Major depressive episodes far more common than previously believed
July 30, 2020
Science Daily/Yale School of Public Health
The number of adults in the United States who suffer from major depressive episodes at some point in their life is far higher than previously believed, a new study by the Yale School of Public Health finds.
National survey data currently shows that approximately 17% of women and 10% of men report having a history of major depressive episodes (MDEs) in their lifetimes. But these data are subject to "recall error," or the tendency of people to forget or misreport their health histories when taking a survey.
Researchers led by Jamie Tam, Ph.D., assistant professor in the Department of Health Policy and Management, created a simulation model to generate corrected estimates of lifetime depression. They found that the proportion of U.S. adults who have had MDEs is actually closer to 30% of women and 17% of men after factoring in recall error.
"Major depressive episodes are far more common than we thought," said Tam. "Our model shows that the probability of someone having a first major depressive episode is especially high during adolescence. We also know from other research that having a first major depressive episode increases the likelihood you'll have a second one. This means that anything we can do to prevent or treat episodes among young people could lead to larger health benefits over the course of their life."
The findings are published in the American Journal of Preventive Medicine.
A major depressive episode is defined as a period of two weeks or longer in which a person experiences feelings of intense sadness and hopelessness, fatigue, weight gain or weight loss, changes in sleeping habits, loss of interest in activities and thoughts of suicide or attempts at suicide. These persistent symptoms cannot be easily changed, even if they are contradictory to a person's circumstances. Depressive episodes typically recur periodically in people diagnosed with major depression.
The study shows that mental health programs that screen for, prevent and treat depression could benefit a much larger segment of the population than previously thought, Tam said.
"If you think about chronic health conditions like heart disease, we do a lot to identify people who might be at risk for additional health events like heart attacks because that group would benefit from maintenance treatment and clinical monitoring," Tam said. "We don't do such a great job when it comes to mental health conditions. So, if we're able to assess how many people actually have histories of depression, that also tells us that more people are at risk of experiencing more depressive episodes."
The researchers also found that older adults are especially likely to under-report their history of having depressive symptoms. Among adults 65 years and older, underreporting for depression was as high as 70%. Older adults often experience what is referred to as "minor depression," where they still report significant depressive symptoms but don't always meet clinical requirements for major depression. Tam said there may be a tendency for older adults to downplay negative experiences of depression from when they were younger, classifying them as "growing pains" rather than major depression.
"Unfortunately, many people with depression or with histories of depression don't access, or don't have access to, treatment or support," Tam said. "There's a broader problem in our society of mental health not receiving the same attention and investment of resources compared to physical health conditions."
https://www.sciencedaily.com/releases/2020/07/200730132813.htm
A child's home environment can impact the risk of developing depression
April 28, 2020
Science Daily/American Psychiatric Association
New research, published online today in the American Journal of Psychiatry, finds that children's rearing environment has a meaningful impact on their risk for major depression later in life, and notes the importance supporting of nurturing environments when children are at risk. In the study, authors analyzed the health records of full and half siblings with at least one biological parent with depression who were raised by either their biological parents or in carefully screened adoptive homes. Generally, the children in adopted homes showed lower risk, but whatever the setting, episodes of major depression in the parents meant the children were more susceptible to depression themselves.
"The Rearing Environment and Risk for Major Depression: A Swedish National High-Risk Home-Reared and Adopted-Away Co-Sibling Control Study" -- led by Kenneth S. Kendler, M.D., with Virginia Commonwealth University in Richmond, and Kristina Sundquist, M.D., Ph.D., from Lund University in Malmö, Sweden -- involved data from the Swedish National Sample. The researchers identified 666 high-risk full sibling pairs and 2,596 high-risk pairs of half siblings each with at least one child reared at home and one adopted. High risk was defined as having at least one biological parent with major depression. In Sweden, the adoptive parents are carefully screened and undergo a rigorous selection process to ensure their ability to "provide a supportive and generally advantaged home for their adoptive child."
In the full sibling group, the risk for major depression among adopted siblings was 23% lower than the sibling raised in the home with their birth family. In the group of half siblings, the risk of depression was 19% lower for the adopted siblings. For both the full and half sibling groups, the protective effect of adoption disappeared when an adoptive parent or step-sibling had major depression or when the
The study authors conclude that their results "further strengthen the evidence that high-quality rearing environments can meaningfully reduce rates of major depression in individuals at high familial risk." The research also "supports efforts to improve the rearing environment in high-risk families as an approach to the primary prevention of major depression," the authors note.
Myrna M. Weissman, Ph.D., from Columbia University Vagelos College of Physicians and Surgeons, noted in her accompanying commentary that to the question of whether it is nature or nurture that contributes to depression risk, the answer remains "yes," it is nature and nurture, with relative proportions and for which type of depression continuing to be examined. Yet, for the present study "the results demonstrate the strong impact of the rearing environment on risk for major depression and support the importance of intervention efforts to improve the rearing environment in high risk families."
https://www.sciencedaily.com/releases/2020/04/200428084705.htm
Anti-inflammatory agents can effectively and safely curb major depressive symptoms
Effects even stronger when added to antidepressant treatment, pooled data analysis shows
October 28, 2019
Science Daily/BMJ
Anti-inflammatory agents, such as aspirin/paracetamol, statins, and antibiotics, can safely and effectively curb the symptoms of major depression, finds a pooled analysis of the available evidence, published online in the Journal of Neurology Neurosurgery & Psychiatry.
And the effects are even stronger when these agents are added on to standard antidepressant treatment, the results show.
Around a third of people who are clinically depressed don't respond well to current drug and talking therapies, and drug side effects are relatively common.
An emerging body of evidence suggests that inflammation contributes to the development of major depression, but the results of clinical trials using various anti-inflammatory agents to treat the condition have proved inconclusive.
The researchers therefore set out to review the available evidence and pool the data to see if anti-inflammatory agents work better than dummy (placebo) treatment either alone or when used as add-on therapy to standard antidepressant treatment.
Anti-inflammatory agents included: non-steroidal anti-inflammatory drugs (NSAIDs); omega 3 fatty acids; drugs that curb production of inflammatory chemicals (cytokine inhibitors); statins; steroids; antibiotics (minocyclines); a drug used to treat sleep disorders (modafinil); and N-acetyl cysteine, known as NAC, and used to loosen the excess phlegm of cystic fibrosis and COPD and also taken as an antioxidant supplement.
The researchers trawled research databases to find suitable studies published up to January 2019. They found 30 relevant randomised controlled trials, involving 1610 people, which reported changes in depression scales. They pooled the data from 26 of these studies.
The pooled data analysis suggested that anti-inflammatory agents were better than placebo and enhanced the effects of standard antidepressant treatment.
These agents were 52% more effective in reducing symptom severity, overall, and 79% more effective in eliminating symptoms than placebo, as measured by an average fall in depression scales of 55.
More detailed analysis indicated that NSAIDs, omega 3 fatty acids, statins, and minocyclines were the most effective at reducing major depressive symptoms compared with placebo.
And the effects were even greater when one or other of these agents was added to standard antidepressant treatment.
But anti inflammatory agents didn't seem to improve quality of life, although this might have been because of the small number of studies which looked at this aspect, say the researchers.
No major side effects were evident, although there were some gut symptoms among those taking statins and NACs, and the trials lasted only 4 to 12 weeks, so it wasn't possible to track side effects over the longer term.
The researchers also point out that not all studies tracked changes in depression scores over the entire study period. The depression scales used in the studies differed, and those involving statins and minocyclines included only small numbers of patients.
Nevertheless, they conclude: "The results of this systematic review suggest that anti-inflammatory agents play an antidepressant role in patients with major depressive disorder and are reasonably safe."
https://www.sciencedaily.com/releases/2019/10/191028213923.htm
Weighing risks and benefits of drug treatment for major depression
June 12, 2019
Science Daily/American Geriatrics Society
For some people, medication is an effective part of treatment for depression. However, when considering whether to prescribe antidepressant medication for older adults, healthcare providers must weigh the safety risks these medications pose against the often modest benefits they can provide compared to other options.
Depression is a common and serious problem for older adults. Some 15 to 20 percent of people aged 65 and older who live independently deal with symptoms of major depressive disorder. For residents of nursing homes, the rates of depression may be as high as 50 percent.
For some people, medication is an effective part of treatment for depression. However, when considering whether to prescribe antidepressant medication for older adults, healthcare providers must weigh the safety risks these medications pose against the often modest benefits they can provide compared to other options.
For example, tools like the American Geriatrics Society (AGS) Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults recommended that healthcare providers avoid prescribing certain antidepressant medications to older adults who have a history of falls or fractures. These include selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). That's because these medications may actually increase the risk of falls and fractures.
Understanding these and other risks associated with "potentially inappropriate medications" is key to building better care for us all as we age. That's why a team of researchers recently reviewed and analyzed studies to learn more specifically about the harmful effects of antidepressants for treating major depressive disorder in adults 65 years of age or older. Their study was published in the Journal of the American Geriatrics Society.
The systematic review was performed at the University of Connecticut Evidence-based Practice Center (EPC). The researchers reviewed studies that examined how many older adults experienced a harmful event during the study.
The researchers looked at patients 65 years of age or older who are prescribed serotonin and norepinephrine reuptake inhibitors (SNRIs) to treat the acute phase of major depressive disorder (the earliest stage of the condition, when the goal is to address the symptoms associated with an episode of depression). They found that taking SNRIs led to a greater number of harmful events compared to people who took a placebo (a harmless sugar pill that has no effect on health and is prescribed to some study participants to help with comparing their results to results from people who were treated with actual medication). Older adults who took SSRIs experienced about the same number of harmful events as did people who took a placebo.
The researchers said that taking either SSRIs or SNRIs led to a greater number of people leaving the study due to harmful events of the drugs compared to placebos. They also noted that the drug duloxetine, an SSRI, increased the risk of falls.
"Some of the antidepressants have not been studied in older patients with major depression, and studies don't often describe specific side effects. Future research in this field is critical to better inform how the safety profiles of different antidepressants compare in older adults," said study co-author Diana M. Sobieraj, Pharm.D., FCCP, BCPS, Assistant Professor, University of Connecticut School of Pharmacy.
https://www.sciencedaily.com/releases/2019/06/190612141302.htm
Depression, obesity, chronic pain could be treated by targeting the same key protein
April 1, 2019
Science Daily/American Chemical Society
Major depression, obesity and chronic pain are all linked to the effects of one protein, called "FK506-binding protein 51," or FKBP51. Until now, efforts to inhibit this target have been hampered by the difficulty of finding something specific enough to do the job and not affect similar proteins. Now a research group has developed a highly selective compound that can effectively block FKBP51 in mice, relieving chronic pain and having positive effects on diet-induced obesity and mood. The new compound also could have applications in alcoholism and brain cancer.
The researchers will present their results today at the American Chemical Society (ACS) Spring 2019 National Meeting & Exposition.
"The FKBP51 protein plays an important role in depression, obesity, diabetes and chronic pain states," says Felix Hausch, Ph.D., the project's principal investigator. "We developed the first highly potent, highly selective FKBP51 inhibitor, called SAFit2, which is now being tested in mice. Inhibition of FKBP51 could thus be a new therapeutic option to treat all of these conditions."
Hausch, who is at the Technical University of Darmstadt, started the project when studies were published linking the protein to depression. "I was intrigued by the peculiar regulatory role it seemed to play in cells," he says. "And there was a known natural product that could serve as a starting point. Collectively, this looked like an interesting protein to work on."
FKBP51 is expressed in multiple places throughout the body, such as the brain, skeletal muscle tissue and fat. It also has multiple effects. For example, the protein can restrict the uptake of glucose and the browning of fat, so that the body stores fat instead of burning it. It also affects stress responses. So, Hausch and his colleagues figured that blocking this protein could be the key to developing drugs to treat a variety of conditions.
But FKBP51 looks a lot like its closest protein cousin, FKBP52. "These two proteins are very similar in structure, but they are doing opposing things in cells," Hausch says. "We have this yin-yang situation. Selectivity between these two proteins is thought to be crucial, but this is hard to achieve since the two proteins are so similar. We discovered that FKBP51 can change its shape in a way that FKBP52 can't, and this allowed the development of highly selective inhibitors."
The researchers have now used nuclear magnetic resonance techniques to detect a previously hidden binding site in FKBP51. The approach could help other researchers identify similar "cryptic" binding sites in challenging drug targets in the future, Hausch says.
His team is now testing SAFit2, the lead FKBP51 inhibitor they developed from these studies, in animals. "It indeed helps mice cope better in stressful situations," Hausch says. In mice, SAFit2 reduced stress hormone levels, promoted more active stress coping, was synergistic with antidepressants, protected against weight gain, helped normalize glucose levels and reduced pain in three animal models.
According to Hausch, much more needs to be done to get FKBP1 inhibitors to the point where they could be used as a drug molecule in human testing. In the meantime, the team is also exploring FKBP51 inhibitors in other applications. So far, the group has conducted a number of mouse studies on the involvement of FKBP51 in alcoholism, but results are still preliminary. In addition, Hausch points out that certain types of glioblastoma tumors overexpress FKBP51. He hopes that this result indicates FKBP51 inhibitors could be used in cancer treatment, when patients' tumors mutate beyond current drugs' capacity to treat them. "We may be able to resensitize them to different types of chemotherapy using these specific inhibitors," he says.
https://www.sciencedaily.com/releases/2019/04/190401075208.htm
Unexpected death of a loved one linked to onset of psychiatric disorders
May 29, 2014
Science Daily/Columbia University's Mailman School of Public Health
The sudden loss of a loved one can trigger a variety of psychiatric disorders in people with no history of mental illness. While previous studies have suggested there is a link between sudden bereavement and an onset of common psychiatric disorders, this is the first study to show the association of acute bereavement and mania in a large population sample.
In people aged 30 years or older, the unexpected death of a loved one roughly doubled the risk for new-onset mania after controlling for prior psychiatric diagnoses, other traumatic experiences, and certain demographic variables like sex, race, income, education, and marital status. For those <50 years of age or ≥70 years, the risk increase was more than fivefold. There was no significant effect in people younger than 30 years.
"Our findings should alert clinicians to the possible onset of a wide range of psychiatric disorders, including disorders such as mania, after an unexpected death in otherwise healthy individuals," says Katherine Keyes, PhD, assistant professor of Epidemiology at the Mailman School of Public Health, and principal investigator. "However, it is also notable that the majority of individuals in the present study did not develop mental health issues in the wake of an unexpected death of a loved one."
Losing a loved one suddenly also raised the risk of major depression, excessive use of alcohol, and anxiety disorders, including panic disorder, post-traumatic stress disorder, and phobias. The largest risk increases were for post-traumatic stress disorder, which was seen across age groups with an increased risk as high as 30-fold. Most other disorders were concentrated in the older age groups.
While developing a psychiatric disorder for the first time in old age is relatively rare, these data indicate that psychiatric disorder onset in older age is commonly associated with the death of a loved one, according to the authors.
"Clinically, our results highlight the importance of considering a possible role for loss of close personal relationships through death in assessment of psychiatric disorders. When someone loses a close personal relationship, even late in life, there is a profound effect on sense of self and self reflection. These data indicate that, even in adults with no history of psychiatric disorders, it is also a vulnerable risk period for the onset of a potentially disabling psychiatric disorder," says Dr. Keyes.
http://www.sciencedaily.com/releases/2014/05/140529154153.htm