Early life stress is associated with youth-onset depression for some types of stress but not others
July 15, 2020
Science Daily/Elsevier
A study in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), published by Elsevier, reports that individuals exposed to early life stress (ELS) were more likely to develop a major depressive disorder (MDD) in childhood or adolescence than individuals who had not been exposed to ELS.
Examining the association between eight different types of ELS and youth-onset depression, the authors found that while some types of ELS (e.g., poverty) were not associated with MDD, other types of stress, including emotional abuse, were associated more strongly with MDD than a broader assessment of ELS.
"Researchers have documented that early life stress increases the risk for developing depression in adulthood. We wanted to know the degree to which it was associated with depression earlier in life -- specifically during childhood or adolescence," said lead author Joelle LeMoult, PhD, a researcher at the University of British Columbia, Vancouver, Canada. "Given that earlier onsets of depression often mean a more recurrent course across the lifespan. We found that exposure to early life stress more than doubled the likelihood someone will develop youth-onset depression.
"These findings indicate that there is a narrow window between adversity and depression during which we have the opportunity to intervene."
The findings are based on a meta-analysis of data from 62 journal articles and over 44,000 unique participants. Studies that assessed early life stress and the presence or absence of MDD before the age of 18 years were also included.
Compared to youth who were not exposed to ELS, youth who were exposed to ELS were 2.5 times more likely to develop MDD (OR=2.50; 95% CI [2.08, 3.00]).
The authors also conducted eight additional meta-analyses to examine the association between different types of ELS and a diagnosis of MDD during childhood or adolescence. Sexual abuse, physical abuse, death of a family member, domestic violence, and emotional abuse were associated with significantly higher risk for youth-onset MDD; in contrast, poverty, illness/injury, and exposure to a natural disaster were not.
Several variables moderated the association between ELS and youth-onset MDD. For example, studies that used interview-based assessments or included larger sample sizes reported stronger associations between ELS and depression.
Taken together, findings provide evidence that the adverse effects of ELS on risk for MDD manifests early in development, before adulthood, and varies by type of ELS. Further, findings support recommendations to use best-practice methods in early life stress research.
https://www.sciencedaily.com/releases/2020/07/200715142326.htm
Handling traumatic grief reactions in children and adolescents post-9/11
October 1, 2019
Science Daily/Elsevier
In the wake of the World Trade Center attack on September 11, 2001 (9/11), researchers defined the 'traumatically bereaved' as those who experienced the loss of a mother, father, sister, brother, grandmother, grandfather, aunt, uncle, other family member, friend, and/or someone else after 9/11 happened. A new study reports that this disorder warrants separate clinical attention.
Grief reactions in traumatically bereaved youth, particularly in relation to a shared trauma, constitute a unique aspect of psychological distress. A new study in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), published by Elsevier, reports that this disorder warrants separate clinical attention.
In the wake of the World Trade Center attack on September 11, 2001 (9/11), researchers from Columbia University Medical Center (CUMC), New York defined the "traumatically bereaved" as those who experienced the loss of a mother, father, sister, brother, grandmother, grandfather, aunt, uncle, other family member, friend, and/or someone else after 9/11 happened.
"Study findings support the potential clinical relevance of a new bereavement disorder during sensitive developmental periods spanning from middle childhood to late-adolescence," said lead author Lupo Geronazzo-Alman, PhD, Assistant Professor of Clinical Medical Psychology, Division of Child and Adolescent Psychiatry at the New York State Psychiatric Institute, CUMC. "Grief reactions have added clinical value and merit clinical attention, because they describe maladaptive reactions after 9/11 that are not adequately captured by other disorders such as posttraumatic stress and major depression."
The findings, based on The World Trade Center (WTC) Board of Education (WTC-BOE) Study, are comprised of responses taken from a sample of 8,236 youth in grades 4 to 12, who answered a questionnaire six months after 9/11. It is representative of 715,966 New York City (NYC) public school students at the time of assessment.
The 277 youth (3.36 percent of the sample) experienced death of a family member; 576 (6.99 percent) and 1,003 (12.18 percent) youth experienced the death of a friend and of someone else they knew, respectively. In total, 1,696 youth were traumatically bereaved on 9/11, representing 133,446 (18.71 percent) 4th- through 12th-graders attending NYC public schools 6 months after 9/11.
The following five items selected from the UCLA Grief Screening Scale queried bereaved youth about the intensity of grief reactions during the previous month: missing the deceased person; continuing to feel connected to them; avoiding conversations; avoiding activities; and unhelpful rumination about the deceased person.
Symptoms of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) were assessed with the Diagnostic Interview Schedule for Children (DISC-IV) Predictive Scales (DPS), a screening measure derived from the DISC-IV.
To establish whether a new bereavement disorder warrants a place in psychiatric nosology, the researchers provided four types of convergent evidence showing that the (1) predictors (i.e., non-loss-related trauma versus traumatic bereavement); (2) clinical correlates (new health problems since 9/11, functional impairment); (3) factorial structure; and (4) phenomenology of grief reactions are independent of, and distinct from, other common types of post-disaster child and adolescent psychopathology, and capture a unique aspect of bereavement-related distress.
Grief reactions, PTSD, and MDD all have different predictors; traumatic bereavement was associated with grief independently of PTSD and MDD but was not associated with PTSD and MDD after adjusting for grief reactions.
After controlling for PTSD and MDD, grief reactions were significantly associated with functional impairment. Furthermore, a factor analysis showed that grief reactions loaded on one factor, which was distinct from factors underlying PTSD and MDD symptoms. Finally, youth with severe grief reactions could be grouped into two classes characterized by (i) negligible and (ii) only moderate probability of co-occurring PTSD and MDD symptoms, respectively.
"A primary benefit of including a new definition of bereavement disorder into the main text of the DSM-V will fill in a current gap in how clinicians are able to describe and explain reactions to traumatic bereavement, allowing us to better predict and prescribe the most appropriate treatment," concluded Dr. Geronazzo-Alman.
https://www.sciencedaily.com/releases/2019/10/191001084005.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
People with anxiety may strategically choose worrying over relaxing
September 30, 2019
Science Daily/Penn State
Relaxing is supposed to be good for the body and soul, but people with anxiety may actively resist relaxation and continue worrying to avoid a large jump in anxiety if something bad does happen, according to Penn State research.
In a new study, the researchers found that people who were more sensitive to shifts in negative emotion -- quickly moving from a relaxed state to one of fear, for example -- were more likely to feel anxious while being led through relaxation exercises.
Michelle Newman, professor of psychology, said the results could help benefit people who experience "relaxation-induced anxiety," a phenomenon that occurs when people actually become more anxious during relaxation training.
"People may be staying anxious to prevent a large shift in anxiety, but it's actually healthier to let yourself experience those shifts," Newman said. "The more you do it, the more you realize you can do it and it's better to allow yourself to be relaxed at times. Mindfulness training and other interventions can help people let go and live in the moment."
Hanjoo Kim, a graduate student in psychology, said the study also sheds light on why relaxation treatments designed to help people feel better can potentially cause more anxiety.
"People who are more vulnerable to relaxation-induced anxiety are often the ones with anxiety disorders who may need relaxation more than others," Kim said. "And of course, these relaxation techniques were meant to help, not make someone more anxious. Our findings will hopefully serve as a cornerstone for providing better care for these populations."
Newman said that while researchers have known about relaxation-induced anxiety since the 1980s, the specific cause of this phenomenon has remained unknown. When Newman developed the contrast avoidance theory in 2011, she thought the two concepts might be connected.
"The theory revolves around the idea that people may make themselves anxious intentionally as a way to avoid the letdown they might get if something bad were to happen," Newman said. "This isn't actually helpful and just makes you more miserable. But, because most of the things we worry about don't end up happening, what's reinforced in the brain is, 'I worried and it didn't happen so I should continue worrying.'"
For this study, the researchers recruited 96 college students. Participants included 32 people with generalized anxiety disorder, 34 people with major depressive disorder and 30 controls with neither disorder.
When the participants arrived at the lab, the researchers led them through relaxation exercises before having them watch videos that may elicit fear or sadness. The participants then answered a list of questions designed to measure how sensitive they were to changes in their emotional state. For example, some people may be uncomfortable with the negative emotions incited by the videos right after relaxing, while others might find the relaxation session helpful in dealing with those emotions.
Next, the researchers led the participants through a relaxation session once more before having them fill out a second survey. These questions were designed to measure the participants' anxiety during the second relaxation session.
After analyzing the data, the researchers found that people with generalized anxiety disorder were more likely to be sensitive to sharp spikes in emotion, like going from feeling relaxed to feeling scared or stressed. Additionally, this sensitivity was linked to feeling anxious during sessions intended to induce relaxation.
The researchers found similar results in people with major depressive disorder, although the effect wasn't as strong.
Kim said he hopes the results -- recently published in the Journal of Affective Disorders -- may help clinicians provide better care for people with anxiety.
"Measuring relaxation-induced anxiety and implementing exposure techniques targeting the desensitization of negative contrast sensitivity may help patients reduce this anxiety," Kim said. "Also, it would be important to examine relaxation-induced anxiety in other disorders, such as panic disorder and persistent mild depression."
https://www.sciencedaily.com/releases/2019/09/190930114737.htm
Childhood trauma has lasting effect on brain connectivity in patients with depression
April 8, 2019
Science Daily/University of Pennsylvania School of Medicine
A study lead by Penn Medicine researchers found that childhood trauma is linked to abnormal connectivity in the brain in adults with major depressive disorder (MDD). The paper, published this week in Proceedings of the National Academy of Sciences (PNAS), is the first data-driven study to show symptom-specific, system-level changes in brain network connectivity in MDD.
"With estimates of approximately 10 percent of all children in the United States having been subjected to child abuse, the significance of child maltreatment on brain development and function is an important consideration," said Yvette I. Sheline, MD, McLure professor of Psychiatry, Radiology, and Neurology, and director of the Center for Neuromodulation in Depression and Stress (CNDS) in the Perelman School of Medicine at the University of Pennsylvania. "This study not only confirms the important relationship between childhood trauma and major depression, but also links patients' experiences of childhood trauma with specific functional brain network abnormalities. This suggests a possible environmental contributor to neurobiological symptoms."
MDD is a common mental disorder characterized by a variety of symptoms -- including persistently depressed mood, loss of interest, low energy, insomnia or hypersomnia, and more. These symptoms impair daily life and increase the risk of suicide. In addition, experiences of childhood trauma, including physical, sexual, or emotional abuse, as well as physical or emotional neglect, have been associated with the emergence and persistence of depressive and anxiety disorders. However, the neurobiological mechanisms underlying MDD are still largely unknown.
To address this challenge, a team led by Sheline utilized functional magnetic resonance imaging (fMRI) to investigate the brain networks and patterns that underlie the disorder. Researchers compared brain activity in 189 participants with MDD to activity of 39 healthy controls. First author Meichen Yu, a post-doctoral fellow in the CNDS, conducted statistical analyses to determine the associations between temporal correlations in connectivity within and between 10 well-established, large-scale resting state networks (RSNs) and clinical measures, including both past history of trauma and current clinical symptoms, such as depression, anxiety, suicidality. These symptoms were measured by 213 item-level survey questions.
The authors found that in patients with MDD, while the strongest correlations were with childhood trauma, abnormal network connectivity was also associated with current symptoms of depression. Even though participants in this study were not selected as participants based on a history of trauma, and the brain imaging took place decades after trauma occurred, prior trauma was evident in abnormal functional connectivity.
"These results suggest that resting-state network connectivity may point to some of the brain mechanisms underlying the symptoms of major depressive disorder," Sheline explains. "It may have the potential to serve as an effective biomarker, aiding in the development of depression biotypes and opening up the possibility of targeted diagnosis."
https://www.sciencedaily.com/releases/2019/04/190408161610.htm
Stress in early life could make people more likely to develop depression
May 8, 2019
Science Daily/University of Bristol
New research by the University of Bristol has found that early life adversity could make an individual more at risk of developing negative thinking, which could lead to major depressive disorder (MDD). The findings provide biological and psychological evidence to support work first proposed in the 1960s.
The study, published in Neuropsychopharmacology and funded by the MRC and BBSRC, using a rodent model of early life adversity, has shown that offspring are much more sensitive to negative biases in their cognition when treated with the stress hormone, corticosterone.
The research has shown a dose of corticosterone had no effect in normal rats but caused a negative bias in the early life adversity animals. The study also found that the early life adversity rats were less likely to anticipate positive events and failed to properly learn about reward value. These impairments in reward-related cognition are particularly interesting as one of the main features of depression is a loss of interest in previously enjoyable activities.
The findings support the idea that those at risk of developing mood disorders may have impairments in the way they learn about and use their memories about how rewarding an experience has been to then guide and motivate them to repeat the activity. The researchers suggest that these neuropsychological effects might explain why early life adversity can make people more likely to develop depression.
Emma Robinson, Professor of Psychopharmacology, School of Physiology, Pharmacology & Neuroscience and lead author on the paper, said: "This study supports a wider body of literature which suggests that depression may develop from an interesting yet complex interaction between biological and psychological processes. As we start to understand these better we hope that the knowledge we generate can be used to better guide current and future treatments.
"Our larger body of work suggests that the effectiveness of current antidepressant treatments might be linked to how much a person is able to re-engage with their environment and their level of social support.
"The findings also add further evidence to support the validity of this relatively new area of research into mood disorders, particularly studies using animals to understand the neurobiology of affective biases and how they contribute to normal and pathological behaviour."
Studies in patients have shown that depression is linked to changes in how the person processes information particularly emotional information. People with depression have a negative view of the world which can be measured by looking at how they process information such as emotional faces and words. However, whether this causes the illness or are a consequence is not known.
The researchers developed a method to use in rodents where similar neuropsychological processes were measured. One of the tasks, the affective bias test, looked at how simple associations between a specific cue, a bowl with a specific digging substrate in it, and a reward, a food pellet, could be biased by the animal's affective state when they learn about it.
When animals learn the association in a negative affective state they remember it in a more pessimistic way whilst memories formed in a positive affective state are remembered in a more positive way. The biases the study was able to measure in rodents correlated exactly with how these same treatments affect peoples' mood in the long-term, something which no other animal test in psychiatry has been able to achieve.
The next step in the research will be to understand how these processes and the deficits seen in the animals respond to current antidepressant treatments including the recently licensed, rapid onset antidepressant ketamine. The researchers already have some evidence about how ketamine interacts with these neuropsychological processes and this latest work will help them bring these findings together with an important disease model and risk factor for depression.
https://www.sciencedaily.com/releases/2019/05/190508113326.htm