Lifetime trauma exposure and arthritis in older adults.

OBJECTIVE: Experiencing potentially traumatic events across one's lifecourse increases risk for poor physical health outcomes. Existing models emphasize the effects of any lifetime trauma exposure, risk accumulation (multiple traumas over time), and sensitive periods of exposure (specific exposure timepoints leading to lasting consequences). We examined how different indices of trauma exposure across the lifecourse were associated with later life arthritis, a common and debilitating health condition. METHODS: Data include 5,717 Health and Retirement Study participants (age mean = 65.3, SD = 12.9) who reported on lifetime adversity and trauma in 2006-2008. Lifetime trauma exposure was modeled as any trauma, accumulation of traumas, and lifecourse profiles (no exposure, childhood only, adulthood only, childhood and adulthood exposure). Outcomes included prevalent arthritis at baseline and incident arthritis across 12 years of follow-up. Covariate-adjusted generalized linear models for prevalence ratios (PR) and Cox proportional hazards models for hazard ratios (HR) were conducted. RESULTS: Any lifetime trauma was associated with both prevalent arthritis at baseline (PR = 1.13, 95%CI 1.05-1.22) and incident arthritis over 12 years (HR = 1.25, 95%CI 1.17-1.47). Greater trauma accumulation was significantly associated with both prevalent and incident arthritis. Childhood exposure was particularly strongly associated with prevalent and incident cases, with adulthood exposure being unassociated with incident arthritis. Across models, trauma exposure was associated with prevalent cases of both immune-related and osteoarthritis types. CONCLUSIONS: Higher lifetime trauma burden, especially during childhood, may predispose individuals to arthritis later in life. Early intervention or prevention efforts should identify trauma as an important risk factor for musculoskeletal health across the lifecourse.

Association of psychiatric disorders with clinical diagnosis of long COVID in US veterans.

BACKGROUND: Psychiatric disorders may be a risk factor for long COVID, broadly defined as COVID-19 conditions continuing three months post-acute infection. In US Veterans with high psychiatric burden, we examined associations between psychiatric disorders and clinical diagnosis of long COVID. METHODS: We conducted a retrospective cohort study using health records from VA patients with a positive SARS-CoV-2 test from February 2020 to February 2023. Generalized linear models estimated associations between any psychiatric disorder and likelihood of subsequent diagnosis with long COVID (i.e. two or more long COVID clinical codes). Models were adjusted for socio-demographic, medical, and behavioral factors. Secondary models examined individual psychiatric disorders and age-stratified associations. RESULTS: Among 660 217 VA patients with positive SARS-CoV-2 tests, 56.3% had at least one psychiatric disorder diagnosis and 1.4% were diagnosed with long COVID. Individuals with any psychiatric disorder had higher risk for long COVID diagnosis in models adjusted for socio-demographic factors, vaccination status, smoking, and medical comorbidities (relative risk, RR = 1.28, 95% CI 1.21-1.35), with the strongest associations in younger individuals. Considering specific disorders, depressive, anxiety, and stress-related disorders were associated with increased risk for long COVID diagnoses (RRs = 1.36-1.48), but associations were in the opposite direction for substance use and psychotic disorders (RRs = 0.78-0.88). CONCLUSIONS: Psychiatric disorder diagnoses were associated with increased long COVID diagnosis risk in VA patients, with the strongest associations observed in younger individuals. Improved surveillance, treatment, and prevention for COVID-19 and its long-term sequelae should be considered for individuals with psychiatric conditions.

Psychological Resilience to Trauma and Risk of COVID-19 Infection and Somatic Symptoms Across 2 Years.

OBJECTIVE: Exposure to trauma increases the risk of somatic symptoms, as well as acute and chronic physical diseases. However, many individuals display psychological resilience, showing positive psychological adaptation despite trauma exposure. Resilience to prior trauma may be a protective factor for physical health during subsequent stressors, including the COVID-19 pandemic. METHODS: Using data from 528 US adults in a longitudinal cohort study, we examined psychological resilience to lifetime potentially traumatic events early in the pandemic and the risk of COVID-19 infection and somatic symptoms across 2 years of follow-up. Resilience was defined as level of psychological functioning relative to lifetime trauma burden, assessed in August 2020. Outcomes included COVID-19 infection and symptom severity, long COVID, and somatic symptoms assessed every 6 months for 24 months. Using regression models, we examined associations between resilience and each outcome adjusting for covariates. RESULTS: Higher psychological resilience to trauma was associated with a lower likelihood of COVID-19 infection over time, with one standard deviation higher resilience score associated with a 31% lower likelihood of COVID-19 infection, adjusting for sociodemographics and vaccination status. Furthermore, higher resilience was associated with lower levels of somatic symptoms during the pandemic, adjusting for COVID-19 infection and long COVID status. In contrast, resilience was not associated with COVID-19 disease severity or long COVID. CONCLUSIONS: Psychological resilience to prior trauma is associated with lower risk of COVID-19 infection and lower somatic symptoms during the pandemic. Promoting psychological resilience to trauma may benefit not only mental but also physical health.

Worse sleep, worsening post-traumatic stress disorder (PTSD): Poor sleep quality associated with increases in PTSD symptoms amongst those experiencing high threat of the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic is a global health crisis with the potential to elicit and worsen psychiatric symptoms, particularly post-traumatic stress disorder (PTSD) symptoms. Identifying modifiable protective factors is critical for preventing and treating PTSD symptoms both during and following the COVID-19 pandemic. The present study examined associations of self-reported sleep quality and anticipatory threat appraisals of the pandemic with PTSD symptoms 6 months later in a sample enriched for pre-pandemic trauma exposure and PTSD. The sample included 590 adults (mean age 38.2 years) who completed a baseline survey in August/September 2020 and follow-up survey in March/April 2021. The sample was recruited from a pool of participants interested in a prior study about traumatic stress. Participants self-reported sleep quality and pandemic-related anticipatory threat appraisals at baseline. PTSD symptoms were assessed at baseline and follow-up. Baseline sleep quality was associated with PTSD symptoms at follow-up controlling for baseline PTSD symptoms (B = -2.49, p = 0.001). Perceived anticipatory threat of the pandemic moderated this association such that worse sleep quality was related to more severe PTSD symptoms at follow-up for participants with higher (B = -4.07, p < 0.001) but not lower (B = -0.43, p = 0.679) anticipatory threat about the COVID-19 pandemic. These findings suggest that poor sleep quality may enhance vulnerability to later PTSD symptoms during the pandemic, particularly among those individuals who perceived the pandemic as threatening for their future. Treatments that address sleep problems may be beneficial for reducing trauma-related symptoms during and following the global health crisis.

Relationships of inflammation trajectories with white matter volume and integrity in midlife.

OBJECTIVE: Elevated inflammation is associated with worse late-life cognitive functioning and brain health. Our goal was to examine the relationship between inflammation trajectories and white matter integrity in midlife. METHODS: Participants were 508 adults from the Coronary Artery Risk Development in Young Adults Study (CARDIA; 51% female). Latent class analysis was used to identify inflammation trajectories based on repeated measures of the inflammatory marker C-reactive protein (CRP) over the 18 years before brain magnetic resonance imaging (MRI). Outcomes were brain MRI measures of total and region-specific white matter volume and integrity at a mean age of 50.6 ± 3.4 years. Linear regression was used to examine if inflammation trajectories were associated with brain MRI outcomes, adjusting for potential confounds in all models and for disease and health behaviors in follow-up models. RESULTS: Lower-stable (38%), moderate-increasing (7%), and consistently-higher (54%), trajectories emerged. Compared to the lower-stable group, the moderate-increasing group showed lower white matter volume (ß = -0.18, 95% CI -0.29, -0.06) and worse white matter integrity as indexed by lower fractional anisotropy (FA; ß = -0.37, 95% CI -0.70, -0.04) and higher mean diffusivity (ß = 0.44, 95% CI 0.11, 0.78) in the whole brain. The consistently-higher group showed lower whole-brain FA (ß = -0.20, -0.38, -0.03). In exploratory analyses, the moderate-increasing group showed lower white matter volume, lower FA and higher MD in the frontal, temporal, and parietal lobes compared to the lower-stable group. The consistently-higher group showed lower white matter volume in the parietal lobe and lower FA in the frontal, temporal, and parietal lobes, but similar MD, compared to the lower-stable group. Findings for the moderate-increasing, but not the consistently-higher, group were robust to adjustment for disease and lifestyle factors. CONCLUSION: Increasing or high inflammation trajectories from early to mid adulthood are associated with worse brain health, as indexed by lower white matter volume and/or worse white matter integrity.

Compounding Stress: Childhood Adversity as a Risk Factor for Adulthood Trauma Exposure in the Health and Retirement Study.

Childhood adversity (CA) and adulthood traumatic experiences (ATEs) are common and unequally distributed in the general population. Early stressors may beget later stressors and alter life-course trajectories of stressor exposure. Gender differences exist regarding the risk of specific stressors. However, few studies have examined the associations between specific types of CA and ATEs. Using a large-scale sample of older adults, we aimed to (a) determine if specific or cumulative CA increased the risk for specific or cumulative ATEs and (b) examine whether these associations were moderated by gender. In a sample from the U.S. Health and Retirement Study (N = 15,717; Mage = 67.57 years, SD = 10.54), cross-sectional Poisson and logistic regression models were fitted to assess the specific and cumulative associations between CA and ATEs. Overall, cumulative CA was associated with a larger risk ratio of ATEs, adjusted for covariates: aRRRs = 1.28, 1.63, and 1.97 for 1, 2, and 3-4 adverse events in childhood, respectively. Cumulative CA was particularly strongly associated with adulthood physical attacks, aOR = 5.66, and having a substance-abusing spouse or child, aOR = 4.00. Childhood physical abuse was the strongest independent risk factor for cumulative ATEs, aRRR = 1.49, and most strongly associated with adulthood physical attacks, aOR = 3.41. Gender moderated the association between cumulative CA and cumulative ATEs, with slightly stronger associations between cumulative CA and ATEs for women than men. Given that CA and ATEs perpetuate health disparities worldwide, reducing their incidence and effects should be major priorities for public health.

Gut microbiome of a porcine model of metabolic syndrome and HF-pEF.

Metabolic syndrome (MetS) is a composite of cardiometabolic risk factors, including obesity, dyslipidemia, hypertension, and insulin resistance, with a range of secondary sequelae such as nonalcoholic fatty liver disease and diastolic heart failure. This syndrome has been identified as one of the greatest global health challenges of the 21st century. Herein, we examine whether a porcine model of diet- and mineralocorticoid-induced MetS closely mimics the cardiovascular, metabolic, gut microbiota, and functional metataxonomic phenotype observed in human studies. Landrace pigs with deoxycorticosterone acetate-induced hypertension fed a diet high in fat, salt, and sugar over 12 wk were assessed for hyperlipidemia, hyperinsulinemia, and immunohistologic, echocardiographic, and hemodynamic parameters, as well as assessed for microbiome phenotype and function through 16S rRNA metataxonomic and metabolomic analysis, respectively. All MetS animals developed obesity, hyperlipidemia, insulin resistance, hypertension, fatty liver, structural cardiovascular changes including left ventricular hypertrophy and left atrial enlargement, and increased circulating saturated fatty acid levels, all in keeping with the human phenotype. A reduction in α-diversity and specific microbiota changes at phylum, family, and genus levels were also observed in this model. Specifically, this porcine model of MetS displayed increased abundances of proinflammatory bacteria coupled with increased circulating tumor necrosis factor-α and increased secondary bile acid-producing bacteria, which substantially impacted fibroblast growth factor-19 expression. Finally, a significant decrease in enteroprotective bacteria and a reduction in short-chain fatty acid-producing bacteria were also noted. Together, these data suggest that diet and mineralocorticoid-mediated development of biochemical and cardiovascular stigmata of metabolic syndrome in pigs leads to temporal gut microbiome changes that mimic key gut microbial population signatures in human cardiometabolic disease.NEW & NOTEWORTHY This study extends a prior porcine model of cardiometabolic syndrome to include systemic inflammation, fatty liver, and insulin sensitivity. Gut microbiome changes during evolution of porcine cardiometabolic disease recapitulate those in human subjects with alterations in gut taxa associated with proinflammatory bacteria, bile acid, and fatty acid pathways. This clinical scale model may facilitate design of future interventional trials to test causal relationships between gut dysbiosis and cardiometabolic syndrome at a systemic and organ level.

Social integration and inflammation in individuals with and without posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with increased risk for morbidity and mortality, which may be mediated through elevated inflammation. In contrast, social support appears to protect against morbidity and mortality, reduce levels of inflammation, and improve PTSD outcomes. METHODS: We examined relationships among social isolation, perceived social support, and inflammation in Veterans Affairs (VA) patients with and without PTSD. Our sample included 735 (35% PTSD+) participants from the Mind Your Heart Study (mean age = 58 ± 11; 94% male). Social isolation was assessed with the Berkman Syme Social Network Index; perceived social support with the Multidimensional Scale of Perceived Social Support; and PTSD with the Clinician Administered PTSD Scale. Inflammation was indexed by high sensitivity C-reactive protein, white blood cell count, and fibrinogen. Hierarchical linear regression was used to examine associations between social measures and inflammation. PROCESS was used to examine the interactive effects of social relationships and PTSD on inflammation. RESULTS: Social isolation, but not low perceived social support, trended towards an association with elevated inflammation in the full sample. However, considering groups with and without PTSD separately, social isolation was significantly associated with all inflammatory markers among individuals without PTSD, but not among those with PTSD. CONCLUSIONS: Social integration is associated with reduced inflammation in individuals without, but not with, PTSD. Socially integrated individuals with PTSD did not have lower levels of inflammatory markers than socially isolated individuals with PTSD.

Adolescent dietary manipulations differentially affect gut microbiota composition and amygdala neuroimmune gene expression in male mice in adulthood.

Adolescence is a critical developmental period that is characterised by growth spurts and specific neurobiological, neuroimmune and behavioural changes. In tandem the gut microbiota, which is a key player in the regulation of health and disease, is shaped during this time period. Diet is one of the most important regulators of microbiota composition. Thus, we hypothesised that dietary disturbances of the microbiota during this critical time window result in long-lasting changes in immunity, brain and behaviour. C57BL/6 male mice were exposed to either high fat diet or cafeteria diet during the adolescent period from postnatal day 28 to 49 and were tested for anxiety-related and social behaviour in adulthood. Our results show long-lasting effects of dietary interventions during the adolescent period on microbiota composition and the expression of genes related to neuroinflammation or neurotransmission. Interestingly, changes in myelination-related gene expression in the prefrontal cortex following high fat diet exposure were also observed. However, these effects did not translate into overt behavioural changes in adulthood. Taken together, these data highlight the importance of diet-microbiota interactions during the adolescent period in shaping specific outputs of the microbiota-gut-brain axis in later life.

Effects of Oxytocin Administration on Cue-Induced Craving in Co-occurring Alcohol Use Disorder and PTSD: A Within-Participant Randomized Clinical Trial.

BACKGROUND: Individuals with alcohol use disorder (AUD) are much more likely to meet criteria for posttraumatic stress disorder (PTSD) than the general population. Compared to AUD alone, those with comorbid AUD-PTSD experience worse outcomes. Prior literature suggests that oxytocin, a hypothalamic neuropeptide, may be effective in the treatment of both AUD and PTSD when administered intranasally, although specific mechanisms remain elusive. METHODS: Forty-seven male patients with comorbid AUD-PTSD were administered intranasal oxytocin in a randomized, double-blind, dose-ranging (20 IU, 40 IU, and matched placebo), within-participant design with study visits at least 1 week apart. A cue-induced craving paradigm was conducted using each participant's preferred alcoholic beverage versus a neutral water cue. Self-reported alcohol craving and heart rate (HR) were recorded and analyzed using linear mixed-effect models. RESULTS: While alcohol cues significantly induced self-reported craving and increased HR compared to neutral water cues, neither dosage of oxytocin compared to placebo reduced self-reported cue-induced alcohol craving nor cue-induced changes in HR in patients with PTSD-AUD. CONCLUSIONS: These preliminary findings suggest that oxytocin does not affect cue-induced craving. Our results contribute to an ever-growing field of research investigating the effects of intranasal oxytocin on the symptoms of substance use disorders and will help further refine methodology and streamline future inquiries in this area.

Gender Differences in Threat Biases: Trauma Type Matters in Posttraumatic Stress Disorder.

Women are diagnosed with posttraumatic stress disorder (PTSD) at twice the rate of men. This gender difference may be related to differences in PTSD experiences (e.g., more hypervigilance in women) or types of trauma experienced (e.g., interpersonal trauma). We examined whether attentional threat biases were associated with gender, PTSD diagnosis, and/or trauma type. Participants were 70 civilians and veterans (38 women, 32 men; 41 with PTSD, 29 without PTSD) assessed with the Clinician Administered PTSD Scale for DSM-IV who completed a facial dot-probe attention bias task and self-report measures of psychiatric symptoms and trauma history. Factorial ANOVA and regression models examined associations between gender, PTSD diagnosis, index trauma type, lifetime traumatic experiences, and attentional threat biases. Results revealed that compared to women without PTSD and men both with and without PTSD, women with PTSD demonstrated attentional biases toward threatening facial expressions, d = 1.19, particularly fearful expressions, d = 0.74. Psychiatric symptoms or early/lifetime trauma did not account for these attentional biases. Biases were related to interpersonal assault index traumas, ηp 2 = .13, especially sexual assault, d = 1.19. Trauma type may be an important factor in the development of attentional threat biases, which theoretically interfere with trauma recovery. Women may be more likely to demonstrate attentional threat biases due to higher likelihood of interpersonal trauma victimization rather than due to gender-specific psychobiological pathways. Future research is necessary to clarify if sexual assault alone or in combination with gender puts individuals at higher risk of developing PTSD.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Diferencias de género en los sesgos de amenaza: el tipo de trauma es importante en TEPT INFLUENCIA DE GÉNERO Y TIPO DE TRAUMA EN SESGOS DE AMENAZA Las mujeres diagnosticadas con trastorno de estrés postraumático (TEPT) duplican la tasa de los hombres. Esta la diferencia de género puede estar relacionada con diferencias en las experiencias de TEPT (por ejemplo, más hipervigilancia en mujeres) o tipos de trauma experimentados (por ejemplo, trauma interpersonal). Examinamos si los sesgos atencionales de la amenaza se asociaron con el género, el diagnóstico de TEPT y/o el tipo de trauma. Los participantes fueron 70 civiles y veteranos (38 mujeres, 32 hombres; 41 con TEPT, 29 sin TEPT) evaluados con la Escala de TEPT Administrada por el Médico para DSM-IV que se completó con una tarea de sesgo atencional con puntos faciales y medidas autoinformadas de síntomas psiquiátricos e historia de trauma. Por medio de una ANOVA factorial y modelos de regresión se examinaron las asociaciones entre género, diagnóstico de TEPT, tipo de trauma índice, experiencias traumáticas a lo largo de la vida y sesgos atencionales de la amenaza. Los resultados revelaron que, en comparación con las mujeres sin TEPT y los hombres con y sin TEPT, las mujeres con TEPT mostraron sesgos atencionales hacia expresiones faciales amenazantes, d = 1.19, especialmente expresiones de miedo, d = 0.74. Los síntomas psiquiátricos o experiencias tempranas de trauma en la vida no explicaron estos sesgos atencionales. Los sesgos se relacionaron con el índice de traumas por asalto interpersonal, ηp 2 = .13, especialmente agresión sexual, d = 1.19. El tipo de trauma puede ser un factor importante en el desarrollo de sesgos atencionales de la amenaza, que teóricamente interfieren con la recuperación del trauma. Las mujeres pueden ser más propensas a demostrar sesgos atencionales de las amenazas debido a una mayor probabilidad de victimización por trauma interpersonal más que debido a vías psicobiológicas específicas del género. La investigación futura es necesaria para aclarar si la agresión sexual sola o en combinación con el género pone a las personas en mayor riesgo de desarrollar TEPT.

Association among anterior cingulate cortex volume, psychophysiological response, and PTSD diagnosis in a Veteran sample.

Posttraumatic stress disorder (PTSD) is associated with fear response system dysregulation. Research has shown that the anterior cingulate cortex (ACC) may modulate the fear response and that individuals with PTSD have abnormalities in ACC structure and functioning. Our objective was to assess whether ACC volume moderates the relationship between PTSD and fear-potentiated psychophysiological response in a sample of Gulf War Veterans. 142 Veteran participants who were associated with a larger study associated with Gulf War Illness were exposed to no threat, ambiguous threat, and high threat conditions in a fear conditioned startle response paradigm and also provided MRI imaging data. PTSD was assessed using the Clinician Administered PTSD Scale (CAPS). Decreased caudal ACC volume predicted greater psychophysiological responses with a slower habituation of psychophysiological magnitudes across trials (p < 0.001). PTSD diagnosis interacted significantly with both caudal and rostral ACC volumes on psychophysiological response magnitudes, where participants with PTSD and smaller rostral and caudal ACC volumes had greater psychophysiological magnitudes across trials (p < 0.05 and p < 0.001, respectively) and threat conditions (p < 0.05 and p < 0.005). Our results suggest that ACC volume may moderate both threat sensitivity and threat response via impaired habituation in individuals who have been exposed to traumatic events. More research is needed to assess whether ACC size and these associated response patterns are due to neurological processes resulting from trauma exposure or if they are indicative of a premorbid risk for PTSD subsequent to trauma exposure.

Effects of Threat Context, Trauma History, and Posttraumatic Stress Disorder Status on Physiological Startle Reactivity in Gulf War Veterans.

In the current study, we explored exaggerated physiological startle responses in posttraumatic stress disorder (PTSD) and examined startle reactivity as a biomarker of PTSD in a large veteran sample. We assessed heart rate (HR), skin conductance (SC), and electromyographic (EMG) startle responses to acoustic stimuli under low-, ambiguous-, and high-threat conditions in Gulf War veterans with current (n = 48), past (n = 42), and no history of PTSD (control group; n = 152). We evaluated PTSD status using the Clinician-Administered PTSD Scale and trauma exposure using the Trauma History Questionnaire. Participants with current PTSD had higher HR, ds = 0.28-0.53; SC, d = 0.37; and startle responses than those with past or no history of PTSD. The HR startle response under ambiguous threat best differentiated current PTSD; however, sensitivity and specificity analyses revealed it to be an imprecise indicator of PTSD status, ROC AUC = .66. Participants with high levels of trauma exposure only showed elevated HR and SC startle reactivity if they had current PTSD. Results indicate that startle is particularly elevated in PTSD when safety signals are available but a possibility of danger remains and when trauma exposure is high. However, startle reactivity alone is unlikely to be a sufficient biomarker of PTSD.

Current posttraumatic stress disorder and exaggerated threat sensitivity associated with elevated inflammation in the Mind Your Heart Study.

OBJECTIVE: Elevated inflammation has been repeatedly observed in posttraumatic stress disorder (PTSD), and it may drive the development of both psychiatric symptoms and physical comorbidities. However, it is not clear if elevated inflammation is a feature of both remitted and current PTSD, and little is known about relationships between specific clusters of PTSD symptoms and inflammation. Exaggerated threat sensitivity, as indexed by threat reactivity and avoidance of perceived threats, may be particularly closely associated with inflammation. METHODS: We assessed PTSD symptoms and threat sensitivity using the Clinician Administered PTSD Scale in 735 Veterans Affairs patients (35% current PTSD; 16% remitted PTSD) who participated in the Mind Your Heart Study (mean age=59±11; 94% male). High sensitivity C-reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen were used as indices of inflammation. Analysis of covariance models with planned contrasts were used to examine differences in inflammation by PTSD status, adjusting for age, sex, race, kidney function and socioeconomic status. RESULTS: Individuals with current PTSD had significantly higher hsCRP and WBC than patients with no history of PTSD, but there were no significant differences in inflammatory markers between those with remitted versus no history of PTSD. Within patients with current PTSD, higher threat reactivity was independently associated with higher hsCRP (ß=0.16, p=0.01) and WBC count (ß=0.24, <0.001), and higher effortful avoidance was associated with higher fibrinogen (ß=0.13, p=0.04). CONCLUSION: Our data indicate that elevated inflammation may be a feature of current, but not remitted, PTSD. Within patients with PTSD, higher threat reactivity was also associated with elevated inflammation. A better understanding of the relationship between threat sensitivity and inflammation may inform interventions for patients with PTSD.

Dementia Risk in Posttraumatic Stress Disorder: the Relevance of Sleep-Related Abnormalities in Brain Structure, Amyloid, and Inflammation.

PURPOSE OF REVIEW: Posttraumatic stress disorder (PTSD) is associated with increased risk for dementia, yet mechanisms are poorly understood. RECENT FINDINGS: Recent literature suggests several potential mechanisms by which sleep impairments might contribute to the increased risk of dementia observed in PTSD. First, molecular, animal, and imaging studies indicate that sleep problems lead to cellular damage in brain structures crucial to learning and memory. Second, recent studies have shown that lack of sleep might precipitate the accumulation of harmful amyloid proteins. Finally, sleep and PTSD are associated with elevated inflammation, which, in turn, is associated with dementia, possibly via cytokine-mediated neural toxicity and reduced neurogenesis. A better understanding of these mechanisms may yield novel treatment approaches to reduce neurodegeneration in PTSD. The authors emphasize the importance of including sleep data in studies of PTSD and cognition and identify next steps.

Associations of childhood adversity and adulthood trauma with C-reactive protein: A cross-sectional population-based study.

Mounting evidence highlights specific forms of psychological stress as risk factors for ill health. Particularly strong evidence indicates that childhood adversity and adulthood trauma exposure increase risk for physical and psychiatric disorders, and there is emerging evidence that inflammation may play a key role in these relationships. In a population-based sample from the Health and Retirement Study (n=11,198, mean age 69 ± 10), we examine whether childhood adversity, adulthood trauma, and the interaction between them are associated with elevated levels of the systemic inflammatory marker high sensitivity C-reactive protein (hsCRP). All models were adjusted for age, gender, race, education, and year of data collection, as well as other possible confounds in follow-up sensitivity analyses. In our sample, 67% of individuals had experienced at least one traumatic event during adulthood, and those with childhood adversity were almost three times as likely to have experienced trauma as an adult. Childhood adversities and adulthood traumas were independently associated with elevated levels of hsCRP (ß=0.03, p=0.01 and ß=0.05, p<0.001, respectively). Those who had experienced both types of stress had higher levels of hsCRP than those with adulthood trauma alone, Estimate=-0.06, 95% CI [-0.003, -0.12], p=0.04, but not compared to those with childhood adversity alone, Estimate=-0.06, 95% CI [0.03, -0.16], p=0.19. There was no interaction between childhood and adulthood trauma exposure. To our knowledge, this is the first study to examine adulthood trauma exposure and inflammation in a large population-based sample, and the first to explore the interaction of childhood adversity and adulthood trauma with inflammation. Our study demonstrates the prevalence of trauma-related inflammation in the general population and suggests that childhood adversity and adulthood trauma are independently associated with elevated inflammation.

Anger is associated with increased IL-6 stress reactivity in women, but only among those low in social support.

BACKGROUND: Social connections moderate the effects of high negative affect on health. Affective states (anger, fear, and anxiety) predict interleukin-6 (IL-6) reactivity to acute stress; in turn, this reactivity predicts risk of cardiovascular disease progression. PURPOSE: Here, we examined whether perceived social support mitigates the relationship between negative affect and IL-6 stress reactivity. METHOD: Forty-eight postmenopausal women completed a standardized mental lab stressor with four blood draws at baseline and 30, 50, and 90 min after the onset of the stressor and anger, anxiety, and fear were assessed 10 min after task completion. Participants self-rated levels of social support within a week prior to the stressor. RESULTS: Only anger was related to IL-6 stress reactivity-those experiencing high anger after the stressor had significant increases in IL-6. IL-6 reactivity was marginally associated with perceived support, but more strikingly, perceived support mitigated anger associations with IL-6 stress reactivity. CONCLUSION: Supportive ties can dampen the relationship of anger to pro-inflammatory reactivity to acute stress. Implications to cardiovascular disease are discussed.

Psychedelic-assisted psychotherapy: where is the psychotherapy research?

RATIONALE: Psychedelic-assisted psychotherapy (PAP) has emerged as a potential treatment for a variety of mental health conditions, including substance use disorders and depression. Current models of PAP emphasize the importance of psychotherapeutic support before, during, and after ingestion of a psychedelic to maximize safety and clinical benefit. Despite this ubiquitous assumption, there has been surprisingly little empirical investigation of the "psychotherapy" in PAP, leaving critical questions about the necessary and sufficient components of PAP unanswered. OBJECTIVES: As clinical trials for psychedelic compounds continue the transition from safety- and feasibility-testing to evaluating efficacy, the role of the accompanying psychotherapy must be better understood to enhance scientific understanding of the mechanisms underlying therapeutic change, optimize clinical outcomes, and inform cost-effectiveness. RESULTS: The present paper first reviews the current status of psychotherapy in the PAP literature, starting with recent debates regarding "psychotherapy" versus "psychological support" and then overviewing published clinical trial psychotherapy models and putative models informed by theory. We then delineate lessons that PAP researchers can leverage from traditional psychotherapy research regarding standardizing treatments (e.g., publish treatment manuals, establish eligibility criteria for providers), identifying mechanisms of change (e.g., measure established mechanisms in psychotherapy), and optimizing clinical trial designs (e.g., consider dismantling studies, comparative efficacy trials, and cross-lagged panel designs). Throughout this review, the need for increased research into the psychotherapeutic components of treatment in PAP is underscored. CONCLUSIONS: PAP is a distinct, integrative, and transdisciplinary intervention. Future research designs should consider transdisciplinary research methodologies to identify best practices and inform federal guidelines for PAP administration.

Content analysis of Reddit posts about coadministration of selective serotonin reuptake inhibitors and psilocybin mushrooms.

RATIONALE: Treatments with the serotonergic psychedelic psilocybin are being investigated for multiple neuropsychiatric disorders. Because many patients with these disorders use selective serotonin reuptake inhibitors (SSRIs), understanding interactions between psilocybin and SSRIs is critical for evaluating the safety, efficacy, and scalability of psilocybin-based treatments. Current knowledge about these interactions is limited, as most clinical psilocybin research has prohibited concomittant SSRI use. OBJECTIVES: We aimed to explore potential interactions between psilocybin and SSRIs by characterizing peoples' real-world experiences using psilocybin mushrooms and SSRIs together. METHODS: We conducted a systematic search of Reddit for posts describing psilocybin mushroom and SSRI coadministration. We identified 443 eligible posts and applied qualitative content analysis to each. RESULTS: 8% of posts reported negative physical or psychological effects resulting from coadministration. These included 13 reports that may reflect serotonin toxicity, and 1 concerning for a psychotic/manic episode. 54% of posts described reduced intensity of the acute psilocybin experience, but 39% reported unchanged intensity with SSRI coadministration. CONCLUSIONS: Psilocybin's interactions with SSRIs are likely complex and may depend on multiple factors. Prospective studies are needed to evaluate whether psilocybin treatments are reliably safe and effective in the setting of SSRI use.

Educational attainment and late life telomere length in the Health, Aging and Body Composition Study.

Morbidity and mortality are greater among socially disadvantaged racial/ethnic groups and those of lower socioeconomic status (SES). Greater chronic stress exposure in disadvantaged groups may contribute to this by accelerating cellular aging, indexed by shorter age-adjusted telomere length. While studies consistently relate shorter leukocyte telomere length (LTL) to stress, the few studies, mostly from the UK, examining associations of LTL with SES have been mixed. The current study examined associations between educational attainment and LTL among 2599 high-functioning black and white adults age 70-79 from the Health, Aging and Body Composition Study. Multiple regression analyses tested associations of race/ethnicity, educational attainment and income with LTL, adjusting for potential confounders. Those with only a high school education had significantly shorter mean LTL (4806 basepairs) than those with post-high school education (4926 basepairs; B=125, SE=47.6, p=.009). A significant interaction of race and education (B=207.8, SE=98.7, p=.035) revealed more beneficial effects of post-high school education for blacks than for whites. Smokers had shorter LTL than non-smokers, but the association of education and LTL remained significant when smoking was covaried (B=119.7, SE=47.6, p=.012). While higher income was associated with longer LTL, the effect was not significant (p>.10). This study provides the first demonstration of an association between educational attainment and LTL in a US population where higher education appears to have a protective effect against telomere shortening, particularly in blacks.