Prior differences in previous trauma exposure primarily drive the observed racial/ethnic differences in posttrauma depression and anxiety following a recent trauma.

BACKGROUND: Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time. METHODS: As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors. RESULTS: Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants. CONCLUSIONS: The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories.

Cerebellar volume and cerebellocerebral structural covariance in schizophrenia: a multisite mega-analysis of 983 patients and 1349 healthy controls.

Although cerebellar involvement across a wide range of cognitive and neuropsychiatric phenotypes is increasingly being recognized, previous large-scale studies in schizophrenia (SZ) have primarily focused on supratentorial structures. Hence, the across-sample reproducibility, regional distribution, associations with cerebrocortical morphology and effect sizes of cerebellar relative to cerebral morphological differences in SZ are unknown. We addressed these questions in 983 patients with SZ spectrum disorders and 1349 healthy controls (HCs) from 14 international samples, using state-of-the-art image analysis pipelines optimized for both the cerebellum and the cerebrum. Results showed that total cerebellar grey matter volume was robustly reduced in SZ relative to HCs (Cohens's d=-0.35), with the strongest effects in cerebellar regions showing functional connectivity with frontoparietal cortices (d=-0.40). Effect sizes for cerebellar volumes were similar to the most consistently reported cerebral structural changes in SZ (e.g., hippocampus volume and frontotemporal cortical thickness), and were highly consistent across samples. Within groups, we further observed positive correlations between cerebellar volume and cerebral cortical thickness in frontotemporal regions (i.e., overlapping with areas that also showed reductions in SZ). This cerebellocerebral structural covariance was strongest in SZ, suggesting common underlying disease processes jointly affecting the cerebellum and the cerebrum. Finally, cerebellar volume reduction in SZ was highly consistent across the included age span (16-66 years) and present already in the youngest patients, a finding that is more consistent with neurodevelopmental than neurodegenerative etiology. Taken together, these novel findings establish the cerebellum as a key node in the distributed brain networks underlying SZ.

Effort-cost decision-making in psychosis and depression: could a similar behavioral deficit arise from disparate psychological and neural mechanisms?

Motivational impairment is a common feature of both depression and psychosis; however, the psychological and neural mechanisms that give rise to motivational impairment in these disorders are poorly understood. Recent research has suggested that aberrant effort-cost decision-making (ECDM) may be a potential contributor to motivational impairment in both psychosis and depression. ECDM refers to choices that individuals make regarding the amount of 'work' they are willing to expend to obtain a certain outcome or reward. Recent experimental work has suggested that those with psychosis and depression may be less willing to expend effort to obtain rewards compared with controls, and that this effort deficit is related to motivational impairment in both disorders. In the current review, we aim to summarize the current literature on ECDM in psychosis and depression, providing evidence for transdiagnostic impairment. Next, we discuss evidence for the hypothesis that a seemingly similar behavioral ECDM deficit might arise from disparate psychological and neural mechanisms. Specifically, we argue that effort deficits in psychosis might be largely driven by deficits in cognitive control and the neural correlates of cognitive control processes, while effort deficits in depression might be largely driven by reduced reward responsivity and the associated neural correlates of reward responsivity. Finally, we will provide some discussion regarding future directions, as well as interpretative challenges to consider when examining ECDM transdiagnostically.

Face processing in adolescents with positive and negative threat bias.

BACKGROUND: Individuals with anxiety disorders exhibit a 'vigilance-avoidance' pattern of attention to threatening stimuli when threatening and neutral stimuli are presented simultaneously, a phenomenon referred to as 'threat bias'. Modifying threat bias through cognitive retraining during adolescence reduces symptoms of anxiety, and so elucidating neural mechanisms of threat bias during adolescence is of high importance. We explored neural mechanisms by testing whether threat bias in adolescents is associated with generalized or threat-specific differences in the neural processing of faces. METHOD: Subjects were categorized into those with (n = 25) and without (n = 27) threat avoidance based on a dot-probe task at average age 12.9 years. Threat avoidance in this cohort has previously been shown to index threat bias. Brain response to individually presented angry and neutral faces was assessed in a separate session using functional magnetic resonance imaging. RESULTS: Adolescents with threat avoidance exhibited lower activity for both angry and neutral faces relative to controls in several regions in the occipital, parietal, and temporal lobes involved in early visual and facial processing. Results generalized to happy, sad, and fearful faces. Adolescents with a prior history of depression and/or an anxiety disorder had lower activity for all faces in these same regions. A subset of results replicated in an independent dataset. CONCLUSIONS: Threat bias is associated with generalized, rather than threat-specific, differences in the neural processing of faces in adolescents. Findings may aid in the development of novel treatments for anxiety disorders that use attention training to modify threat bias.

A Data-Driven Latent Variable Approach to Validating the Research Domain Criteria Framework.

Despite the widespread use of the Research Domain Criteria (RDoC) framework in psychiatry and neuroscience, recent studies suggest that the RDoC is insufficiently specific or excessively broad relative to the underlying brain circuitry it seeks to elucidate. To address these concerns of the RDoC framework, our study employed a latent variable approach, specifically utilizing bifactor analysis. We examined a total of 84 whole-brain task-based fMRI (tfMRI) activation maps from 19 studies with a total of 6,192 participants. Within this set of 84 maps, a curated subset of 37 maps with a balanced representation of RDoC domains constituted the training set of our analysis, and the remaining held-out maps formed the internal validation set. External validation was performed with 36 peak coordinate activation maps from Neurosynth, using terms of RDoC constructs as seeds for topic meta-analysis. Our results indicate that a bifactor model with a task-general domain and splitting the cognitive systems domain into sub-domains better fits the current corpus of tfMRI data than the current RDoC framework. Our data-driven validation supports revising the RDoC framework to accurately reflect underlying brain circuitry.

Cognition in schizophrenia and schizo-affective disorder: impairments that are more similar than different.

BACKGROUND: Cognition is increasingly being recognized as an important aspect of psychotic disorders and a key contributor to functional outcome. In the past, comparative studies have been performed in schizophrenia and schizo-affective disorder with regard to cognitive performance, but the results have been mixed and the cognitive measures used have not always assessed the cognitive deficits found to be specific to psychosis. A set of optimized cognitive paradigms designed by the Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRACS) Consortium to assess deficits specific to schizophrenia was used to measure cognition in a large group of individuals with schizophrenia and schizo-affective disorder. METHOD: A total of 519 participants (188 with schizophrenia, 63 with schizo-affective disorder and 268 controls) were administered three cognitive paradigms assessing the domains of goal maintenance in working memory, relational encoding and retrieval in episodic memory and visual integration. RESULTS: Across the three domains, the results showed no major quantitative differences between patient groups, with both groups uniformly performing worse than healthy subjects. CONCLUSIONS: The findings of this study suggests that, with regard to deficits in cognition, considered a major aspect of psychotic disorder, schizophrenia and schizo-affective disorder do not demonstrate major significant distinctions. These results have important implications for our understanding of the nosological structure of major psychopathology, providing evidence consistent with the hypothesis that there is no natural distinction between cognitive functioning in schizophrenia and schizo-affective disorder.

Cognitive and neural effects of semantic encoding strategy training in older adults.

Prior research suggests that older adults are less likely than young adults to use effective learning strategies during intentional encoding. This functional magnetic resonance imaging (fMRI) study investigated whether training older adults to use semantic encoding strategies can increase their self-initiated use of these strategies and improve their recognition memory. The effects of training on older adults' brain activity during intentional encoding were also examined. Training increased older adults' self-initiated semantic encoding strategy use and eliminated pretraining age differences in recognition memory following intentional encoding. Training also increased older adults' brain activity in the medial superior frontal gyrus, right precentral gyrus, and left caudate during intentional encoding. In addition, older adults' training-related changes in recognition memory were strongly correlated with training-related changes in brain activity in prefrontal and left lateral temporal regions associated with semantic processing and self-initiated verbal encoding strategy use in young adults. These neuroimaging results demonstrate that semantic encoding strategy training can alter older adults' brain activity patterns during intentional encoding and suggest that young and older adults may use the same network of brain regions to support self-initiated use of verbal encoding strategies.

Childhood adversities and risk of posttraumatic stress disorder and major depression following a motor vehicle collision in adulthood.

AIMS: Childhood adversities (CAs) predict heightened risks of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) among people exposed to adult traumatic events. Identifying which CAs put individuals at greatest risk for these adverse posttraumatic neuropsychiatric sequelae (APNS) is important for targeting prevention interventions. METHODS: Data came from n = 999 patients ages 18-75 presenting to 29 U.S. emergency departments after a motor vehicle collision (MVC) and followed for 3 months, the amount of time traditionally used to define chronic PTSD, in the Advancing Understanding of Recovery After Trauma (AURORA) study. Six CA types were self-reported at baseline: physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect and bullying. Both dichotomous measures of ever experiencing each CA type and numeric measures of exposure frequency were included in the analysis. Risk ratios (RRs) of these CA measures as well as complex interactions among these measures were examined as predictors of APNS 3 months post-MVC. APNS was defined as meeting self-reported criteria for either PTSD based on the PTSD Checklist for DSM-5 and/or MDE based on the PROMIS Depression Short-Form 8b. We controlled for pre-MVC lifetime histories of PTSD and MDE. We also examined mediating effects through peritraumatic symptoms assessed in the emergency department and PTSD and MDE assessed in 2-week and 8-week follow-up surveys. Analyses were carried out with robust Poisson regression models. RESULTS: Most participants (90.9%) reported at least rarely having experienced some CA. Ever experiencing each CA other than emotional neglect was univariably associated with 3-month APNS (RRs = 1.31-1.60). Each CA frequency was also univariably associated with 3-month APNS (RRs = 1.65-2.45). In multivariable models, joint associations of CAs with 3-month APNS were additive, with frequency of emotional abuse (RR = 2.03; 95% CI = 1.43-2.87) and bullying (RR = 1.44; 95% CI = 0.99-2.10) being the strongest predictors. Control variable analyses found that these associations were largely explained by pre-MVC histories of PTSD and MDE. CONCLUSIONS: Although individuals who experience frequent emotional abuse and bullying in childhood have a heightened risk of experiencing APNS after an adult MVC, these associations are largely mediated by prior histories of PTSD and MDE.

The Human Connectome Project: a data acquisition perspective.

The Human Connectome Project (HCP) is an ambitious 5-year effort to characterize brain connectivity and function and their variability in healthy adults. This review summarizes the data acquisition plans being implemented by a consortium of HCP investigators who will study a population of 1200 subjects (twins and their non-twin siblings) using multiple imaging modalities along with extensive behavioral and genetic data. The imaging modalities will include diffusion imaging (dMRI), resting-state fMRI (R-fMRI), task-evoked fMRI (T-fMRI), T1- and T2-weighted MRI for structural and myelin mapping, plus combined magnetoencephalography and electroencephalography (MEG/EEG). Given the importance of obtaining the best possible data quality, we discuss the efforts underway during the first two years of the grant (Phase I) to refine and optimize many aspects of HCP data acquisition, including a new 7T scanner, a customized 3T scanner, and improved MR pulse sequences.

Selective processing of body image words in women at-risk for developing an eating disorder: a preliminary study.

We evaluated the utility of the Modified Stroop task as a measure of body image concerns in women at-risk for an eating disorder. Data were collected among 31 participants from an eating disorder prevention program. The Modified Stroop was significantly associated with overeating episodes and an explicit measure of shape concern. The traditional Stroop effect was found while the Modified Stroop effect was non-significant. The results raise questions about the Modified Stroop task's utility in identifying at-risk women. Methodological and clinical implications are discussed.

Baseline brain function in the preadolescents of the ABCD Study.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.

Substance use patterns in 9-10 year olds: Baseline findings from the adolescent brain cognitive development (ABCD) study.

BACKGROUND: The Adolescent Brain Cognitive Development ™ Study (ABCD Study®) is an open-science, multi-site, prospective, longitudinal study following over 11,800 9- and 10-year-old youth into early adulthood. The ABCD Study aims to prospectively examine the impact of substance use (SU) on neurocognitive and health outcomes. Although SU initiation typically occurs during teen years, relatively little is known about patterns of SU in children younger than 12. METHODS: This study aims to report the detailed ABCD Study® SU patterns at baseline (n = 11,875) in order to inform the greater scientific community about cohort's early SU. Along with a detailed description of SU, we ran mixed effects regression models to examine the association between early caffeine and alcohol sipping with demographic factors, externalizing symptoms and parental history of alcohol and substance use disorders (AUD/SUD). PRIMARY RESULTS: At baseline, the majority of youth had used caffeine (67.6 %) and 22.5 % reported sipping alcohol (22.5 %). There was little to no reported use of other drug categories (0.2 % full alcohol drink, 0.7 % used nicotine, <0.1 % used any other drug of abuse). Analyses revealed that total caffeine use and early alcohol sipping were associated with demographic variables (p's<.05), externalizing symptoms (caffeine p = 0002; sipping p = .0003), and parental history of AUD (sipping p = .03). CONCLUSIONS: ABCD Study participants aged 9-10 years old reported caffeine use and alcohol sipping experimentation, but very rare other SU. Variables linked with early childhood alcohol sipping and caffeine use should be examined as contributing factors in future longitudinal analyses examining escalating trajectories of SU in the ABCD Study cohort.

Appearance of a new nucleosomal protein during differentiation of human leukemia (HL-60) cells.

A 60-kilodalton protein was identified in chromatin digested by micrococcal nuclease during retinoic acid-induced differentiation of human leukemia (HL-60) cells to mature-like granulocytes. The protein was not detected in a retinoic acid-resistant variant of the HL-60 cell line treated with retinoic acid, in HL-60 cells induced with dimethyl sulfoxide, or in normal human granulocytes. This protein may have an important role in the regulation of retinoic acid-induced leukemic cell differentiation.

Anterior cingulate cortex, error detection, and the online monitoring of performance.

An unresolved question in neuroscience and psychology is how the brain monitors performance to regulate behavior. It has been proposed that the anterior cingulate cortex (ACC), on the medial surface of the frontal lobe, contributes to performance monitoring by detecting errors. In this study, event-related functional magnetic resonance imaging was used to examine ACC function. Results confirm that this region shows activity during erroneous responses. However, activity was also observed in the same region during correct responses under conditions of increased response competition. This suggests that the ACC detects conditions under which errors are likely to occur rather than errors themselves.

Adolescent neurocognitive development and impacts of substance use: Overview of the adolescent brain cognitive development (ABCD) baseline neurocognition battery.

Adolescence is characterized by numerous social, hormonal and physical changes, as well as a marked increase in risk-taking behaviors. Dual systems models attribute adolescent risk-taking to tensions between developing capacities for cognitive control and motivational strivings, which may peak at this time. A comprehensive understanding of neurocognitive development during the adolescent period is necessary to permit the distinction between premorbid vulnerabilities and consequences of behaviors such as substance use. Thus, the prospective assessment of cognitive development is fundamental to the aims of the newly launched Adolescent Brain and Cognitive Development (ABCD) Consortium. This paper details the rationale for ABC'lected measures of neurocognition, presents preliminary descriptive data on an initial sample of 2299 participants, and provides a context for how this large-scale project can inform our understanding of adolescent neurodevelopment.

Perceived stress is associated with increased rostral middle frontal gyrus cortical thickness: a family-based and discordant-sibling investigation.

Elevated stress perception and depression commonly co-occur, suggesting that they share a common neurobiology. Cortical thickness of the rostral middle frontal gyrus (RMFG), a region critical for executive function, has been associated with depression- and stress-related phenotypes. Here, we examined whether RMFG cortical thickness is associated with these phenotypes in a large family-based community sample. RMFG cortical thickness was estimated using FreeSurfer among participants (n = 879) who completed the ongoing Human Connectome Project. Depression-related phenotypes (i.e. sadness, positive affect) and perceived stress were assessed via self-report. After accounting for sex, age, ethnicity, average whole-brain cortical thickness, twin status and familial structure, RMFG thickness was positively associated with perceived stress and sadness and negatively associated with positive affect at small effect sizes (accounting for 0.2-2.4% of variance; p-fdr: 0.0051-0.1900). Perceived stress was uniquely associated with RMFG thickness after accounting for depression-related phenotypes. Further, among siblings discordant for perceived stress, those reporting higher perceived stress had increased RMFG thickness (P = 4 × 10-7 ). Lastly, RMFG thickness, perceived stress, depressive symptoms, and positive affect were all significantly heritable, with evidence of shared genetic and environmental contributions between self-report measures. Stress perception and depression share common genetic, environmental, and neural correlates. Variability in RMFG cortical thickness may play a role in stress-related depression, although effects may be small in magnitude. Prospective studies are required to examine whether variability in RMFG thickness may function as a risk factor for stress exposure and/or perception, and/or arises as a consequence of these phenotypes.

What can research on schizophrenia tell us about the cognitive neuroscience of working memory?

Work with individuals with lesions to specific brain regions has long been used to test or even generate theories regarding the neural systems that support specific cognitive processes. Work with individuals who have neuropsychiatric disorders that also involve neurobiological disturbances may be able to play a similar role in theory testing and building. For example, schizophrenia is a psychiatric disorder thought to involve a range of neurobiological disturbances. Further, individuals with schizophrenia are known to suffer from deficits in working memory, meaning that examining the work on the neurobiology of working memory deficits in schizophrenia may help to further our understanding of the cognitive neuroscience of working memory. This article discusses the pros and cons of extrapolating from work in schizophrenia to models of healthy working memory function, and reviews the literature on working memory function in schizophrenia in relationship to existing human and non-human primate models of the cognitive neuroscience of working memory.

Histopathology of methylbenzylnitrosamine-induced esophageal carcinoma in the rat: comparison with cytomorphology.

The incidence of human carcinoma of the esophagus is increased in association with environmental nitrosamines and dietary zinc deficiency. For examination of the role of zinc deficiency in esophageal carcinogenesis, methylbenzylnitrosamine [(MBN) CAS: 937-40-6] was used to induce esophageal carcinoma in rats fed either a zinc-deficient or control diet. Histologic examination of the MBN-treated Sprague-Dawley rat esophagi revealed a significantly higher incidence of esophageal carcinoma in the zinc-deficient rats vs. controls (62 vs. 33%). In addition, three distinct cytologic and histologic patterns were observed in the animals with esophageal carcinoma: pattern I--basal cell hyperplasia, atypical basal cells, few dyskeratotic cells; pattern II--basal cell hyperplasia, atypical basal cells, many dyskeratotic cells; and pattern III--many dyskeratotic cells without basal cell hyperplasia. These three patterns did not occur simultaneously in the same esophagi, and zinc deficiency did not alter the appearance of these patterns. A strong correlation between the appearance of moderate or severe dysplasia cytologically and microinvasive carcinoma histologically was demonstrated. In those animals with histologically evident microinvasive carcinoma, there was no cytologic evidence of carcinoma in situ or invasive carcinoma. Cytology of these esophageal carcinomas revealed only moderate or severe dysplasia. To the extent that the rat model represents the evolution of esophageal carcinoma in humans, the results presented here suggest that the cytologic appearance of moderate or severe dysplasia indicates the need for further evaluation of patients at risk for esophageal carcinoma.

Selective inhibition of methylbenzylnitrosamine-induced formation of esophageal O6-methylguanine by dietary ellagic acid in rats.

Ellagic acid is a naturally occurring plant phenol which has been shown to reduce the incidence of a number of carcinogen-induced tumors including methylbenzylnitrosamine (MBN)-induced esophageal carcinoma in the rat. The postulated mechanism of MBN-induced esophageal carcinogenesis is through oxidation of MBN to form benzaldehyde and an activated metabolite which methylates DNA forming a variety of methylated DNA adducts including O6-methylguanine (O6-mGua) and 7-methylguanine (m7Gua). O6-mGua adducts have been shown to induce DNA mutations which can lead to cancer, while m7Gua adducts do not appear to be related to tumor induction. In this study, we examined whether the decreased incidence of MBN-induced esophageal carcinoma observed with dietary ellagic acid was associated with a decrease in the in vivo and in vitro formation of MBN-induced DNA adducts and whether this reduction was specific to O6-mGua or due to a reduction in total methylation. Weanling male Sprague-Dawley rats were fed a nutritionally complete diet with and without the addition of 0.4 g of ellagic acid per kg of diet. This dose of dietary ellagic acid has previously been shown to reduce the incidence of MBN-induced esophageal carcinoma by 30 to 50%. After 3 wk on the diets, rats were given injections of a single dose of MBN (2.0 mg/kg of body weight i.p.) and sacrificed 1 h after injection. Dietary ellagic acid significantly reduced the MBN-induced in vivo formation of esophageal O6-mGua, without significantly reducing the formation of esophageal m7Gua. Examination of this effect in an in vitro methylation assay demonstrated that dietary ellagic acid did not reduce the ability of esophageal microsomes to methylate purified calf thymus DNA; however, pretreatment of the calf thymus DNA with ellagic acid selectively reduced the MBN-induced formation of O6-mGua by microsomes from both ellagic acid-fed and control animals without altering the in vitro formation of m7Gua. These results suggest that ellagic acid bound to DNA selectively blocks methylation of the O6-position of guanine without inhibiting the activation of MBN or the ability of MBN to methylate DNA.

Esophageal microsomal metabolism of N-nitrosomethylbenzylamine in the zinc-deficient rat.

Epidemiological studies in China suggest that dietary zinc deficiency and environmental exposure to N-nitrosamine carcinogens, such as N-nitrosomethylbenzylamine (NMBA), are among the factors associated with an increased incidence of esophageal carcinoma in humans. NMBA belongs to a class of nitrosamines which require activation by the cytochrome P-450-dependent mixed-function oxidases in order to be mutagenic. Rats maintained on a zinc-deficient diet exhibited an increased incidence of NMBA-induced esophageal carcinoma when compared to rats on a control diet. The increased tumor formation was associated with an alteration of the microsomal metabolism of NMBA. Weanling male Sprague-Dawley rats were raised on egg protein diets containing 2.3 ppm zinc (low zinc) or 50 ppm zinc (control zinc). Analysis of tissues revealed a rapid decline in the levels of zinc in serum and esophagi of the animals fed the low-zinc diet. Gastric and hepatic zinc content did not differ significantly between the animals fed the low-zinc diet and the animals fed the control zinc diet, even after 6 weeks. Microsomes were prepared from esophageal mucosa, livers, and forestomachs from weanling animals fed these diets for 3 weeks. The rate of formation of benzaldehyde from NMBA by esophageal mucosal microsomes prepared from the rats fed the low-zinc diet was nearly 10-fold higher than that of the rats fed the control zinc diet [0.230 +/- 0.047 (S.E.) versus 0.024 +/- 0.008 nmol/min/mg microsomal protein; p less than 0.001]. The rate of benzaldehyde formation by hepatic microsomes was 0.062 +/- 0.005 nmol/min/mg microsomal protein in the rats fed the low-zinc diet and 0.042 +/- 0.002 nmol/min/mg microsomal protein in the rats fed the control zinc diet (p less than 0.01). The rate of benzaldehyde formation by forestomach microsomes was not detectable in tissue from rats on either diet. This increased rate of NMBA metabolism by esophageal mucosal microsomes from the zinc-deficient rats may explain the increased incidence of esophageal carcinoma in these animals.