Demographic characteristics and epigenetic biological aging among post-9/11 veterans: Associations of DunedinPACE with sex, race, and age.

Measures of epigenetic aging derived from DNA methylation (DNAm) have enabled the assessment of biological aging in new populations and cohorts. In the present study, we used an epigenetic measure of aging, DunedinPACE, to examine rates of aging across demographic groups in a sample of 2,309 United States military veterans from the VISN 6 MIRECC's Post-Deployment Mental Health Study. As assessed by DunedinPACE, female veterans were aging faster than male veterans (ß = 0.39, 95 % CI [0.29, 0.48], p < .001), non-Hispanic Black veterans were aging faster than non-Hispanic White veterans (ß = 0.58, 95 % CI [0.50, 0.66], p < .001), and older veterans were biologically aging faster than younger veterans (ß = 0.21, 95 % CI [0.18, 0.25], p < .001). In secondary analyses, these differences in rates of aging were not explained by a variety of biopsychosocial covariates. In addition, the percentage of European genetic admixture in non-Hispanic Black veterans was not associated with DunedinPACE. Our findings suggest that female and non-Hispanic Black veterans are at greater risk of accelerated aging among post-9/11 veterans. Interventions that slow aging might provide relatively greater benefit among veterans comprising these at-risk groups.

Genome-wide DNA methylation analysis of cannabis use disorder in a veteran cohort enriched for posttraumatic stress disorder.

Cannabis use has been increasing over the past decade, not only in the general US population, but particularly among military veterans. With this rise in use has come a concomitant increase in cannabis use disorder (CUD) among veterans. Here, we performed an epigenome-wide association study for lifetime CUD in an Iraq/Afghanistan era veteran cohort enriched for posttraumatic stress disorder (PTSD) comprising 2,310 total subjects (1,109 non-Hispanic black and 1,201 non-Hispanic white). We also investigated CUD interactions with current PTSD status and examined potential indirect effects of DNA methylation (DNAm) on the relationship between CUD and psychiatric diagnoses. Four CpGs were associated with lifetime CUD, even after controlling for the effects of current smoking (AHRR cg05575921, LINC00299 cg23079012, VWA7 cg22112841, and FAM70A cg08760398). Importantly, cg05575921, a CpG strongly linked to smoking, remained associated with lifetime CUD even when restricting the analysis to veterans who reported never smoking cigarettes. Moreover, CUD interacted with current PTSD to affect cg05575921 and cg23079012 such that those with both CUD and PTSD displayed significantly lower DNAm compared to the other groups. Finally, we provide preliminary evidence that AHRR cg05575921 helps explain the association between CUD and any psychiatric diagnoses, specifically mood disorders.

In-nest mortality and pathology of hawksbill sea turtle (Eretmochelys imbricata) embryos and hatchlings in St. Kitts and Nevis.

Strategies to improve the hatch success and survival of critically endangered hawksbill turtles (Eretmochelys imbricata) require knowledge of threats to them including pathological conditions. The objective of this study was to describe the mortality and pathology of embryos and dead-in-nest hatchlings on St. Kitts and Nevis. Over the 2019/20 and 2020/21 nesting seasons, the combined mean (SD) hatch success for the two islands was 81.9% (13.2%) and deceased individuals within excavated nests were early-stage embryos (70.7%), late-stage embryos (17.7%), pipped-hatchlings (8.2%) or dead-in-nest hatchlings (3.4%). From 2017 to 2021, a post-mortem examination was performed on 183 turtles, including histology for 116. Anatomical malformations affected 77 (42.1%) examined turtles and included abnormal scute shape or number (22.4%), dysmelia (8.7%), schistosomus reflexus (7.7%) and compressed carapace (7.7%). Microscopic lesions were found in 49.1% of turtles and included tissue mineralization (26.7%, including renal, fetal membrane, liver, heart or muscle), chorioallantoitis (16.2%) and skeletal muscle degeneration and necrosis (10%). Inflammatory lesions associated with fungal or bacterial infections were in the skin (n = 3), chorioallantois (n = 4), lung (n = 3) or yolk sac (n = 1). These lesions may reflect non-specific terminal conditions but their presence in-nest helps explain some of the mortality and pathology documented in hatchlings that die during rehabilitative care. All of the gonads adequately represented for histological determination of sex were female (n = 62), supporting concern for feminization of Caribbean hawksbill turtle nests. The study identifies lesions that could affect hatch and emergence success. The high frequency of skeletal malformations indicates the need for investigations addressing regional impact and pathogenesis, especially genetic and environmental aetiologies including nest temperature. Immediate examination of live hatchlings on nest emergence is warranted to better determine the prevalence of non-fatal malformations that could impact fitness and population genetics.

Posttraumatic stress disorder, trauma, and accelerated biological aging among post-9/11 veterans.

People who experience trauma and develop posttraumatic stress disorder (PTSD) are at increased risk for poor health. One mechanism that could explain this risk is accelerated biological aging, which is associated with the accumulation of chronic diseases, disability, and premature mortality. Using data from 2309 post-9/11 United States military veterans who participated in the VISN 6 MIRECC's Post-Deployment Mental Health Study, we tested whether PTSD and trauma exposure were associated with accelerated rate of biological aging, assessed using a validated DNA methylation (DNAm) measure of epigenetic aging-DunedinPACE. Veterans with current PTSD were aging faster than those who did not have current PTSD, ß = 0.18, 95% CI [0.11, 0.27], p < .001. This effect represented an additional 0.4 months of biological aging each year. Veterans were also aging faster if they reported more PTSD symptoms, ß = 0.13, 95% CI [0.09, 0.16], p < 0.001, or higher levels of trauma exposure, ß = 0.09, 95% CI [0.05, 0.13], p < 0.001. Notably, veterans with past PTSD were aging more slowly than those with current PTSD, ß = -0.21, 95% CI [-0.35, -0.07], p = .003. All reported results accounted for age, gender, self-reported race/ethnicity, and education, and remained when controlling for smoking. Our findings suggest that an accelerated rate of biological aging could help explain how PTSD contributes to poor health and highlights the potential benefits of providing efficacious treatment to populations at increased risk of trauma and PTSD.

Development of Mobile Contingency Management for Cannabis Use Reduction.

Many interventions for cannabis use disorder (CUD) are associated with decreases in frequency and quantity of use but fail to increase overall rates of sustained abstinence. It is currently unknown whether reductions in use (in the absence of sustained abstinence) result in clinically significant improvements in functioning. The objective of this study was to refine a mobile contingency management approach to reduce cannabis use to ultimately evaluate whether reductions in frequency and quantity of cannabis are related to improvements in functional and mental health status. Three cohorts of participants (n = 18 total, n = 10 women) were enrolled and completed 2 weeks of ecological momentary assessment (EMA) during a baseline ad lib cannabis use period, followed by a 6-week reduction period. Participants completed EMA assessments multiple times per day and were prompted to provide videotaped saliva cannabis testing 2-3 times daily. Data from participants who were at least 80% adherent to all EMA prompts were analyzed (13 out of 18). During the ad lib phase, participants were using cannabis on 94% of the days and reported using a mean of 1.42 grams daily. The intervention was a mobile application that participants used to record cannabis use by saliva tests to bioverify abstinence and participants completed electronic diaries to report their grams used. During the 6-week intervention phase, participants reported reducing their use days to 47% of the days with a reported mean of .61 grams daily. In the last cohort, at least 50% of the heavy users were able to reduce their cannabis use by at least 50%. The effect of cannabis reduction (versus abstinence) is largely unknown. Observations suggest that it is possible to develop a mobile intervention to reduce cannabis use among heavy users, and this paradigm can be utilized in future work to evaluate whether reductions in cannabis use among heavy users will result in improvements in functional and mental health status.

Development and Implementation of Web-Based Safety Planning Intervention Training for Firefighter Peer Support Specialists.

Background: Recent findings indicate that firefighters may be at increased risk for death by suicide; however, there has been only limited suicide prevention work in fire service to date. Aim: The objective of this program evaluation project was to develop and evaluate a web-based Safety Planning Intervention (SPI) training course for firefighter peer support specialists. Method: Peer support specialists who completed the web-based SPI training were administered evaluation questionnaires before the training and then again at a 3-month follow-up assessment. Results: A total of 213 peer support specialists completed the SPI training. Most participants took 2-3 h to complete the training. Participants generally reported high levels of satisfaction with the course, with the vast majority (94.4%) indicating they would recommend it to their peers. Course completers also demonstrated significant gains in SPI knowledge and self-efficacy from baseline to 3-month follow-up (all p's < .001). Moreover, the percentage of participants who reported completing a safety plan with someone they suspected at being of risk for suicide increased approximately 7-fold from baseline (3.5%) to 3-month follow-up (25.2%; p < .001). Participants further reported that 97.6% of the safety plans that they completed resulted in a positive outcome. Limitations: This was a program evaluation project that did not include a control group. Thus, causality cannot be inferred. Conclusions: The present findings suggest that web-based SPI training is a feasible and scalable approach for training peer support specialists to deliver the SPI to at-risk individuals.

Spinal disease in a captive population of Panthera species: Review of 86 cases (2003-2021).

This retrospective study aimed to characterize and determine the prevalence of spinal disease in nondomestic felids within a sanctuary population. A review of 304 postmortem examination reports in Panthera species from 2003 to 2021 revealed that 86/304 (28%) were diagnosed with spinal disease. Spinal lesions were categorized according to pathologic process: degenerative (78/86, 91%), developmental (8/86, 9%), inflammatory (6/86, 7%), or neoplastic (8/86, 9%). Degenerative lesions included intervertebral disk disease (IVDD; 66/78, 85%), spondylosis without concurrent IVDD (4/78, 5%), and idiopathic (noncompressive) degenerative myelopathies (8/78, 10%). Fourteen individuals had lesions in more than 1 category. Developmental cases were vertebral (4/8) or spinal cord (3/8) malformations or both (1/8). Inflammatory lesions included meningitis (4/6) and meningomyelitis (2/6). Neoplasia included vertebral multiple myeloma (4/8) and others (4/8). IVDD often involved multiple disks but primarily affected the cervical (41/66, 62%) and thoracic spine (32/66, 48%). A multivariate binary logistic model predicted the diagnosis of IVDD at postmortem examination, where odds of being affected were highest for males, lions (Panthera leo), and geriatric age group (>14 years). The spinal lesions documented in this study provide insight into high-risk signalment categories and predominant associated lesions affecting captive Panthera populations. Specifically, spinal disease, especially cervical IVDD, is common among Panthera species, and lions, males, and older felids are at increased risk.

First molecular identification of the trematode Pulmonicola cochleotrema (Platyhelminthes: Opisthotrematidae) in West Indian manatees (Trichechus manatus, Sirenia: Trichechidae) from Puerto Rico and Florida.

West Indian manatees (Trichechus manatus) harbor a variety of endoparasites, including the nasal trematode Pulmonicola cochleotrema, which infects the respiratory tract, especially the nasal passages. Previous studies have described and identified this digenean using morphological data only. This study presents the first molecular identification of P. cochleotrema in West Indian manatees from Puerto Rico and Florida. Samples of the trematode were collected from seven manatees found stranded dead at both locations. The small subunit ribosomal DNA (18S rDNA) was amplified from each sample using universal primers for different regions of the gene, resulting in a consensus sequence of 1871 base pairs. The phylogenetic reconstruction was carried out using DNA sequences of other species of digenean parasites from other hosts, including a trematode of the same taxonomic family from another sirenian species. Specimens collected from both locations show the same molecular identity using SSU rDNA sequence data. The identity of P. cochleotrema was confirmed using the Basic Local Alignment Search Tool from the National Center for Biotechnology Information database, yielding a high similarity of 98.8 % with Opisthotrema dujonis and 98.2 % with Lankatrema mannarense located in the same clade in our analysis. The latter two digeneans belong to the Opisthotrematidae as does P. cochleotrema and previous studies reported them infecting the Eustachian tubes, esophagus, and digestive tract in dugongs (Dugong dugon). These findings evidence that the nasal trematode of manatees in Florida and Puerto Rico and the dugong, all inhabiting and feeding in marine environments, will have a marine mollusk as an intermediate host, probably a gastropod. The question remains, which species of nasal trematode are harbored by lotic-dwelling manatees in other parts of their distribution like South America.

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. CONCLUSIONS: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.

Multimodal smoking cessation treatment combining transcranial magnetic stimulation, cognitive behavioral therapy, and nicotine replacement therapy in veterans with posttraumatic stress disorder: A feasibility randomized controlled trial protocol.

Tobacco-related deaths exceed those resulting from homicides, suicides, motor vehicle accidence, alcohol consumption, illicit substance use, and acquired immunodeficiency syndrome (AIDS), combined. Amongst U.S. veterans, this trend is particularly concerning given that those suffering from posttraumatic stress disorder (PTSD)-about 11% of those receiving care from the Department of Veterans Affairs (VA)-have triple the risk of developing tobacco use disorder (TUD). The most efficacious strategies being used at the VA for smoking cessation only result in a 23% abstinence rate, and veterans with PTSD only achieve a 4.5% abstinence rate. Therefore, there is a critical need to develop more effective treatments for smoking cessation. Recent studies have revealed the insula as integrally involved in the neurocircuitry of TUD, specifically showing that individuals with brain lesions involving this region had drastically improved quit rates. Some of these studies show a probability of quitting up to 5 times greater compared to non-insula lesioned regions). Altered activity of the insula may be involved in the disruption of the salience network's (SN) connectivity to the executive control network (ECN), which compromises that patient's ability to switch between interoceptive states focused on cravings to executive and cognitive control. Thus, we propose a feasibility phase II randomized controlled trial (RCT) to study a patterned form of repetitive transcranial magnetic stimulation (rTMS), intermittent theta burst stimulation (iTBS), at 90% of the subject's resting motor threshold (rMT) applied over a region in the right post-central gyrus most functionally connected to the right posterior insula. We hypothesize that by increasing functional connectivity between the SN with the ECN to enhance executive control and by decreasing connectivity with the default mode network (DMN) to reduce interoceptive focus on withdrawal symptoms, we will improve smoking cessation outcomes. Fifty eligible veterans with comorbid TUD and PTSD will be randomly assigned to two conditions: active-iTBS + cognitive behavioral therapy (CBT) + nicotine replacement therapy (NRT) (n=25) or sham-iTBS + CBT + NRT (n=25). The primary outcome, feasibility, will be determined by achieving a recruitment of 50 participants and retention rate of 80%. The success of iTBS will be evaluated through self-reported nicotine use, cravings, withdrawal symptoms, and abstinence following quit date (confirmed by bioverification) along with evaluation for target engagement through neuroimaging changes, specifically connectivity differences between the insula and other regions of interest.

Large epigenome-wide association study identifies multiple novel differentially methylated CpG sites associated with suicidal thoughts and behaviors in veterans.

Introduction: The U.S. suicide mortality rate has steadily increased during the past two decades, particularly among military veterans; however, the epigenetic basis of suicidal thoughts and behaviors (STB) remains largely unknown. Methods: To address this issue, we conducted an epigenome-wide association study of DNA methylation (DNAm) of peripheral blood samples obtained from 2,712 U.S. military veterans. Results: Three DNAm probes were significantly associated with suicide attempts, surpassing the multiple testing threshold (FDR q-value <0.05), including cg13301722 on chromosome 7, which lies between the genes SLC4A2 and CDK5; cg04724646 in PDE3A; and cg04999352 in RARRES3. cg13301722 was also found to be differentially methylated in the cerebral cortex of suicide decedents in a publicly-available dataset (p = 0.03). Trait enrichment analysis revealed that the CpG sites most strongly associated with STB in the present sample were also associated with smoking, alcohol consumption, maternal smoking, and maternal alcohol consumption, whereas pathway enrichment analysis revealed significant associations with circadian rhythm, adherens junction, insulin secretion, and RAP-1 signaling, each of which was recently associated with suicide attempts in a large, independent genome-wide association study of suicide attempts of veterans. Discussion: Taken together, the present findings suggest that SLC4A2, CDK5, PDE3A, and RARRES3 may play a role in STB. CDK5, a member of the cyclin-dependent kinase family that is highly expressed in the brain and essential for learning and memory, appears to be a particularly promising candidate worthy of future study; however, additional work is still needed to replicate these finding in independent samples.

An introduction to lesions and histology of scleractinian corals.

Stony corals (Scleractinia) are in the Phylum Cnidaria (cnidae referring to various types of stinging cells). They may be solitary or colonial, but all secrete an external, supporting aragonite skeleton. Large, colonial members of this phylum are responsible for the accretion of coral reefs in tropical and subtropical waters that form the foundations of the most biodiverse marine ecosystems. Coral reefs worldwide, but particularly in the Caribbean, are experiencing unprecedented levels of disease, resulting in reef degradation. Most coral diseases remain poorly described and lack clear case definitions, while the etiologies and pathogenesis are even more elusive. This introductory guide is focused on reef-building corals and describes basic gross and microscopic lesions in these corals in order to serve as an invitation to other veterinary pathologists to play a critical role in defining and advancing the field of coral pathology.

Pathology and infectious agents of unionid mussels: A primer for pathologists in disease surveillance and investigation of mortality events.

Freshwater mussels are one of the most imperiled groups of organisms in the world, and more than 30 species have gone extinct in the last century. While habitat alteration and destruction have contributed to the declines, the role of disease in mortality events is unclear. In an effort to involve veterinary pathologists in disease surveillance and the investigation of freshwater mussel mortality events, we provide information on the conservation status of unionids, sample collection and processing techniques, and unique and confounding anatomical and physiological differences. We review the published accounts of pathology and infectious agents described in freshwater mussels including neoplasms, viruses, bacteria, fungi, fungal-like agents, ciliated protists, Aspidogastrea, Digenea, Nematoda, Acari, Diptera, and Odonata. Of the identified infectious agents, a single viral disease, Hyriopsis cumingii plague disease, that occurs only in cultured mussels is known to cause high mortality. Parasites including ciliates, trematodes, nematodes, mites, and insects may decrease host fitness, but are not known to cause mortality. Many of the published reports identify infectious agents at the light or ultrastructural microscopy level with no lesion or molecular characterization. Although metagenomic analyses provide sequence information for infectious agents, studies often fail to link the agents to tissue changes at the light or ultrastructural level or confirm their role in disease. Pathologists can bridge this gap between identification of infectious agents and confirmation of disease, participate in disease surveillance to ensure successful propagation programs necessary to restore decimated populations, and investigate mussel mortality events to document pathology and identify causality.

A combined diagnostic approach for the investigation of lesions resembling aspergillosis in Caribbean sea fans (Gorgonia spp.).

Aspergillosis of gorgonian sea fans is a Caribbean-wide disease characterized by focal, annular purple pigmentation with central tissue loss. We applied a holistic diagnostic approach including histopathology and a combination of culture and direct molecular identification of fungi to evaluate these lesions with the goal of determining the diversity of associated micro-organisms and pathology. Biopsies were collected from 14 sea fans without gross lesions and 44 sea fans with lesions grossly consistent with aspergillosis in shallow fringing reefs of St. Kitts. Histologically, the tissue loss margin had exposure of the axis and amoebocyte encapsulation with abundant mixed micro-organisms. Polyp loss, gastrodermal necrosis, and coenenchymal amoebocytosis were at the lesion interface (purpled area transitioning to grossly normal tissue) with algae (n = 21), fungus-like hyphae (n = 20), ciliate protists (n = 16), cyanobacteria (n = 15), labyrinthulomycetes (n = 5), or no micro-organisms (n = 8). Slender, septate hyaline hyphae predominated over other morphological categories, but were confined to the axis with little host response other than periaxial melanization. Hyphae were absent in 6 lesioned sea fans and present in 5 control biopsies, questioning their pathogenicity and necessary role in lesion causation. From cultivation, different fungi were isolated and identified by sequencing of the nuclear ribosomal internal transcribed spacer region. In addition, 2 primer pairs were used in a nested format to increase the sensitivity for direct amplification and identification of fungi from lesions, thereby circumventing cultivation. Results suggest mixed and opportunistic infections in sea fans with these lesions, requiring longitudinal or experimental studies to better determine the pathogenesis.

Effect of cognitive processing therapy on markers of cardiovascular risk in posttraumatic stress disorder patients: A randomized clinical trial.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with elevated risk of coronary heart disease (CHD); however, the effects of PTSD treatment on CHD biomarkers is unknown. This study examined whether cognitive processing therapy (CPT) improves 24-hourheart rate variability (HRV), a predictor of CHD mortality. METHODS: Individuals between the ages of 40 and 65 years with PTSD (n = 112) were randomized to receive 12 sessions of CPT or a Waiting List (WL) intervention comprised of 6 weekly telephone checks of emotional status. The primary outcome variable was 24-hour HRV estimated from the standard deviation of all normal R-R intervals (SDNN); secondary outcomes were the root mean square of successive differences between heart beats (RMSSD), low-frequency HRV (LF-HRV) and high-frequency HRV (HF-HRV). Secondary outcomes also included 24-hour urinary catecholamine excretion, plasma C-reactive protein (CRP), and flow-mediated dilation (FMD) of the brachial artery. For outcomes, linear mixed longitudinal models were used to estimate mean differences (Mdiff). RESULTS: Participants randomized to the CPT group did not show improved SDNN (Mdiff = 9.8; 95%CI, -2.7 to 22.3; p = 0.12), the primary outcome variable, but showed improved RMSSD (Mdiff = 3.8; 95% CI, 0.5 to 7.1; p = 0.02), LF- HRV (Mdiff =0.3; 95% CI, 0.1 to 0.5; p = 0.01), and HF-HRV (Mdiff = 0.3; 95% CI, 0.0 to 0.6; p = 0.03) compared to WL. There were no differences between groups in catecholamine excretion, FMD, or inflammatory markers. CONCLUSION: Treating PTSD may not only improve quality of life but may also help ameliorate heightened CHD risk characteristics of PTSD.

Genome-wide association study identifies four pan-ancestry loci for suicidal ideation in the Million Veteran Program.

Suicidal ideation (SI) often precedes and predicts suicide attempt and death, is the most common suicidal phenotype and is over-represented in veterans. The genetic architecture of SI in the absence of suicide attempt (SA) is unknown, yet believed to have distinct and overlapping risk with other suicidal behaviors. We performed the first GWAS of SI without SA in the Million Veteran Program (MVP), identifying 99,814 SI cases from electronic health records without a history of SA or suicide death (SD) and 512,567 controls without SI, SA or SD. GWAS was performed separately in the four largest ancestry groups, controlling for sex, age and genetic substructure. Ancestry-specific results were combined via meta-analysis to identify pan-ancestry loci. Four genome-wide significant (GWS) loci were identified in the pan-ancestry meta-analysis with loci on chromosomes 6 and 9 associated with suicide attempt in an independent sample. Pan-ancestry gene-based analysis identified GWS associations with DRD2, DCC, FBXL19, BCL7C, CTF1, ANNK1, and EXD3. Gene-set analysis implicated synaptic and startle response pathways (q's<0.05). European ancestry (EA) analysis identified GWS loci on chromosomes 6 and 9, as well as GWS gene associations in EXD3, DRD2, and DCC. No other ancestry-specific GWS results were identified, underscoring the need to increase representation of diverse individuals. The genetic correlation of SI and SA within MVP was high (rG = 0.87; p = 1.09e-50), as well as with post-traumatic stress disorder (PTSD; rG = 0.78; p = 1.98e-95) and major depressive disorder (MDD; rG = 0.78; p = 8.33e-83). Conditional analysis on PTSD and MDD attenuated most pan-ancestry and EA GWS signals for SI without SA to nominal significance, with the exception of EXD3 which remained GWS. Our novel findings support a polygenic and complex architecture for SI without SA which is largely shared with SA and overlaps with psychiatric conditions frequently comorbid with suicidal behaviors.

PATHOLOGY OF HATCHLING HAWKSBILL SEA TURTLE (ERETMOCHELYS IMBRICATA) MORTALITIES OCCURRING WHILE UNDER REHABILITATIVE CARE, 2015-21.

Increasing hatchling survival is an important element of conservation of the critically endangered hawksbill sea turtle (Eretmochelys imbricata). Yet, there is little information regarding mortality-associated pathological states of hawksbill hatchlings. The aim of this study was to describe lesions affecting hawksbill hatchlings that died while under rehabilitative care. Forty-four turtles representing the nesting sites of two islands and a 7-yr study period were subjected to comprehensive postmortem examination. The most common lesions included dermatitis (34%), skeletal malformations (23%), and pneumonia (23%). Dermatitis and pneumonia were caused by a variety of presumptively opportunistic bacterial and fungal infections. Fungal infections affected 23% of study turtles, also causing rhinitis and esophagitis. Around half of the cases of dermatitis presented with history of skin lesions, and all those involving periocular areas had clinical history of eye lesions. Pneumonia was not predicted by clinical signs or time in rehabilitation. Malformations included carapace compressions, supra- or subnumerary scutes, and dysmelias with many of those affected having concurrent pathology involving other organs. Other lesions included bacterial yolk sacculitis (15%), skeletal muscle degeneration and necrosis (13%), and acute renal tubular necrosis (13%). The study population was female biased (93%), raising concern for skewed hatchling sex ratios and high incubation temperatures in the eastern Caribbean. The pathology described by this study improves our understanding of threats to hawksbill hatchlings and may be taken into consideration by clinicians when implementing strategies for rehabilitative care.

Identification of Novel, Replicable Genetic Risk Loci for Suicidal Thoughts and Behaviors Among US Military Veterans.

Importance: Suicide is a leading cause of death; however, the molecular genetic basis of suicidal thoughts and behaviors (SITB) remains unknown. Objective: To identify novel, replicable genomic risk loci for SITB. Design, Setting, and Participants: This genome-wide association study included 633 778 US military veterans with and without SITB, as identified through electronic health records. GWAS was performed separately by ancestry, controlling for sex, age, and genetic substructure. Cross-ancestry risk loci were identified through meta-analysis. Study enrollment began in 2011 and is ongoing. Data were analyzed from November 2021 to August 2022. Main Outcome and Measures: SITB. Results: A total of 633 778 US military veterans were included in the analysis (57 152 [9%] female; 121 118 [19.1%] African ancestry, 8285 [1.3%] Asian ancestry, 452 767 [71.4%] European ancestry, and 51 608 [8.1%] Hispanic ancestry), including 121 211 individuals with SITB (19.1%). Meta-analysis identified more than 200 GWS (P < 5 × 10-8) cross-ancestry risk single-nucleotide variants for SITB concentrated in 7 regions on chromosomes 2, 6, 9, 11, 14, 16, and 18. Top single-nucleotide variants were largely intronic in nature; 5 were independently replicated in ISGC, including rs6557168 in ESR1, rs12808482 in DRD2, rs77641763 in EXD3, rs10671545 in DCC, and rs36006172 in TRAF3. Associations for FBXL19 and AC018880.2 were not replicated. Gene-based analyses implicated 24 additional GWS cross-ancestry risk genes, including FURIN, TSNARE1, and the NCAM1-TTC12-ANKK1-DRD2 gene cluster. Cross-ancestry enrichment analyses revealed significant enrichment for expression in brain and pituitary tissue, synapse and ubiquitination processes, amphetamine addiction, parathyroid hormone synthesis, axon guidance, and dopaminergic pathways. Seven other unique European ancestry-specific GWS loci were identified, 2 of which (POM121L2 and METTL15/LINC02758) were replicated. Two additional GWS ancestry-specific loci were identified within the African ancestry (PET112/GATB) and Hispanic ancestry (intergenic locus on chromosome 4) subsets, both of which were replicated. No GWS loci were identified within the Asian ancestry subset; however, significant enrichment was observed for axon guidance, cyclic adenosine monophosphate signaling, focal adhesion, glutamatergic synapse, and oxytocin signaling pathways across all ancestries. Within the European ancestry subset, genetic correlations (r > 0.75) were observed between the SITB phenotype and a suicide attempt-only phenotype, depression, and posttraumatic stress disorder. Additionally, polygenic risk score analyses revealed that the Million Veteran Program polygenic risk score had nominally significant main effects in 2 independent samples of veterans of European and African ancestry. Conclusions and Relevance: The findings of this analysis may advance understanding of the molecular genetic basis of SITB and provide evidence for ESR1, DRD2, TRAF3, and DCC as cross-ancestry candidate risk genes. More work is needed to replicate these findings and to determine if and how these genes might impact clinical care.

Impact of traumatic life events and polygenic risk scores for major depression and posttraumatic stress disorder on Iraq/Afghanistan Veterans.

Traumatic experiences and genetic heritability are among the most widely acknowledged risk factors leading to the development of psychopathology; including posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). The purpose of this study was to investigate if polygenic risk scores (PRS) among Veterans interacted with traumatic stress to predict PTSD and MDD. 1,389 Iraq-Afghanistan military service Veterans from the Mental Illness Research Education and Clinical Center dataset were analyzed. Genome-wide association study (GWAS) statistics were utilized to generate PRS for PTSD (PRSPTSD) and PRS for MDD (PRSMDD) in order to analyze PRS-by-environment (PRSxE) with trauma exposure to predict PTSD and MDD diagnoses. Trauma exposure and PRSPTSD, were independently associated with a current PTSD diagnosis (p < 0.001 and p < 0.001, respectively). The interaction between trauma exposure and PRSMDD to predict a current diagnosis of PTSD trended towards significance (p = 0.053). Stratifying by trauma thresholds, among those within the lowest trauma load, the association of PRSMDD with PTSD was found to be nominally significant (p = 0.03). For a MDD diagnosis, there was a significant association with trauma exposure (p < 0.001); and the association with PRSMDD was found to be nominally significant (p = 0.03). No significant PRSxE effects were found with MDD. Our findings corroborate previous research highlighting trauma exposure, and genetic heritability, as risk factors for the development of PTSD and MDD in a Veteran population. Additionally, findings suggest that genetic vulnerability may be less important as trauma exposure increases, with high levels of trauma likely to result in PTSD and MDD, regardless of genetic vulnerability.