Within the past few years, depression has entered the spotlight of the medical arena due to a huge paradigm shift within its etiology. With pharmaceutical intervention usually pertaining to Selective Serotonin Reuptake Inhibitors (SSRIs), and depression being now characterised as a non-serotonin related condition, the effectiveness of our interventions is under scrutiny. Essentially, a review on the cause of depression found no significant difference in depression symptomology in control vs placebo. The importance of this cannot be understated. As a result of this research, we come to a hugely important question, why are we treating a non-serotonin related condition with serotonin reuptake therapies?

Not only this, but it leads us into a separate way of thinking. For instance, if depression has little to do with serotonin, as the current paradigm suggests, then what could be the cause of our skyrocketing rates. Either there are other culprits, or no culprit at all, and depression is just a part of life.

From current understanding, depression stems from a materialist view. In other words, all mental states, no matter our situation, are ultimately rooted in a neurological process. For example, decades of neuroscientific research have suggested that there is an incredibly strong correlation between brain activity and mental states such as love, anxiety, pleasure, confusion, concentration and so on. However, the one mental state, if you can even call it that, which we have not been able to derive from physical processes is our consciousness, but that’s a much deeper, philosophical concept.               

This leads us into an attempt to uncover other culprits and bring them into the spotlight for further examination. If I were an avid researcher, with the capability to conduct any research of choice, I would put funding into understanding the effects of vegetable oils, heavy metals, vaccines, PUFAS, and PFAS in relation to conditions such as depression. For many, this may be the first time the idea of metal toxicity or poly-unsaturated fats have been correlated with the proliferation of depression. However, I assure you that these factors should not be ignored.

Firstly, we should understand what the risks are in relation to depression. As currently understood, this condition thrives on poor motivation, unwillingness to participate, extreme pessimism and a flawed reward processing system. Unfortunately, lots of our daily life can be the culprit of such manifestations. From social media and poor relationships to work stress and lack of sleep, many factors could be to blame.

Therefore, instead of suggesting that depression has a singular, or even numerous categorical box, I prefer to state that depression is the formulation of multiple symptoms that can be caused by an extreme number of factors. However, this does not mean each culprit should not be studied because with proper investigations, as with proper investigation we may be able to curate a society with minimal external applications of depression.

The previously mentioned factors contribute to depression through several interconnected biomechanisms. Firstly, the factors induce oxidative stress by generating reactive oxygen species (ROS), overwhelming the brain’s antioxidant defences. Secondly, these toxins activate pro-inflammatory pathways in the brain, triggering chronic neuroinflammation. Thirdly, they disrupt critical mood-regulating neurotransmitter systems, altering levels of dopamine, and norepinephrine. Furthermore, they impair neuroplasticity by reducing levels of Brain-Derived Neurotrophic Factor (BDNF), crucial for neuron growth and repair. Lastly, acting as endocrine-disrupting chemicals (EDCs), these elements interfere with hormone systems like the thyroid and sex steroids, causing imbalances that alter brain function and neurotransmitter activity.

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Vegetable oils:

Oxidative Stress and 4-hydroxy-2-nonenal (4-HNE): Implications in the Pathogenesis and Treatment of Aging-related Diseases – PMC

Trans Fatty Acids Induce Vascular Inflammation and Reduce Vascular Nitric Oxide Production in Endothelial Cells | PLOS ONE

The Lipid Peroxidation By-product 4-Hydroxynonenal is Toxic to Axons and Oligodendrocytes – Eileen McCracken, V. Valeriani, C. Simpson, T. Jover, James McCulloch, Deborah Dewar, 2000

Involvement of peroxisome proliferator-activated receptor β/δ (PPAR β/δ) in BDNF signaling during aging and in Alzheimer disease: Possible role of 4-hydroxynonenal (4-HNE) – PMC

Cell death and diseases related to oxidative stress:4-hydroxynonenal (HNE) in the balance | Cell Death & Differentiation

Heavy metals:

Heavy metal associated health hazards: An interplay of oxidative stress and signal transduction – PubMed

Inflammation in Metal-Induced Neurological Disorders and Neurodegenerative Diseases | Biological Trace Element Research

Positive Health Online | Article – How Heavy Metals Affect Neurotransmitters Production and Balance

Exploring the relationship between metal exposure, BDNF, and behavior in adolescent males – ScienceDirect

Effects of Endocrine-Disrupting Heavy Metals on Human Health – PMC

Vaccines:

Exposure to Mercury and Aluminum in Early Life: Developmental Vulnerability as a Modifying Factor in Neurologic and Immunologic Effects – PMC

Acute exposure and chronic retention of aluminum in three vaccine schedules and effects of genetic and environmental variation – ScienceDirect

Aluminum and vaccines: Current state of knowledge – PubMed

Examining vaccination-related adverse events in frequent neurodegenerative diseases – ScienceDirect

PUFAS:

(PDF) Oxidation of Polyunsaturated Fatty Acids and its Impact on Food Quality and Human Health

Omega-6 fatty acids and inflammation – Prostaglandins, Leukotrienes and Essential Fatty Acids

Omega-6 to omega-3 polyunsaturated fatty acid ratio and subsequent mood disorders in young people with at-risk mental states: a 7-year longitudinal study – PMC

Role of Polyunsaturated Fatty Acids in Human Brain Structure and Function Across the Lifespan: An Update on Neuroimaging Findings – PMC

PFAS:

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) and their effects on the ovary – PubMed

PFAS Chemicals: EDCs Contaminating Our Water and Food Supply | Endocrine Society

Thyroid Disrupting Effects of Old and New Generation PFAS – PMC

Perfluoroalkyl Substance Exposure and the BDNF Pathway in the Placental Trophoblast – PubMed

Prenatal PFAS and psychosocial stress exposures in relation to fetal growth in two pregnancy cohorts: Applying environmental mixture methods to chemical and non-chemical stressors – PubMed

Neurotransmission Targets of Per- and Polyfluoroalkyl Substance Neurotoxicity: Mechanisms and Potential Implications for Adverse Neurological Outcomes – PubMed

PFAS Environmental Pollution and Antioxidant Responses: An Overview of the Impact on Human Field

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The shift from the serotonin hypothesis into a complex relationship between an extreme number of factors has caused a complete overhaul in our understanding of depression’s etiology. Instead of focusing on a singular neurotransmitter, and administering drugs purely based on fixing a supposed issue, we should prescribe gut altering therapies to allow our body to run at full capability. For example, the NICE guidelines recommend physical activity as part of the treatment for depression based on numerous pieces of successful research. Furthermore, a meta-analysis of 46,000 people found that fat loss and a complete nutritional profile reduced the symptoms of depression.

In fact, these two methods were more effective than SSRI therapy, suggesting little need for intrusive and dangerous drug administration.

Overall, depression’s skyrocketing rates demands we look beyond the brain’s serotonin levels to the world we inhabit – our food, water, air, clothes, and exercise regiment. By studying these overlooked culprits and their cascading effects, we can move towards a society that minimises the external drivers of despair. It is not about finding a single villain, it is about collecting recognising the harm our environment is doing to us and opting for practical change. The research is there, waiting to guide us – we just have to be bold enough to follow.