6 Levels of Biomarkers for Preventive Mental Health and Cognitive Function

Biomarkers and mental health may appear puzzling, but many of our psychological challenges stem from underlying biological factors

A preventive approach to our health is crucial as addressing diseases once they happen can be onerous, inflict suffering, and cause substantial costs. Therefore, regular health check-ups are necessary to identify risk factors and detect early signs of mental health conditions causing millions of deaths and sicknesses globally.

Assessing our health status can be achieved using biomarkers as valuable indicators. It may seem perplexing to relate biomarkers to mental health and cognitive function. However, considering them merely psychological and detached from biology disregards the crucial principle of holistic health.

The intricate relationship between the body and mind is indisputable. Thus, understanding and accepting the connection between our physical and mental aspects can provide insight into the importance of using biomarkers to identify the root causes and secondary influences of mental health conditions and address them proactively with professional support.

Our family physicians and specialists can gain valuable insights into the biological and psychological processes by examining biomarkers for underlying mental health conditions.

Mind you, checking biomarkers alone cannot prevent mental health disorders. But, they can contribute to preventive maintenance via risk assessment, early detection, treatment response monitoring, and personalized and lifestyle interventions.

Mental health comprises complex biological, psychological, environmental, social, and genetic factors. Therefore biomarkers alone do not provide a comprehensive understanding of our mental well-being. We must integrate them with clinical assessments, psychosocial evaluations, emotional profiles, and ethical considerations for a holistic approach to mental health care.

Besides biomarkers and self-report measures, mental health professionals use psychological, psychophysiological, cognitive, emotional, and behavioral markers. I will cover them in another article. These markers are usually assessed via psychological assessments, questionnaires, or behavioral observations.

Empirical evidence indicates a close and bidirectional relationship between physical and mental health disorders. The literature highlights the intricate association between these domains, emphasizing their mutual influence on each other’s position. As I wrote about bidirectional links, I will not repeat them in this story.

In this article, I cover six levels of biomarkers that can indicate mental health risks. However, as there are hundreds of biomarkers, I encapsulate them under six topical headings to show the big picture and give you an idea of key factors to consider for preventive mental health.

This story is not prescriptive. I wrote it for awareness and to provide essential information based on my research and experience in the field.

An Overview of Common Mental Health Disorders and Cognitive Decline

The DSM5 (Diagnostic and Statistical Manual of Mental Disorders) by the American Psychiatric Association includes more than 70 disorders.

However, in psychology, psychiatry, and mental health literature, the most common mental health disorders include depression, anxiety, bipolar, schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD).

I want to touch on their symptoms briefly for those unfamiliar with them. I wrote about some of them and linked the previous stories if you want details.

Depression reflects persistent sadness, loss of interest, not having pleasure (anhodenia), and symptoms impacting thoughts, feelings, and behaviors.

Anxiety disorders include generalized anxiety (excessive worry), panic disorder (recurrent panic attacks), phobias, and social anxiety (intense fear of social situations).

Bipolar disorder causes extreme mood swings, like episodes of mania (elevated mood and energy) and sudden depressive thoughts and feelings.

Schizophrenia show symptoms like hallucinations, delusions, disorganized thinking, and impaired social functioning.

ADHD is a neurodevelopmental disorder depicting inattention, hyperactivity, and impulsivity. The symptoms of ADHD, usually manifest during early childhood and continue into adolescence and adulthood.

PTSD can occur in people who have experienced or witnessed a traumatic event, like a life-threatening situation, physical or sexual assault, natural disaster, combat, or other forms of stressors.

These are distinct mental health disorders. However, they have commonalities and overlapping neurobiological mechanisms.

Cognitive decline is a gradual and progressive deterioration of functions in acquiring, processing, and retaining information. It can affect our ability to think, reason, solve problems, make decisions, and engage in daily activities. It can also trigger or aggravate mental health disorders.

Cognitive decline is associated with the normal aging process. However, it might also indicate a neurodegenerative condition, like Alzheimer’s disease or other forms of dementia.

To ensure a focused discussion, I explicitly cover common mental health disorders and do not include neurological disorders, which are also interconnected with mental health conditions. I will cover them in another article due to their comprehensive scope.

In the following section, I briefly describe each domain and provide some indicative biomarkers you might consider if you have symptoms of mentioned mental health conditions.

1 — Neurotransmitter Imbalances and the Nervous System Dysregulation

Neurotransmitters are produced by endocrine glands and neurons in the brain and the nervous system. They are transported across synapses. By carrying the messages, they create a neural network of information.

Their imbalances, mainly due to nervous system dysregulation, can cause developing and progressing mental health disorders.

Examples of neurotransmitters affecting mental health are imbalances of serotonin, norepinephrine, GABA, dopamine, oxytocin, glutamate, acetylcholine, adrenaline, and histamine. A combination of various neurotransmitter imbalances might affect different conditions.

Neurotransmitter imbalances and dysfunction of their receptors might disrupt signaling pathways. Thus, they cause impaired communication in the brain and nervous system. This disruption might affect mood, emotions, cognition, and behaviors, critical elements of mental health disorders.

Dysregulation of the sympathetic nervous system might cause elevated arousal, anxiety, and hyperactivity. Overactivation of the sympathetic nervous system can cause anxiety disorders.

Neuroinflammation (inflammatory processes in the nervous system) can cause neuronal damage, oxidative stress, and disruption of neurotransmitter systems.

Key Biomarkers

✍ The key biomarkers for neurotransmitters are the measurement of serotonin or its metabolites (5-HIAA); dopamine levels and its metabolite (HVA); norepinephrine and its metabolites (MHPG), and GABA levels to evaluate GABAergic system function.

✍ They can be measured indirectly via cerebrospinal fluid sampling, blood tests, or neuroimaging methods. However, direct measurement of neurotransmitter levels in the brain is challenging and typically not performed in routine clinical practice.

✍ Elevated CRP levels and pro-inflammatory cytokines might be used to detect neuroinflammation as they indicate inflammatory immune system dysregulation.

✍ fMRI can measure brain activity and connectivity, providing insights into the functional dysregulation of the nervous system, which is a significant cause of mental health disorders.

2 — Hormonal Imbalances and Neuroendocrine System Dysregulation

The neuroendocrine system is a complicated network covering the interactions between the nervous and endocrine systems. It regulates hormone production and release. This system includes the hypothalamus, pituitary gland, and endocrine glands.

It is crucial in maintaining physiological processes like metabolism, growth, stress response, reproduction, and mood regulation.

Dysregulation can cause anomalies in hormone levels, altered feedback mechanisms, and disrupted signaling between the brain and the endocrine glands. This dysregulation can happen in different ways.

For example, dysregulation of the HPA axis can cause abnormal cortisol levels and impaired stress regulation leading to chronic stress, anxiety, depression, and cognitive decline.

Key Biomarkers

✍ Besides cortisol and adrenocorticotropic hormone, other hormones affecting mental health disorders are insulin, sex hormones (estrogen, progesterone, testosterone, gonadotropins), growth hormone, and thyroid hormones. Therefore checking these hormones is necessary for our mental health.

3 — Inflammation and Immune System Dysregulation

The relationship between inflammation, immune dysregulation, and mental health is complex and multifaceted. The mechanisms and interactions are still at a nascent stage. However, the literature indicates several mechanisms that we can consider.

Chronic inflammation can disrupt the balance of neurotransmitters and hormones. Inflammatory molecules can interfere with the production, release, and reuptake of neurotransmitters and hormones, contributing to imbalances and altering brain function.

They can harm neuroplasticity. Lessened neuroplasticity can adversely affect learning, memory, and mood regulation, leading to mental health disturbances and cognitive decline.

Chronic inflammation can also compromise the integrity of the blood-brain barrier. When this delicate barrier becomes leaky, immune cells and inflammatory molecules can enter the brain, triggering inflammation within the central nervous system. This neuroinflammation can cause mental health disorders and cognitive impairments.

Inflammatory processes can induce reactive oxygen species as byproducts, leading to oxidative stress. Excessive oxidative stress can damage neurons and neuronal connections. I cover oxidative stress in the next section.

Key Biomarkers

✍ Evaluating immune system markers can provide insights into chronic and neuroinflammation and immune dysregulation.

✍Immune system markers can be measured through blood tests and assessments of cytokine levels and inflammation markers like CRP.

✍Checking toxins like heavy metals, industrial chemicals, and air pollutants can be invaluable.

4 — Oxidative Stress and HPA Axis Dysregulation

I mentioned the HPA axis in section #2, but I’d like to highlight it again, as oxidative stress can dysregulate this critical axis.

Both oxidative stress and HPA axis dysregulation can interact and amplify each other’s effects, creating a vicious cycle contributing to mental health disorders and cognitive decline.

Oxidative stress can damage the synthesis, release, and reuptake of neurotransmitters. Disruptions in neurotransmitter balance can alter communication between brain cells and disrupt normal mood regulation. Oxidative stress can impair neuroplasticity.

More importantly, oxidative stress can damage mitochondria. Impaired mitochondrial function can cause decreased energy metabolism in the brain, disrupted cellular signaling, and increased oxidative damage.

Oxidative stress can dysregulate the HPA axis, producing excessive or insufficient cortisol. Elevated or too low cortisol levels and inadequate stress response can cause mental health conditions.

HPA axis dysregulation can cause immune and inflammatory responses and increased production of pro-inflammatory cytokines. Excessive HPA axis activation (elevated cortisol levels) might cause structural damage in the hippocampus, a brain region for memory and emotion regulation.

These changes create a risk for reduced volume, impaired neurogenesis, and increased vulnerability to mood disorders and cognitive deficits.

Key Biomarkers

✍ Specialists can check oxidative stress markers via blood tests assessing oxidative damage and antioxidant capacity.

✍ HPA axis markers, like cortisol and adrenocorticotropic hormone levels, can be measured through blood, saliva, or urine tests.

✍ As sleep is critical in managing stress and the HBA axis regulation, it is also necessary to check circadian rhythm markers to assess biological rhythms, like sleep-wake patterns and melatonin secretion.

5 —Brain-Gut Axis Dysregulation

Brain-gut axis dysregulation indicates an imbalance or disruption in the bidirectional communication between the gastrointestinal tract and the central nervous system. Studies indicate that alterations in this axis can cause developing and worsening mental health disorders.

The gut has trillions of microorganisms. They are crucial in physiological processes (production of neurotransmitters, immune system regulation, and gut barrier integrity maintenance). Imbalances in the composition and diversity of the gut microbiota (dysbiosis) relate to mental health disorders.

Gut bacteria can produce neurotransmitters. Alterations in the gut microbiota composition can influence the production and availability of these neurochemicals, which can impact mood, cognition, and behavior.

The gut covers a portion of the immune system called the GALT (Gut-associated lymphoid tissue). Dysregulation of the GALT can cause chronic inflammation in the gut, adversely impacting the nervous system.

Dysregulation of the gut barrier can cause an increase in intestinal permeability (leaky gut). A leaky gut allows harmful substances to enter the bloodstream. Harmful molecules can activate immune responses and trigger inflammation.

The vagus nerve is a communication pathway for signals and information in the brain-gut axis. It regulates stress responses, immune function, and neurotransmitter release. Dysregulation of the vagus nerve can disrupt these processes and cause mental health disorders.

Key Biomarkers

✍ Intestinal permeability markers are required to detect leaky gut and prevent leaky brain syndrome. Increased zonulin levels in the bloodstream might indicate increased intestinal permeability (leaky gut).

✍ Checking inflammatory markers and proinflammatory cytokines can provide insights into the immune response and gut inflammation. Checking toxins in the gut is vital.

✍ Analyzing the diversity and comparative abundance of different organisms in the gut via techniques like metagenomic sequencing or microbial DNA analysis can provide helpful information about the gut microbiota composition.

✍ Measuring short-chain fatty acids levels, like acetate, propionate, and butyrate, can provide insights into gut microbial activity and fermentation.

✍ Assessing levels of serotonin metabolites can provide information about its turnover and disruptions in gut-brain serotonin signaling.

✍ Checking heart rate variability can be helpful because reduced HRV may indicate decreased vagal nerve activity and poor communication in the brain-gut axis.

6 — Low Neurogenesis and Structural Dysfunctions

BDNF (Brain-Derived Neurotrophic Factor), NGF (Nerve Growth Factor), GDNF (Glial Cell Line-Derived Neurotrophic Factor), and structural dysfunctions might cause the development and progression of mental health disorders via various mechanisms.

BDNF stimulates the growth, maturation, and survival of neurons. It is vital for neurogenesis and neuroplasticity. Reduced levels of BDNF are associated with impaired neurogenesis and neuroplasticity. A shrinking brain can cause cognitive decline and mental health conditions.

NGF promotes neurons' survival, growth, and maintenance, particularly in the peripheral nervous system. NGF can influence the development and function of specific neuronal populations—dysregulation of NGF is implicated in neurodegenerative disorders and mental health conditions.

GDNF is critical for the survival and maintenance of dopaminergic neurons. Disruptions in GDNF signaling can contribute to the vulnerability of dopaminergic neurons, adversely impacting mental health.

Structural abnormalities (reduced hippocampus volume) have been observed in people with mental health disorders like depression and PTSD. These structural changes may impact hippocampal function and contribute to symptoms and cognitive impairments.

The prefrontal cortex (executive functions, decision-making, and emotion regulation) can show structural abnormalities in people with mental health disorders. These dysfunctions may adversely affect cognitive processes, emotional regulation, and behavior.

Key Biomarkers

✍ Measuring BDNF, NGF, and GNDF levels in the blood, cerebrospinal fluid, or specific brain regions might provide insights into dysregulation and its potential role in mental health disorders.

✍ Checking BDNF, NGF, and GNDF gene polymorphisms can provide insights into risks and susceptibility to mental health disorders and inform targeted therapeutic approaches.

✍ Brain imaging techniques (MRI/fMRI) can provide structural information. Measures like hippocampal volume, cortical thickness, and white matter integrity might indicate structural dysfunctions increasing the risks of mental health disorders.

Conclusions and Takeaways

Preventive medicine is necessary to maintain good health. Focusing on prevention can mitigate the challenges, suffering, and financial burden of treating diseases once they have already manifested.

I highlight the importance of checking biomarkers proactively because it is a preventive approach. This approach operates on the principle that preventing an illness or condition from occurring is far easier than addressing it once it has taken hold.

Prevention is undoubtedly valuable. Yet, there will always be a need for effective treatments and interventions for existing diseases. Finding the right balance between prevention and treatment ensures we receive the necessary care at every stage of our health journey.

Empirical evidence supports the close and bidirectional relationship between physical and mental health disorders. Recognizing the bidirectional relationship between physical and mental health is paramount for comprehensively understanding well-being.

Thus, approaching healthcare holistically, considering the importance of physical and mental health domains, is invaluable.

The key takeaway of this story is to leverage biomarkers to proactively lower the risks of mental health disorders with support from professionals.

The objective reality is that if we fail to take personal responsibility, our health will not be a priority for anyone else.

Thank you for reading my perspectives. I wish you a healthy and happy life.

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