Depression and the inflammatory process

Most people feel down, tired and inactive when they’re injured or ill. This “sickness behavior” is caused by the activation of the body’s immune response. It’s the brain’s way of conserving energy so the body can heal.

This immune response can also occur in people with depression. This has prompted some researchers and clinicians to hypothesise that depression is actually a side effect of the inflammatory process.

But while there may be a connection between inflammation and depression, one doesn’t necessarily lead to the other. So it’s too simplistic to say depression is a physical, rather than a psychiatric, illness.

The inflammation hypothesis

University of California clinical psychologist and researcher George Slavich is one of the key recent proponents of depression as a physical illness. He hypothesises that social threats and adversity trigger the production of pro-inflammatory “cytokines”. These are messenger molecules of the immune system that play a critical role in orchestrating the host’s response to injury and infection.

This inflammatory process, Slavich argues, can initiate profound behavioral changes, including the induction of depression.5241352878_f53a343088.jpg

The idea that the activation of the immune response may trigger depression in some people is by no means a new one. Early descriptions of post-influenza depression appeared in the 19th century in the writings of English physician Daniel Tuke.

But it was not until the 1988 seminal paper, published by veterinarian Benjamin Hart, that the phenomenon of acute “sickness behavior” caught the interest of the scientific community.

Hart described his detailed observations of the “behavior of sick animals”. During acute infection, and in response to fever, the animals sought sleep, lost their appetite, showed a reduction in activity, grooming and social interactions, as well as showing signs of “depression”.

Just like the immune response itself, these changes reflect an evolved survival strategy that shifts priorities toward energy conservation and recovery.

Putting the theory into practice

Cytokine-induced sickness behavior has subsequently been studied as an example of communication between the immune system and the brain.

The behavioral changes during sickness resemble those associated with depression, so it didn’t take long for researchers to make a connection between the phenomenon of sickness behavior and mental disorders.

Such speculation was strengthened by research showing that depressive states can be experimentally induced by administering cytokines and other immunogenic agents (such as vaccines) that cause an inflammatory response.

Depression is frequently associated with inflammatory illnesses such as heart disease and rheumatoid arthritis. It’s also a side effect of treatment with cytokines to enhance the immune system.

Over recent decades, researchers have made progress in understanding how inflammation may impact on the activity of signalling pathways to and from the brain, as well as on the functioning of key neural systems involved in mood regulation.

But there’s not always a link

From the available evidence it’s clear, however, that not everyone who suffers from depression has evidence of inflammation. And not all people with high levels of inflammation develop depression.

brain-anatomy-colored.jpgTrajectories of depression depend on a complex interplay of a spectrum of additional risk and resilience factors, which may be present to varying degrees and in a different combination in any individual at different times. These factors include the person’s:

  • genetic vulnerabilities affecting the intensity of our inflammatory response
  • other medical conditions
  • acquired hyper-vigilance in the stress response systems due to early life trauma, current adversities, or physical stressors
  • coping strategies, including social support
  • health behaviors, such as sleep, diet and exercise.

Implications for treatment

In line with the notion that inflammation drives depression, some researchers have already trialled the effectiveness of anti-inflammatory therapy as a treatment for depression.

While some recipients (such as those with high levels of inflammation) showed benefit from the treatment, others without increased inflammation did not. This supports the general hypothesis.

However, in our desire to find more effective treatments for depression, we should not forget that the immune response, including inflammation, has a specific purpose. It protects us from infection, disease and injury.

Cytokines act at many different levels, and often in subtle ways, to fulfill their numerous roles in the orchestration of the immune response. Undermining their vital role could have negative consequences.

Mind versus body

The recent enthusiasm to embrace inflammation as the major culprit in psychiatric conditions ignores the reality that “depression” is not a single condition. Some depressive states, such as melancholia, are diseases; some are reactions to the environment; some are existential; and some normal.

Such separate states have differing contributions of biological, social and psychological causes. So any attempt to invoke a single all-explanatory “cause” should be rejected. Where living organisms are concerned it is almost never that simple.

In the end, we cannot escape the reality that changes must occur at the level of the brain, in regions responsible for mood regulation, for “depression” to be experienced.


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Joseph Campbell the Art of Living

“Nietzsche was the one who did the job for me. At a certain moment in his life, the idea came to him of what he called ‘the love of your fate.’ Whatever your fate is, whatever the hell happens, you say, ‘This is what I need.’ It may look like a wreck, but go at it as though it were an opportunity, a challenge. If you bring love to that moment—not discouragement—you will find the strength is there. Any disaster you can survive is an improvement in your character, your stature, and your life. What a privilege! This is when the spontaneity of your own nature will have a chance to flow.


“Then, when looking back at your life, you will see that the moments which seemed to be great failures followed by wreckage were the incidents that shaped the life you have now. You’ll see that this is really true. Nothing can happen to you that is not positive. Even though it looks and feels at the moment like a negative crisis, it is not. The crisis throws you back, and when you are required to exhibit strength, it comes.”


Joseph Campbell, A Joseph Campbell Companion: Reflections on the Art of Living.


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Lack of sleep

Dark puffy eyes, a feeling of deep exhaustion, and a foul mood to match – we’ve all experienced the side effects of a lack of sleep. It’s no wonder that sleep-deprivation has been used as a method of torture.

Our brains seem to lose the ability to distinguish between the innocuous and emotional in such circumstances, turning us into overreacting, exhausted wrecks.

Man Sleeping In
We all know that a good night’s sleep is vital for a day of clear thinking, but exactly why sleep is so important remains a mystery. Talma Hendler of Tel Aviv University in Israel is particularly interested in how lack of sleep leaves us with a short emotional fuse. “We know that sleep affects our emotional behaviour, but we don’t know how,” she says.

To investigate further, Hendler and her colleagues kept 18 adults awake all night. “It took a great effort,” she says. “During the night, we repeatedly measured their sleepiness, and unsurprisingly they got more and more tired.”

The volunteers were put through two rounds of tests while their brains were scanned, both the day after a good night’s sleep and after being awake for 24 hours. In one test, volunteers were asked to give the direction in which yellow dots moved on a screen. In each case, the dots were laid over a potentially distracting picture that was either positively emotional (of a kitten or a couple in love, for example), negatively emotional (such as a mutilated body or a snake) or neutral (such as a cow or spoon).

When the volunteers were well-rested, they were quickest and best at telling the direction of movement when the background image was neutral. But after a night without sleep, their performance was equally bad whether neutral or emotional images were used.

That might simply be because a sleepless night universally impairs judgement, but it’s also possible that the result hints at something more subtle – that lack of sleep makes neutral images suddenly provoke an emotional response, says Hendler.

Scanning the detail
To probe the link in more detail, her team conducted a similar experiment in an fMRI scanner, which is used to measure activity in different areas of the brain.feelings-45.jpg

Inside the scanner, volunteers were again shown potentially distracting neutral and emotional images while they tried to complete a task – and again, sleep-deprived people found all images distracting, whereas the non-sleep-deprived were only distracted by emotional images.

Moreover, a region of the brain called the amygdala, which is known to play a part in emotion, fired up in response only to emotional images when the volunteers had had a good night’s sleep. But when they were sleep-deprived, it reacted to neutral images in the same way as emotional ones.

The team also found unusual activity in a frontal part of the brain called the anterior cingulate cortex (ACC), which is thought to regulate the amygdala and our emotions. In well-rested people, the two brain regions fired together. But they seemed out of sync when the volunteers were sleep-deprived, with the ACC tending not to fire when the amygdala did. As a result, this part of the brain doesn’t seem as able to control our emotional responses when we don’t get enough sleep, says Hendler.

Together, the experiments suggest that when we’re sleep-deprived we tend to see normal, everyday situations as particularly worthy of our attention, says Hendler. “You lose neutrality,” she says. “The ability of the brain to tell what’s important is compromised – it’s as if everything is important.”

There is one obvious way to protect yourself from the effects of sleep loss: try to get enough shut-eye. Hendler thinks people might also be able to strengthen the connection between the ACC and amygdala using neurofeedback – a technique that uses brain-monitoring technology to allow people to record and watch their own brain activity and attempt to control it.

But Mary Carskadon at Brown University in Providence, Rhode Island, isn’t sold on the idea. “Despite wishes some have to the contrary, we all need sleep,” she says. “I don’t want to stimulate the activity between my amygdala and frontal cortex – I want to get plenty of sleep.”

Journal reference: Journal of Neuroscience, DOI:10.1523/jneurosci.1314-15.2015

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Kestenberg Movement Profile (KMP) Introduction

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A food pyramid is a graphical pyramid shaped nutrition guide, divided into sections. Each section represents a specific food group and shows the recommended intake for each food group. The pyramid shape graphic, illustrates a higher daily intake of foods at the bottom of the pyramid, and a smaller intake of foods at the top of the pyramid. Listed below are some of the more popular food graphics.

Dr. Weil’s Anti-Inflammatory Food Pyramid

“Following an anti-inflammatory diet can help counteract the chronic inflammation that is a root cause of many serious diseases, including those that become more frequent as people age. It is a way of selecting and preparing foods based on science that can help people achieve and maintain optimum health over their lifetime.”

Harvard’s Healthy Eating Food Pyramid is a food pyramid that focuses on diet and healthThis food pyramid was developed by the Harvard School of Public Health and is based on scientific evidence on the links between diet and health.

Oldways Preservation and Exchange Trust has come up with a vegetarian food pyramid called the Traditional Healthy Vegetarian Diet Pyramid, see graphics below.

The Mediterranean food pyramid is recognized as the “gold standard” eating pattern that promotes life long good health. In 1993, the Oldways Preservation and Exchange Trust, the Harvard School of Public Health, and the European Office of the World Health Organization made the Mediterranean diet even more popular when they came up with the food pyramid called The Mediterranean Diet Pyramid.

Oldways Preservation and Exchange Trust are the ones behind the Asian Diet Pyramid see graphical illustration below.

USDA’s My Plate was developed as an effort to promote healthy eating to consumers. The My Plate icon is easy to understand and it helps to promote messages based on the 2010 Dietary Guidelines for Americans. The new My Plate icon builds on a familiar image — a plate — and is accompanied by messages to encourage consumers to make healthy choices.


Harvard’s Healthy Eating Plate built by faculty members in the Department of Nutrition at the Harvard School of Public Health, in conjunction with colleagues at Harvard Health Publications. The Healthy Eating Plate fixes the flaws in USDA’s My Plate, just as the Healthy Eating Pyramid rectifies the mistakes of the USDA’s food pyramids. Both the Healthy Eating Plate and the Healthy Eating Pyramid are based on the latest science about how our food, drink, and activity choices affect our health—and are unaffected by businesses and organizations with a stake in their messages.

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“Words mean more than what is set down on paper. It takes the human voice to infuse them with deeper meaning.” Maya Angelou


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believe in ourselves

“We do not believe in ourselves until someone reveals that deep inside us something is valuable, worth listening to, worthy of our trust, sacred to our touch. Once we believe in ourselves we can risk curiosity, wonder, spontaneous delight or any experience that reveals the human spirit.” E.E. Cummings

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