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Toxic causes of mental illness are overlooked
NeuroToxicology 29 (2008) 1147–1149
Contents lists available at ScienceDirect
NeuroToxicology
Commentary
Toxic causes of mental illness are overlooked Stephen J. Genuis * University of Alberta, Faculty of Medicine, 2935-66 Street, Edmonton, Alberta, Canada T6K 4C1
A R T I C L E I N F O
A B S T R A C T
Article history: Received 3 May 2008 Accepted 13 June 2008 Available online 24 June 2008
While proper brain function requires the complex interaction of chemicals perpetually occupied in purposeful biochemistry, it is well established that certain toxic substances have the potential to disrupt normal brain physiology and to impair neurological homeostasis. As well as headache, cognitive dysfunction, memory disturbance, and other neurological signs and symptoms, disruption of brain function may also manifest as subtle or overt alteration in thoughts, moods, or behaviors. Over the last four decades, there has been the unprecedented development and release of a swelling repertoire of potentially toxic chemicals which have the capability to inflict brain compromise. Although the ability of xenobiotics to induce clinical illness is well established, the expanding public health problem of widespread toxicant exposure in the general population is a relatively new phenomenon that has spawned escalating concern. The emerging area of clinical care involving the assessment and management of accrued toxic substances such as heavy metals, pesticides, plasticizers and other endocrine disrupting or neurotoxic compounds has not been fully appreciated by the medical community and has yet to be incorporated into the clinical practice of many consultants or primary care practitioners. ß 2008 Elsevier Inc. All rights reserved.
Keywords: Environmental medicine Human exposure assessment Neurotoxicology Toxicology Depression Mental illness
All great truths begin as blasphemies. (George Bernard Shaw)
1. Introduction For patients presenting with myriad forms of psychiatric illness including bipolar disease, depression, personality disorders, obsessive-compulsive affliction, and various psychotic maladies, the unfolding medical approach usually follows a consistent algorithm: clinical assessment, perhaps some laboratory investigations, followed by drug treatment with or without psychotherapy and social support. Although psychosocial triggers are often identified, many believe that the underlying etiology of most psychiatric infirmity is a ‘chemical imbalance’ ultimately resulting from genetic predestination; the best available therapeutic intervention is thus believed to lie with psychopharmacologic measures designed to modify the pathological biochemistry resulting from aberrant DNA. Increasing evidence, however, has begun to suggest that commonly overlooked determinants may account for the anguished psyche in some ‘mentally ill’ individuals (Dumont, 1989; Eicher and Avery, 2005). The worldwide prevalence of mental health affliction accounts for staggering rates of suffering and disability. While mental illness was previously thought to result from disordered lives, * Tel.: +1 780 450 3504; fax: +1 780 490 1803. E-mail address: [email protected]. 0161-813X/$ – see front matter ß 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.neuro.2008.06.005
troubled emotions and psychological problems, neuropsychiatric disease is increasingly recognized to be the consequence of disordered brain biochemistry, perhaps precipitated or aggravated by adverse life events. Recent research in biological psychiatry, however, has explored the question: ‘What causes disordered brain chemistry?’ Although various hypotheses have been explored (Middleton et al., 2007; Panksepp, 2006), increasing attention has focused on the field of neurotoxicology (Eicher and Avery, 2005). The ever-expanding industrial and technological world has witnessed the unprecedented release of a swelling repertoire of solvents, pesticides, heavy metals, as well as other endocrinedisrupting and neurotoxic agents which have potential to inflict brain compromise. A recent paper explores how common brain toxicants induce varying degrees of ‘‘an encephalopathic state directly by affecting the brain itself or indirectly by compromising the brain’s supportive systems’’ (Eicher and Avery, 2005), such as the endocrine system. In another paper entitled ‘‘Psychotoxicology—the return of the mad hatter,’’ the psychiatrist-author alleges that providers of mental health care ‘‘have not been attentive to the huge and expanding capacity of neurotoxic substances to induce symptoms of emotional and behavioral dysfunction’’ (Dumont, 1989) and that ‘‘patients are being poisoned and rendered psychiatrically disabled as a result of a disregard for occupational and environmental health’’ (Dumont, 1989). The case of a despondent patient with unremitting mental anguish is presented for consideration.
1148
S.J. Genuis / NeuroToxicology 29 (2008) 1147–1149
2. Case history As well as dizziness, migrating joint pain and chronic fatigue, this 38-year-old disabled peace officer presented with a 4-year history of severe depression, inordinate anger, insomnia, and intrusive thoughts regarding self-mutilation. After seeking help from a psychologist, a family physician, a neurologist and three psychiatrists, the patient was distressed with the lack of improvement despite interventions including numerous antidepressants, antipsychotics, lithium and ECT. With no apparent response to therapy, the patient was plagued by ongoing suicidal ideation as his prognosis was considered poor. Subsequent exposure assessment, however, revealed high levels of mercury. In keeping with recommended interventions (Lindh et al., 2002; Wojcik et al., 2006) several mercury-containing dental amalgams (the greatest source of mercury body burden in the nonoccupationally exposed population, according to the WHO (Bigham et al., 2002)) were removed followed by interventions to detoxify accumulated tissue mercury. His condition progressively improved and after 24 months, all joint symptoms, neurological complaints and psychiatric problems had resolved. 3. Discussion In the lay and medical press, evidence linking brain malfunction to adverse exposure has received considerable attention. Various infectious agents have been correlated with mental health afflictions. Research for example, suggests that psychotic illness in some patients may represent the sequelae of a prenatal or perinatal exposure to maternal herpes simplex virus (Buka et al., 2001). Much attention has also been given to the evolving story of PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections)—a debilitating constellation of mental health problems resulting from exposure to streptococcus (Swedo et al., 1998). Other microbial-mental health correlates include the purported link between Borna Disease Virus and severe depression (Bode and Ludwig, 2003), as well as mold exposures and mental dysfunction (Genuis, 2007). Metabolic exposures including hyperinsulinemia (Pan et al., 2008; Timonen et al., 2007) and intense electromagnetic field exposure (Genuis, 2008a; Sobel et al., 1996; van Wijngaarden et al., 2000) have also been positively associated with psychiatric disease in some cases. In addition to biological, metabolic and electromagnetic exposures, toxic chemicals have long been recognized as potential sources of psychiatric affliction. Early in the first millennium, rates of mental compromise and infertility were high among Roman aristocracy. As both the conduits for drinking water and vessels for imbibing wine were made of lead, some historians suggest that lead poisoning contributed to declining mental function among the ruling elite and the subsequent demise of the Roman Empire (Nriagu, 1983). Arguably the most influential classical composer of all time, Ludwig van Beethoven struggled to endure a turmoiled existence in his later years suffering from both acquired deafness and erratic episodes of mania and depression (Hershman and Lieb, 1998) As he crashed and banged his piano, dousing his head with copious amounts of water while scribbling his melodies and harmonies on walls and shutters, this gifted man is often thought to have contracted syphilis as the source of his psycho-neurological suffering. According to recent study and analysis of Beethoven’s hair and bone, however, bioaccumulation of lead appears to be a prime determinant of his disordered behavior and tragic disability (Weiss, 2005). The famous painter Vincent Van Gogh is reported to have displayed erratic and disordered behavior, including his own suicide. Some believe his routine conusmption of lead-based paint
chips contributed to his affliction and that the halo-like circles around objects portrayed in his famous work ‘The Starry Night’ are the result of retinal swelling—a common symptom of severe lead intoxication (Arnold, 1992). The enduring influence of this heavy metal is evident as recent research suggests that childhood lead exposure may be a significant determinant of contemporary criminal activity (Nevin, 2007). Exposure to another toxic metal, mercury, has also been correlated with brain dysfunction. ‘‘Mad Hatter Syndrome’’ was a phrase coined to describe the various symptoms including irritability, anxiety, depression and various personality changes that arose in individuals occupationally exposed to mercury (Fraser-Moodie, 2003). In the production of felt hats, an industry that traces back to the mid-17th century in France, a mercury compound was applied to animal fur—a process which involved the licking of brushes doused with this toxic heavy metal. The laborers frequently manifested a constellation of psychiatric symptoms earning them the dubious designation: mad hatters. More recently, the front page of the Wall Street Journal unveiled a story about the travails of a young student afflicted with neurologic dysfunction—after the case baffled various physicians, parental prompting followed by laboratory testing confirmed mercury intoxication (Waldman, 2005). As well as commonly known neurotoxicants including lead and mercury, recent medical literature discusses common environmental exposures such as certain pesticides (Beseler and Stallones, 2003; Stallones and Beseler, 2002), industrial solvents (Ng et al., 1992) and mold byproducts (Genuis, 2007) which may affect neuroendocrine function resulting in depression, memory problems, sleep disturbance, concentration impairment, and various other difficulties. Furthermore, various industrial chemicals have potential to seriously disrupt neurological development (Grandjean and Landrigan, 2006) while lifelong sexual behavior may be influenced by exposure to toxic chemicals at critical phases of development (Dorner et al., 2001; Rapp, 2004). Is toxicant exposure a common event in the 21st century? Rather than isolated occurrences, recent Canadian and American population studies demonstrate routine toxicant bioaccumulation in adults and children (Centers for Disease Control and Prevention, 2005; Neumann et al., 2006) and cord-blood research suggests widespread in-utero contamination from vertical transmission (Environmental Working Group, 2005). Furthermore, contact with toxicants occurring many years prior may continue to alter thinking and behavior as some chemicals including lead remain stockpiled within tissues (Nevin, 2007), even in the absence of ongoing exposure. The troubling trend of widespread xenobiotic bioaccumulation has ignited increased exploration of the pathogenetic mechanisms of toxicant-induced clinical illness. Crudely stated, the human organism is a collection of chemicals perpetually occupied in purposeful biochemical reactions. Accordingly, coordinated brain activity is reliant upon an intricate and precise network of interacting infinitesimal biochemical compounds including neurotransmitters, nutrients, and hormones. Various toxic chemical substances – whether consumed in tainted foodstuffs, inhaled, applied to skin, vertically transmitted or introduced into the body by surgery, dental work, or injection – have the potential to disturb the finely tuned network responsible for healthy brain function. Thinking is just as physiological as digestion, and emotions are just as biological as pain. While sick stomachs may regurgitate or sick lungs may induce cough, the language of a disordered brain includes impaired thinking, intellectual compromise, failed memory and altered moods (Feldman, 1999)—manifestations frequently indicative of compromised physiology rather than compromised psychology. In the face of chemical or other toxic insult to the brain, common
S.J. Genuis / NeuroToxicology 29 (2008) 1147–1149
psychiatric interventions including psychotherapy and psychopharmacology may assist in coping but do not address etiology nor restore optimal mental health. Adverse exposure is only one potential determinant of psychiatric disorder; a comprehensive approach to mental illness includes assessment of physical, emotional, social and spiritual factors. Adverse exposure assessment, however, remains largely ignored or rejected for two reasons. First, demonstrating cause and effect between exposure and illness is difficult as slow bioaccumulation of chronic low-level exposures often leads to vague and insidious symptoms in the early stages. As individual response to specific toxins involves a kaleidoscope of factors including genetic vulnerability, psychological status, individual physiology, and a varying multiplicity of exposures, outcomes are frequently nonspecific and the clinical index of suspicion often remains low. Second, there has been insufficient attention to environmental health and human exposure assessment in medical education; physicians are generally not equipped to assess and manage chemical exposures. 4. Conclusion As state-of-the-art medicine is a work in progress, prevailing assumptions about medical dogma need to be continuously challenged, including the common notion that mental illness is generally the result of genetic predestination. Recent study suggests that rather than genomic fatalism, illness is the result of the complex interaction between the fixed genome and the modifiable environment of the individual (Genuis, 2008b; Office of Genomics and Disease Prevention, 2000). In combination with vulnerable DNA, the etiology or trigger for many diagnoses originates in practices and conditions injurious to the human organism. Although manifest symptoms may apparently be emotional or behavioral in their presentation, the underlying cause of some mental health afflictions is patho-physiological rather than patho-psychological. Mood and emotion are biological processes dependent on complex biochemical functioning—disordered mood and emotion often result from disordered biochemistry, a potential consequence of toxicant exposure. In an era marked by ubiquitous synthetic chemicals and an unprecedented proclivity to toxicant exposures, it is important that health practitioners comprehensively consider and explore toxicological factors when encountering patients with mental health complaints (Genuis, 2008c). 5. Conflict of interest None declared. References Arnold WN. Vincent Van Gogh: chemicals, crises, and creativity. Boston: Birkha˜user; 1992 pp. 164–192. Beseler C, Stallones L. Safety practices, neurological symptoms, and pesticide poisoning. J Occup Environ Med 2003;45:1079–86. Bigham M, Copes R, Srour L. Exposure to thimerosal in vaccines used in Canadian infant immunization programs, with respect to risk of neurodevelopmental disorders. Can Commun Dis Rep 2002;28:69–80. Bode L, Ludwig H. Borna disease virus infection, a human mental-health risk. Clin Microbiol Rev 2003;16:534–45. Buka SL, Tsuang MT, Torrey EF, Klebanoff MA, Bernstein D, Yolken RH. Maternal infections and subsequent psychosis among offspring. Arch Gen Psychiatry 2001;58:1032–7.
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Centers for Disease Control and Prevention. Department of Health and Human Services. Third National Report on Human Exposure to Environmental Chemicals. NCEH Pub. No. 05-0570 Atlanta, Georgia; July 2005: p. 1–475. Dorner G, Gotz F, Rohde W, Plagemann A, Lindner R, Peters H, et al. Genetic and epigenetic effects on sexual brain organization mediated by sex hormones. Neuro Endocrinol Lett 2001;22:403–9. Dumont MP. Psychotoxicology: the return of the mad hatter. Soc Sci Med 1989;29: 1077–82. Eicher T, Avery E. Toxic encephalopathies. Neurol Clin 2005;23:353–76. Environmental Working Group. Body burden-the pollution in newborns: a benchmark investigation of industrial chemicals, pollutants and pesticides in umbilical cord blood (Executive Summary); July 14, 2005. http://ewg.org/reports/bodyburden2/ execsumm.php. [Accessed September 16, 2005] Feldman RG. Approach to diagnosis. occupational and environmental neurotoxicology. Philadelphia: Lippincott-Raven; 1999 pp. 189–317. Fraser-Moodie A. Mad as a hatter. Emerg Med J 2003;20:568. Genuis SJ. Clinical medicine and the budding science of mold exposure. Eur J Intern Med 2007;18:516–23. Genuis SJ. Fielding a current idea: exploring the public health impact of electromagnetic radiation. Public Health 2008a;122:113–24. Genuis SJ. Our genes are not our destiny: incorporating molecular medicine into clinical practice. J Eval Clin Pract 2008b;14:94–102. Genuis SJ. Medical practice and community health care in the 21st century: a time of change. Public Health 2008c;122:671–80. Grandjean P, Landrigan PJ. Developmental neurotoxicity of industrial chemicals. Lancet 2006;368:2167–78. Hershman DJ, Lieb J. Manic depression and creativity. Amherst, NY: Prometheus; 1998 pp. 12–225. Lindh U, Hudecek R, Danersund A, Eriksson S, Lindvall A. Removal of dental amalgam and other metal alloys supported by antioxidant therapy alleviates symptoms and improves quality of life in patients with amalgam-associated ill health. Neuroendocrinol Lett 2002;23:459–82. Middleton FA, Rosenow C, Vailaya A, Kuchinsky A, Pato MT, Pato CN. Integrating genetic, functional genomic, and bioinformatics data in a systems biology approach to complex diseases: application to schizophrenia. Methods Mol Biol 2007;401:337–64. Neumann J, Winterton S, Lu J, Roja DED. Polluted children, toxic nation: a report on pollution in Canadian families; Published June 2006. [Accessed October 8, 2006] at http://www.environmentaldefence.ca/reports/toxicnationFamily.htm. Nevin R. Understanding international crime trends: the legacy of preschool lead exposure. Environ Res 2007;104:315–36. Ng T, Lim L, Win K. An investigation of solvent-induced neuro-psychiatric disorders in spray painters. Ann Acad Med Singapore 1992;21:797–803. Nriagu JO. Lead and lead poisoning in antiquity. New York: John Wiley; 1983pp. 1–437. Office of Genomics and Disease Prevention. Centers for Disease Control and Prevention. Department of Health and Human Services 2000. Gene-Environment Interaction Fact Sheet. Pan A, Ye X, Franco OH, Li H, Yu Z, Zou S, et al. Insulin resistance and depressive symptoms in middle-aged and elderly Chinese: findings from the Nutrition and Health of Aging Population in China Study. J Affect Disord 2008;109: 75–82. Panksepp J. Emotional endophenotypes in evolutionary psychiatry. Prog Neuropsychopharmacol Biol Psychiatry 2006;30:774–84. Rapp DJ. Our toxic world: a wake up call-chemicals damage your body, brain, behavior and sex. Buffalo: Environmental Medical Research Foundation; 2004pp. 142–194. Sobel E, Dunn M, Davanipour Z, Qian Z, Chui HC. Elevated risk of Alzheimer’s disease among workers with likely electromagnetic field exposure. Neurology 1996;47: 1477–81. Stallones L, Beseler C. Pesticide illness, farm practices, and neurological symptoms among farm residents in Colorado. Environ Res 2002;90:89–97. Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry 1998;155:264–71. Timonen M, Salmenkaita I, Jokelainen J, Laakso M, Harkonen P, Koskela P, et al. Insulin resistance and depressive symptoms in young adult males: findings from Finnish military conscripts. Psychosom Med 2007;69:723–8. van Wijngaarden E, Savitz DA, Kleckner RC, Cai J, Loomis D. Exposure to electromagnetic fields and suicide among electric utility workers: a nested case-control study. Occup Environ Med 2000;57:258–63. Waldman P. Mercury and tuna: U.S. advice leaves lots of questions. Wall Street Journal (August 1):2005;A1. Weiss R. Study concludes Beethoven died from lead poisoning. Washington Post. December 6, 2005, p. A08. Wojcik DP, Godfrey ME, Christie D, Haley BE. Mercury toxicity presenting as chronic fatigue, memory impairment and depression: diagnosis, treatment, susceptibility, and outcomes in a New Zealand general practice setting (1994–2006). Neuro Endocrinol Lett 2006;27:415–23.
Contents lists available at ScienceDirect
NeuroToxicology
Commentary
Toxic causes of mental illness are overlooked Stephen J. Genuis * University of Alberta, Faculty of Medicine, 2935-66 Street, Edmonton, Alberta, Canada T6K 4C1
A R T I C L E I N F O
A B S T R A C T
Article history: Received 3 May 2008 Accepted 13 June 2008 Available online 24 June 2008
While proper brain function requires the complex interaction of chemicals perpetually occupied in purposeful biochemistry, it is well established that certain toxic substances have the potential to disrupt normal brain physiology and to impair neurological homeostasis. As well as headache, cognitive dysfunction, memory disturbance, and other neurological signs and symptoms, disruption of brain function may also manifest as subtle or overt alteration in thoughts, moods, or behaviors. Over the last four decades, there has been the unprecedented development and release of a swelling repertoire of potentially toxic chemicals which have the capability to inflict brain compromise. Although the ability of xenobiotics to induce clinical illness is well established, the expanding public health problem of widespread toxicant exposure in the general population is a relatively new phenomenon that has spawned escalating concern. The emerging area of clinical care involving the assessment and management of accrued toxic substances such as heavy metals, pesticides, plasticizers and other endocrine disrupting or neurotoxic compounds has not been fully appreciated by the medical community and has yet to be incorporated into the clinical practice of many consultants or primary care practitioners. ß 2008 Elsevier Inc. All rights reserved.
Keywords: Environmental medicine Human exposure assessment Neurotoxicology Toxicology Depression Mental illness
All great truths begin as blasphemies. (George Bernard Shaw)
1. Introduction For patients presenting with myriad forms of psychiatric illness including bipolar disease, depression, personality disorders, obsessive-compulsive affliction, and various psychotic maladies, the unfolding medical approach usually follows a consistent algorithm: clinical assessment, perhaps some laboratory investigations, followed by drug treatment with or without psychotherapy and social support. Although psychosocial triggers are often identified, many believe that the underlying etiology of most psychiatric infirmity is a ‘chemical imbalance’ ultimately resulting from genetic predestination; the best available therapeutic intervention is thus believed to lie with psychopharmacologic measures designed to modify the pathological biochemistry resulting from aberrant DNA. Increasing evidence, however, has begun to suggest that commonly overlooked determinants may account for the anguished psyche in some ‘mentally ill’ individuals (Dumont, 1989; Eicher and Avery, 2005). The worldwide prevalence of mental health affliction accounts for staggering rates of suffering and disability. While mental illness was previously thought to result from disordered lives, * Tel.: +1 780 450 3504; fax: +1 780 490 1803. E-mail address: [email protected]. 0161-813X/$ – see front matter ß 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.neuro.2008.06.005
troubled emotions and psychological problems, neuropsychiatric disease is increasingly recognized to be the consequence of disordered brain biochemistry, perhaps precipitated or aggravated by adverse life events. Recent research in biological psychiatry, however, has explored the question: ‘What causes disordered brain chemistry?’ Although various hypotheses have been explored (Middleton et al., 2007; Panksepp, 2006), increasing attention has focused on the field of neurotoxicology (Eicher and Avery, 2005). The ever-expanding industrial and technological world has witnessed the unprecedented release of a swelling repertoire of solvents, pesticides, heavy metals, as well as other endocrinedisrupting and neurotoxic agents which have potential to inflict brain compromise. A recent paper explores how common brain toxicants induce varying degrees of ‘‘an encephalopathic state directly by affecting the brain itself or indirectly by compromising the brain’s supportive systems’’ (Eicher and Avery, 2005), such as the endocrine system. In another paper entitled ‘‘Psychotoxicology—the return of the mad hatter,’’ the psychiatrist-author alleges that providers of mental health care ‘‘have not been attentive to the huge and expanding capacity of neurotoxic substances to induce symptoms of emotional and behavioral dysfunction’’ (Dumont, 1989) and that ‘‘patients are being poisoned and rendered psychiatrically disabled as a result of a disregard for occupational and environmental health’’ (Dumont, 1989). The case of a despondent patient with unremitting mental anguish is presented for consideration.
1148
S.J. Genuis / NeuroToxicology 29 (2008) 1147–1149
2. Case history As well as dizziness, migrating joint pain and chronic fatigue, this 38-year-old disabled peace officer presented with a 4-year history of severe depression, inordinate anger, insomnia, and intrusive thoughts regarding self-mutilation. After seeking help from a psychologist, a family physician, a neurologist and three psychiatrists, the patient was distressed with the lack of improvement despite interventions including numerous antidepressants, antipsychotics, lithium and ECT. With no apparent response to therapy, the patient was plagued by ongoing suicidal ideation as his prognosis was considered poor. Subsequent exposure assessment, however, revealed high levels of mercury. In keeping with recommended interventions (Lindh et al., 2002; Wojcik et al., 2006) several mercury-containing dental amalgams (the greatest source of mercury body burden in the nonoccupationally exposed population, according to the WHO (Bigham et al., 2002)) were removed followed by interventions to detoxify accumulated tissue mercury. His condition progressively improved and after 24 months, all joint symptoms, neurological complaints and psychiatric problems had resolved. 3. Discussion In the lay and medical press, evidence linking brain malfunction to adverse exposure has received considerable attention. Various infectious agents have been correlated with mental health afflictions. Research for example, suggests that psychotic illness in some patients may represent the sequelae of a prenatal or perinatal exposure to maternal herpes simplex virus (Buka et al., 2001). Much attention has also been given to the evolving story of PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections)—a debilitating constellation of mental health problems resulting from exposure to streptococcus (Swedo et al., 1998). Other microbial-mental health correlates include the purported link between Borna Disease Virus and severe depression (Bode and Ludwig, 2003), as well as mold exposures and mental dysfunction (Genuis, 2007). Metabolic exposures including hyperinsulinemia (Pan et al., 2008; Timonen et al., 2007) and intense electromagnetic field exposure (Genuis, 2008a; Sobel et al., 1996; van Wijngaarden et al., 2000) have also been positively associated with psychiatric disease in some cases. In addition to biological, metabolic and electromagnetic exposures, toxic chemicals have long been recognized as potential sources of psychiatric affliction. Early in the first millennium, rates of mental compromise and infertility were high among Roman aristocracy. As both the conduits for drinking water and vessels for imbibing wine were made of lead, some historians suggest that lead poisoning contributed to declining mental function among the ruling elite and the subsequent demise of the Roman Empire (Nriagu, 1983). Arguably the most influential classical composer of all time, Ludwig van Beethoven struggled to endure a turmoiled existence in his later years suffering from both acquired deafness and erratic episodes of mania and depression (Hershman and Lieb, 1998) As he crashed and banged his piano, dousing his head with copious amounts of water while scribbling his melodies and harmonies on walls and shutters, this gifted man is often thought to have contracted syphilis as the source of his psycho-neurological suffering. According to recent study and analysis of Beethoven’s hair and bone, however, bioaccumulation of lead appears to be a prime determinant of his disordered behavior and tragic disability (Weiss, 2005). The famous painter Vincent Van Gogh is reported to have displayed erratic and disordered behavior, including his own suicide. Some believe his routine conusmption of lead-based paint
chips contributed to his affliction and that the halo-like circles around objects portrayed in his famous work ‘The Starry Night’ are the result of retinal swelling—a common symptom of severe lead intoxication (Arnold, 1992). The enduring influence of this heavy metal is evident as recent research suggests that childhood lead exposure may be a significant determinant of contemporary criminal activity (Nevin, 2007). Exposure to another toxic metal, mercury, has also been correlated with brain dysfunction. ‘‘Mad Hatter Syndrome’’ was a phrase coined to describe the various symptoms including irritability, anxiety, depression and various personality changes that arose in individuals occupationally exposed to mercury (Fraser-Moodie, 2003). In the production of felt hats, an industry that traces back to the mid-17th century in France, a mercury compound was applied to animal fur—a process which involved the licking of brushes doused with this toxic heavy metal. The laborers frequently manifested a constellation of psychiatric symptoms earning them the dubious designation: mad hatters. More recently, the front page of the Wall Street Journal unveiled a story about the travails of a young student afflicted with neurologic dysfunction—after the case baffled various physicians, parental prompting followed by laboratory testing confirmed mercury intoxication (Waldman, 2005). As well as commonly known neurotoxicants including lead and mercury, recent medical literature discusses common environmental exposures such as certain pesticides (Beseler and Stallones, 2003; Stallones and Beseler, 2002), industrial solvents (Ng et al., 1992) and mold byproducts (Genuis, 2007) which may affect neuroendocrine function resulting in depression, memory problems, sleep disturbance, concentration impairment, and various other difficulties. Furthermore, various industrial chemicals have potential to seriously disrupt neurological development (Grandjean and Landrigan, 2006) while lifelong sexual behavior may be influenced by exposure to toxic chemicals at critical phases of development (Dorner et al., 2001; Rapp, 2004). Is toxicant exposure a common event in the 21st century? Rather than isolated occurrences, recent Canadian and American population studies demonstrate routine toxicant bioaccumulation in adults and children (Centers for Disease Control and Prevention, 2005; Neumann et al., 2006) and cord-blood research suggests widespread in-utero contamination from vertical transmission (Environmental Working Group, 2005). Furthermore, contact with toxicants occurring many years prior may continue to alter thinking and behavior as some chemicals including lead remain stockpiled within tissues (Nevin, 2007), even in the absence of ongoing exposure. The troubling trend of widespread xenobiotic bioaccumulation has ignited increased exploration of the pathogenetic mechanisms of toxicant-induced clinical illness. Crudely stated, the human organism is a collection of chemicals perpetually occupied in purposeful biochemical reactions. Accordingly, coordinated brain activity is reliant upon an intricate and precise network of interacting infinitesimal biochemical compounds including neurotransmitters, nutrients, and hormones. Various toxic chemical substances – whether consumed in tainted foodstuffs, inhaled, applied to skin, vertically transmitted or introduced into the body by surgery, dental work, or injection – have the potential to disturb the finely tuned network responsible for healthy brain function. Thinking is just as physiological as digestion, and emotions are just as biological as pain. While sick stomachs may regurgitate or sick lungs may induce cough, the language of a disordered brain includes impaired thinking, intellectual compromise, failed memory and altered moods (Feldman, 1999)—manifestations frequently indicative of compromised physiology rather than compromised psychology. In the face of chemical or other toxic insult to the brain, common
S.J. Genuis / NeuroToxicology 29 (2008) 1147–1149
psychiatric interventions including psychotherapy and psychopharmacology may assist in coping but do not address etiology nor restore optimal mental health. Adverse exposure is only one potential determinant of psychiatric disorder; a comprehensive approach to mental illness includes assessment of physical, emotional, social and spiritual factors. Adverse exposure assessment, however, remains largely ignored or rejected for two reasons. First, demonstrating cause and effect between exposure and illness is difficult as slow bioaccumulation of chronic low-level exposures often leads to vague and insidious symptoms in the early stages. As individual response to specific toxins involves a kaleidoscope of factors including genetic vulnerability, psychological status, individual physiology, and a varying multiplicity of exposures, outcomes are frequently nonspecific and the clinical index of suspicion often remains low. Second, there has been insufficient attention to environmental health and human exposure assessment in medical education; physicians are generally not equipped to assess and manage chemical exposures. 4. Conclusion As state-of-the-art medicine is a work in progress, prevailing assumptions about medical dogma need to be continuously challenged, including the common notion that mental illness is generally the result of genetic predestination. Recent study suggests that rather than genomic fatalism, illness is the result of the complex interaction between the fixed genome and the modifiable environment of the individual (Genuis, 2008b; Office of Genomics and Disease Prevention, 2000). In combination with vulnerable DNA, the etiology or trigger for many diagnoses originates in practices and conditions injurious to the human organism. Although manifest symptoms may apparently be emotional or behavioral in their presentation, the underlying cause of some mental health afflictions is patho-physiological rather than patho-psychological. Mood and emotion are biological processes dependent on complex biochemical functioning—disordered mood and emotion often result from disordered biochemistry, a potential consequence of toxicant exposure. In an era marked by ubiquitous synthetic chemicals and an unprecedented proclivity to toxicant exposures, it is important that health practitioners comprehensively consider and explore toxicological factors when encountering patients with mental health complaints (Genuis, 2008c). 5. Conflict of interest None declared. References Arnold WN. Vincent Van Gogh: chemicals, crises, and creativity. Boston: Birkha˜user; 1992 pp. 164–192. Beseler C, Stallones L. Safety practices, neurological symptoms, and pesticide poisoning. J Occup Environ Med 2003;45:1079–86. Bigham M, Copes R, Srour L. Exposure to thimerosal in vaccines used in Canadian infant immunization programs, with respect to risk of neurodevelopmental disorders. Can Commun Dis Rep 2002;28:69–80. Bode L, Ludwig H. Borna disease virus infection, a human mental-health risk. Clin Microbiol Rev 2003;16:534–45. Buka SL, Tsuang MT, Torrey EF, Klebanoff MA, Bernstein D, Yolken RH. Maternal infections and subsequent psychosis among offspring. Arch Gen Psychiatry 2001;58:1032–7.
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