Depression is a serious and sometimes devastating health problem which affects millions of people worldwide. In her previous work with depressed patients, Rachel Maddux often felt frustrated that treatments were not helpful for all of those diagnosed with depression. The main focus of her thesis therefore asked the question: why is it that some people are helped but others are not?

Her hypothesis was that those with depressive personality traits – chronic melancholics – are more difficult to treat, especially when they suffer from depression. These people generally feel down and worried, have low self-esteem and are dissatisfied with their lives and environment.

Rachel Maddux found that 13 per cent of residents in Lund have these personality traits.

“This is a very large number, but the results are in line with other studies carried out in the US and Canada.”

The next study looked at how many of those who seek help from a psychologist have depressive personality traits – a large portion, 44 per cent. These people were more seriously ill than other patients when they sought specialist help, according to Rachel Maddux.

Contrary to what she had believed, psychotherapy – both cognitive-behavioural and psychodynamic therapy – helped the depressive personality types as much as those without the disposition.

“The interesting thing was that therapy not only improved the depression itself, it also ameliorated the pervasive depressive traits”, says Rachel Maddux.

She cannot say whether the effect is maintained over time. However, she thinks the study indicates that therapy is good for people with this characteristic manner of depressive thinking and behaviour, even if they are not suffering from acute depression.

The main issue for Rachel Maddux’s research still remains: why aren’t all those diagnosed with depression helped by the treatment they receive? Why do antidepressants or talk therapy work for some but not others?

“But now I know that there is hope for those with depressive personality”, says Rachel Maddux. “The next step will be to study other factors that could affect the outcome of treatment; biology, childhood and development, trauma, etc.”

The authors, led by Marianna Virtanen of the Finnish Institute of Occupational Health and University College London, followed about 2000 middle aged British civil servants and found a robust association between overtime work and depression.

This correlation was not affected when the analysis was adjusted for various possible confounders, including socio-demographics, lifestyle, and work-related factors.

There have been a number of previous studies on the subject, with varying results, but the researchers emphasize that it is hard to compare results across these studies because the cut-off for “overtime” work has not been standardized.

“Although occasionally working overtime may have benefits for the individual and society, it is important to recognize that working excessive hours is also associated with an increased risk of major depression”, says Dr Virtanen.

Led by Thomas Lynch, Professor of Clinical Psychology at the University of Southampton, the approach is based on Dialectical Behaviour Therapy (DBT), a treatment with a proven track record in overcoming other serious mental health problems.

Refractory Depression is a common and chronic condition which severely disrupts the family, social and working lives of sufferers. Patients are often rigid and self-critical, exert unnecessary control over their emotions, and show little mental flexibility. At its most extreme, this pattern of behavior constitutes a maladaptive personality style known as emotional over-control. Particularly when under stress, such people prefer order to novelty and are relatively sensitive to threat, but insensitive to reward, for example, in a rose garden, they see the thorns but miss the flowers.

The REFRAMED (REFRActory Depression: Mechanisms and Efficacy of Dialectical Behaviour Therapy) study is the first large clinical trial to extend the principles of DBT to refractory depression. Professor Lynch’s key insight is the idea that pre-existing personality characteristics-rooted in brain processes that emerge in childhood-are central to understanding why some individuals are prone to the disorder.

Professor Lynch comments: “Self-control, the ability to manage competing urges, impulses, behaviours, or desires, is highly valued in society. In fact, a lack of self-control characterizes many of the personal and social problems that afflict modern civilisation. But too much self-control can be equally damaging. People who are emotionally closed-off may find it difficult to get on with others or to recruit help when they encounter difficulties. This social isolation may lead to the development of severe and difficult-to-treat mental health problems-such as refractory depression.”

To assess the impact of the new therapy, the REFRAMED study will recruit up to 276 patients in Dorset, Hampshire, and North Wales. Over six months, half will receive 24 individual sessions and 24 group sessions of DBT from specially trained clinicians, while the remaining patients will receive standard NHS care for depression (usually anti-depressant medication). Patients will be assessed before and after the treatment to gauge its benefits, but researchers will additionally focus on mood changes during treatment through telephone messages that assess patients’ moods, ways of coping, and their self-compassion.

The study has been deliberately designed to recruit the most difficult-to-treat patients. Previous studies into treatment-resistant or chronic depression have excluded patients with other psychological problems, such as suicidal behaviour or personality disorders; unlike other studies, REFRAMED wants to include these patients.

“There is one fundamental difference between DBT and other evidence-based treatments for depression,” says Professor Lynch. “REFRAMED is based on the idea that depression is not the primary problem for many hard-to-help patients. Rather, their over-controlled personality style limits opportunities to interact flexibly with others and to learn new skills. So, when these people experience a depression-triggering life event, they find it hard to get help and their depression becomes more entrenched, resistant to change, and chronic in nature. Our therapy assumes that depressed, emotionally over-controlled patients lack the skills needed to be flexible, express vulnerable emotions, or establish close relationships; thus, we focus on teaching a range of skills that target these specific difficulties.”

The study is particularly significant at a time when the Canadian economy continues to face uncertainty. Mental illness costs the Canadian economy an estimated $51 billion annually, with a third of that attributed to productivity losses.

Published in the current issue of the Canadian Journal of Psychiatry, the study examined data from a large-scale community survey of employed and recently employed people in Alberta.

People who experienced a depressive episode were significantly less likely to be highly productive, the study showed. “We expected this, as past research has found that depression has adverse effects on comprehension, social participation, and day-to-day-functioning,” said Dr. Carolyn Dewa, head of CAMH’s Centre for Research on Employment and Workplace Health and lead author.

“What’s exciting is we found that treatment for depression improves work productivity. People who had experienced a moderate depressive episode and received treatment were 2.5 times more likely to be highly productive compared with those who had no treatment,” she said. “Likewise, people who experienced severe depression were seven times more likely to be high-performing than those who had no treatment.”

Of the 3,000 workers in the in the sample, 8.5 per cent experienced a depressive episode, representing 255 workers.

Though the results showed the effectiveness of treatment on work and performance, the data also showed a troubling trend. “We found that among all study participants who had been diagnosed with a severe depressive episode, 57 per cent did not receive treatment; 40 per cent of those who experienced a moderate depressive episode did not receive treatment,” said Dr. Dewa. “When we look at the success of workers in the sample who received treatment while still in the workplace, it really speaks to the importance of prevention and the need for employers to facilitate treatment and support. If people are able to receive treatment early, disability leave, which costs companies $18,000 per leave, may be avoided.”

“Stigma and discrimination have often affected people’s willingness to access to services, as has the lack of knowledge around supports available in the workplace,” added Dr. Dewa. “It is crucial that employers offer mental health interventions to their employees and support them in engaging in treatment, as well as continuing to support them as they transition back into the workplace.”

The data for this analysis was collected by the Institute for Health Economics, Alberta.

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.”

Inflammation in the body is common to many diseases, including high blood pressure, coronary artery disease, and diabetes. Depression has also been linked to an inflammation marker in blood called C-reactive protein (CRP).

Dr. William Copeland at Duke University Medical Center and his colleagues tested the direction of association between depression and CRP in a large sample of adolescent and young adult volunteers. By following the children into young adulthood, they were able to assess the changes over time in both their CRP levels and any depressive symptoms or episodes.

They found that elevated levels of CRP did not predict later depression, but the number of cumulative depressive episodes was associated with increased levels of CRP.

“Our results support a pathway from childhood depression to increased levels of CRP, even after accounting for other health-related behaviors that are known to influence inflammation. We found no support for the pathway from CRP to increased risk for depression,” said Copeland.

These findings suggest that, by this measure, depression is more likely to contribute to inflammation in the body as opposed to arise as a consequence of inflammation in the body. The highest levels of CRP were found in those who had endured the wear and tear of multiple depressive episodes. This suggests the possibility that long-term emotional distress, beginning in childhood, may lay the foundation for inflammatory processes that lead, in middle age, to cardiovascular disease and diabetes.

“Depression is a recurring disorder for many people. Thus the finding that repeated episodes of depression contribute to inflammation in the body highlights a potentially important role for untreated depression as a contributor to a range of serious medical problems,” commented Dr. John Krystal, Editor of Biological Psychiatry. “These data add to growing evidence of the medical importance of effectively treating depression.”

Low levels of vitamin D already are associated with a cavalcade of health woes from cardiovascular diseases to neurological ailments. This new study – published in Mayo Clinic Proceedings – helps clarify a debate that erupted after smaller studies produced conflicting results about the relationship between vitamin D and depression. Major depressive disorder affects nearly one in 10 adults in the U.S.

“Our findings suggest that screening for vitamin D levels in depressed patients – and perhaps screening for depression in people with low vitamin D levels – might be useful,” said Dr. E. Sherwood Brown, professor of psychiatry and senior author of the study, done in conjunction with The Cooper Institute in Dallas. “But we don’t have enough information yet to recommend going out and taking supplements.”

UT Southwestern researchers examined the results of almost 12,600 participants from late 2006 to late 2010. Dr. Brown and colleagues from The Cooper Institute found that higher vitamin D levels were associated with a significantly decreased risk of current depression, particularly among people with a prior history of depression. Low vitamin D levels were associated with depressive symptoms, particularly those with a history of depression, so primary care patients with a history of depression may be an important target for assessing vitamin D levels. The study did not address whether increasing vitamin D levels reduced depressive symptoms.

The scientists have not determined the exact relationship – whether low vitamin D contributes to symptoms of depression, whether depression itself contributes to lower vitamin D levels, or chemically how that happens. But vitamin D may affect neurotransmitters, inflammatory markers and other factors, which could help explain the relationship with depression, said Dr. Brown, who leads the psychoneuroendocrine research program at UT Southwestern.

Vitamin D levels are now commonly tested during routine physical exams, and they already are accepted as risk factors for a number of other medical problems: autoimmune diseases; heart and vascular disease; infectious diseases; osteoporosis; obesity; diabetes; certain cancers; and neurological disorders such as Alzheimer’s and Parkinson’s diseases, multiple sclerosis, and general cognitive decline.

Investigators used information gathered by the institute, which has 40 years of data on runners and other fit volunteers. UT Southwestern has a partnership with the institute, a preventive medicine research and educational nonprofit located at the Cooper Aerobics Center, to develop a joint scientific medical research program aimed at improving health and preventing a wide range of chronic diseases. The institute maintains one of the world’s most extensive databases – known as the Cooper Center Longitudinal Study – that includes detailed information from more than 250,000 clinic visits that has been collected since Dr. Kenneth Cooper founded the institute and clinic in 1970.

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.”

People with celiac disease often suffer from abdominal pain, constipation, decreased appetite, diarrhea, nausea and vomiting. The disease affects somewhere between one in 105 to one in 1,750 people in the United States and is typically controlled by avoiding gluten-containing foods such as wheat, barley and rye.

“It is easy to see how people who are not managing their disease well can frequently feel unwell and, therefore, be more stressed and have higher rates of depression,” said Josh Smyth, professor of biobehavioral health and medicine, Penn State, “But researchers had not carefully looked at whether people who are effectively managing celiac disease exhibit a greater risk for such difficulties.”

Smyth and his colleagues used a web-mediated survey to assess a range of physical, behavioral and emotional experiences in 177 American women over the age of 18 who reported a physician-provided diagnosis of celiac disease. The survey questions explored respondents’ levels of adherence to a gluten-free diet and assessed various symptoms of celiac disease, how physical symptoms interfere with functioning, the respondents’ experience and management of stressful situations, symptoms of clinical depression, and frequency of thoughts and behaviors associated with eating and body image.

The results are posted online and will appear in a future issue of Chronic Illness.

“We found that most participants frequently adhered to a gluten-free diet, and this greater compliance with diet was related to increased vitality, lower stress, decreased depressive symptoms and greater overall emotional health,” said Smyth. “However, even those people who were managing their illness very well reported higher rates of stress, depression and a range of issues clustered around body image, weight and shape when compared to the general population.”

Smyth noted that he and his colleagues did not survey people without celiac disease; rather, they compared their results to those previously determined for the non-celiac population.

It is understandable to find that women with celiac disease tend to suffer from disordered eating, given that the focus of celiac-disease management is to pay careful attention to what and how one eats, said Smyth.

“What we don’t know is what leads to what and under what circumstances,” he said. “It’s likely that the disease, stress, weight, shape and eating issues, and depression are interconnected. But we don’t know if women who are higher stressed and have celiac disease are more likely to develop symptoms of disordered eating and then become depressed, or if women with celiac disease are depressed and then become stressed, which leads to disordered eating. In the future, we plan to investigate the temporal sequence of these symptoms.”

The team’s results may have implications for people with food allergies and Crohn’s disease, a form of inflammatory bowel disease, as well as celiac disease, according to Smyth.

“Going out to eat with friends or to a holiday potluck is a much different experience for these people because they have to be vigilant and monitor their diets,” he said. “They may feel that they are a burden on a host or hostess. In many cases the only treatment option they are given is to manage their diets. I think we need to educate patients at diagnosis or post-diagnosis about some of the other associated difficulties they might experience and provide strategies for how to better manage those things. I am a proponent of elaborating our treatment models to not just address diseases, but also to address the psychological, social and behavioral aspects of disease as well, as they can influence disease outcomes and the well being of patients.”

The study also found that most of the women reporting postnatal depressive symptoms first reported this at six months after birth or later.

Intimate partner violence (both physical and emotional abuse) in the perinatal period is associated with a range of physical and psychological health problems including adverse pregnancy and birth outcomes, postnatal depression, and future behavioural problems for children.

This Australian study looked at 1305 nulliparous women. They were recruited from six public hospitals between 6 and 24 weeks of gestation. Written questionnaires were completed at recruitment and at 3, 6 and 12 months postpartum.

Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) and intimate partner violence was assessed using the short version of the Composite Abuse Scale.

Information on depressive symptoms was collected at multiple time points, while data on intimate partner violence was only collected at the 12 month follow-up.

The study found that one in six women reported intimate partner violence in the year after having their first baby. Emotional violence was more common than physical violence (14% versus 8%).

Sixteen percent of women reported depressive symptoms in the 12 months postpartum, with most women first reporting depressive symptoms in the second 6 months after birth. Factors associated with postpartum depressive symptoms include: emotional abuse alone, physical abuse, depression in pregnancy and unemployment in early pregnancy.

The significant associations between intimate partner violence and depressive symptoms over the course of the first postpartum year persisted after adjusting for the known confounders of prior depression and relevant socio-demographic characteristics (maternal age, relationship status, and employment status in early pregnancy).

Dr Hannah Woolhouse of the Healthy Mothers Healthy Families Research Group, Murdoch Childrens Research Institute in Victoria, Australia and co-author of the paper said:

“Depression after childbirth has received a lot of attention in recent decades. Known risk factors for developing postnatal depression include a history of depression, poor partner relationships, stressful life events/social health issues, low social support, and low income. Our findings indicate that intimate partner violence is very common among women reporting postnatal depressive symptoms, and may be an important factor for health professionals to consider in managing postnatal distress.

“In both the UK and Australia, universal screening for depressive symptoms in the first few months after childbirth is now recommended as part of routine perinatal care. However we found that most of the women reporting postnatal depressive symptoms first reported this at six months postpartum or later.

“This finding has major implications for clinical practice as many women who develop depression after six months will be missed. Health professionals should regularly enquire about a woman’s mental health in the 12 months after birth, rather than at one specific time point.”

Professor Philip Steer, Editor of BJOG added:

“This study shows that pregnancy and the postnatal period is a good time to identify and support women who experience both depression and partner violence.”