchers brought into the lab 50 women and exposed them to standard experimental tasks known to induce stress: giving a speech about their personal strengths and weaknesses and completing a difficult math problem out loud. Some of the women were caregivers for chronically ill children and therefore had presumably more stressful lives. But telomere length didn't seem to depend on whether a woman was one of the caregivers or not. Instead, the telomeres were shorter only in those women who reported greater levels of anxiety about having to perform the experimental tasks—seemingly the ones who tended to get more stressed about life's challenges. The research, led by UCSF postdoctoral fellow Aoife O'Donovan, was published online in March in the journal Brain, Behavior, and Immunity.

Researchers believe it takes months, or even years, for stress or depression to affect telomere length. However, the level of activity of the enzyme telomerase may be affected more quickly. In a pilot study involving 24 patients with prostate cancer, Dean Ornish, founder of the Preventive Medicine Research Institute, a nonprofit research group in Sausalito, Calif., demonstrated that telomerase activity in blood cells increased after three months of changes in the patients' lifestyle, including lowering of cholesterol and psychological distress. Although the study didn't measure telomere length, the researchers suggested that increased telomerase activity in the patients could be signaling greater telomere protection at the cellular level. The study, performed together with UCSF researchers, was published in the Lancet Oncology in 2008.

Heightened telomerase levels have been found in some depressed people who are given an antidepressant. These patients also show improvement in clinical measurements of their depression. Other depressed patients, however, who don't show clinical improvements after being given medication, also didn't experience an increase in levels of the enzyme. The findings are from a small study published in February in Molecular Psychiatry.

After finding that some psychological conditions appear to affect telomere length, researchers at UCSF are trying to find out whether information about what is going on in a patient's cells can be used to change the person's psychology. In an ongoing study, researchers are telling patients how their telomere length, which can be detected through a blood sample, compares with that of an average person of the same age. Researchers are then tracking whether the patients, armed with that information, are more motivated to adopt a healthier lifestyle.

Early Aging

People who have major bouts of depression have an increased risk at a younger age of developing conditions typically associated with getting older. This may be because depression makes cells age prematurely, new research suggests.

•Heart disease

•Atherosclerosis

•Hypertension

•Stroke

•Dementia

•Osteoporosis

•Type 2 diabetes

Source: Owen Wolkowitz, UCSF

Ruled by the Body: How Physical Illness Affects the Brain

'Many common ailments and physical conditions can influence the brain, leaving you depressed, anxious or slow-witted.' says Erich Kasten,professor of medical psychology at the University of Lbeck in Germany in an article that appeared in Scientific American on March 3, 2011.

According to Kasten, doctors often forget to ask patients about psychological symptoms. Conversely, psychologists and psychiatrists may treat mental troubles in isolation without looking for a physical cause. But now some doctors and psychologists are reviving the decades-old discipline of somatopsychology, which centers on the effects of physical illness on the brain.

'In Western culture people have long treated body and mind as separate. This dichotomy, popularized by French philosopher René Descartes in the 17th century, is still reflected in medical practice, as the specialists who look after our bodies remain different from those who attend to our psyches. Of course, the division has blurred in recent decades. We now know, after all, that the mind is housed in a physical entity, the brain, which is part of the body. And most people are also aware that psychological problems can produce physical symptoms in the form of psychosomatics; for instance, mental stress can spawn headaches, an upset stomach or even heart problems.

'But fewer people appreciate that the influence also runs in the other direction—that changes in your body can profoundly perturb your mental state,' he says.

Full article available at Scientific American website

Serotonin cell discoveries mean rethink of depression

If you thought depression was caused by low serotonin levels, think again. It looks as if the brain chemistry of a depressed person is much more complex, with mounting evidence suggesting that too much serotonin in some brain regions is to blame.

Read the full article by Linda Geddes at: NewScientist 22 July 2010 Issue 2770

Source: Neuroscience and Pain Science for Manual Physical Therapists on Face Book

Feeling blue, seeing gray: Reduced contrast sensitivity as a marker for depression

Depression has long been associated with vision - and to colour perception in particular - and the link between them is evident in everyday language. Depression is, of course, often referred to as "feeling blue", and those who suffer from it are sometimes told to "lighten up". The link can be found in art, too - Picasso's so-called "Blue Period", for example, which was brought on by the suicide of his close friend Carlos Casagemas, is characterised by a series of striking paintings in shades of cold blue, which express the deep melancholy he felt at the time.

Although the association between depression and colour is largely metaphorical, there is actually some evidence that they are closely linked. The most recent comes from a new study by German researchers published in the journal Biological Psychiatry. The study shows that depressed people have reduced sensitivity to contrast, and therefore that they may perceive the world differently from others. It also suggests that depression can be diagnosed by objective measurements of electrical activity in the eye.

Earlier work has already shown that there is a physiological link between depression and vision. It has long been known, for example, that reserpine, a drug which is prescribed for psychosis and hypertension and which induces depression in humans, causes excessive sensitivity to light in various animals. Other studies have shown that patients with major depressive disorder (MDD) may also be supersensitive to light and that this can be reversed by anti-depressants; that depression causes changes in the electrical activity of the brain in response to visual stimuli; and that this change in activity can be altered by antidepressants.

Last year, neuropsychiatrist Ludger Tebartz van Elst of the University of Freiburg and his colleagues reported that patients with MDD exhibited a reduced sensitivity to contrast, while a team of researchers from Yale showed that visual motion perception is enhanced in depression. But these experiments could not establish whether the observed changes were due to alterations in the retina or the various parts of the brain through which visual information travels and is processed. And because they were based on the conscious experiences of the participants, the reported effects could have been modulated by attentional or other mechanisms.

For their latest study, van Elst's group sought to confirm their previous findings using objective methods, and to determine if any observed changes in the contrast sensitivity of depressed patients are due to changes in the eye or brain. They recruited 40 patients diagnosed with MDD and 40 matched, healthy controls. They presented the participants with visual stimuli consisting of black and white checkerboard patterns, and used pattern electroretinography (PERG) to measure the response to the patterns. The PERG is evoked by viewing patterned stimuli and, in this case, its size is indicative of contrast gain. It is recorded at the cornea, and is thought to represent the activity of the retinal ganglion cells, which are involved in the early processing of visual information and whose axons form the optic nerve that carries the information into the brain.

Specifically, the researchers looked for differences between the two groups of participants in activity reflecting contrast gain, the process by which cells in the retina adapt to variance in the light intensity of the visual scene so that the amount of information extracted from it can be maximized. They found a significant difference in the contrast gain-related activity between the depressed patients and controls. The participants diagnosed with depression displayed a marked reduction in contrast gain when compared with the controls. The reduction was observed in both medicated and unmedicated patients. Those taking medication for their depression, however, had slightly lower depressivity scores and correspondingly better contrast gain than unmedicated patients.

Furthermore, the reduction in contrast gain was strongly correlated with the severity of depression - the more severe the depression, the greater was the observed reduction in contrast gain. No difference was observed between patients with recurrent depression and those experiencing their first episode of the condition, or between depressed patients taking selective serotonin uptake inhibitors such as fluoxetine (Prozac) and those taking tricyclic antidepressants such as imipramine. The intensity of the treatment, or dose being taken, did not affect the reduction in contrast gain observed in the depressed patients. Finally, the researchers could predict, with an accuracy of greater than 90%, which of the participants had been diagnosed with depression on the basis of their electroretinographic recordings.

This is a pilot study whose results need to be replicated. Nevertheless, it shows that processing of visual information related to contrast is altered in the retinae of depressed patients. A likely consequence of this is a reduced ability to perceive contrast - depressed people may indeed experience the world as being less colourful. The study further suggests that PERG could be useful in diagnosing and objectively measuring depression. It's still unclear, however, whether reduced contrast processing is a specific marker of depression. The same effect could possibly occur in patients with other neuropsychiatric conditions such as schizophrenia, and this is could be investigated in future work.

Bubl, E., et al. (2010). Seeing Gray When Feeling Blue? Depression Can Be Measured in the Eye of the Diseased. Biol. Psychiatry 68: 205-208. DOI: 10.1016/j.biopsych.2010.02.009.

Source: http://networkedblogs.com/66zEG

A related article by Sandy Gantaum on The Mouse Trap also asks the question: Why is the world vivid in mania but bleak in depression?

Is pain all in the mind? New research shows why some people are better at coping with pain than others

By Vivienne Parry in TIMESONLINE

Pain is a simple enough concept to grasp. You stub your toe, shout, perhaps utter a few expletives, rub it better and it eventually fades. But neuroscientists are realising that pain is much more complex than anyone thought possible, comprising not just physical sensations, but emotional ones too. Pioneering studies are providing insights into why some people experience debilitating chronic pain long after an injury has healed, as well as why some are more prone to pain than others, and why certain people never recover from bereavement.

“Pain is much more than mere sensation. The psychological component is at least as important as the physiological processes giving rise to it,” says Dr Jonathan Brooks, a scientist at the Centre for Functional Magnetic Resonance Imaging of the Brain, at Oxford University. His research centre scans the brains of people with chronic pain and compares them with those of healthy people.

While most pain goes away as an injury gets better, sometimes it remains for months or even years, long outlasting its original purpose. Chronic physical pain is debilitating and can cause disability, depression and post-traumatic stress disorder. It is also very common. A group from the University of Washington reported in the journal Archives of Surgery earlier this year that 63 per cent of patients who had sustained serious trauma still had injury-related pain a year later. It was most common in the 35-44 age group and in women, and least common in those with a college education.

Other chronic pain conditions include arthritis and lower back pain. In the latter, a physical source can be identified in only about 10 per cent of cases. No one really knows why some people experience chronic pain and others do not, but recent imaging studies at Northwestern University, Chicago, have found a series of abnormalities in the brains of chronic pain sufferers in which the part linked to decision-making (the prefrontal cortex) is reduced, while an area of the prefrontal cortex linked to emotion is hyperactive. What is known for certain is that the brain changes in those with chronic pain so that they experience pain differently from the way they did before.

We all have a system for suppressing pain when necessary so that we can flee attackers even when injured. Those who suffer from chronic pain appear unable to access this and cannot use distraction as a means of suppressing pain; their brains seem to amplify pain signals rather than inhibit them.

Treatment for the condition comprises both physical and psychological interventions, says Dr Michael Platt, the lead clinician for pain services at St Mary's Hospital, London, part of Imperial College Healthcare NHS Trust, where he holds weekly pain clinics. “Most physicians realise that you have to heal the mind as much as the body. For example, if you have pain, then depression is worse, and if you have depression, then pain is worse.” He adds that gaining a better indication of which parts of the brain are involved in pain sensations may lead to better treatments for patients.

We all respond to pain differently

Scientists are increasingly realising that everyone responds to pain differently. “There are many physiological and psychological factors that determine how much pain you feel,” says Dr Brooks. “Personality, how worried a person is, and, in the case of women, the time in the menstrual cycle, can all have an effect.”

He adds that our genes can also influence our sensitivity to pain. This was first brought to the attention of scientists by the “ginger-whinger” syndrome. Anaesthetists reported that redheaded women complain of pain more than other patients, and consequently need more pain relief. Why? Not because redheads are wimps; it was later discovered that their genetic make-up makes them less sensitive to certain types of pain medication.

Neuroscience is also revealing a host of similarities between emotional and physical pain. In the same way that in some people injury can cause long-lasting chronic pain, science reveals why some will never get over heartbreak.

Professor David Alexander, the director of the Aberdeen Centre for Trauma Research, has been involved in many disasters: the 2004 tsunami; Iraq; and the recent earthquake in Pakistan. He is not surprised about the link between physical and emotional pain. “If you listen to people who are damaged emotionally, they will often translate their pain into physical similes: ‘my head is bursting, my guts are aching', and so on. The parallel is very strong.”

It is only in the past few years, however, that scientists have begun to investigate what is going on in the brain during an episode of emotional pain. The neuroscientist Mary Frances O'Connor, of the University of California, Los Angeles (UCLA), is one of the scientists who has propelled emotional pain up the research agenda. “We're at a very new time when we can use technologies to look at the brain and the heart.” Naomi Eisenberger, one of her colleagues at UCLA, has shown which parts of the brain are active when we feel emotional pain. She devised a computer game in which participants were made to feel left out. Simultaneous brain scanning revealed that the pain of being socially rejected was processed in much the same way in the brain as physical pain, and in the same area, the anterior cingulate cortex, which is located towards the front of the brain, roughly at the height of the temples.

Eisenberger theorises as to why this should be so. Pain is often interpreted as a warning, so that you take your hand away from a hot surface. Social relationships are crucial to our survival as a species. In dangerous situations, a lone human being is in peril, whereas a group may survive. “The social attachment system piggybacked on to the physical pain system to make sure that we stay connected to close others,” Eisenberger says. Being wrenched from another or rejected by a group is painful, so we learn to avoid it.

A related issue is “complicated grief”, which O'Connor estimates occurs in about 10 per cent of people, who fail to adapt to bereavement over time. Her imaging work shows that this sort of grief activates neurons in the reward centre of the brain, giving addictive-like properties to memories of the lost one. There is a strong suspicion, as yet unproven, that sufferers might also be among those who experience the greatest levels of chronic physical pain. This is an area that deserves urgent research because of its terrible emotional and physical toll.

http://www.timesonline.co.uk/tol/life_and_style/health/article4397377.ece