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Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
The global food system puts enormous pressure on the environment. Managing these pressures requires understanding not only where they occur (i.e., where food is produced), but also who drives them (i.e., where food is consumed). However, the size and complexity of global supply chains make it difficult to trace food production to consumption. Here, we provide the most comprehensive dataset of bilateral trade flows of environmental pressures stemming from food production from producing to consuming nations. The dataset provides environmental pressures for greenhouse gas emissions, water use, nitrogen and phosphorus pollution, and the area of land/water occupancy of food production for crops and animals from land, freshwater, and ocean systems. To produce these data, we improved upon reported food trade and production data to identify producing and consuming nations for each food item, allowing us to match food flows with appropriate environmental pressure data. These data provide a resource for research on sustainable global food consumption and the drivers of environmental impact.
The impact of chronic pain and opioid use on cognitive decline and mild cognitive impairment (MCI) is unclear. We investigated these associations in early older adulthood, considering different definitions of chronic pain.
Methods:
Men in the Vietnam Era Twin Study of Aging (VETSA; n = 1,042) underwent cognitive testing and medical history interviews at average ages 56, 62, and 68. Chronic pain was defined using pain intensity and interference ratings from the SF-36 over 2 or 3 waves (categorized as mild versus moderate-to-severe). Opioid use was determined by self-reported medication use. Amnestic and non-amnestic MCI were assessed using the Jak-Bondi approach. Mixed models and Cox proportional hazards models were used to assess associations of pain and opioid use with cognitive decline and risk for MCI.
Results:
Moderate-to-severe, but not mild, chronic pain intensity (β = −.10) and interference (β = −.23) were associated with greater declines in executive function. Moderate-to-severe chronic pain intensity (HR = 1.75) and interference (HR = 3.31) were associated with a higher risk of non-amnestic MCI. Opioid use was associated with a faster decline in verbal fluency (β = −.18) and a higher risk of amnestic MCI (HR = 1.99). There were no significant interactions between chronic pain and opioid use on cognitive decline or MCI risk (all p-values > .05).
Discussion:
Moderate-to-severe chronic pain intensity and interference related to executive function decline and greater risk of non-amnestic MCI; while opioid use related to verbal fluency decline and greater risk of amnestic MCI. Lowering chronic pain severity while reducing opioid exposure may help clinicians mitigate later cognitive decline and dementia risk.
Background: Attitudes toward aging influence many health outcomes, yet their relationship with cognition and Alzheimer’s disease (AD) remains unknown. To better understand their impact on cognition and AD risk, we examined whether positive attitudes predict better cognition and diminished risk on AD biomarkers. Methods: A subsample of older adults with a family history of AD (n=54; women=39) from the McGill PREVENT-AD cohort participated in this study. Participants completed the Attitudes to Ageing Questionnaire (AAQ-24), providing three scores: psychosocial loss, psychological growth and physical change. Participants underwent cognitive testing (Rey Auditory Verbal Learning Test, RAVLT; Delis-Kaplan Executive Function System-Color Word Interference Test, D-KEFS-CWIT), and AD blood-based biomarker assessments (p-tau217, Aβ42/40). Regression models tested associations, adjusting for covariates (age, sex, education, depression, APOE4), and were Bonferroni corrected. Results: Positive attitudes were associated with better recall and recognition (RAVLT) and improved word reading, colour naming, switching, and inhibition (D-KEFS-CWIT) (p<0.00077), while negative attitudes showed the opposite pattern. Negative attitudes were correlated with lower Aβ42/40 ratios, while positive attitudes were linked to lower p-tau217 (p<0.0167). Conclusions: These findings demonstrate that positive attitudes predict better cognition and a lower risk profile for AD biomarkers, suggesting that life outlook may be an early disease feature or a risk factor.
Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.
Dietary intake modulates the gut microbiota by providing fermentation substrates. Both microbiota-accessible nutrients and digestible food components have been shown to modulate microbial abundance and function(1). A range of dietary assessment methods are used to investigate diet-microbe interactions, with two commonly used methods being food frequency questionnaires (FFQ) to assess ‘habitual’ dietary intake and food recalls which measure recent intake proximal to sampling of microbiota. This study aimed to compare diet-microbiome associations identified from habitual and proximal dietary intake aligned with stool microbiota sampling in a healthy adult cohort. Military trainees (n = 35), and non-military personnel (junior doctors during hospital placement; n = 21) self-reported proximal dietary intake using digital (Easy Diet Diary) or paper-based 24-hr recalls. Habitual intake was assessed using the Comprehensive Nutrition Assessment Questionnaire (CNAQ)(2) FFQ. Both measures were assessed at baseline and study completion. Diet recalls matched to the same week of FFQ were analysed using Foodworks 10(3). Stool samples were collected for metagenomic shotgun sequencing and annotated against the Microba Life Sciences platform. MaAsLin2 identified linear associations between nutrients and microbe abundance, controlling for total energy intake and individual variation with repeated measures. Thirty dietary variables common to both dietary assessment methods were used in analysis. Mean daily intakes for total energy and macronutrients were not significantly different between habitual and proximal data. Nutrients that differed between methods were polyols (p < 0.001), sugar (p = 0.006), sodium (p = 0.03), alcohol (p < 0.001), vitamin A equivalents (p < 0.001), b-carotene equivalents (p < 0.001) and dietary fibre (p = 0.01). Associations between nutrient intake and microbes also differed between dietary collection methods. Most significant associations were found with nutrients measured by 24-hr recall. Mean (M) proximal intake of polyols (M = 0.9 g, standard deviation (SD) = 1.8 g) was significantly associated with increased relative abundance of Akkermansia spp. and CAG460 spp. but not with habitual intake (M = 3.4 g, SD = 3.2 g). Proximal alcohol intake (M = 2.5 g, SD = 8.8 g) was associated with CAG1427 spp. and Collinsella spp., which was not identified with habitual intake (M = 4.4 g, SD = 6.7 g). In contrast, habitual sugar intake (M = 149 g, SD = 103 g) was associated with Bacteroides spp. and Blautia spp. This association was not evident for proximal intake (M = 112 g, SD = 68 g), suggesting that some diet-microbiota associations may depend on the dietary assessment method used. These findings demonstrate the relevance of considering both habitual diet and proximal intake when conducting diet-microbiome research. Further analysis will investigate the role of these microbes and further associations between these nutrients and the functional capacity of the microbiota.
Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.
Methods
We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).
Results
Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.
Conclusions
Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.
In Michigan, United States of America, where Asian parasitoids were released to manage emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), we monitored four native parasitoids that also attack the invasive beetle – Atanycolus cappaerti Marsh and Strazanac, A. simplex (Cresson), and Spathius laflammei Provancher (all Hymenoptera: Braconidae), and Phasgonophora sulcata Westwood (Hymenoptera: Chalcididae) – using yellow pan traps and tree dissections. Adult A. cappaerti, followed by A. simplex, had the broadest seasonal activity, S. laflammei was captured primarily in the first half of the growing season, and P. sulcata was restricted to mid-summer. Adult abundances of native species varied among years but, except for P. sulcata, were never significantly lower than the established Asian emerald ash borer larval parasitoids, Tetrastichus planipennisi Yang (Hymenoptera: Eulophidae) and Spathius galinae Belokobylskij and Strazanac (Hymenoptera: Braconidae). Densities of emerald ash borer larvae parasitised by A. cappaerti or P. sulcata did not differ significantly from those of the two Asian species. Although adult A. simplex and S. laflammei were frequently captured, we did not confirm parasitisation of any emerald ash borer larvae by these two species, suggesting that they rarely attack emerald ash borer. We did not find any negative correlations between adult or immature parasitoid abundance of any parasitoid species, suggesting that any interspecific competition that may be occurring is negligible.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
Suicidal thoughts and behaviors are elevated among active-duty service members (ADSM) and veterans compared to the general population. Hence, it is a priority to examine maintenance factors underlying suicidal ideation among ADSM and veterans to develop effective, targeted interventions. In particular, interpersonal risk factors, hopelessness, and overarousal have been robustly connected to suicidal ideation and intent.
Methods
To identify the suicidal ideation risk factors that are most relevant, we employed network analysis to examine between-subjects (cross-sectional), contemporaneous (within seconds), and temporal (across four hours) group-level networks of suicidal ideation and related risk factors in a sample of ADSM and veterans (participant n = 92, observations n = 10 650). Participants completed ecological momentary assessment (EMA) surveys four times a day for 30 days, where they answered questions related to suicidal ideation, interpersonal risk factors, hopelessness, and overarousal.
Results
The between-subjects and contemporaneous networks identified agitation, not feeling close to others, and ineffectiveness as the most central symptoms. The temporal network revealed that feeling ineffective was most likely to influence other symptoms in the network over time.
Conclusion
Our findings suggest that ineffectiveness, low belongingness, and agitation are important drivers of moment-to-moment and longitudinal relations between risk factors for suicidal ideation in ADSM and veterans. Targeting these symptoms may disrupt suicidal ideation.
OBJECTIVES/GOALS: Contingency management (CM) procedures yield measurable reductions in cocaine use. This poster describes a trial aimed at using CM as a vehicle to show the biopsychosocial health benefits of reduced use, rather than total abstinence, the currently accepted metric for treatment efficacy. METHODS/STUDY POPULATION: In this 12-week, randomized controlled trial, CM was used to reduce cocaine use and evaluate associated improvements in cardiovascular, immune, and psychosocial well-being. Adults aged 18 and older who sought treatment for cocaine use (N=127) were randomized into three groups in a 1:1:1 ratio: High Value ($55) or Low Value ($13) CM incentives for cocaine-negative urine samples or a non-contingent control group. They completed outpatient sessions three days per week across the 12-week intervention period, totaling 36 clinic visits and four post-treatment follow-up visits. During each visit, participants provided observed urine samples and completed several assays of biopsychosocial health. RESULTS/ANTICIPATED RESULTS: Preliminary findings from generalized linear mixed effect modeling demonstrate the feasibility of the CM platform. Abstinence rates from cocaine use were significantly greater in the High Value group (47% negative; OR = 2.80; p = 0.01) relative to the Low Value (23% negative) and Control groups (24% negative;). In the planned primary analysis, the level of cocaine use reduction based on cocaine-negative urine samples will serve as the primary predictor of cardiovascular (e.g., endothelin-1 levels), immune (e.g., IL-10 levels) and psychosocial (e.g., Addiction Severity Index) outcomes using results from the fitted models. DISCUSSION/SIGNIFICANCE: This research will advance the field by prospectively and comprehensively demonstrating the beneficial effects of reduced cocaine use. These outcomes can, in turn, support the adoption of reduced cocaine use as a viable alternative endpoint in cocaine treatment trials.
OBJECTIVES/GOALS: Assess molecular and cellular mechanisms of allograft loss in kidney biopsies using digital spatial profiling and clinical outcomes data. METHODS/STUDY POPULATION: Patients with chronic allograft dysfunction (CGD), enrolled in the Deterioration of Kidney Allograft Function (DeKAF) study, with or without eventual allograft loss, were included. CGD was defined as a >25% increase in creatinine over 3 months relative to a baseline. Kidney biopsy tissue was assessed by Nanostring GeoMX digital spatial profiling (DSP) after staining with anti-pan-cytokeratin, anti-CD45, anti-CD68, Syto-13, to identify specific cell populations, and Nanostring’s Whole Transcriptome Atlas (WTA), to quantify the distribution of transcripts across the biopsy. Up to 14 regions of interest (ROIs) were selected, with or without glomerulus. CIBERSORT was used to perform cell deconvolution. Clinical and outcomes data were from the DeKAF study and United States Renal Data System. RESULTS/ANTICIPATED RESULTS: Macrophage (M1) cell population abundance was significantly different in ROIs with glomerulus between graft loss and no graft loss. Principle component analysis of differentially expressed genes resulted in transcriptomes in ROIs that cluster together by clinical outcome of graft loss or no graft loss. There were 203 DEGs in ROIs with glomerulus that were different by graft loss or no graft loss. By pathway analysis, these 203 DEGS were enriched in the T-cell activation, integrin signaling and inflammation pathways. DISCUSSION/SIGNIFICANCE: DSP of kidney allograft biopsies allows for the identification and quantification of specific cell types, such as macrophages and molecular transcripts as potential drug targets. This data can be used to understand mechanisms of kidney allograft loss and may lead to improved immune suppression in kidney transplant recipients.
Medically important ixodid ticks often carry multiple pathogens, with individual ticks frequently coinfected and capable of transmitting multiple infections to hosts, including humans. Acquisition of multiple zoonotic pathogens by immature blacklegged ticks (Ixodes scapularis) is facilitated when they feed on small mammals, which are the most competent reservoir hosts for Anaplasma phagocytophilum (which causes anaplasmosis in humans), Babesia microti (babesiosis) and Borrelia burgdorferi (Lyme disease). Here, we used data from a large-scale, long-term experiment to ask whether patterns of single and multiple infections in questing nymphal I. scapularis ticks from residential neighbourhoods differed from those predicted by independent assortment of pathogens, and whether patterns of coinfection were affected by residential application of commercial acaricidal products. Quantitative polymerase chain reaction was used for pathogen detection in multiplex reactions. In control neighbourhoods and those treated with a fungus-based biopesticide deployed against host-seeking ticks (Met52), ticks having only single infections of either B. microti or B. burgdorferi were significantly less common than expected, whereas coinfections with these 2 pathogens were significantly more common. However, use of tick control system bait boxes, which kill ticks attempting to feed on small mammals, eliminated the bias towards coinfection. Although aimed at reducing the abundance of host-seeking ticks, control methods directed at ticks attached to small mammals may influence human exposure to coinfected ticks and the probability of exposure to multiple tick-borne infections.
The swelling of n-butylammonium vermiculite in water was investigated as a function of the sol concentration (r), the salt concentration (c) and the temperature (T).
The interlayer spacing in the gel phase was investigated as a function of r and c by neutron diffraction and by laboratory experiments which measured how many times its own volume a crystal would absorb. The salt concentration was found to be the stronger variable with the interlayer spacing decreasing proportional to c0.5, which is consistent with previous results and with the Coulombic attraction theory. The sol concentration was found to affect the swelling for two reasons, the salt fractionation effect and the trapped salt effect. Both of these cause the salt concentration in the supernatant fluid to be greater than that originally added to the crystals and so reduce the swelling.
A new method was used for extracting the solution from inside the gels by collapsing the gels by the addition of potassium hydrogen carbonate. The Volhardt titration was carried out on the extracted and supernatant solutions from about 250 gels. The ratio of the external to the internal chloride concentration was found to be approximately constant across the range of salt concentrations. Its average value was equal to 2.6, again in agreement with Coulombic attraction theory and showing the surface potential to be constant at about 70 mV.
The (r, c, T) boundary of the two phase colloid region was investigated by three methods. A plot of log c against Tc was linear within experimental accuracy, with a gradient of 0.077 K−1 or 13 K per log unit. This shows that the surface potential varies by only 1 mV per decade in the salt concentration. The system is therefore governed by the Dirichlet boundary condition and not by the Nernst equation.
While mentors can learn general strategies for effective mentoring, existing mentorship curricula do not comprehensively address how to support marginalized mentees, including LGBTQIA+ mentees. After identifying best mentoring practices and existing evidence-based curricula, we adapted these to create the Harvard Sexual and Gender Minority Health Mentoring Program. The primary goal was to address the needs of underrepresented health professionals in two overlapping groups: (1) LGBTQIA+ mentees and (2) any mentees focused on LGBTQIA+ health. An inaugural cohort (N = 12) of early-, mid-, and late-career faculty piloted this curriculum in spring 2022 during six 90-minute sessions. We evaluated the program using confidential surveys after each session and at the program’s conclusion as well as with focus groups. Faculty were highly satisfied with the program and reported skill gains and behavioral changes. Our findings suggest this novel curriculum can effectively prepare mentors to support mentees with identities different from their own; the whole curriculum, or parts, could be integrated into other trainings to enhance inclusive mentoring. Our adaptations are also a model for how mentorship curricula can be tailored to a particular focus (i.e., LGBTQIA+ health). Ideally, such mentor trainings can help create more inclusive environments throughout academic medicine.
The reading the mind in the eyes test (RMET) – which assesses the theory of mind component of social cognition – is often used to compare social cognition between patients with schizophrenia and healthy controls. There is, however, no systematic review integrating the results of these studies. We identified 198 studies published before July 2020 that administered RMET to patients with schizophrenia or healthy controls from three English-language and two Chinese-language databases. These studies included 41 separate samples of patients with schizophrenia (total n = 1836) and 197 separate samples of healthy controls (total n = 23 675). The pooled RMET score was 19.76 (95% CI 18.91–20.60) in patients and 25.53 (95% CI 25.19–25.87) in controls (z = 12.41, p < 0.001). After excluding small-sample outlier studies, this difference in RMET performance was greater in studies using non-English v. English versions of RMET (Chi [Q] = 8.54, p < 0.001). Meta-regression analyses found a negative association of age with RMET score and a positive association of years of schooling with RMET score in both patients and controls. A secondary meta-analysis using a spline construction of 180 healthy control samples identified a non-monotonic relationship between age and RMET score – RMET scores increased with age before 31 and decreased with age after 31. These results indicate that patients with schizophrenia have substantial deficits in theory of mind compared with healthy controls, supporting the construct validity of RMET as a measure of social cognition. The different results for English versus non-English versions of RMET and the non-monotonic relationship between age and RMET score highlight the importance of the language of administration of RMET and the possibility that the relationship of aging with theory of mind is different from the relationship of aging with other types of cognitive functioning.
Word finding or “naming” difficulty is a symptom of multiple neurological disorders; therefore, naming assessment is an integral component of neuropsychological evaluation. Prior work has found weaker second-language naming in healthy proficient bilingual youth than monolingual youth, and similar findings have been shown in adults with epilepsy. Considering the potential influences of both early onset epilepsy and bilingualism on brain development, we compared naming in English second language (ESL) and monolingual youth with epilepsy. To assess the impact of bilingualism independent of the known effects of seizure laterality (i.e., poor naming in those with left, dominant-hemisphere seizures), we excluded patients with left language dominance and unilateral seizures. We hypothesized that like other groups, naming would be weaker in ESL than in monolingual youth with epilepsy.
Participants and Methods:
Participants included 84 children with seizures that could not be lateralized clinically (n=36), bilateral seizures (n=20), centrotemporal spikes (n=3), and those with unilateral seizures and atypical language dominance (n=25), ages 6-15 years old: 66 monolingual, English (mean age: 10.87 ± 2.70 years) and 18 ESL (mean age: 10.78 ± 2.88 years). Those with FSIQ < 70 and vocabulary SS < 6 were excluded to ensure English proficiency. Independent samples t-tests, multivariate ANOVA, and chi-square tests compared groups on demographic factors and test performance. All measures (FSIQ, WISC/WASI Vocabulary, letter and category fluency, Children’s Auditory (AN) and Visual Naming (VN) Tests) were administered in English.
Results:
Monolingual and ESL groups did not differ in: age, sex, SES, seizure type (i.e., non-lateralized, bilateral, centrotemporal spikes, or atypical language dominance), epilepsy onset age, or number of AEDs. Comparisons also showed no differences in FSIQ, vocabulary, letter fluency, or category fluency (all ps > 0.05). By contrast, auditory and visual naming performances were weaker among ESL patients than monolingual patients: AN accuracy, F(1,81) = 10.89, p = 0.001; AN tip-of-the-tongues (TOTs), F(1,81) = 6.35, p = 0.014; AN Summary Scores (SS), F(1,81) = 6.17, p = 0.015; VN accuracy, F(1,81) = 4.66, p = 0.034; VN SS, F(1,81) = 4.87, p = 0.030, with the exception of VN TOTs, which approached significance, F(1,81) = 3.55, p = 0.063.
Conclusions:
Consistent with findings in bilingual healthy youth and ESL adults with epilepsy, naming in ESL youth with epilepsy was weaker than in monolingual children. The groups did not differ on other aspects of language. Thus, unlike other expressive verbal functions, naming is adversely affected in the second language of bilingual people with epilepsy across the age span. These results suggest that poor naming in ESL patients cannot be used to infer a naming deficit, and/or left (dominant) temporal lobe dysfunction.
Radiotherapy for pediatric brain tumor has been associated with late cognitive effects. Compared to conventional photon radiotherapy (XRT), proton radiotherapy (PRT) delivers less radiation to healthy brain tissue. PRT has been associated with improved long term cognitive outcomes compared to XRT. However, there is limited research comparing the effects of XRT and PRT on verbal memory outcomes.
Participants and Methods:
Survivors of pediatric brain tumor treated with either XRT (n = 29) or PRT (n = 51) completed neuropsychological testing > 1 year following radiotherapy. XRT and PRT groups were similar with respect to sex, handedness, race, age at diagnosis, age at evaluation, tumor characteristics, and treatment history (i.e., craniospinal irradiation, craniotomy, shunting, chemotherapy, radiation dose). Verbal learning and memory were assessed using the age-appropriate version of the California Verbal Learning Test (CVLT-II/CVLT-C). Measures of intellectual functioning, executive functioning, attention and adaptive behavior were also collected. Performance on neuropsychological measures was compared between treatment groups (XRT vs. PRT) using analysis of covariance (ANCOVA). On the CVLT, each participant was classified as having an encoding deficit profile (i.e., impaired learning, recall, and recognition), retrieval deficit profile (i.e., impaired recall but intact recognition), intact profile, or other profile. Chi-squared tests of independence were used to compare the probability of each memory profile between treatment groups. Pearson correlation was used to examine associations between memory performance and strategy use, intellectual functioning, adaptive behavior, attention, and executive functioning.
Results:
Overall, patients receiving PRT demonstrated superior verbal learning (CVLT Trials 1-5; t(76) = 2.61, p = .011), recall (CVLT Long Delay Free; t(76) = 3.57, p = .001) and strategy use (CVLT Semantic Clustering; t(76) = 2.29, p = .025) compared to those treated with XRT. Intact performance was more likely in the PRT group than the XRT group (71% PRT, 38% XRT; X2 = 8.14, p = .004). Encoding and retrieval deficits were both more common in the XRT group, with encoding problems being most prevalent (Encoding Deficits: 31% XRT, 12% PRT, X2 = 4.51, p = .034; Retrieval Deficits: 17% XRT, 4% PRT, X2 = 4.11, p = .043). Across all participants, semantic clustering predicted better encoding (r = .28, p = .011) and retrieval (r = .26, p = .022). Better encoding predicted higher intellectual (r = .56, p < .001) and adaptive functioning (r = .30, p = .011), and fewer parent-reported concerns about day-today attention (r = -.36, p = .002), and cognitive regulation (r = -.35, p = .002).
Conclusions:
Results suggest that PRT is associated with superior verbal memory outcomes compared to XRT, which may be driven by encoding skills and use of learning strategies. Moreover, encoding ability predicted general intellectual ability and day-to-day functioning. Future work may help to clarify underlying neural mechanisms associated with verbal memory decline following radiotherapy, which will better inform treatment approaches for survivors of pediatric brain tumor.