Inflammatory Response to Fine Particulate Air Pollution Exposure: Neutrophil versus Monocyte

Objectives

Studies have shown that chronic exposure to ambient fine particulate matter (less than 2.5 µm in aerodynamic diameter, PM_2.5) pollution induces insulin resistance through alterations in inflammatory pathways. It is critical to study how the immune system responds to this stimulant, which has been linked to cardiovascular and autoimmune diseases, but few studies have been focused on such involvement of both neutrophils and monocytes in a timely manner. We hypothesized that the neutrophil was involved in the inflammatory response to air pollution.

Methods and Results

C57BL/6 mice were exposed to PM_2.5 or filtered air (6 hours/day, 5 days/week) for 5, 14, and 21 days, respectively, in Columbus, OH. At the end of each of the exposure periods, we investigated the inflammatory response through flow cytometry, histology, intravital microscopy, and real-time PCR. PM_2.5-exposed mice demonstrated a significant inflammatory response after 5 days of exposure. In the lung tissue and bronchoalveolar lavage fluid, monocytes/macrophages showed a transient response, while neutrophils showed a cumulative response. In addition, exposure to PM_2.5 resulted in elevation of the monocyte chemoattractant protein 1 (MCP-1) cytokine, a monocyte/macrophage attractant in blood, at an early stage of exposure.

Conclusions

These findings suggest that PM_2.5 exposure induces the inflammatory responses from both macrophages and neutrophils involvement.     

孕期大鼠暴露PFOS对胎鼠肝脏毒性的影响

目的:研究在孕期暴露PFOS对胎鼠的肝脏毒性的影响.方法:将孕期为12天的16只SD雌性大鼠,随机分为4组给予不同剂量的PFOS[0(对照),5,10,20 mg·kg-1],连续灌胃7天,在GD19天时对母鼠和胎鼠的体重、胎鼠肝脏的生化指标、母鼠血清的生化指标进行了相应的检测.结果:与对照组相比,母鼠体重在20 mg·kg-1组显著下降(P＜0.001);胎鼠的体重和体长在20mg·kg-1组显著下降(P＜0.001);胎鼠的肝脏重量降低,呈剂量依赖性,并伴有肝细胞浊肿、变性甚至坏死;10 mg· kg-1组胎鼠肝脏中的酶活性(ALT、AST、GGT和ALP等)显著升高(P＜0.001);母鼠血清的大部分生化指标未发生明显变化.结论:孕期大鼠暴露在PFOS的环境下会严重损伤胎鼠的肝脏功能.     

Chronic Household Air Pollution Exposure Is Associated with Impaired Alveolar Macrophage Function in Malawian Non-Smokers

Background

Household air pollution in low income countries is an important cause of mortality from respiratory infection. We hypothesised that chronic smoke exposure is detrimental to alveolar macrophage function, causing failure of innate immunity. We report the relationship between macrophage function and prior smoke exposure in healthy Malawians.

Methods

Healthy subjects exposed daily to cooking smoke at home volunteered for bronchoalveolar lavage. Alveolar macrophage particulate content was measured as a known correlate of smoke exposure. Phagocytosis and intraphagosomal function (oxidative burst and proteolysis) were measured by a flow cytometric assay. Cytokine responses in macrophages were compared following re-exposure in vitro to wood smoke, before and after glutathione depletion.

Results

Volunteers had a range of alveolar macrophage particulate loading. The macrophage capacity for phagosomal oxidative burst was negatively associated with alveolar macrophage particulate content (n = 29, r² = 0.16, p = 0.033), but phagocytosis per se and proteolytic function were unaffected. High particulate content was associated with lower baseline CXCL8 release (ratio 0.51, CI 0.29–0.89) and lower final concentrations on re-exposure to smoke in vitro (ratio 0.58, CI 0.34–0.97). Glutathione depletion augmented CXCL8 responses by 1.49x (CI 1.02–2.17) compared with wood smoke alone. This response was specific to smoke as macrophages response to LPS were not modulated by glutathione.

Conclusion

Chronic smoke exposure is associated with reduced human macrophage oxidative burst, and dampened inflammatory cytokine responses. These are critical processes in lung defence against infection and likely to underpin the relationship between air pollution and pneumonia.     

Premature Mortality in the Kingdom of Saudi Arabia Associated with Particulate Matter Air Pollution from the 1991 Gulf War

The State of Kuwait oil fires and military operations associated with the 1991 Gulf War resulted in substantially increased levels of airborne particulate matter (PM) in the Kingdom of Saudi Arabia (KSA) during 1991 and 1992. Using quantitative risk assessment methodology, this article estimates the increase in premature deaths in citizens of the KSA associated with the Gulf War–related increase in PM air pollution levels. Meta-analysis of daily time-series studies of non-accidental mortality associated with increased PM₁₀ levels using two alternative methodologies yielded exposure-response relative risk functions of 2.7% and 3.5% per 50 μ g/m³ increase in PM₁₀ concentration. Combining these exposure-response functions with estimates of the magnitude and duration of the increased PM₁₀ exposure, the size of the exposed population and baseline mortality rates provided an estimate of approximately 1,080 to 1,370 excess non-accidental deaths of Saudi citizens during 1991–1992 associated with the Gulf War–related increase in PM levels.     

Disrupted Nitric Oxide Metabolism from Type II Diabetes and Acute Exposure to Particulate Air Pollution

Type II diabetes is an established cause of vascular impairment. Particulate air pollution is known to exacerbate cardiovascular and respiratory conditions, particularly in susceptible populations. This study set out to determine the impact of exposure to traffic pollution, with and without particle filtration, on vascular endothelial function in Type II diabetes. Endothelial production of nitric oxide (NO) has previously been linked to vascular health. Reactive hyperemia induces a significant increase in plasma nitrite, the proximal metabolite of NO, in healthy subjects, while diabetics have a lower and more variable level of response. Twenty type II diabetics and 20 controls (ages 46–70 years) were taken on a 1.5hr roadway traffic air pollution exposure as passengers. We analyzed plasma nitrite, as a measure of vascular function, using forearm ischemia to elicit a reactive hyperemic response before and after exposure to one ride with and one without filtration of the particle components of pollution. Control subjects displayed a significant increase in plasma nitrite levels during reactive hyperemia. This response was no longer present following exposure to traffic air pollution, but did not vary with whether or not the particle phase was filtered out. Diabetics did not display an increase in nitrite levels following reactive hyperemia. This response was not altered following pollution exposure. These data suggest that components of acute traffic pollution exposure diminish vascular reactivity in non-diabetic individuals. It also confirms that type II diabetics have a preexisting diminished ability to appropriately respond to a vascular challenge, and that traffic pollution exposure does not cause a further measureable acute change in plasma nitrite levels in Type II diabetics.     

Human Exposure to Particulate Matter Potentially Contaminated with Sin Nombre Virus

The most common mechanism for human exposure to hantaviruses throughout North America is inhalation of virally contaminated particulates. However, risk factors associated with exposure to particulates potentially contaminated with hantaviruses are generally not well understood. In North America, Sin Nombre virus (SNV) is the most common hantavirus that infects humans, causing hantavirus pulmonary syndrome, which has a significant mortality rate (approximately 35%). We investigated human exposure to particulate matter and evaluated the effects of season, location (sylvan and peridomestic environment), and activity (walking and sweeping) on generation of particulates at the breathing zone (1.5 m above the ground). We found greater volumes of small inhalable particulates during the spring and summer compared to the fall and winter seasons and greater volumes of small inhalable particulates produced in peridomestic, compared to sylvan, environments. Also, greater volumes of particulates were generated at the breathing zone while walking compared to sweeping. Results suggest that more aerosolized particles were generated during the spring and summer months. Our findings suggest that simply moving around in buildings is a significant source of human exposure to particulates, potentially contaminated with SNV, during spring and summer seasons. These findings could be advanced by investigation of what particle sizes SNV is most likely to attach to, and where in the respiratory tract humans become infected.     

Venous Thromboembolism in an Industrial North American City: Temporal Distribution and Association with Particulate Matter Air Pollution

Background

Emerging evidence, mainly from Europe and Asia, indicates that venous thromboembolism (VTE) occurs most often in winter. Factors implicated in such seasonality are low temperature-mediated exacerbation of coagulation and high levels of particulate matter (PM) air pollution. However, in contrast to most European and Asian cities, particulate matter pollution peaks in the summer in many North American cities.

Objectives

We aimed to exploit this geographical difference and examine the temporal distribution of VTE in a cold-weather, North American city, Detroit, with a summer PM peak. Our goal was thereby to resolve the influence of temperature and PM levels on VTE.

Methods

Our retrospective, analytical semi-ecological study used chart review to confirm 1,907 acute, ambulatory VTE cases, divided them by location (Detroit versus suburban), and plotted monthly VTE frequency distributions. We used Environmental Protection Agency data to determine the temporal distribution of PM pollution components in Detroit. Suburban PM air pollution is presumed negligible and therefore not monitored.

Results

Acute VTE cases in Detroit (1,490) exhibited a summer peak (June 24^th) and differed from both a uniform distribution (P<0.01) and also that of 1,123 no-VTE cases (P<0.02). Levels of 10 µm diameter PM and coarse particle (2.5 to 10 µm) PM also exhibited summer peaks versus a winter peak for 2.5 µm diameter PM. Contrary to their urban counterparts, suburban cases of acute VTE (417) showed no monthly variation.

Conclusions

The summer peak of acute VTE in Detroit indicates that low temperature is not a major factor in VTE pathogenesis. In contrast, concordance of the 10 µm diameter PM, coarse particle, and the Detroit VTE monthly distributions, combined with no monthly suburban VTE variation, is consistent with a role for PM pollution. Furthermore, divergence of the VTE and 2.5 µm PM distributions suggests that particle size may play a role.     

Mitochondrial Complex III-generated Oxidants Activate ASK1 and JNK to Induce Alveolar Epithelial Cell Death following Exposure to Particulate Matter Air Pollution

We have previously reported that airborne particulate matter air pollution (PM) activates the intrinsic apoptotic pathway in alveolar epithelial cells through a pathway that requires the mitochondrial generation of reactive oxygen species (ROS) and the activation of p53. We sought to examine the source of mitochondrial oxidant production and the molecular links between ROS generation and the activation of p53 in response to PM exposure. Using a mitochondrially targeted ratiometric sensor (Ro-GFP) in cells lacking mitochondrial DNA (ρ⁰ cells) and cells stably expressing a small hairpin RNA directed against the Rieske iron-sulfur protein, we show that site III of the mitochondrial electron transport chain is primarily responsible for fine PM (PM_2.5)-induced oxidant production. In alveolar epithelial cells, the overexpression of SOD1 prevented the PM_2.5-induced ROS generation from the mitochondria and prevented cell death. Infection of mice with an adenovirus encoding SOD1 prevented the PM_2.5-induced death of alveolar epithelial cells and the associated increase in alveolar-capillary permeability. Treatment with PM_2.5 resulted in the ROS-mediated activation of the oxidant-sensitive kinase ASK1 and its downstream kinase JNK. Murine embryonic fibroblasts from ASK1 knock-out mice, alveolar epithelial cells transfected with dominant negative constructs against ASK1, and pharmacologic inhibition of JNK with SP600125 (25 μm) prevented the PM_2.5-induced phosphorylation of p53 and cell death. We conclude that particulate matter air pollution induces the generation of ROS primarily from site III of the mitochondrial electron transport chain and that these ROS activate the intrinsic apoptotic pathway through ASK1, JNK, and p53.Epidemiologic studies have consistently demonstrated a strong link between the daily levels of particulate matter air pollution <2.5 μm in diameter (PM_2.5)³ and PM <10 μmin diameter (PM₁₀) and cardiopulmonary morbidity and mortality (1–3). In humans, exposure to PM₁₀ has been associated with an increase in mortality from ischemic cardiovascular events including stroke and myocardial infarction, an acceleration in the age-related decline in lung function in normal adults, impairment in normal lung development in children, exacerbations of asthma in children and adults, accelerated atherosclerosis in women, increased rates of lung cancer, and the development of myocardial ischemia in men with stable coronary artery disease (4–10). The intracellular generation of reactive oxygen species (ROS) has emerged as a common mechanism by which particulates might initiate signaling pathways that end in these diverse pathologic conditions (11). We have reported that the PM-induced generation of ROS requires a functional electron transport chain, suggesting that PM might induce the inadvertent transfer of electrons from one or more sites in the electron transport chain to molecular oxygen (12).One of the mechanisms by which exposure to PM can contribute to alveolar epithelial dysfunction, lung injury and inflammation, and lung cancer is by activating the intrinsic apoptotic pathway to induce cell death (11, 12). We have reported that this process requires the activation of p53; however, the molecular events linking the generation of ROS by the mitochondrial electron transport chain with the activation of p53 are not known (12). In this paper, we show that exposure of alveolar epithelial cells to PM_2.5 induces the generation of ROS from site III of the mitochondrial electron transport chain. These mitochondrially derived oxidants activate the mitogen-activated signaling kinase kinase kinase (MAPKKK) apoptosis signaling kinase 1 (ASK1), which activates the c-Jun N-terminal kinase (JNK) signaling pathway. The activation of JNK is required for the phosphorylation of p53 and the subsequent cell death. Inhibition of mitochondrial oxidant production in mouse lungs prevents PM_2.5-induced cell death and the associated PM_2.5-induced increase in the permeability of the alveolar-capillary barrier.     

Exposure to Ionizing Radiation during Dental X-Rays Is Not Associated with Risk of Developing Meningioma: A Meta-Analysis Based on Seven Case-Control Studies

BackgroundMany observational studies have found that exposure to dental X-rays is associated with the risk of development of meningioma. However, these findings are inconsistent. We conducted a meta-analysis to assess the relationship between exposure to dental X-rays and the risk of development of meningioma.MethodsThe PubMed and EMBASE databases were searched to identify eligible studies. Summary odds ratio (OR) estimates and 95% confidence intervals (95% CIs) were used to compute the risk of meningioma development according to heterogeneity. Subgroup and sensitivity analyses were performed to further explore the potential heterogeneity. Finally, publication bias was assessed.ResultsSeven case-control studies involving 6,174 patients and 19,459 controls were included in the meta-analysis. Neither exposure to dental X-rays nor performance of full-mouth panorex X-rays was associated with an increased risk of development of meningioma (overall: OR, 0.97; 95% CI, 0.70–1.32; dental X-rays: OR, 1.05; 95% CI, 0.89–1.25; panorex X-rays: OR, 1.01; 95% CI, 0.76–1.34). However, exposure to bitewing X-rays was associated with a slightly increased risk of development of meningioma (OR, 1.73; 95% CI, 1.28–2.34). Similar results were obtained in the subgroup and sensitivity analyses. Little evidence of publication bias was observed.ConclusionBased on the currently limited data, there is no association between exposure to dental X-rays and the risk of development of meningioma. However, these results should be cautiously interpreted because of the heterogeneity among studies. Additional large, high-quality clinical trials are needed to evaluate the association between exposure to dental X-rays and the risk of development of meningioma.     

Exposure to Bovine Leukemia Virus Is Associated with Breast Cancer: A Case-Control Study

Background

Age, reproductive history, hormones, genetics, and lifestyle are known risk factors for breast cancer, but the agents that initiate cellular changes from normal to malignant are not understood. We previously detected bovine leukemia virus (BLV), a common oncogenic virus of cattle, in the breast epithelium of humans. The objective of this study was to determine whether the presence of BLV DNA in human mammary epithelium is associated with breast cancer.

Methods

This was a case-control study of archival formalin fixed paraffin embedded breast tissues from 239 donors, received 2002–2008 from the Cooperative Human Tissue Network. Case definition as breast cancer versus normal (women with no history of breast cancer) was established through medical records and examination of tissues by an anatomical pathologist. Breast exposure to BLV was determined by in situ-PCR detection of a biomarker, BLV DNA, localized within mammary epithelium.

Results

The frequency of BLV DNA in mammary epithelium from women with breast cancer (59%) was significantly higher than in normal controls (29%) (multiply- adjusted odds ratio = 3.07, confidence interval = 1.66–5.69, p = .0004, attributable risk = 37%). In women with premalignant breast changes the frequency of BLV DNA was intermediate (38%) between that of women with breast cancer and normal controls (p for trend < .001).

Conclusions

Among the specimens in this study, the presence of amplified BLV DNA was significantly associated with breast cancer. The odds ratio magnitude was comparable to those of well-established breast cancer risk factors related to reproductive history, hormones, and lifestyle and was exceeded only by risk factors related to genetics (familial breast cancer), high dose ionizing radiation, and age. These findings have the potential for primary and secondary prevention of breast cancer.     

Long-Term Exposure to Ambient Air Pollution and Metabolic Syndrome in Adults

Air pollutants (AP) play a role in subclinical inflammation, and are associated with cardiovascular morbidity and mortality. Metabolic syndrome (MetS) is inflammatory and precedes cardiovascular morbidity and type 2 diabetes. Thus, a positive association between AP and MetS may be hypothesized. We explored this association, (taking into account, pathway-specific MetS definitions), and its potential modifiers in Swiss adults. We studied 3769 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults, reporting at least four-hour fasting time before venepuncture. AP exposures were 10-year mean residential PM₁₀ (particulate matter <10μm in diameter) and NO₂ (nitrogen dioxide). Outcomes included MetS defined by World Health Organization (MetS-W), International Diabetes Federation (MetS-I) and Adult Treatment Panel-III (MetS-A) using four- and eight-hour fasting time limits. We also explored associations with individual components of MetS. We applied mixed logistic regression models to explore these associations. The prevalence of MetS-W, MetS-I and MetS-A were 10%, 22% and 18% respectively. Odds of MetS-W, MetS-I and MetS-A increased by 72% (51-102%), 31% (11-54%) and 18% (4-34%) per 10μg/m³ increase in 10-year mean PM₁₀. We observed weaker associations with NO₂. Associations were stronger among physically-active, ever-smokers and non-diabetic participants especially with PM₁₀ (p<0.05). Associations remained robust across various sensitivity analyses including ten imputations of missing observations and exclusion of diabetes cases. The observed associations between AP exposure and MetS were sensitive to MetS definitions. Regarding the MetS components, we observed strongest associations with impaired fasting glycemia, and positive but weaker associations with hypertension and waist-circumference-based obesity. Cardio-metabolic effects of AP may be majorly driven by impairment of glucose homeostasis, and to a less-strong extent, visceral adiposity. Well-designed prospective studies are needed to confirm these findings.     

Passive Smoking Is Associated with Poor Asthma Control during Pregnancy: A Prospective Study of 500 Pregnancies

Background and Aim

Asthma and tobacco exposure is common among pregnant women. We investigated the effect of passive and active smoking on asthma control during pregnancy.

Methods

Prospective observational design. Patients had their asthma control, based on symptoms, use of medication, spirometry, and exhaled nitric oxide [F_ENO], assessed every four weeks during 2^nd and 3^rd trimester of pregnancy; data on tobacco exposure were also collected prospectively. The primary outcome was episodes of uncontrolled and partly controlled asthma during pregnancy (defined according to GINA-guidelines).

Results

A total of 500 pregnant women with asthma (mean age 30.8 years, range 17 to 44) were consecutively included, of whom 32 (6.4%), 115 (23.0%) and 353 (70.6%), respectively, were current smokers, ex-smokers and never smokers [NS]. Sixty-five NS (18.4%) reported passive tobacco exposure. NS with passive tobacco exposure had significantly lower FEV₁% predicted (p<0.02) and F_ENO (p = 0.01) compared to NS without passive tobacco exposure. The relative risk [RR] of an episode of uncontrolled asthma during pregnancy was 4.5 (95% CI 2.7–7.5: p<0.001) in current and ex-smokers compared with never smokers, and 2.9 (95% CI 1.4–5.9; p = 0.004) in NS-women with passive tobacco exposure compared with NS-women not reporting passive tobacco exposure. Treatment with inhaled corticosteroids, most likely as a marker of more severe asthma, was also associated with a higher risk (RR 8.1, 95% CI 5.1–13.0; p<0.001) of an episode of uncontrolled asthma.

Conclusion

Passive tobacco exposure in never smokers is associated with an increased risk of episodes of uncontrolled asthma during pregnancy, which is likely to have adverse effects on pregnancy outcome.     

Social Isolation-Induced Territorial Aggression in Male Offspring Is Enhanced by Exposure to Diesel Exhaust during Pregnancy

Diesel exhaust particles are a major component of ambient particulate matter, and concern about the health effects of exposure to ambient particulate matter is growing. Previously, we found that in utero exposure to diesel exhaust affected locomotor activity and motor coordination, but there are also indications that such exposure may contribute to increased aggression in offspring. Therefore, the aim of the present study was to test the effects of prenatal diesel exhaust exposure on social isolation-induced territorial aggression. Pregnant mice were exposed to low concentrations of diesel exhaust (DE; mass concentration of 90 μg/m³: DE group: n = 15) or clean air (control group: n = 15) for 8 h/day during gestation. Basal locomotion of male offspring was measured at 10 weeks of age. Thereafter, male offspring were individually housed for 2 weeks and subsequently assessed for aggression using the resident−intruder test at 12 weeks of age, and blood and brain tissue were collected from the male offspring on the following day for measuring serum testosterone levels and neurochemical analysis. There were no significant differences in locomotion between control and DE-exposed mice. However, DE-exposed mice showed significantly greater social isolation-induced territorial aggressive behavior than control mice. Additionally, socially-isolated DE-exposed mice expressed significantly higher concentrations of serum testosterone levels than control mice. Neurochemical analysis revealed that dopamine levels in the prefrontal cortex and nucleus accumbens were higher in socially isolated DE-exposed mice. Serotonin levels in the nucleus accumbens, amygdala, and hypothalamus were also lower in the socially isolated DE-exposed mice than in control mice. Thus, even at low doses, prenatal exposure to DE increased aggression and serum testosterone levels, and caused neurochemical changes in male socially isolated mice. These results may have serious implications for pregnant women living in regions with high levels of traffic-related air pollution.     

Intimate Partner Violence Is Associated with Stress-Related Sleep Disturbance and Poor Sleep Quality during Early Pregnancy

Objectives

To examine the associations of Intimate partner violence (IPV) with stress-related sleep disturbance (measured using the Ford Insomnia Response to Stress Test [FIRST]) and poor sleep quality (measured using the Pittsburgh Sleep Quality Index [PSQI]) during early pregnancy.

Methods

This cross-sectional study included 634 pregnant Peruvian women. In-person interviews were conducted in early pregnancy to collect information regarding IPV history, and sleep traits. Adjusted odds ratios (aOR) and 95% confidence intervals (95%CIs) were calculated using logistic regression procedures.

Results

Lifetime IPV was associated with a 1.54-fold increased odds of stress-related sleep disturbance (95% CI: 1.08–2.17) and a 1.93-fold increased odds of poor sleep quality (95% CI: 1.33–2.81). Compared with women experiencing no IPV during lifetime, the aOR (95% CI) for stress-related sleep disturbance associated with each type of IPV were: physical abuse only 1.24 (95% CI: 0.84–1.83), sexual abuse only 3.44 (95%CI: 1.07–11.05), and physical and sexual abuse 2.51 (95% CI: 1.27–4.96). The corresponding aORs (95% CI) for poor sleep quality were: 1.72 (95% CI: 1.13–2.61), 2.82 (95% CI: 0.99–8.03), and 2.50 (95% CI: 1.30–4.81), respectively. Women reporting any IPV in the year prior to pregnancy had increased odds of stress-related sleep disturbance (aOR = 2.07; 95% CI: 1.17–3.67) and poor sleep quality (aOR = 2.27; 95% CI: 1.30–3.97) during pregnancy.

Conclusion

Lifetime and prevalent IPV exposures are associated with stress-related sleep disturbance and poor sleep quality during pregnancy. Our findings suggest that sleep disturbances may be important mechanisms that underlie the lasting adverse effects of IPV on maternal and perinatal health.     

Anorexia Nervosa during Adolescence Is Associated with Decreased Gray Matter Volume in the Inferior Frontal Gyrus

Anorexia nervosa (AN) is an eating disorder characterized by the relentless pursuit to lose weight, mostly through self-starvation, and a distorted body image. AN tends to begin during adolescence among women. However, the underlying neural mechanisms related to AN remain unclear. Using voxel-based morphometry based on magnetic resonance imaging scans, we investigated whether the presence of AN was associated with discernible changes in brain morphology. Participants were 20 un-medicated, right-handed patients with early-onset AN and 14 healthy control subjects. Group differences in gray matter volume (GMV) were assessed using high-resolution, T1-weighted, volumetric magnetic resonance imaging datasets (3T Trio scanner; Siemens AG) and analyzed after controlling for age and total GMV, which was decreased in the bilateral inferior frontal gyrus (IFG) (left IFG: FWE corrected, p < 0.05; right IFG: uncorrected, p < 0.05) of patients with AN. The GMV in the bilateral IFG correlated significantly with current age (left IFG: r = -.481, p < .05; right IFG: r = -.601, p < .01) and was limited to the AN group. We speculate that decreased IFG volume might lead to deficits in executive functioning or inhibitory control within neural reward systems. Precocious or unbalanced neurological trimming within this particular region might be an important factor for the pathogenesis of AN onset.