by Dr Greg Brown
Modern psychiatry exemplifies the reductionist approach which plagues much of modern medicine.
What do I mean by this? Well, reductionism comprises breaking down complex systems into individual components, often in an effort to explain how things work in terms of the functioning of these smaller, simpler elements. Carried to an extreme, reductionism can end up creating errors, unintended consequences, or inappropriate focus on things which logically might make sense, but practically have little relevance. Most of all, reductionism reduces the wonder that is humankind to a state of “nothing buttery” – the pervasive idea that because at the basic level we consist of molecules and elements, we are “nothing but” molecules and elements.
Well, nice simple, binary explanations are much loved by doctors. They make us feel happy and clever. We like thinking that we’ve got it all sewn up and strenuously resist anything which challenges our narrow frame of reference. In the mental health arena, let’s take the totality of a person’s experiences, background, lifestyle, personality, circumstances, genetic makeup, misfortune, and pigeon-hole all that, stuff it down, into a diagnostic category. Slap a label on the problem. Blame a neurotransmitter deficiency, and give a drug to increase the levels.
Is that it? Is one simply afflicted with a neurotransmitter deficiency, like catching the flu? Are some people simply more mentally resilient than others, like natural musical talent?
When I was at med school, we were taught that depression was a simple deficiency of serotonin. It can just happen one day, like flicking a switch. It’s no different to other diseases of deficiency, like type 1 diabetes. We were also taught by one particular psychiatrist that love was just a “dopamine flush”. Is that it? Really? Just because dopamine is involved in a loving feeling, or a loving response, does that mean that love is “nothing but” dopamine?
Among the general increase in non-communicable diseases worldwide, mental disorders, particularly major depression and anxiety, have been described as an impending global epidemic. Up to one-third of all visits to primary care clinicians like me involve patients with emotional disorders, and there is a strong bi-directional association between depression and other chronic diseases, like obesity and type 2 diabetes.
I think that this epidemic of anxiety and depression has a lot to do with the mismatch we spend considerable time concerning ourselves with in the Ancestral Health world, as we attempt to move beyond reductionist, pharmacocentric explanations.
This man, Irving Kirsch, was the first person to open my eyes to some of the issues, contradictions, and downright bad science which has abounded in the area of psychiatry. I read his book “The Emperor’s New Drugs” back in my GP training days and it made a powerful impression, despite not agreeing with every conclusion he came to. As well as exposing some of the tactics the pharmaceutical industry employed in relation to antidepressants, particularly the non-publication of unfavourable trials, he raised significant questions for me on the neurotransmitter theory of depression.
Kirsch described trials using the little known drug reserpine, a medication which depletes serotonin and noradrenaline levels in the brain. One might expect reserpine to induce depression, but it didn’t. More than that, some people with depression actually got better on reserpine. Kirsch references over 90 studies where neurotransmitter depletion was attempted in healthy volunteers. No effect on mood was seen.
But what about antidepressants – surely they work because they boost neurotransmitter levels? Well it turns out that plenty of drugs seem to have an antidepressant effect. Sedatives, stimulants, antipsychotics, even opioids – all these produce response rates of 50% or more, despite having wildly different mechanisms of action and nothing to do with monoamine reuptake. Furthermore, activated placebos like atropine, otherwise benign drugs which had a mild side-effect, like a dry mouth, performed just as well as antidepressants in randomised controlled trials.
And yet, in clinical practice and amongst my own close friends, I had seen these drugs work, in some cases dramatically.
So many questions, but little in the way of answers. If they do work, why? If they don’t work, why do they seem to? If it’s just an advanced placebo effect, how on earth can that be harnessed in clinical practice without feeling like you’re lying to patients?
In seeking answers from an Ancestral Health perspective, two main themes emerge: nutrition and circadian rhythms. Both contribute in distinct, but interlocking ways, and on the journey we learn some interesting things about antidepressants.
At the previous AHSNZ Conference, Mikki Williden expertly elucidated the topic of nutrition and the brain, reminding us that the brain operates at a very high metabolic rate, using up a substantial proportion of the body’s energy and nutrient intake. Around 20% of the body’s basal metabolic rate at any given time is utilised by the brain and this can be as high as 50% in children or potentially up to 70% in infants Both the structure and the correct functioning of the brain is dependent upon its inputs: amino acids (from protein), fats, vitamins, minerals and trace elements. And in the Ancestral Health community, we are acutely aware that these inputs come from food.
In addition, the body’s immune system is also only as good as the inputs it receives in the form of nutrients, and it turns out that immunity is very much linked to mental health.
Those of us who are practitioners in this field will probably all be able to think of patients whose mental health has miraculously improved while we have been treating them nutritionally for some other issue.
A very recent paper on the emerging discipline of nutritional psychiatry makes this bold statement:
A theoretical framework of biological mechanisms whereby nutrition could exert its influence along a continuum ranging from general mental well-being to neuropsychiatric disorders is highly probable.
Let’s unpick some of these mechanisms and see if we can come to a working theory as to why we might see our patients getting better psychologically as well as physically.
At that troublesome, much misused population level, where we can only comment on associations and remembering that correlation doesn’t equal causation, there would appear to be strong association in multiple studies between healthful dietary patterns (which tends to be the Mediterranean Diet) and a lowered risk of anxiety and/or depression. Many of these studies suggest that nutrition provides a level of resiliency which is clinically meaningful.
There has been explosion of papers, mostly published this year, which strongly suggest that the mechanism in play here is our old friend, inflammation.
Inflammation is what happens when your body receives some sort of an insult. Cut your finger and the inflammatory response ensures that the blood clots and the immune cells required to deal with infection are dispatched. Inflammation is a rapid reaction-type force. It should arrive on the scene quickly, do its job, then deactivate. The problem comes when it doesn’t do this, the rapid reaction force becomes mired down without an exit strategy. Chronic inflammation ensues.
It’s well understood that chronic inflammation relates to a number of physical conditions — arthritis, inflammatory bowel disease, some chronic skin problems, thyroid disease — but at the bleeding edge of nutritional research is the concept that depression specifically is associated with a chronic low-grade inflammatory response.
Higher levels of inflammation appear to increase the risk for the development of depression. Specifically, we’re talking about elevated levels of cytokines, small proteins involved in the inflammatory cascade and aspects of cell signalling. If you inject people with substances to trigger the release of these cytokines, you can induce depressive-like behaviour. A good example is the use of interferon (a cytokine) in the treatment of hepatitis C. A well-known side-effect is depression. Remission of depression is accompanied by normalisation of these inflammatory markers. And those who fail to respond to antidepressants are characterised by persistently raised inflammatory markers.
Food is also potentially inflammatory. A Western dietary pattern has been shown to be highly correlated with higher levels of CRP, a marker of inflammation in the blood. A Mediterranean diet pattern is associated with lower inflammatory markers, with trials reporting observable reductions in CRP from switching people onto a Mediterranean diet under controlled conditions.
As I said earlier, there has been a huge question mark for years over how antidepressants really work, and (disagreeing with Kirsch here) I believe they really do work. It turns out in some of these studies that antidepressants have anti-inflammatory properties. So maybe it was nothing to do with serotonin reuptake all along, just like statins, we have a pleiotropic anti-inflammatory effect.
How does all this tie in with the traditional risk factors for mood disorders, like stress and trauma, which we tend to target with psychological interventions? Well, there is good evidence that different types of psychosocial stressors stimulate these inflammatory cytokines as well and they also lower the level of the body’s own natural anti-inflammatory compounds. We have a potential mechanism here for the triggering of mood disorders by acute psychotrauma.
The Dunedin Multidisciplinary Health and Development Study an amazing undertaking which has followed 1000 people from birth to 32 years has demonstrated that individuals experiencing stress in childhood resulting from maltreatment, abuse, social isolation and economic hardship are twice as likely to suffer chronic inflammation. So stress occurring early in life can exert persistent effects over long periods of time and this inflammatory model give us an idea why some people may become less mentally resilient than others, in addition to other factors like learned responses to stress, personality, and so on.
Food is also potentially inflammatory. A Western dietary pattern has been shown to be highly correlated with higher levels of CRP, a commonly used marker of inflammation in the blood. A Mediterranean diet pattern is associated with lower inflammatory markers, with trials reporting observable reductions in CRP from switching people onto a Mediterranean diet under controlled conditions.
The leaky gut we’ve all been going on about for some time is critical in the pathogenesis of mood disorders as well. Clinical depression has recently been shown to be accompanied by increased levels of IgG and IgM immunoglobulins acting against gut flora bacteria. This is huge. Those bacteria should be in the gut, not in the bloodstream where they provoke an antibody response. Leaky gut enables this bacterial translocation and consequent inflammation.
In addition, the same foods which cause leaky gut seem to have a similar effect on the crucial blood-brain barrier. It turns out this highly selective barrier which separates circulating blood from the brain’s extracellular fluid also relies on intact tight junctions. The potential consequences of unfiltered access to the fluid which bathes your very brain tissue are untold. It’s not hard to see the possible relevance to the development of mental disorders and indeed other brain pathologies. This would seem to be largely uncharted waters at the present time but an excessively permeable blood-brain barrier sounds like something to be avoided at all costs to me.
To be continued…