Tag Archives: BDNF

The lost art of joy – Move!

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What’s your vision of bliss? Massage? Sitting by the beach with a pina colada? Enjoying a sumptuous dinner with friends?

Most relaxation fantasies don’t involve sweat.

So it’s almost a bit counter-intuitive that exercise is one of the most frequently associated habits of happy people. Although maybe it’s not so counter-intuitive, as there is strong anecdotal evidence of the “runner’s high” – the feeling of euphoria that some people feel after a session of vigorous exercise, the “endorphin buzz” that ironically doesn’t have anything to do with endorphins!

Endorphin buzz or no, exercise is certainly one way of enhancing the joy in your life. I previously wrote about the work of George MacKerron from the University of Sussex, who used an app he created to map the correlation of happiness to activity and location. Using the hundreds of thousands of data points from the tens of thousands of users, he found that the times that people recorded the highest levels of happiness and life satisfaction were during sexually intimate moments (on a date, kissing, or having sex). Number two was during exercise.

Physical fitness is good for us. I’ve never seen a study that shows exercise to be a bad thing. Ultimately, it’s not how fat you are that’s important for your longevity, it’s how fit you are, and the way to get fit is to exercise. Physical exercise isn’t just good for the body but good for the brain as well. While the exact pathways are still being determined, there’s good evidence that moderate regular physical activity improves the balance of pro- and anti-inflammatory mediators in the body and in the brain. In the brain, this improves the overall function of our brain cells. Exercise is also thought to increase the production of a growth factor called BDNF which helps the brain cells grow new branches and improves their ability to form new pathways, which in turn, has been shown to improve mood disorders like anxiety and depression.

Exercise is great, but not everyone is ready to suddenly get up and run a half-marathon, me included. These days, I’m like a walrus on tranquillisers. I’m certainly not about to jump up and go for a jog. Some people have physical injuries or conditions that limit their capacity for physical exercise.

So how do you find the balance between maximising the joy-enhancing effects of exercise while not pushing yourself so far and causing yourself some unhappiness?

Simply, move more.

Where are you at with you’re level of exercise right now? If you could turn it into a scale from 1 to 10 (where 1 is completely sedentary, and 10 is your ideal version of regular exercise), what would you rate? The next question is, what’s one thing you could do to go one point closer to 10? So let’s just say that you walk 200m from your house to the bus stop in the morning, and the same on the way home at night. For you, that might be a 3/10. What else could you do to make that 3 turn into a 4?

You don’t have to go for vigorous two-hour walks or run up every set of stairs you come across to be happy. Just move, and move that little bit more. That will help build joy in your life.

Can an aspirin a day keep the psychiatrist away?

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Floating across my Facebook feed this morning was an article on the possible link between depression and inflammation.  Its premise was that depression, the joyless soul-sucking disease affecting millions of people around the world, is related to inflammation.  If that were true, might mean that we could cure depression with medications that stop inflammation.  Maybe we should be consuming an aspirin a day to keep the doctor away, and not the proverbial apple?

Inflammation is a hot topic right now.  Inflammation in the medical sense refers to a normal body process to promote healing and recovery from sickness or injury.  It’s a complex dance of chemical signals which is triggered by damage to tissue.  Inflammation is essential to life. Without it, we would be unable to repair our tissues if they were damaged.

When tissues are damaged, a number of local cells in the damaged area release pro-inflammatory cytokines which then trigger a cascade of responses; increase in the size of the local blood vessels to allow greater blood flow to the area, attracting pus-cells (neutrophils) to the area, and increasing the ‘leakiness’ of the blood vessels to allow the pus cells into the area. This response is governed by a number of chemical mediators throughout the body, including histamine, serotonin, complement system, kinins, substance P, prostaglandins and leukotrienes, cytokines and nitric oxide. Anti-inflammatory cytokines balance out the process, keeping the pro-inflammatory cytokines in check so that the process doesn’t spiral out of control.

Despite the literal plethora of chemical reactions going on simultaneously, most of the time the reaction eventually runs out of noxious agents, the anti-inflammatory cytokines dampen down the reaction, and the tissue returns to either normal, or at least functional.  Though inflammation isn’t just limited to repairing damage but also preparing for damage –psychological stress prepares the inflammation system for potential damage.  Physical stress triggers the inflammation system to repair any damage.

Chronic inflammation occurs when the acute illness or injury does not fully resolve and continues to smoulder, the natural healing pathway is obstructed, or the body remains in a psychological state in which it is always expecting a fight.  In chronic inflammation, the processes of active inflammation, tissue destruction and attempts at healing occur simultaneously. In terms of cytokines, the anti-inflammatory cytokines can’t balance out the excess pro-inflammatory cytokines.

There’s a theory about depression which is gaining momentum within the scientific community, that depression and a number of other psychiatric and neurodegenerative conditions are the result of chronic inflammation which occurs because of chronic stress.

Remember when I said before that psychological stress readies the inflammatory system for potential damage?  Well, what if that damage never comes?  If there’s chronic psychological stress, the system is constantly being worn down, and never getting a chance to recover.  This seems to make sense – chronic stress reduces new nerve cell production and growth, and may interfere with the action of nerve growth factors like BDNF and neurotransmitters like serotonin.  Hence why this article by Feelguide seems to ring true.

But is it true?  Is depression fundamentally an inflammatory disease, and if so, can we treat it with medications that decrease inflammation, like aspirin?

Let’s go through the various statements made in the Feelguide article and see what the medical evidence says.

First, a necessary correction to avoid confusion.  The Feelguide article says that, “New research is revealing that many cases of depression are caused by an allergic reaction to inflammation.”  Depression is not an allergic reaction.  A true allergy is an antibody response which releases a chemical called histamine from cells called mast cells.  If the current theory about depression and inflammation is true, then depression is related to cytokines, chemicals that are entirely different to histamine.  It may be really annoying to sneeze like you’re demon possessed if a cat’s been in the same room a week ago, but it’s not going to make you depressed.

Is inflammation caused by obesity, high sugar diets, high quantities of trans fats, unhealthy diets in general?  There’s limited evidence that the foods you eat result in inflammation.  Most of the positive data comes from observational studies which are relatively weak.  Better, stronger studies generally give conflicting information [1].  For example, if high fat, sugary foods were really the cause of low grade inflammation, then diets like the Palaeolithic diet, which replace sugary, fatty processed foods with a bucket load of vegetables should improve inflammation.  Yet there have been no statistically significant changes in inflammatory markers recorded in subjects following the Palaeolithic diet [2].

The Feelguide article claims that, “By treating the inflammatory symptoms of depression – rather than the neurological ones – researchers and doctors are opening up an exciting new dimension in the fight against what has become a global epidemic”, but let’s not get too excited.  Again, there’s precious little evidence that medications or supplements reported to reduce inflammation make any difference to depression.  For example, the article mentions omega-3 and curcumin as having some benefit in the treatment of depression, which is half-right.  There’s some evidentiary support that EPA-predominant omega-3 supplements may have some effect on depression, but none at all for DHA omega-3’s [3] or curcumin [4].

When it comes to other medications with an anti-inflammatory effect, the results are similarly mixed.  The issue seems to be the specific cellular action of the medication on a particular immune cell in the brain called the microglial cell.  For example, normal anti-inflammatory medications like aspirin and other Non-Steroidal Anti-Inflammatory Drugs (NSAID’s) increased the activity of these special microglial cells which resulted in an increase in depressive symptoms in otherwise healthy individuals, whereas a medication called minocycline has been noted to decrease the activity of these microglia, and reduced the risk of depressive symptoms (in animal studies at least) [5].

So we really can’t say whether medications believed to have an anti-inflammatory effect really have any significant benefit.  As neuroscientists, Dr Dora Brites and Dr Adelaide Fernandes wrote,

“Nevertheless, we should be cautious in believing that depression can be treated by therapies targeting inflammation. Further studies are required to evaluate whether a combined therapy with anti-inflammatory compounds and antidepressants will result in additional clinical benefits.” [5]

That’s really because we don’t know whether inflammation causes depression, or if depression causes inflammation.  The article by Feelguide seem pretty confident, but the science is still a long way from being settled.

The final word is this:
1. Depression is complicated and still poorly understood.
2. It may be related to inflammation, but please don’t rely on herbs or medications that claim to have anti-inflammatory or “immune boosting” properties.
3. If you really want to try and treat your depression without pharmaceutical medications, take some EPA Omega 3 supplements by all means, although I’d encourage you to exercise and engage with a good psychologist too, both of which have more evidence of benefit overall.

References

[1]        Minihane AM, Vinoy S, Russell WR, et al. Low-grade inflammation, diet composition and health: current research evidence and its translation. The British journal of nutrition 2015 Oct 14;114(7):999-1012.
[2]        Pitt CE. Cutting through the Paleo hype: The evidence for the Palaeolithic diet. Aust Fam Physician 2016 Jan-Feb;45(1):35-8.
[3]        Hallahan B, Ryan T, Hibbeln JR, et al. Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression. The British journal of psychiatry : the journal of mental science 2016 Apr 21.
[4]        Andrade C. A critical examination of studies on curcumin for depression. J Clin Psychiatry 2014 Oct;75(10):e1110-2.
[5]        Brites D, Fernandes A. Neuroinflammation and Depression: Microglia Activation, Extracellular Microvesicles and microRNA Dysregulation. Front Cell Neurosci 2015;9:476.

The Prospering Soul – Christians and Depression Part 1

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In the average charismatic church, from the time you park your car in the parking lot, to the time the music starts at the beginning of the service, the smiles of at least a hundred people beam at you, and at least one third of those smiles are also attached to enthusiastic handshakes and exhortations like, “Isn’t it great to be in church this morning!”

When you’re a Christian, especially at the happy-clappy end of the church spectrum, you’re supposed to be constantly full of the Holy Spirit and experiencing the joy of the Lord.

Which is why for most church-goers, putting the terms “Christian” and “depression” in the same sentence just doesn’t seem natural, even though depression affects a lot more of the church than the church is aware of.

So, how much of the church is affected by depression? The lifetime prevalence (how likely you are to suffer from depression at one stage through your life) is about twenty-five percent, or about one in four people. The point prevalence (those who are suffering from clinical depression at any particular time) is about six percent.

I used to attend a church which had a regular congregation of about 2500 people. So statistically, one hundred and fifty people in that congregation are suffering from depression every Sunday, and more than 600 will experience depression in their lifetime.

And by ‘depression’, we’re not talking about feeling a little sad … that Bill Shorten might become Prime Minister one day, or Ben Hunt can’t catch, or that One Direction isn’t the same without Zayn. Sadness for genuine reasons … you broke up with a long term partner, someone stole your purse out of your bag, or there’s the threat of redundancies at your office … also doesn’t mean you’re depressed.

The DSM5 is the current standard for psychiatric diagnoses around the world. I’ve included the full definition of depression at the end of this blog, but suffice to say, depression is more than just unhappiness. Proper depression symptoms “cause clinically significant distress or impairment in social, occupational or other important areas of functioning.” In other words, you’re so low that your social life or work is affected, and for more than two whole weeks. It’s also important to know that depression isn’t just low mood but can also be experienced as “Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day”.

Depression has a number of causes and correlations. People who are chronically unwell, be that from chronic pain, long term illness such as cancer or autoimmune disease, or life threatening illnesses such as those who’ve suffered from heart attacks or meningitis, have a higher rate of depression. People who have experienced significant physical or psychological trauma also have a higher rate of depression. In fact, stress of any form is highly correlated with depression (that is, people who suffer from any severe stress are more likely to develop depression).

This observation led to a theory about the development of depression, called the Stress Exposure Model of depression [1] – You develop depression because you’ve suffered from stress. This is one of the most common assumptions about depression in our society, and there are some important consequences from this line of thinking. Like, if being stressed is the cause of depression then the cure for depression is simply reducing stress. This is probably why most people assume that depression is a choice, or a simple weakness, and why depressed people are often told just to snap out of it.

But there’s more to depression than just better dealing with stress. Fundamentally, I understand depression as the end result of the brains capacity to deal with the demands of life. Too many demands or not enough resources overwhelms the brain and low mood is the end result.

Some depression is predominantly biological. People with biological depression can’t effectively deal with even a normal amount of demand on their system, because their brain doesn’t have the resources to process the incoming signals correctly or efficiently. The main biological cause is a deficiency of a growth factor called BDNF, which is needed for the nerve cells to grow new branches, which enable the brain to process new information. This theory is called the Neurotrophic Hypothesis of Depression [2] (‘neuro’ = nerve and ‘trophic’ = growth). BDNF isn’t the only critical factor in the biological story of depression. There are many others, including the stress hormone system [3], the serotonin system [4] and the dopamine/rewards system [5].

Some depression is predominantly psychological. There are certain situations in which there’s so much going on and so much change and adaptation is required, and the brains coping systems simply can’t cope. So, severe and sudden stressors would fit into this category. For example, people trying to cope with natural disasters, or a tragedy like a massive house fire.

Most of the time, depression is a combination of both biological and psychological. Genetic factors change our capacity to handle the incoming. The nerve cells don’t have enough BDNF and are slow to grow new branches. Genetics are also important in determining other mechanisms of resilience, and people with poor resilience are also more prone to depression [6-8]. Genetic factors also determine other factors involved in the way we process the incoming stream of sensory input – our personality. People with the neurotic personality type, the classical introverts/pessimists, are more prone to depression, because of the way their brain naturally biases the flavour of the incoming information [9]. What’s also very interesting is that these tendencies to depression also tend to create more stress [1, 10]. So stress is important to the risk of depression, but ironically, it is the risk of depression which influences the risk of stress.

The risk of depression is related to an increased tendency towards stress, and poor processing of that stress because of personality factors and a reduced capacity to cope. All three of these factors are influenced by a broad array of genetic factors.

What’s also important to see here is that being depressed isn’t because of “toxic thinking” or because of “negative confessions”. What we say and what we think are signs of what is going on underneath, not the cause of it. And more importantly, you can make as many faith-filled confessions as you like, but if they don’t help you to change your capacity to cope, then they’re just hot air.

In the next instalment, we’ll look at ways to handle depression, and what the Bible says about being depressed.

References

[1]        Liu RT, Alloy LB. Stress generation in depression: A systematic review of the empirical literature and recommendations for future study. Clinical psychology review 2010 Jul;30(5):582-93.
[2]        Duman RS, Li N. A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists. Philosophical transactions of the Royal Society of London Series B, Biological sciences 2012 Sep 5;367(1601):2475-84.
[3]        Hauger RL, Risbrough V, Oakley RH, Olivares-Reyes JA, Dautzenberg FM. Role of CRF receptor signaling in stress vulnerability, anxiety, and depression. Annals of the New York Academy of Sciences 2009 Oct;1179:120-43.
[4]        Caspi A, Hariri AR, Holmes A, Uher R, Moffitt TE. Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. The American journal of psychiatry 2010 May;167(5):509-27.
[5]        Felten A, Montag C, Markett S, Walter NT, Reuter M. Genetically determined dopamine availability predicts disposition for depression. Brain and behavior 2011 Nov;1(2):109-18.
[6]        Karatsoreos IN, McEwen BS. Resilience and vulnerability: a neurobiological perspective. F1000prime reports 2013;5:13.
[7]        Wu G, Feder A, Cohen H, et al. Understanding resilience. Frontiers in behavioral neuroscience 2013;7:10.
[8]        Russo SJ, Murrough JW, Han M-H, Charney DS, Nestler EJ. Neurobiology of resilience. Nature neuroscience 2012 November;15(11):1475-84.
[9]        Hansell NK, Wright MJ, Medland SE, et al. Genetic co-morbidity between neuroticism, anxiety/depression and somatic distress in a population sample of adolescent and young adult twins. Psychological medicine 2012 Jun;42(6):1249-60.
[10]      Boardman JD, Alexander KB, Stallings MC. Stressful life events and depression among adolescent twin pairs. Biodemography and social biology 2011;57(1):53-66.

The DSM5 Formal Diagnostic Criteria for Depression

A. Five (or more) of the following symptoms have been present during the same 2- week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.

(Note: Do not include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or hallucinations.)

  • Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful). Note: In children and adolescents, can be irritable mood.
  • Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others).
  • Significant weight loss when not dieting or weight gain (e.g., a change of more than 5 percent of body weight in a month), or decrease or increase in appetite nearly every day. Note: In children, consider failure to make expected weight gains.
  • Insomnia or hypersomnia nearly every day.
  • Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down).
  • Fatigue or loss of energy nearly every day.
  • Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick).
  • Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others).
  • Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

B. The symptoms cause clinically significant distress or impairment in social, occupational or other important areas of functioning.
C. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism).