Although the review above may have important implications for the current controversy over the toxicity and permissible levels of human exposure to BPA, the focus of this study has been whether endocrine disruption like that from BPA might be involved in schizophrenia. However, the current debate over the safety of human BPA exposure has raised the question whether endocrine disruption increases the incidence of diseases such as autism and ADHD, diseases that may have associated risk with schizophrenia. For this reason, perhaps the current study may apply to other diseases like autism and ADHD. Because schizophrenia epidemiology has similarities to that of MS,322,323
the role of BPA in promoting autoimmune reactions and repressing myelin basic protein described above supports the addition of diseases like MS to the list of diseases as possibly related to endocrine disruption. The primary goal of the foregoing discussion was, however, to emphasize the several lines of evidence suggesting a possible role of endocrine disruption in the pathogenesis of schizophrenia.
The author does not suggest that BPA is the only purported cause of endocrine disruption leading to schizophrenia. The review above demonstrates that an estrogen mimic or other endocrine signal from some source in prenatal life could be reduced, delayed, increased, or premature which disrupts brain development so as to cause schizophrenia. The theory's validity also does not depend on whether experiments with BPA and other EDCs have used environmentally significant levels of exposure. The purpose of the review was to show the similarities of endocrine disruption to schizophrenia at whatever dose is necessary to induce disruption regardless of the specific agent involved.
The proposed theory is also not limited to suggesting that only fetal or neonatal exposures to EDCs are psychiatrically pathogenic. BPA tissue levels, or exposures to any other major EDCs, have not been studied in children or adults with schizophrenia or other major mental illnesses. It is possible that such studies could reveal previously unsuspected exposures or undiscovered metabolic and/or other abnormalities that would render children or adults with schizophrenia more susceptible to EDCs. It is also possible that exposure of adults with schizophrenia to EDCs could explain certain adverse reactions to medications or disease states believed to have been traits.
However, EDCs invented during the 20th century such as BPA and other plastic-related endocrine disruptors could not be directly related to the existence of schizophrenia in centuries prior to the invention of plastics. This does not mean such chemicals could not enhance the disease's prevalence or severity in the 21st century, and this possibility should be ruled out before any final policy is made about the safety of endocrine disruptors in the environment. This is especially true now that endocrine disruptors have been shown to cause transgenerational mutations that evolve new disease conditions that perpetuate in future generations.324,325
There are several synthetic and naturally occurring endocrine disruptors that were not examined in detail in this study. Many of these, such as cadmium and genistein, have been in the human environment perhaps for thousands of years. The human exposure to cadmium as an environmental contaminant from coal burning326
and tobacco smoking327
probably increased with urbanization, a risk factor often associated with schizophrenia.328
The higher urban risk of schizophrenia has been attributed to higher urban rates of infectious diseases, risk-prone genetic populations, poor nutrition, and stress.329
Although cadmium has never been mentioned as a risk factor in this context before, perhaps it should be included as it has estrogenic-disrupting potential at low doses.330
More than one pathway may exist for endocrine disruption from infections, genetics, malnutrition, and stress. The influence of maternal influenza on gender-related birth defects has been mentioned previously, and nutritional sources of endocrine disruptors include modern chemicals like BPA and naturally occurring substances like genistein. Fetal injury from maternal influenza could be enhanced in an endocrine-disrupted fetus as perinatal exposure to low doses of the endocrine disruptor, PCB-126, impairs maternal and neonatal immunity in a fashion similar to the immune effects induced by perinatal exposure to DES that acts through estrogenic mechanisms.331
Stress has been shown to alter the changes of sex-related behaviors in mice that are influenced by intrauterine positions.332
Studies have shown that gender-related behaviors of both male and female mice are influenced by intrauterine positions that cause variations in exposure to estradiol and T.332,333
Prenatal stress can eliminate these effects,332
acting as an endocrine disruptor of the intrauterine hormonal state. In an endocrine disruption model of schizophrenia, this would imply that the maternal genetics of responding to stress influences the prenatal risk factors of schizophrenia. The notion of “disentangling” maternal genes from environmental risk factors for chronic diseases is not new334
and should be considered for future genetic studies of schizophrenia. Other assessments of schizophrenia that should be performed based on the proposed model would be measures of exposure to endocrine disruption or disruptors, whether synthetic, endogenous, or natural substances, in utero and in later life. This author is proceeding with review of the literature to identify and describe other endocrine disruptors that cause pathological changes similar to those observed in schizophrenia and other diseases as described above.