Posttraumatic Stress Disorder and Type 2 Diabetes Outcomes in Veterans.

Importance: Posttraumatic stress disorder (PTSD) symptom reduction is linked with lower risk of incident type 2 diabetes (T2D), but little is known about the association between PTSD and comorbid T2D outcomes. Whether PTSD is a modifiable risk factor for adverse T2D outcomes is unknown. Objective: To determine whether patients with PTSD who improved and no longer met diagnostic criteria for PTSD had a lower risk of adverse T2D outcomes compared with patients with persistent PTSD. Design, Setting, and Participants: This retrospective cohort study used deidentified data from US Veterans Health Administration (VHA) historical medical records (from October 1, 2011, to September 30, 2022) to create a cohort of patients aged 18 to 80 years with comorbid PTSD and T2D. Data analysis was performed from March 1 to June 1, 2024. Exposures: Diagnoses of PTSD and T2D. Main Outcomes and Measures: The main outcomes were insulin initiation, poor glycemic control, any microvascular complication, and all-cause mortality. Improvement of PTSD was defined as no longer meeting PTSD diagnostic criteria, per a PTSD Checklist score of less than 33. Entropy balancing controlled for confounding. Survival and competing risk models estimated the association between meeting PTSD criteria and T2D outcomes. Subgroup analyses examined variation by age, sex, race, PTSD severity, and comorbid depression status. Results: The study cohort included 10 002 veterans. More than half of patients (65.3%) were aged older than 50 years and most (87.2%) were men. Patients identified as Black (31.6%), White (62.7%), or other race (5.7%). Before controlling for confounding with entropy balancing, patients who no longer met PTSD diagnostic criteria had similar incidence rates for starting insulin (22.4 vs 24.4 per 1000 person-years), poor glycemic control (137.1 vs 133.7 per 1000 person-years), any microvascular complication (108.4 vs 104.8 per 1000 person-years), and all-cause mortality (11.2 vs 11.0 per 1000 person-years) compared with patients with persistent PTSD. After controlling for confounding, no longer meeting PTSD criteria was associated with a lower risk of microvascular complications (hazard ratio [HR], 0.92 [95% CI, 0.85-0.99]). Among veterans aged 18 to 49 years, no longer meeting PTSD criteria was associated with a lower risk of insulin initiation (HR, 0.69 [95% CI, 0.53-0.88]) and all-cause mortality (HR, 0.39 [95% CI, 0.19-0.83]). Among patients without depression, no longer meeting PTSD criteria was associated with a lower risk of insulin initiation (HR, 0.73 [95% CI, 0.55-0.97]). Conclusions and Relevance: The findings of this cohort study of patients with comorbid PTSD and T2D suggest that PTSD is a modifiable risk factor associated with a modest reduction in microvascular complications. Further research is needed to determine whether findings are similar in non-VHA health care settings.

An empirical investigation of definitions of subthreshold posttraumatic stress disorder.

Subthreshold posttraumatic stress disorder (PTSD) has long been recognized as an important construct that identifies a subgroup of individuals who report significant PTSD symptoms and associated disability but do not endorse enough symptoms to meet the criteria for a full PTSD diagnosis. Different investigators have defined subthreshold PTSD in various ways, making it difficult to interpret findings across studies. To address this problem, we systematically compared individuals who met criteria for nine different subthreshold PTSD definitions with individuals diagnosed with either full PTSD or no PTSD (i.e., failed to meet the criteria for a subthreshold definition) with respect to prevalence and associated clinical outcomes of interest. Participants were 1,082 veterans enrolled in the Veterans After Discharge Longitudinal Registry. PTSD and subthreshold PTSD diagnostic status were determined using the Structured Clinical Interview for DSM-5 (SCID-5) and validated self-report instruments were used to assess clinical outcomes. Across outcomes, subthreshold definitions generally identified a group of participants that was distinguishable from participants in both the PTSD and no PTSD groups, rs = .02-.47. We discuss the benefits and drawbacks of various subthreshold definitions and highlight the need for additional work evaluating these definitions across additional outcomes and samples. In the interim, we propose a working case definition of subthreshold PTSD as meeting any three of the four DSM-5 symptom criteria (i.e., Criteria B, C, D, and E) along with Criterion A and Criteria F-H. The results suggest subthreshold PTSD is a clinically meaningful construct.

The PTSD Criterion A debate: A brief history, current status, and recommendations for moving forward.

Posttraumatic stress disorder (PTSD) Criterion A, also known as the "stressor criterion," has been a major source of debate ever since PTSD was added to the third edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM) in 1980. Since then, the traumatic stress field has held an ongoing debate about how to best define Criterion A and the events that it covers. Because of the COVID-19 pandemic and recent race-based incidents, the Criterion A debate has been reinvigorated. In this paper, we review briefly the history of Criterion A and changes in its language across different editions of the DSM. We then describe the four main positions held by scholars involved in the Criterion A debate and carefully examine the support for those positions. We conclude by offering recommendations for moving forward.

The New Hampshire Hospital Screening and Referral Algorithm (NHHSRA) for Substance Use in People With Serious Mental Illness.

Objective: Substance use is a common co-occurrence among psychiatrically hospitalized adults, yet it is especially difficult to identify in those with serious mental illness. Existing screening instruments are not feasible for individuals with serious mental illness, as they rely heavily on subjective self-report. This study aimed to develop and validate an objective substance use screening instrument for use in seriously mentally ill patient populations.Methods: Objective elements were extracted from existing substance use screening instruments and used to develop a new, data-driven referral tool, the New Hampshire Hospital screening and referral algorithm (NHHSRA). Descriptive statistics were employed to compare NHHSRA summed score and individual patient data elements in a convenience sample of patients who were referred to the Addiction Services by expert addiction psychiatrist evaluation to those who were not referred. Pearson correlation coefficients and logistic regression models assessed the association between patient referral and the overall NHHSRA score and individual items. The NHHSRA was then piloted in a smaller convenience sample of patients against the standard clinical-based identification for substance use treatment needs.Results: The instrument consists of 5 objective items. These were tested in a sample of 302 sequentially admitted adults with serious mental illness. Three of the items were significantly associated with likelihood of benefitting from referral for substance use interventions (maximum likelihood estimate and standard deviation [SD] for positive non-tetrahydrocannabinol [non-THC] toxicology screen or > 0% blood alcohol level = 3.61 [0.6]; diagnosis of a substance use disorder = 4.89 [0.73]; and medication-assisted treatment or relapse prevention = 2.78 [0.67]), and these were prioritized in building a decision tree algorithm. The area under the receiver operating characteristic (ROC) curve for the NHHSRA was 0.96, indicating that the NHHSRA has high overall sensitivity and the algorithm was capable of distinguishing between patients needing substance use intervention versus those who do not with 96% accuracy. In the pilot implementation study of another 20 patient admissions, the NHHSRA accurately identified 100% (n = 6) of patients deemed to benefit from substance use interventions by expert addiction psychiatric evaluation. The standard clinical-based referral process identified only 33% (n = 2) and erroneously identified another 4 for referral to substance use intervention that would not have been warranted.Conclusions: The NHHSRA holds promise in its ability to improve objective and timely identification of substance use in a seriously mentally ill inpatient population, helping to facilitate treatment.

Prevalence of Depression and Posttraumatic Stress Disorder in Flint, Michigan, 5 Years After the Onset of the Water Crisis.

Importance: Environmental disasters, such as the Flint, Michigan, water crisis, are potentially traumatic events (PTEs) that may precipitate long-term psychiatric disorders. The water crisis was associated with acute elevations in mental health problems in the Flint community, but long-term psychiatric sequelae have not yet been evaluated using standardized diagnostic measures. Objective: To investigate the prevalence of and factors associated with current presumptive diagnostic-level major depression and posttraumatic stress disorder (PTSD) among Flint residents 5 years after the onset of the crisis. Design, Setting, and Participants: In this cross-sectional study, a household probability sample of 1970 adults living in Flint, Michigan, during the crisis were surveyed about their crisis experiences, their psychological symptoms 5 years later, and their access to and use of mental health services in the intervening years. Analyses were weighted to produce population-representative estimates. Main Outcomes and Measures: Presumptive Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) diagnostic-level past-year major depression and PTSD. Results: Among 1970 respondents, 1061 of 1946 reporting sex (54.5%) were women; 1043 of 1951 reporting race (53.5%) were Black or African American and 829 (42.5%) were White; and 1895 of 1946 reporting ethnicity (97.4%) were non-Hispanic. Overall, 435 (22.1%) met DSM-5 criteria for presumptive past-year depression, 480 (24.4%) for presumptive past-year PTSD, and 276 (14.0%) for both disorders. Residents who believed that their or their family's health was harmed by contaminated water (eg, risk ratio [RR] for depression: 2.23; 95% CI, 1.80-2.76), who had low confidence in public-official information (eg, RR for PTSD, 1.44; 95% CI, 1.16-1.78), who had previous exposure to PTEs (eg, RR for both disorders: 5.06; 95% CI, 2.99-8.58), or who reported low social support (eg, RR for PTSD, 2.58; 95% CI, 1.94-3.43) had significantly higher risk for depression, PTSD, and comorbidity. PTEs involving prior physical or sexual assault were especially potent risk factors (eg, both disorders: RR, 7.30; 95% CI, 4.30-12.42). Only 685 respondents (34.8%) were ever offered mental health services to assist with water-crisis-related psychiatric symptoms; most (543 [79.3%]) who were offered services utilized them. Conclusions and Relevance: In this cross-sectional study of psychiatric disorder in Flint, Michigan, presumptive depression and PTSD were highly prevalent 5 years after the onset of the water crisis. These findings suggest that public-works environmental disasters have large-scale, long-term psychological sequelae. The Flint community may require expanded mental health services to meet continued psychiatric need. National disaster preparedness and response programs should consider psychiatric outcomes.

Deimplementation of Benzodiazepine Prescribing in Posttraumatic Stress Disorder in the Veterans Health Administration.

Objective: Our objective was to characterize benzodiazepine prescribing changes among veterans with posttraumatic stress disorder (PTSD) and inform efforts to deimplement low-value prescribing practices.Methods: This retrospective observational study used national Veterans Health Administration (VHA) administrative databases to examine annual period prevalence and incidence of benzodiazepine prescribing from 2009 through 2019 in veterans with PTSD. International Classification of Diseases (ICD-9/10) codes were used to identify PTSD. Temporal trends in discontinuation rates, incidence rates, and prevalent prescribing among patients newly engaged in PTSD care were measured.Results: Benzodiazepine prevalence in veterans with PTSD declined from 31.3% in 2009 to 10.7% in 2019, and incidence decreased from 11.4% to 2.9%, along with a 30% decrease in daily doses. Increasing discontinuation rates accounted for 21.0% of the decline in prevalence, while decreasing incidence among existing patients accounted for 36.8%, and decreased prevalence among new PTSD cohort entrants accounted for 42.2%. Women received benzodiazepines more commonly than men (odds ratio [OR] = 1.67; 95% CI, 1.64-1.70). The proportion of older adults increased over time among both existing (2009: 14.5%; 2019: 46.5%) and new (2009: 8.6%; 2019: 24.3%) benzodiazepine recipients.Conclusions: Benzodiazepine prescribing in VHA among veterans with PTSD showed changes driven by decreases in prevalence among new PTSD cohort entrants, with smaller changes in discontinuation and decreased incidence among existing patients. Educational initiatives may have curtailed benzodiazepine prescribing through promotion of effective alternative treatment options and supporting discontinuation through various tapering strategies. These initiatives offer resources and lessons to other health care systems to deimplement inappropriate benzodiazepine prescribing and other potentially harmful practices through patient-centered approaches that promote viable treatment alternatives.

Decoding Shared Versus Divergent Transcriptomic Signatures Across Cortico-Amygdala Circuitry in PTSD and Depressive Disorders.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is a debilitating neuropsychiatric disease that is highly comorbid with major depressive disorder (MDD) and bipolar disorder. The overlap in symptoms is hypothesized to stem from partially shared genetics and underlying neurobiological mechanisms. To delineate conservation between transcriptional patterns across PTSD and MDD, the authors examined gene expression in the human cortex and amygdala in these disorders. METHODS: RNA sequencing was performed in the postmortem brain of two prefrontal cortex regions and two amygdala regions from donors diagnosed with PTSD (N=107) or MDD (N=109) as well as from neurotypical donors (N=109). RESULTS: The authors identified a limited number of differentially expressed genes (DEGs) specific to PTSD, with nearly all mapping to cortical versus amygdala regions. PTSD-specific DEGs were enriched in gene sets associated with downregulated immune-related pathways and microglia as well as with subpopulations of GABAergic inhibitory neurons. While a greater number of DEGs associated with MDD were identified, most overlapped with PTSD, and only a few were MDD specific. The authors used weighted gene coexpression network analysis as an orthogonal approach to confirm the observed cellular and molecular associations. CONCLUSIONS: These findings provide supporting evidence for involvement of decreased immune signaling and neuroinflammation in MDD and PTSD pathophysiology, and extend evidence that GABAergic neurons have functional significance in PTSD.

Risk factors for suicide in the Vietnam-era twin registry.

BACKGROUND: The risk of suicide among Veterans is of major concern, particularly among those who experienced a combat deployment and/or have a history of PTSD. DESIGN AND METHODS: This was a retrospective cohort study of post-discharge suicide among Vietnam-era Veterans who are members of the Vietnam Era Twin (VET) Registry. The VET Registry is a national sample of male twins from all branches of the military, both of whom served on active duty between 1964 and 1975. Military service and demographic factors were available from the military records. Service in-theater was based on military records; combat exposure and PTSD symptoms were assessed in 1987 by questionnaire. Mortality follow-up, from discharge to 2016, is identified from Department of Veterans Affairs, Social Security Administration, and National Death Index records; suicide as a cause of death is based on the International Classification of Death diagnostic codes from the death certificate. Statistical analysis used Cox proportional hazards regression to estimate the association of Vietnam-theater service, combat exposure, and PTSD symptoms with suicide while adjusting for military service and demographic confounding factors. RESULTS: From the 14,401 twins in the VET Registry, there were 147 suicide deaths during follow-up. In adjusted analyses, twins who served in the Vietnam theater were at similar risk of post-discharge suicide compared with non-theater Veterans; there was no association between combat and suicide. An increase in severity of PTSD symptoms was significantly associated with an increased risk of suicide in adjusted analyses (hazard ratio = 1.13 per five-point increase in symptom score; 95% CI: 1.02-1.27). CONCLUSIONS: Service in the Vietnam theater is not associated with greater risk of suicide; however, PTSD symptom severity poses a degree of risk of suicide in Vietnam-era Veterans. Adequate screening for PTSD in Veterans may be promising to identify Veterans who are at increased risk of suicide.

Comparison of Prolonged Exposure vs Cognitive Processing Therapy for Treatment of Posttraumatic Stress Disorder Among US Veterans: A Randomized Clinical Trial.

Importance: Posttraumatic stress disorder (PTSD) is a prevalent and serious mental health problem. Although there are effective psychotherapies for PTSD, there is little information about their comparative effectiveness. Objective: To compare the effectiveness of prolonged exposure (PE) vs cognitive processing therapy (CPT) for treating PTSD in veterans. Design, Setting, and Participants: This randomized clinical trial assessed the comparative effectiveness of PE vs CPT among veterans with military-related PTSD recruited from outpatient mental health clinics at 17 Department of Veterans Affairs medical centers across the US from October 31, 2014, to February 1, 2018, with follow-up through February 1, 2019. The primary outcome was assessed using centralized masking. Tested hypotheses were prespecified before trial initiation. Data were analyzed from October 5, 2020, to May 5, 2021. Interventions: Participants were randomized to 1 of 2 individual cognitive-behavioral therapies, PE or CPT, delivered according to a flexible protocol of 10 to 14 sessions. Main Outcomes and Measures: The primary outcome was change in PTSD symptom severity on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) from before treatment to the mean after treatment across posttreatment and 3- and 6-month follow-ups. Secondary outcomes included other symptoms, functioning, and quality of life. Results: Analyses were based on all 916 randomized participants (730 [79.7%] men and 186 [20.3%] women; mean [range] age 45.2 [21-80] years), with 455 participants randomized to PE (mean CAPS-5 score at baseline, 39.9 [95% CI, 39.1-40.7] points) and 461 participants randomized to CPT (mean CAPS-5 score at baseline, 40.3 [95% CI, 39.5-41.1] points). PTSD severity on the CAPS-5 improved substantially in both PE (standardized mean difference [SMD], 0.99 [95% CI, 0.89-1.08]) and CPT (SMD, 0.71 [95% CI, 0.61-0.80]) groups from before to after treatment. Mean improvement was greater in PE than CPT (least square mean, 2.42 [95% CI, 0.53-4.31]; P = .01), but the difference was not clinically significant (SMD, 0.17). Results for self-reported PTSD symptoms were comparable with CAPS-5 findings. The PE group had higher odds of response (odds ratio [OR], 1.32 [95% CI, 1.00-1.65]; P < .001), loss of diagnosis (OR, 1.43 [95% CI, 1.12-1.74]; P < .001), and remission (OR, 1.62 [95% CI, 1.24-2.00]; P < .001) compared with the CPT group. Groups did not differ on other outcomes. Treatment dropout was higher in PE (254 participants [55.8%]) than in CPT (215 participants [46.6%]; P < .01). Three participants in the PE group and 1 participant in the CPT group were withdrawn from treatment, and 3 participants in each treatment dropped out owing to serious adverse events. Conclusions and Relevance: This randomized clinical trial found that although PE was statistically more effective than CPT, the difference was not clinically significant, and improvements in PTSD were meaningful in both treatment groups. These findings highlight the importance of shared decision-making to help patients understand the evidence and select their preferred treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT01928732.

Instruments for Measuring Violence on Acute Inpatient Psychiatric Units: Review and Recommendations.

OBJECTIVE: Violence by patients against inpatient psychiatric unit staff is common, causing considerable suffering. Despite the Joint Commission's 2018 requirement for behavioral health organizations to use standardized instruments, no identified gold standard measures of violence and aggression exist. Therefore, accurate data are lacking on the frequency of patient-to-staff violence to guide development of safer institutional clinical policies or to assess the impact of targeted interventions to reduce violence. To inform recommendations for developing standardized scales, the authors reviewed the scoring instruments most commonly used to measure violence in recent studies. METHODS: A comprehensive literature search for violence measurement instruments in articles published in English from June 2008 to June 2018 was performed. Review criteria included use of instruments measuring patient-to-staff violence or aggression in acute, nonforensic, nongeriatric populations. Exclusion criteria included child or adolescent populations, staff-to-staff violence, and staff- or visitor-to-patient violence. RESULTS: Overall, 74 studies were identified, of which 74% used structured instruments to measure aggression and violence on inpatient psychiatric units during the past 10 years. The instruments were primarily variants of the Observed Aggression Scale (OAS); 26% of the studies used unstructured clinical notes and researcher questionnaires. Major obstacles to implementing measurement instruments included time and workflow constraints and difficulties with use. CONCLUSIONS: In the past 10 years, OAS variants with evidence of validity and reliability that define aggression and violence have been consistently used. The authors propose that adapting the Modified OAS to collect real-time clinical data could help overcome barriers to implementing standardized instruments to quantify violence against psychiatric staff.

Increased Smoking Cessation Among Veterans With Large Decreases in Posttraumatic Stress Disorder Severity.

INTRODUCTION: Improvement in posttraumatic stress disorder (PTSD) is associated with better health behavior such as better medication adherence and greater use of nutrition and weight loss programs. However, it is not known if reducing PTSD severity is associated with smoking cessation, a poor health behavior common in patients with PTSD. AIMS AND METHODS: Veterans Health Affairs (VHA) medical record data (2008-2015) were used to identify patients with PTSD diagnosed in specialty care. Clinically meaningful PTSD improvement was defined as ≥20 point PTSD Checklist (PCL) decrease from the first PCL ≥50 and the last available PCL within 12 months and at least 8 weeks later. The association between clinically meaningful PTSD improvement and smoking cessation within 2 years after baseline among 449 smokers was estimated in Cox proportional hazard models. Entropy balancing controlled for confounding. RESULTS: On average, patients were 39.4 (SD = 12.9) years of age, 86.6% were male and 71.5% were white. We observed clinically meaningful PTSD improvement in 19.8% of participants. Overall, 19.4% quit smoking in year 1 and 16.6% in year 2. More patients with versus without clinically meaningful PTSD improvement stopped smoking (n = 36, cumulative incidence = 40.5% vs. 111, cumulative incidence = 30.8%, respectively). After controlling for confounding, patients with versus without clinically meaningful PTSD improvement were more likely to stop smoking within 2 years (hazard ratio = 1.57; 95% confidence interval: 1.04-2.36). CONCLUSIONS: Patients with clinically meaningful PTSD improvement were significantly more likely to stop smoking. Further research should determine if targeted interventions are needed or whether improvement in PTSD symptoms is sufficient to enable smoking cessation. IMPLICATIONS: Patients with PTSD are more likely to develop chronic health conditions such as heart disease and diabetes. Poor health behaviors, including smoking, partly explain the risk for chronic disease in this patient population. Our results demonstrate that clinically meaningful PTSD improvement is followed by greater likelihood of smoking cessation. Thus, PTSD treatment may enable healthier behaviors and reduce risk for smoking-related disease.

Does COVID-19 count?: Defining Criterion A trauma for diagnosing PTSD during a global crisis.

INTRODUCTION: The ongoing coronavirus disease 2019 (COVID-19) pandemic is a globally significant crisis with a rapid spread worldwide, high rates of illness and mortality, a high degree of uncertainty, and a disruption of daily life across the sociodemographic spectrum. The clinically relevant psychological consequences of this catastrophe will be long-lasting and far-reaching. There is an emerging body of empirical literature related to the mental health aspects of this pandemic and this body will likely expand exponentially. The COVID-19 pandemic is an example of a historic catastrophe from which we can learn much and from which the field will need to archive, interpret, and synthesize a multitude of clinical and research observations. METHODS: In this commentary, we discuss situations and contexts in which a diagnosis of posttraumatic stress disorder (PTSD) may or may not apply within the context of diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) criteria. RESULTS: Our consensus is that a COVID-related event cannot be considered traumatic unless key aspects of DSM-5's PTSD Criterion A have been established for a specific type of COVID-19 event (e.g., acute, life-threatening, and catastrophic). CONCLUSION: The application of a more liberal interpretation of Criterion A will dilute the PTSD diagnosis, increase heterogeneity, confound case-control research, and create an overall sample pool with varying degrees of risk and vulnerability factors.

Five Essential Elements of Immediate and Mid-Term Mass Trauma Intervention: Empirical Evidence.

Given the devastation caused by disasters and mass violence, it is critical that intervention policy be based on the most updated research findings. However, to date, no evidence-based consensus has been reached supporting a clear set of recommendations for intervention during the immediate and the mid-term post mass trauma phases. Because it is unlikely that there will be evidence in the near or mid-term future from clinical trials that cover the diversity of disaster and mass violence circumstances, we assembled a worldwide panel of experts on the study and treatment of those exposed to disaster and mass violence to extrapolate from related fields of research, and to gain consensus on intervention principles. We identified five empirically supported intervention principles that should be used to guide and inform intervention and prevention efforts at the early to mid-term stages. These are promoting: 1) a sense of safety, 2) calming, 3) a sense of self- and community efficacy, 4) connectedness, and 5) hope.

PTSD improvement and substance use disorder treatment utilization in veterans: Evidence from medical record data.

BACKGROUND: Clinical trials reveal posttraumatic stress disorder (PTSD) improvement leads to decreased substance use among patients with comorbid substance use disorder (SUD). Using administrative medical record data, we determined whether clinically meaningful PTSD Checklist (PCL) (≥20 points) score decreases were positively associated with SUD treatment utilization. METHODS: We used a retrospective cohort of Veterans Health Affairs (VHA) medical record data (2008-2015). PTSD Checklist (PCL) scores were used to categorize patients into those with a clinically meaningful PTSD improvement (≥20 point decrease) or not (<20 point decrease or increase). PTSD and SUD were measured by ICD-9 codes. Propensity score weighting controlled for confounding in logistic and negative binomial models that estimated the association between clinically meaningful PTSD improvement and use of SUD treatment and number of SUD clinic visits. RESULTS: The 699 eligible patients were, on average, 40.4 (±13.2) years old, 66.2% white and 33.1% were married. After controlling for confounding, there was a 56% increased odds of any SUD treatment utilization among those with a PCL decrease ≥20 vs < 20 (OR = 1.56; 95%CI = 1.04-2.33) but there was no association with number of SUD treatment visits. CONCLUSIONS: Clinically meaningful reductions in PTSD symptoms were associated with any SUD treatment utilization but not amount of utilization. Improvement in PTSD symptoms, independent of the treatment modality, may enable SUD treatment seeking.

Transcriptomic organization of the human brain in post-traumatic stress disorder.

Despite extensive study of the neurobiological correlates of post-traumatic stress disorder (PTSD), little is known about its molecular determinants. Here, differential gene expression and network analyses of four prefrontal cortex subregions from postmortem tissue of people with PTSD demonstrate extensive remodeling of the transcriptomic landscape. A highly connected downregulated set of interneuron transcripts is present in the most significant gene network associated with PTSD. Integration of this dataset with genotype data from the largest PTSD genome-wide association study identified the interneuron synaptic gene ELFN1 as conferring significant genetic liability for PTSD. We also identified marked transcriptomic sexual dimorphism that could contribute to higher rates of PTSD in women. Comparison with a matched major depressive disorder cohort revealed significant divergence between the molecular profiles of individuals with PTSD and major depressive disorder despite their high comorbidity. Our analysis provides convergent systems-level evidence of genomic networks within the prefrontal cortex that contribute to the pathophysiology of PTSD in humans.

PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies.

Despite well-known peripheral immune activation in posttraumatic stress disorder (PTSD), there are no studies of brain immunologic regulation in individuals with PTSD. [11C]PBR28 Positron Emission Tomography brain imaging of the 18-kDa translocator protein (TSPO), a microglial biomarker, was conducted in 23 individuals with PTSD and 26 healthy individuals-with or without trauma exposure. Prefrontal-limbic TSPO availability in the PTSD group was negatively associated with PTSD symptom severity and was significantly lower than in controls. Higher C-reactive protein levels were also associated with lower prefrontal-limbic TSPO availability and PTSD severity. An independent postmortem study found no differential gene expression in 22 PTSD vs. 22 controls, but showed lower relative expression of TSPO and microglia-associated genes TNFRSF14 and TSPOAP1 in a female PTSD subgroup. These findings suggest that peripheral immune activation in PTSD is associated with deficient brain microglial activation, challenging prevailing hypotheses positing neuroimmune activation as central to stress-related pathophysiology.

PTSD improvement and incident cardiovascular disease in more than 1000 veterans.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with increased risk for cardiovascular disease (CVD). Whether clinically meaningful PTSD improvement is associated with lowering CVD risk is unknown. METHODS: Eligible patients (n = 1079), were 30-70 years old, diagnosed with PTSD and used Veterans Health Affairs PTSD specialty clinics. Patients had a PTSD Checklist score (PCL) ≥ 50 between Fiscal Year (FY) 2008 and FY2012 and a second PCL score within 12 months and at least 8 weeks after the first PCL ≥ 50. Clinically meaningful PTSD improvement was defined by ≥20 point PCL decrease between the first and second PCL score. Patients were free of CVD diagnoses for 1 year prior to index. Index date was 12 months following the first PCL. Follow-up continued to FY2015. Cox proportional hazard models estimated the association between clinically meaningful PTSD improvement and incident CVD and incident ischemic heart disease (IHD). Sensitivity analysis stratified by age group (30-49 vs. 50-70 years) and depression. Confounding was controlled using propensity scores and inverse probability of exposure weighting. RESULTS: Patients were 48.9 ± 10.9 years of age on average, 83.3% male, 60.1% white, and 29.5% black. After controlling for confounding, patients with vs. without PTSD improvement did not differ in CVD risk (HR = 1.08; 95%CI: 0.72-1.63). Results did not change after stratifying by age group or depression status. Results were similar for incident IHD. CONCLUSIONS: Over a 2-7 year follow-up, we did not find an association between clinically meaningful PTSD improvement and incident CVD. Additional research is needed using longer follow-up.

Clinically meaningful posttraumatic stress disorder (PTSD) improvement and incident hypertension, hyperlipidemia, and weight loss.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with increased risk for cardiometabolic disease. Clinically meaningful PTSD improvement is associated with a lower risk for diabetes, but it is not known if similar associations exist for incident hypertension, hyperlipidemia, and clinically relevant weight loss (i.e., ≥5% loss). METHOD: Medical record data from Veterans Health Affairs patients with clinic encounters between fiscal year (FY) 2008 to 2015 were used to identify patients with worsening or no PTSD improvement (i.e., PTSD checklist (PCL) score decrease <10), small (10-19 point PCL decrease), and large (≥20 point PCL decrease) PTSD improvement. To estimate the association between degree of PTSD improvement and incident hypertension (n = 979), incident hyperlipidemia (n = 1,139) and incident ≥5% weight loss (1,330), we computed Cox proportional hazard models, controlling for confounding using inverse probability of exposure weighting (IPEW). RESULTS: Overall, patients were about 40 years of age, 80% male and 65% White. Worsening or no PCL change occurred in about 60%, small improvement in 20%, and large improvement in 20%. After weighting data, compared with worsening or no change, both small and large PTSD improvements were associated, albeit not significantly, with lower risks for hypertension (HR = 0.68; 95% confidence interval, CI [0.46, 1.01] and HR = 0.79; 95% CI [0.53, 1.18], respectively). In weighted data, PTSD improvement was not associated with incident hyperlipidemia or ≥5% weight loss. CONCLUSIONS: We observed limited evidence for an association between PTSD improvement and decreased hypertension risk. PCL decreases were not associated with hyperlipidemia or ≥5% weight loss. Further studies that measure potential physical health benefits of change in specific PTSD symptoms are needed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).