depression

Posted on Mental health

THIS COULD EXPLAIN A LOT – When chronic stress activates these neurons, behavioural problems like loss of pleasure, and depression result

When chronic stress activates these neurons, behavioral problems like loss of pleasure, depression result


Xin-Yun Lu, MD, PhD, (center) with Graduate Student Kirstyn Denney (left) and Postdoctoral Fellow Yuting Chen, PhD, both coauthors on the new paper CREDIT Michael Holahan, Augusta University

 It’s clear that chronic stress can impact our behavior, leading to problems like depression, reduced interest in things that previously brought us pleasure, even PTSD.

Now scientists have evidence that a group of neurons in a bow-shaped portion of the brain become hyperactive after chronic exposure to stress. When these POMC neurons become super active, these sort of behavioral problems result and when scientists reduce their activity, it reduces the behaviors, they report in the journal Molecular Psychiatry.

Scientists at the Medical College of Georgia at Augusta University looked in the hypothalamus, key to functions like releasing hormones and regulating hunger, thirst, mood, sex drive and sleep, at a population of neurons called the proopiomelanocortin, or POMC, neurons, in response to 10 days of chronic, unpredictable stress. Chronic unpredictable stress is widely used to study the impact of stress exposure in animal models, and in this case that included things like restraint, prolonged wet bedding in a tilted cage and social isolation.  

They found the stressors increased spontaneous firing of these POMC neurons in male and female mice, says corresponding author Xin-Yun Lu, MD, PhD, chair of the MCG Department of Neuroscience and Regenerative Medicine and Georgia Research Alliance Eminent Scholar in Translational Neuroscience.

When they directly activated the neurons, rather than letting stress increase their firing, it also resulted in the apparent inability to feel pleasure, called anhedonia, and behavioral despair, which is essentially depression. In humans, indicators of anhedonia might include no longer interacting with good friends and a loss of libido. In mice, their usual love for sugar water wains, and male mice, who normally like to sniff the urine of females when they are in heat, lose some of their interest as well.

Conversely when the MCG scientists inhibited the neurons’ firing, it reduced these types of stress-induced behavioral changes in both sexes.

The results indicate POMC neurons are “both necessary and sufficient” to increase susceptibility to stress, and their increased firing is a driver of resulting behavioral changes like depression. In fact, stress overtly decreased inhibitory inputs onto POMC neurons, Lu says.  

The POMC neurons are in the arcuate nucleus, or ARC, of the hypothalamus, a bow-shaped brain region already thought to be important to how chronic stress affects behavior.

Occupying the same region is another population of neurons, called AgRP neurons, which are important for resilience to chronic stress and depression, Lu and her team reported in Molecular Psychiatry in early 2021.  

In the face of chronic stress, Lu’s lab reported that AgRP activation goes down as behavioral changes like anhedonia occur, and that when they stimulated those neurons the behaviors diminished. Her team also wanted to know what chronic stress does to the POMC neurons.

AgRP neurons, better known for their role in us seeking food when we are hungry, are known to have a yin-yang relationship with POMC neurons: When AgRP activation goes up, for example, POMC activation goes down.

“If you stimulate AgRP neurons it can trigger immediate, robust feeding,” Lu says. Food deprivation also increases the firing of these neurons. It’s also known that when excited by hunger signals, AgRP neurons send direct messages to the POMC neurons to release the brake on feeding.

Their studies found that chronic stress disrupts the yin-yang balance between these two neuronal populations. Although AgRP’s projection to POMC neurons is clearly important for their firing activity, the intrinsic mechanism is probably the major mechanism underlying hyperactivity of POMC neurons by chronic stress, Lu says.

The intrinsic mechanism may include potassium channels in POMC neurons that are known to respond to a range of different signals, and when open, lead to potassium flowing out of the cell, which dampens neuronal excitation. While the potential role of these potassium channels in POMC neurons in response to stress needs study, the scientists suspect stress also affects the potassium channels and that opening those channels might be a possible targeted treatment to restrain the wildly firing POMC neurons.

Excessive activity of neurons is also known to produce seizures and there are anticonvulsants given to open potassium channels and decrease that excessive firing. There is even some early clinical evidence that these drugs might also be helpful in treating depression and anhedonia, and what the Lu lab is finding may help explain why.

Lu hasn’t looked yet, but she wants to further explore the role of these channels to better understand how stress affects them in POMC neurons and how best to target the channels if their findings continue to indicate they play a key role in exciting POMC neurons.  

Chronic stress affects all body systems, according to the American Psychological Association. Even muscles tense to keep our guard up against injury and pain. Stress can cause shortness of breath, particularly in those with preexisting respiratory problems like asthma. Longer term, it can increase the risk for hypertension, heart attack and stroke, even alter the good bacteria in our gut that helps us digest food.

Posted on Multiple Sclerosis

Researchers uncover a connection between multiple sclerosis lesions and depression

Brigham team found MS lesions that were consistent with a previously discovered depression circuit, uncovering new therapeutic targets

Multiple Sclerosis and depression
Multiple Sclerosis and depression


“If we want to find specific locations of brain damage that cause specific symptoms, it sometimes works, but only for simpler brain functions like vision or movement. When it comes functions like those associated with depression, it’s not that simple,” said corresponding author Shan Siddiqi, MD, an assistant professor of psychiatry at Harvard Medical School and director of psychiatric neuromodulation research at Brigham and Women’s Center for Brain Circuit Therapeutics. “When a patient has lesions all over the brain, we used to assume they were unrelated to depression because they seemed so disconnected. But with lesion network mapping (LNM), we can see even when lesions don’t directly overlap with each other; they may overlap with the same circuit.”

While many clinicians have assumed that specific lesions were more likely to cause depression in MS, it had never been proven before. Neither had a specific pattern that connected those lesions. LNM is fundamental in seeing such a pattern for depression since LNM allows researchers to envision networks of connectivity rather than just solitary sites of damage. In a 2021 study, the same Brigham team identified a common brain circuit that connected seemingly disparate brain lesion sites for patients who experienced depression after stroke or penetrating head trauma. The team set out to determine if MS lesions and depression could be connected through this new circuit.

To conduct their study, Siddiqi, co-first author Isaiah Kletenik, MD, and co-authors relied on a database of 281 patients with MS, which Drs have curated. Tanuja Chitnis, Bonnie Glanz, and Rohit Bakshi of the Brigham Multiple Sclerosis Center in the Department of Neurology. Dr. Charles Guttmann and his team in the Brigham Center for Neurological Imaging in the Department of Radiology developed a virtual laboratory environment that allows systematic data collection and analysis, greatly facilitating this work. Drs. Guttmann and Bakshi also collaborated to develop an automated lesion detection and outlining protocol, allowing the researchers to locate lesions with relative ease. For each patient, estimated connectivity between lesion locations was determined using a connectome database, a large-scale wiring diagram of the human brain made possible by initiatives such as the Human Connectome Project. Using the connectome database and LNM, the team found significant functional connectivity between MS lesion locations and their a priori depression circuit. Additionally, the data-driven circuit for MS depression showed similar topography to the a priori depression circuit. Together, these findings provide novel localization of MS depression.

While offering critical insight into MS depression, the study had a few key limitations. All patient history was unknown, meaning, on top of other potentially unknown histories, some patients may have had depression before MS. Additionally, the sample size — albeit the largest so far — was limited. The next step is clinical trials, as this novel localization of MS depression enables a host of possibilities for therapeutic targeting.

“The more we know about the connectivity of lesions that cause symptoms, the better our ability to target an ideal stimulation site for those symptoms,” said Siddiqi. “We’ve already shown the success of targeting our a priori depression circuit in other patients. Now that we’ve shown that the circuit can be applied to MS depression, we should be able to find a treatment target for these patients, too.”

Posted on Cardiovascular disease, Insomnia, Mental health

Frequent visits to green spaces linked to lower use of certain prescription meds

Lower use of drugs for depression, anxiety, insomnia, high blood pressure, and asthma in city dwellers. Findings independent of income and educational attainment


Frequent visits to urban green spaces, such as parks and community gardens in Finland, rather than the amount, or views of them from home, may be linked to lower use of certain prescription meds, suggests research published online in Occupational & Environmental Medicine.

The observed associations between frequent green space visits and lower use of drugs for depression, anxiety, insomnia, high blood pressure, and asthma were not dependent on socio-economic position.

Exposure to natural environments is thought to be good for health, but the evidence is inconsistent, say the researchers.

They wanted to determine if the amount of residential green and blue space (bodies of water), frequency of green space visits, and views of green and blue spaces from home might be separately associated with certain prescription meds.

They chose prescription meds as a proxy for ill health and those for anxiety and insomnia, depression, high blood pressure, and asthma, mainly because they are used to treat common and potentially severe health issues.

They drew on the responses of 16,000 randomly selected residents of Helsinki, Espoo, and Vantaa, to the Helsinki Capital Region Environmental Health Survey in 2015-16. These three cities make up the largest urban area in Finland. 

The survey gathered information on how city dwellers, aged at least 25, experience residential green and blue spaces within a 1 km radius of their homes.

Respondents were also asked to report their use of prescribed meds—drugs for anxiety, insomnia, and depression, collectively known as psychotropic drugs; high blood pressure and asthma drugs—if applicable, for periods ranging from within the past week up to more than a year ago or never.

They were also asked how often they spent time, or exercised outdoors, in green spaces, during May and September, with options ranging from never to 5 or more times a week. 

And they were asked whether they could see green or blue spaces from any of their windows at home, and, if so, how often they took in these views, with options ranging from seldom to often.

Green areas were forests, gardens, parks, castle parks, cemeteries, zoos, herbaceous vegetation associations such as natural grassland and moors, and wetlands. Blue areas were defined as seas, lakes, and rivers.

Potentially influential factors were also considered, including health behaviours, outdoor air pollution and noise, household income and educational attainment.

The final analysis included approximately 6000 participants who provided complete information.

This showed that the amount of residential green and blue spaces, or views of them from home, weren’t associated with prescription meds for mental health, insomnia, high blood pressure or asthma.

But the frequency of green space visits was. Compared with less than one weekly visit, visiting 3-4 times weekly was associated with 33% lower odds of using mental health meds, 36% lower odds of using blood pressure meds, and 26% lower odds of using asthma meds. 

The equivalent figures for visiting at least five times a week were 22%, 41%, and 24% lower.

These observed associations were weakened when weight (BMI) was factored in, particularly for asthma meds, as obesity is a known risk factor for asthma, point out the researchers. 

The effects of visiting green spaces were also stronger among those reporting the lowest annual household income ( below €30, 000). But overall, the associations found didn’t depend on household income and educational attainment.

This is an observational study, so we can’t establish cause and effect. No information was available on illness severity, and better health may enable a person to spend more time outdoors.

Finland has high forest cover, while Finnish cities are relatively green, making it easy for those willing to use green spaces to access them with minimal effort, they add. 

But they conclude: “Mounting scientific evidence supporting the health benefits of nature exposure is likely to increase the supply of high-quality green spaces in urban environments and promote their active use. This might be one way to improve health and welfare in cities.”

Posted on Cardiovascular disease, Mental health

Deep meditation may alter gut microbes for better health


Regular deep meditation, practised for several years, may help to regulate the gut microbiome and potentially lower the risks of physical and mental ill health, finds a small comparative study published in the open-access journal General Psychiatry.

The gut microbes found in a group of Tibetan Buddhist monks differed substantially from those of their secular neighbours. They have been linked to a lower risk of anxiety, depression, and cardiovascular disease.

Research shows the gut microbiome can affect mood and behaviour through the gut–brain axis. This includes the body’s immune response, hormonal signalling, stress response and the vagus nerve—the main component of the parasympathetic nervous system, which oversees an array of crucial bodily functions.

The significance of the group and specimen design is that these deep-thinking Tibetan monks can represent some more profound meditations. Although the number of samples is small, they are rare because of their location.

Meditation is increasingly being used to help treat mental health disorders, such as depression, anxiety, substance abuse, traumatic stress, and eating disorders as well as chronic pain. But it’s not clear if it might also be able to alter the composition of the gut microbiome, say the researchers.

The researchers analysed the stool and blood samples of 37 Tibetan Buddhist monks from three temples and 19 secular residents in the neighbouring areas to find out.

Tibetan Buddhist meditation originates from the ancient Indian medical system known as Ayurveda, and is a form of psychological training, say the researchers. The monks in this study had been practising it for at least 2 hours a day for 3 and 30 years.

None of the participants had used agents that can alter the volume and diversity of gut microbes: antibiotics; probiotics; prebiotics; or antifungal drugs in the preceding 3 months.

Both groups were matched for age, blood pressure, heart rate, and diet.

Stool sample analysis revealed significant differences in the diversity and volume of microbes between the monks and their neighbours. 

Bacteroidetes and Firmicutes species were dominant in both groups, as would be expected. But Bacteroidetes were significantly enriched in the monks’ stool samples (29% vs 4%), which also contained abundant Prevotella (42% vs 6%) and a high volume of Megamonas and Faecalibacterium.

“Collectively, several bacteria enriched in the meditation group [have been] associated with the alleviation of mental illness, suggesting that meditation can influence certain bacteria that may have a role in mental health,” write the researchers.

The previously published research suggests these include Prevotella, Bacteroidetes, Megamonas and Faecalibacterium species.

The researchers then applied an advanced analytical technique to predict which chemical processes the microbes might influence. This indicated that several protective anti-inflammatory pathways, in addition to metabolism—the conversion of food into energy—were enhanced in the meditation people.

Finally, blood sample analysis showed that levels of agents associated with a heightened risk of cardiovascular disease, including total cholesterol and apolipoprotein B, were significantly lower in the monks than in their secular neighbours by their functional analysis with the gut microbes.

Although a comparative study, it is observational. The numbers of participants were small, all male, and lived at high altitudes, making it difficult to draw any firm or generalisable conclusions. And the potential health implications could only be inferred from previously published research.

But based on their findings, the researchers suggest that the role of meditation in helping to prevent or treat psychosomatic illness merits further research.

And they conclude: “These results suggest that long-term deep meditation may have a beneficial effect on gut microbiota, enabling the body to maintain an optimal state of health.”

Posted on Mental health

1 in 8 older adults experienced depression for the first time during the COVID-19 pandemic


A new, large-scale study of more than 20,000 older adults in Canada found that approximately 1 in 8 older adults developed depression for the first time during the pandemic.

For those who had experienced depression in the past, the numbers were even worse. By the autumn of 2020 almost half (45%) of this group reported being depressed.

Published in the International Journal of Environmental Research and Public Health, the research analysed responses from the Canadian Longitudinal Study on Aging, which collected data from participants for an average of seven years.

“The high rate of first-onset depression in 2020 highlights the substantial mental health toll that the pandemic caused in a formerly mentally healthy group of older adults.” says first author, Andie MacNeil, a recent Master of Social Work graduate from the Factor-Inwentash Faculty of Social Work (FIFSW) and the Institute for Life Course and Aging, University of Toronto.

While the surge in prevalence of depression among older adults during the pandemic is well known, few studies prior to this have identified the percentage of people who experienced it for the first time or the percentage of people with a history of the disorder who experienced a relapse.

“The devastation of the pandemic which upended so many aspects of daily life hit those with a history of depression particularly hard,” says co-author Sapriya Birk, a researcher formerly based in the Department of Neuroscience, Carleton University, Ottawa who is currently a medical student at McMaster University, Hamilton, Canada. “Health professionals need to be vigilant in screening their patients who had mental health problems at an earlier time in their life.”

The researchers identified several factors that were associated with depression among older adults during the pandemic, including inadequate income and savings, loneliness, chronic pain, trouble accessing healthcare, a history of adverse childhood experiences, and family conflict.

Older adults who, prior to the pandemic perceived their income to be inadequate for satisfying their basic needs, and those who had fewer savings were more likely to develop depression during the pandemic.

“These findings highlight the disproportionate mental health burden borne by individuals with low socioeconomic status during the pandemic. Many of these socioeconomic risk factors may have been exacerbated by the economic precarity of the pandemic, particularly for individuals with fewer resources,” says co-author Margaret de Groh, Scientific Manager at the Public Health Agency of Canada.

Individuals who experienced various dimensions of loneliness, such as feeling left out, feeling isolated, and lacking companionship had approximately 4 to 5 times higher risk of both incident and recurrent depression.

“It is not surprising that the lock-down was particularly difficult for older adults who were isolated and lonely during the pandemic.  Social connections and social support are essential for well-being and mental health. Better support and outreach are needed for those who are isolated,” says co-author Ying Jiang, Senior Epidemiologist at the Public Health Agency of Canada.

Older adults in chronic pain and those who had trouble accessing their usual healthcare, medication or treatments were more likely to be depressed during the autumn of 2020.

“This finding underlines the importance of streamlining service provision to ensure less disruption of medical services when future pandemics arise,” says co-author Professor Paul J. Villeneuve, Department of Neuroscience, Carleton University, Canada.

Individuals with a childhood history of adversity were more likely to be depressed during the Autumn of 2020.  Older adults who experienced family conflict during the pandemic had more than triple the risk of depression compared to their peers who did not.

“Family conflict is a major stressor that can impacts mental health even in the best of times. With the enforced close quarters of lockdown and the stress of the pandemic, there was considerable strain on many family relationships. The ensuing conflict was a major risk for depression,” says senior author, Professor Esme Fuller-Thomson at University of Toronto’s FIFSW and director of the Institute for Life Course & Aging.

The study was published in the International Journal of Environmental Research and Public Health.  The study included 22,622 participants of the Canadian Longitudinal Study on Aging (CLSA) who provided data at the baseline wave (2011–2015), follow-up 1 wave (2015–2018), and during the pandemic (September–December 2020).  The impact of the pandemic on depression among older Canadians may even be greater than observed because vulnerable populations were under-represented in the CLSA.

“We hope our findings can help health and social work professionals improve targeted screening and outreach to identify and serve older adults most at risk for depression,” said Andie MacNeil.