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Depression: Goodbye Serotonin, Hello Stress and Inflammation

New research on depression focuses on the immune system.

Inflammation plays a key role in the pathology of stress-related diseases.
Inflammation can contribute to the development and severity of depression.
Conventional mechanisms linking stress and disease have focused on the HPA axis and the sympathetic nervous system.

Accumulating evidence indicates that stress is a common risk factor for more than 75 percent of physical and mental diseases, increasing the morbidity and mortality of these diseases. Psychiatric disorders such as depression are the most common stress-related disease.

In the past, medical experts believed that depression was essentially a brain illness due to a deficit of serotonin that led to treating depression with drugs that increased the concentrations of serotonin in the brain. Depression may be much more complex than that.

New research shows that stress can induce inflammatory changes in the brain and the peripheral immune system. This results in the production of inflammation-enhancing cytokines that travel to the brain’s reward center and largely deactivate it, leading to anhedonia, or loss of interest and pleasure. Anhedonia is a prominent symptom of depression.

Stress, Inflammation, and Depression
For a long time, inflammation was considered an essential response to tissue injury or microbial invasion. Increasingly, it is viewed as being precipitated by stress and a significant contributor to psychiatric disorders, including depression. People with depression often have higher levels of inflammatory cytokines in their blood. Many studies have demonstrated that treating inflammation can improve depression.

Stressful events activate the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis, which trigger the “fight or flight” response that floods the body with catecholamines, glucocorticoids, and other stress-related substances, which, in turn, activates certain cells of the immune system to produce cytokines.

Cytokines are a broad category of small proteins, such as interferon, interleukin, and others. There are pro-inflammatory cytokines, which promote inflammation, and anti-inflammatory cytokines, which fight inflammation. We are learning now that certain pro-inflammatory cytokines are involved in anxiety, chronic pain, and, by blocking the function of the brain’s reward center, the development of depression. The reward system comes to associate diverse stimuli (substances, situations, events, or activities) with a positive or desirable outcome (i.e., feeling good and happy). When it is down, a person finds no pleasure in anything. The depressed person isolates and feels sad.

Dr. Steve Cole, professor of medicine, psychiatry, and behavioral science at the UCLA School of Medicine, has pioneered research on the signal transduction pathways that give rise to psychological and social states in the context of gene regulation. Signal transduction pathways relay information from outside the cell, through the cell membrane into the interior of the cell, where it can then start a chain reaction that ultimately leads to turning on or turning off genes inside the nucleus.

In a recent paper, Cole reported on his study of Black mothers in racially segregated neighborhoods on the South Side of Chicago. The overwhelming feeling that a majority of the subjects expressed was one of “being trapped.” These women suffered increased mental distress in the form of posttraumatic stress disorder (PTSD), depressive symptoms, and glucocorticoid receptor gene regulation. Feeling trapped, living in a violent environment was associated with greater cortisol output from the HPA axis and consequent negative feedback inhibition of the glucocorticoid receptor (GR) mRNA levels.

Writing on the subject of biological determinants of discrimination, Cole found that discrimination was associated with alterations of brain networks related to emotion, cognition, and self-perception, and structural and functional changes in the gut microbiome. This study contributes toward our understanding of how social inequalities become a whole-body experience and how a common expression like “racism makes me sick to my stomach” actually makes scientific sense.

Intestinal bacteria, the microbiome, produce metabolites such as bile acids, choline, and short-chain fatty acids (SCFAs) that are essential for host health as well as myriad neuroactive compounds such as serotonin, dopamine, and other brain chemicals that regulate mood. Therefore, it is not surprising that psychiatric and neurological illnesses, including multiple sclerosis, autism, schizophrenia, and depression, are often present simultaneously with gastrointestinal disease. Recent research expands our understanding of how the microbiome communicates with the enteric nervous system (“The Thoughtful Bowel”), the immune system, and, by way of the vagus nerve, the brain.

There is now considerable evidence that loneliness is a risk factor for poor psychological and physical health. Loneliness typically refers to the feelings of distress and dysphoria resulting from a discrepancy between a person’s desired and achieved levels of social relations. Scientists from the University of California, San Diego, La Jolla, found that loneliness was associated with a lack of diversity in the gut microbiome and, consequently, reduced resistance and resilience to stress-related disruptions, leading to downstream physiological effects, such as systemic inflammation and depression.

It follows that many factors such as stress and inflammation, in addition to “a chemical imbalance,” read “serotonin deficit” as promulgated by Big Pharma, are responsible for the development of depression and other mental and physical diseases.

Stress Busting
Depending on a person’s microbiome, certain antidepressants may benefit some people but not others. No doubt, assessing an individual’s microbiome before commencing treatment will be an important lab test in the future.
Moreover, nonpharmacological treatments for major depression such as exercise may be mediated by anti-inflammatory actions. Omega-3 fatty acids have been identified as potential treatments for major depressive disorder–related inflammations.

Enhancing good gut microbes—whether with probiotics or by adding yogurt or other fermented foods to the diet—may be an answer to intractable depression, the kind conventional treatments can’t touch.

Steve Cole has written much on the subject of self-regulation. He holds, and I totally agree with him, that we are architects of our own lives more than we realize. Our subjective experience carries more power than our objective situation. If we feel good about ourselves, not only will our health improve but so will our relationships. There are many ways in which we can raise our self-esteem and become more optimistic.

Treatment approaches that target inflammation and the gut microbiome in conjunction with SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin-norepinephrine reuptake inhibitors) may be more effective than SSRIs or SNRIs alone.

Reference: Psychology Today

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Performing acts of kindness may help people suffering from depression or anxiety

Social connection is one of the ingredients of life most strongly associated with well-being. Performing acts of kindness seems to be one of the best ways to promote those connections.”

People suffering from symptoms of depression or anxiety may help heal themselves by doing good deeds for others, new research shows.

The study found that performing acts of kindness led to improvements not seen in two other therapeutic techniques used to treat depression or anxiety.

Most importantly, the acts of kindness technique was the only intervention tested that helped people feel more connected to others, said study co-author David Cregg, who led the work as part of his PhD dissertation in psychology at The Ohio State University.
Cregg conducted the research with Jennifer Cheavens, professor of psychology at Ohio State. Their study was published recently in The Journal of Positive Psychology.

The research also revealed why performing acts of kindness worked so well: It helped people take their minds off their own depression and anxiety symptoms.

This finding suggests that one intuition many people have about people with depression may be wrong, Cheavens said.

"We often think that people with depression have enough to deal with, so we don't want to burden them by asking them to help others. But these results run counter to that," she said.

"Doing nice things for people and focusing on the needs of others may actually help people with depression and anxiety feel better about themselves."

The study involved 122 people in central Ohio who had moderate to severe symptoms of depression, anxiety, and stress.

After an introductory session, the participants were split into three groups. Two of the groups were assigned to techniques often used in cognitive behavioral therapy (CBT) for depression: planning social activities or cognitive reappraisal.

The social activities group was instructed to plan social activities for two days a week. Another group was instructed in one of the staples of CBT: cognitive reappraisal. These participants kept records for at least two days each week that helped them identify negative thought patterns and revise their thoughts in a way that could reduce depression and anxiety.
Members of the third group were instructed to perform three acts of kindness a day for two days out of the week. Acts of kindness were defined as "big or small acts that benefit others or make others happy, typically at some cost to you in terms of time or resources."

Some of the acts of kindness that participants later said they did included baking cookies for friends, offering to give a friend a ride, and leaving sticky notes for roommates with words of encouragement.

Participants followed their instructions for five weeks, after which they were evaluated again. The researchers then checked with the participants after another five weeks to see if the interventions were still effective.

The findings showed that participants in all three groups showed an increase in life satisfaction and a reduction of depression and anxiety symptoms after the 10 weeks of the study.

"These results are encouraging because they suggest that all three study interventions are effective at reducing distress and improving satisfaction," Cregg said.

"But acts of kindness still showed an advantage over both social activities and cognitive reappraisal by making people feel more connected to other people, which is an important part of well-being," he said.

In addition, the acts of kindness group showed greater improvements than the cognitive reappraisal group for life satisfaction and symptoms of depression and anxiety, results showed.

Cheavens noted that just participating in social activities did not improve feelings of social connection in this study.

"There's something specific about performing acts of kindness that makes people feel connected to others. It's not enough to just be around other people, participating in social activities," she said.

Cregg said that while this study used techniques of CBT, it is not the same experience as going through CBT. Those who undergo the full treatment may have better results than those in this study.

But the findings also show that even the limited CBT exposure given in this study can be helpful, Cheavens said.

"Not everyone who could benefit from psychotherapy has the opportunity to get that treatment," she said. "But we found that a relatively simple, one-time training had real effects on reducing depression and anxiety symptoms."

And beyond traditional CBT, acts of kindness may have additional benefits in creating social connections, Cregg said.

"Something as simple as helping other people can go above and beyond other treatments in helping heal people with depression and anxiety," he said.

Ohio State University

Journal reference:
Cregg, D.R., et al. (2022) Healing through helping: an experimental investigation of kindness, social activities, and reappraisal as well-being interventions. The Journal of Positive Psychology. doi.org/10.1080/17439760.2022.2154695.
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Timely treatment of depression could reduce the risk of dementia

Importance of Continuous Psychotherapy: Once again, the course of ineffectively treated depression carries significant medical risk.”

Depression has long been associated with an increased risk of dementia, and now a new study provides evidence that timely treatment of depression could lower the risk of dementia in specific groups of patients.

Over 55 million people worldwide live with dementia, a disabling neurocognitive condition that mainly affects older adults. No effective treatment for dementia exists but identifying ways to help minimize or prevent dementia would help to lessen the burden of the disease.

The study, led by Jin-Tai Yu, MD, PhD, Huashan Hospital, Shanghai Medical College, Fudan University, and Wei Cheng, PhD, Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China, appears in Biological Psychiatry, published by Elsevier.

Professor Yu and Professor Cheng used data collected by the UK Biobank, a population-based cohort of over 500,000 participants. The current study included more than 350,000 participants, including 46,280 participants with depression. During the course of the study, 725 of the depressed patients developed dementia.

Previous studies examining whether depression therapies such as pharmacotherapy and psychotherapy could lower the risk for dementia produced mixed results, leaving the question unresolved. "Older individuals appear to experience different depression patterns over time," said Professor Yu. "Therefore, intra-individual variability in symptoms might confer different risk of dementia as well as heterogeneity in effectiveness of depression treatment in relation to dementia prevention."

To address that heterogeneity, the researchers then categorized participants into one of four courses of depression: increasing course, in which mild initial symptoms steadily increase; decreasing course, starting with moderate- or high-severity symptoms but subsequently decreasing; chronically high course of ongoing severe depressive symptoms; and chronically low course, where mild or moderate depressive symptoms are consistently maintained.
As expected, the study found that depression elevated the risk of dementia – by a striking 51% compared to non-depressed participants. However, the degree of risk depended on the course of depression; those with increasing, chronically high, or chronically low course depression were more vulnerable to dementia, whereas those with decreasing course faced no greater risk than participants without depression.

The researchers most wanted to know whether the increased risk for dementia could be lowered by receiving depression treatment. Overall, depressed participants who received treatment had reduced risk of dementia compared to untreated participants by about 30%. When the researchers separated the participants by depression course, they saw that those with increasing and chronically low courses of depression saw lower risk of dementia with treatment, but those with a chronically high course saw no benefit of treatment in terms of dementia risk.
He notes that, "in this case, symptomatic depression increases dementia risk by 51%, whereas treatment was associated with a significant reduction in this risk."

"This indicates that timely treatment of depression is needed among those with late-life depression," added Professor Cheng. "Providing depression treatment for those with late-life depression might not only remit affective symptoms but also postpone the onset of dementia."

"The new findings shed some light on previous work as well," said Professor Cheng. "The differences of effectiveness across depression courses might explain the discrepancy between previous studies."
Yang, L., et al. (2022) Depression, Depression Treatments, and Risk of Incident Dementia: A Prospective Cohort Study of 354,313 Participants. Biological Psychiatry. doi.org/10.1016/j.biopsych.2022.08.026.


Cognitive Fitness

Develop a Clearer, Sharper, Healthier Brain in 6 Simple Steps

STEP #1: Enjoy a Brain-Healthy Diet

Discover plant-based foods that can help prevent cognitive decline. The flexible, unrestrictive diet shown to reduce Alzheimer’s risk by up to 53% in a study. The best vitamins and nutrients for brain health and their food sources. Brain-damaging foods to avoid. Downloadable diet plans and recipes. And more.
STEP #2: Brain-Healthy Exercise

People who are more physically active are at less risk of dementia and score better on attention, verbal fluency, verbal memory and other cognitive abilities. Discover the benefits of three type of exercises plus mind/body exercises for better brain health. You’ll also get a printable exercise tracker to keep you motivated!
STEP #3: Brain-Healthy Sleep

Find out why getting the right amount of sleep is essential for locking long-term memory. Plus, see what to do if you have trouble falling asleep...daytime tips to improve nighttime sleep...non-drug approaches to help you relax and fall asleep...doctor-recommended over-the-counter and prescription sleep aids...and more.

STEP #4: Brain-Healthy Stress Management

Find out how chronic stress can damage your brain and lead to memory problems. Plus, discover practical tools and strategies to manage stress and boost resilience...stress-busting foods...how improving your gut health can relieve chronic stress...how to identify and deal with stress triggers...and more. PLUS: How stressed are you, really? Find out with our interactive quiz!
STEP #5: Brain-Healthy Relationships

Find out why healthy relationships are as important as physical activity and healthy diet for brain health. Discover simple steps to widen your social network...games that improve your ability to remember specific events...specific relationships that improve your ability to think on your feet...and more. PLUS: How lonely are you, really? Find out with our interactive quiz!
STEP #6: Brain-Healthy Challenges

Evidence shows that the more you stimulate your brain, the better you can protect yourself against the detrimental effects of aging. Discover the three rules for mental stimulation... how a certain puzzle can slow the onset of memory decline by as much as 2½ years...the astounding impact of computer-based brain training...and more.

PLUS — you’ll get a printable cognitive fitness checklist and a goal-planning worksheet to help keep you on target in your brain-building efforts!

Reference :
Harvard Medical School.
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Positive Parenting, Brain Development, and Teen Alcohol Use

Parents’ closeness in teen years enhances resiliency and reduces alcohol abuse.

Not only does positive parenting make for a happier family life, but it also enhances children’s cognitive, physical, social, and emotional development going forward. A recently published study shows that this remains true through the teen years, and that it's particularly important for kids at risk of substance abuse.
Adolescence is a time of rapid and critically important brain development, a time during which positive parenting leads to better self-regulation, cognitive processing, decision-making, and judgement. The developing brain can be nurtured by positive parenting, and it can also be damaged by drug or alcohol abuse, very much including binge drinking.
Research Findings Support Parental Closeness During Adolescence
In a recently published study, Gayathri Pandey and colleagues investigated whether parents’ closeness to their children aged 12 to 17 had an impact on the teens’ binge drinking behavior. They found that young people at risk of alcohol abuse were less likely to be binge drinkers, and more likely to show signs of healthy brain development, if they felt close to their parents through the teen years.
There were some differences by sex (e.g., closeness to mothers was more strongly related to avoidance of binge drinking; closeness to fathers showed a bigger impact on neurocognitive factors), but in general both parents’ closeness to their adolescent child made a difference in the likelihood of binge drinking and healthy brain development.
Pandey and colleagues concluded that, “Positive parenting and parent–child closeness promote children's efficient executive functions and self-regulation, which in turn reduce risky drinking and other externalizing behaviors.”
How to Practice Positive Parenting in the Teen Years
1-Take good care of yourself. It can be very challenging to be the parent of a teenager. In order to maintain a patient, loving relationship with your child, do your best to get good nutrition, enough sleep and exercise, and time for yourself.
 2-Be positive. The teen years are filled with anxieties, insecurities, and self-doubts, as well as a heightened alertness to possible criticism. No matter how challenging it might be, look for ways to show your approval every day, and be careful to avoid critical judgement.
3-Show up. As much as possible, be there for your teenager. Quality time is important, but so is the amount of time you’re present and available.
4-Listen. Your teenager may not always want to talk to you, but when they do, listen with an open heart, without criticism or judgement. Do your best to avoid lecturing or pontificating. Just listen, with empathy and (as much as possible) approval.
5-Be calm and confident. It’s normal and healthy for you and your teen to see things differently and to argue about that. No matter how you feel at the time, it’s good for their development if they contest your attitudes, beliefs, and values. That’s the best way for them to hear why you think the way you do. If you can be calm and confident about your position, you’ll increase the likelihood they’ll see things your way.
6-Respect your child’s autonomy. Treat your teenager as the young adult they are in the process of becoming. Give them as much respect and independence as they can safely handle. Let them learn from making small mistakes now, as a way to prevent larger mistakes later.
7-Support your child’s solution-finding. Even if your child asks for advice, if they come to you with a problem, be empathetic and start with questions that help them define their own solutions. “What do you think you should do?” is always a good start. Followed by, “What do you think would happen if you did that?” After that kind of conversation, if your child still wants you to weigh in, or if they haven’t come to a good solution, you might say, “If I were you, I think I’d probably…”
8-Set expectations, rules, and consequences collaboratively. Discuss with your child what you need from them, and what they need from you, to keep your home running smoothly. Make as few rules as possible, and make sure they’re clear and understood. Get your child involved in deciding on consequences for violations. Rather than removing privileges like screens, discuss additional chores as possible consequences.
9-Be a good role model. You may not realize how closely your child is watching what you do, how you relate to others, how reliable and trustworthy you are, whether or not your actions match your admonitions to them. They learn so much more from what you do than from what you say.
10-Stay connected. Keep your focus on your connection with your child, not on the mistakes they make, or the bad judgement they show, or the disrespect they show for you and others. What matters most in the long run is their feeling that you love and support them, that you believe in them, not whether or not they fail a grade, drink too much at a party, or stay out past their curfew.
There are many good reasons to practice positive parenting with your teenager. These new research findings show that supporting their healthy brain development and reducing the likelihood of substance abuse are two more.

psychology today


Discover how to keep your brain its healthiest best!

Learn the 6 simple steps that can enhance your mental stamina, boost your memory, and provide added years of robust cognitive fitness.

Dear Reader,

Cognitive fitness goes far beyond just memory. It embraces thinking, learning, recognition, and sound decision-making. Cognitive fitness is the bedrock of a rewarding and self-sufficient life.
You can be “brain-healthy” for life!
This Special Health Report will show you how to sidestep threats to your brain’s wellness. You’ll learn how to build a “cognitive reserve” to address your brain’s changes. And most of all, you’ll gain the tools to shape and secure lasting and fulfilling cognitive vitality.
As never before, you can attain enduring brain health. Doctors at Harvard Medical School have identified six steps, which together can spur and protect cognitive fitness.
This multi-pronged brain fitness program includes and integrates proven approaches like optimal nutrition, exercise, stress reduction, social interaction, sleep, and stimulating activities.
A program that makes good sense — and designed for your success!
This guide will equip you to give your brain the attention it needs to stay at its best. The program will help you maintain a responsive memory, sustain your learning abilities, and remain confident that your mental skills will continue to serve you well.
This guide shares the wisest choices to defend your brain against the effects of aging. At the heart of the program are modest — but specific — changes in your diet, exercise regimen, and your lifestyle.
You’ll master the strategies that will stimulate your thinking!
You’ll be introduced to easy-to-follow brain-friendly diets. You’ll find five delicious foods linked to better brainpower. And you'll learn a little-known secret to maximizing exercise’s cognitive benefits.

You’ll find tips to ease stress and to get the sleep essential for memory. You’ll learn the keys to a brain-power nap, 10 tested methods to manage stress, and tricks to beat insomnia naturally.

The Special Health Report will help you strengthen your brain’s agility and nurture the personal interactions that keep your mind engaged. You’ll be briefed on techniques to supercharge your mental workouts, effective ways to foster an invigorating social network, and much more.
Don’t wait. See this empowering report for yourself. After all, there’s nothing better than making up your own mind!
In A Guide to Cognitive Fitness, you’ll find...
✓ 	Cognitive fitness: Your No. 1 health goal
✓ 	How cognitive function is shaped over a lifetime
✓ 	STEP 1: Eat a plant-based diet
✓ 	STEP 2: Exercise regularly
✓ 	STEP 3: Get enough sleep
✓ 	STEP 4: Challenge your brain
✓ 	And more!

Harvard Health Publishing
Harvard Medical School