Overview of Common Mental Health Disorders and Cognitive Decline

The DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) from the American Psychiatric Association recognizes over 70 disorders.

In the realm of psychology, psychiatry, and mental health, the most prevalent disorders include depression, anxiety, bipolar disorder, schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD).

For those unfamiliar with these conditions, I will briefly outline their symptoms. I have previously written about some of them and linked those articles for further reading.

> Depression manifests as persistent sadness, a lack of interest, anhedonia, and symptoms that affect thoughts, feelings, and behaviors.

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

> Bipolar disorder involves extreme mood fluctuations, including episodes of mania (elevated mood and energy) and sudden depressive states.

> Schizophrenia is characterized by symptoms such as hallucinations, delusions, disorganized thinking, and impaired social interactions.

> ADHD is a neurodevelopmental disorder marked by inattention, hyperactivity, and impulsiveness, with symptoms often emerging in early childhood and persisting into later life.

> PTSD may develop in individuals who have experienced or witnessed traumatic events, such as life-threatening situations, assaults, natural disasters, or combat.

While these mental health disorders are distinct, they share similarities and overlapping neurobiological mechanisms.

Cognitive decline refers to the gradual deterioration of abilities related to acquiring, processing, and retaining information. This decline can impair reasoning, problem-solving, decision-making, and daily functioning, potentially exacerbating mental health issues.

Although cognitive decline is often associated with the aging process, it can also signal neurodegenerative diseases like Alzheimer's or other forms of dementia.

To maintain focus, this discussion will center on common mental health disorders, excluding neurological disorders, which I will cover in a separate article due to their extensive nature.

In the following sections, I will provide a brief overview of each category along with indicative biomarkers to consider if you experience symptoms of the mentioned mental health conditions.

1 — Neurotransmitter Imbalances and Nervous System Dysregulation

Neurotransmitters, produced by endocrine glands and neurons within the brain and nervous system, facilitate communication across synapses, forming a network of information.

Imbalances in these neurotransmitters, primarily resulting from nervous system dysregulation, can lead to the development and progression of mental health disorders.

Key neurotransmitters affecting mental health include serotonin, norepinephrine, GABA, dopamine, oxytocin, glutamate, acetylcholine, adrenaline, and histamine. A combination of neurotransmitter imbalances may influence various conditions.

Disruptions in neurotransmitter signaling pathways can hinder communication within the brain and nervous system, impacting mood, emotions, cognition, and behaviors, which are vital aspects of mental health.

Dysregulation of the sympathetic nervous system may lead to heightened arousal, anxiety, and hyperactivity, with overactivation causing anxiety disorders.

Neuroinflammation, or inflammatory processes in the nervous system, can induce neuronal damage, oxidative stress, and disrupt neurotransmitter systems.

Key Biomarkers - Key biomarkers for neurotransmitter activity include measuring serotonin or its metabolites (5-HIAA), dopamine levels and its metabolite (HVA), norepinephrine and its metabolites (MHPG), and GABA levels to assess GABAergic function. - These can be measured indirectly through cerebrospinal fluid sampling, blood tests, or neuroimaging. Direct measurement of neurotransmitter levels in the brain is typically not part of routine clinical practice. - Elevated levels of CRP and pro-inflammatory cytokines may indicate neuroinflammation and immune system dysregulation. - fMRI can assess brain activity and connectivity, shedding light on functional dysregulation of the nervous system, a major contributor to mental health disorders.

2 — Hormonal Imbalances and Neuroendocrine System Dysregulation

The neuroendocrine system is a complex network encompassing the interactions between the nervous and endocrine systems, regulating hormone production and release through components like the hypothalamus and pituitary gland.

This system plays a crucial role in various physiological processes, including metabolism, growth, stress responses, reproduction, and mood regulation.

Dysregulation can lead to abnormal hormone levels, altered feedback mechanisms, and disrupted signaling between the brain and endocrine glands, occurring in various ways.

For instance, dysfunction of the HPA axis can result in irregular cortisol levels and impaired stress management, contributing to chronic stress, anxiety, depression, and cognitive decline.

Key Biomarkers - In addition to cortisol and adrenocorticotropic hormone, other hormones influencing mental health include insulin, sex hormones (estrogen, progesterone, testosterone, gonadotropins), growth hormone, and thyroid hormones. Monitoring these hormones is essential for mental well-being.

3 — Inflammation and Immune System Dysregulation

The interplay between inflammation, immune dysregulation, and mental health is intricate and multifaceted, with emerging mechanisms still under investigation.

Chronic inflammation can disturb the balance of neurotransmitters and hormones. Inflammatory molecules may interfere with neurotransmitter production, release, and reuptake, leading to imbalances and altered brain function.

Such inflammation can negatively impact neuroplasticity, which is essential for learning, memory, and mood regulation, ultimately contributing to mental health disturbances and cognitive decline.

Additionally, chronic inflammation can compromise the integrity of the blood-brain barrier. A weakened barrier allows immune cells and inflammatory molecules to enter the brain, potentially triggering central nervous system inflammation and mental health disorders.

Inflammatory processes can produce reactive oxygen species, resulting in oxidative stress, which may damage neurons and their connections.

Key Biomarkers - Evaluating immune system markers can provide insight into chronic inflammation and immune dysregulation. - These markers can be assessed through blood tests measuring cytokine levels and inflammation indicators like CRP. - Monitoring toxins such as heavy metals, industrial chemicals, and air pollutants is also valuable.

4 — Oxidative Stress and HPA Axis Dysregulation

While the HPA axis was previously mentioned, it’s important to emphasize how oxidative stress can disrupt this critical axis.

Oxidative stress and HPA axis dysregulation can interact and exacerbate each other’s effects, creating a detrimental cycle that contributes to mental health disorders and cognitive decline.

Oxidative stress can affect neurotransmitter synthesis, release, and reuptake, disrupting communication among brain cells and normal mood regulation. It can also impair neuroplasticity.

Furthermore, oxidative stress can damage mitochondria, leading to diminished energy metabolism in the brain, disrupted cellular signaling, and increased oxidative damage.

This stress can also dysregulate the HPA axis, resulting in either excessive or insufficient cortisol levels, which can cause various mental health conditions.

Dysregulation of the HPA axis can provoke immune and inflammatory responses, increasing pro-inflammatory cytokine production. Overactivation may lead to structural changes in the hippocampus, a region crucial for memory and emotion regulation.

These alterations can increase vulnerability to mood disorders and cognitive deficits.

Key Biomarkers - Oxidative stress markers can be evaluated through blood tests assessing oxidative damage and antioxidant capacity. - HPA axis markers, such as cortisol and adrenocorticotropic hormone levels, can be measured using blood, saliva, or urine tests. - Assessing circadian rhythm markers is also important for evaluating biological rhythms, including sleep-wake patterns and melatonin production.

5 — Brain-Gut Axis Dysregulation

Dysregulation of the brain-gut axis indicates an imbalance in the communication between the gastrointestinal system and the central nervous system. Research suggests that disruptions in this axis can lead to the development and worsening of mental health disorders.

The gut is home to trillions of microorganisms, which are integral to processes such as neurotransmitter production, immune regulation, and maintaining gut barrier integrity. Dysbiosis, or imbalances in gut microbiota composition, is linked to mental health conditions.

Gut bacteria can produce neurotransmitters, and changes in gut microbiota can influence the availability of these neurochemicals, ultimately impacting mood, cognition, and behavior.

The gut-associated lymphoid tissue (GALT) is part of the immune system. Dysregulation here can lead to chronic gut inflammation, adversely affecting the nervous system.

An impaired gut barrier may increase intestinal permeability, allowing harmful substances into the bloodstream. This exposure can trigger immune responses and inflammation.

The vagus nerve facilitates communication within the brain-gut axis, regulating stress responses, immune function, and neurotransmitter release. Dysregulation of this nerve can disrupt these critical processes, leading to mental health disorders.

Key Biomarkers - Markers of intestinal permeability are crucial for identifying leaky gut, which can lead to "leaky brain" syndrome. Elevated zonulin levels in the bloodstream may indicate increased permeability. - Assessing inflammatory markers and pro-inflammatory cytokines can offer insights into gut inflammation and immune responses. - Techniques like metagenomic sequencing or microbial DNA analysis can help analyze gut microbiota composition and diversity. - Measuring short-chain fatty acids like acetate, propionate, and butyrate can provide insights into gut microbial activity and fermentation. - Monitoring serotonin metabolites can reveal disruptions in gut-brain serotonin signaling. - Evaluating heart rate variability may also be beneficial, as reduced HRV could indicate decreased vagal nerve activity and impaired communication within the brain-gut axis.

6 — Low Neurogenesis and Structural Dysfunctions

Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), and various structural dysfunctions can contribute to the onset and progression of mental health disorders through several mechanisms.

BDNF is essential for neuron growth, maturation, and survival, playing a critical role in neurogenesis and neuroplasticity. Lower levels of BDNF are associated with reduced neurogenesis and neuroplasticity, which can lead to cognitive decline and mental health issues.

NGF supports the survival, growth, and maintenance of neurons, particularly in the peripheral nervous system, and its dysregulation is linked to neurodegenerative and mental health disorders.

GDNF is vital for the survival of dopaminergic neurons; disruptions in GDNF signaling can heighten the vulnerability of these neurons, affecting mental health.

Structural abnormalities, such as reduced hippocampal volume, are observed in individuals with mental health disorders like depression and PTSD. These changes may affect hippocampal function and contribute to symptoms and cognitive deficits.

The prefrontal cortex, responsible for executive functions, decision-making, and emotional regulation, may also exhibit structural abnormalities in those with mental health disorders, adversely impacting cognitive processes and behavior.

Key Biomarkers - Measuring BDNF, NGF, and GDNF levels in blood, cerebrospinal fluid, or specific brain regions can provide insights into dysregulation and its potential implications for mental health disorders. - Assessing gene polymorphisms related to BDNF, NGF, and GDNF can inform on susceptibility to mental health disorders and guide targeted therapeutic strategies. - Brain imaging techniques like MRI/fMRI can reveal structural information. Metrics such as hippocampal volume, cortical thickness, and white matter integrity can indicate structural dysfunctions that heighten mental health disorder risks.

Conclusions and Key Insights

Preventive medicine is vital for maintaining overall health. Emphasizing prevention can alleviate the challenges, suffering, and financial burdens associated with treating diseases after their onset.

This article underscores the significance of proactively monitoring biomarkers as a preventive strategy. This approach is based on the principle that it is much easier to avert an illness than to tackle it once it has developed.

While prevention is undeniably valuable, there remains a persistent need for effective treatments and interventions for existing conditions. Striking a balance between prevention and treatment is essential to ensure that care is provided throughout our health journeys.

Research supports the close and reciprocal relationship between physical and mental health disorders. Acknowledging this interconnectedness is crucial for a holistic understanding of well-being.

Therefore, adopting a comprehensive approach to healthcare that considers the significance of both physical and mental health domains is invaluable.

The essential takeaway from this discussion is to utilize biomarkers to proactively mitigate the risks of mental health disorders, aided by professional support.

Ultimately, if we do not take personal responsibility for our health, it is unlikely to become a priority for anyone else.