All mental health conditions are affected by stress, so we've decided to focus the content of this issue on stress, depression and the link with cortisol as well as the benefits of zinc and magnesium for augmentation.
What is stress?
From a medical perspective the usual explanation of stress relates to the biological and psychological issue of the fight or flight response. This response involves a cascade of neuroendocrine events as well as corticotrophic hormone release that engages us for performance or more obviously to flee danger. The trouble with this response is that we are not well adapted to being able to turn it off quickly and this is an important concept in terms of exposure to stress over time.
Our psychological processes may exacerbate the intensity of stress or help us reduce this stress.
How does stress lead to problems?
Medical science is increasingly uncovering clues as to the mechanisms that underpin damage caused by stress. Cortisol in particular has been identified as a problem in diabetes, depression and heart disease and probably many other conditions.
In diabetes, excessive exposure to cortisol through stress may impact on insulin sensitivity over time and progressively deteriorate glucose uptake. With depression, constant 'adrenal fatigue' sets of a cascade of inflammatory processes that lead to further neuroendocrine and neurotransmitter uptake dysregulation.
Stress also damages the heart and it's a major obvious risk for having a heart attack. There is vascular damaged caused by inflammatory processes from prolonged exposure to stress hormones.
Model of stress
One of the common psychological models is known as General Adaptation Syndrome which involves these 3 phases:
- Alarm: stress response begins in reaction to a threat or stressor.
- Resistance: if the stressor continues, some mechanism initiates in order to deal with the stress. For example; increasing alcohol consumption after work.
- Exhaustion: the body is essentially fatigued, tired and it has been over-exposed to the cascade of hormones, so there is some recalibration of physiological processes.
Effects of poor stress management
Most people don't exercise or do any kind of physical labour that would stress their body effectively. Let's be honest.
Thanks to the cutting edge contribution to longevity research done by Dan Beutner and National Geographic, it's widely understood that centenarians (or those who live to 100) rarely needed to do deliberate exercise because it was such a major part of their lives. They are farmers, shepherds or they just have active lives. Additionally, they have an outlook on life, which at its core involves effective stress management.
Stress leads to chronic disease. It's not the only cause, but it's a major influence and it can worsen symptoms.
People often try to self-medicate their stress, and this may be through alcohol and other drugs, partying in general, sex, watching TV or doing nothing.
Sometimes these strategies catch up with people, and this is when their condition worsens and they end up doing nothing all the time because they cannot get out of bed.
Unfortunately, once it gets to this stage, exercise, diet and most other things don't really work that well. And more often than not, talking to a friend or 'going through the issues' just rehashes the person's anxiety or stress. And if it's a first episode of anxiety or depression, the person may be feeling quite unsure of themselves and just 'want to be normal again'. This is the time that professional help hopefully becomes a serious consideration.
Stress & Depression: The Cortisol Concern
Cortisol and depression have been linked in a number of studies. Excessive cortisol secretion is a characteristic of depression and cortisol abnormalities may be markers of depression and a vulnerability for depression and anxiety[1]. In other studies, abnormal maternal cortisol in mothers with postnatal depression predicts more variable morning cortisol in offspring and this pattern has been found to predict major depression[2]. Cortisol secretion in depression also appears to be related to cognitive deficits, particularly those related to hippocampus function. High cortisol may down-regulate mineralocorticoid and glucocorticoid receptors in the hippocampus which may be related to the cognitive deficits seen in depressed patients[3].
Effective Stress Management
It is generally our view that psychiatric conditions are largely unpreventable, especially schizophrenia and bipolar disorder. There may be more chance with depression and anxiety, which is why we are focusing on stress and cortisol. We now know there are many genetic factors at work and poly gene systems responsible for symptoms and disease processes. As previously discussed, some of these have to do with stress and inflammatory responses. Even the most resilient characters may progress to depression and/or anxiety under stressful circumstances or pressures. In any instance, early intervention is required. The longer one waits to take action when symptoms surface, the worse the prognosis.
When people are very proactive and have highly engaging active lives, there are a number of strategies people use. People often drink coffee in an attempt to deal with their stress, although this may exacerbate cortisol problems. People also may resort to herbal alternatives, some of which do have benefits although these will not be discussed here. Once the stress has become major depression or anxiety, we advocate medical intervention through evidence based psychiatry.
Augmentation
Minerals, vitamins, herbs and essential fatty acids play a role in modulating stress. At this stage, we identify magnesium and zinc as important augmenters because they may affect a future response to antidepressants.
Magnesium
Magnesium is a highly effective cortisol modulator and can help people get to sleep and stay asleep. Some time ago, we reported the poor remission rates from antidepressants and have previously discussed the potentiating effect of zinc. Poleszak et al (2005) demonstrated that magnesium administered with imiprimine increased the antidepressant effect[4]. Mice display depressive and anxiety symptoms when deliberately fed low magnesium diets[5]. Eby and Eby (2010) reported that inadequate magnesium intake was a main cause of treatment resistant depression. They suggested that physicians prescribe magnesium and that increasing magnesium intake would be of benefit in nearly all cases. Findings of a randomised trial showed that magnesium was as effective as imiprimine in treating depression in diabetics[6]. The antidepressant effect of magnesium is well recognized by studies based on the forced mouse swim test and in several studies the mechanisms of action points to the involvement of the NMDA/Glutamate pathway[4, 7].
In a recent study, the researchers found involvement of serotonergic, noradrenergic and dopaminergic receptor mediation[8].
Zinc
Low zinc levels are also correlated with depressive symptoms. In several studies, it has been shown that antidepressants can reverse some of the effects of low zinc levels[9]. Low zinc correlates with treatment resistance in depression. As with diabetes, immune and inflammatory processes appear to be altered[10, 11]. Low serum zinc has been suggested as a marker for treatment resistance depression and of that immune and inflammatory response[11]. Furthermore, zinc deficiencies may lead to depression-like symptoms that may not resolve from antidepressant treatment alone[12]. A recent article in the Journal Affective Disorders concluded that low serum zinc is a marker of depression[13].
References
1. Beluche, I., et al., Persistence of abnormal cortisol levels in elderly persons after recovery from major depression. Journal of Psychiatric Research, 2009. 43(8): p. 777-783.
2. Halligan, S.L., et al., Exposure to postnatal depression predicts elevated cortisol in adolescent offspring. Biological Psychiatry, 2004. 55(4): p. 376-381.
3. Hinkelmann, K., et al., Cognitive Impairment in Major Depression: Association with Salivary Cortisol. Biological Psychiatry, 2009. 66(9): p. 879-885.
4. Poleszak, E., et al., Enhancement of antidepressant-like activity by joint administration of imipramine and magnesium in the forced swim test: Behavioral and pharmacokinetic studies in mice. Pharmacology Biochemistry and Behavior, 2005. 81(3): p. 524-529.
5. Singewald, N., et al., Magnesium-deficient diet alters depression- and anxiety-related behavior in mice--influence of desipramine and Hypericum perforatum extract. Neuropharmacology, 2004. 47(8): p. 1189-1197.
6. Eby Iii, G.A. and K.L. Eby, Magnesium for treatment-resistant depression: A review and hypothesis. Medical Hypotheses, 2010. 74(4): p. 649-660.
7. Poleszak, E., et al., NMDA/glutamate mechanism of antidepressant-like action of magnesium in forced swim test in mice. Pharmacology Biochemistry and Behavior, 2007. 88(2): p. 158-164.
8. Cardoso, C.C., et al., Evidence for the involvement of the monoaminergic system in the antidepressant-like effect of magnesium. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2009. 33(2): p. 235-242.
9. Szewczyk, B., M. Kubera, and G. Nowak, The role of zinc in neurodegenerative inflammatory pathways in depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry. In Press, Corrected Proof.
10. Maes, M., et al., Hypozincemia in depression. Journal of Affective Disorders, 1994. 31(2): p. 135-140.
11. Maes, M., et al., Lower serum zinc in major depression is a sensitive marker of treatment resistance and of the immune/inflammatory response in that illness. Biological Psychiatry, 1997. 42(5): p. 349-358.
12. Tassabehji, N.M., et al., Zinc deficiency induces depression-like symptoms in adult rats. Physiology & Behavior, 2008. 95(3): p. 365-369.
13. Siwek, M., et al., Serum zinc level in depressed patients during zinc supplementation of imipramine treatment. Journal of Affective Disorders, 2010. 126(3): p. 447-452.
