Study: Aerobic Exercise Has Antidepressant Effects for Those With Major Depression

It seems like doctors should prescribe this sort of moderate intensity aerobic exercise instead of pharmaceutical drugs much more.

An analysis of randomized controlled clinical trials indicates that supervised aerobic exercise has large antidepressant treatment effects for patients with major depression. The systematic review and meta-analysis is published in Depression and Anxiety.

Across 11 eligible trials involving 455 adult patients (18-65 years old) with major depression as a primary disorder, supervised aerobic exercise was performed on average for 45 minutes, at moderate intensity, 3 times per week, and for 9.2 weeks. It showed a significantly large overall antidepressant effect compared with antidepressant medication and/or psychological therapies.

Also, aerobic exercise revealed moderate-to-large antidepressant effects among trials with lower risk of bias, as well as large antidepressant effects among trials with short-term interventions (up to 4 weeks) and trials involving preferences for exercise.

Subgroup analyses revealed comparable effects for aerobic exercise across various settings and delivery formats, and in both outpatients and inpatients regardless of symptom severity.

“Collectively, this study has found that supervised aerobic exercise can significantly support major depression treatment in mental health services,” said lead author Dr. Ioannis D. Morres, of the University of Thessaly, in Greece.

Three Types of Depression Identified in Research for the First Time

More knowledge about the societal problem of depression should lead to more effective treatments for it.

According to the World Health Organization, nearly 300 million people worldwide suffer from depression and these rates are on the rise. Yet, doctors and scientists have a poor understanding of what causes this debilitating condition and for some who experience it, medicines don’t help.

Scientists from the Neural Computational Unit at the Okinawa Institute of Science and Technology Graduate University (OIST), in collaboration with their colleagues at Nara Institute of Science and Technology and clinicians at Hiroshima University, have for the first time identified three sub-types of depression. They found that one out of these sub-types seems to be untreatable by Selective Serotonin Reuptake Inhibitors (SSRIs), the most commonly prescribed medicines for the condition. The study was published in the journal Scientific Reports.

Serotonin is a neurotransmitter that influences our moods, interactions with other people, sleep patterns and memory. SSRIs are thought to take effect by boosting the levels of serotonin in the brain. However, these drugs do not have the same effect on everyone, and in some people, depression does not improve even after taking them. “It has always been speculated that different types of depression exist, and they influence the effectiveness of the drug. But there has been no consensus,” says Prof. Kenji Doya.

For the study, the scientists collected clinical, biological, and life history data from 134 individuals — half of whom were newly diagnosed with depression and the other half who had no depression diagnosis- using questionnaires and blood tests. Participants were asked about their sleep patterns, whether or not they had stressful issues, or other mental health conditions.

Researchers also scanned participants’ brains using magnetic resonance imaging (MRI) to map brain activity patterns in different regions. The technique they used allowed them to examine 78 regions covering the entire brain, to identify how its activities in different regions are correlated. “This is the first study to identify depression sub-types from life history and MRI data,” says Prof. Doya.

With over 3000 measurable features, including whether or not participants had experienced trauma, the scientists were faced with the dilemma of finding a way to analyze such a large data set accurately. “The major challenge in this study was to develop a statistical tool that could extract relevant information for clustering similar subjects together,” says Dr. Tomoki Tokuda, a statistician and the lead author of the study. He therefore designed a novel statistical method that would help detect multiple ways of data clustering and the features responsible for it. Using this method, the researchers identified a group of closely-placed data clusters, which consisted of measurable features essential for accessing mental health of an individual. Three out of the five data clusters were found to represent different sub-types of depression.

The three distinct sub-types of depression were characterized by two main factors: functional connectivity patterns synchronized between different regions of the brain and childhood trauma experience. They found that the brain’s functional connectivity in regions that involved the angular gyrus — a brain region associated with processing language and numbers, spatial cognition, attention, and other aspects of cognition — played a large role in determining whether SSRIs were effective in treating depression.

Patients with increased functional connectivity between the brain’s different regions who had also experienced childhood trauma had a sub-type of depression that is unresponsive to treatment by SSRIs drugs, the researchers found. On the other hand, the other two subtypes — where the participants’ brains did not show increased connectivity among its different regions or where participants had not experienced childhood trauma — tended to respond positively to treatments using SSRIs drugs.

This study not only identifies sub-types of depression for the first time, but also identifies some underlying factors and points to the need to explore new treatment techniques. “It provides scientists studying neurobiological aspects of depression a promising direction in which to pursue their research,” says Prof. Doya. In time, he and his research team hope that these results will help psychiatrists and therapists improve diagnoses and treat their patients more effectively.

Mental Health Disorder Rates Rising Globally

This is a sign of regression or stagnation, not progress, and it suggests that there needs to be a shift in the general direction human societies are on. Outside of the economic impacts of lost productivity, there are many collateral effects (e.g., worsened interpersonal relationships) that are associated with widespread mental health problems continuing as well.

The “Lancet Commission” report by 28 global specialists in psychiatry, public health and neuroscience, as well as mental health patients and advocacy groups, said the growing crisis could cause lasting harm to people, communities and economies worldwide.

While some of the costs will be the direct costs of healthcare and medicines or other therapies, most are indirect – in the form of loss of productivity, and spending on social welfare, education and law and order, the report’s co-lead author Vikram Patel said.

The wide-ranging report did not give the breakdown of the potential $16 trillion economic impact it estimated by 2030.

“The situation is extremely bleak,” Patel, a professor at Harvard Medical School in the United States, told reporters.

He said the burden of mental illness had risen “dramatically” worldwide in the past 25 years, partly due to societies ageing and more children surviving into adolescence, yet “no country is investing enough” to tackle the problem.

“No other health condition in humankind has been neglected as much as mental health has,” Patel said.

The World Health Organization (WHO) estimates that around 300 million people worldwide have depression and 50 million have dementia. Schizophrenia is estimated to affect 23 million people, and bipolar disorder around 60 million.

The Lancet report found that in many countries, people with common mental disorders such as depression, anxiety and schizophrenia routinely suffer gross human rights violations – including shackling, torture and imprisonment.

Richard Horton, editor-in-chief of the medical journal the Lancet, which commissioned the report, said it highlighted the “shameful and shocking treatment of people with mental ill health around the world”.

It called for a human rights-based approach to ensure that people with mental health conditions are not denied fundamental human rights, including access to employment, education and other core life experiences.

Breakthrough in Making Much Less Addictive Opioids

Important research this is, for it shows that the powerful pain relief opioids provide doesn’t have to be such a dangerous double-edged sword.

In the US, more than one-third of the population experiences some form of acute or chronic pain; in older adults this number rises to 40 percent.

The most common condition linked to chronic pain is chronic depression, which is a major cause of suicide.

To relieve severe pain, people go to their physician for powerful prescription painkillers, opioid drugs such as morphine, oxycodone and hydrocodone.

Almost all the currently marketed opioid drugs exert their analgesic effects through a protein called the “mu opioid receptor” (MOR).

MORs are embedded in the surface membrane of brain cells, or neurons, and block pain signals when activated by a drug.

However, many of the current opioids stimulate portions of the brain that lead to additional sensations of “rewarding” pleasure, or disrupt certain physiological activities. The former may lead to addiction, or the latter, death.

Which part of the brain is activated plays a vital role in controlling pain. For example, MORs are also present in the brain stem, a region that controls breathing.

Activating these mu receptors not only dulls pain but also slows breathing. Large doses stop breathing, causing death.

Activating MORs in other parts of the brain, including the ventral tegmental area and the nucleus accumbens, block pain and trigger pleasure or reward, which makes them addictive. But so far there is no efficient way to turn these receptors “on” and “off” in specific areas.

But there is another approach because not all opioids are created equal. Some, such as morphine, bind to the receptor and activate two signaling pathways: one mediating pain cessation and the other producing side effects like respiratory depression.

Other drugs favor one pathway more than the other, like only blocking pain – this is the one we want.

“Biased opioids” to kill pain

But MOR isn’t the only opioid receptor. There are two other closely related proteins called kappa and delta, or KOR and DOR respectively, that also alter pain perception but in slightly different ways.

Yet, currently there are only a few opioid medications that target KOR, and none that target DOR. One reason is that the function of these receptors in the brain neurons remains unclear.

Recently KOR has been getting attention as extensive studies from different academic labs show that it blocks pain without triggering euphoria, which means it isn’t addictive.

Another benefit is that it doesn’t slow respiration, which means that it isn’t lethal. But although it isn’t as dangerous as MOR, activating KOR does promote dysphoria, or unease, and sleepiness.

This work suggests it is possible to design a drug that only targets the pain pathway, without side effects. These kind of drugs are called “biased” opioids.

[…]

The exciting news is that researchers in the Roth lab have discovered several promising compounds based on the KOR structure that selectively binds and activates KOR, without cavorting with the more than 330 other related protein receptors.

Now our challenge is to transform these molecules into safer drugs.

Research: Depressive Episodes Can Damage Memory

The extent of the damage depends on the severity and length of the depressive episodes. This new research gives a concrete example of why it is important to improve mental health outcomes — it turns out that depression can have directly negative effects on the brain, and there are plenty of implications for human society based on that.

During a depressive episode the ability of the brain to form new brain cells is reduced. Scientists of the Ruhr-Universität Bochum examined how this affects the memory with a computational model. It was previously known that people in an acute depressive episode were less likely to remember current events. The computational model however suggests that older memories were affected as well. How long the memory deficits reach back depends on how long the depressive episode lasts. The team around the computational neuroscientist Prof Dr Sen Cheng published their findings in the journal PLOS ONE on 7th June 2018.

Computational model simulates a depressive brain

In major depressive disorder patients may suffer from such severe cognitive impairments that, in some cases, are called pseudodementia. Unlike in the classic form of dementia, in pseudodementia memory recovers when the depressive episode ends. To understand this process, the scientists from Bochum developed a computational model that captures the characteristic features of the brain of a patient with depressions. They tested the ability of the model to store and recall new memories.

As is the case in patients, the simulation alternated between depressive episodes and episodes without any symptoms. During a depressive episode, the brain forms fewer new neurons in the model.

Whereas in previous models, memories were represented as static patterns of neural activity, the model developed by Sen Cheng and his colleagues views memories as a sequence of neural activity patterns. “This allows us not only to store events in memory but also their temporal order,” says Sen Cheng.

Impact on brain stronger than thought

The computational model was able to recall memories more accurately, if the responsible brain region was able to form many new neurons, just like the scientists expected. However, if the brain region formed fewer new brain cells, it was harder to distinguish similar memories and to recall them separately.

The computational model not only showed deficits in recalling current events, it also struggled with memories that were collected before the depressive episode. The longer the depressive episode lasted the further the memory problems reached back.

“So far it was assumed that memory deficits only occur during a depressive episode,” says Sen Cheng. “If our model is right, major depressive disorder could have consequences that are more far reaching. Once remote memories have been damaged, they do not recover, even after the depression has subsided.”

Article Examining Depression

The article mentions standards such as medication and counseling, but perhaps the best way to reduce high depressive rates in the population is to restructure society to make it much better for most people than it is currently.

Clinical depression has surged to epidemic proportions in recent decades, from little-mentioned misery at the margins of society to a phenomenon that is rarely far from the news. It is widespread in classrooms and boardrooms, refugee camps and inner cities, farms and suburbs.

At any one time it is estimated that more than 300 million people have depression – about 4% of the world’s population when the figures were published by the World Health Organization (WHO) in 2015. Women are more likely to be depressed than men.

Depression is the leading global disability, and unipolar (as opposed to bipolar) depression is the 10th leading cause of early death, it calculates. The link between suicide, the second leading cause of death for young people aged 15-29, and depression is clear, and around the world two people kill themselves every minute.

While rates for depression and other common mental health conditions vary considerably, the US is the “most depressed” country in the world, followed closely by Colombia, Ukraine, the Netherlands and France. At the other end of the scale are Japan, Nigeria and China.

[…]

Things have improved since people with mental illness were believed to be possessed by the devil and cast out of their communities, or hanged as witches. But there remains a widespread misunderstanding of the illness, particularly the persistent trope that people with depression should just “buck up”, or “get out more”.

[…]

The WHO estimates that fewer than half of people with depression are receiving treatment. Many more will be getting inadequate help, often focused on medication, with too little investment in talking therapies, which are regarded as a crucial ally.

[…]

There have been positive experiments with both ketamine and psilocybin, the active ingredient in magic mushrooms. Further hopes for a new generation of treatments have been raised by recent discoveries of 44 gene variants that scientists believe raise the risk of depression. Another controversial area of research is treatment for low immunity and mooted links between depression and inflammation.

Countries are increasingly recognising the need to train more psychologists to replace or complement drug treatments.

And perhaps most importantly, there is a cultural movement to make it easier for people to ask for help and speak out about their illness.

Link Between Depression and Increased Brain Aging in Older Adults Found

The new research shows another reason to take mental health problems seriously. Suboptimal cognitive function in older adults both decreases general welfare and leads to worse outcomes via less informed decisions in political democracy.

Psychologists at the University of Sussex have found a link between depression and an acceleration of the rate at which the brain ages. Although scientists have previously reported that people with depression or anxiety have an increased risk of dementia in later life, this is the first study that provides comprehensive evidence for the effect of depression on decline in overall cognitive function (also referred to as cognitive state), in a general population.

For the study, published today, Thursday 24 May 2018, in the journal Psychological Medicine, researchers conducted a robust systematic review of 34 longitudinal studies, with the focus on the link between depression or anxiety and decline in cognitive function over time. Evidence from more than 71,000 participants was combined and reviewed. Including people who presented with symptoms of depression as well as those that were diagnosed as clinically depressed, the study looked at the rate of decline of overall cognitive state — encompassing memory loss, executive function (such as decision making) and information processing speed — in older adults.

Importantly, any studies of participants who were diagnosed with dementia at the start of study were excluded from the analysis. This was done in order to assess more broadly the impact of depression on cognitive ageing in the general population. The study found that people with depression experienced a greater decline in cognitive state in older adulthood than those without depression. As there is a long pre-clinical period of several decades before dementia may be diagnosed, the findings are important for early interventions as currently there is no cure for the disease.

Lead authors of the paper, Dr Darya Gaysina and Amber John from the EDGE (Environment, Development, Genetics and Epigenetics in Psychology and Psychiatry) Lab at the University of Sussex, are calling for greater awareness of the importance of supporting mental health to protect brain health in later life.

Dr Gaysina, a Lecturer in Psychology and EDGE Lab Lead, comments: “This study is of great importance — our populations are ageing at a rapid rate and the number of people living with decreasing cognitive abilities and dementia is expected to grow substantially over the next thirty years.

“Our findings should give the government even more reason to take mental health issues seriously and to ensure that health provisions are properly resourced. We need to protect the mental wellbeing of our older adults and to provide robust support services to those experiencing depression and anxiety in order to safeguard brain function in later life.”