A breakthrough study of the brain shows the stress code

Neuroscientists investigating the 'brain code' claim to have made a significant step forwards in understanding how the brain deals with stress- and mitigates its impact. Examining what they term 'thin' and 'mushroom-like' parts of nerve cells in the brain, which are responsible for learning and remembering, they discovered that it is possible to alter what is remembered thereby mitigating the stress of painful memories.
A team from the University of Leicester has identified a particular protein that the brain produces in response to stress. Tests on mice revealed that those without this protein were less 'outgoing' and preferred to 'hide in the dark'.
The findings, published in Proceedings of the National Academy of Sciences (PNAS), are potentially important for understanding stress-related psychiatric diseases in humans. The work was supported by a Marie Curie Excellence Grant from the European Commission.
Dr Robert Pawlak, lecturer in Neuroscience at the University of Leicester, said the breakthrough study had determined that production of the protein by the brain may help to protect individuals from "too much anxiety" and help organisms to cope with various adverse life events.
Dr Pawlak, from the University Department of Cell Physiology and Pharmacology, said: "Every day stress "reshapes" the brain -- nerve cells change their morphology, the number of connections with other cells and the way they communicate with other neurons. In most cases these responses are adaptive and beneficial they help the brain to cope with stress and shape adequate behavioural reaction. However, upon severe stress things can get out of control, the brain "buffering" capacity is exhausted and the nerve cells in the hippocampus an area of the brain responsible for learning and memory -- start to withdraw their processes, don't effectively communicate with other cells and show signs of disease.
"One strategy that brain cells particularly like to use to cope with stress is changing the shape of tiny processes they normally employ to exchange information with other neurons, called dendritic spines. Spines can be as small as 1/1000 of a millimeter and have various shapes. Long spines (called "thin" spines) are like children -- very mobile and inquisitive, constantly change shape and "conversation" partners -- they help us learn new things. Once spines learn, they change into mature "couch potatoes" -- they are mushroom-shaped, have stable connections, do not change partners and do not like to move."
"Mushroom spines help us remember things we once learned -- but it is not always good. Some very stressful events would better be forgotten quickly or they may result in anxiety disorders. There is a constant battle of forces in our brain to help maintain the right balance of thin and mushroom spines -- or how much to remember and what better to forget.
"We have identified a protein that the brain produces in response to stress in order to reduce the number of mushroom spines and therefore reduce future anxiety associated with stressful events. This protein, lipocalin-2, is normally not produced, but its fabrication dramatically increases in response to stress in the hippocampus. When we added lipocalin-2 to neurons in culture the way it occurs on stress, neurons started losing their "memory spines" -- the mature, mushroom-shaped ones.
"We therefore asked -- what if we remove lipocalin-2 from the brain and subject mice to stress? Would that affect the way they react? To this end we used mice in which the lipocalin-2 gene was disrupted and found that, on stress, they were more anxious than normal mice. For example, they were less "outgoing" and preferred hiding in dark, enclosed spaces instead of exploring the neighborhood normally. We found that in these mice mushroom spines were more readily formed in the brain after stress and therefore they had stronger memories of the stressful event.
"Thus, the brain produces lipocalin-2 in order to protect us from "too much anxiety" and help us cope with various adverse life events.
"Identification of lipocalin-2 as a new player the brain uses to help us cope with stress is an important step forward. We are getting closer to deciphering molecular mechanisms of buy cheap Valium, if not functioning properly, may lead to stress-related psychiatric diseases."
"Stress-related psychological and mental disturbances are extremely common and affect more than 30% of the population. We are keen to investigate whether the mechanisms discovered by us apply to humans and could help inform clinical strategies to deal with anxiety disorders and depression."

Brain Tissue Signals Increased Risk Of Inherited Depression

In cases of familial depression, changes in tissue thickness in key brain structures in the right half of the brain may increase a person's risk for developing depression, according to NIMH-funded researchers. Similar changes in the left half of the brain were linked to the severity of a person's existing depression or anxiety symptoms. Based on their findings, the researchers proposed a possible mechanism for how these brain changes affect depression risk in the Proceedings of the National Academy of Sciences.
Background
Some types of depression run in families, and certain changes in brain structure and function have been observed in people with the disorder. However, until recently, scientists have been unclear on the exact relationship between these brain changes and depression.
Building on previous research with a three-generation study population, Myrna Weissman, Ph.D., and Bradley Peterson, M.D., both of Columbia University College of Physicians & Surgeons and New York State Psychiatric Institute, and colleagues used magnetic resonance imaging (MRI) to assess brain changes in 131 people, ages 6-54. Roughly half of these participants were considered at high risk for major depressive disorder (MDD), due to having at least one parent or grandparent in the study diagnosed with the illness. The other half, considered at low risk, had no family history of the illness.
Results of the Study
From pre-scanning interviews, the researchers found that people in the high-risk group were more likely than those in the low-risk group to report having MDD or an anxiety disorder at some point in their lives. MRI scans showed that, on average, those in the high-risk group had 28 percent thinner brain tissue across a broad range of brain structures in the right half of the brain. These changes were observed in young children in the high-risk group and in older high-risk individuals who had never suffered from MDD or an anxiety disorder themselves.
The brain areas most affected by this thinning govern attention and the ability to process emotional or social cues (such as faces or family pictures). In tests involving these right-brain tasks, the researchers found that thinner tissue in these areas was linked to greater inattention and poorer performance in immediate and delayed visual memory.
Similar patterns of tissue thinning in the left half of the brain appeared to be related to the severity of a person's existing MDD or anxiety disorder symptoms in both the high- and low-risk groups. This thinning was not as pronounced as the thinning in the right half of the brain, and the difference in tissue thickness between the high- and low-risk groups was not statistically significant.
Significance
The findings strongly suggest that changes in tissue thickness in the right half of the brain directly affect a person's inherited risk for developing MDD. The pattern of tissue thinning appears to be related to problems with attention and processing of emotional or social signals. Such problems may increase a person's vulnerability to developing mood or anxiety disorders, according to the researchers.
That the thinning was present in people at high risk, but who had never had MDD or an anxiety disorder, as well as in high-risk children who had not been diagnosed with depression, shows that these brain changes likely come before illness onset and that they occur very early in life, possibly before birth, say the researchers. Furthermore, while thinning in the right half of the brain contributes to risk, thinning in the left half of the brain appears to be required in order for a person to show symptoms of these illnesses.
What's Next
More research is needed to determine if the inherited risk for MDD is purely genetic, if there are specific environmental factors necessary for triggering genetic risk, or whether there is a combination of factors involved. Increased understanding of how risk translates into developing MDD or other mental disorders may lead to new methods of diagnosing, treating, or preventing these illnesses.

Red Clover May Relieve Depression in Older Women

Depression and anxiety are common among older women, and those who want to avoid drugs as treatment may want to consider red clover. A new study from Austria found that symptoms of depression were reduced by about 80 percent after older women took the supplement for 90 days.
The randomized, double-blind, placebo-controlled trial enrolled 109 post-menopausal women older than age 40 who received either a red clover supplement (80 mg of red clover isoflavones) or a placebo. The supplement used in the study contained isoflavones in their aglycone form, and specifically the compounds biochanin A, formononetin, genistein, and daidzein.
Among the women who took red clover, anxiety was reduced by 76 percent and depression by 78 to 80 percent. Women in the placebo group experienced a decrease in anxiety and depression of about 21 percent.
Whenever the topic of treatment with red clover is raised, some people voice concern about the possible risk of breast cancer, as red clover contains phytoestrogens. Based on data gathered during a recent (2009) European Food Safety Authority working group that investigated isoflavones, the experts concluded that red clover-derived isoflavones do not increase the risk of breast cancer and in fact provide real relief for post-menopausal women.
Red clover has been the subject of much scientific investigation. Some research has suggested that the herb may help protect against heart disease, with red clover isoflavones showing an ability to increase “good” high-density lipoprotein (HDL) cholesterol in pre- and post-menopausal women.
Other studies have suggested that red clover isoflavones may slow bone loss in pre- and post-menopausal women, but this has not been definitively determined. Red clover is also being investigated for its possible use in preventing cancer. Traditionally, red clover ointments have been used to treat eczema, psoriasis, and other skin problems.
Results of this new study may be good news for older women who suffer with depression and who want to avoid treatment with a prescription drug. Women who are interested in red clover to treat depression should talk to a knowledgeable professional. It is important to remember that extracts of red clover isoflavones are not the same as the whole herb. In fact, extracts of red clover isoflavones are only a small, highly concentrated part of the entire herb.