Social determinants of health, the microbiome, and surgical injury.

ABSTRACT: Postinjury infection continues to plague trauma and emergency surgery patients fortunate enough to survive the initial injury. Rapid response systems, massive transfusion protocols, and the development of level 1 trauma centers, among others, have improved the outcome for millions of patients worldwide. Nonetheless, despite this excellent initial care, patients still remain vulnerable to postinjury infections that can result in organ failure, prolonged critical illness, and even death. While risk factors have been identified (degree of injury, blood loss, time to definitive care, immunocompromise, etc.), they remain probabilistic, not deterministic, and do not explain outcome variability at the individual case level. Here, we assert that analysis of the social determinants of health, as reflected in the patient's microbiome composition (i.e., community structure, membership) and function (metabolomic output), may offer a "window" with which to define individual variability following traumatic injury. Given emerging knowledge in the field, a more comprehensive evaluation of biomarkers within the patient's microbiome, from stool-based microbial metabolites to those in plasma and those present in exhaled breath, when coupled with clinical metadata and machine learning, could lead to a more deterministic assessment of an individual's risk for a poor outcome and those factors that are modifiable. The aim of this piece is to examine how measurable elements of the social determinants of health and the life history of the patient may be buried within the ecologic memory of the gut microbiome. Here we posit that interrogation of the gut microbiome in this manner may be used to inform novel approaches to drive recovery following a surgical injury.

TXA does not affect levels of TBI-related biomarkers in blunt TBI with ICH: A secondary analysis of the prehospital TXA for TBI trial.

BACKGROUND: Brain specific biomarkers such as glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), and microtubule-associated protein-2 (MAP-2) have been identified as tools for diagnosis in traumatic brain injury (TBI). Tranexamic acid (TXA) has been shown to decrease mortality in patients with intracranial hemorrhage (ICH). The effect of TXA on these biomarkers is unknown. We investigated whether TXA affects levels of GFAP, UCH-L1, and MAP-2, and whether biomarker levels are associated with mortality in patients receiving TXA. METHODS: Patients enrolled in the prehospital TXA for TBI trial had GFAP, UCHL-1 and MAP-2 levels drawn at 0 hour and 24 hours postinjury (n = 422). Patients with ICH from blunt trauma with a GCS <13 and SBP >90 were randomized to placebo, 2 g TXA bolus, or 1 g bolus +1 g/8 hours TXA infusion. Associations of TXA and 24-hour biomarker change were assessed with multivariate linear regression. Association of biomarkers with 28-day mortality was assessed with multivariate logistic regression. All models were controlled for age, GCS, ISS, and AIS head. RESULTS: Administration of TXA was not associated with a change in biomarkers over 24 hours postinjury. Changes in biomarker levels were associated with AIS head and age. On admission, higher GFAP (odds ratio [OR], 1.75; confidence interval [CI], 1.31-2.38; p < 0.001) was associated with increased 28-day mortality. At 24 hours postinjury, higher levels of GFAP (OR, 2.09; CI, 1.37-3.30; p < 0.001 and UCHL-1 (OR, 2.98; CI, 1.77-5.25; p < 0.001) were associated with mortality. A change in UCH levels from 0 hour to 24 hours postinjury was also associated with increased mortality (OR, 1.68; CI, 1.15-2.49; p < 0.01). CONCLUSION: Administration of TXA does not impact change in GFAP, UCHL-1, or MAP-2 during the first 24 hours after blunt TBI with ICH. Higher levels of GFAP and UCH early after injury may help identify patients at high risk for 28-day mortality. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Social Vulnerability and Firearm Violence: Geospatial Analysis of 5 US Cities.

BACKGROUND: Firearm violence is now endemic to certain US neighborhoods. Understanding factors that impact a neighborhood's susceptibility to firearm violence is crucial for prevention. Using a nationally standardized measure to characterize community-level firearm violence risk has not been broadly studied but could enhance prevention efforts. Thus, we sought to examine the association between firearm violence and the social, structural, and geospatial determinants of health, as defined by the Social Vulnerability Index (SVI). STUDY DESIGN: In this cross-sectional study, we merged 2018 SVI data on census tract with shooting incidents between 2015 and 2021 from Baltimore, Chicago, Los Angeles, New York City, and Philadelphia. We used negative binomial regression to associate the SVI with shooting incidents per 1,000 people in a census tract. Moran's I statistics and spatial lag models were used for geospatial analysis. RESULTS: We evaluated 71,296 shooting incidents across 4,415 census tracts. Fifty-five percent of shootings occurred in 9.4% of census tracts. In all cities combined, a decile rise in SVI resulted in a 37% increase in shooting incidents (p < 0.001). A similar relationship existed in each city: 30% increase in Baltimore (p < 0.001), 50% in Chicago (p < 0.001), 28% in Los Angeles (p < 0.001), 34% in New York City (p < 0.001), and 41% in Philadelphia (p < 0.001). Shootings were highly clustered within the most vulnerable neighborhoods. CONCLUSIONS: In 5 major US cities, firearm violence was concentrated in neighborhoods with high social vulnerability. A tool such as the SVI could be used to inform prevention efforts by directing resources to communities most in need and identifying factors on which to focus these programs and policies.

Tranexamic Acid, Mortality, and Intracranial Hemorrhage Type in Moderate or Severe Traumatic Brain Injury.

This cohort study examines the association of tranexamic acid administration with intracranial hemorrhage type, neurologic outcomes, and mortality in patients with traumatic brain injury.

A novel machine-learning tool to identify community risk for firearm violence: The Firearm Violence Vulnerability Index.

BACKGROUND: Firearm violence in the United States is a public health crisis, but accessing accurate firearm assault data to inform prevention strategies is a challenge. Vulnerability indices have been used in other fields to better characterize and identify at-risk populations during crises, but no tool currently exists to predict where rates of firearm violence are highest. We sought to develop and validate a novel machine-learning algorithm, the Firearm Violence Vulnerability Index (FVVI), to forecast community risk for shooting incidents, fill data gaps, and enhance prevention efforts. METHODS: Open-access 2015 to 2022 fatal and nonfatal shooting incident data from Baltimore, Boston, Chicago, Cincinnati, Los Angeles, New York City, Philadelphia, and Rochester were merged on census tract with 30 population characteristics derived from the 2020 American Community Survey. The data set was split into training (80%) and validation (20%) sets; Chicago data were withheld for an unseen test set. XGBoost, a decision tree-based machine-learning algorithm, was used to construct the FVVI model, which predicts shooting incident rates within urban census tracts. RESULTS: A total of 64,909 shooting incidents in 3,962 census tracts were used to build the model; 14,898 shooting incidents in 766 census tracts were in the test set. Historical third grade math scores and having a parent jailed during childhood were population characteristics exhibiting the greatest impact on FVVI's decision making. The model had strong predictive power in the test set, with a goodness of fit ( D2 ) of 0.77. CONCLUSION: The Firearm Violence Vulnerability Index accurately predicts firearm violence in urban communities at a granular geographic level based solely on population characteristics. The Firearm Violence Vulnerability Index can fill gaps in currently available firearm violence data while helping to geographically target and identify social or environmental areas of focus for prevention programs. Dissemination of this standardized risk tool could also enhance firearm violence research and resource allocation. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Social Vulnerability Index is strongly associated with urban pediatric firearm violence: An analysis of five major US cities.

BACKGROUND: Firearm-related injury in children is a public health crisis. The Social Vulnerability Index (SVI) identifies communities at risk for adverse effects due to natural or human-caused crises. We sought to determine if SVI was associated with pediatric firearm-related injury and thus could assist in prevention planning. METHODS: The Centers for Disease Control and Prevention's 2018 SVI data were merged on census tract with 2015 to 2022 open-access shooting incident data in children 19 years or younger from Baltimore, Chicago, Los Angeles, New York City, and Philadelphia. Regression analyses were performed to uncover associations between firearm violence, SVI, SVI themes, and social factors at the census tract level. RESULTS: Of 11,654 shooting incidents involving children, 52% occurred in just 6.7% of census tracts, which were on average in the highest quartile of SVI. A decile increase in SVI was associated with a 45% increase in pediatric firearm-related injury in all cities combined (incidence rate ratio, 1.45; 95% confidence interval, 1.41-1.49; p < 0.001). A similar relationship was found in each city: 30% in Baltimore, 51% in Chicago, 29% in Los Angeles, 37% in New York City, and 35% in Philadelphia (all p < 0.001). Socioeconomic status and household composition were SVI themes positively associated with shootings in children, as well as the social factors below poverty, lacking a high school diploma, civilian with a disability, single-parent household, minority, and no vehicle access. Living in areas with multi-unit structures, populations 17 years or younger, and speaking English less than well were negatively associated. CONCLUSION: Geospatial disparities exist in pediatric firearm-related injury and are significantly associated with neighborhood vulnerability. We demonstrate a strong association between SVI and pediatric shooting incidents in multiple major US cities. Social Vulnerability Index can help identify social and structural factors, as well as geographic areas, to assist in developing meaningful and targeted intervention and prevention efforts. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Rising Mortality in Pediatric Self-Inflicted Firearm Trauma Associated With Distinct Anatomic Injury.

INTRODUCTION: Self-inflicted injuries are the second leading cause of pediatric (10-18 y old) mortality. Self-inflicted firearm trauma (SIFT) was responsible for up to half of these deaths in certain age groups. We hypothesized that SIFT prevalence has increased and is associated with specific demographics, injury patterns, and outcomes. MATERIALS AND METHODS: Data were abstracted from the 2007-2018 American College of Surgeons (ACS) Trauma Quality Programs Participant Use Files (TQP-PUF). Pediatric (1-17 yold) victims of firearm violence were eligible. Age, race, gender, anatomic region, and intent were abstracted. Variables were analyzed using chi-squared tests, t-tests, and single-variate linear regression models. Temporal trends were analyzed using ANCOVA tests. Multivariate logistic regressions were conducted to identify factors influencing mortality. Significance was P < 0.05. RESULTS: There were 41,239 pediatric firearm trauma patients (SIFT: 5.5% [n = 2272]). SIFT incidence increased over the 12-y period (2007 (n = 67) versus 2018 (n = 232), P < 0.05). SIFT was significantly associated with Caucasian race, 67% (n = 1537), teenagers, 90% (n = 2056), male gender, 87% (n = 1978), and a higher median injury severity score (ISS) than other intents of injury (SIFT: 20.0 (IQR: 9.0, 25.0) versus other: 9.0 (IQR: 1.0-13.0), P < 0.001). The SIFT mortality rate was 44% (n = 1005). On multivariate regression head gunshot wounds (OR: 21.1, 95% C.I.: 9.9-45.2, P = 0.001), and ISS (OR:1.1, 95% C.I.: 1.1-1.1, P = 0.001) were significantly associated with mortality. Compared to other intents, SIFT mortality rates increased at a higher annual rate (P < 0.001). CONCLUSIONS: Comprehensive local and federal policy changes to reduce firearms access and increase pediatric mental health support may mitigate these injuries.

Review Paper on Penetrating Brain Injury: Ethical Quandaries in the Trauma Bay and Beyond.

OBJECTIVE: The aim of this review was to review the ethical and multidisciplinary clinical challenges facing trauma surgeons when resuscitating patients presenting with penetrating brain injury (PBI) and multicavitary trauma. BACKGROUND: While there is a significant gap in the literature on managing PBI in patients presenting with multisystem trauma, recent data demonstrate that resuscitation and prognostic features for such patients remains poorly described, with trauma guidelines out of date in this field. METHODS: We reviewed a combination of recent multidisciplinary evidence-informed guidelines for PBI and coupled this with expert opinion from trauma, neurosurgery, neurocritical care, pediatric and transplant surgery, surgical ethics and importantly our community partners. RESULTS: Traditional prognostic signs utilized in traumatic brain injury may not be applicable to PBI with a multidisciplinary team approach suggested on a case-by-case basis. Even with no role for neurosurgical intervention, neurocritical care, and neurointerventional support may be warranted, in parallel to multicavitary operative intervention. Special considerations should be afforded for pediatric PBI. Ethical considerations center on providing the patient with the best chance of survival. Consideration of organ donation should be considered as part of the continuum of patient, proxy and family-centric support and care. Community input is crucial in guiding decision making or protocol establishment on an institutional level. CONCLUSIONS: Support of the patient after multicavitary PBI can be complex and is best addressed in a multidisciplinary fashion with extensive community involvement.

Trauma patients in the pediatric ICU: rational use of a limited resource.

PURPOSE OF REVIEW: Traumatic injuries are a leading cause of pediatric mortality; pediatric ICUs (PICUs) are an important but potentially limited resource associated with high costs. In an era of rising healthcare costs, appropriate resource utilization is important. Here, we examine evidence-based guidelines supporting the management of pediatric traumatic injury outside of the PICU. RECENT FINDINGS: Historical management of solid organ injury and traumatic brain injury was focused on operative management. However, over the past four decades, management of solid organ injury has shifted from invasive management to nonsurgical management with a growing body of evidence supporting the safety and efficacy of this trend. The management of traumatic brain injury (TBI) has had a similar evolution to that of solid organ injury with regard to nonoperative management and management outside the critical care setting. SUMMARY: The use of evidence-based guidelines to support expectant management in the setting of pediatric trauma has the potential to reduce unnecessary resource utilization of the PICU. In this review, we present findings that support nonoperative management and management of pediatric trauma outside of the PICU setting. In resource-poor areas, this approach may facilitate care for pediatric trauma patients. The implications are also important in resource-rich settings because of the unintended risks associated with PICU.

Health Care for the Homeless Transgender Community: Psychiatric Services and Transition Care at a Student-Run Clinic.

Transgender individuals disproportionately experience homelessness and health disparities, including lack of access to gender-affirming care. The student-run Lotus Wellness Center provides care to transgender individuals experiencing homelessness, including primary care, mental health stabilization, and transition via hormone therapy, while medical students learn of the unique health needs of this community.

Large, extra-abdominal leiomyoma of the round ligament with carneous degeneration.

Round ligament tumours represent a rare entity that can present similarly to an incarcerated hernia. Basic understanding and appropriate preoperative management is imperative in order to differentiate between the two diagnoses. Leiomyoma is the most common type of round ligament tumour. It is associated with oestrogen exposure and is more common in the presence of uterine leiomyomas. Here we discuss a 68-year-old woman who presented with a palpable left inguinal mass that progressively grew in size, associated with pelvic pressure and discomfort. On surgical resection, the mass was found to be derived from the round ligament at the entrance of the external inguinal ring. Pathology confirmed a round ligament leiomyoma, measuring 25×9×8.5 cm. This case is the largest round ligament leiomyoma recorded to date and the first to exhibit carneous degeneration. A review of the current literature is also provided.

Actigraph measures discriminate pediatric bipolar disorder from attention-deficit/hyperactivity disorder and typically developing controls.

BACKGROUND: Distinguishing pediatric bipolar disorder (BD) from attention-deficit hyperactivity disorder (ADHD) can be challenging. Hyperactivity is a core feature of both disorders, but severely disturbed sleep and circadian dysregulation are more characteristic of BD, at least in adults. We tested the hypothesis that objective measures of activity, sleep, and circadian rhythms would help differentiate pediatric subjects with BD from ADHD and typically developing controls. METHODS: Unmedicated youths (N = 155, 97 males, age 5-18) were diagnosed using DSM-IV criteria with Kiddie-SADS PL/E. BD youths (n = 48) were compared to typically developing controls (n = 42) and children with ADHD (n = 44) or ADHD plus comorbid depressive disorders (n = 21). Three-to-five days of minute-to-minute belt-worn actigraph data (Ambulatory Monitoring Inc.), collected during the school week, were processed to yield 28 metrics per subject, and assessed for group differences with analysis of covariance. Cross-validated machine learning algorithms were used to determine the predictive accuracy of a four-parameter model, with measures reflecting sleep, hyperactivity, and circadian dysregulation, plus Indic's bipolar vulnerability index (VI). RESULTS: There were prominent group differences in several activity measures, notably mean 5 lowest hours of activity, skewness of diurnal activity, relative circadian amplitude, and VI. A predictive support vector machine model discriminated bipolar from non-bipolar with mean accuracy of 83.1 ± 5.4%, ROC area of 0.781 ± 0.071, kappa of 0.587 ± 0.136, specificity of 91.7 ± 5.3%, and sensitivity of 64.4 ± 13.6%. CONCLUSIONS: Objective measures of sleep, circadian rhythmicity, and hyperactivity were abnormal in BD. Wearable sensor technology may provide bio-behavioral markers that can help differentiate children with BD from ADHD and healthy controls.

Mood dysregulation and affective instability in emerging adults with childhood maltreatment: An ecological momentary assessment study.

Childhood maltreatment increases risk for mood, anxiety, substance use and personality disorders and is associated with alterations in structure, function and connectivity of brain regions involved in emotional regulation. We sought to assess whether maltreatment was specifically associated with disturbances in positive or negative mood regulation. Ecological momentary ratings were collected with a wristwatch-like device with joy-stick (Seiko ecolog) approximately six times per day over a week in 60 unmedicated participants (22 control, 38 maltreated, 18-25 years old). Forty-five percent of maltreated subjects had a history of major depression but all were currently euthymic. Principal component analysis with varimax rotation was used to provide orthogonal measures of positive and negative valence, which were analyzed for indices of variability, circadian rhythmicity and persistence, using linear and non-linear hierarchical modeling and Hurst analysis. Groups did not differ in mean levels of positive or negative affect. Maltreated subjects had increased variability and circadian and hemicircadian abnormalities in ratings of positive but not negative affect. Conversely, they had higher estimated Hurst exponents for negative but not positive affect ratings indicating a greater degree of persistence. Abnormalities in variability, rhythmicity and persistence were present in both maltreated subjects with and without histories of major depression. These findings suggest that both positive and negative valence systems may be dysregulated in individuals with childhood maltreatment. However the nature of the dysregulation appears to differ fundamentally in these domains, as positive mood ratings were more variable and negative ratings more persistent.

Childhood Maltreatment, Depression, and Suicidal Ideation: Critical Importance of Parental and Peer Emotional Abuse during Developmental Sensitive Periods in Males and Females.

BACKGROUND: The adverse childhood experience (ACE) study found that risk for depression increased as a function of number of types of childhood maltreatment, and interpret this as a result of cumulative stress. An alternative hypothesis is that risk depends on type and timing of maltreatment. This will also present as a linear increase, since exposure to more types of abuse increases likelihood of experiencing a critical type of abuse at a critical age. METHODS: 560 (223M/337F) young adults (18-25 years) were recruited from the community without regard to diagnosis and balanced to have equal exposure to 0-4 plus types of maltreatment. The Maltreatment and Abuse Chronology of Exposure Scale assessed severity of exposure to 10 types of maltreatment across each year of childhood. Major depressive disorder (MDD) and current symptoms were evaluated by SCID, interview, and self-report. Predictive analytics assessed importance of exposure at each age and evaluated whether exposure at one or two ages was a more important predictor than number, severity, or duration of maltreatment across childhood. RESULTS: The most important predictors of lifetime history of MDD were non-verbal emotional abuse in males and peer emotional abuse (EA) in females at 14 years of age, and these were more important predictors across models than number of types of maltreatment (males: t 9 = 16.39, p < 10(-7); females t 9 = 5.78, p < 10(-4)). Suicidal ideation was predicted, in part, by NVEA and peer EA at age 14, but most importantly by parental verbal abuse at age 5 in males and sexual abuse at age 18 in females. CONCLUSION: This study provides evidence for sensitive exposure periods when maltreatment maximally impacts risk for depression, and provides an alternative interpretation of the ACE study results. These findings fit with emerging neuroimaging evidence for regional sensitivity periods. The presence of sensitive exposure periods has important implications for prevention, preemption, and treatment of MDD.

Childhood maltreatment: altered network centrality of cingulate, precuneus, temporal pole and insula.

BACKGROUND: Childhood abuse is a major risk factor for psychopathology. Previous studies have identified brain differences in maltreated individuals but have not focused on potential differences in network architecture. METHODS: High-resolution T1-weighted magnetic resonance imaging scans were obtained from 265 unmedicated, right-handed 18- to 25-year-olds who were classified as maltreated (n = 142, 55 men/87 women) or nonmaltreated (n = 123, 46 men/77 women) based on extensive interviews. Cortical thickness was assessed in 112 cortical regions (nodes) and interregional partial correlations across subjects were calculated to derive the lowest equivalent cost single-cluster group networks. Permutation tests were used to ascertain whether maltreatment was associated with significant alterations in key centrality measures of these regions and membership in the highly interconnected "rich club." RESULTS: Marked differences in centrality (connectedness, "importance") were observed in a handful of cortical regions. Left anterior cingulate had the second highest number of connections (degree centrality) and was a component of the "rich club" in the control network but ranked low in connectedness (106th of 112 nodes) in the network derived from maltreated-subjects (p < .01). Conversely, right precuneus and right anterior insula ranked first and 15th in degree centrality in the maltreated network versus 90th (p = .01) and 105th (p < .03) in the control network. CONCLUSIONS: Maltreatment was associated with decreased centrality in regions involved in emotional regulation and ability to accurately attribute thoughts or intentions to others and with enhanced centrality in regions involved in internal emotional perception, self-referential thinking, and self-awareness. This may provide a potential mechanism for how maltreatment increases risk for psychopathology.

Parental verbal affection and verbal aggression in childhood differentially influence psychiatric symptoms and wellbeing in young adulthood.

Previous research has shown that exposure to parental verbal aggression is common and associated with increased levels of depression, anxiety, dissociation, and drug use. A key question that has not been addressed is whether verbal affection from the same or opposite parent can attenuate the effects of verbal aggression. This cross-sectional study examined the effects of parental verbal aggression and affection during childhood on measures of psychopathology and wellbeing in a community sample of 2,518 individuals (18-25 years). Data were analyzed for moderating influences using mixed effect models and for direct and indirect effects using structural equation models. The moderation analysis suggested that high levels of exposure to verbal affection did not mitigate the effects of verbal aggression from the same parent, and high levels of verbal affection from another parent did not generally result in a significant attenuation of the effects of verbal aggression. Structural equation models showed that verbal aggression was predominantly associated with effects on psychiatric symptoms scores, whereas verbal affection was primarily associated with effects on measures of wellbeing. These findings highlight the relatively independent effects of verbal aggression and verbal affection and suggest that the latter may be particularly important in establishing a foundation for emotional and physical wellbeing. These findings also suggest that ridicule, disdain, and humiliation cannot be easily counteracted by praise and warmth from the same or another parent.

Hyperactivity persists in male and female adults with ADHD and remains a highly discriminative feature of the disorder: a case-control study.

BACKGROUND: Symptoms of hyperactivity are believed to fade with age leaving ADHD adults mostly inattentive and impulsive. Our aim was to test this assertion using objective measures of hyperactivity, impulsivity and inattention. METHOD: Participants were 40 subjects with ADHD (23M/17F; 35±10 yrs) and 60 healthy adults (28M/32F; 29±9 yrs) blindly assessed using Wender-Reimherr interview ratings, Structured Clinical Interview for DSM-IV Disorders and DSM-IV criteria. Infrared motion capture systems tracked head and leg movements during performance of a No-4's cognitive control task. Subjects also completed the Conners' CPT-II. RESULTS: ADHD and controls differed significantly in activity and attention. Effect sizes for activity measures (d' = 0.7-1.6) were, on average, two-fold larger than differences in attention or impulsivity, correlated more strongly with executive function ratings and were more discriminatory (ROC area = 0.83 for activity composite, 0.65 for No-4's distraction composite, 0.63 for Conners' CPT-II confidence index, 0.96 for the combined activity and attention diagnostic index). This finding was true for subjects with the predominantly inattentive subtype as well as subjects with combined or predominantly hyperactive/impulsive subtype. Males and females with ADHD were equally active. The superior accuracy of activity measures was confirmed using Random Forest and predictive modeling techniques. CONCLUSIONS: Objectively measured hyperactivity persists in adults with ADHD and is a more discriminative feature of the disorder than computerized measures of inattention or impulsivity. This finding supports the hypothesis that a deficient ability to sit still remains a defining feature of the disorder in adults when it is measured objectively.

Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum.

Childhood maltreatment or abuse is a major risk factor for mood, anxiety, substance abuse, psychotic, and personality disorders, and it is associated with reduced adult hippocampal volume, particularly on the left side. Translational studies show that the key consequences of stress exposure on the hippocampus are suppression of neurogenesis in the dentate gyrus (DG) and dendritic remodeling in the cornu ammonis (CA), particularly the CA3 subfield. The hypothesis that maltreatment is associated with volume reductions in 3-T MRI subfields containing the DG and CA3 was assessed and made practical by newly released automatic segmentation routines for FreeSurfer. The sample consisted of 193 unmedicated right-handed subjects (38% male, 21.9 ± 2.1 y of age) selected from the community. Maltreatment was quantified using the Adverse Childhood Experience study and Childhood Trauma Questionnaire scores. The strongest associations between maltreatment and volume were observed in the left CA2-CA3 and CA4-DG subfields, and were not mediated by histories of major depression or posttraumatic stress disorder. Comparing subjects with high vs. low scores on the Childhood Trauma Questionnaire and Adverse Childhood Experience study showed an average volume reduction of 6.3% and 6.1% in the left CA2-CA3 and CA4-DG, respectively. Volume reductions in the CA1 and fimbria were 44% and 60% smaller than in the CA2-CA3. Interestingly, maltreatment was associated with 4.2% and 4.3% reductions in the left presubiculum and subiculum, respectively. These findings support the hypothesis that exposure to early stress in humans, as in other animals, affects hippocampal subfield development.

Reduced fractional anisotropy in the visual limbic pathway of young adults witnessing domestic violence in childhood.

Witnessing domestic violence (WDV) is a traumatic childhood experience associated with increased risk for depression, posttraumatic stress disorder and reduced IQ scores. Specific affects of WDV on brain development have not been assessed. We sought to ascertain whether WDV was associated with abnormalities in white matter (WM) tract integrity using diffusion tensor imaging (DTI). Twenty subjects who witnessed domestic violence (16F/4M, mean age 22.4 ± 2.48 years) but were not physically or sexually abused were compared to 27 healthy controls (19F/8M, 21.9 ± 1.97 years) without exposure to trauma or Axis I and II disorders. DTI images were acquired with a 3T Siemens Trio scanner. Group differences in fractional anisotropy (FA), covaried by age, gender, parental education, perceived financial sufficiency, IQ and degree of exposure to parental verbal aggression were assessed using tract-based spatial statistics (TBSS), which projects FA values onto an alignment-invariant fiber tract representation. FA values in the inferior longitudinal fasciculus of left lateral occipital lobe were significantly lower (P<0.05 corrected for multiple comparison) in the WDV group. FA values correlated inversely with ratings of depression, anxiety, somatization, 'limbic irritability' and neuropsychological measures of processing speed. Measures of radial but not axial diffusivity were affected suggesting alterations in myelination. Degree of FA reduction was associated with duration of witnessing interparental verbal aggression and with exposure between ages 7 and 13 years. The inferior longitudinal fasciculus connects occipital and temporal cortex and is the main component of the visual-limbic pathway that subserves emotional, learning and memory functions that are modality specific to vision. This finding is consistent with the hypothesis that exposure to childhood maltreatment is associated with alterations in fiber pathways that convey the adverse experience to frontal, temporal or limbic regions.