Within subject cross-tissue analyzes of epigenetic clocks in substance use disorder postmortem brain and blood

There is a possible accelerated biological aging in patients with substance use disorders (SUD). The evaluation of epigenetic clocks, which are accurate estimators of biological aging based on DNA methylation changes, has been limited to blood tissue in patients with SUD. Consequently, the impact of biological aging in the brain of individuals with SUD remains unknown. In this study, we evaluated multiple epigenetic clocks (DNAmAge, DNAmAgeHannum, DNAmAgeSkinBlood, DNAmPhenoAge, DNAmGrimAge, and DNAmTL) in individuals with SUD (n = 42), including alcohol (n = 10), opioid (n = 19), and stimulant use disorder (n = 13), and controls (n = 10) in postmortem brain (prefrontal cortex) and blood tissue obtained from the same individuals. We found a higher DNAmPhenoAge (β = 0.191, p-value = 0.0104) and a nominally lower DNAmTL (β = −0.149, p-value = 0.0603) in blood from individuals with SUD compared to controls. SUD subgroup analysis showed a nominally lower brain DNAmTL in subjects with alcohol use disorder, compared to stimulant use disorder and controls (β = 0.0150, p-value = 0.087). Cross-tissue analyzes indicated a lower blood DNAmTL and a higher blood DNAmAge compared to their respective brain values in the SUD group. This study highlights the relevance of tissue specificity in biological aging studies and suggests that peripheral measures of epigenetic clocks in SUD may depend on the specific type of drug used.     

Randomized Trial of the Parent And Caregiver Active Participation Toolkit for Child Mental Health Treatment

The purpose of this pilot study was to examine preliminary feasibility, acceptability, and effectiveness of a toolkit (Parent And Caregiver Active Participation Toolkit) to increase parent participation in community-based child mental health services. Study participants included 29 therapists (93% female; M age = 34.1 years; 38% Latino) and 20 parent/child dyads (children 80% female; M age = 8.6 years; parents 40% Latino) in 6 diverse community mental health clinics. Therapists were randomly assigned to standard care or the toolkit with standard care. Therapist and parent survey data and observational coding of treatment sessions were utilized. Mean comparisons and repeated measures analyses were used to test differences between study conditions over 4 months. Results supported preliminary feasibility and acceptability of the toolkit, with therapists assigned to the toolkit participating in ongoing training, adhering to toolkit use, and perceiving the toolkit as feasible and acceptable within their setting. Results preliminarily demonstrated improvement in therapists’ job attitudes, as well as actual use of parent engagement strategies. Results also preliminarily demonstrated increases in parent participation in child therapy sessions and more regular attendance, as well as some indication of support for perceived treatment effectiveness. Overall, results suggest the feasibility, acceptability, and potential effectiveness of the toolkit to enhance therapist job attitudes; practices that support parent engagement, parent engagement itself, and consumer perspectives on treatment outcomes; and the potential promise of future research in the area of parent participation interventions in child mental health services.     

How important are Phase 1 interventions for complex interpersonal trauma? A pilot randomized control trial of a group psychoeducational intervention

Although psychoeducational interventions are recommended as Phase 1 interventions for complex trauma, there is limited evidence on their efficacy. This pilot randomized control trial (RCT) investigated the efficacy of a pure psychoeducational intervention for complex trauma. A brief 10‐session intervention was delivered to n = 44 female prisoners in a compressed format to accommodate short sentence lengths and was compared with usual care (n = 42). Results from an intent‐to‐treat (ITT) analysis indicated that there were no statistically significant differences between the two arms across the three assessment time points (including 1‐month postintervention) for the main outcomes (Behavioural Assessment Checklist‐Revised, β = 4.60, 95% CI [?1.60, 10.88], p = .148; posttraumatic stress disorder [PTSD] Checklist, β = ?1.47, 95% CI [?4.30, 1.36], p = .303). Post hoc reliable change analyses suggested twice the number of adequate dose participants made progress in addressing PTSD symptoms compared with usual care (30.3% vs. 17.6%, OR 2.03, 95% CI [.64, 6.43]). Although further work in this area is required, initial results, overall, suggest that psychoeducational group‐based treatment modalities achieve only small effect sizes in comparison with usual care.     

The assessment of cognitive‐behavioral therapy skills in patients diagnosed with health anxiety: Development and pilot study on an observer‐based rating scale

Cognitive‐behavioral therapy is a highly effective treatment of health anxiety, but it remains unclear through which mechanisms treatment effects prevail. Some evidence suggests that patients acquire skills—understood as techniques helping them reach therapy goals—through psychotherapy. In the current study, an observer‐based rating scale for the skills assessment of patients with health anxiety (SAPH) was developed and validated in a pilot study. Based on 177 videotapes, four independent raters evaluated the frequency of skills acquired during cognitive and exposure therapy among 66 patients diagnosed with health anxiety with the SAPH. Predictive validity was evaluated by the Yale–Brown Obsessive‐Compulsive Scale for Hypochondriasis. The SAPH demonstrated good interrater reliability (ICC_(1,2) = .88, p < .001, 95% CI [.81, .92]) and internal consistency (α = .94). Although patient skills did not significantly increase during three sessions, they significantly predicted a reduction in health anxiety symptoms at the end of treatment (R² = .35). Patients' skills are highly important within the treatment of health anxiety. By providing external ratings of patients' skills with good psychometric properties, our pilot data suggest that the SAPH may complement current tools for the assessment of skills, specifically in targeting health anxiety.     

Helping Vulnerable Populations: A Comprehensive Review of the Treatment Outcome Literature on Substance Use Disorder and PTSD

We review treatment studies for comorbid substance use disorder (SUD) and posttraumatic stress disorder (PTSD). Results show positive outcomes on multiple domains. Most models had more effect on PTSD than SUD, suggesting SUD is harder to treat. Seeking Safety (SS) is the most studied model. It shows positive outcomes, and is the only treatment outperforming a control on both PTSD and SUD. Partial‐dose SS had more mixed results than the full dose. This first‐generation of PTSD/SUD research addresses complex samples excluded from “gold standard” PTSD‐alone literature. Treatments for PTSD/SUD are generally longer than PTSD‐alone treatments and present‐focused, emphasizing stabilization and coping. The few models with past‐focused (exposure‐based) components also incorporated present‐focused approaches for these vulnerable clients. We discuss public health perspectives to advance the field.     

Examining Insomnia and PTSD Over Time in Veterans in Residential Treatment for Substance Use Disorders and PTSD

Objective/Background: Insomnia occurs in 66–90% of individuals with posttraumatic stress disorder (PTSD) and 36–72% of individuals with substance use disorder (SUD). Individuals with both PTSD and SUD are more likely to have insomnia than individuals with only one disorder. Insomnia is associated with poorer treatment outcomes for both PTSD and SUD, increased daytime symptomology for PTSD, and increased relapse for SUDs. As such, it is important to understand how sleep affects PTSD treatment among patients dually diagnosed with SUD and how sleep changes over time in a residential unit for SUDs. Participants: Participants were 40 veterans with comorbid PTSD and SUD in a 28-day Substance Abuse Residential Rehabilitation Treatment Program (SARRTP) PTSD track. Methods: Analyses used mixed models with Time (baseline, posttreatment, 3-month follow-up) to examine PTSD and insomnia severity over time. Results: Results of the longitudinal mixed model showed that PTSD symptoms improved over time but that insomnia symptoms did not. Although baseline insomnia did not affect follow-up PTSD symptoms, individuals with greater insomnia severity at the start of treatment had more severe baseline PTSD symptomatology. However, there was not an interaction of insomnia and PTSD severity over time such that baseline insomnia did not affect PTSD trajectories. Conclusions: These findings are consistent with the PTSD outpatient treatment findings and further adds evidence that insomnia is unremitting without direct intervention. Given the relationship insomnia has with PTSD severity, SUD, and relapse, directly targeting insomnia may further help improve both PTSD and SUD treatment outcomes.     

Breaking the Mold or Business as Usual? Meeting the Challenges of HIV Prevention in People With Serious Mental Illness and Substance Use Disorders

Meade and Weiss (2007 ) present a timely review of HIV sexual risk behavior in serious mental illness (SMI) and substance use disorders (SUD), and identify a critical paucity of relevant HIV prevention research. They suggest pathways by which SMI/SUD may combine to create risks for HIV. This commentary suggests that the complexities of this patient population may be better suited to hybrid models ( Carroll & Rounsaville, 2003 ) combining the priorities of efficacy and effectiveness. We consider some recent modifications to cognitive-behavioral therapy (CBT) interventions that may provide useful tools to support HIV prevention. The challenges presented by HIV infection in this group are also considered in relation to our current work adapting traditional CBT to treat mental health and substance use issues in the context of HIV infection and/or prevention.     

A cancer genetics toolkit improves access to genetic services through documentation and use of the family history by primary-care clinicians

PurposeWe developed, implemented, and evaluated a multicomponent cancer genetics toolkit designed to improve recognition and appropriate referral of individuals at risk for hereditary cancer syndromes.MethodsWe evaluated toolkit implementation in the women’s clinics at a large Veterans Administration medical center using mixed methods, including pre–post semistructured interviews, clinician surveys, and chart reviews, and during implementation, monthly tracking of genetic consultation requests and use of a reminder in the electronic health record. We randomly sampled 10% of progress notes 6 months before (n = 139) and 18 months during implementation (n = 677).ResultsThe toolkit increased cancer family history documentation by almost 10% (26.6% pre- and 36.3% postimplementation). The reminder was a key component of the toolkit; when used, it was associated with a twofold increase in cancer family history documentation (odds ratio = 2.09; 95% confidence interval: 1.39–3.15), and the history was more complete. Patients whose clinicians completed the reminder were twice as likely to be referred for genetic consultation (4.1–9.6%, P < 0.0001).ConclusionA multicomponent approach to the systematic collection and use of family history by primary-care clinicians increased access to genetic services.Genet Med16 1, 60–69.     

Beginning with high value care in mind: A scoping review and toolkit to support the content,delivery, measurement,and sustainment of high value care

Objective

To create a shared vision for the content, delivery, measurement, and sustainment of patient-centered high value care.

Epilepsy‐related sudden unexpected death: targeted molecular analysis of inherited heart disease genes using next‐generation DNA sequencing

Inherited heart disease causing electric instability in the heart has been suggested to be a risk factor for sudden unexpected death in epilepsy (SUDEP). The purpose of this study was to reveal the correlation between epilepsy‐related sudden unexpected death (SUD) and inherited heart disease. Twelve epilepsy‐related SUD cases (seven males and five females, aged 11–78 years) were examined. Nine cases fulfilled the criteria of SUDEP, and three cases died by drowning. In addition to examining three major epilepsy‐related genes, we used next‐generation sequencing (NGS) to examine 73 inherited heart disease‐related genes. We detected both known pathogenic variants and rare variants with minor allele frequencies of <0.5%. The pathogenicity of these variants was evaluated and graded by eight in silico predictive algorithms. Six known and six potential rare variants were detected. Among these, three known variants of LDB3, DSC2 and KCNE1 and three potential rare variants of MYH6, DSP and DSG2 were predicted by in silico analysis as possibly highly pathogenic in three of the nine SUDEP cases. Two of three cases with desmosome‐related variants showed mild but possible significant right ventricular dysplasia‐like pathology. A case with LDB3 and MYH6 variants showed hypertrabeculation of the left ventricle and severe fibrosis of the cardiac conduction system. In the three drowning death cases, one case with mild prolonged QT interval had two variants in ANK2. This study shows that inherited heart disease may be a significant risk factor for SUD in some epilepsy cases, even if pathological findings of the heart had not progressed to an advanced stage of the disease. A combination of detailed pathological examination of the heart and gene analysis using NGS may be useful for evaluating arrhythmogenic potential of epilepsy‐related SUD.     

Parental reflective functioning and executive functioning in mothers with substance use disorder

Having a substance use disorder (SUD) may adversely affect caregiving capacities. Reflective functioning (RF) and executive functioning (EF) are both important capacities for sensitive parenting, and are often impaired in a SUD. Only a few studies have explored the possible association between the two phenomena. In this study, we used a neuropsychological test battery to assess EF, and the Parent Development Interview to assess RF in a sample of mothers with a SUD (N = 43). Although parental RF (PRF) was associated with EF, when controlled for intelligence (IQ) and mental health, there was no significant association between EF and PRF. Mental health, however, showed a significant negative association with PRF. Splitting the group in two based on PRF level, mothers with a negative to low PRF exhibited more severe difficulties in SUD-related aspects, as well as in several EF components, compared to mothers with an adequate to high PRF, highlighting the association between EF and PRF. The results from this study contribute to enhance our understanding of the dynamics underlying vulnerability in PRF that mothers with small children may experience. We suggest EF to be a prerequisite for adequate PRF, and for interventions to be customized accordingly regarding parents with a SUD.     

Systemic Trauma

Substantial theoretical, empirical, and clinical work examines trauma as it relates to individual victims and perpetrators. As trauma professionals, it is necessary to acknowledge facets of institutions, cultures, and communities that contribute to trauma and subsequent outcomes. Systemic trauma—contextual features of environments and institutions that give rise to trauma, maintain it, and impact posttraumatic responses—provides a framework for considering the full range of traumatic phenomena. The current issue of the Journal of Trauma & Dissociation is composed of articles that incorporate systemic approaches to trauma. This perspective extends conceptualizations of trauma to consider the influence of environments such as schools and universities, churches and other religious institutions, the military, workplace settings, hospitals, jails, and prisons; agencies and systems such as police, foster care, immigration, federal assistance, disaster management, and the media; conflicts involving war, torture, terrorism, and refugees; dynamics of racism, sexism, discrimination, bullying, and homophobia; and issues pertaining to conceptualizations, measurement, methodology, teaching, and intervention. Although it may be challenging to expand psychological and psychiatric paradigms of trauma, a systemic trauma perspective is necessary on both scientific and ethical grounds. Furthermore, a systemic trauma perspective reflects current approaches in the fields of global health, nursing, social work, and human rights. Empirical investigations and intervention science informed by this paradigm have the potential to advance scientific inquiry, lower the incidence of a broader range of traumatic experiences, and help to alleviate personal and societal suffering.     

A case–control genome wide association study of substance use disorder (SUD) identifies novel variants on chromosome 7p14.1 in patients from the United Arab Emirates (UAE)

Genome wide association studies (GWASs) have provided insights into the molecular basis of the disorder in different population. This study presents the first GWAS of substance use disorder (SUD) in patients from the United Arab Emirates (UAE). The aim was to identify genetic association(s) that may provide insights into the molecular basis of the disorder. The GWAS discovery cohort consisted of 512 (250 cases and 262 controls) male participants from the UAE. Controls with no prior history of SUD were available from the Emirates family registry. The replication cohort consisted of 520 (415 cases and 105 controls) Australian male Caucasian participants. The GWAS discovery samples were genotyped for 4.6 million single nucleotide polymorphism (SNP). The replication cohort was genotyped using TaqMan assay. The GWAS association analysis identified three potential SNPs rs118129027 (p‐value = 6.24 × 10^?8), rs74477937 (p‐value = 8.56 × 10^?8) and rs78707086 (p‐value = 8.55 × 10^?8) on ch7p14.1, that did not meet the GWAS significance threshold but were highly suggestive. In the replication cohort, the association of the three top SNPs did not reach statistical significance. In a meta‐analysis of the discovery and the replication cohorts, there were no strengthen evidence for association of the three SNPs. The top identified rs118129027 overlaps with a regulatory factor (enhancer) region that targets three neighboring genes LOC105375237, LOC105375240, and YAE1D1. The YAE1D1, which represents a potential locus that is involved in regulating translation initiation pathway. Novel associations that require further confirmation were identified, suggesting a new insight to the genetic basis of SUD.     

Developing a toolkit for patients with COPD or chronic heart failure and their informal caregivers to improve person-centredness in conversations with healthcare professionals: A Design Thinking approach

BackgroundThe perspective of patients and informal caregivers is often not expressed in conversations with healthcare professionals which can have a negative impact on quality of care and quality of life.ObjectiveDescribe the development of a toolkit for patients with COPD or chronic heart failure and their informal caregivers enabling them to explore and express their perspective in conversations with healthcare professionals.Patient involvement: Patients, informal caregivers and healthcare professionals were involved in the design process from problem definition to solution development.MethodDesign Thinking Approach using eight co-creation sessions and qualitative data-collection methods. Nineteen patients, ten informal caregivers and thirteen healthcare professionals participated in one or more co-creation sessions. Homogenous subgroups of participants were used in session 1, 2 and 4 and mixed groups were used in session 3, 5 and 6. Session 7 and 8 were used to test prototype toolkits.ResultsThree challenges to expressing the personal perspective to healthcare professionals, four statements defining the desired situation for conversations, eleven design criteria for the toolkit and ten selection criteria for tools were identified. This information was used to develop a prototype toolkit.DiscussionMost patients and informal caregivers had moderate to high levels of education and all participating healthcare professionals were female with a majority of nurses and only three physicians. It is possible that this has influenced the design of the toolkit.Practical valueThe toolkit can support patients and informal caregivers in exploring and expressing their perspective in conversations with healthcare professionals. Feasibility of the toolkit and implications for healthcare professionals will be examined in a pilot implementation study.     

Just Think About It: How Can Cognitive Therapy Contribute to the Treatment of Posttraumatic Stress Disorder?

[Clin Psychol Sci Prac 17: 128–133, 2010] As documented by the review by Hassija and Gray (2010 ), reports of the death of cognitive therapy (CT) for posttraumatic stress disorder (PTSD) are greatly exaggerated. CT has shown evidence of efficacy with adult PTSD comparable with that of prolonged exposure therapy (PE). The cognitive restructuring interventions provided by CT also are an integral component of evidence‐based PTSD psychotherapies, such as PE for adults and trauma‐focused cognitive‐behavior therapy for children and adolescents. Moreover, CT offers a “present‐centered” alternative to PTSD psychotherapy that can include, but does not require, trauma memory narrative disclosure. Inclusion of systematic approaches to not only changing thoughts but also enhancing thinking—i.e., self‐regulatory information processing—represents an important next step in the development of models of CT for PTSD.     

The Nature of Trauma Pain and Its Association with Catastrophizing and Sleep

Background

Nearly 2.8 million people are hospitalized in the USA annually for traumatic injuries, which include orthopedic and internal organ injuries. Early post-injury pain is predictive of poor outcomes, including inability to eventually return to work, and long-term psychological distress. The goal of the present study was to improve our scientific understanding of trauma-related pain by examining (1) the nature and frequency of inpatient trauma pain and (2) the associations between inpatient trauma pain, education, opioid analgesic equivalent use, pain catastrophizing, and sleep quality.

Method

The study included 120 patients hospitalized at a major level I regional trauma center for the care of (1) closed long bone or calcaneus fractures and/or (2) an intraabdominal injury caused by blunt force trauma and requiring surgical repair (i.e., laparotomy). Medical records were reviewed to obtain demographic information and information about opioid use during hospitalization. In addition, participants were administered measures of average pain intensity, pain catastrophizing, and sleep quality.

Results

Education, opioid analgesic equivalents, catastrophizing, and poor sleep quality together accounted for 28% of the variance of average pain intensity over a 24-h period (p?<?.001), with each variable making a significant independent association.

Conclusion

Two of the factors associated with pain intensity in the study sample—catastrophizing and sleep quality—are modifiable. It is therefore possible that interventions that target these variables in patients who are hospitalized for trauma could potentially result in better long-term outcomes, including a reduced risk for developing chronic pain. Research to evaluate this possibility is warranted.

     

Genetic variation in key genes associated with statin therapy in the Azores Islands (Portugal) healthy population

Background: Inter-individual variation in response to statins (efficacy and toxicity) has been described and may be due to polymorphisms implicated in drug pharmacokinetics or pharmacodynamics.

Aim: This study investigates clinically relevant pharmacogenes underlying statin response in 170 healthy Azoreans.

Methods: Eight SNPs in candidate genes—HMGCR (rs3846662, rs17238540, rs17244841), CETP (rs708272), APOE (rs7412, rs429358) and SLCO1B1 (rs2306283, rs4149056)—were genotyped.

Results: The allele frequencies were similar to those reported for European derived populations, excepting SLCO1B1 c.388A>G (rs2306283), which has a significant difference when compared with the HapMap CEU population (p?=?1?×?10^?8). The results of statin efficacy showed that 9.1% of Azoreans are APOE4 carriers. This allele has been associated with lower LDLc reduction from statin therapy and also higher LDLc levels at baseline. Regarding SLCO1B1, associated with statin toxicity, 1.8% of individuals have two reduced-function alleles (c.521CC).

Conclusion: The results contribute to overcome the lack of knowledge regarding the frequency of pharmacogenetic SNPs and their corresponding haplotypes in targeted populations, such as Azores islands. Moreover, the present work constitutes an initial step to implementing pharmacogenomics in clinical practice where physicians could use a patient’s genetic make-up to optimize statin therapy, regarding efficiency and myopathy risk.     

Post-traumatic stress disorder: A theory of perception

This paper applies the concept of being-in-the-world, in particular the notion that we are in the world through our body, to the study of trauma. Since (i) trauma is experienced and remembered bodily, and since (ii) we are in the world through our bodies, for the post-traumatic survivor the body itself can become a source of pain and unstructured-bodily somatic memory. Thus, in radical cases, the post-traumatic survivor may feel threatened by her own body. This can result in a complex and chronic dissociative subtype of post-traumatic stress disorder (PTSD) that, in turn, may be accompanied by a sense of disownership toward the body. This sense of disownership has yet to receive appropriate attention. This paper will argue that phenomenological work is needed in order to improve our understanding of this phenomenon and, by so doing, improve treatment for those suffering from complex PTSD.     

A novel virtual reality-based theory of mind intervention for outpatients with schizophrenia: A proof-of-concept pilot study

Schizophrenia is a severe and highly disabling mental illness. Although several pharmacological solutions are available to alleviate symptoms of schizophrenia, they do not seem to provide solution for accompanying social dysfunctions. To handle this unmet clinical need, many innovative interventions have been developed recently. Considering the promising results on this field and the development trend, characterized by the growing proportion of included interactive technology, our research team developed a novel virtual reality (VR)-based targeted theory of mind (ToM) intervention (VR-ToMIS) for stable outpatients with schizophrenia. VR-ToMIS is a nine-session long structured and individualized method that uses cognitive and behavioural therapeutic techniques in an immersive VR environment. Our study was a randomized, controlled pilot study. Twenty-one patients have been recruited and randomly allocated to either VR-ToMIS or passive VR condition. Patients assigned to passive VR condition could use the same VR software as the VR-ToMIS group, but without any interventions. Effects on psychiatric symptoms, neurocognitive and social cognitive functions, pragmatic language skills and quality of life were evaluated by using analysis of covariance. According to our results, VR-ToMIS was associated with improvements in negative symptoms, in one neurocognitive field (immediate memory), ToM and pragmatic language skills, but no significant change in quality of life scores was detected. Significant changes in VR-ToMIS group were associated with moderate to large therapeutic effects (η_p² = .24–.46, φ = .55–.67). On the background of the presented pilot results, VR-ToMIS is concluded to be feasible and tolerable.     

Understanding the burden of trauma and victimization among American Indian and Alaska native elders: historical trauma as an element of poly-victimization

ABSTRACT

Research on recognition of adverse childhood experiences (ACEs) and poly-victimization has transformed our understanding of violence and trauma exposure. Both concepts point to the importance of understanding the cumulative burden of trauma and the interconnections among forms of violence and abuse. However, there has been little conceptualization about what these two constructs mean for American Indian and Alaska Native (AI/AN) individuals, families, and communities, and even less attention to the experiences of AI/AN elders. This paper summarizes prior work on adverse childhood experiences and poly-victimization, addresses the limitations of past research on these issues, and expands these constructs to include concepts of historical trauma in order to better understand victimization and trauma among AI/AN elders. We call for the integration of historical trauma into the poly-victimization framework for AI/AN communities in order to more accurately capture the true burden of victimization among AI/AN peoples. Future research, prevention, and intervention can better incorporate historical trauma and we provide suggestions for doing so, including adding items on historical trauma to poly-victimization surveys and creating programs to promote cultural connectedness.