Depression and Alzheimer’s — What could they possibly have in common?
A new systematic umbrella study published in the highly reputable journal Molecular Psychiatry[1] that disputes the long-held public belief that chemical imbalances are the root cause of depression has caused quite a stir among both the media and the public.
The aim of the study was to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity by going through all published evidence up to December 2020.
The idea that depression is the result of abnormalities in brain chemicals, particularly serotonin has been influential for decades and has been used as evidence to justify the worldwide distribution of antidepressants such as SSRIs (selective-serotonin reuptake inhibitors).
Doctors are prescribing those drugs with the belief that they are effective,[2] upping the dosage to ensure their effectiveness as often as required, and so many people are taking those on a daily basis often for decades.
A growing number of children and young adults are also on this type of drug daily. The number of 12-to-17-year-old prescribed antidepressants in England more than doubled between 2005 and 2017.[3]
Coming off is also extremely difficult due to withdrawal symptoms that can be severe and last several months,[4] and so popping a pill can become a daily automatism for a multitude of people around the world who believe that there is something wrong inside their brains[5,6], even though antidepressants are not recommended over a period of 6-12 months.[7]
The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.[1]
It is often assumed that the effects of antidepressants are enough to demonstrate that these drugs work on the basis that they ‘treat’ a brain-based chemical abnormality, which involves serotonin. It has also been speculated that these drugs only offer a placebo effect or that they work through their ability to restrict or blunt emotions in general.[8,9]
The use of antidepressants like SSRIs and their study has been challenged many times throughout the last decades and it was found that SSRIs significantly increased the risk of both serious and non-serious adverse events and that there is also a great risk that the results of the studies overestimate the beneficial effects and underestimate their harmful effects.[10,11,12]
We concluded that the harmful effects of SSRIs seem to outweigh the possible small beneficial effects.[7]
What are the implications of the review study?
To start with, those taking SSRIs and similar antidepressants may be extremely concerned about the findings, especially since the media are mostly portraying the issues as being black and white with big flashy headlines.
Placebo effect or not, numbing or mood-improving, these are not the real issues here. The problem is that many people, as well as young adults, have come to rely on antidepressants over the years and they may feel ill-equipped to come off those pills or even consider stopping completely. Just thinking to be without them may cause them a lot of distress.
It is thus essential to have a discussion with your doctor about your intentions or his/her intentions for you to take antidepressants, upping the dosage and coming off those drugs. You should never go “cold turkey” with antidepressants. Your doctor should warn you before prescribing these to you.
This becomes more important the longer you are taking antidepressants, as long-term SSRI treatment is associated with a lowered concentration of serotonin[13,14] and, therefore, you may experience withdrawal symptoms ranging from severe to very severe that may last for one week or two to several months and, therefore, create the very problems they are supposed to treat.[15,16]
What this study has to do with Alzheimer’s?
We know that the pharmaceutical industry is only interested in patenting drugs, especially if they bring billions in revenue. And so, what transpires from the study above is that the one-pill-for-one-ailment approach offers similar results to the failures of the billion-dollar-backed research on Alzheimer’s.
That is because drugs are designed to suppress symptoms and so a culprit must be found. Once it is brought to light all efforts are thus directed to fighting it.
Depression — as is Alzheimer’s disease — is so much more of a multi-factorial condition involving a wide range of factors. In fact, a recent meta-analysis study published in the same journal Molecular Psychiatry reveals that major depressive disorder (MMD) is in no way a result of any molecular imbalance in the brain.[17]
What the researchers found is that there is a lack of evidence for leading biological theories for the onset and maintenance of depression. Only cortisol was identified as a potential predictor for MDD. This means that cortisol, which is intrinsically linked to poor sugar and lipid management and, therefore, inflammation, is only one component in a cascade of issues that impact the gut, the immune and endocrine system, and the central nervous system; the liver and bile system may also be involved, as is cellular detoxification; all of which are affected by oxidative stress (free radical) and DNA damage.
Diet, therefore, play a pivotal role when it comes to malnutrition (nutrient deficiencies, ultra-processed diet), inflammation (sugar-based and ultra-processed diet), dysbiosis (low-fibre and ultra-processed diet) and increased intestinal permeability (ultra-processed diet, hypersensitivities and food allergies), as well as non-alcoholic fatty liver disease (dysbiosis, endotoxins and ultra-processed diet).
Alzheimer’s has been coined type 3 diabetes, demonstrating the direct effect of diet on brain health and that poor sugar management is a major stressor and driver of dysfunction in the body that may also impact cognitive function and brain physiology, chemistry and neuroplasticity.
A sugar-based (and ultra-processed) diet is shown to dysregulate the insulin system and, therefore, is a key marker of inflammation and imbalances in stress hormone concentrations and energy levels, and the way they all influence gut health, cognition and mood.
Approaches to Depression
Before modern medicine, the body was seen as a complete set of interconnected systems but it was also observed as a whole part of its environment.
This is why naturopathic medicine looks at the body as a whole and its interaction with its environment.
It also looks at Inflammation and gut health, and any obvious dysfunction based on our client’s medical (and family) history and specific circumstances. We also give particular attention to genetics and various antecedents, triggers and drivers that may be involved, as can the environment. We look at the physical, social and spiritual (e.g., absence of purpose, social disconnection, etc.) aspects of our client’s life.
Also, WE DO NOT TREAT DISEASES.
We don’t care so much about the symptoms, because what is of interest are the causes of these symptoms. What is the point to put a bandaid over a cut if you don’t remove the piece of glass that is causing the bleeding?
These are typical questions in practice:
What are the triggers and mediators? Why do our clients suffer from low mood or are in pain? Why could they possibly feel “depressed”? What is happening in their life that is impacting the way they feel about themselves, others and the world around them? Are they under tremendous stress or extremely anxious, or dealing with grief and trauma? Do they have supportive relationships, friends they can count on and talk to?
What is their diet? Do they eat regularly or skip meals? Do they take the time to eat or are they fast eaters? Do they in front of the TV, while working or walking? How often do they eat processed food and junk food? Do they cook, ever?
Do they keep hydrated? Do they exercise? Do they use stress-management techniques? How often? Do they sleep properly?
Let's consider this: you mostly don’t sleep well. You don’t eat a healthy diet and eat ready-made meals from an aluminium or plastic tray that you’ve reheated in the microwave. you never exercise (or very rarely). And, you hate your job (or your job is causing you a lot of stress, which you also take home, both that is)…
How do you think your gut feels? Your gut microbiome? Your brain?
How do you manage your energy levels? How many coffees do you drink a day? How many soft drinks? How much sugar? What is your first instinct when you feel your energy levels dip?
There are many questions that we ask ourselves during a consultation and we usually get the answers directly from our clients, but we may also suggest blood tests if we suspect malnutrition or if we need to look at certain biomarkers that may be associated with depression or anxiety, which may include: homocysteine (may affect neurotransmitter responses and neuroendocrine function), glucose and lipid levels, cortisol, thyroid function (especially antibodies), liver function and heavy metal toxicity, among others.
We may also recommend a food intolerance test or a stool test to identify the markers of inflammation and microbial imbalances.
By understanding their dietary habits and lifestyle, their place in their environment and stress levels, and how their body works, we are thus more equipped to help them take back control of their body, and their mood, and live the life they ought to be.
Because no two persons are the same there are many different approaches to restoring your health and vitality, something a drug (that appears to work for most people) cannot do…
Isn’t it time you took back control and became the hero of your own journey, to stand strong and more resilient, the person you can finally be proud to be?
References:
Moncrieff, J. et al. (2022). The serotonin theory of depression: a systematic umbrella review of the evidence. Molecular Psychiatry. doi:10.1038/s41380-022-01661-0
Read, J. et al. (2020). Survey of UK general practitioners about depression, antidepressants and withdrawal: implementing the 2019 Public Health England report. Therapeutic Advances in Psychopharmacology. 10:204512532095012.
Jack, RH. et al. (2020). Incidence and prevalence of primary care antidepressant prescribing in children and young people in England, 1998–2017: A population-based cohort study. PLOS Medicine. 17, e1003215
Source: NHS.UK. (2021). Stopping or coming off antidepressants. Available at: https://www.nhs.uk/mental-health/talking-therapies-medicine-treatments/medicines-and-psychiatry/stopping-or-coming-off-antidepressants/#:~:text=Withdrawal%20symptoms%20usually%20come%20on,after%20you%20stop%20taking%20antidepressants.
Pilkington, PD. Reavley, N.J. Jorm, AF. (2013). The Australian public's beliefs about the causes of depression: Associated factors and changes over 16 years. Journal of affective disorders. 150(2), pp.356–362. doi:10.1016/j.jad.2013.04.019
Pescosolido, BA. et al. (2010). "A disease like any other"? A decade of change in public reactions to schizophrenia, depression, and alcohol dependence. The American Journal of Psychiatry. 167(11), pp. 1321–1330. doi:10.1176/appi.ajp.2010.09121743
Burn, W. et al. (2020). Stopping antidepressants by the Royal College of Psychiatrists available at: https://www.rcpsych.ac.uk/mental-health/treatments-and-wellbeing/stopping-antidepressants; based on NICE guidelines available at: https://www.nice.org.uk/guidance/ng222
Jakobsen, JC. Gluud, C. Kirsch, I. (2020). Should antidepressants be used for major depressive disorder? BMJ Evidence-Based Medicine. 25(4), pp. 130–130. doi:10.1136/bmjebm-2019-111238
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Savović, J. et al. (2012). Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. Annals of Internal Medicine. 157(6), pp. 429–438. doi:10.7326/0003-4819-157-6-201209180-00537
Savovic, J. et al. (2018). Association between risk-of-bias assessments and results of randomized trials in Cochrane Reviews: The ROBES meta-epidemiologic study. American Journal of Epidemiology. 187(5), pp. 1113–1122. doi:10.1093/aje/kwx344
Wood, L. et al. (2008). Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: Meta-epidemiological study. BMJ. 336, pp. 601–605. doi:10.1136/bmj.39465.451748.AD
Huang, T. et al. (2021). Associations of depression status with plasma levels of candidate lipid and amino acid metabolites: A meta-analysis of individual data from three independent samples of US postmenopausal women. Molecular psychiatry. 26(7), pp. 3315–3327. doi:10.1038/s41380-020-00870-9
Pech, J. et al. (2018). Poor evidence for putative abnormalities in cerebrospinal fluid neurotransmitters in patients with depression versus healthy non-psychiatric individuals: A systematic review and meta-analyses of 23 studies. Journal of Affective Disorders, 240, pp. 6–16. doi:10.1016/j.jad.2018.07.031
Kitaichi, Y. et al. (2010). Sertraline increases extracellular levels not only of serotonin, but also of dopamine in the nucleus accumbens and striatum of rats. European Journal of Pharmacology. 647(1-3), pp. 90–96. doi:10.1016/j.ejphar.2010.08.026
Gartside, SE. et al. (1995). Interaction between a selective 5-HT1A receptor antagonist and an SSRI in vivo: Effects on 5-HT cell firing and extracellular 5-HT. British Journal of Pharmacology. 115(6), pp. 1064–1070. doi:10.1111/j.1476-5381.1995.tb15919.x
Kennis, M. et al. (2020). Prospective biomarkers of major depressive disorder: A systematic review and meta-analysis. Molecular psychiatry, 25(2), pp. 321–338. doi:10.1038/s41380-019-0585-z