Search results
Found 12532 matches for
Trends in use of electroconvulsive therapy in South London from 1949 to 2006.
OBJECTIVES: Electroconvulsive therapy (ECT) remains the most acutely effective treatment for severe depression, but its use has declined since its introduction more than 70 years ago. To provide some historical perspective on changes in ECT practice, the objective of the present study was to identify trends in ECT practice in selected teaching hospitals in South London, UK, between 1949 and 2006. METHODS: Annual rates of ECT for 1949-1970 were estimated from the contemporary hospital reports of the Maudsley and Bethlem Royal hospitals in South London, UK. Case notes were also retrospectively reviewed to calculate annual rates of ECT administration and extract demographic and clinical information for approximately every 5 years between 1987 and 2006. RESULTS: The annual rate of ECT peaked at 35% of total admission in 1956 and declined gradually thereafter to 10.8% by 1970 and fell below 2.2% from 1991 onward. Depressed and female patients were more likely to receive ECT. Compared to previous years, patients were more severely ill and treatment resistant in 2006, whereas ethnic minorities made up 30% of patients receiving ECT compared to approximately 14% in the preceding years. CONCLUSIONS: Currently, ECT seems to be provided increasingly late in more severe illness episodes. The ethnicity of patients receiving ECT in South London may be becoming more representative of the background population, but ECT is being used relatively more frequently for nonaffective disorders in ethnic minorities.
Treating trauma-driven OCD with narrative exposure therapy alongside cognitive behavioural therapy
When post-Traumatic stress disorder (PTSD) co-occurs with obsessive compulsive disorder (OCD), symptoms of the former can interfere with evidence-based treatment of the latter. As a result, exposure-based treatments are recommended for both OCD and PTSD, potentially facilitating a concurrent treatment approach. This case study describes the application of concurrent cognitive behaviour therapy (CBT including exposure and response prevention; ERP) for OCD and narrative exposure therapy to treat a patient whose PTSD symptoms of intrusive images of memories and hyperarousal were interfering with standard CBT (including ERP) treatment for OCD. Following this concurrent approach, the patient's symptoms of OCD reduced to non-clinical levels and showed reliable improvement in PTSD symptoms. Whilst further methodologically robust research is required, this case study highlights that this approach may be beneficial to the treatment of OCD where PTSD symptoms are impacting on treatment. Key learning aims (1) To explore the literature considering explanations of the co-occurrence of OCD and PTSD symptomology. (2) To consider how symptoms of two mental health conditions can maintain one another and attenuate the effectiveness of evidence-based treatment for the other mental health condition. (3) Consider the use of concurrent therapeutic approaches to treat co-occurring mental health conditions.
Bitemporal Versus High-Dose Unilateral Twice-Weekly Electroconvulsive Therapy for Depression (EFFECT-Dep): A Pragmatic, Randomized, Non-Inferiority Trial.
OBJECTIVE: ECT is the most effective treatment for severe depression. Previous efficacy studies, using thrice-weekly brief-pulse ECT, reported that high-dose (6× seizure threshold) right unilateral ECT is similar to bitemporal ECT but may have fewer cognitive side effects. The authors aimed to assess the effectiveness and cognitive side effects of twice-weekly moderate-dose (1.5× seizure threshold) bitemporal ECT with high-dose unilateral ECT in real-world practice. METHOD: This was a pragmatic, patient- and rater-blinded, noninferiority trial of patients with major depression (N=138; 63% female; age=56.7 years [SD=14.8]) in a national ECT service with a 6-month follow-up. Participants were independently randomly assigned to bitemporal or high-dose unilateral ECT. The primary outcome was change in the 24-item Hamilton Depression Rating Scale (HAM-D) score after the ECT course; the prespecified noninferiority margin was 4.0 points. Secondary outcomes included response and remission rates, relapse status after 6 months, and cognition. RESULTS: Of the eligible patients, 69 were assigned to bitemporal ECT and 69 to unilateral ECT. High-dose unilateral ECT was noninferior to bitemporal ECT regarding the 24-item HAM-D scores after the ECT course (mean difference=1.08 points in favor of unilateral ECT [95% CI=-1.67 to 3.84]). There were no significant differences for response and remission or 6-month relapse status. Recovery of orientation was quicker following unilateral ECT (median=19.1 minutes versus 26.4 minutes). Bitemporal ECT was associated with a lower percent recall of autobiographical information (odds ratio=0.66) that persisted for 6 months. CONCLUSIONS: Twice-weekly high-dose unilateral ECT is not inferior to bitemporal ECT for depression and may be preferable because of its better cognitive side-effect profile.
Automated virtual reality (VR) cognitive therapy for patients with psychosis: study protocol for a single-blind parallel group randomised controlled trial (gameChange).
INTRODUCTION: Many patients with psychosis experience everyday social situations as anxiety-provoking. The fears can arise, for example, from paranoia, hallucinations, social anxiety or negative-self beliefs. The fears lead patients to withdraw from activities, and this isolation leads to a cycle of worsening physical and mental health. Breaking this cycle requires highly active treatment directly in the troubling situations so that patients learn that they can safely and confidently enter them. However patients with psychosis seldom receive such life-changing interventions. To solve this problem we have developed an automated psychological treatment delivered in virtual reality (VR). It allows patients to experience computer simulations of the situations that they find anxiety-provoking. A virtual coach guides patients, using cognitive techniques, in how to overcome their fears. Patients are willing to enter VR simulations of anxiety-provoking situations because they know the simulations are not real, but the learning made transfers to the real world. METHODS AND ANALYSIS: 432 patients with psychosis and anxious avoidance of social situations will be recruited from National Health Service (NHS) secondary care services. In the gameChange trial, they will be randomised (1:1) to the six-session VR cognitive treatment added to treatment as usual or treatment as usual alone. Assessments will be conducted at 0, 6 (post-treatment) and 26 weeks by a researcher blind to allocation. The primary outcome is avoidance and distress in real-life situations, using a behavioural assessment task, at 6 weeks. The secondary outcomes are psychiatric symptoms, activity levels and quality of life. All main analyses will be intention-to-treat. Moderation and mediation will be tested. An economic evaluation will be conducted. ETHICS AND DISSEMINATION: The trial has received ethical approval from the NHS South Central - Oxford B Research Ethics Committee (19/SC/0075). A key output will be a high-quality automated VR treatment for patients to overcome anxious avoidance of social situations. TRIAL REGISTRATION NUMBER: ISRCTN17308399.
Psychological framework to understand interpersonal violence by forensic patients with psychosis.
BACKGROUND: Forensic patients with psychosis often engage in violent behaviour. There has been significant progress in understanding risk factors for violence, but identification of causal mechanisms of violence is limited. AIMS: To develop a testable psychological framework explaining violence in psychosis - grounded in patient experience - to guide targeted treatment development. METHOD: We conducted in-depth interviews with 20 patients with psychosis using forensic psychiatric services across three regions in England. Interviews were analysed using reflexive thematic analysis. People with lived experience contributed to the analysis. RESULTS: Analysis of interviews identified several psychological processes involved in the occurrence of violence. Violence was the dominant response mode to difficulties that was both habitual and underpinned by rules that engaged and justified an attack. Violence was triggered by a trio of sensitivities to other people: sensitivity to physical threat, from which violence protected; sensitivity to social disrespect, by which violence increased status; and sensitivity to unfairness, by which violence delivered revenge. Violence was an attempt to regulate difficult internal states: intense emotions were released through aggression and violence was an attempt to escape being overwhelmed by voices, visions or paranoia. There were different patterns of emphasis across these processes when explaining an individual participant's offending behaviour. CONCLUSIONS: The seven-factor model of violence derived from our analysis of patient accounts highlights multiple modifiable psychological processes that can plausibly lead to violence. The model can guide the research and development of targeted treatments to reduce violence by individuals with psychosis.
Understanding agoraphobic avoidance: the development of the Oxford Cognitions and Defences Questionnaire (O-CDQ).
BACKGROUND: Many patients with mental health disorders become increasingly isolated at home due to anxiety about going outside. A cognitive perspective on this difficulty is that threat cognitions lead to the safety-seeking behavioural response of agoraphobic avoidance. AIMS: We sought to develop a brief questionnaire, suitable for research and clinical practice, to assess a wide range of cognitions likely to lead to agoraphobic avoidance. We also included two additional subscales assessing two types of safety-seeking defensive responses: anxious avoidance and within-situation safety behaviours. METHOD: 198 patients with psychosis and agoraphobic avoidance and 1947 non-clinical individuals completed the item pool and measures of agoraphobic avoidance, generalised anxiety, social anxiety, depression and paranoia. Factor analyses were used to derive the Oxford Cognitions and Defences Questionnaire (O-CDQ). RESULTS: The O-CDQ consists of three subscales: threat cognitions (14 items), anxious avoidance (11 items), and within-situation safety behaviours (8 items). Separate confirmatory factor analyses demonstrated a good model fit for all subscales. The cognitions subscale was significantly associated with agoraphobic avoidance (r = .672, p < .001), social anxiety (r = .617, p < .001), generalized anxiety (r = .746, p < .001), depression (r = .619, p < .001) and paranoia (r = .655, p < .001). Additionally, both the O-CDQ avoidance (r = .867, p < .001) and within-situation safety behaviours (r = .757, p < .001) subscales were highly correlated with agoraphobic avoidance. The O-CDQ demonstrated excellent internal consistency (cognitions Cronbach's alpha = .93, avoidance Cronbach's alpha = .94, within-situation Cronbach's alpha = .93) and test-re-test reliability (cognitions ICC = 0.88, avoidance ICC = 0.92, within-situation ICC = 0.89). CONCLUSIONS: The O-CDQ, consisting of three separate scales, has excellent psychometric properties and may prove a helpful tool for understanding agoraphobic avoidance across mental health disorders.
Digital Mental Health for Schizophrenia and Other Severe Mental Illnesses: An International Consensus on Current Challenges and Potential Solutions.
BACKGROUND: Digital approaches may be helpful in augmenting care to address unmet mental health needs, particularly for schizophrenia and severe mental illness (SMI). OBJECTIVE: An international multidisciplinary group was convened to reach a consensus on the challenges and potential solutions regarding collecting data, delivering treatment, and the ethical challenges in digital mental health approaches for schizophrenia and SMI. METHODS: The consensus development panel method was used, with an in-person meeting of 2 groups: the expert group and the panel. Membership was multidisciplinary including those with lived experience, with equal participation at all stages and coproduction of the consensus outputs and summary. Relevant literature was shared in advance of the meeting, and a systematic search of the recent literature on digital mental health interventions for schizophrenia and psychosis was completed to ensure that the panel was informed before the meeting with the expert group. RESULTS: Four broad areas of challenge and proposed solutions were identified: (1) user involvement for real coproduction; (2) new approaches to methodology in digital mental health, including agreed standards, data sharing, measuring harms, prevention strategies, and mechanistic research; (3) regulation and funding issues; and (4) implementation in real-world settings (including multidisciplinary collaboration, training, augmenting existing service provision, and social and population-focused approaches). Examples are provided with more detail on human-centered research design, lived experience perspectives, and biomedical ethics in digital mental health approaches for SMI. CONCLUSIONS: The group agreed by consensus on a number of recommendations: (1) a new and improved approach to digital mental health research (with agreed reporting standards, data sharing, and shared protocols), (2) equal emphasis on social and population research as well as biological and psychological approaches, (3) meaningful collaborations across varied disciplines that have previously not worked closely together, (4) increased focus on the business model and product with planning and new funding structures across the whole development pathway, (5) increased focus and reporting on ethical issues and potential harms, and (6) organizational changes to allow for true communication and coproduction with those with lived experience of SMI. This study approach, combining an international expert meeting with patient and public involvement and engagement throughout the process, consensus methodology, discussion, and publication, is a helpful way to identify directions for future research and clinical implementation in rapidly evolving areas and can be combined with measurements of real-world clinical impact over time. Similar initiatives will be helpful in other areas of digital mental health and similarly fast-evolving fields to focus research and organizational change and effect improved real-world clinical implementation.
Improving Attitudes Towards Personality Disorder: Is Training for Health and Social Care Professionals Effective?
Health and social care professionals are more likely to hold negative attitudes towards people with a diagnosis of personality disorder than toward people with other mental health diagnoses. Negative attitudes have also been found to adversely impact care and service provision. This review sought to systemically evaluate training aimed at improving professional attitudes towards people with a diagnosis of personality disorder. Electronic databases PsychINFO, PubMed, Embase, Web of Science, and ProQuest were searched, and 19 articles were identified. Results show that training is effective and that improvements tend to be maintained. The results suggest that (1) co-production with people with personal experience of a personality disorder diagnosis, (2) communicating a psychological model to participants, and (3) teaching participants clinical skills for use in their work improve effectiveness. Further research in the form of randomized controlled trials that use validated measures and follow-up participants for at least 6 months is needed.
Autism and the transition to university from the student perspective.
University provides individuals with the opportunity to develop greater independence in living skills and social networks, while also gaining valuable qualifications. Despite a high proportion of autistic individuals aspiring to attend university, many either do not seek or gain entry or drop out prematurely. Although some steps have been taken to develop effective support, a recent review highlighted the scarcity of research into programmes designed to support autistic students transitioning to university. In addition, few studies have examined the views of autistic students themselves. This study investigated the perspectives of autistic students transitioning to university. Three focus groups were conducted with 25 autistic students preparing to start university. Participants were asked about their hopes for starting university, as well as their worries and concerns. Data were analysed using thematic analysis, from which five main themes were identified: The Social World, Academic Demands, Practicalities of University Living, Leaving the Scaffolding of Home and Transition to Adulthood. The results provide an important account of the challenges autistic students face when transitioning to university, as well as their aspirations. These findings have a number of practical implications.
The Role of Narcissism in Aggression and Violence: A Systematic Review.
It has long been hypothesized that feelings of inferiority or low self-esteem lead individuals to aggress against those they view as being threatening. However, recent studies suggest that it is not just the level of self-esteem but stability that is relevant to understanding this process. As such, researchers have looked to related constructs, such as narcissism, in trying to understand aggressive behaviors. Narcissism is characterized by a dissociation between an unconscious sense of inadequacy and a conscious feeling of superiority. A large number of studies examining the relationship between narcissism and violence have recently been published within both clinical and student populations. This review aimed to systematically collate the findings of such studies and integrate them within current theories of violence. Electronic literature databases such as Web of Science, MEDLINE, PsychINFO, EMBASE, Cochrane databases, and LexisNexis (legal database) were searched to identify studies examining the relationship between narcissism and violence. Twenty articles were included in this review, describing 25 separate samples. Findings suggest that narcissism is relevant in understanding aggression and violence. This was consistent across both clinical and nonclinical populations and therefore does not appear to be an artifact of studying either very violent or student samples. Evidence from student samples strongly supported the association between narcissism and aggression following an ego threat, while studies using clinical samples did not examine the effect of an ego threat. These findings may have an impact on how we understand, predict, and reduce violence.
Neurocognitive Remediation Therapy for Depression: A Feasibility Study and Randomized Controlled Pilot Protocol Testing.
Major depression is the most prevalent psychiatric disorder with high relapse rates. When mood can improve or fully recover, the neurocognitive difficulties associated with depression often persist, preventing complete functional recovery. They have also been shown to predict relapse. The efficacy of neurocognitive remediation therapy (NCRT) to rehabilitate cognition has been demonstrated in several clinical populations but randomized controlled trials (RCTs) have not been conducted in depression. The present study aimed to test the feasibility and to conduct a pilot protocol testing for an RCT of computerized NCRT for inpatients with major depressive episode. The feasibility assessment demonstrated excellent acceptance of randomization and very satisfactory recruitment and compliance rates. The RCT procedures' assessment was overall consistent with a successful pilot study with the condition of protocol modification in terms of resources. Preliminary outcome data suggested specific NCRT efficacy to improve targeted neurocognitive processes in depression.
Misconceptions about Psychological Science: A review
This article provides an overview of the available evidence on psychological misconceptions, including key findings, current directions and emerging issues for investigation. We begin by defining misconceptions and then examine their prevalence and persistence, discuss their implications for student learning and highlight potential strategies to eliminate or reduce their influence. Thereafter, several theoretical and methodological issues that have traditionally defined research in this area are discussed. In particular, we highlight the possibility that reported rates of misconceptions may in part be driven by particular features of the measurement procedures employed. On the basis of this analysis, potential avenues for future research are outlined.
Automated virtual reality therapy to treat agoraphobic avoidance and distress in patients with psychosis (gameChange): a multicentre, parallel-group, single-blind, randomised, controlled trial in England with mediation and moderation analyses.
BACKGROUND: Automated delivery of psychological therapy using immersive technologies such as virtual reality (VR) might greatly increase the availability of effective help for patients. We aimed to evaluate the efficacy of an automated VR cognitive therapy (gameChange) to treat avoidance and distress in patients with psychosis, and to analyse how and in whom it might work. METHODS: We did a parallel-group, single-blind, randomised, controlled trial across nine National Health Service trusts in England. Eligible patients were aged 16 years or older, with a clinical diagnosis of a schizophrenia spectrum disorder or an affective diagnosis with psychotic symptoms, and had self-reported difficulties going outside due to anxiety. Patients were randomly assigned (1:1) to either gameChange VR therapy plus usual care or usual care alone, using a permuted blocks algorithm with randomly varying block size, stratified by study site and service type. gameChange VR therapy was provided in approximately six sessions over 6 weeks. Trial assessors were masked to group allocation. Outcomes were assessed at 0, 6 (primary endpoint), and 26 weeks after randomisation. The primary outcome was avoidance of, and distress in, everyday situations, assessed using the self-reported Oxford Agoraphobic Avoidance Scale (O-AS). Outcome analyses were done in the intention-to-treat population (ie, all participants who were assigned to a study group for whom data were available). We performed planned mediation and moderation analyses to test the effects of gameChange VR therapy when added to usual care. This trial is registered with the ISRCTN registry, 17308399. FINDINGS: Between July 25, 2019, and May 7, 2021 (with a pause in recruitment from March 16, 2020, to Sept 14, 2020, due to COVID-19 pandemic restrictions), 551 patients were assessed for eligibility and 346 were enrolled. 231 (67%) patients were men and 111 (32%) were women, 294 (85%) were White, and the mean age was 37·2 years (SD 12·5). 174 patients were randomly assigned to the gameChange VR therapy group and 172 to the usual care alone group. Compared with the usual care alone group, the gameChange VR therapy group had significant reductions in agoraphobic avoidance (O-AS adjusted mean difference -0·47, 95% CI -0·88 to -0·06; n=320; Cohen's d -0·18; p=0·026) and distress (-4·33, -7·78 to -0·87; n=322; -0·26; p=0·014) at 6 weeks. Reductions in threat cognitions and within-situation defence behaviours mediated treatment outcomes. The greater the severity of anxious fears and avoidance, the greater the treatment benefits. There was no significant difference in the occurrence of serious adverse events between the gameChange VR therapy group (12 events in nine patients) and the usual care alone group (eight events in seven patients; p=0·37). INTERPRETATION: Automated VR therapy led to significant reductions in anxious avoidance of, and distress in, everyday situations compared with usual care alone. The mediation analysis indicated that the VR therapy worked in accordance with the cognitive model by reducing anxious thoughts and associated protective behaviours. The moderation analysis indicated that the VR therapy particularly benefited patients with severe agoraphobic avoidance, such as not being able to leave the home unaccompanied. gameChange VR therapy has the potential to increase the provision of effective psychological therapy for psychosis, particularly for patients who find it difficult to leave their home, visit local amenities, or use public transport. FUNDING: National Institute of Health Research Invention for Innovation programme, National Institute of Health Research Oxford Health Biomedical Research Centre.
Cognitive Behaviour Therapy for Health Anxiety: A Systematic Review and Meta-Analysis.
BACKGROUND: Health anxiety (HA), or hypochondriasis, is a psychological problem characterized by a preoccupation with the belief that one is physically unwell. A 2007 Cochrane review (Thomson and Page, 2007) found cognitive behavioural therapy (CBT) to be an effective intervention for individuals with HA. Similar findings were reported in a recent meta-analysis (Olatunji et al., 2014), which did not employ a systematic search strategy. The current review aimed to investigate the efficacy of CBT for HA, and to update the existing reviews. METHOD: A systematic search was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance, including randomized controlled trials that compared CBT with a control condition for people with HA. Five hundred and sixty-seven studies were found in the original search, of which 14 were included in the meta-analysis. RESULTS: Meta-analysis was conducted on 21 comparisons and a large effect size for CBT compared with a control condition was found at post therapy d = 1.01 (95% confidence interval 0.77-1.25), as well as at 6- and 12-month follow-up. CONCLUSIONS: This systematic review and meta-analysis provides support for the hypothesis that CBT is an effective intervention for HA when compared with a variety of control conditions, e.g. treatment-as-usual, waiting list, medication, and other psychological therapies.
The Oxford Agoraphobic Avoidance Scale.
BACKGROUND: Agoraphobic avoidance of everyday situations is a common feature in many mental health disorders. Avoidance can be due to a variety of fears, including concerns about negative social evaluation, panicking, and harm from others. The result is inactivity and isolation. Behavioural avoidance tasks (BATs) provide an objective assessment of avoidance and in situ anxiety but are challenging to administer and lack standardisation. Our aim was to draw on the principles of BATs to develop a self-report measure of agoraphobia symptoms. METHOD: The scale was developed with 194 patients with agoraphobia in the context of psychosis, 427 individuals in the general population with high levels of agoraphobia, and 1094 individuals with low levels of agoraphobia. Factor analysis, item response theory, and receiver operating characteristic analyses were used. Validity was assessed against a BAT, actigraphy data, and an existing agoraphobia measure. Test-retest reliability was assessed with 264 participants. RESULTS: An eight-item questionnaire with avoidance and distress response scales was developed. The avoidance and distress scales each had an excellent model fit and reliably assessed agoraphobic symptoms across the severity spectrum. All items were highly discriminative (avoidance: a = 1.24-5.43; distress: a = 1.60-5.48), indicating that small increases in agoraphobic symptoms led to a high probability of item endorsement. The scale demonstrated good internal reliability, test-retest reliability, and validity. CONCLUSIONS: The Oxford Agoraphobic Avoidance Scale has excellent psychometric properties. Clinical cut-offs and score ranges are provided. This precise assessment tool may help focus attention on the clinically important problem of agoraphobic avoidance.
A randomized controlled experiment testing the use of virtual reality to trigger cigarette craving in people who smoke.
Automated delivery of therapy in virtual reality (VR) has the potential to be used for smoking cessation. Most obviously, it could be used to practise and establish alternative reactions to smoking cues. The first step in treatment development is to show that VR environments can trigger sufficient cravings in smokers. We evaluated a new VR public house outdoor scenario with 100 individuals who smoked daily. Participants were randomly assigned to the VR scenario with smoking cues or a neutral experience in VR. The VR experiences were presented in a standalone VR headset. Before and after VR, we collected self-reported craving scores for cigarettes and alcohol using the Tobacco Craving Questionnaire (TCQ) and visual analogue scales (VAS). Physiological data were also collected. Compared to the neutral condition, exposure to the smoking cues led to a large increase in craving for a cigarette (TCQ β = 11.44, p
Systematic review of risk factors for violence in psychosis: 10-year update.
BACKGROUND: Understanding risk factors for violence in people with psychosis can inform risk management and violence prevention. However, much of the evidence comes from cross-sectional studies, and previous reviews require updating. AIMS: To synthesise evidence from longitudinal studies on risk factors for violence in people with schizophrenia-spectrum disorders, bipolar disorder or other affective psychoses. METHOD: We searched five bibliographic databases up to June 2022. We identified longitudinal studies reporting risk factors for violence in individuals diagnosed with schizophrenia or other psychoses using DSM or ICD criteria. If ≥3 independent samples reported a risk factor, we conducted random-effects meta-analyses to provide a pooled estimate. We also meta-analysed risk factors by major domains. RESULTS: We identified 47 longitudinal studies on risk factors for violence in psychosis, representing 41 independent samples - 21 from the original and 20 from the updated review - and 203 297 individuals. A total of 30 risk factors were present in ≥3 independent samples. Criminal history factors were associated with the greatest risk of violent outcomes (pooled odds ratio 3.50, 95% CI = 2.37, 5.16), followed by substance misuse factors (odds ratio 2.36, 95% CI = 1.99, 2.80). Many treatment-related factors were protective (odds ratio 0.54, 95% CI = 0.34, 0.85). Effect estimates were attenuated in inpatient settings. We also identified novel risk factors, including cannabis use, in a secondary analysis (odds ratio 3.34, 95% CI = 2.32, 4.82). CONCLUSIONS: Using longitudinal evidence, we have validated comorbid substance misuse and criminal history as major risk factors for violence in psychosis. Novel factors such as cannabis use need further replication. Several identified factors are possible intervention targets if associations are found to be causal.