Lower Folate Levels Increase Risk for Depressive Symptoms, Particularly in Women

Lower serum folate levels appear to be associated with an increased risk for depressive symptoms, a large population-based, cross-sectional study suggests.

Data on US adults from the National Health and Nutrition Examination Survey (NHANES) show elevated depressive symptoms were inversely associated with folate status, particularly among women.

"We found that the odds of having elevated depressive symptoms among individuals with the highest serum folate levels were about half that of those with the lowest levels," lead investigator May A. Beydoun, PhD, MPH, National Institute on Aging, told Medscape Medical News.

The study was published online September 14 in Psychosomatic Medicine.

First Nationally Representative Study

Previous research indicates that high levels of total homocysteine (tHcy) and low levels of folate and vitamin B12 are associated with depression or elevated depressive symptoms in adults.

However, investigators note that earlier studies examining the impact of low folate, low vitamin B12, and elevated tHcy status simultaneously on depressive symptoms did not examine interaction among those 3 risk factors and have had inconsistent findings as to the individual associations.

"To our knowledge this is the first nationally representative study conducted among U.S. adults after mandatory fortification of food with folic acid that examines associations of serum folate, vitamin B12, and tHcy levels with depressive symptoms," they write.

For the study the researchers used cross-sectional data from NHANES from 2005 to 2006 by assessing interactions (2 way and 3 way) among the 3 exposures and testing effect modification of the associations by sex.

The study sample included 2524 adults aged 20 to 85 years with complete data on demographics, diet, plasma folate, vitamin B12, and tHcy status, as well as information on physical activity, smoking status, blood pressure, and depressive symptoms.

Depressive symptoms were measured using the Patient Health Questionnaire (PHQ), and elevated symptoms were defined as a PHQ total score of 10 or greater.

Study Underpowered to Detect Effect in Men

With an odds ratio of 0.52 (95% confidence interval [CI], 0.35 – 0.76), adjusted analyses revealed that among the total population the odds of having elevated depressive symptoms was close to half that in the lowest tertile.

Further, with an odds ratio of 0.37 (95% CI, 0.17 – 0.86), the likelihood of women in the highest tertile of serum folate (mean ± SE, 21.1 ±0.29 ng/mL) to experience elevated depressive symptoms was about a third that of their counterparts in the lowest tertile (7.02 ± 0.08 ng/mL).

The study showed no relationship between B12 and tHcy levels and elevated depressive symptom risk — a finding that is consistent with previous research the researchers note.

In addition, researchers report that B12 and tHcy did not interact with folate status to affect its inverse association with depressive symptoms among women.

However, elevated homocysteine level was positively associated with elevated depressive symptoms in adults 50 years and older.

Although a significant association between folate levels and risk for elevated depressive symptoms was only observed in women, the investigators believe this is because the study was underpowered to detect the effect in men.

Boosting Folate Levels

The investigators point out that although the study has several strengths, it also has limitations, including its cross-sectional design, which prevents examination of the relationship between depression and serum folate levels over time.

Therefore, they note, it is possible that reverse causality is at play such that depressed individuals may be more likely to have a poor diet and therefore lower folate intake than nondepressed individuals.

Future interventions to improve mental health outcomes among US adult should focus on increasing levels of serum folate say investigators.

For instance, said Dr. Beydoun, clinicians should consider screening patients with depressive symptoms for serum folate and, if indicated, consider supplementation in addition to standard antidepressant therapy.

In addition, dietary and lifestyle advice to enhance serum folate should also be considered. Such counseling, she said, should include education about folate-rich foods, the beneficial effect of physical activity on folate levels, and the negative impact of cigarette smoking.

Diet Important in Mental Health

Commenting on the study, Felice Jacka, PhD, a researcher from the University of Melbourne in Australia, who has conducted a number of studies examining the impact of diet on mental health status, said given the fact that previous studies have reported this relationship the results are not surprising.

"However," she said, "the NHANES data are very good quality and, therefore, a very good vehicle to examine the relationships between nutritional status and mental health."

"This is the first large-scale population-based study in the US to show that folate status is associated with the presence of depressive symptoms since the fortification of foods with folate became mandatory," she added.

Dr. Jacka said this study also lends further support to the premise that diet is an important factor for mental health in the general population.

"It also suggests that blood tests to examine folate and homocysteine levels (and levels of other nutrients) in individuals with depressive symptoms may be of utility in clinical settings. If nutrient deficiencies and/or excess homocysteine are identified, dietary and/or supplementation strategies could then be considered," she said.

The study authors have disclosed no relevant financial relationships

Antipsychotic drugs 'appear to raise blood clot risk'

Antipsychotic drugs taken by thousands in the UK raise the risk of dangerous blood clots, scientists believe.

The latest research, published in the British Medical Journal, provides the strongest evidence yet of a link.

People given antipsychotics in the past two years had a third greater risk of clots like deep vein thrombosis (DVT).

The Nottingham University study looking at 25,000 cases found the risk was even higher for the newer "atypical" antipsychotics.

Antipsychotic drugs are usually given to patients with conditions such as schizophrenia and bipolar disorder, but are sometimes used to ease persistent nausea and vertigo or to calm agitated dementia patients.

Higher stroke risk

Some scientists had already spotted a higher risk of clots in people taking antipsychotics, but the new study, which looked at more than 25,500 cases, appears to confirm this.

Almost 16,000 of the people in the study suffered a DVT and just over 9,000 suffered a clot on the lung, called a pulmonary embolism.
Those taking newer "atypical" antipsychotics had 73% more chance of developing a clot, compared with a 28% increase for other types of antipsychotic.

Patients appeared to be most at risk shortly after starting to take the new drug.

But the researchers stress that blood clots remain uncommon, and the increase in risk equates to only a handful of new cases per 10,000 patients treated with the drugs.

Nevertheless, they say that if other studies further confirm their results, the drugs might need to be used "more cautiously" for patients who either have less serious conditions, or who are at higher risk of clots for other reasons.

Also writing in the BMJ, Professor Giovanni Gambassi and Dr Rosa Liperoti, from the Centro di Medicina dell'Invecchiamento in Rome, said it was important for doctors to identify those patients at highest risk of side-effects.

Other studies have already revealed a higher stroke risk among patients taking antipsychotics, and Dr Sharlin Ahmed, from the Stroke Association, said that anyone concerned should contact their GP.

"Although the overall risk of a stroke is low, the results of this study remind us that antipsychotics are powerful drugs and should be prescribed carefully, with regular follow-ups."

According to the Medicines and Healthcare products Regulatory Agency (MHRA), the following atypical antipsychotics are licensed for use in the UK: amisulpride (brand name Solian), aripiprazole (Abilify), clozapine (Clozaril, Denzapine), olanzapine (Zyprexa), paliperidone (Invega), risperidone (Risperdal, Risperdal Consta) and zotepine (Zoleptil).

Blood clots can be deadly, with up to one in four patients dying within a week.

It's good to think - but not too much, scientists say

People who think more about whether they are right have more cells in an area of the brain known as the frontal lobes.

UK scientists, writing in Science, looked at how brain size varied depending on how much people thought about decisions.

But a nationwide survey recently found that some people think too much about life.

These people have poorer memories, and they may also be depressed.

Stephen Fleming, a member of the University College London (UCL) team that carried out the research, said: "Imagine you're on a game show such as 'Who Wants to Be a Millionaire' and you're uncertain of your answer. You can use that knowledge to ask the audience, ask for help."

The London group asked 32 volunteers to make difficult decisions. They had to look at two very similar black and grey pictures and say which one had a lighter spot.

They then had to say just how sure they were of their answer, on a scale of one to six. Although it was hard to tell the difference, the pictures were adjusted to make sure that no-one found the task harder than anyone else.

People who were more sure of their answer had more brain cells in the front-most part of the brain - known as the anterior prefrontal cortex.

This part of the brain has been linked to many brain and mental disorders, including autism. Previous studies have looked at how this area functions while people make real time decisions, but not at differences between individuals.

Illness link

The study is the first to show that there are physical differences between people with regards to how big this area is. These size differences relate to how much they think about their own decisions.

The researchers hope that learning more about these types of differences between people may help those with mental illness.

Co-author Dr Rimona Weil, from UCL's Institute of Cognitive Neuroscience, said: "I think it has very important implications for patients with mental ill health who perhaps don't have as much insight into their own disease."

She added that they hope they may be able to improve patients' ability to recognise that they have an illness and to remember to take their medication.

However, thinking a lot about your own thoughts may not be all good.

Cognitive psychologist Dr Tracy Alloway from the University of Stirling, who was not involved in the latest study, said that some people have a tendency to brood too much and this leads to a risk of depression.

More than 1,000 people took part in a nationwide study linking one type of memory - called "working memory" - to mental health.

Working memory involves the ability to remember pieces of information for a short time, but also while you are remembering them, to do something with them.

For example, you might have to keep hold of information about where you saw shapes and colours - and also answer questions on what they looked like. Dr Alloway commented: "I like to describe it as your brain's Post-It note."

Those with poorer working memory, the 10-15% of people who could only remember about two things, were more likely to mull over things and brood too much.

Both groups presented their findings at the British Science Festival, held this year at the University of Aston in Birmingham.

Drinking Coffee Lowers Risk of Gout in Older Women

NEW YORK (Reuters Health) Sep 16 - A few cups of coffee every day over many years cuts the risk of gout in postmenopausal women in half, Boston researchers report.

"The pain is described as one of the most severe pains a human being experiences, like a breaking bone. You can't walk and even the weight of a bed sheet is not bearable," lead author, Dr. Hyon Choi of Boston University's School of Medicine, told Reuters Health.

Dr. Choi had previously shown that drinking coffee lowers gout risk for men. He and his colleagues wanted to see if the same held true in women, especially older women who, after menopause, lose the uric-acid clearing benefits of estrogen. Gout is rare in younger women but occurs in about one in 20 postmenopausal women.

The researchers looked for cases of gout in 89,433 women enrolled in the Nurses' Health Study, which began in 1976. The researchers also analyzed the lifestyles, diet, and beverage consumption habits of the women since 1980, as reported in questionnaires they filled out every two to four years.

Eight-hundred ninety-six cases of gout were confirmed among the study participants. But within that group, the number of cases dropped as coffee consumption increased from less than a cup a day (226 cases) to more than four cups a day (85 cases).

After statistically controlling for other gout risk factors such as body-fat mass, alcohol consumption, use of diuretics and dairy intake, they found that a lifetime of drinking coffee appeared to make a significant difference in the risk of a first attack of gout.

"The higher the consumption level, the lower the risk," Dr. Choi said.

"The risk of gout was 22% lower with coffee intake of 1-3 cups a day and 57% lower with a coffee intake of more than 4 cups a day" compared to those with no coffee consumption, the authors wrote in the August 25th issue of American Journal of Clinical Nutrition.

Caffeinated tea or soda pop did not confer a similar advantage, whereas drinking decaffeinated coffee did offer a "modest" benefit. That observation led the researchers to conclude that "components other than caffeine may also contribute" to the risk reduction.

How coffee staves off gout is still not clear, Dr. Choi said. And not everybody can tolerate it, he added, so he is not advocating that all older women start gulping coffee.

It would be "too much of a jump" for a doctor to recommend that anyone, especially an older woman, take up coffee drinking to reduce their gout risk, he said. Not only can caffeine raise blood pressure and leach calcium, he noted, but the research only speaks to a benefit in long-term consumption.

"If you start coffee in a gout patient, it's possible this benefit does not exist and might make it worse," he said.

On the other hand, if you already drink coffee, and have a family history of gout -- it does run in families -- "I wouldn't stop," Dr. Choi said.

Am J Clin Nutr. Posted August 25, 2010. Abstract

NSAID Use Associated With Atrial Fibrillation

September 15, 2010 (Chieti, Italy) — The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of chronic atrial fibrillation (AF), a new study suggests [1]. However, the researchers do not believe the drugs are causing AF; rather, they suggest that the underlying inflammation necessitating the NSAID therapy might be the culprit.

Dr Raffaele De Caterina (G d'Annunzio University, Chieti, Italy) and colleagues found a statistically significant 44% increase in the risk of chronic AF, but no association with paroxysmal AF, in users of NSAIDs. They also confirmed previous findings regarding the association of steroids with AF, with those taking steroids two and a half times more likely to develop chronic AF than those not taking them, they report in their paper in the September 13, 2010 issue of the Archives of Internal Medicine.

"A likely explanation for our findings is the existence of an underlying inflammatory condition, increasing the risk of AF on the one hand and prompting the use of NSAIDs on the other," they say. Future research should ideally include a description of left ventricular function, atrial size and/or function, and inflammatory markers, which would help make the association "more biologically plausible," they add.

A Hypothesis That Deserves Further Investigation

De Caterina et al identified patients aged 40 to 89 years with a first-ever diagnosis of AF in 1996 in the UK General Practice Research Database and classified them as having paroxysmal or chronic AF. After validation with their primary-care physicians, 1035 patients were confirmed as having incident chronic AF and 525 as having paroxysmal AF. Two separate nested case-control analyses estimated the risk of first-time chronic and paroxysmal AF among users of steroids and NSAIDS.

Increased risk of chronic AF with NSAID use was present irrespective of treatment duration, although the researchers did find an even greater risk associated with long-term use (RR 1.80 in those who used NSAIDs for more than one year). But there was no apparent dose-response relationship when they divided daily use into low, medium, and high.

The findings cannot be explained by the occurrence of heart failure, either, say De Caterina and colleagues, because further stratification found the increased risk of AF associated with NSAIDs was absent in those with prior HF (but present in those without HF).

They go on to explain that the most frequent pathoanatomical changes in AF are atrial fibrosis and loss of atrial muscle mass, and although it is difficult to distinguish between changes due to AF and those due to associated heart disease, fibrosis may precede the onset of AF and may be caused by inflammation.

"It is possible, and we would like to propose, that conditions presenting systemic inflammation, such as autoimmune and rheumatic disorders, represent an independent risk factor for atrial fibrosis and subsequently for an increased risk of onset or persistence of AF. We believe this hypothesis deserves further investigation," they conclude.

Data collection for the determination of AF cases was performed with an unrestricted research grant to Centro Español de Investigación Farmacoepidemiológica from AstraZeneca. The authors report no disclosures.

Depressed heart patients 'at risk'

The combination of depression and coronary heart disease in a patient could be much more deadly than either condition alone, researchers say.

French and British experts say people with both conditions could be four times more likely to die from heart or circulatory disease.

The study, in Heart journal, tracked the mental and physical health of 6,000 middle-aged people over five years.

Experts said doctors must pay more heed to depression in heart patients.

Experts from the University College London and the University of Versailles followed the health of just under 6,000 male and female civil servants for an average of five and a half years.

The volunteers were taking part in the British Whitehall Study II, which is looking at social and economic factors in long-term health.

Exercise

They found people with heart disease alone had a 67% higher chance of dying from any cause than those without either heart disease or depression.

But the combination of heart disease and depression tripled the risk of death from any cause and quadrupled the risk of dying from cardiovascular disease.

Amy Thompson, a senior cardiac nurse at the British Heart Foundation, which partly funded the study, said: "This study builds on previous research which suggests that depression is linked to coronary heart disease.

"Enjoying regular exercise and eating a healthy, balanced diet can help if you are feeling low - so, good news for your mental health as well as your heart health.

"Whether or not you have heart disease, if you feel depressed it's essential to talk to your doctor."

Gene therapy for blood disorder a 'success'

Gene therapy has been used for the first time to treat an inherited blood disorder in what doctors say is a major step forward.

A man given pioneering treatment to correct a faulty gene has made "remarkable" progress, a US and French team has revealed.

Gene therapy is an experimental technique that manipulates genes in order to treat disease.

It has seen some successes, but also setbacks, including a patient's death.

Beta thalassaemia is an inherited blood disorder that affects the body's ability to create red blood cells.

The first gene therapy trial was in an 18-year-old man with a severe form of the condition, who had been receiving regular blood transfusions since the age of three.

Stem cells from his bone marrow were treated with a gene to correct for the faulty one.

They were then transfused back into his body, where they gradually gave rise to healthy red blood cells.

Three years after the treatment, which took place in 2007, the man remains mildly anaemic, but no longer needs blood transfusions, doctors said.

The team, led by Philippe Leboulch, of Harvard Medical School in Boston, said: "At present, approximately three years post-transplantation, the biological and clinical evolution is remarkable and the patient's quality of life is good."

But, reporting in the science journal Nature, the doctors sounded a note of caution, saying there was a possibility that the patient could be at risk of developing leukaemia in the future due to side effects from the gene therapy.

Gene therapy has been used since the 1990s as a new approach to treating a number of incurable conditions, including inherited disorders, some cancers, and viral infections.

There have been some positive results, but in 1999 an 18-year-old US volunteer, Jesse Gelsinger, died after the treatment.

And some children given gene therapy for the immune disorder "bubble baby" syndrome have developed cancer.

Proof of principle

Prof Adrian Thrasher, of University College London, has carried out gene therapy on children with immune disorders.

He said the latest study was an encouraging proof of principle that gene therapy could have genuine therapeutic effects in other blood disorders.

"The good news is that technology is advancing rapidly, and it shouldn't be too long before diseases such as thalassaemia can be reliably and safely treated in this way," he said.

Dr Derek Persons, of St Jude Children's Research Hospital in Memphis, Tennessee, said the work was "a major step forward for the gene therapy of haemoglobin disorder".

He said further trials were planned at several centres in the US, including his own.

"This is very early days," he added. "The field will advance from people doing different trials."