Orthomolecular Psychiatry and Schizophrenia

Orthomolecular Psychiatry and Schizophrenia by Dr. Christopher Jackson, PhD, DOM (FL)


In developed countries, mental illness leads to the largest proportion of disabilities compared to physical ailments (World Health Organization, 2004). Additionally, the percentage currently experiencing mental illness are about 25% of all U.S. adults, and those with at least one lifetime incident are close to 50% (CDC, 2011a). These statistics are devastating to our society and economy, as well as the lives of the affected individuals and their families. It might also be pertinent to point out that, from an orthomolecular point of view, all psychiatric conditions could be considered to have underlying physiological root causes. Therefore, this entire argument might be moot with the discovery of the underlying physiological cause(s) for any particular psychological condition.

One particularly devastating and disruptive illness is schizophrenia, with a common onset about age 21 for men, 90% with full signs and symptoms by age 30. Onset is about age 27 for women with 20% showing full signs and symptoms by age 30 (CDC, 2011b). On average, 10% of individuals with schizophrenia successfully commit suicide with a rate of attempts at 30%. Schizophrenic individuals, up to 1% of the world population, also have a high unemployment rate, adding to their own economic burdens and lessening their contributions to society (CDC, 2011b). It is estimated that the disease costs the U.S. and Canadian economies 6.85 billion U.S. Dollars annually (CDC, 2011b).

Due to the large economic and societal burden, including an association between mental illness and chronic biomedical disorders, it is suggested that there is a need for improved monitoring (CDC, 2011b). Since symptomatic treatment using antipsychotic drugs can lead to many side-effects and immune-compromising effects, some life-threatening (Tseng, 2011), it could be argued that there is a great need for understanding and treatment of the underlying cause(s), as opposed to just the symptoms of the disorders (Lesser, 2012). It is the underlying root(s) that orthomolecular psychiatry, the application of the particular (or right) molecules to psychological disorders to reverse the conditions, has begun to thoroughly explore.

Since the early days of the 1950s, when the adrenochrome theory of Abram Hoffer and Humphry Osmond defined a potential biochemical origin for schizophrenia (Mills, 2010), and the 1960s and 70s, when Nobel Laureate Linus Pauling created the term orthomolecular, based on ortho (right) molecular - finding the right molecule for the job - an evolving specialty of orthomolecular psychiatry has earned increasing recognition by mainstream medicine and psychiatry. An approach based upon nutrition and precursors to brain and neurological function may truly address the underlying causes.

The conventional approach tends to focus on correction of symptoms, rather than treatment of underlying causal factors. Treatment of symptoms may lead to a patient who feels better or is adapted better to societal norms, but whose long-term success is tied to the use of toxic drugs that damage the workings of the human body. Addressing the underlying physiological basis of each disorder (the root cause) via orthomolecular medicine/psychiatry provides hope for a true cure without dependency on refined chemicals.

Hence, this study will attempt to uncover and define the potential causal factors of schizophrenia addressed by orthomolecular medicine and psychiatry, including neurotransmitter deficiencies, genomic polymorphisms, pellagra, mercury poisoning, hyperthyroidism, stress-induced metabolites, and potential nutritional or precursor treatments for the disorder.

The fundamental theory and application of orthomolecular medicine to psychiatry, particularly schizophrenia, may help to expand the influence of the natural approach. It would be most beneficial to expand upon and complement the current approaches used in psychiatry, which too often has been dominated by cook-book dissemination of potentially harmful anti-psychotics, SSRIs, and the like (Lesser, 2012). Often, the patient is given a prescription drug or drugs to address the symptoms of the closest diagnosis. The drugs, much of the time, do not address the underlying causes (or physiological basis) of the disorders (Lesser, 2012).

The detrimental effects of the drugs have included less quality of life, a broad range of side-effects of the drugs themselves, and the hard costs and opportunity costs involved. The pursuit of an approach that offers no promise of a cure or reversal of the root causes of the disorders may simply tie the patient to a life-long pursuit of a better life via a better drug.

Addressing the Root Cause

Initially, anti-psychotic drugs may have a positive effect of recovery from psychotic episodes. This is in the short-term. Although the underlying root cause is not being addressed in most cases, the situation is reasonably resolved for a period of time. However, long-term anti-psychotic drug treatment of schizophrenia results in negative effects on quality of life. Effects include difficulty performing routine tasks due to lack of energy, lack of awareness, and lack of clarity of thought, as well as apathy, lethargy, fatigue, and a general reduction in stimulation from daily experience, largely due to tranquilizing effects (Lesser, 2012) and brain shrinkage (Ho, Andreasen, Ziebell, Pierson, & Magnotta, 2011).

Negative side-effects of anti-psychotic drug therapies include the loss or reduction of normal function physically and cognitively, while the underlying causal factors could be related to body systems, therefore quite treatable, such as thyroid function elevation, nutritional deficiencies, or the existence of heavy metals in the brain (Lesser, 2012). Neutropenia leads to lowered immunity and a potential for agranulocytosis, which may subsequently lead to fatality of the patient (Cohen & Monden, 2013; Tseng, 2011). Brain shrinkage in both white and gray matter, possibly related to a reduction of blood flow into the cerebral cortex, has also been indicated (Ho et al., 2011).

The topic of healthcare costs has been prevalent in the news and media recently, with the relatively new Affordable Care Act gradually inserting itself into the United States healthcare system. The rising cost of healthcare includes the cost of physiological and psychological care, and both areas must be considered for the needs of our nation to be properly addressed. One such consideration is the annual societal cost of childhood psychological disorders, which is approximately $247 billion, and on the rise (Perou et al., 2013). Healthcare costs exceeded general inflation between 1999 and 2009, virtually wiping out income gains (Auerbach & Kellermann, 2011).

As we have discussed, the anti-psychotic drugs do not typically address the underlying causal factors involved in the pathology of schizophrenia, and they may actually exacerbate, and further complicate, the condition with long-term exposure (Ho et al., 2011). Delving into the root cause or causes of schizophrenia and related disorders, much research has developed in the last decade, research that focuses on many underlying physiological processes. Some of the primary areas of focus are Endogenous Schizogens, Inflammation, and Genetic Polymorphisms. From related studies, one may glean greater understanding of the possible underlying factors leading to development of the disorder.

The underlying causal factors involved in the genesis of the symptoms of schizophrenia are apparently multivariate, but several possible cores come to the fore. Of these, endogenous schizogens may be metabolic by-products, hormonally active compounds, substances resulting from nutritional deficiencies, heavy metals, and others (Baumeister, 2011; Lesser, 2012; Mills, 2010). The studies presented involve the protein Taraxein, the injection of which supposedly produces the symptoms of schizophrenia (Baumeister, 2011), as well as adrenochrome, a metabolite of adrenaline, related to the production of adrenaline from stress (Mills, 2010).

Endogenous Schizogens

The Taraxein study by Baumeister (2011), a literature review, failed to substantiate the presence of this protein, indicating that its presence was unlikely. However, the author allowed for the possibility of experimental error due to incomplete or inadequate criteria. Further research into metabolites from adrenaline and other catecholamines would be suggested. In his meta-analysis, Mills (2010) examined several prior studies and concluded that he could not validate the adrenochrome hypothesis.

However, related theory would indicate that stressful circumstances may be a precursor to, or underlying trigger of, the processes leading to the development of schizophrenia. Administration of niacin (a methyl acceptor) improved symptoms of a studied schizophrenic population, theoretically by preventing or reducing the production of adrenochrome (Mills, 2011). Seybolt , 2010 showed similar results with the combination of niacin and alpha lipoic acid (ALA) administration, although results reportedly diminished after the study.


Inflammation is an inherent process involved in the etiology of many common health conditions. It is also evident that inflammatory processes, including hyperlipidemia, either exacerbate the condition known as schizophrenia or contribute to it (Hsu et al., 2012; Mansur et al., 2012; Müller & Schwarz, 2008; Paul-Samojedny et al., 2013; Sood et al., 2011). Hsu et al. (2012) was a large-scale study showing a prevalence of hyperlipidemia in individuals with schizophrenia.

Cytokines are chemicals involved in message transmission between cells, neuro-inflammatory responses, and the activities of the immune system. Paul-Samojedny et al. (2013) correlated cytokine polymorphisms with brain cross-talk in paranoid schizophrenia in a well-controlled study of human participants (Polish). Mansur et al. (2012) conducted a literature review demonstrating the correlation between schizophrenia and pro-inflammatory cytokines, whereas Müller and Schwarz (2008) was a literature review that also tied major depression into the relationship with pro-inflammatory cytokines. Sood et al. (2011) conducted a small, but well-controlled, rat study using aluminum to create the neurodegenerative environment.

Luckily, there are many natural approaches to the treatment of inflammation, outside the realm of the standard over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) and steroids. NSAIDs can lead to gastrointestinal disorders, as well as liver and kidney damage. Steroidal treatments can cause hormonal disruption and lead to bone disorders. A prominent member of the alternative group of natural anti-inflammatories is curcumin, and related turmeric. These are shown to address inflammatory neurodegenerative processes like those involved in schizophrenia (Sood et al., 2011).

Genetic Polymorphisms

Similarly, genetic polymorphisms are indicated as possible underlying factors in the pathogenesis of schizophrenia. A subset of cytokines is interleukins (IL). As referenced above, pro-inflammatory cytokines IL-2, TNFa, and IL-6 polymorphisms were correlated with incidence of schizophrenia. IL-6 is also involved in dopamine production, as well as other adrenal hormones that may be involved in the stress response and inflammatory responses (Paul-Samojedny et al., 2013). Effects of BDNF val66met polymorphism on dopamine receptors may relate to neurodevelopmental disturbances and severity of schizophrenia (Chang et al., 2009). Chang et al. (2009) was a well-controlled study with a reasonable sample size of 251 schizophrenic patients differentiated by age of onset and family history, as well as specific symptomatology. The sample population was compared to 284 healthy individuals. One study, also well-controlled with a sample of 208 paranoid schizophrenic inpatients and 254 control participants, indicated that correlation did not exist between polymorphism and pathology, but did exist between age of onset and pathology (Suchanek et al., 2013).


To truly treat the underlying cause(s) of schizophrenia and similar or related disorders, we need to focus on pathophysiology, not psychology alone. A viable route to the understanding and uncovering of the information needed to treat the root cause is provided through the on-going research and theory behind the practice of orthomolecular medicine and psychiatry. The field of orthomolecular medicine has evolved from its beginnings over the last sixty plus years to a very sophisticated and scientific approach to address the need for an alternative or a complement to refined chemicals that dope and damage the body of the patient who only seeks to be helped.

Orthomolecular medicine and psychiatry may be considered a form of natural medicine, since the focus is on finding the right nutritional and precursor molecules to address the underlying causal factors involved in any disorder, particularly that of schizophrenia. Research shows that integration of natural medicine into the conventional system is strongly supported by the public (Moshe, Eran Ben, Carol, & Victor, n.d). Natural (complementary and alternative) medicine is more prevalent in higher income groups, showing that a greater proportion of individuals with discretionary spending funds tend to opt for more natural approaches to their healthcare (Hae Jin et al., n.d).

Conclusions and Recommendations

The research has shown that there are many routes to treatment, but the best solutions may be found using combinations of some or all of the following. Reducing adrenochrome (using methyl acceptors) may help to improve schizophrenia (Mills, 2010). Treatment with ALA and niacin (a methyl acceptor) improves schizophrenia (Seybolt, 2010). Further research is needed into metabolites from adrenaline and other catecholamines, and their influence on schizophrenia.

Curcumin ameliorates neuro-inflammatory processes involved in schizophrenia and other disorders (Sood et al., 2011). As stated previously, Sood et al. (2011) was based on a small population of rats. More and larger studies would be appropriate, especially in humans, relating to the effects of aluminum, pro-inflammatory cytokines, and other inflammatory substances, and their reduction using curcumin or other anti-inflammatory antioxidant substances.

Boosting immunity may offset side-effects of treatment drugs, particularly neutropenia (Cohen & Monden, 2013; Tseng, 2011). Research is needed into the underlying reason for the resultant decrease in white blood cell counts, using larger sample sizes. In the meantime, it would be prudent to test WBCs of all patients on anti-psychotics for any prolonged period of time. Research into possible nutritional, herbal, homeopathic or drug offsets to the condition would be appropriate, as well.

Treatment using omega 3 fatty acids with high concentration of eicosopentaenoic acid (EPA) may reverse brain shrinkage seen with the application of anti-psychotics. In all cases, the lowest effective dosage should be applied to avoid unnecessary diminishment of brain function, while researching an underlying cause. Thyroid function should be tested thoroughly (not just TSH), and vitamin and mineral levels should be checked for any deficiencies or excesses, as well as any significant presence of heavy metals (Lesser, 2012).

Copyright December, 2013



Auerbach, D., & Kellermann, A. (2011). A decade of health care cost growth has wiped out real income gains for an average U.S. family. Health Affairs, 30(9):1630-1636.

Baumeister, A. (2011). The search for an endogenous schizogen: The strange case of taraxein. Journal of the History of the Neurosciences, 20(2), 106-122. doi:10.1080/0964704X.2010.487427

Centers for Disease Control and Prevention. (2011a). Burden of mental illness. Atlanta, GA: Author. Retrieved from http://www.cdc.gov/mentalhealth/basics /burden.htm

Centers for Disease Control and Prevention. (2011b). CDC report: Mental illness surveillance among adults in the United States. Atlanta, GA: Author. Retrieved from http://www.cdc.gov/mentalhealthsurveillance/fact_sheet.html

Chang et al. (2009). Brain-derived neurotrophic factor val66met polymorphism: Association with psychopathological symptoms of schizophrenia? The Journal of Neuropsychiatry and Clinical Neurosciences, 21 (1), 30-37.

Chen, T-J., Cheng, H-M., Wang, D-C., & Hung, H-S. (2010). Nonlethal aluminum maltoate can reduce brain-derived neurotrophic factor-induced Arc expression through interrupting the ERK signaling in SH-SY5Y neuroblastoma cells. Toxicology Letters, 200(1): 67-76. doi: 10.1016 /j.toxlet.2010.10.016

Cohen, D., & Monden, M. (2013). White blood cell monitoring during long-term clozapine treatment. American Journal of Psychiatry, 170(4), 366-369. doi: 10.1176/appi.ajp.2012.12081036

Hae Jin, K., Ki Hong, C., Dae Jung, K., Seung Jin, H., Young Seol, K., Jeong Taek, W., & ... Kwan Woo, L. (n.d). Utilization patterns and cost of complementary and alternative medicine compared to conventional medicine in patients with type 2 diabetes mellitus. Diabetes Research and Clinical Practice, 93115-122. doi:10.1016/j.diabres.2011.03.031

Ho B, Andreasen NC, Ziebell S, Pierson R, & Magnotta V. (2011). Long-term antipsychotic treatment and brain volumes: A longitudinal study of first-episode schizophrenia. Archives of General Psychiatry., 68(2):128-137. doi:10.1001/archgenpsychiatry.2010.199

Hsu, J-H., Chien, I-C., Lin, C-H., Chou, Y-J., & Chou, P. (2012). Psychiatric-medical comorbidity: Hyperlipidemia in patients with schizophrenia: a national population-based study. General Hospital Psychiatry, 34(4):360-367. doi: 10.1016/j.genhosppsych.2012.02.004

Lesser, I. (2012). Seeing schizophrenia through a personalized medicine prism. Personalized Medicine Universe, 1(1), 84. Retrieved from http://www.sciencedirect.com/science/article/pii /S2186495012000041

Lieberman, J. A., Stroup, T. S., McEvoy, J. P., Swartz, M. S., Rosenheck, R. A., Perkins, D. O., ...Hsiao, J. K.(2005).Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.New England Journal of Medicine, 353(12), 1209-1223. 

Mansur, R. B., et al. (2012). Cytokines in schizophrenia: possible role of anti-inflammatory medications in clinical and preclinical stages. Psychiatry and Clinical Neurosciences, 66(4): 247-260.

Mills, J. A. (2010). Hallucinogens as hard science: The adrenochrome hypothesis for the biogenesis of schizophrenia. History of Psychology, 13(2), 178-195. doi:10.1037/a0019394

Müller, N., & Schwarz, M. (2008). A psychoneuroimmunological perspective to Emil Kraepelins dichotomy: schizophrenia and major depression as inflammatory CNS disorders. European Archives of Psychiatry and Clinical Neuroscience, 258 Suppl 2: 97-106. doi:10.1007/s00406-008-2012-3

Moshe, F., Eran Ben, A., Carol, C., & Victor, S. (n.d). Integrating complementary and alternative medicine into conventional primary care: The patient perspective. Explore: The Journal of Science and Healing, 4178-186. doi:10.1016/j.explore.2008.02.001

Paul-Samojedny et al. (2013). Association of interleukin 2 (IL-2), interleukin 6 (IL-6), and TNF-alpha (TNFa) gene polymorphisms with paranoid schizophrenia in a polish population. The Journal of Neuropsychiatry and Clinical Neurosciences, 25 (1), 72-82. doi: 10.1176/appi.neuropsych.12020021

Perou, R., Bitsko, R. H., Blumberg, S. J., Pastor, P., Ghandour, R. M., Gfroerer, J. C., & … Huang, L. N. (2013, May 17). Mental health surveillance among children - United States, 2005-2011. Morbidity and Mortality Weekly Report, 62(2), 1-35. Retrieved from Centers for Disease Control and Prevention website: http://www.cdc.gov/mmwr/preview/mmwrhtml/su6202a1.htm

Rowland et al. (2013). GABA predicts inhibition of frequency-specific oscillations in schizophrenia. The Journal of Neuropsychiatry and Clinical Neurosciences, 25 (1), 83-87. doi: 10.1176/appi.neuropsych.11120368

Seybolt, S. (2010). Is it time to reassess alpha lipoic acid and niacinamide therapy in schizophrenia?. Medical Hypotheses, 75(6), 572-575. Retrieved from http://www.sciencedirect.com/science/article /pii/S0306987710002720

Sood, P.K., Nahar, U., & Nehru, B. (2011). Curcumin attenuates aluminum-induced oxidative stress and mitochondrial dysfunction in rat brain. Neurotoxicology Research, 20: 351-361. doi: 10.1007 /s12640-011-9249-8

Suchanek, R., Owczarek, A., Paul-Samojedny, M., Kowalczyk, M., Kucia, K., & Kowalski, J. (2013). BDNF val66met polymorphism is associated with age at onset and intensity of symptoms of paranoid schizophrenia in a polish population. The Journal of Neuropsychiatry and Clinical Neurosciences, 25 (1); 88-94. doi: 10.1176/appi.neuropsych.11100234

Tseng, C. (2011). Neutropenia during risperidone treatment. The Journal of Neuropsychiatry and Clinical Neurosciences, 23(4), E19-E19. doi: 10.1176/appi.neuropsych.23.4.e19

The World Health Organization (WHO). (2004). The world health report 2004: Changing history. Annex Table 3: Burden of disease in DALYs by cause, sex, and mortality stratum in WHO regions, Estimates for 2002; A126-A127. Geneva: WHO; 2004.