Air Pollution and Mental Health �������������������������������������������������������

Suicide is one of the most complicated mental health issues� The World Health Organization (WHO) estimates that approximately one million people die by suicide each year (WHO, 2005)� The term “suicidal behaviors” refers to suicide attempt and completed suicide (i�e�, death from suicide), and it has been known that suicide attempt and completed suicide have divergent characteristics� Both are prevalent in young adults, but men are at higher risk for completed suicide, whereas women are more likely to attempt suicide� In general, suicide attempters use less lethal methods such as poisoning while suicide completers harness lethal methods such as hanging and firearms� Suicide is involved in a variety of factors encompassing mental disorders (depression, bipolar disorder, schizophrenia, and anxiety disorders), environmental circumstances (access to means for suicide, chronic stress, and stressful life events), and historical factors (family history of suicide and mental disorders)� In addition to these individual factors, ecological factors such as unemployment rate and celebrity suicide have been reported in the literature, but environmental factors, especially air pollution, have been relatively marginalized� So far, only a small number of investigations on the relationship between environmental pollution and suicidal behaviors were conducted by researchers in several countries�

Szyszkowicz et al� (2010) reported on the relationship between carbon monoxide (CO), nitrogen dioxide (NO2), and particulate with the diameter of 10 μm or less (PM10) exposure and emergency department visits for suicide attempt in Vancouver, Canada� With time-series data, the authors harnessed the generalized linear mixed models on clusters, in which days of the same day of the week in the same month and year were bracketed� As the authors described, the number of emergency department visits for suicide attempt was low and suicide mortality might have been more appropriate�

In the Republic of Korea, deaths from suicide soared in early 2000s; thus, our research team took notice of the remarkable increase in suicide mortality in the middle-aged and elderly, indicating a rising prevalence of late-onset depression� In particular, the middle-aged and elderly with cardiovascular disease might be at risk of late-onset depression through the development of vascular depression� As many studies reported, cardiovascular disease such as myocardial infarction is associated with ambient air pollution through the mechanism of systemic inflammation� We therefore hypothesized that air pollution had a short-term effect on suicide, especially among those with underlying cardiovascular disease (Kim et al�, 2010)� We obtained particulate matter data from automatic monitoring systems of seven big cities in the Republic of Korea and data from suicide completers in 2004� To identify underlying diseases, data of suicide completers were merged with medical care utilization data based on their national health insurance claims� Using a time-stratified

case-crossover study design, we found a 9�1% greater risk of suicide due to PM10 exposure (interquartile range 27�59 μg/m3), and an 18�9% greater risk in patients with preexisting cardiovascular disease�

In Taiwan, Yang et al� (2011) suggested that the pattern of rising suicide mortality was predicted by increasing PM10� Sulfur dioxide (SO2) and ozone (O3) also increased the risk for suicide with a longer secular trend� After conducting empirical mode decomposition for decomposing time-series data of suicide mortality and for detrending air pollution, weather, and unemployment data, the authors performed multiple linear regression analysis� Interestingly, this study made a distinction between violent suicides (e�g�, hanging and jumping from heights) and nonviolent suicides (e�g�, poisoning) and showed that air pollution contributed more to nonviolent suicides than violent suicides� As suggested by this study, the incidence of suicide is known to be affected by meteorological variables� However, meteorological factors vary across geographical regions, where various characteristics of population, including demographic distribution and cultural aspects, may lead to inconsistent results� Comparing the characteristics of suicide between Asian and Western countries suggests that Asians are more likely to commit impulsive suicidal behaviors (WHO, 2009)� Impulsiveness of suicidal behaviors may affect the choice of suicide methods, which more likely consist of easier-access means� Because of these complex aspects of suicide, it might be inevitable to see a discrepancy between results from different countries� In the United States, Bakian et al� (2015) reported associations between exposure to NO2 and PM2�5 and suicide mortality in Salt Lake County, Utah, in 2000−2010� Dissimilar to the Taiwanese study, this study presented the significant association only for violent suicides� The study by Bakian et al� categorized drug overdose, drowning, poisoning, and gas into nonviolent suicides, while the study by Yang et al� included jumping from heights in the violent suicides� It is possible that jumping from heights includes drowning, so the different categorization might have influenced this discrepancy� However, it is difficult to exclude the possibility of racial and cultural differences� Thus, a result from a city or a country may be difficult to be generalized to other populations; therefore, there is a need of more replication studies in various regions�

The link between air pollution and suicide behaviors suggested by above studies does not secure a causal relationship� Moreover, these studies focused on the shortterm effect of air pollution� Therefore, it would be more adequate to describe that polluted air “triggers” suicidal behaviors in individuals with predisposing factors for suicidal behaviors� Despite the criticism that the finding is just a statistical inference when considering the complexity of suicide mechanism, these air pollution studies could underscore the adverse effects of ambient particulate matter on the brain in that they might be able to induce suicidal behaviors�

It is estimated that almost 350 million people are suffering from depression globally, according to the WHO statement (WHO, 2012)� Unipolar depressive disorder, which was the third leading cause of disease burden in 2004, is expected to become the

primary cause of disease burden worldwide by 2030 (WHO, 2008)� Depression or depressive disorder is characterized by depressed mood, decreased interest, fatigue, guilt/worthlessness, suicidal ideation, decreased ability to concentrate, and changes in weight, sleep, and activity� Depression can present in various ways: major depression, psychotic depression (occurring with psychotic symptoms), seasonal depression, and postpartum depression� According to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), when one of the first two symptoms are persistent for more than 2 weeks and at least five of the nine symptoms above are present nearly every day, a patient is diagnosed with major depressive disorder; additionally, patients likely have social, occupational, and educational impairments� The biological mechanism of depression has known to be mainly related to a decrease in neurotransmitters (e�g�, serotonin, norepinephrine, dopamine, and gamma-aminobutyric acid)� The dysregulation of the HPA axis is also involved in the development of depression because it may lead to sustained high levels of stress hormones like the corticotropin-releasing hormone, which is toxic to various brain structures such as the hippocampus�

Szyszkowicz et al� (2009) analyzed 27,047 emergency department visits for depression in six cities in Canada� The generalized linear mixed model with Poisson distribution was used, with temperature and relative humidity as covariates� CO and NO2 were associated with increased daily emergency department visits for depression in the warm period (April-September)� For PM10, the largest increase, 7�2% (95% confidence interval [CI]: 3�0%–11�6%) per 19�4 µg/m3, was observed in the cold period (October-March)�

In the Republic of Korea, Lim et al� (2012) assessed 537 elders for depressive symptoms using the Korean version of the Geriatric Depression Scale-Short Form (SGDS-K)� In the results from generalized estimating equations (GEE) analyses, SGDS-K scores were positively associated with interquartile range increases in the 3-day moving average concentration of PM10 (17�0%; 95% CI: 4�9%–30�5%), the 0-7day moving average of NO2 (32�8%; 95% CI: 12�6%–56�6%), and the 3-day moving average of O3 (43�7%; 95% CI: 11�5%–85�2%)�

Similar to the study by Lim et al� in the Republic of Korea, Wang et al� (2014) assessed depressive symptoms among participants in the Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly of Boston (MOBILIZE Boston) study using another depression screening tool, the Revised Center for Epidemiological Studies Depression Scale (CESD-R)� They used residential proximity to the nearest major road as a proxy of long-term exposure to traffic-related pollution and assessed short-term exposure to PM2�5, sulfates, black carbon, ultrafine particles, O3, CO, NO, and NO2 (2-week averages before evaluation)� GEE was used to estimate the odds ratio of a CESD-R score ≥ 16 associated with exposure� There was no evidence of a positive association between depressive symptoms and longterm exposure to traffic pollution or short-term exposure to ambient air pollution� The authors discussed that the discrepancy with the Korean study might have been derived from the different depression screening tool and less severe air pollution in Boston� In addition, the prevalence of depressive symptoms in their samples was less than 10%, which limited the statistical power of the study�

Following our suicide research, we targeted mental disorders, which are one of the risk factors for suicide� Among mental disorders, depression is regarded as the

major mental disorder leading to suicidal behavior� Moreover, considering the possible biological mechanism of “vascular depression” suggested by our previous study on suicide, it seemed plausible that air pollution could induce depression� Thus, we conducted a time-stratified case-crossover study revealing the association between air pollution and depression (Cho et al�, 2014)�

Although a previous Canadian study used emergency department data, one major question was how to define “depression” and what kind of data could be used in our setting when designing our study� Because the Republic of Korea adopted the system of national health insurance, researchers can obtain the information on medical care utilization from national health insurance claims data through the Health Insurance Review and Assessment (HIRA)� The HIRA data contain the date of visit, the code of diagnosis based on the International Classification of Diseases 10th revision (ICD10), clinic or hospital code, the duration of care, and the type of visit (outpatient, emergency department visit, and inpatient)� In this study, we aimed to investigate the short-term effect of air pollution on the occurrence of depressive symptoms� In this context, outpatient and inpatient data were deemed to be inappropriate because the data included scheduled visits, in which we could not ascertain whether a depressive symptom occurred on the date of a patient’s visit� Therefore, the most reasonable option was emergency department visit data, which can moderately reflect time and place when depressive symptoms started� Although there was a concern that depressive patients might rarely visit emergency departments, nearly 5000 cases of depressive episode (F32) were observed during the 5-year study period in Seoul�

In the results of the conditional logistic regression, SO2, PM10, NO2, and CO were positively associated with emergency department visits for depressive episode: the maximum risk was observed in the distributed lag 0−3 model for PM10 (odds ratio, 1�120; 95% CI: 1�067−1�176)� Interestingly, O3 did not show any significance, which might result from the fact that O3 is a secondary air pollutant generated from primary air pollutants such as NO2 via photochemical reaction� Regarding this notion, there is a possibility that the primary air pollutants might trigger depressive symptoms before O3 level starts to rise�

This single city study had several limitations, one of which was that we used data only from Seoul� Seoul is the capital of the Republic of Korea and has higher air pollution levels compared with other cities� This raises the question if the association between air pollution and depression might exist only in a city with severe air pollution� To look into this possibility of threshold, we illustrated curve graphs showing the risk estimates according to air pollution levels� It seemed that there was no significant threshold, suggesting that the effect of air pollution on depression might be found even in a city with a low level of air pollution�

In our previous study on suicide, we suggested a higher risk in individuals with preexisting cardiovascular illness� In this study, in addition to cardiovascular disease, the most interesting finding was a significantly higher risk for emergency department visits for depressive episode in individuals with underlying diabetes mellitus or asthma� Regarding this finding, we hypothesized that air pollution has an interactive effect on neuro-psycho-endocrine-immune connections via an inflammatory process: air pollution might function as an effect modifier in the bidirectional associations of depression with diabetes (endocrine disease) or allergic asthma (immune disease)� This speculation

is consistent with the finding of chronic obstructive pulmonary disease, without any significant results� However, we could not obtain information on prescribed medication such as steroids in the setting of this study, so further research is required� Nonetheless, the findings of this research indicated the population potentially susceptible to air pollution in terms of their mental health, which may have public health implications�

As mentioned earlier, the biological mechanism of air pollution effects on suicide and depression involves neuroinflammation via systemic inflammation� There have been numerous animal experiments showing the process that can affect brain regions, such as the amygdala, and that can result in changes in levels of neurotransmitters such as dopamine and serotonin (Gonzalez-Pina and Paz, 1997)� Together with depression, anxiety is related to these neurotransmitters and brain regions that may be affected by air pollution, and depression and anxiety share a common pathophysiology� Nonetheless, the effect of ambient air pollution on anxiety has been little investigated� Thus, we performed a time-series study to identify the association (Cho et al�, 2015) but encountered the first question about how to define anxiety� Anxiety disorders include phobic anxiety, in which the symptom trigger factor is situational and specific; thus, if we encompassed all anxiety symptoms, we would observe nothing significant� Therefore, we focused on nonspecific and spontaneous anxiety, which is a major feature of panic disorder, and used emergency department visit data� Although there were only 2320 cases of panic disorder in emergency department visits in Seoul over 5 years, a slight but significant increased risk was observed in our time-series study� Interestingly, the significant association was found only for O3� Previous occupational studies have reported the occurrences of panic symptom in workers dealing with organic solvents, and these authors suggested that the major route of exposure was inhalation� According to the Haagen-Smit theory, O3 can be generated secondly by photochemical reaction with primary pollutants such as volatile organic compounds (VOCs)� Collectively, the association of panic disorder with O3 exposure suggests that further measurement of VOCs would be helpful to examine this speculation� Nonetheless, the association between O3 exposure and panic disorder seems biologically plausible according to an animal study suggesting that O3 induces strong local inflammation in the lungs, which can reach the brain via the vagus nerve, indicating the potential effect of O3 on the ANS� This consecutive process includes the involvement of the nucleus tractus solitarius, which is a central chemoreceptor and respiratory center, in the medulla oblongata� If this region is affected, the respiratory center can be erroneously activated, causing respiratory symptoms such as hyperventilation and shortness of breath� According to the false suffocation alarm theory, this mechanism plays a role in the development of panic disorder with respiratory symptoms� Panic disorder with respiratory symptoms, as one of the subtypes of panic disorder, is more likely to induce spontaneous attacks and is distinctive from panic disorder without respiratory symptoms in terms of characteristics� Our study targeted spontaneous development of panic symptoms; thus, the possible mechanism we suggested was consistent with our finding that the increased risks remained significant only in women, who are more likely to suffer from the respiratory subtype of panic disorder�

The most questionable aspect is the interactive effect of temperature on the relationship between O3 and panic disorder� After stratification of season, we found that the risks were higher in spring and summer and lower in autumn and winter� This might be related to higher average temperature and ambient O3 concentrations in spring and summer compared with the other seasons� Thus, we assumed that there could be a threshold of O3 concentration that can trigger panic disorder and found a rough value through further analysis� There might be a synergistic effect of temperature and O3 exposure, or temperature itself might be associated with panic disorder, so further studies would be required� Although many epidemiological studies on the effect of air pollution on the brain have suggested the biological mechanism of neuroinflammation in the CNS, this study highlighted the O3 effect on the ANS, leading to the development of panic symptoms� Additional nervous diseases can be related to the effect of air pollution on the ANS, which deserve further investigations�

While our study focused on the short-term effect of ambient O3 exposure on nonphobic anxiety, Power et al� (2015) suggested a long-term effect of PM2�5 exposure on high symptoms of phobic anxiety� Among 71,271 women registered in the Nurses’ Health Study, subjects with the phobic anxiety subscale of the Crown-Crisp index score ≥ 6 were considered as having high symptoms of anxiety (15%)� Having high anxiety symptoms was associated with higher exposure to PM2�5; odds ratios were 1�12 (95% CI: 1�06-1�19) and 1�15 (95% CI: 1�06-1�26) for the previous 1-month and 12-month exposure periods, respectively�

Despite a growing body of literature, how air pollutants contribute to the development of depression and anxiety symptoms is poorly understood� Considering results from several experimental and epidemiological studies, the possible mechanisms mentioned earlier are summarized in Figure 7�1�

FIGURE 7.1 Possible mechanisms of how air pollutants contribute to the development of depression and anxiety symptoms�

Neurodegeneration refers to progressive neuronal loss, including functional and structural loss� This process results in the development of neurodegenerative diseases such as dementia, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS)�

Dementia is the umbrella term for chronic and progressive loss of memory and thinking ability� The number of dementia patients globally is currently estimated at 47�5 million and is expected to increase to 75�6 million by 2030, and more than triple by 2050 (WHO and Alzheimer’s Disease International, 2012)� The major causes of dementia are Alzheimer’s disease, vascular dementia, and frontotemporal dementia� Alzheimer’s disease accounts for the largest body of dementia� Known risk factors for Alzheimer’s disease include age, heredity, family history, and previous head injuries� What causes Alzheimer’s disease is not fully understood, but the pathophysiology involves the ε4 allele of the apolipoprotein E (ApoE), Aβ deposits, and tau protein abnormalities forming neurofibrillary tangles� Cytokines and inflammatory responses may also play a role in the pathophysiology�

Parkinson’s disease is a neurodegenerative disease of the CNS, in particular the movement system� The pathophysiology involves the death of dopamine-generating cells in the substantia nigra, a part of the midbrain� Symptoms include pill-rolling tremor, cogwheel rigidity, and slowness of movement at the early stage; and eventually dementia develops at the advanced stage� The motor symptoms are referred to as parkinsonism, which is classified as primary and secondary according to its cause� Primary parkinsonism has no obvious cause (i�e�, idiopathic) but may have a genetic origin� Secondary parkinsonism results from preexisting health problems such as brain injury, stroke, and chemical or drug poisonings� As for the risk and protective factors of Parkinson’s disease, exposure to pesticides is the best-known risk factor, but the role of heavy metals and the protective effect of tobacco smoking are in controversy�

Symptoms of ALS involve motor neurons and muscles and include stiffness, twitching, wasting, and gradually worsening weakness of muscles, followed by difficulty moving, speaking, swallowing, and finally breathing� It is known that about 10% of cases are related to heredity (Kiernan et al�, 2011) while the remainder have an unclear etiology�

The short-term effect of air pollution on mental health deserves more attention in terms of environmental health, but it would be difficult to apply the results directly to environmental health policy because the associations are diminutive and still in controversy-especially when it comes to the causal relationship� Therefore, to investigate the causal relationship between air pollution and mental health, it is imperative to perform a longitudinal study on the long-term effects with a careful design� Moreover, risk assessment, which is useful in environmental health policy establishment, should be accompanied by the process of identifying dose-response relationship, which can be obtained by conducting a longitudinal study� With regard to mental health problems such as neurodegenerative diseases, the pathological process develops slowly, and the symptoms are more likely to be detectable when the diseases have progressed, which makes it less plausible to examine the short-term effect of air pollution on the occurrence of neurodegenerative diseases� So far, several studies linked long-term exposure to air pollution with the incidence of neurodegenerative diseases� Finkelstein and Jerrett reported

the relation between ambient manganese levels and Parkinson’s disease (Finkelstein and Jerrett, 2007)� The authors established a cohort of 110,348 subjects in Hamilton and Toronto and ascertained Parkinson’s cases by linking administrative records� In Hamilton, the odds ratio for Parkinson’s disease was 1�034 (95% CI: 1�00-1�07) per 10 ng/m3 increase in manganese in total suspended particulate, whereas no association was found in Toronto� For ALS, Malek et al� (2015) suggested an association with ambient aromatic solvents in 12 counties of the United States in 1999 and 2002 through conducting a case-control study with 51 cases and 51 matched controls� However, the other neurotoxic hazardous air pollutants (HAPs) did not show significances�

In conducting studies on neurodegenerative diseases, one of the major challenges is how to define the outcome� Neurodegenerative diseases such as dementia have a relatively low prevalence compared with other chronic diseases such as cardiovascular disease and diabetes mellitus despite their growing number for decades� In addition, the effect of environmental pollution is more likely to be slight, which makes it more difficult to detect an association� Therefore, obtaining a sufficiently large sample size is needed to obtain significance but could be demanding in terms of time and cost unless administrative data are used as Finkelstein and Jerrett did� Considering that, measuring brain function will be more useful rather than using the incidence of disease as an outcome� Moreover, for early intervention, it would be worthwhile to find subtle brain changes before symptoms are evident� In line with this, several epidemiological studies have reported the association of air pollution with cognitive function among cohort subjects�

Power et al� (2011) reported the association between black carbon and cognitive function among 680 older men (50-99 years) from the US Department of Veterans Affairs Normative Aging Study� Doubling in black carbon was associated with having a mini-mental state examination (MMSE) score ≤ 25 (odds ratio, 1�3; 95% CI: 1�1-1�6]� For global cognitive function, doubling in black carbon was inversely associated with the cognitive test score�

With 19,409 older US women (70-81 years) from the Nurses’ Health Study Cognitive Cohort, Weuve et al� (2012) associated recent (1 month) and long-term (7-14 years) exposures to PM2�5-10 and PM2�5 with cognitive decline based on the telephone interview for cognitive status� The authors analyzed the exposure levels before the baseline cognitive test and three repeated measures of cognitive function with GEE and found that a decrease in global cognitive score per 2 years was associated with higher PM2�5-10 and PM2�5 exposure�

In the United Kingdom, Tonne et al� (2014) found that PM10 and PM2�5 were associated with cognitive decline in 2867 participants (mean age, 66; standard deviation, 6 years) of the Whitehall II cohort who were residents of Greater London� The authors assessed four cognitive functions (reasoning, memory, semantic fluency, phonemic fluency) twice with a 5-year interval� For the second assessment, a 5-year exposure to higher PM2�5 exposure was associated with lower cognitive scores on reasoning� When excluding movers out of Greater London between the two assessments, exposure 4 years prior to the second assessment was significantly associated with a decline in memory score�

Because Alzheimer’s disease is related to the ε4 allele of the ApoE, there may be interactive effects of the genotype on the relationship between air pollution and

cognitive function� Schikowski et al� (2015) investigated the effect modification of the ApoE gene variants among 789 elderly women (mean age, 73; standard deviation, 3 years) from the Study on the influence of Air pollution on Lung function, Inflammation, and Aging (SALIA) cohort in Germany� The researchers assessed subjects’ cognitive function using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological assessment battery� In this study, traffic load was inversely associated with the score on the figure-copying subtest in women with one or more ApoE ε4 risk allele but not in women without this risk allele�

Previous studies mentioned above used questionnaire-based tools for the evaluation of cognitive function� Questionnaire-based tests can identify functional changes of the brain, which may be preceded by subtle anatomical changes (Jack et al�, 2013)� To detect fine anatomical changes in the brain, it would be helpful to perform brain magnetic resonance imaging (MRI) and analyze the images to identify any microbleeds or estimate cortical thickness� A recent study by Wilker et al� (2015) associated long-term air pollution exposure with brain MRI findings such as total cerebral brain volume, hippocampal volume, white matter hyperintensities, and covert brain infarct� In this study, long-term exposure to higher PM2�5 was associated with smaller total cerebral brain volume and more covert brain infarcts in 943 older (aged ≥ 60 years) adults residing in the New England region� Since 2014, our group also has conducted a cohort study (Environmental Pollution Induced Neurological Effect, EPINEF study) targeting brain structural and functional changes in relation to exposure to various air pollutants, using brain MRI and neuropsychological assessment� Despite its beginning stage, the multidisciplinary approach encompassing environmental epidemiology and brain science technology will be useful for detecting diminutive brain changes associated with air pollution and for identifying the underlying biological mechanism�

Neurodevelopmental disorders refer to a constellation of neuropathological conditions occurring during developmental periods, which are accompanied by personal, social, educational, or occupational impairments� Symptoms in neurodevelopmental disorders range from specific deficits of learning or social communication to global deteriorations of intelligence� There are two well-known neurodevelopmental disorders: ADHD and autism spectrum disorder� ADHD is characterized by inattentiveness, impulsivity, and overactivity� Children with autism spectrum disorder have deficits of social skills, excessive repetitive behaviors, limited interests, and craving sameness� These disorders have a strong genetic and familial tendency, but it is widely accepted that both genetics and environmental factors may play a role� Recently, literature has accumulated on environmental factors for ADHD and autism, outdoor air pollution in particular� Exposure to traffic-related air pollution (TRAP) and heavy metals during prenatal or early-life period is considered as a potential culprit for developing ADHD and autism�

Newman et al� (2013) investigated the relationship between early-life exposure to TRAP (elemental carbon attributed to traffic [ECAT] as a surrogate) and ADHD symptoms at 7 years of age among 576 children of the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort� They found that exposure to the

highest tertile of ECAT during infancy was significantly associated with hyperactivity T-scores > 59, and the association was stronger in mothers with higher education�

Volk et al� (2013) conducted a case-control study including 279 children with autism and 245 controls� In this study, exposure to TRAP, NO2, PM2�5, and PM10 during pregnancy and infancy was associated with autism� Further, Raz et al� (2015) suggested that higher exposure to PM2�5 during pregnancy, the third trimester in particular, was associated with an increased risk for autism spectrum disorder through conducting a nested case-control study of participants from the Nurses’ Health Study II (NHS II)�

Several epidemiological studies evaluated preclinical changes in psychomotor and cognitive development� A study by Guxens et al� (2014) found that NO2 and PM2�5 exposure during pregnancy was inversely associated with psychomotor development, but not with cognitive development, among 9482 children from six European birth cohorts� Prenatal polycyclic aromatic hydrocarbons (PAHs) exposure is also of interest, and a brain imaging study showed that PAHs were associated with reduced white matter surface in children aged 7-9 years (Peterson et al�, 2015)�

In this chapter, we summarized major epidemiological findings on the relationship between air pollution and mental health problems: suicidal behaviors, depression, anxiety, neurodegenerative diseases, and neurodevelopmental disorders� These findings are supported by numerous experimental studies suggesting the biological plausibility; thus, concern of the effect of air pollution on the brain is growing� Although the results from epidemiological studies are heterogeneous, the growing evidence suggests that research is heading toward a better understanding of mental disorders with poorly known causes�

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Block, M� L� and Calderon-Garciduenas, L� 2009� Air pollution: Mechanisms of neuroinflammation and CNS disease� Trends Neurosci, 32, 506-16�

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