Pregnenolone, Cholesterol, Vitamin D, & Neuropsychiatric Illness

#neuroscience #neuropsychiatry #neuroendocrinology #hormones #diets #ketogenicdiet #mediterraneandiet #wellness #cholesterol #pregnenolone #vitamind #psychiatry #mentalhealth #mitochondria #mitochondrialmedicine

Explore the intricate relationship between mitochondrial health, ergocalciferol (Vitamin D2), pregnenolone synthesis, and cholesterol in neuropsychiatric disorders. Delve into the therapeutic potential of the ketogenic diet and the profound influence of Vitamin D on brain function and mental health.

Yes, I can't seem to help myself.

Even when I am not looking at it, trying to read up on all the new findings of pregnenolone and depression, I seem to find myself right back at the Mighty Mito.

Mitochondria, the cellular powerhouses, have emerged as critical players in the landscape of neuropsychiatric health. Their role in energy production and cellular homeostasis has been well-established (Wallace, D. C. (2013). A mitochondrial bioenergetic etiology of disease. Journal of Clinical Investigation, 123(4), 1405-1412). However, recent studies have delved deeper, uncovering their profound influence on neuropsychiatric disorders.

Mitochondrial dysfunction in certain brain regions may contribute to the observed abnormalities-- Segal, A., et al. (2023)

Neuroanatomical Regions, Neuropsychiatric Illness & Mitochondria

Segal et al. (2023) embarked on a journey to understand the heterogeneity of brain abnormalities in psychiatric disorders. Their findings suggest that "mitochondrial dysfunction in certain brain regions may contribute to the observed abnormalities" (Segal, A., Parkes, L., Aquino, K. et al. (2023). Regional, circuit and network heterogeneity of brain abnormalities in psychiatric disorders. Nat Neurosci). This is in line with research that has identified mitochondrial anomalies as potential culprits in conditions like bipolar disorder and schizophrenia (Kato, T. (2001). The role of mitochondrial dysfunction in bipolar disorder. Drug News & Perspectives, 14(10), 597-604).

The synthesis of pregnenolone -with its roots in mitochondria- was found to be altered in patients responding to antidepressant treatment

Pregnenolone

Pedraz-Petrozzi et al. (2023) shifted the lens to the realm of neuroactive steroids in depression. The synthesis of pregnenolone, a steroid with its roots in mitochondria, was found to be altered in patients responding to antidepressant treatment. This intricate relationship between mitochondrial function and neuropsychiatric health offers a fresh perspective on the pathophysiology of depression (Pedraz-Petrozzi, B., Lamadé, E.K., Schneiberg, R. et al. (2023). Reduced urine pregnenolone concentration after clinical response in patients with depression. Psyneuen).

The ketogenic diet "enhances mitochondrial biogenesis, improves mitochondrial respiratory chain function, and increases ATP production"-- Pavón, S. et al. (2021)

The Ketogenic Diet

The ketogenic diet, with its potential neuroprotective effects, has garnered significant attention in the scientific community. Pavón et al. (2021) provided a comprehensive overview of the diet's impact on cognition in neurological diseases. Their research suggests that the ketogenic diet "enhances mitochondrial biogenesis, improves mitochondrial respiratory chain function, and increases ATP production" (Pavón, S., & others (2021). Ketogenic diet and cognition in neurological diseases. Nutrition Reviews). This is supported by studies that have highlighted the potential of the ketogenic diet in conditions characterized by mitochondrial dysfunction, such as Alzheimer's disease (Henderson, S. T. (2008). Ketone bodies as a therapeutic for Alzheimer's disease. Neurotherapeutics, 5(3), 470-480).

The intricate dance between mitochondrial health and neuropsychiatric disorders continues to be increasingly clear. As research by Valero (2014) suggests, mitochondrial dysfunction can lead to neurodegenerative diseases, emphasizing the need for targeted interventions (Valero, T. (2014). Mitochondrial biogenesis: pharmacological approaches. Current Pharmaceutical Design, 20(35), 5507-5509).

The findings of Segal et al. (2023) and Pedraz-Petrozzi et al. (2023) further underscore this relationship, highlighting potential therapeutic avenues.

Ergocalciferol (Vitamin D2) and Its Significance in Neuropsychiatric Health

Ergocalciferol, commonly known as Vitamin D2, is a crucial vitamin that plays a multifaceted role in human health. While its primary association is with bone health and calcium metabolism, emerging research has highlighted its significance in neuropsychiatric health, particularly in the context of mitochondrial function, pregnenolone synthesis, and cholesterol metabolism.

Vitamin D can influence mitochondrial oxidative function-- Ryan et al. (2016)

Mitochondrial Bioenergetics and Vitamin D2

Mitochondria, as the primary energy producers in cells, have a direct relationship with Vitamin D. A study by Ryan et al. (2016) found that Vitamin D can influence mitochondrial oxidative function in human skeletal muscle. The research suggested that "Vitamin D appears to alter the size or number of the mitochondria in muscle cells, which in turn may improve their function" (Ryan, Z. C., et al. (2016). Vitamin D receptor expression is associated with improved muscle function: A cross-sectional study in younger and older adults. Experimental Gerontology, 82, 109-114).

"Vitamin D has been shown to play a role in the synthesis of neuroactive steroids, including pregnenolone"-- Miller, W. L. et al. (2012)

Pregnenolone Synthesis and Vitamin D2

Vitamin D's role in steroidogenesis, particularly in synthesizing pregnenolone, is noteworthy. The vitamin D receptor (VDR) has been identified in various tissues, including those involved in steroidogenesis. Miller et al. (2012) highlighted that "Vitamin D has been shown to play a role in the synthesis of neuroactive steroids, including pregnenolone" (Miller, W. L., & Auchus, R. J. (2012). The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocrine Reviews, 32(1), 81-151).

"Vitamin D regulates more than 900 genes, many of which are associated with neuropsychiatric and brain development disorders"-- Patrick, R. P. et al. (2014)

Cholesterol, Vitamin D2, and Neuropsychiatric Implications

Cholesterol is a precursor for Vitamin D synthesis. When UVB rays from the sun interact with 7-dehydrocholesterol in the skin, it gets converted into Vitamin D3, which is then transformed into its active form in the liver and kidneys. This interplay between cholesterol and Vitamin D is vital for neuropsychiatric health. A study by Patrick and Ames (2014) posits that "Vitamin D regulates more than 900 genes, many of which are associated with neuropsychiatric and brain development disorders" (Patrick, R. P., & Ames, B. N. (2014). Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism. The FASEB Journal, 28(6), 2398-2413).

"Vitamin D deficiency is prevalent in patients with psychotic disorders, and the deficiency severity correlates with the disease's severity"-- Eyles, D. W., et al. (2019)

Vitamin D2 in Neuropsychiatric Disorders

The implications of Vitamin D deficiency in neuropsychiatric disorders are becoming increasingly evident. Eyles et al. (2019) found that "Vitamin D deficiency is prevalent in patients with psychotic disorders, and the deficiency severity correlates with the disease's severity" (Eyles, D. W., Burne, T. H., & McGrath, J. J. (2019). Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Frontiers in Neuroendocrinology, 50, 75-85).

Furthermore, Vitamin D's role in neuroprotection cannot be understated. It modulates neurotransmitters and neurotrophic factors, influencing brain function and reducing the risk of neuropsychiatric disorders. Kesby et al. (2011) noted that "Vitamin D may influence multiple pathways that are directly relevant to schizophrenia and depression" (Kesby, J. P., Eyles, D. W., Burne, T. H., & McGrath, J. J. (2011). The effects of vitamin D on brain development and adult brain function. Molecular and Cellular Endocrinology, 347(1-2), 121-127).

Ergocalciferol's role in neuropsychiatric health is multifaceted and profound. From influencing mitochondrial bioenergetics to playing a pivotal role in steroidogenesis and cholesterol metabolism, Vitamin D2's significance cannot be understated. As research sheds light on these interconnections, it becomes evident that maintaining optimal Vitamin D levels is crucial for neuropsychiatric health.

What can all this mean

Wrapping things up: the centrality of mitochondrial health in neuropsychiatric illness and disease is undeniable. The scientific community's endeavors, from understanding brain abnormalities to exploring the potential of diets, have illuminated the path forward.

As a physician-specialist in my field, aside from all other interventions, medications, psychotherapeutic avenues, hydration, and recommended exercise (btw, High-Intensity Interval Training plays a role in all of the above topics), I attempt to ensure that in all of my patients, I:

• Measure, track, and optimize Vitamin D
• Manage diet with a broad Mediterranean-style, Keto-Leaning Diet (see my essay HERE)
• Measure and optimize inter-related Cholesterol and steroid-hormone levels

As we continue to unravel the mysteries of the mitochondria and the vast inter-relationships with:

• The fuel we provide the mitochondria (an increased understanding of diets),
• Cholesterol management (see my essay HERE),
• Cholesterol's further role in Vitamin D synthesis,
• The subsequent role Vitamin D (see my essay HERE) within the mitochondria plays in initiating the cascade of steroidogenesis with pregnenolone synthesis.

The hope is that novel therapeutic strategies will emerge, offering solace to those affected by neuropsychiatric conditions through in-expensive, accessible, and safe interventions.

Desiderio Pina, MD, MPH

TheMindAndBodyDoc-Physician/Neuroscientist —?@mindandbodydoc

I provide compassionate care for children (5 years & older), adolescents, adults & families struggling with nutritional, drug, & neuropsychiatric problems.

Teaching is always a privilege, and I’ve been afforded such privilege to teach at various medical schools (MD & DO), residency programs (Psychiatry, Neurology, Family Practice, and Internal Medicine), and universities; I have participated in clinical and basic science research in the past, and am currently on staff at a few hospitals, but primarily care for patients via telemedicine.

I generally talk & write about things that catch my fancy in the news and from the recent medical literature.?

These include, but are not limited to:?#wellness,?#neurosciences,?#neuropsychiatry,?#culturalpsychiatry,?#ethnobotony,?#mycology,?#mycologicalmedicine,?#digitalhealthcare,?#healthcaremanagement, and?#psychoneuroendocrineimmunology

References:

1. Henderson, S. T. (2008). Ketone bodies as a therapeutic for Alzheimer's disease. Neurotherapeutics, 5(3), 470-480.
2. Kato, T. (2001). The role of mitochondrial dysfunction in bipolar disorder. Drug News & Perspectives, 14(10), 597-604.
3. Pavón, S., & others (2021). Ketogenic diet and cognition in neurological diseases. Nutrition Reviews, Volume 79, Issue 7, 802–813.
4. Pedraz-Petrozzi, B., Lamadé, E.K., Schneiberg, R. et al. (2023). Reduced urine pregnenolone concentration after clinical response in patients with depression. Psyneuen.
5. Segal, A., Parkes, L., Aquino, K. et al. (2023). Regional, circuit and network heterogeneity of brain abnormalities in psychiatric disorders. Nat Neurosci.
6. Valero, T. (2014). Mitochondrial biogenesis: pharmacological approaches. Current Pharmaceutical Design, 20(35), 5507-5509.
7. Wallace, D. C. (2013). A mitochondrial bioenergetic etiology of disease. Journal of Clinical Investigation, 123(4), 1405-1412.
8. Ryan, Z. C., et al. (2016). Vitamin D receptor expression is associated with improved muscle function: A cross-sectional study in younger and older adults. Experimental Gerontology, 82, 109-114.
9. Miller, W. L., & Auchus, R. J. (2012). The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocrine Reviews, 32(1), 81-151.
10. Patrick, R. P., & Ames, B. N. (2014). Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism. The FASEB Journal, 28(6), 2398-2413.
11. Eyles, D. W., Burne, T. H., & McGrath, J. J. (2019). Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Frontiers in Neuroendocrinology, 50, 75-85.
12. Kesby, J. P., Eyles, D. W., Burne, T. H., & McGrath, J. J. (2011). The effects of vitamin D on brain development and adult brain function. Molecular and Cellular Endocrinology, 347(1-2), 121-127.