Why are so many people that we know irritable, anxious or depressed all the time?

Over the past few years, you may have noticed that people, even some of those that we know well, are more irritable, anxious or depressed all the time. I have certainly noticed this in day to day interactions.

Clearly the last five years have been an unprecedented time, certainly within my lifetime, for a number of good reasons. These include the COVID pandemic, fear of debilitating illness, lockdowns, vaccination mandates, testing, isolation, school closures, and economic and political uncertainty to name but a few of them.

These fears and anxieties can certainly have an effect on mental health. In this article, we will look at the causes, and what we can do to help ourselves and those around us.

Two recent studies, including one very large scale study involving over two million subjects, give us clues as to what may be going on with people’s psychological and mental health at the present time. Anxiety and stress-related disorders are major concerns for COVID-19 infection and vaccination.

Some of the diagnostic terms  associated with psychiatric/mental health issues are technical and may convey meanings that need explanation. I will try to avoid these technical terms, and put them into everyday language in order to avoid any confusion. An example is ‘conversion disorders‘, which may mean any number of different things to different people or groups, and in psychiatric terms means specifically a series of neurological problems characterized by abnormal sensory experiences and movement problems during periods of high psychological stress.

Such disorders, characterized by paralysis, sensory disturbances, and seizures are associated with alteration of brain function networks. The Korean study showed increased risks of

which were heightened by combining different Covid-19 vaccinations.

Most patients who were infected with COVID-19 experienced chronic fatigue with mild cognitive impairment (i.e., brain fog). Abel et al. described from the UK primary care data that COVID-19 infection increased the risks of fatigue and sleep disorders. The mechanism is thought to be caused by a decrease in cerebral blood flow, and it is similar to neuro-psychiatric disorders affected by inflammatory processes and immune responses. My previous two Newsletters, here and here, dealt with the effects on the immune system and the effects of inflammatory processes from both the Covid-19 virus and the vaccinations.

From the very large scale Korean study it would appear that the COVID-19 vaccination increases the manifestation of neurosis-related disorders such as anxiety, but decreases that of psychosis-related disorders such as schizophrenia. Neurosis-related disorders are characterized by persistent patterns of

Individuals with ‘neurotic disorders’ often experience excessive worry, irrational fears, intrusive thoughts, compulsive behaviors, and difficulties managing stress.

Psychosis-related disorders are characterized by a loss of touch with reality, such as

With the increasing evidence of extra-pulmonary (in organ systems other than the lungs) manifestations including both neurological and psychiatric symptoms, COVID-19 infection as well as vaccination may affect the central and peripheral nervous system with profound cellular and molecular mechanisms. The SARS-CoV-2 spike protein is known to cross the Blood Brain Barrier. Your blood brain barrier (BBB) is a filtering layer of cells surrounding blood vessels in most areas of your brain. It’s a critical line of defense, keeping most harmful things out and most helpful things in. If things that should not be there cross that barrier into the brain, there can be severe consequences.

Although the pathogenesis remains unclear, the study suggests that neuro-inflammation caused by spike proteins may contribute to occurrences of some mental health adverse events (AEs), such as depression and anxiety, dissociative, stress related, and somatoform disorders.

Somatic symptom disorder is diagnosed when a person has a significant focus on physical symptoms, such as pain, weakness or shortness of breath, to a level that results in major distress and/or problems functioning.

The study hypothesized the mechanism of action after COVID-19 vaccination, and found that schizophrenia-related genes share the enrichment pathway for bile acid metabolism. Bile acids prevent the binding of spike protein with angiotensin-converting enzyme II (ACE2) receptors, and modulate the expression of ACE2, suggesting the protective role against schizophrenia, and therefore the reduced risks of schizophrenia.

For depression, as an increased risk after COVID-19 vaccination, the results were shown for the deep interaction of spike protein-related factors such as NLRP3 inflammasome; for more on this click here.

This supports the hypothesis that the presence of the spike protein plays a crucial role in the manifestation of diseases after COVID-19 vaccination. Regarding the neurosis, the Rap1 signaling was observed as an enrichment pathway in the genes of neuroticisms (anxiety, distress, emotional worries etc..). It regulates MAPK pathways that are important for SARS-CoV-2 virus replication.

Neuro-inflammation and microglial activation are implicated in the pathophysiology of psychiatric disorders such
as

Increased inflammatory responses and oxidative stress can stimulate microglia (the primary immune cells of the central nervous system), leading to the release of pro-inflammatory cytokines like interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), which contribute to brain pathology leading to mental health issues.

Neurotrophic factors (biomolecules that support the growth, survival, and differentiation of neurons), such as brain-derived neurotrophic factor (BDNF) and its interactions with immune-inflammatory pathways are key components in the pathophysiology of mood disorders and schizophrenia.

Lowered BDNF levels are associated with disruptions in neurotrophic signaling and activated immune-inflammatory pathways, leading to neurotoxicity and synaptic dysfunction. The causative relationship between environmental factors and mental disorders has been recognized for a long time. These factors include psychological and physical stress and exposure to pollutants, toxins, medications, etc.

Psychological stress appears to be especially impactful, (and we have all suffered a huge amount of stress over the past five years), and can produce a variety of serious mental health issues through mechanisms including

Previously underappreciated metabolic factors appear to play a significant role in the pathogenesis of mental disorders. Specifically, mitochondrial dysfunction and impaired brain energy metabolism have been recently proposed as mechanisms underlying psychiatric disorders. Evidence suggests that mitochondrial abnormalities and oxidative stress play a role in the etiology and progression of mental conditions including bipolar disorder, major depressive disorder, schizophrenia, and autism.

Chronic psychological stress can induce structural and functional changes in mitochondria, leading to oxidative stress, inflammation, and brain cell apoptosis. This process is thought to predispose individuals to psychiatric disorders by disrupting cellular homeostasis. Additionally, alterations in mitochondrial dynamics, such as fission, fusion, biogenesis, and mitophagy have been observed in psychiatric conditions, further supporting the role of mitochondrial dysfunction in these disorders.

Alterations in neurotransmitter systems, particularly dopamine and glutamate, are central to the pathophysiology of psychotic disorders such as schizophrenia. Excess synaptic levels of dopamine and glutamate lead to increased postsynaptic stimulation, contributing to psychotic symptoms. Deficiencies in γ-aminobutyric acid (GABA) inhibitory interneurons and hypofunctioning N-methyl-D-aspartate (NMDA) glutamate receptors disrupt the inhibitory-excitatory balance, further exacerbating these symptoms.

In summary, it has been well established that mental disorders result from the complex interplay of genetic, epigenetic, immune, metabolic, neurobiological and environmental factors. While the specific details of these interactions remain unknown, the current knowledge is sufficient to implicate COVID-19 spike protein as a potential culprit in triggering a variety of mental health issues. For more on this, see my article on ‘Spike Protein: a Proven Psycho-pathogenic Factor.’

So what can we do to help ourselves and others?

Spike protein Detox

Proteolytic enzymes such as Nattokinase, Serrapeptidase and Lumbrokinase (Boluoke) have shown promise in reducing spike proteins. Lumbrokinase in particular has been found to be the most active proteolytic enzyme, functioning at 10+ times (an order of magnitude) the enzymatic power of Nattokinase and Serrapeptase. As each of these enzymes acts on a variation of proteins, a blend of multiple enzymes appears to be the most likely approach, at least until we know more.

Antioxidants

Again, a mix of antioxidants, just like a broad approach for enzymes, appears to produce the greatest support. A few key antioxidants stand out.  Liposomal glutathione has been shown to be particularly beneficial. Its ability to cross the blood-brain barrier supports neural inflammation (seen corresponding with the brain fog and cognitive impact of spike protein) but also inflammation seen along the enteric nerve tissue and debris-caused capillary inflammation. Glutathione has a very strong sulphur taste, which many finde very unpleasant. An alternative is to take N-Acetyl Cysteine (NAC), a precusrsor to Glutathione instead; this avoids the tatse.  Nrf-2 is also a potent antioxidant, supporting the glutathione detoxification pathways.

Anti-inflammatories

Addressing inflammation and cytokine storms is another key aspect of management. Broad-spectrum approaches found in fish oils (EPA/DHA/SPMs) and liposomal vitamin C are trending as the most utilised options. Curcumin, especially Nano-Curcumin, Quercetin, Boswellia and PEA have replaced NSAIDS and show promise in supporting the modulation of chronic inflammation. .

Mitochondrial boost

Boosting mitochondrial function, especially in the brain, is a vital way to avoid impaired brain energy metabolism.

Ubiquinol (reduced Co-enzyme Q10 for ease of absorption), NAD+ and Methylene Blue are all good options.

Neurotransmitter rebalancing

SAMe (S-adenosyl-L-methionine) is a naturally occurring compound in the body synthesized from methionine and ATP, and is available as a supplement. Some studies suggest it may reduce depressive symptoms, potentially comparable to tricyclic antidepressants.

NAC (N-Acetylcysteine) is a supplement and precursor to glutathione which regulates oxidative stress and inflammation which are both implicated in depression and anxiety..

Omega 3 Fatty acids reduce inflammation, support brain cell function and modulate neurotransmitters, potentially stabilising mood and reducing anxiety.

5 -HTP is a precursor to serotonin which regulates mood, sleep and anxiety. It may help to stabilize emotions and reduce symptoms associated with low mood and anxiety.

L-Tyrosine supports the synthesis of dopamine, and norepinephrine, neurotransmitters involved in mood regulation. stress response and cognitive function.

Non-nutrition interventions include:

Cognitive Behavioural Therapy is a structured, goal-oriented therapy highly effective for anxiety, depression and emotional regulation. It teaches skills like cognitive restructuring and coping strategies.

Dialectical Behaviour Therapy is similar to CBT, and teaches mindfulness to manage intense emotions, and tolerance for stress.

Mindfulness based therapies are effective for reducing anxiety, depression and stress-reactivity by propmoting awareness of thoughts and emotions without judgement.

Acceptance and Commitment Therapy encourages the acceptance of negative emotions and focusses on meaningful behaviours, reducing rumination and worry.

Interpersonal Therapy addresses interpersonal conflicts, role transitions or social isolation that may fuel emotional instability or anxiety.

Exposure Therapy desensitizes individuals to triggers of anxiety or distress, thereby reducing over reactivity.

Psychodynamic Therapy helps to uncover root causes of anxiety and emotional instability, such as unresolved conflicts.