Interaction between mental disorders and social disconnectedness on mortality: a population-based cohort study.

BACKGROUND: Despite the recognised importance of mental disorders and social disconnectedness for mortality, few studies have examined their co-occurrence. AIMS: To examine the interaction between mental disorders and three distinct aspects of social disconnectedness on mortality, while taking into account sex, age and characteristics of the mental disorder. METHOD: This cohort study included participants from the Danish National Health Survey in 2013 and 2017 who were followed until 2021. Survey data on social disconnectedness (loneliness, social isolation and low social support) were linked with register data on hospital-diagnosed mental disorders and mortality. Poisson regression was applied to estimate independent and joint associations with mortality, interaction contrasts and attributable proportions. RESULTS: A total of 162 497 individuals were followed for 886 614 person-years, and 9047 individuals (5.6%) died during follow-up. Among men, interaction between mental disorders and loneliness, social isolation and low social support, respectively, accounted for 47% (95% CI: 21-74%), 24% (95% CI: -15 to 63%) and 61% (95% CI: 35-86%) of the excess mortality after adjustment for demographics, country of birth, somatic morbidity, educational level, income and wealth. In contrast, among women, no excess mortality could be attributed to interaction. No clear trends were identified according to age or characteristics of the mental disorder. CONCLUSIONS: Mortality among men, but not women, with a co-occurring mental disorder and social disconnectedness was substantially elevated compared with what was expected. Awareness of elevated mortality rates among socially disconnected men with mental disorders could be of importance to qualify and guide prevention efforts in psychiatric services.

The impact of relationship type and closeness on mental health following suicide loss.

BACKGROUND: Most research investigating the effect of suicide on loss survivors has been limited to first-degree family members. Few studies examine the impact of suicide on others outside the immediate family and the influence of relationship type and closeness on mental health. METHODS: This study used data from a sample obtained through random digit dialing (n = 805) to assess exposure to suicide loss, relationship types, perceived closeness, and mental health symptoms (prolonged grief, depression, anxiety, and posttraumatic stress disorder). RESULTS: Familial status, friend status, and higher perceived closeness were associated with prolonged grief, depression, and posttraumatic stress disorder, with the strongest adjusted associations observed for posttraumatic stress disorder and prolonged grief. In general, the magnitude of adjusted standardized associations for closeness and mental health symptoms was stronger than those observed for familial status and mental health symptoms and friend status and mental health symptoms. CONCLUSION: Closeness, familial status, and friend status are associated with mental health symptoms experienced after suicide loss, but the magnitude of associations was strongest for closeness. Future studies should examine perceived closeness in addition to other factors related to relationship type and dynamics to assess the complexities of suicide bereavement reactions.

Mediation of the association between depression and coronary heart disease by metabolic syndrome components.

BACKGROUND: Depression is associated with incident coronary heart disease (CHD) via a pathway that may be causal, but the mechanisms underlying this association are unclear. We assessed the extent to which metabolic syndrome (MetS) and its components (i.e., elevated waist circumference, low high-density lipoprotein [HDL] cholesterol, elevated triglycerides, elevated blood pressure, and elevated fasting plasma glucose) may mediate this association. METHODS: Data were Framingham Heart Study Research Materials obtained from the National Heart, Lung, and Blood Institute (NHLBI) Biologic Specimen and Data Repository Information Coordinating Center. We used Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) representing the total effect (aHRTE) of probable depression, measured via the Centers for Epidemiological Studies - Depression scale, on incident CHD over approximately 18 years. Using inverse odds ratio weighting, we decomposed this estimate into natural direct effects (aHRNDE) and natural indirect effects (aHRNIE) through potential mediators (measured approximately three years after depression). RESULTS: Probable depression was associated with incident CHD (aHRTE=1.45, 95% confidence interval [CI]: 0.93, 2.25), and elevated waist circumference partially mediated this association (aHRNDE=1.34, 95% CI: 0.76-2.32; aHRNIE=1.08, 95% CI: 0.63-1.91). We did not find evidence of additional mediation by additional MetS components. CONCLUSIONS: Elevated waist circumference appears to play a role in the association between depression and CHD.

Sex Differences in Psychopathology Following Potentially Traumatic Experiences.

Importance: Various psychopathology may follow trauma; however, sex differences in these ranging manifestations of posttraumatic psychopathology remain understudied. Objective: To investigate sex-specific incidence of posttraumatic psychopathology. Design, Setting, and Participants: This population-based cohort study of Danish national health registries included a cohort of individuals who experienced a potentially traumatic event (PTE) from 1994 to 2016. Individuals were further categorized by presence of any pretrauma psychopathology. A comparison group of individuals who experienced a nontraumatic stressor (nonsuicide death of a first-degree relative) was examined as a reference cohort. Exposures: At least 1 of 8 PTEs (eg, physical assault, transportation accident) derived through health registry International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes, with additional qualifiers to improve classification accuracy. Main Outcomes and Measures: Incidence of 9 categories of ICD-10 psychiatric disorders recorded in registries within 5 years of PTEs. The standardized morbidity ratios (SMRs) for psychopathology outcomes were also calculated to compare individuals experiencing PTEs with those experiencing a nontraumatic stressor. Results: This study included 1 398 026 individuals who had been exposed to trauma (475 280 males [34.0%]; 922 750 females [66.0%]). The group of males who had been exposed to trauma were evenly distributed across age, while most females in the trauma-exposed group were aged 16 to 39 years (592 385 [64.2%]). Males and females were equally distributed across income quartiles and predominantly single. Following PTEs, the most common diagnosis was substance use disorders for males (35 160 [7.4%]) and depressive disorders for females (29 255 [3.2%]); incidence proportions for these and other disorders were higher among males and females with any pretrauma psychopathology. Certain PTEs had elevated onset of various psychiatric disorders and some sex differences emerged. Following physical assault, associations were found with schizophrenia or psychotic disorders for males (SMR, 17.5; 95% CI, 15.9-19.3) and adult personality disorders for females (SMR, 16.3; 95% CI, 14.6-18.3). For noninterpersonal PTEs, males had larger SMRs for substance use, schizophrenia or psychotic disorders, and adult personality disorders (SMR, 43.4; 95% CI, 41.9-45.0), and females had larger SMRs for depressive disorders (SMR, 19.0; 95% CI, 18.6-19.4). Sex differences were also observed, particularly when considering pretrauma psychopathology. For example, among interpersonal PTEs, males were most likely to develop substance use disorders after physical assault, whereas females were more likely to develop various disorders, with stronger associations seen for females without pretrauma psychiatric diagnoses. Among noninterpersonal PTEs, exposure to toxic substance showed robust associations with psychopathology, particularly in those without pretrauma psychopathology, with sex-specific differences across psychiatric categories. Conclusions and Relevance: Mental disorders after trauma were wide-ranging for males and females, and sex differences in patterns of posttraumatic psychopathology were more pronounced when accounting for pretrauma psychopathology. Findings provide new insights for sex-relevant PTEs and their mental health consequences. It also outlines future directions for advancing understanding of a constellation of posttraumatic psychopathology in males and females.

Incidence Trajectories of Psychiatric Disorders After Assault, Injury, and Bereavement.

Importance: Traumatic events have been associated with elevated risks of psychiatric disorders, while the contributions of familial factors to these associations remain less clear. Objective: To determine the contribution of familial factors to long-term incidence trajectories of psychiatric disorders following potentially traumatic events. Design, Setting, and Participants: This cohort study evaluated 3 separate cohorts of individuals residing in Sweden who were free of previous diagnosed psychiatric disorders when first exposed to assault (n = 49 957), injury (n = 555 314), or bereavement (n = 321 263) from January 1987 to December 2013, together with their unexposed full siblings, and 10 age-, sex-, and birthplace-matched unexposed individuals (per exposed individual). Cohorts were created from the Swedish Total Population Register linked to health and population registers. Data were analyzed from March 2022 to April 2023. Exposures: Potentially traumatic events, including various types of assault, injuries, and bereavement (death of a child or of a spouse or partner), were ascertained from the Swedish national registers. Main Outcomes and Measures: Incident psychiatric disorders were ascertained from the Swedish Patient Register. Flexible parametric and Cox models were used to estimate associations of potentially traumatic events with incident psychiatric disorders after multivariable adjustment. Results: The median (IQR) age at exposure to assault, injury, and bereavement was 22 (18-31), 19 (8-40), and 60 (51-68) years, respectively. During a median (IQR) follow-up of 4.9 (2.2-8.2), 9.1 (4.1-15.6), and 8.1 (3.4-14.8) years, the incidence rates of any psychiatric disorder were 38.1, 13.9, and 9.0 per 1000 person-years for the exposed groups of the 3 cohorts, respectively. Elevated risk of any psychiatric disorder was observed during the first year after exposure to any assault (hazard ratio [HR], 4.55; 95% CI, 4.34-4.77), injury (HR, 3.31; 95% CI,3.23-3.38), or bereavement (HR, 2.81; 95% CI, 2.72-2.91) and thereafter (assault HR, 2.50; 95% CI, 2.43-2.56; injury HR, 1.69; 95% CI, 1.68-1.70; bereavement HR, 1.42; 95% CI, 1.40-1.44). Comparable associations were obtained in sibling comparison (first year: assault HR, 3.70; 95% CI, 3.37-4.05; injury HR, 2.98; 95% CI, 2.85-3.12; bereavement HR, 2.72; 95% CI, 2.54-2.91; thereafter: assault HR, 1.93; 95% CI, 1.84-2.02; injury HR, 1.51; 95% CI, 1.48-1.53; bereavement HR, 1.35; 95% CI, 1.31-1.38). The risk elevation varied somewhat by type of traumatic events and psychiatric disorders, with the greatest HR noted for posttraumatic stress disorder after sexual assault (sibling comparison HR, 4.52; 95% CI, 3.56-5.73 during entire follow-up period). Conclusions and Relevance: In this study, the long-term risk elevation of psychiatric disorders after potentially traumatic events was largely independent of familial factors. The risk elevation observed immediately after these events motivates early clinical surveillance and mental health services for these vulnerable populations.

Report on the Joint Workshop on the Relations between Health Inequalities, Ageing and Multimorbidity, Iceland, May 3-4, 2023.

This paper is a summary of key presentations from a workshop in Iceland on May 3-4, 2023 arranged by Aarhus University and with participation of the below-mentioned scientists. Below you will find the key messages from the presentations made by: Professor Jan Vandenbroucke, Department of Clinical Epidemiology, Aarhus University, Emeritus Professor, Leiden University; Honorary Professor, London School of Hygiene & Tropical Medicine, UKProfessor, Chair Henrik Toft Sørensen, Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, DenmarkProfessor David H. Rehkopf, Director, the Stanford Center for Population Health Sciences, Stanford University, CA., USProfessor Jaimie Gradus, Department of Epidemiology, School of Public Health, Boston University, Boston, Massachusetts, USProfessor Johan Mackenbach, Emeritus Professor, Department of Public Health, Erasmus University Rotterdam, HollandProfessor, Chair M Maria Glymour, Department of Epidemiology, Boston University School of Public Health, Boston University, Boston, Massachusetts, USProfessor, Dean Sandro Galea, School of Public Health, Boston University, Boston, Massachusetts, USProfessor Victor W. Henderson, Departments of Epidemiology & Population Health and of Neurology & Neurological Sciences, Stanford University, Stanford, CA, US; Department of Clinical Epidemiology, Aarhus University, Aarhus, DK.

Divergent trends in accidental deaths since return from an Afghanistan/Iraq deployment among army soldiers.

PURPOSE: Accidental death is a leading cause of mortality among military members and Veterans; however, knowledge is limited regarding time-dependent risk following deployment and if there are differences by type of accidental death. METHODS: Longitudinal cohort study (N = 860,930) of soldiers returning from Afghanistan/Iraq deployments in fiscal years 2008-2014. Accidental deaths (i.e., motor vehicle accidents [MVA], accidental overdose, other accidental deaths), were identified through 2018. Crude and age-adjusted mortality rates, rate ratios, time-dependent hazard rates and trends postdeployment were compared across demographic and military characteristics. RESULTS: During the postdeployment observation period, over one-third of deaths were accidental; most were MVA (46.0 %) or overdoses (37.9 %). Across accidental mortality categories (all, MVA, overdose), younger soldiers (18-24, 25-29) were at higher risk compared to older soldiers (40+), and females at lower risk than males. MVA death rates were highest immediately postdeployment, with a significant decreasing hazard rate over time (annual percent change [APC]: -6.5 %). Conversely, accidental overdose death rates were lowest immediately following deployment, with a significant increasing hazard rate over time (APC: 9.9 %). CONCLUSIONS: Observed divergent trends in risk for the most common types of accidental deaths provide essential information to inform prevention and intervention planning for the immediate postdeployment transition and long-term.

Trends in Prevalence of Cannabis Use Disorder Among U.S. Veterans With and Without Psychiatric Disorders Between 2005 and 2019.

OBJECTIVE: Cannabis use disorder diagnoses are increasing among U.S. adults and are more prevalent among people with comorbid psychiatric disorders. Recent changes in cannabis laws, increasing cannabis availability, and higher-potency cannabis may have placed people with cannabis use and psychiatric disorders at disproportionately increasing risk for cannabis use disorder. The authors used Veterans Health Administration (VHA) data to examine whether trends in cannabis use disorder prevalence among VHA patients differ by whether they have psychiatric disorders. METHODS: VHA electronic health records from 2005 to 2019 (N range, 4,332,165-5,657,277) were used to identify overall and age-group-specific (<35, 35-64, and ≥65 years) trends in prevalence of cannabis use disorder diagnoses among patients with depressive, anxiety, posttraumatic stress, bipolar, or psychotic spectrum disorders and to compare these to corresponding trends among patients without any of these disorders. Given transitions in ICD coding, differences in trends were tested within two periods: 2005-2014 (ICD-9-CM) and 2016-2019 (ICD-10-CM). RESULTS: Greater increases in prevalence of cannabis use disorder diagnoses were observed among patients with psychiatric disorders compared to those without (difference in prevalence change, 2005-2014: 1.91%, 95% CI=1.87-1.96; 2016-2019: 0.34%, 95% CI=0.29-0.38). Disproportionate increases in cannabis use disorder prevalence among patients with psychiatric disorders were greatest among those under age 35 between 2005 and 2014, and among those age 65 or older between 2016 and 2019. Among patients with psychiatric disorders, the greatest increases in cannabis use disorder prevalences were observed among those with bipolar and psychotic spectrum disorders. CONCLUSIONS: The findings highlight disproportionately increasing disparities in risk of cannabis use disorder among VHA patients with common psychiatric disorders. Greater public health and clinical efforts are needed to monitor, prevent, and treat cannabis use disorder in this population.

Prediction of Suicide Attempts Among Persons with Depression: A Population-Based Case Cohort Study.

Studies have highlighted the potential importance of modeling interactions for suicide attempt prediction. This case-cohort study identified risk factors for suicide attempts among persons with depression in Denmark using statistical approaches that do (random forests) or do not model interactions (least absolute shrinkage and selection operator regression [LASSO]). Cases made a non-fatal suicide attempt (n = 6,032) between 1995 and 2015. The comparison subcohort was a 5% random sample of all persons in Denmark on January 1, 1995 (n = 11,963). We used random forests and LASSO for sex-stratified prediction of suicide attempts from demographic variables, psychiatric and somatic diagnoses, and treatments. Poisonings, psychiatric disorders, and medications were important predictors for both sexes. Area under the receiver operating characteristic curve (AUC) values were higher in LASSO models (0.85 [95% CI = 0.84, 0.86] in men; 0.89 [95% CI = 0.88, 0.90] in women) than random forests (0.76 [95% CI = 0.74, 0.78] in men; 0.79 [95% CI = 0.78, 0.81] in women). Automatic detection of interactions via random forests did not result in better model performance than LASSO models that did not model interactions. Due to the complex nature of psychiatric comorbidity and suicide, modeling interactions may not always be the optimal statistical approach to enhancing suicide attempt prediction in high-risk samples.

Trends in Cannabis-positive Urine Toxicology Test Results: US Veterans Health Administration Emergency Department Patients, 2008 to 2019.

OBJECTIVES: This study aimed to examine trends in cannabis-positive urine drug screens (UDSs) among emergency department (ED) patients from 2008 to 2019 using data from the Veterans Health Administration (VHA) health care system, and whether these trends differed by age group (18-34, 35-64, and 65-75 years), sex, and race, and ethnicity. METHOD: VHA electronic health records from 2008 to 2019 were used to identify the percentage of unique VHA patients seen each year at an ED, received a UDS, and screened positive for cannabis. Trends in cannabis-positive UDS were examined by age, race and ethnicity, and sex within age groups. RESULTS: Of the VHA ED patients with a UDS, the annual prevalence positive for cannabis increased from 16.42% in 2008 to 27.2% in 2019. The largest increases in cannabis-positive UDS were observed in the younger age groups. Male and female ED patients tested positive for cannabis at similar levels. Although the prevalence of cannabis-positive UDS was consistently highest among non-Hispanic Black patients, cannabis-positive UDS increased in all race and ethnicity groups. DISCUSSION: The increasing prevalence of cannabis-positive UDS supports the validity of previously observed population-level increases in cannabis use and cannabis use disorder from survey and administrative records. Time trends via UDS results provide additional support that previously documented increases in self-reported cannabis use and disorder from surveys and claims data are not spuriously due to changes in patient willingness to report use as it becomes more legalized, or due to greater clinical attention over time.

Chronic pain, cannabis legalisation, and cannabis use disorder among patients in the US Veterans Health Administration system, 2005 to 2019: a repeated, cross-sectional study.

BACKGROUND: Cannabis use disorder is associated with considerable comorbidity and impairment in functioning, and prevalence is increasing among adults with chronic pain. We aimed to assess the effect of introduction of medical cannabis laws (MCL) and recreational cannabis laws (RCL) on the increase in cannabis use disorder among patients in the US Veterans Health Administration (VHA). METHODS: Data from patients with one or more primary care, emergency, or mental health visit to the VHA in 2005-19 were analysed using 15 repeated cross-sectional VHA electronic health record datasets (ie, one dataset per year). Patients in hospice or palliative care were excluded. Patients were stratified as having chronic pain or not using an American Pain Society taxonomy of painful medical conditions. We used staggered-adoption difference-in-difference analyses to estimate the role of MCL and RCL enactment in the increases in prevalence of diagnosed cannabis use disorder and associations with presence of chronic pain, accounting for the year that state laws were enacted. We did this by fitting a linear binomial regression model stratified by pain, with time-varying cannabis law status, fixed effects for state, categorical year, time-varying state-level sociodemographic covariates, and patient covariates (age group [18-34 years, 35-64 years, and 65-75 years], sex, and race and ethnicity). FINDINGS: Between 2005 and 2019, 3 234 382-4 579 994 patients were included per year. Among patients without pain in 2005, 5·1% were female, mean age was 58·3 (SD 12·6) years, and 75·7%, 15·6%, and 3·6% were White, Black, and Hispanic or Latino, respectively. In 2019, 9·3% were female, mean age was 56·7 (SD 15·2) years, and 68·1%, 18·2%, and 6·5% were White, Black, and Hispanic or Latino, respectively. Among patients with pain in 2005, 7·1% were female, mean age was 57·2 (SD 11·4) years, and 74·0%, 17·8%, and 3·9% were White, Black, and Hispanic or Latino, respectively. In 2019, 12·4% were female, mean age was 57·2 (SD 13·8) years, and 65·3%, 21·9%, and 7·0% were White, Black, and Hispanic or Latino, respectively. Among patients with chronic pain, enacting MCL led to a 0·135% (95% CI 0·118-0·153) absolute increase in cannabis use disorder prevalence, with 8·4% of the total increase in MCL-enacting states attributable to MCL. Enacting RCL led to a 0·188% (0·160-0·217) absolute increase in cannabis use disorder prevalence, with 11·5% of the total increase in RCL-enacting states attributable to RCL. In patients without chronic pain, enacting MCL and RCL led to smaller absolute increases in cannabis use disorder prevalence (MCL: 0·037% [0·027-0·048], 5·7% attributable to MCL; RCL: 0·042% [0·023-0·060], 6·0% attributable to RCL). Overall, associations of MCL and RCL with cannabis use disorder were greater in patients with chronic pain than in patients without chronic pain. INTERPRETATION: Increasing cannabis use disorder prevalence among patients with chronic pain following state legalisation is a public health concern, especially among older age groups. Given cannabis commercialisation and widespread public beliefs about its efficacy, clinical monitoring of cannabis use and discussion of the risk of cannabis use disorder among patients with chronic pain is warranted. FUNDING: NIDA grant R01DA048860, New York State Psychiatric Institute, and the VA Centers of Excellence in Substance Addiction Treatment and Education.

The Effects of Suicide Exposure on Mental Health Outcomes Among Post-9/11 Veterans: Protocol for an Explanatory, Sequential, Mixed Methods Study.

BACKGROUND: The toll associated with suicide goes well beyond the individual who died. This study focuses on a risk factor for veteran suicide that has received little previous empirical attention-exposure to the suicide death of another person. OBJECTIVE: The study's primary objective is to describe the mental health outcomes associated with suicide exposure among veterans who served on active duty after September 2001 ("post-9/11"). The secondary objective is to elucidate why some veterans develop persistent problems following suicide exposure, whereas others do not. METHODS: This is an explanatory, sequential, mixed methods study of a nationally representative sample of post-9/11 veterans enrolled in Department of Veterans Affairs (VA) health care. Our sampling strategy was designed for adequate representation of female and American Indian and Alaska Native veterans to allow for examination of associations between suicide exposure and outcomes within these groups. Primary outcomes comprise mental health problems associated with trauma and loss (posttraumatic stress disorder and prolonged grief disorder) and suicide precursors (suicidal ideation, attempts, and planning). Data collection will be implemented in 3 waves. During wave 1, we will field a brief survey to a national probability sample to assess exposure history (suicide, other sudden death, or neither) and exposure characteristics (eg, closeness with the decedent) among 11,400 respondents. In wave 2, we will include 39.47% (4500/11,400) of the wave-1 respondents, stratified by exposure history (suicide, other sudden death, or neither), to assess health outcomes and other variables of interest. During wave 3, we will conduct interviews with a purposive subsample of 32 respondents exposed to suicide who differ in mental health outcomes. We will supplement the survey and interview data with VA administrative data identifying diagnoses, reported suicide attempts, and health care use. RESULTS: The study began on July 1, 2022, and will end on June 30, 2026. This is the only national, population-based study of suicide exposure in veterans and the first one designed to study differences based on sex and race. Comparing those exposed to suicide with those exposed to sudden death for reasons other than suicide (eg, combat) and those unexposed to any sudden death may allow for the identification of the common and unique contribution of suicide exposure to outcomes and help seeking. CONCLUSIONS: Integrating survey, qualitative, and VA administrative data to address significant knowledge gaps regarding the effects of suicide exposure in a national sample will lay the foundation for interventions to address the needs of individuals affected by a suicide death, including female and American Indian and Alaska Native veterans. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51324.

Antihypertensive Medications and PTSD Incidence in a Trauma Cohort.

Objective: Antihypertensive medications have been examined as agents for posttraumatic stress disorder (PTSD) prevention in trauma-exposed individuals, given well-documented associations between PTSD and increased risk of cardiovascular disease and purported trauma-relevant mechanisms of action for these medications. Evidence regarding the effectiveness of such drugs for this purpose remains mixed.Methods: We conducted a national population-based cohort study using data from Danish national registries to assess whether 4 classes of antihypertensive drugs (beta-adrenoceptor blockers [beta blockers], angiotensin II receptor blockers [ARBs], angiotensin-converting enzyme [ACE] inhibitors, and calcium channel blockers) were associated with a decreased incidence of PTSD (diagnosed according to ICD-10) over a 22-year study period. Data for this study originated from a population-based cohort of over 1.4 million persons who experienced a traumatic event between 1994 and 2016 in Denmark. We calculated the incidence rate of PTSD per 100,000 person-years among persons who filled a prescription for each class of drug in the 60 days prior to a traumatic event and for corresponding unexposed comparison groups. We then used Cox proportional hazards regression to compare the rate of PTSD among persons who filled an antihypertensive medication prescription within 60 days before their trauma to the rate among persons who did not.Results: We found evidence that calcium channel blockers were associated with a decreased incidence of PTSD (adjusted hazard ratio = 0.63, 95% confidence interval [CI] = 0.34, 1.2); all other antihypertensive medication classes had null or near null associations.Conclusions: These findings lay a foundation for additional research focusing on antihypertensive medications that appear most effective in reducing PTSD incidence following trauma and for additional replication work aimed at continuing to clarify the disparate findings reported in the literature to date.

Chronic Pain, Cannabis Legalization and Cannabis Use Disorder in Veterans Health Administration Patients, 2005 to 2019.

Background: The risk for cannabis use disorder (CUD) is elevated among U.S. adults with chronic pain, and CUD rates are disproportionately increasing in this group. Little is known about the role of medical cannabis laws (MCL) and recreational cannabis laws (RCL) in these increases. Among U.S. Veterans Health Administration (VHA) patients, we examined whether MCL and RCL effects on CUD prevalence differed between patients with and without chronic pain. Methods: Patients with ≥1 primary care, emergency, or mental health visit to the VHA and no hospice/palliative care within a given calendar year, 2005-2019 (yearly n=3,234,382 to 4,579,994) were analyzed using VHA electronic health record (EHR) data. To estimate the role of MCL and RCL enactment in the increases in prevalence of diagnosed CUD and whether this differed between patients with and without chronic pain, staggered-adoption difference-in-difference analyses were used, fitting a linear binomial regression model with fixed effects for state, categorical year, time-varying cannabis law status, state-level sociodemographic covariates, a chronic pain indicator, and patient covariates (age group [18-34, 35-64; 65-75], sex, and race and ethnicity). Pain was categorized using an American Pain Society taxonomy of painful medical conditions. Outcomes: In patients with chronic pain, enacting MCL led to a 0·14% (95% CI=0·12%-0·15%) absolute increase in CUD prevalence, with 8·4% of the total increase in CUD prevalence in MCL-enacting states attributable to MCL. Enacting RCL led to a 0·19% (95%CI: 0·16%, 0·22%) absolute increase in CUD prevalence, with 11·5% of the total increase in CUD prevalence in RCL-enacting states attributable to RCL. In patients without chronic pain, enacting MCL and RCL led to smaller absolute increases in CUD prevalence (MCL: 0·037% [95%CI: 0·03, 0·05]; RCL: 0·042% [95%CI: 0·02, 0·06]), with 5·7% and 6·0% of the increases in CUD prevalence attributable to MCL and RCL. Overall, MCL and RCL effects were significantly greater in patients with than without chronic pain. By age, MCL and RCL effects were negligible in patients age 18-34 with and without pain. In patients age 35-64 with and without pain, MCL and RCL effects were significant (p<0.001) but small. In patients age 65-75 with pain, absolute increases were 0·10% in MCL-only states and 0·22% in MCL/RCL states, with 9·3% of the increase in CUD prevalence in MCL-only states attributable to MCL, and 19.4% of the increase in RCL states attributable to RCL. In patients age 35-64 and 65-75, MCL and RCL effects were significantly greater in patients with pain. Interpretation: In patients age 35-75, the role of MCL and RCL in the increasing prevalence of CUD was greater in patients with chronic pain than in those without chronic pain, with particularly pronounced effects in patients with chronic pain age 65-75. Although the VHA offers extensive behavioral and non-opioid pharmaceutical treatments for pain, cannabis may seem a more appealing option given media enthusiasm about cannabis, cannabis commercialization activities, and widespread public beliefs about cannabis efficacy. Cannabis does not have the risk/mortality profile of opioids, but CUD is a clinical condition with considerable impairment and comorbidity. Because cannabis legalization in the U.S. is likely to further increase, increasing CUD prevalence among patients with chronic pain following state legalization is a public health concern. The risk of chronic pain increases as individuals age, and the average age of VHA patients and the U.S. general population is increasing. Therefore, clinical monitoring of cannabis use and discussion of the risk of CUD among patients with chronic pain is warranted, especially among older patients. Research in Context: Evidence before this study: Only three studies have examined the role of state medical cannabis laws (MCL) and/or recreational cannabis laws (RCL) in the increasing prevalence of cannabis use disorder (CUD) in U.S. adults, finding significant MCL and RCL effects but with modest effect sizes. Effects of MCL and RCL may vary across important subgroups of the population, including individuals with chronic pain. PubMed was searched by DH for publications on U.S. time trends in cannabis legalization, cannabis use disorders (CUD) and pain from database inception until March 15, 2023, without language restrictions. The following search terms were used: (medical cannabis laws) AND (pain) AND (cannabis use disorder); (recreational cannabis laws) AND (pain) AND (cannabis use disorder); (cannabis laws) AND (pain) AND (cannabis use disorder). Only one study was found that had CUD as an outcome, and this study used cross-sectional data from a single year, which cannot be used to determine trends over time. Therefore, evidence has been lacking on whether the role of state medical and recreational cannabis legalization in the increasing US adult prevalence of CUD differed by chronic pain status.Added value of this study: To our knowledge, this is the first study to examine whether the effects of state MCL and RCL on the nationally increasing U.S. rates of adult cannabis use disorder differ by whether individuals experience chronic pain or not. Using electronic medical record data from patients in the Veterans Health Administration (VHA) that included extensive information on medical conditions associated with chronic pain, the study showed that the effects of MCL and RCL on the prevalence of CUD were stronger among individuals with chronic pain age 35-64 and 65-75, an effect that was particularly pronounced in older patients ages 65-75.Implications of all the available evidence: MCL and RCL are likely to influence the prevalence of CUD through commercialization that increases availability and portrays cannabis use as 'normal' and safe, thereby decreasing perception of cannabis risk. In patients with pain, the overall U.S. decline in prescribed opioids may also have contributed to MCL and RCL effects, leading to substitution of cannabis use that expanded the pool of individuals vulnerable to CUD. The VHA offers extensive non-opioid pain programs. However, positive media reports on cannabis, positive online "information" that can sometimes be misleading, and increasing popular beliefs that cannabis is a useful prevention and treatment agent may make cannabis seem preferable to the evidence-based treatments that the VHA offers, and also as an easily accessible option among those not connected to a healthcare system, who may face more barriers than VHA patients in accessing non-opioid pain management. When developing cannabis legislation, unintended consequences should be considered, including increased risk of CUD in large vulnerable subgroups of the population.

Associations of Military-Related Traumatic Brain Injury With New-Onset Mental Health Conditions and Suicide Risk.

Importance: Research to identify the direct and indirect associations of military-related traumatic brain injury (TBI) with suicide has been complicated by a range of data-related challenges. Objective: To identify differences in rates of new-onset mental health conditions (ie, anxiety, mood, posttraumatic stress, adjustment, alcohol use, and substance use disorders) among soldiers with and without a history of military-related TBI and to explore the direct and indirect (through new-onset mental health disorders) associations of TBI with suicide. Design, Setting, and Participants: This retrospective cohort study used data from the Substance Use and Psychological Injury Combat Study (SUPIC) database. Demographic, military, and health data from the Department of Defense within SUPIC were compiled and linked with National Death Index records to identify deaths by suicide. Participants included US Army soldiers who returned from an Afghanistan or Iraq deployment. Data were analyzed from September to December 2022. Exposures: Military-related TBI. Main Outcomes and Measures: The outcome of interest was suicide. Secondary outcomes were incidence of new-onset mental health conditions. Mediation analyses consisted of accelerated failure time (AFT) models in conjunction with the product of coefficients method. The 6 new-onset mental health diagnosis categories and the 2 or more categories variable were each considered separately as potential mediators; therefore, a total of 14 models plus the overall AFT model estimating the total effect associated with TBI in suicide risk were fit. Results: The study included 860 892 soldiers (320 539 soldiers [37.2%] aged 18-24 at end of index deployment; 766 454 [89.0%] male), with 108 785 soldiers (12.6%) with at least 1 documented TBI on their military health record. Larger increases in mental health diagnoses were observed for all conditions from before to after documented TBI, compared with the matched dates for those without a history of TBI, with increases observed for mood (67.7% vs 37.5%) and substance use (100% vs 14.5%). Time-to-suicide direct effect estimates for soldiers with a history of TBI were similar across mediators. For example, considering new-onset adjustment disorders, time-to-suicide was 16.7% faster (deceleration factor, 0.833; 95% CI, 0.756-0.912) than for soldiers without a history of TBI. Indirect effect estimates of associations with TBI were substantial and varied across mediators. The largest indirect effect estimate was observed through the association with new-onset substance use disorder, with a time to suicide 63.8% faster (deceleration factor, 0.372; 95% CI, 0.322-0.433) for soldiers with a history of TBI. Conclusions and Relevance: In this longitudinal cohort study of soldiers, rates of new-onset mental health conditions were higher among individuals with a history of TBI compared with those without. Moreover, risk for suicide was both directly and indirectly associated with history of TBI. These findings suggest that increased efforts are needed to conceptualize the accumulation of risk associated with multiple military-related exposures and identify evidence-based interventions that address mechanisms associated with frequently co-occurring conditions.

Association of Early-, Middle-, and Late-Life Depression With Incident Dementia in a Danish Cohort.

Importance: Late-life depressive symptoms are associated with subsequent dementia diagnosis and may be an early symptom or response to preclinical disease. Evaluating associations with early- and middle-life depression will help clarify whether depression influences dementia risk. Objective: To examine associations of early-, middle-, and late-life depression with incident dementia. Design, Setting, and Participants: This was a nationwide, population-based, cohort study conducted from April 2020 to March 2023. Participants included Danish citizens from the general population with depression diagnoses who were matched by sex and birth year to individuals with no depression diagnosis. Participants were followed up from 1977 to 2018. Excluded from analyses were individuals followed for less than 1 year, those younger than 18 years, or those with baseline dementia. Exposure: Depression was defined using diagnostic codes from the International Classification of Diseases (ICD) within the Danish National Patient Registry (DNPR) and Danish Psychiatric Central Research Register (DPCRR). Main Outcomes and Measure: Incident dementia was defined using ICD diagnostic codes within the DPCRR and DNPR. Cox proportional hazards regression was used to examine associations between depression and dementia adjusting for education, income, cardiovascular disease, chronic obstructive pulmonary disease, diabetes, anxiety disorders, stress disorders, substance use disorders, and bipolar disorder. Analyses were stratified by age at depression diagnosis, years since index date, and sex. Results: There were 246 499 individuals (median [IQR] age, 50.8 [34.7-70.7] years; 159 421 women [64.7%]) with diagnosed depression and 1 190 302 individuals (median [IQR] age, 50.4 [34.6-70.0] years; 768 876 women [64.6%]) without depression. Approximately two-thirds of those diagnosed with depression were diagnosed before the age of 60 years (684 974 [67.7%]). The hazard of dementia among those diagnosed with depression was 2.41 times that of the comparison cohort (95% CI, 2.35-2.47). This association persisted when the time elapsed from the index date was longer than 20 to 39 years (hazard ratio [HR], 1.79; 95% CI, 1.58-2.04) and among those diagnosed with depression in early, middle, or late life (18-44 years: HR, 3.08; 95% CI, 2.64-3.58; 45-59 years: HR, 2.95; 95% CI, 2.75-3.17; ≥60 years: HR, 2.31; 95% CI, 2.25-2.38). The overall HR was greater for men (HR, 2.98; 95% CI, 2.84-3.12) than for women (HR, 2.21; 95% CI, 2.15-2.27). Conclusions and Relevance: Results suggest that the risk of dementia was more than doubled for both men and women with diagnosed depression. The persistent association between dementia and depression diagnosed in early and middle life suggests that depression may increase dementia risk.

Increasing risk of cannabis use disorder among U.S. veterans with chronic pain: 2005-2019.

ABSTRACT: In the United States, cannabis is increasingly used to manage chronic pain. Veterans Health Administration (VHA) patients are disproportionately affected by pain and may use cannabis for symptom management. Because cannabis use increases the risk of cannabis use disorders (CUDs), we examined time trends in CUD among VHA patients with and without chronic pain, and whether these trends differed by age. From VHA electronic health records from 2005 to 2019 (∼4.3-5.6 million patients yearly), we extracted diagnoses of CUD and chronic pain conditions ( International Classification of Diseases [ ICD ]- 9-CM , 2005-2014; ICD-10-CM , 2016-2019). Differential trends in CUD prevalence overall and age-stratified (<35, 35-64, or ≥65) were assessed by any chronic pain and number of pain conditions (0, 1, or ≥2). From 2005 to 2014, the prevalence of CUD among patients with any chronic pain increased significantly more (1.11%-2.56%) than those without pain (0.70%-1.26%). Cannabis use disorder prevalence increased significantly more among patients with chronic pain across all age groups and was highest among those with ≥2 pain conditions. From 2016 to 2019, CUD prevalence among patients age ≥65 with chronic pain increased significantly more (0.63%-1.01%) than those without chronic pain (0.28%-0.47%) and was highest among those with ≥2 pain conditions. Over time, CUD prevalence has increased more among VHA patients with chronic pain than other VHA patients, with the highest increase among those age ≥65. Clinicians should monitor symptoms of CUD among VHA patients and others with chronic pain who use cannabis, and consider noncannabis therapies, particularly because the effectiveness of cannabis for chronic pain management remains inconclusive.

Moving From Traumatic Events to Traumatic Experiences in the Study of Traumatic Psychopathology.

Trauma is defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) as an event that includes "actual or threatened death, serious injury, or sexual violence" (p. 271). The list of traumatic events included in the DSM-5 represents a long history of psychiatry and psychology's attempts to define trauma and differentiate these events from less severe stressors. In this commentary, we suggest that this strict distinction between traumatic events and stressful events is not useful for public health. The current DSM-5 list of traumatic events may work well for identifying people with the most severe experiences and highest conditional probability of distress who need clinical care. However, the public health field has different priorities. If we think about posttraumatic psychological distress on a population scale, it is not only helping those with the most severe experiences that is needed; rather, public health requires paying attention to all people experiencing distressing stress and trauma reactions. We propose that context is crucial to the development of a population-relevant definition of trauma and provide examples of situations in which stressors have resulted in posttraumatic psychological distress and in which traumatic event reactions have been mitigated by the context in which they occur. We discuss trauma context from an epidemiologic perspective and conclude with recommendations for the field. This article is part of a Special Collection on Mental Health.

Early prediction of mental health problems following military deployment: Integrating pre- and post-deployment factors in neural network models.

Military personnel deployed to war zones are at increased risk of mental health problems such as posttraumatic stress disorder (PTSD) or depression. Early pre- or post-deployment identification of those at highest risk of such problems is crucial to target intervention to those in need. However, sufficiently accurate models predicting objectively assessed mental health outcomes have not been put forward. In a sample consisting of all Danish military personnel who deployed to war zones for the first (N = 27,594), second (N = 11,083) and third (N = 5,161) time between 1992 and 2013, we apply neural networks to predict psychiatric diagnoses or use of psychotropic medicine in the years following deployment. Models are based on pre-deployment registry data alone or on pre-deployment registry data in combination with post-deployment questionnaire data on deployment experiences or early post-deployment reactions. Further, we identified the most central predictors of importance for the first, second, and third deployment. Models based on pre-deployment registry data alone had lower accuracy (AUCs ranging from 0.61 (third deployment) to 0.67 (first deployment)) than models including pre- and post-deployment data (AUCs ranging from 0.70 (third deployment) to 0.74 (first deployment)). Age at deployment, deployment year and previous physical trauma were important across deployments. Post-deployment predictors varied across deployments but included deployment exposures as well as early post-deployment symptoms. The results suggest that neural network models combining pre- and early post-deployment data can be utilized for screening tools that identify individuals at risk of severe mental health problems in the years following military deployment.