Medicine, Faculty of
Population and Public Health (SPPH), School of
DSpace
UBCV
Prangnell, Amy
Master of Science - MSc
University of British Columbia
Background: Childhood emotional abuse is an under-researched but significant public health problem. Impacts may include a higher risk for initiating injection drug use, as indicated by emerging evidence. Yet in Canada, there is a lack of research among people who inject drugs (PWID) regarding the impact of childhood emotional abuse on chronic pain and related outcomes. As such, this thesis will examine the relationships between childhood emotional abuse, injection drug use, and adult chronic pain. Methods: A systematic literature search was undertaken to identify previous studies that investigated relationships between childhood abuse (sexual, physical, or emotional) and adult injection drug use. Drawing on longitudinal cohort data from the Vancouver Injection Drug User Study (VIDUS) and the AIDS Care Cohort to Evaluate Exposure to Survival Services (ACCESS) between June 2014 and November 2016, I employed generalized estimating equations (GEE) to examine potential associations between childhood emotional abuse and adult chronic pain among PWID (Study Two), and between childhood emotional abuse and adult pain interference among PWID with chronic pain (Study Three). Results: Among the 17 articles included in the systematic review, there was strong evidence for physical abuse increasing the risk of adult injection drug use, with mixed results for sexual and emotional abuse. Study Two included 1459 PWID. In a multivariable GEE analysis, experiencing childhood emotional abuse was significantly and positively associated with experiencing chronic pain after adjusting for other types of childhood abuse and relevant socio-demographic, drug-use, and health related confounders. Study Three followed 822 PWID with chronic pain. In a multivariable GEE analysis, childhood emotional abuse remained significantly and positively associated with pain interference after adjusting for relevant socio-demographic, drug-use, and health related confounders. In addition, a history of mental illness diagnosis partially mediated this association. Conclusions: Findings of this thesis emphasize the detrimental and long-term impact of childhood abuse. It is imperative to utilize a variety of universal and targeted approaches in order to prevent childhood abuse. The results also further strengthen the rationale for expanding trauma-informed care approaches for chronic pain management, combined with strategies to prevent or ameliorate mental illness.
Childhood emotional abuse: relationships with injection drug use and chronic pain by Amy Prangnell B.Sc., The University of British Columbia, 2009 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Population and Public Health) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) June 2019 © Amy Prangnell, 2019 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, a thesis/dissertation entitled: Childhood emotional abuse: relationships with injection drug use and chronic pain Submitted by Amy Prangnell in partial fulfillment of the requirements for the degree of Master of Science ________________________ in Population and Public Health ____________________________________ Examining Committee: Kanna Hayashi, PhD Co-supervisor Jeannie Shoveller, PhD Co-supervisor Thomas Kerr, PhD Supervisory Committee Member Martin Guhn, PhD Additional Examiner iii ABSTRACT Background: Childhood emotional abuse is an under-researched but significant public health problem. Impacts may include a higher risk for initiating injection drug use, as indicated by emerging evidence. Yet in Canada, there is a lack of research among people who inject drugs (PWID) regarding the impact of childhood emotional abuse on chronic pain and related outcomes. As such, this thesis will examine the relationships between childhood emotional abuse, injection drug use, and adult chronic pain. Methods: A systematic literature search was undertaken to identify previous studies that investigated relationships between childhood abuse (sexual, physical, or emotional) and adult injection drug use. Drawing on longitudinal cohort data from the Vancouver Injection Drug User Study (VIDUS) and the AIDS Care Cohort to Evaluate Exposure to Survival Services (ACCESS) between June 2014 and November 2016, I employed generalized estimating equations (GEE) to examine potential associations between childhood emotional abuse and adult chronic pain among PWID (Study Two), and between childhood emotional abuse and adult pain interference among PWID with chronic pain (Study Three). Results: Among the 17 articles included in the systematic review, there was strong evidence for physical abuse increasing the risk of adult injection drug use, with mixed results for sexual and emotional abuse. Study Two included 1459 PWID. In a multivariable GEE analysis, experiencing childhood emotional abuse was significantly and positively associated with experiencing chronic pain after adjusting for other types of childhood abuse and relevant socio-demographic, drug-use, and health related confounders. Study Three followed 822 PWID with chronic pain. In a multivariable GEE analysis, childhood emotional abuse remained iv significantly and positively associated with pain interference after adjusting for relevant socio-demographic, drug-use, and health related confounders. In addition, a history of mental illness diagnosis partially mediated this association. Conclusions: Findings of this thesis emphasize the detrimental and long-term impact of childhood abuse. It is imperative to utilize a variety of universal and targeted approaches in order to prevent childhood abuse. The results also further strengthen the rationale for expanding trauma-informed care approaches for chronic pain management, combined with strategies to prevent or ameliorate mental illness. v LAY SUMMARY Experiencing childhood emotional abuse is known to contribute to a variety of adult health conditions and behaviours through many complex pathways. Injecting illicit drugs is one way in which individuals may cope with the impact of childhood emotional abuse. Additionally, chronic pain is common among people who inject drugs, and increases the risk of drug-related harm. However, research into the impact of childhood emotional abuse on chronic pain is lacking among this population despite that previous research suggested an association between the two in the general population. The aim of this research is to explore the complex relationships between childhood emotional abuse, injection drug use, and chronic pain. By identifying the lasting impacts of childhood emotional abuse among people who inject drugs, findings from this research can inform trauma-informed care approaches for chronic pain management among this population. vi PREFACE Work for this thesis was conducted using data from ongoing studies (VIDUS and ACCESS) supported by the US National Institutes of Health (U01DA038886, U01DA021525) and the Canadian Institutes of Health Research (CIHR) Canadian Research Initiative on Substance Misuse (SMN–139148), and a systematic review. All data pertaining to the quantitative analysis of Chapters Three and Four were collected, cleaned, and coded previously by staff at the British Columbia Centre on Substance Use (BCCSU). These studies have been approved by the University of British Columbia/Providence Health Care Ethics Board (VIDUS: H14 - 01396; ACCESS: H05 - 50233). In addition, ethics approval was also obtained for this thesis specifically. With the guidance and assistance of my supervising committee (Dr. Kanna Hayashi, Dr. Jean Shoveller, and Dr. Thomas Kerr), I conceptualized the systematic review chapter (Chapter Two) and the empirical research chapters (Chapters Three and Four). For Chapters Three and Four, I worked closely with statisticians from the BCCSU to develop a data analysis plan, which was carried out by them using R software. I created all tables and figures using Microsoft Word or Microsoft Excel. A version of Chapter Two has been submitted for publication in a peer-reviewed journal: Prangnell A, Imtiaz S, Karamouzian M, & Hayashi K. Childhood abuse as a risk factor for injection drug use: A systematic review of observational studies (Under Review). Co-author Sameer Imtiaz (a postdoctoral fellow at BCCSU) contributed to this work by independently screening full-text articles, and confirming the accuracy of final article data and quality scores. Co-author Mohammad Karamouzian (a PhD candidate at UBC) contributed to this work by providing input on the search strategy, criteria, and data analysis. vii Versions of Chapter Three and Four have also been submitted for publication in peer-reviewed journals: Prangnell A, Voon P, Shulha H, Shoveller J, Milloy MJ, Kerr T, & Hayashi K. The impact of childhood emotional abuse on chronic pain among people who inject drugs in Vancouver, Canada (Under Review). Prangnell A, Shoveller J, Voon P, Shulha H, Milloy MJ, Kerr T, & Hayashi K. The impact of childhood emotional abuse on pain interference among people with chronic pain who inject drugs in Vancouver, Canada (Under Review). viii TABLE OF CONTENTS ABSTRACT........................................................................................................................... iii LAY SUMMARY.................................................................................................................... v PREFACE .............................................................................................................................vi TABLE OF CONTENTS ................................................................................................... viii LIST OF TABLES ............................................................................................................... xii LIST OF FIGURES ........................................................................................................... xiii LIST OF ABBREVIATIONS ............................................................................................xiv ACKNOWLEDGEMENTS ................................................................................................. xv CHAPTER 1. STUDY BACKGROUND AND OBJECTIVES .......................................... 1 1.1 BACKGROUND ................................................................................................... 1 1.1.1 Childhood Abuse ..................................................................................... 1 1.1.2 Unique Aspects of Childhood Emotional Abuse ..................................... 2 1.1.3 Chronic Pain ............................................................................................ 3 1.1.4 Life Course Mechanisms and Childhood Emotional Abuse.................... 4 Physiological Pathways ........................................................................ 5 Psychosocial Pathways ......................................................................... 6 Behavioural Pathways .......................................................................... 8 Social Pathways .................................................................................... 8 1.2 RATIONALE ........................................................................................................ 9 1.3 STUDY SETTING AND SAMPLE ................................................................... 10 1.4 OVERALL AIM AND OBJECTIVES OF THESIS ....................................... 12 ix CHAPTER 2. THE IMPACT OF CHILDHOOD ABUSE ON INJECTION DRUG USE: A SYSTEMATIC REVIEW ............................................................................................... 15 2.1 INTRODUCTION .............................................................................................. 15 2.2 METHODS .......................................................................................................... 16 2.2.1 Search Strategy ...................................................................................... 16 2.2.2 Inclusion and Exclusion Criteria ........................................................... 17 2.2.3 Screening Process .................................................................................. 18 2.2.4 Data Extraction and Analysis ................................................................ 18 2.2.5 Risk of Bias Assessment ........................................................................ 18 2.3 RESULTS ............................................................................................................ 19 2.3.1 Characteristics of Included Studies ....................................................... 19 Sexual Abuse ...................................................................................... 19 Physical Abuse.................................................................................... 20 Emotional Abuse ................................................................................ 20 Gender Analysis.................................................................................. 21 2.3.2 Risk of Bias Assessment ........................................................................ 21 2.4 DISCUSSION ...................................................................................................... 22 Future Directions ............................................................................................ 24 Limitations ...................................................................................................... 25 Conclusions..................................................................................................... 25 CHAPTER 3. THE IMPACT OF CHILDHOOD EMOTIONAL ABUSE ON CHRONIC PAIN AMONG PEOPLE WHO INJECT DRUGS ........................................................... 35 3.1 INTRODUCTION .............................................................................................. 35 x 3.2 METHODS .......................................................................................................... 36 3.2.1 Study Procedure ..................................................................................... 36 3.2.2 Study Variables ...................................................................................... 37 3.2.3 Statistical Analysis................................................................................. 39 3.3 RESULTS ............................................................................................................ 39 3.4 DISCUSSION ...................................................................................................... 40 CHAPTER 4. THE IMPACT OF CHILDHOOD EMOTIONAL ABUSE ON PAIN INTERFERENCE AMONG PEOPLE WITH CHRONIC PAIN WHO INJECT DRUGS .................................................................................................................................. 49 4.1 INTRODUCTION .............................................................................................. 49 4.2 METHODS .......................................................................................................... 51 4.2.1 Study Procedure ..................................................................................... 51 4.2.2 Study Variables ...................................................................................... 51 4.2.3 Statistical Analysis................................................................................. 52 4.3 RESULTS ............................................................................................................ 54 4.4 DISCUSSION ...................................................................................................... 55 CHAPTER 5. SUMMARY OF FINDINGS AND FUTURE DIRECTIONS .................. 63 5.1 SUMMARY OF FINDINGS .............................................................................. 63 5.2 STUDY STRENGTHS AND SIGNIFICANT CONTRIBUTIONS ............... 64 5.3 IMPLICATIONS FOR POLICY AND PRACTICE....................................... 66 5.4 DIRECTIONS FOR FUTURE RESEARCH ................................................... 68 5.5 CONCLUSIONS ................................................................................................. 69 REFERENCES ..................................................................................................................... 71 xi APPENDIX ............................................................................................................................ 96 xii LIST OF TABLES Table 2.1: Sample search strategy for the Medline Database via the OVID Platform; September 26, 2018 ............................................................................................................... 28 Table 2.2: Population, exposures, comparisons, outcomes, and study design (PECOS) criteria for study inclusion .................................................................................................................. 29 Table 2.3: Characteristics of included studies ....................................................................... 30 Table 2.4: Main study findings ............................................................................................. 32 Table 3.1: Baseline sample characteristics, stratified by reporting chronic pain in the past six months among people who inject drugs in Vancouver, Canada (n = 1,459) ......................... 45 Table 3.2: Extent of overlap with additional maltreatment categories among people who inject drugs who reported childhood emotional abuse in Vancouver, Canada (n = 591) ............... 46 Table 3.3: Bivariable and multivariable GEE analysis of reporting chronic pain among people who inject drugs in Vancouver, Canada (n = 1,459) .................................................. 47 Table 4.1: Baseline sample characteristics, stratified by reporting moderate to severe pain interference in the past six months among people who inject drugs with chronic pain in Vancouver, Canada (n = 822) ................................................................................................ 60 Table 4.2: Bivariable and multivariable GEE analysis of reporting moderate to severe pain interference among people who inject drugs with chronic pain in Vancouver, Canada (n = 822) ........................................................................................................................................ 61 xiii LIST OF FIGURES Figure 1.1: Conceptual framework ........................................................................................ 14 Figure 2.1: Study inclusion flowchart for papers measuring the impact of childhood abuse on adult injection drug use ..................................................................................................... 27 xiv LIST OF ABBREVIATIONS ACCESS: AIDS Care Cohort to evaluate Exposure to Survival Services AOR: Adjusted odds ratio BC: British Columbia CI: Confidence interval CTQ: Childhood Trauma Questionnaire DTES: Downtown Eastside GEE: Generalized estimating equation HIV: Human immunodeficiency virus IQR: Interquartile range MeSH: Medical Subject Heading NIAAA: National Institute on Alcohol Abuse and Alcoholism OR: Odds Ratio OAT: Opioid agonist therapy PWID: People who inject drugs VIDUS: Vancouver Injection Drug Users Study VIF: Variance inflation factor xv ACKNOWLEDGEMENTS I would like to sincerely thank my supervisors, Dr. Kanna Hayashi and Dr. Jean Shoveller, and committee member Dr. Thomas Kerr for their unwavering support and encouragement through this whole learning process. Specifically, the early support from Dr. Hayashi years before I ever began my Masters was instrumental to where I am now. Without the generous contribution of data from the participants of the VIDUS and ACCESS study this research would not be possible. I would also like to sincerely thank the British Columbia Centre on Substance Use (BCCSU) statisticians, Ekaterina Nosova and Hennady Shulha, for all of their help with the analyses. In addition, Sameer Imtiaz for assisting me with my systematic review. I would also like to thank my friends at the At-Risk Youth Study (ARYS) office for being the best sources of entertainment possible on endless days of writing. Without the support and love from family and friends, I would likely never have returned to school in the first place. Specifically, my parents for always supporting my choices and letting me choose my own path. A final thank you to my dear friend Mohammad for absolutely everything. My Masters training was generously supported by funding through a research assistant position from the BCCSU. 1 CHAPTER 1. STUDY BACKGROUND AND OBJECTIVES 1.1 BACKGROUND 1.1.1 Childhood Abuse Childhood abuse continues to be a major public health issue with detrimental impacts experienced by individuals throughout their lifespan and extending into communities. Childhood abuse typically includes physical, sexual, or emotional abuse (1). Physical abuse has been defined as the intentional use of physical force against a child likely to cause physical injury. Sexual abuse is defined as any sexual activity, where the child is unable to provide informed consent, unable to fully comprehend, developmentally unprepared, or situations that violate local laws (1). Emotional abuse, also sometimes referred to as psychological abuse, has been defined as a failure to provide developmentally appropriate and supportive environments for a child, which have reason to result in psychological harm to the child (1, 2). This can take the form of intentional rejection of the child, isolating the child and preventing them from engaging with others, terrorizing through threatening behaviours and creating an environment of fear, and belittling them through frequent ridicule (1, 3). It is generally accepted that repeated patterns of inappropriate behaviours are required for emotional abuse (4). In addition to abuse, children may also be subjected to neglect (emotionally or physically). Physical neglect arises when caregiver(s) fail to provide for a child’s physical needs, including food and shelter. Emotional neglect includes situations when a child’s emotional needs are ignored or when caregiver(s) fail to provide a loving, emotionally supportive environment (1). The prevalence of childhood abuse differs by study, setting, and form of exposure. For example, Dube et al. (2001) reported the overall prevalence of emotional abuse at 10.5%, physical 2 abuse at 28.3%, and sexual abuse at 20.7% in a general American population (5). However, a similar study by Cammack et al. (2017) estimated the prevalence of emotional abuse at 25.6%, physical abuse at 12.0%, and sexual abuse at 4.9% (6). The prevalence also differs by the exact abuse definition used. It is generally believed that emotional abuse may be the most underreported but also the most prevalent abuse form, due to its frequent co-occurrence with sexual and physical abuse, as well as often occurring on its own (7). In general, boys are more likely to experience physical abuse, while girls are more likely to experience sexual and emotional abuse (5, 8). Further, boys experience abusive situations at a significantly earlier age than girls, and for children not raised by both biological parents emotional and physical abuse occur at a significantly earlier age (6). There is ample evidence suggesting children exposed to one form of abuse are at an increased risk for additional forms of abuse (9, 10). 1.1.2 Unique Aspects of Childhood Emotional Abuse Research investigating the life-long impact of childhood abuse has previously focused more on childhood physical and sexual abuse (1, 3, 11). This has been partially attributed to previously held beliefs that evidence of physical damage is required for a child to be considered abused (12). However, there is now compelling research suggesting childhood emotional abuse may be the most significant predictor of negative health outcomes, among the various forms of maltreatment (3, 7, 12, 13). This may be largely due to the increased risk of psychological distress, poor mental health outcomes, decreased ability to cope with stressful situations, and detrimental impact on family relationships (12, 14). Additionally, definitions of childhood sexual and physical abuse have well-defined criteria that are universally agreed upon, while childhood emotional abuse has been debated as to what separates emotional abuse from suboptimal parenting (4). Due to this, evidence suggests there is a 3 lack of effective screening tools to identify and substantiate emotional abuse among children (15). Even for trained professionals, differentiating parenting approaches that are not ideal from ones that are deemed abusive remains challenging, especially given that emotional abuse is characterized by repeated abusive behaviours that often occur in private (16). Given the absence of physical evidence, identifying emotionally abused children remains challenging. Experiencing childhood emotional abuse has wide-ranging and life-long impacts on the health during adulthood. These can include poor peer relationships, delays in complex language, cognitive deficiencies, emotional dysregulation, and low self-esteem (17, 18). Mental health impacts include an increased risk of depression, anxiety, eating disorders, conduct disorders, and suicidal behaviours (1). Childhood emotional abuse has also been shown to be associated with substance use, including tobacco smoking, alcohol abuse, and illicit drug use, as well as other behavioural and life-style patterns such as risky sexual practices and unhealthy eating (1, 19, 20). These behaviours would partially explain why childhood emotional abuse has been significantly associated with human immunodeficiency virus (HIV) acquisition, heart disease, and Type 2 diabetes (1, 20). Additionally, childhood emotional abuse has been found to significantly increase the risk of mortality, including suicide (5, 21). While a number of adult health impacts have been identified, there is a lack of research focused on marginalized populations including people who use illicit drugs, who due to a variety of social and structural vulnerabilities may demonstrate varying impacts from abuse. 1.1.3 Chronic Pain The existing literature indicates that childhood abuse is also associated with chronic pain during adulthood (22). Chronic pain, classified as significant pain lasting longer than three months and beyond normal healing time, occurs in approximately 20% of general, adult populations (23- 4 25). In comparison, higher proportions of people who use drugs (33% to 37%) report chronic pain (26, 27). Other population subgroups also report increased risk of chronic pain including women, seniors, and those from low socio-economic status backgrounds (23). Medical conditions associated with chronic pain range from general widespread pain, migraines, headaches, low back pain, musculoskeletal pain, fibromyalgia, to joint pain (28). The consequences of chronic pain are vast and include a reduced ability to maintain work, lower quality of life, increased mortality, increased risk of depression and anxiety, and hampered ability to participate fully in daily life (29-31). In addition, individuals with chronic pain report significantly higher health care utilization (e.g., physician visits; medication use) (31). Research has begun to explore the potential for childhood abuse to increase the risk of chronic pain conditions, however, significantly less attention has been paid to emotional abuse, compared with sexual or physical (32-34). 1.1.4 Life Course Mechanisms and Childhood Emotional Abuse Childhood emotional abuse and its links to subsequent adverse health outcomes is complex. Childhood abuse often pre-dates subsequent adverse health outcomes by decades and little is known about the specific mechanisms and pathways involved. Each survivor of childhood emotional abuse exhibits varying levels of individual and structural vulnerabilities, and as such mechanisms are intertwined and difficult to individually differentiate. Kendall-Tackett (2002) previously proposed four distinct pathways through which childhood exposures impact adult health, which I have adapted for my research (35). In general, the four pathways proposed involve: (1) physiological; (2) psychosocial; (3) behavioural; and (4) social pathways. These pathways may intersect and act together to produce the health outcomes observed later in life (e.g., adulthood). Below I explain how each pathway operates in general, as well as links with chronic pain. Figure 5 1.1 also delineates a conceptual framework showing how childhood emotional abuse would relate to chronic pain during adulthood. Physiological Pathways From approximately 18 days post conception to five years of age, rapid brain growth and development occurs (36, 37). During this time important synaptic connections and pruning, axonal and dendritic growth, myelination, and cortical building essential for proper development occur resulting in strong nutritional needs (38, 39). Poor nutrition and stress, for the mother before birth and the child after, can result in stunted growth as indicated by small for gestational age measurements, with the potential to profoundly impact neurodevelopment (36, 38, 39). While nutrition is essential for healthy brain development, so too are stimulating and supportive environments allowing children to explore with confidence. These experiences are essential for appropriate synaptic connections between brain cells (39). Due to this, children who do not experience optimal development and stimulation, as in the case of emotional abuse, often lag behind similarly aged children in cognitive functioning, school performance, and motor development (38). As brain development continues up until 25 years of age, albeit at a slower rate, experiences during this time continue to impact healthy brain development (40). The left temporal lobe structure, partly responsible for processing language and speech, has been identified as a brain region known to be larger in childhood emotional abuse survivors (41). This may partially explain deficiencies in verbal comprehension experienced by survivors of childhood emotional abuse and potentially caused by a lack of synaptic pruning (41). The presence of stress resulting from emotional abuse in childhood also continually stimulates the hypothalamus-pituitary-adrenal axis to release cortisol. Over time with continual activation of this system, what originally appeared as hyper-activation can also transform into 6 hypo-activation for some (42). This hypo-activation is observed primarily in situations when abuse is expected. In novel situations, an abnormal increase in cortisol production occurs followed by impaired recovery to baseline levels (43, 44). Regardless of whether hyper-activation or hypo-activation occurs, an impaired regulation of cortisol is observed leading to an increased risk for negative adult health outcomes through allostatic stress, or increased wear and tear on the body (43). Further, the inflammatory arm of the immune system has been implicated as a factor in increasing risk for negative health outcomes resulting from childhood emotional abuse. Inflammation is part of a normal response to infection, injury, or stress through the action of cytokines to protect against outside attacks. When stress is chronic, increased release of cytokines and noradrenaline results in chronic inflammation, a known contributor to many chronic diseases (44). An impaired release of cortisol and increased overall inflammation is known to increase the risk of chronic pain conditions (42, 43). Psychosocial Pathways Essential social and emotional development is also concentrated during birth to five years of age (45). Early social and emotional development has generally been defined as “the developing capacity of the child from birth through five years of age to form close and secure adult and peer relationships; experience, regulate, and express emotions in socially and culturally appropriate ways; and explore the environment and learn – all in the context of family, community, and culture” according to the Center on the Social Emotional Foundations for Early Learning (46). Healthy relationships with caregivers provide children with the ability to confidently explore the environment around them to successfully regulate emotions in order to cope with changing stimulus (45). This is especially important for coping with negative stimulus both in terms of immediate and sustained reactions (47). Further, supportive caregiver relationships in childhood 7 is also important for developing appropriate future relationships with peers and other adults, impulse control, understanding of social environments, and appropriate emotional expression (48). Emotional dysregulation is generally defined as the inability to control not only what emotions are expressed, but also the intensity and timing (49). This trait is commonly seen in adult survivors of childhood emotional abuse, partly due to biological changes previously described, but also to disrupted secure attachment with caregivers (50). Appropriate emotional responses are highly influenced by the strength of the caregiver interactions (49). Children obtain cues regarding emotional management through caregivers, and when those attachments are weak due to emotional abuse, children lack skills to display appropriate emotional responses. Additionally, children in emotionally abusive situations show a decreased ability to accurately identify other people’s emotional state (51). This has been shown to negatively impact the number and quality of relationships, in terms of friends, family, and romantic partnerships (52). Having strong social supports can improve health and quality of life through mitigating feelings of hopelessness and depression, by providing a financial safety net, and by an increased likelihood of engaging in health-promoting activities (35, 53). However, such social supports may be diminished among survivors of childhood emotional abuse due to the decreased ability to trust and relate to others (35). As childhood emotional abuse is often characterized by feelings of being unloved and worthless, these feelings can be internalized to define underlying assumptions about one’s value and self-identity (54). Identifying oneself as worthless, defective, or vulnerable has been found to predict psychological distress in the form of depression and anxiety (55, 56). Psychological distress can result directly from emotional abuse or through proximal mechanisms associated with emotional abuse, including reduced social support and feeling worthless. In turn, depression and 8 anxiety are known to negatively impact sleep quality and duration, imparting stress on the body (52). For depressed patients the immune system is frequently suppressed, through disrupted sleep and stress, limiting the ability of the body to protect itself from infectious agents (57). The increased risk of depression, anxiety, and maladaptive coping skills associated with childhood abuse has been shown to be partially responsible for the increased risk of chronic pain conditions (35, 58). Behavioural Pathways In part to cope with the emotional abuse itself, or mediating factors including the above-described poor social connections, negative internalized feelings about self, and psychological distress, individuals who have been emotionally abused may engage in unhealthy behaviours. These can include smoking, unhealthy eating, illicit drug use, and high-risk sexual practices, all of which are associated with negative health outcomes (52). There are numerous mechanisms through which unhealthy behaviours can contribute to chronic pain disorders. For example, unhealthy eating significantly contributes to obesity, a known risk factor for chronic pain conditions, as excess body weight causes stress on joints as well as increased inflammation (59, 60). As well, the acquisition of infectious diseases, through high-risk sexual practices and illicit drug use, can contribute to overall chronic pain, especially if left untreated (61-63). Social Pathways Emotional abuse often occurs in family situations with decreased support and increased chaotic environments, including households where substance use disorders, mental illness, domestic violence, crime, and parental separation are present (10, 64). In turn, such unstable environments are not conducive to attending school and excelling academically. Even when children are in class the ability to concentrate can be diminished. Due to these factors, and many 9 others, school-aged emotionally abused children report lower academic performance and higher levels of absenteeism (65, 66). In turn, high levels of absenteeism are strongly linked with grade failure and school dropout (66). This may partially explain the low rates of high-school graduation for children who suffer emotional abuse (66). Low educational attainment has far-reaching impacts decades after grade school age and has been strongly linked with adult negative health partially through decreased employment opportunities and decreased financial stability. Decreased employment opportunities also frequently forces individuals into physically demanding jobs, with an increased risk of injury and stress, leading to chronic pain conditions (67). Social forces can also impart negative impacts on general health. Low socioeconomic status has been identified as a risk factor for children experiencing poor emotional and social development (68). This alone increases the risk for poor health outcomes. However, childhood maltreatment is also associated with low socioeconomic status families/neighbourhoods, compounding the risk factors and resulting in these children disproportionately experiencing negative health outcomes. Neighbourhood level variables associated with low socioeconomic status and contributing to poor health include a lack of nutritious food, a lack of exercise facilities, decreased availability of support services for parents, and school systems with a lack of resources (23). 1.2 RATIONALE Due to the intensive and extensive development during childhood, emotionally abusive experiences during this time are particularly damaging. As such, there is an urgent need to identify negative health outcomes resulting from childhood emotional abuse. While researchers have begun to explore this among the general population, little research has focused on marginalized populations, including people who inject drugs (PWID) who are characterized by high prevalence 10 of both childhood abuse and chronic pain. In particular, while studies have examined the relationship between childhood abuse and injection drug use during adulthood (69, 70), the evidence has not been summarized, which makes it difficult to understand if the relationship differs by populations, settings, or forms of abuse. In addition, while preliminary research has identified childhood emotional abuse as a significant risk factor for chronic pain during adulthood in the general population (71), there remains a critical gap in understanding whether this relationship holds among PWID, and if so, how it operates among this population. Understanding relationships between childhood emotional abuse, injection drug use, and chronic pain is important to inform the ongoing efforts to prevent childhood abuse and promote trauma-informed care among this marginalized population. 1.3 STUDY SETTING AND SAMPLE Data driven Chapters Three and Four, included in this thesis use data collected through the Vancouver Injection Drug Users Study (VIDUS) and the AIDS Care Cohort to evaluate Exposure to Survival Services (ACCESS), which are ongoing open prospective cohorts of adult drug users recruited through word of mouth, street outreach, and referrals from community organizations in Vancouver, Canada. A large proportion of VIDUS and ACCESS participants reside in the Downtown Eastside (DTES) neighbourhood, which is home to Canada’s largest open drug scene and regarded as the poorest postal code in Canada (72, 73). Among the estimated 18,000 residents there are high rates of mental illness, substance use disorders, and infectious diseases including HIV and Hepatitis C virus, leaving many residents without viable employment opportunities and resulting in high poverty levels supplemented by government assistance (73). The high cost of living in Vancouver leaves many residents of the DTES with housing options limited to single- 11 room occupancy hotels, frequently dilapidated and in urgent need of repairs, as the only alternative to homelessness (73). The VIDUS cohort commenced enrolment in May 1996 to investigate the HIV outbreak in the community and originally included HIV negative and positive participants (74). It was extended in 2005 and the ACCESS cohort was created to separate individuals according to HIV status and included all the original HIV positive participants. Briefly, VIDUS enrols HIV-negative persons who reported injecting an illicit drug at least once in the month preceding enrolment; ACCESS enrols HIV positive individuals who report using an illicit drug (other than, or in addition to, cannabis) in the previous month. For both cohorts, other eligibility criteria included being aged 18 years or older, residing in the greater Vancouver region, and providing written informed consent. The questionnaire provided is in English only, however migrants or foreigners are able to participate, provided they speak English and reside in the Greater Vancouver region. The study instruments and all other follow-up procedures for each study are harmonized to allow for combined analyses. At baseline and semi-annually thereafter, participants complete an interviewer-administered questionnaire eliciting socio-demographic data as well as information pertaining to drug use patterns, risk behaviours, health care utilization, and participation in drug treatment programs. Nurses collect blood samples for Hepatitis C and HIV virus serology. HIV tests that are reactive by enzyme-linked immunosorbent assay are confirmed by Western blot and any VIDUS participants who seroconverted during follow up are transferred to the ACCESS cohort so that VIDUS includes HIV negative individuals only, and ACCESS includes HIV positive individuals only. If required, nurses provide basic medical care and arrange referrals to appropriate health care services. Participants receive a $40 (CDN) honorarium for each study visit. The University of British Columbia/Providence Healthcare Research Ethics Board provided ethical 12 approval for both studies, as well as my thesis research. To date there are approximately 1400 VIDUS and 900 ACCESS participants who have completed at minimum a baseline interview. 1.4 OVERALL AIM AND OBJECTIVES OF THESIS Overall Aim: This thesis will add to the understanding of the relationships between childhood emotional abuse, injection drug use, and adult chronic pain. Specific objectives include: 1. To systematically review the literature regarding an association between childhood abuse and injection drug use. 2. To characterize the association between childhood emotional abuse and self-reported chronic pain among PWID. 3. To characterize the association between childhood emotional abuse and pain interference (i.e., the extent to which chronic pain hinders daily activities) among PWID who report chronic pain and to further assess if mental health illness may mediate this relationship. The thesis is divided into five chapters: Chapter One presents an introduction into the topic of childhood abuse and why abuse during this time, in particular emotional abuse, is detrimental and important to understand. Chapter Two presents findings from a systematic review summarizing research on the impact of childhood abuse on adult injection drug use. Chapter Three presents an original empirical study investigating potential associations between chronic pain and childhood emotional abuse. Chapter Four presents another original empirical study investigating whether pain interference is associated with childhood emotional abuse among those with chronic 13 pain. Finally, Chapter Five summarizes the study findings presented and discusses areas for future research. 14 Psychosocial Emotional dysregulation Social support Psychological distress Social Determinants of Health Educational attainment Social Services Physiological Inflammation Cortisol levels Behavioural Injection drug use Unhealthy eating Unsafe sex practices Childhood Emotional Abuse Health Outcomes Chronic pain Pain interference Figure 1.1: Conceptual framework* *Framework adapted from Kendall–Tackett (2002) 15 CHAPTER 2. THE IMPACT OF CHILDHOOD ABUSE ON INJECTION DRUG USE: A SYSTEMATIC REVIEW 2.1 INTRODUCTION As previously described, childhood abuse is a detrimental but all too common global public health problem, resulting in numerous long-term physical and mental harms, including depression, anxiety, and eating disorders, as well as suicidal behaviours, cardiovascular disease, diabetes, respiratory diseases, ulcers, headaches, cancer, arthritis, and obesity (1). In addition, one of the commonly identified harms of childhood abuse is future harmful substance use (1, 75, 76). For example, Widow et al. (2006) identified childhood sexual and physical abuse as significant risk factors for reporting adult illicit drug use (77). Further, Norman et al. (2012) provided evidence for a significant and positive relationship between experiencing emotional and physical abuse in childhood and harmful alcohol and illicit drug use later in life (1). The relationship between childhood abuse and illicit drug use in later life is concerning given that illicit drug use is a significant contributor to the global burden of premature death, disability, and disease, with young adults disproportionately impacted (78). While drugs can be administered by various methods, including smoking, snorting, and injecting, injection drug use is known to be associated with particularly increased harms, including an increased risk of overdose, injection-related trauma, and infectious disease acquisition including Hepatitis C, Hepatitis B, and human immunodeficiency virus (HIV) (79). Overall there are an estimated 15 million people who inject drugs (PWID) internationally (80). As injection drug use is highly stigmatized, PWID typically face 16 significant social marginalization, which is associated with an increased risk of violence, mental health challenges, homelessness, suboptimal access to healthcare, and incarceration (78-80). There is a growing body of evidence pointing to a relationship between childhood experiences and initiation of injection drug use; however, the findings to date have been diverse. For example, Kerr et al. (2009) found childhood physical abuse was associated with an increased likelihood of injecting drugs, while emotional or sexual abuse was not (69). Meanwhile, Quinn et al. (2016) found only childhood sexual abuse was positively associated with injection drug use, while physical or emotional abuse were not (70). As such, there is a need to summarize the impact of childhood exposures on injection drug use to have a clear understanding of these relationships in order to inform relevant public health interventions. Therefore, this chapter provides a systematic review of the literature on the impact of childhood abuse on adult injection drug use. The primary research question that guided the systematic review is: Are individuals who experienced childhood sexual, physical, and/or emotional abuse (not childhood abuse in general) at a higher risk for engaging in injection drug use as adults compared with those who did not experience childhood abuse? 2.2 METHODS 2.2.1 Search Strategy Following the Systematic Reviews (PRISMA) checklist (81), studies related to child abuse and injection drug use that were published in English were searched. For peer-reviewed studies, MEDLINE, EMBASE, PsycINFO, CINAHL, and Web of Science were searched from inception to September 26, 2018. For grey literature, Google Scholar, 17 ProQuest, OpenGrey, openDOAR, and Grey Literature Report were also searched. Search terms were combined using appropriate Boolean operators and included subject heading terms or keywords for two key themes: child abuse (e.g. child abuse OR child neglect OR early life stress OR adverse childhood experience OR child maltreatment) AND injection drug use (e.g. intravenous substance abuse OR people who inject drugs OR injection drug user). These terms were tailored to fit each database requirements. Hand searches of the bibliographies of relevant published works and previous reviews were also performed (i.e., citation snowballing). The full electronic search strategy is reported in Table 2.1. 2.2.2 Inclusion and Exclusion Criteria The population, exposures, comparisons, outcome, and study designs considered for review are listed in Table 2.2. Studies were included provided they met the following inclusion criteria: 1) The study reported original research results published in English; 2) The study utilized prospective cohort, retrospective cohort, cross-sectional, or case-control designs (i.e., review articles, commentaries or letters, case reports, or case-series were excluded); 3) The study considered childhood abuse (sexual, physical, and emotional but not combined abuse) as potential risk factors for lifetime history of injection drug use, with childhood considered to be between birth and age of 18, as is consistent with previous definitions (82); 4) The study participants had to have a mean age over 18, when assessing lifetime injection drug use, to attempt to ensure temporality. Studies were excluded if they only reported a combined measurement for childhood abuse. This was done to isolate the measurement of different forms of abuse as aggregate measures of adverse childhood events typically include other adverse experiences that are independent of abuse (i.e. parental death or household mental illness). As has previously been done for reviews 18 assessing the impact of child abuse (83-85), this review only included studies that measured abuse, and not more general neglect or adverse family situations. Studies that did not permit calculation of odds ratios or risk ratios or hazard ratios and confidence intervals were excluded. 2.2.3 Screening Process All records were imported into Endnote X7 and deduplicated. Titles and abstracts of retrieved articles were screened to identify studies that potentially met the inclusion criteria. Articles potentially relevant moved onto the subsequent screening stage where both reviewers (AP and SI) independently screened full-text versions of articles. Studies were independently marked as included or if excluded marked with reasons why, with often multiple exclusion reasons reported. The reviewers compared classifications and discussed discrepancies until a consensus was reached. 2.2.4 Data Extraction and Analysis Information for each included study was extracted and input into a Microsoft Excel spreadsheet. Information was extracted by the primary reviewer (AP) and independently reviewed for accuracy by the second reviewer (SI). It included study characteristics (e.g. study date and location), participant characteristics (e.g. target population, age, gender, ethnicity), exposures (e.g. exposures measured, definitions), and main outcome findings. Data were summarized across studies with respect to participants, characteristics of studies, abuse exposures, and impacts. 2.2.5 Risk of Bias Assessment Risk of bias was assessed using the modified Newcastle-Ottawa Scale (86). This scale consists of eight questions for cohort and case-control studies and six for cross- 19 sectional studies, utilizing components assessing selection bias, comparability, and exposure assessment. 2.3 RESULTS 2.3.1 Characteristics of Included Studies Of the original 1994 abstracts initially identified through databases, 754 were identified as duplicates. Based on title and abstract information, 105 were included for full-text screening. In total, 17 papers met the inclusion criteria to be included in data synthesis (69, 70, 87-101). Figure 2.1 outlines the study inclusion flowchart. Most studies were conducted in the United States (eleven studies) (70, 88-92, 94, 95, 97, 98, 101), with others conducted in Canada (two studies) (69, 96), Scotland (one study) (93), Australia (one study) (87), Malaysia (one study) (100), and India (one study) (99). Overall, twelve of the studies employed cross-sectional study designs (69, 88, 90-92, 94, 95, 97-101), with three cohort studies (70, 87, 96), and two case-control studies (89, 93). Regarding the study inclusion criteria, three studies restricted enrolment to those currently incarcerated (94, 95, 98), three studies restricted enrolment to those who reported the recent use of illicit drugs (69, 89, 100), two studies restricted enrolment to those who were HIV seropositive (90, 92), two studies only included youth who reported a lack of regular housing or who used street youth services regularly (69, 89), two studies used data from general population-based surveys (70, 87), and two studies were restricted to gay and bisexual males (88, 92). Across all studies the outcome measurement of a lifetime history of injection drug use was consistently measured using a variation of the question “Have you ever injected drugs”? Full details of the studies and participants are reported in Table 2.3. Sexual Abuse 20 All 17 included studies assessed the impact of childhood sexual abuse on injection drug use, with eight proceeding with an adjusted model accounting for potential confounders (69, 70, 87, 90, 93, 94, 96, 97). Of the nine studies that did not proceed with an adjusted model, four found sexual abuse was significantly and positively associated with injection drug use (88, 92, 95, 100). Of the eight that did include an adjusted model, four identified a statistically significant and positive relationship between sexual abuse and injection drug use; however, one of those found it significant for males only and not females (70, 94, 96, 97). Across the studies the reported prevalence of sexual abuse ranged from 1.4% to 42%, with a mean of 23.8%. Full details on main findings are reported in Table 2.4. Physical Abuse Overall, six studies (38%) included a measurement for physical abuse with all but one proceeding with an adjusted model (69, 70, 87, 93, 94, 100). One study that only included an unadjusted model found reporting childhood physical abuse was significantly and positively associated with injection drug use (100). Of the five remaining studies, four identified a statistically significant and positive relationship with injection drug use; however, one was significant for females only and not males (69, 87, 93, 94). Across the studies the reported prevalence of physical abuse ranged from 1.9% to 49.5%, with a mean of 29.7%. Emotional Abuse Only three studies (19%) included a measurement for emotional abuse and all proceeded with a multivariable model (69, 70, 87). Of the three studies, one found a statistically significant and positive relationship with injection drug use, among males and 21 females (87). The other two studies did not identify a significant association with injection drug use (69, 70). Only two of the three studies reported the prevalence of emotional abuse, which were 2.3% and 49.6%. Gender Analysis Five studies were restricted to males (88, 90-92, 99), and four to females (95, 97, 98, 100), with the remaining eight studies including a mix of males and females. No studies specified the inclusion of transgender individuals. Of the eight studies that included males and females, two did not include an adjusted model. Among the six that did proceed with an adjusted model, one included gender as a confounder (94), and two conducted separate analyses by gender, uncovering statistically significant gender differences (87, 96). Therefore, three studies did not account for gender in their analysis or study design. 2.3.2 Risk of Bias Assessment Results from the risk of bias assessment using the Newcastle Ottawa Scale are reported in Appendix Table 1. Of the two case-control studies all met criteria for selection bias (i.e. adequate case definition, cases representative, selection of control from same population, and adequate definition of controls), comparability and same ascertainment for outcome, however, none met criteria for ascertainment of exposure or non-response rate. For studies using a cohort study design all met criteria for non-exposed from same community, ascertainment of exposure, comparability, and sufficient follow-up. However, none met criteria for outcome assessment, two met criteria for exposed representative and outcome not present at start of study, and only one met criteria for lost to follow-up assessment. Of the cross-sectional studies, all met criteria for an appropriate statistical test. However, none met criteria for outcome assessment; and only one met criteria for an 22 analysis between respondents and non-respondents. Additionally, only one met criteria for a validated exposure tool, four met criteria for representative, and finally, four met criteria for comparability. 2.4 DISCUSSION The present systematic review identified 17 articles that investigated the relationship between childhood emotional, physical, or sexual abuse and a history of injection drug use. All of the studies measured childhood sexual abuse, with six measuring physical abuse, and three measuring emotional abuse. The majority of studies employed cross-sectional study designs and the majority were conducted in North America. Among the studies measuring childhood sexual abuse, findings were mixed for both unadjusted and adjusted analyses. Due to this, no conclusion could be reached regarding the question of whether individuals who experienced childhood sexual abuse are at a higher risk for engaging in injection drug use as adults compared with those who did not experience childhood sexual abuse. Vast differences in how sexual abuse was measured across studies may have hampered the ability to draw conclusions. Some definitions referred specifically to rape/penetration, while most others included a vague reference to sexual abuse, forced contact, or mistreatment. Additionally, as a result of setting a strict age criteria defining childhood, a methodologically rigorous, relevant study was excluded, which identified a significantly increased risk of injection initiation for survivors of childhood sexual abuse among street-involved youth (102). The findings for physical abuse were generally consistent with the majority of adjusted studies identifying a significant association with injection drug use, regardless of the exact terminology used. Likewise, there is evidence for emotional abuse increasing the 23 risk of engaging in injection drug use. Even though there were only three studies that measured emotional abuse, the study with the strongest definition of emotional abuse identified a significant relationship, among males and females, with adult injection drug use (87). One of the studies not identifying a significant relationship relied on a vague measurement of emotional abuse (70). Likewise, in the remaining study, the lack of statistical significance may have been due to collinearity with other child exposures (69). There are many potential reasons for the observed varying levels of association with injection drug use. First, there were differences in how researchers measured the abuse variable, as well as how childhood was defined. For example, of the 17 included studies only one study used a validated instrument (69): The Childhood Trauma Questionnaire (CTQ) (103). Many of the studies were simultaneously measuring multiple outcomes and exposures. Due to the overall interview burden, some researchers may have opted to reduce the number of questions assessing each exposure to a single question. However, this may have resulted in studies assessing varying abuse intensities, reflected in the divergent findings. Meanwhile, definitions of childhood included references to non-descript time periods such as “childhood”, “adolescents”, “while growing up”, in addition to other specified age cut-offs younger than 18. Secondly, cultural differences can dictate what parental behaviours are seen as abusive (104). For example, it is known that black respondents tend to report more physical discipline by parental figures, which may have been inaccurately reported as physical abuse and may have also contributed to differential findings (104). The overall lack of consideration in accounting for gender-based differences is a further concern given the current understanding of how gender impacts not only the type 24 of abuse exposed to, but also the long-term impacts. For example, males are more likely to experience physical abuse, while females are more likely to experience sexual and emotional abuse (5, 8, 105). Yet, females have been identified as being impacted more severely from early abuse exposures (105). In terms of abuse definitions, many of the studies considered participants exposed to maltreatment if they responded affirmatively to measurements referring to the word “abuse” specifically. However, previous research has found that females are more likely to respond affirmatively to responses where abuse is explicit, as opposed to when behaviours indicative of abuse are mentioned, which may have contributed to divergent findings (104, 106). These findings stress the importance of applying a gender lens when conducting research on childhood exposures. Future Directions Although the included studies for this review provide evidence for childhood abuse increasing the likelihood of adult injection drug use, there remain several areas for future research. Firstly, only two studies assessed childhood abuse prospectively (70, 87), with the remaining relying on retrospective memories of abuse as young adults or adults. Since recall bias has been identified as a concern with retrospectively obtained information, more longitudinal studies beginning in childhood are needed (107, 108). Secondly, an important consideration is to build upon previously validated instruments to identify the specific variables pertaining to childhood abuse that are so detrimental. These could include abuse severity, duration, age at first incident, and the relationship to the perpetrator. In doing so, new studies could unmask significant associations that may have been obscured by more general abuse variables. It would also assist in identification of those children at the highest risk of adverse outcomes and the provision of tailored interventions. Preliminary evidence 25 suggests that an earlier age of abuse and abuse perpetrated by mother figures results in stronger associations with negative adult outcomes (109). Finally, there is a considerable gap in research focused on physical and emotional abuse in childhood despite the significant harms associated with these exposures. Future studies assessing the impact of childhood abuse on adult behaviours should strive to include measurements of emotional and physical abuse. Limitations Limitations include an inability to include non-English articles due to language restrictions among the co-authors. Secondly, while efforts were made to minimize selection bias, including having a second reviewer involved in screening the full-text of potentially relevant articles, there is an inherent human factor in screening and important articles may have been missed. Conclusions This summary of the evidence suggests a significant association between childhood physical abuse and injection drug use, alongside mixed results for sexual abuse and emotional abuse. Overall, the results support the need for additional high-quality prospective studies assessing the impact of childhood abuse on adult behaviours. This is especially important for emotional abuse given the identified lack of attention it has received and the strong potential to significantly increase the risk of future injection drug use through the pathways previously discussed in this thesis. Further, in order to prevent childhood abuse it is essential to make universal support programs available for all parents, with an increased scale and intensity for families in relation to their social disadvantage. 26 Finally, there is a need to address the drivers of social inequity that contribute to childhood abuse for long-term change. 27 Figure 2.1: Study inclusion flowchart for papers measuring the impact of childhood abuse on adult injection drug use 28 Table 2.1: Sample search strategy for the Medline Database via the OVID Platform; September 26, 2018 No. Search Terms 1 Child Abuse/ 2 ((child* or school age child* or adolescent* or school child* or middle childhood* or elementary school* or Junior high school* or middle school* or primary school* or preschool* or early life) adj1 (abus* or neglect* or harm* or depriv* or mistreat* or maltreat* or trauma* or advers* or abandon* or assault)).tw. 3 Early life stress.tw. 4 Adverse childhood experience.tw. 5 Adult Survivors of Child Abuse/ 6 ((emotion* or psych* or sex* or physical*) adj1 (abus* or neglect* or harm* or depriv* or mistreat* or maltreat* or trauma or advers* or abandon* or assault)).tw. 7 1 or 2 or 3 or 4 or 5 or 6 8 ((opiate* or opioid* or heroin* or cocaine* or crack* or coke* or crack cocaine or meth* or dilaudid or fentanyl or w-18 or carfentanyl or carfentanil or drug* or substance*) adj2 inject*).tw. 9 Substance Abuse, Intravenous/ 10 (IDU or IDUs or inject* drug user).tw. 11 (PWID or People who inject drugs).tw. 12 ((intra* or inject*) adj2 (substance or drug* or abus* or use*)).tw. 13 8 or 9 or 10 or 11 or 12 14 7 and 13 29 Table 2.2: Population, exposures, comparisons, outcomes, and study design (PECOS) criteria for study inclusion Criteria Definition Population Participants with a mean age over 18 Exposuresa Childhood abuse (sexual, physical, and emotional but not combined abuse), either self-reported or substantiated by court system from age of 0 – 18 Comparisons Groups of children determined as not exposed to childhood abuse (sexual, physical, or emotional), either self-reported or substantiated by court system from age of 0 – 18 Outcomes Lifetime history of injection drug use Study Designs Original quantitative studies aChildhood sexual abuse was defined as any sexual activity, where the child is unable to provide consent or fully comprehend. Physical abuse is defined as the intentional use of physical force against a child likely to cause physical injury. Emotional abuse is defined as a failure to provide developmentally appropriate and supportive environments for a child, which have reason to result in psychological harm to the child. Objective and subjective measures for abuse were included (i.e. substantiated reports, self-report measure or standard questionnaire such as Childhood Trauma Questionnaire). 30 Table 2.3: Characteristics of included studies Author (Year) Study design Location Participants Ethnicity Exposure measured Inclusion criteria Abajobir et al. (2017) Cohort Australia 3,750 Offspring of mothers in Mater-University of Queensland Study of Pregnancy; Mean age = 20.6; 47.2% Female 92.4% White; 3.9% Aboriginal-Torres Strait Islander; 3.7% Asian Sexual abuse; Physical abuse; Emotional abuse Adult offspring of mothers enrolled in The Mater-University of Queensland Study of Pregnancy with complete follow-up data at 21 years of age Bartholow et al. (1994) Cross-sectional USA 1,001 Homosexual and bisexual men; Mean age = 32.5; 0% Female 73% White, 12% Black, 12% Hispanic, and 4% Asian, Native American, or other ethnic group Sexual abuse 18 years of age or older; Self-reported oral or anal sex with a male sex partner within the past 5 years or self-identified as homosexual or bisexual; Male Fuller et al. (2002) Case-control USA 270 Street recruited drug users; Median age = 26; 61% Female 78% African–American; 22% Other Sexual abuse 15 – 30 years of age; Reported recent illicit drug use; Agreed to HIV testing Holmes (1997) Cross-sectional USA 95 HIV Seropositive Men; Mean age = 37.2; 0% Female 67% White; 27% African-American; 4% Hispanic; 1% Native-American Sexual abuse ≥18 years of age; English speaking; HIV seropositive; Male Holmes (2010) Cross-sectional USA 197 Men; Mean age = 34; 0% Female 68% Racial or ethnic minorities; 32% Racial or ethnic majority Sexual abuse 18 - 49 years of age; Living in a high-risk urban area; Male Ibanez et al. (2005) Cross-sectional USA 1,168 HIV seropositive gay and bisexual men; Mean age = NR; 0% Female 45.2% White; 28.0% Black; 16.9% Hispanic; 9.6% Other Sexual abuse ≥ 18 years or age; HIV seropositive; Reported having had sex with at least one partner who was HIV seronegative or of unknown status; Male Kerr et al. (2009) Cross-sectional Canada 560 Street-involved drug using youth; Median age = 21.9; 34% Female 76.6% Non-Aboriginal; 23.4% Aboriginal Sexual abuse; Physical abuse; Emotional abuse 14 - 26 years of age; Street-involved; Reported recent illicit drug use Macleod et al. (2013) Case–control Scotland 864 Primary health centre recruited participants; Mean age = NR; % Female = NR NR Sexual abuse; Physical abuse Patient at primary health centre Marotta (2017) Cross-sectional USA 16,043 Inmates in state and federal prisons; Mean age = NR; 6.92% Female 40.8% Black; 35.5% White; 17.9% Hispanic; 5.8% Other Sexual abuse; Physical abuse Inmate at state or federal prison 31 Author (Year) Study design Location Participants Ethnicity Exposure measured Inclusion criteria Mullings et al. (2000) Cross-sectional USA 500 Female inmates; Mean age = 32.3; 100% Female 47.4% African- American; 32.2% White; 19.5% Hispanics Sexual abuse New female admission to the prison system Quinn et al. (2016) Cohort USA 12,141 Participants of Add Health survey data; Mean age = NR; % Female = NR N/R Sexual abuse; Physical abuse; Emotional abuse Students recruited in middle or high school for Add Health survey; Complete data for third wave of collection Roy et al. (2011) Cohort Canada 817 Street youth; Mean age = 19.6; 30.0% Female N/R Sexual abuse Street-active; English or French speaking Schwartz et al. (2014) Cross-sectional USA 736 Female participants of Women’s Interagency HIV Study (WIHS); Mean age = 45.17; 100% Female 74% African American; 13% Hispanic; 10% White; 3% Other Sexual abuse Female; English or Spanish speaking; Enrolled in Women’s Interagency HIV Study (WIHS) Stevens et al. (1995) Cross-sectional USA 88 Incarcerated females; Mean age = 31; 100% Female 53.4% White; 31.8% Hispanic; 14.8% Black Sexual abuse Age ≥ 18 years; Agreed to HIV testing; Incarcerated; Female Tomori et al. (2016) Cross-sectional India 11,788 Men who have sex with men; Median age = 25; 0% Female N/R Sexual abuse Age ≥ 18 years; Self-identify as male; Reported oral or anal sex with another male in the prior 12 months Wickersham et al. (2016) Cross-sectional Malaysia 103 Female drug users; Mean age = 39.4; 100% Female 61.2% Malay; 16.5% Indian; 14.6% Chinese; 7.8% Other Sexual abuse; Physical abuse Age ≥ 18 years; Reported illicit substance within the past 12 months; Female Zierler et al. (1991) Cross-sectional USA Sexually active community recruited participants; Mean age = NR; 51% Female 79% White; 21% Other Sexual abuse Age ≥ 18 years; Currently or recently sexually active with someone of the opposite sex NR = not reported. 32 Table 2.4: Main study findings Study (Year) Exposure definition Unadjusted finding Adjusted finding Variables adjusted for Sexual abuse findings Abajobir et al. (2017) Notified cases of being exposed or involved in inappropriate sexual activities up to 14 years of age Female OR = 3.64; 95% CI 1.49-8.86 Male OR = 1.40; 95% CI 0.18-11.05 Female AOR = 2.41; 95% CI 0.96-6.07 Male AOR = 1.45; 95% CI 0.18-11.96 Receiving social security benefits; Educational level; Marital status; Race; Maternal alcohol use; Maternal chronic depressive symptoms Bartholow et al. (1994) Encouraged or forced sexual contact with someone older or in a position of power as a child or adolescent OR = 2.53; 95% CI 1.84-3.49 NR NR Fuller et al. (2002) Rape or sexual assault at or before 13 years of age OR = 2.17; 95% CI 0.82-5.70 NR NR Holmes (1997) Sexual abuse as child OR = 5.4; 95% CI 1.5-19.6 AOR = 2.4; 95% CI 0.6-10.6 Age; Sexual orientation; Income status Holmes (2010) Any sexual experience before 18 years of age either (a) with someone significantly older or in a position of power (b) in which coercion was reported or (c) penetrative sex occurred with someone older OR = 4.08; 95% CI 0.79- 21.04 NR NR Ibanez et al. (2005) Sexual abuse as child OR = 2.03; 95% CI 1.52-2.70 NR NR Kerr et al. (2009) Five questions from Childhood Trauma Questionnaire utilizing a five-point likert scale OR = 1.49; 95% CI 1.02-2.17 AOR = 1.26; 95% CI 0.83-1.93 Age; Parental drug use; Physical abuse Macleod et al. (2013) Sexual abuse as child or adolescent OR = 1.69; 95% CI 1.14-2.51 AOR =1.29; 95% CI 0.76-2.19 Care experience; Housing stability; Family problems; Carer substance use; Physical victimization; Conduct problems Marotta (2017) Pressured or forced into sexual contact against will before age of 18 NR AOR = 1.31; Standard error =0.10 Sex; Race; Education; Primary caregiver; Economic hardship Mullings et al. (2000) Sexually mistreated, abused, or raped while growing up OR = 1.63; 95% CI 1.09-2.43 NR NR Quinn et al. (2016) Forced to touch or been touch sexually by adult caregiver before 18 years of age OR = 4.47; 95% CI 2.61-7.66 AOR = 4.77; 95% CI 2.44-9.34 Age; Ethnicity; Poverty; Education; Physical abuse; Emotional abuse; Neglect 33 Study (Year) Exposure definition Unadjusted finding Adjusted finding Variables adjusted for Roy et al. (2011) Sexual abuse before 14 years of age Female HR = 1.41 Male HR = 1.60 Female AHR = Not significant Male AHR = 1.98; 95% CI 1.18-3.3 Age; Cocaine or crack use; Heroin use; Youth homelessness; Current homelessness; Hanging out with PWID; Drug binge before age 15 Schwartz et al. (2014) Sexual abuse before 18 years of age OR = 3.51; 95% CI 2.22-5.55 AOR = 2.59; 95% CI 1.52-4.40 Depression; Hopelessness; Non-IDU; Age; Race; Birthplace Stevens et al. (1995) Forced sex below the age of 18 OR = 2.06; 95% CI 0.70-6.03 NR NR Tomori et al. (2016) Any unwanted sexual experiences before 16 years old OR = 0.63; 95% CI 0.28-1.43 NR NR Wickersham et al. (2016) Forced to touch or be touched or forced sex against will by someone older before the age of 18 OR = 3.33; 95% CI 1.36-8.11 NR NR Zierler et al. (1991) Raped or forced to have sex in childhood or adolescence OR = 0.97; 95% CI 0.46-2.06 NR NR Physical abuse findings Abajobir et al. (2017) Notified cases of non-accidental physical injury by a caregiver up to 14 years of age Female OR = 4.23; 95% CI 1.72-10.42 Male OR = 3.22; 95% CI 1.30-7.97 Female AOR = 2.69; 95% CI 1.06-6.87 Male AOR = 2.56; 95% CI 0.99-6.58 Receiving social security benefits; Educational level; Marital status; Race; Maternal alcohol use; Maternal chronic depressive symptoms Kerr et al. (2009) Five questions from Childhood Trauma Questionnaire utilizing a five-point likert scale OR = 1.82; 95% CI 1.28-2.57 AOR = 1.91; 95% CI 1.29-2.83 Age; Parental drug use; Sexual abuse Macleod et al. (2013) Experienced physical violence from caregiver as child or adolescent OR = 2.69; 95% CI 1.89-3.83 AOR = 2.06; 95% CI 1.26-3.38 Care experience; Housing stability; Family problems; Carer substance use; Sexual victimization; Conduct problems Marotta (2017) Physical abuse or violence with or without weapon before age of 18 N/R AOR = 1.39; Standard error =0.07 Sex; Race; Education; Primary caregiver; Economic hardship Quinn et al. (2016) Slapped, hit, kicked, or thrown by adult caregiver 6 or more times before 18 years of age OR = 1.94; 95% CI 1.13-3.34 AOR = 1.36; 95% CI 0.71-2.60 Age; Ethnicity; Poverty; Education; Sexual abuse; Emotional abuse; Neglect Wickersham et al. (2016) Hit, slapped, punched, or kicked by adult before age of 18 OR = 2.83; 95% CI 1.19-6.73 NR NR 34 Study (Year) Exposure definition Unadjusted finding Adjusted finding Variables adjusted for Emotional abuse findings Abajobir et al. (2017) Notified cases of emotional deprivation or trauma up to 14 years of age Female OR = 4.69; 95% CI 2.13-10.39 Male OR = 3.09; 95% CI 1.34-7.15 Female AOR = 3.02; 95% CI 1.30-6.97 Male AOR = 2.51; 95% CI 1.05-5.98 Receiving social security benefits; Educational level; Marital status; Race; Maternal alcohol use; Maternal chronic depressive symptoms Kerr et al. (2009) Five questions from Childhood Trauma Questionnaire utilizing a five-point likert scale OR = 1.20; 95% CI 0.85-1.69 Not included in multivariable model NR Quinn et al. (2016) Caregiver said hurtful things or felt unloved 6 or more times before 18 years of age OR = 1.96; 95% CI 1.18-3.24 AOR = 1.53; 95% CI 0.81-2.87 Age; Ethnicity; Poverty; Education; Physical abuse; Sexual abuse; Neglect AHR = adjusted hazard ratio; AOR = adjusted odds ratio; CI = confidence interval; HR = hazard ratio; IDU = injection drug use; NR = not reported; OR = odds ratio; PWID = people who inject drugs. 35 CHAPTER 3. THE IMPACT OF CHILDHOOD EMOTIONAL ABUSE ON CHRONIC PAIN AMONG PEOPLE WHO INJECT DRUGS 3.1 INTRODUCTION Chronic pain, as described in Chapter 1, Section 1.3, is a significant contributor to poor quality of life and increased psychological distress. To date prescription opioids remain the most common form of medical therapy for severe acute pain. However, there are increasing concerns with long-term use of prescription opioids: primarily questions regarding their effectiveness/benefits (particularly over long-term use), concerns relating to side effects, and recently, a recognition that prescription opioids can contribute to substance use disorders and overdose-related mortality (110-112). These concerns, alongside the implementation of clinical practice guidelines in some jurisdictions (113), have contributed to uncertainty and reluctance in clinical practice to initiate or maintain opioid treatment regimens for patients presenting with chronic pain (114). As a result, people who inject drugs (PWID) are often forced to resort to self-medication for chronic pain, such as injecting illicitly acquired heroin or contraband prescription opioids (115). In light of the high proportion of chronic pain experienced by PWID, alongside the significant impacts of both pain and substance use disorders, clinicians and patients face complex challenges in terms of the provision of effective pain treatment options. Prior research has identified a significant positive association between both childhood physical and sexual abuse and the risk of chronic pain conditions in adulthood (32-34). However, only recently has research begun to explore the impact of childhood emotional abuse on pathologies among adults (71, 116). For example, a significant positive association has been 36 found between childhood emotional abuse and chronic pelvic pain among American adults (71), and between childhood emotional abuse and overall chronic pain among Indigenous and non-indigenous Norwegian adults (116). Potential pathways linking childhood emotional abuse and adult chronic pain likely involve psychological factors in addition to physiological impacts from emotional abuse, including negative impacts on brain development, over-activation of the hypothalamus-pituitary-adrenal axis, and negative impacts on the immune system (42, 117). To my knowledge, no studies have focused on the association between childhood emotional abuse and chronic pain among PWID. This is concerning, as PWID are known to have higher rates of both chronic pain and childhood emotional abuse compared with non-drug using populations. Further, inadequate pain control has been associated with subsequent substance use following withdrawal management among people with substance use disorders (118). In light of these serious concerns, and using data from long-running prospective cohorts of people who use drugs in Vancouver, the present study aims to evaluate the relationship between childhood emotional abuse and chronic pain among PWID in Vancouver, Canada. 3.2 METHODS 3.2.1 Study Procedures This study included participants from the VIDUS and ACCESS cohorts, which were described in detail in Chapter 1, Section 3. Participants were included in the present analysis if they reported ever injecting drugs and had completed at least one study visit between June 1, 2014 (the first follow-up period that included questions about chronic pain via the Brief Pain Inventory (119)) and November 30, 2016 (the most recent follow-up data available for the present analysis). 37 3.2.2 Study Variables The primary outcome variable of interest was reporting chronic pain in the previous six months (yes vs. no). Having chronic pain was defined as responding “Yes” to the question: “Throughout our lives, most of us have had pain from time to time. In the last 6 months, have you had any major or persistent pain (other than minor headaches, sprains, etc.)?” and subsequently responding either “4 to 6 months” or “Longer than 6 months” to the question: “How long have you experienced this pain? (For multiple pain types, check the longest pain duration to date.)” This measure of chronic pain is consistent with that of the International Association for the Study of Pain, which defines chronic pain as “pain that persists beyond normal tissue healing time, which is assumed to be three months” (120). The primary explanatory variable of interest was experiencing moderate to extreme emotional abuse during childhood, as measured during the baseline interview by the Childhood Trauma Questionnaire (CTQ). The CTQ is a 28-item validated instrument used to retrospectively assess three forms of childhood abuse (sexual, physical, and emotional abuse) and two forms of childhood neglect (physical and emotional neglect) (103). The CTQ provides a score for five subscales that correspond to each type of abuse and neglect, based on responses to five items. Using a five-point Likert scale from “never true” (1) to “very often true” (5), participants respond to statements such as “People in my family called me things like ‘stupid,’ ‘lazy,’ or ‘ugly’” (emotional abuse). All questions refer only to events that occurred during childhood. Each subscale produces scores ranging from 5 to 25. We used recommended and pre-determined cut-off scores to translate the emotional abuse subscale score into one of four levels of childhood trauma: none or minimal (5–8), low to moderate (9–12), moderate to severe (13–15), and severe to extreme (>15) (121). For this analysis, we chose to collapse these four 38 trauma levels into two: none/low and moderate/extreme, as has been done in previous studies (122). The reliability of validity of the CTQ has been demonstrated previously, and the instrument has been used successfully in several studies of illicit drug-using populations (19, 103, 123). Secondary explanatory variables were also considered that might confound the relationship between childhood emotional abuse and reporting recent chronic pain, based on previous research (33). These included socio-demographic characteristics, including: age (per year older); biological sex at birth (female vs. male); ancestry (white vs. non-white); homelessness in the previous six months, defined as having no fixed address, sleeping on the street, or staying in a shelter or hostel (yes vs. no); residing in the downtown eastside (DTES) in the previous six months (yes vs. no); and educational attainment (less than high school diploma vs. high school diploma or higher). Drug-use variables referred to behaviours in the previous six months, and included: ≥ daily heroin use (yes vs. no); ≥ daily prescription opioid non-medical use (yes vs. no); ≥ daily cocaine use (yes vs. no); ≥ daily crack cocaine use (yes vs. no); ≥ daily crystal methamphetamine use (yes vs. no); and heavy alcohol use, defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) as more than 3 drinks per day or more than 7 drinks per week for females and more than 4 drinks per day or more than 14 drinks per week for males (yes vs. no) (124). Other exposures included: childhood physical abuse (moderate/extreme vs. none/low); childhood sexual abuse (moderate/extreme vs. none/low); childhood physical neglect (moderate/extreme vs. none/low); childhood emotional neglect (moderate/extreme vs. none/low); ever diagnosed with mental health illness (yes vs. no); engagement in opioid agonist therapy in the previous six months (yes vs. no); and HIV serostatus (positive vs. negative). 39 3.2.3 Statistical Analysis As a first step, we examined the baseline sample characteristics stratified by chronic pain, using the Pearson’s Chi-squared test (for binary variables) and Wilcoxon Rank Sum test (for continuous variables). Fisher’s exact test was used when one or more of the cells contained expected values less than or equal to five. Since the analyses of reporting chronic pain included serial measures for each participant, we used generalized estimating equations (GEE) with logit link, which provided standard errors adjusted by multiple observations per person using an exchangeable correlation structure. We first used bivariable GEE analyses to examine the association between each explanatory variable and chronic pain. To examine the relationship between childhood emotional abuse and chronic pain, we fit multivariable GEE models using a conservative confounding model selection approach. We included all variables that were associated with chronic pain in unadjusted analyses at p < 0.10 in a full multivariable model, and used a stepwise approach to fit a series of reduced models. After comparing the value of the coefficient of childhood emotional abuse in each reduced model, we dropped the secondary variable associated with the smallest relative change. We continued this iterative process until the minimum change exceeded 5 %. We also quantified the severity of multicollinearity using the variance inflation factor (VIF). All p-values are two sided and tests were considered statistically significant at p <0.05. All statistical analyses were performed using R software version 3.2.4 (R Foundation for Statistical Computing, Vienna, Austria [2016]). 3.3 RESULTS In total, 1,459 participants were eligible for the present study. Among this sample, 518 (35.5%) were women, 820 (56.2%) self-reported white ancestry, and the median age at 40 baseline was 47.7 years (interquartile range [IQR] = 39.1–54.0). Overall, the 1,459 individuals contributed 5,428 observations to the analysis and the median number of follow-up visits was 4 (IQR: 3–5) per person. The baseline characteristics of all participants stratified by reporting chronic pain are presented in Table 3.1. As shown, among the 1,459 individuals included in the study, 591 (40.5%) reported moderate to extreme childhood emotional abuse and 760 (52.1%) reported chronic pain in the previous six months at baseline. In addition, the extent of overlap among those who reported childhood emotional abuse with additional maltreatment categories are presented in Table 3.2. Among the 591 participants who reported childhood emotional abuse, 418 (70.7%) also reported physical abuse, 328 (55.5%) also reported sexual abuse, 297 (50.3%) also reported physical neglect, and 450 (76.1%) also reported emotional neglect. The results of the bivariable and multivariable GEE analyses of reporting chronic pain are presented in Table 3.3. Childhood physical abuse was removed from the multivariable model due to collinearity with childhood emotional abuse. As shown, in the final multivariable model after adjusting for a range of potential confounders, experiencing childhood emotional abuse remained independently and positively associated with reporting chronic pain (adjusted odds ratio [AOR] = 1.25; 95% confidence interval [CI]: 1.01-1.53). 3.4 DISCUSSION There was a substantial prevalence (40.5%) of self-reported childhood emotional abuse (of moderate to extreme extent) among this sample of PWID in Vancouver, Canada. In addition, a high prevalence of chronic pain (52.1%) was observed at baseline. In a multivariable analysis, childhood emotional abuse remained independently and positively 41 associated with reporting adult chronic pain after adjusting for a range of potential confounders. The finding of a significant positive association between childhood emotional abuse and chronic pain is consistent with previous research documented in non-substance using populations (116, 125). This provides further evidence that childhood exposures might increase the likelihood of chronic pain in adulthood beyond what is already conferred through injection drug use. Given the detrimental impact of childhood emotional abuse on long-term health outcomes, effective early interventions are needed to address this ongoing problem. The information gained through the current study could be used to tailor and target support services for parents and children in safe and supportive non-judgemental ways. Known risk factors for emotional abuse include children whose parents have mental illness challenges, substance use disorders, are unemployed, and those younger than 22 years of age (17). The relationship between childhood emotional abuse and chronic pain persisted even after adjusting for other forms of childhood maltreatments such as sexual abuse, emotional neglect, and physical neglect, suggesting the profound impact of emotional abuse as indicated in previous research (9). Although we were unable to discern the effect of emotional abuse from that of physical abuse due to the collinearity, other research has shown that the vast majority of physical abuse cases in childhood also demonstrate signs of childhood emotional abuse (7). Due to this overlap, existing interventions aimed at addressing childhood physical abuse should also consider emphasizing novel responses to address concomitant childhood emotional abuse. Prior research has suggested some potential physiological and psychological pathways linking childhood emotional abuse and chronic pain during adulthood. Physiologically, 42 chronic stress from emotional abuse in childhood has been shown to impact brain development. For example, exposures to emotional forms of abuse during childhood have been found to over-activate the hypothalamus-pituitary-adrenal axis resulting in a sustained release of cortisol, leading to inappropriate and chronic activation of the inflammatory arm of the immune system (42, 43). In turn, the resulting increase of allostatic load, or increased wear and tear on the body, increases the risk of pain conditions (43). In addition, psychological development can be impaired by emotional abuse resulting in inappropriate emotional regulation and increased risk of depression and anxiety (35, 58). This can lead to utilizing inappropriate coping strategies for pain, including catastrophizing and activity avoidance, which are known contributors for acute pain becoming chronic (126). Importantly, the physiological and psychological maldevelopments are also shaped by broader social and structural forces. Adult survivors of childhood emotional abuse often have poor social networks limiting the ability to depend on others, which is known to be associated with increased stress and isolation, leading to physiological and mental health damages (35). Also, households with a low socioeconomic status and educational attainment have been associated with children experiencing maltreatment, challenges relating to others, and poor emotional control (68, 127, 128). These can result in low educational attainment for the children themselves, reducing employment opportunities and forcing individuals into low-paying and physically demanding positions, increasing risk of injury and stress (67). The physiological, psychological, and social vulnerabilities work together to increase not only the likelihood of pain occurring but also that pain becoming chronic. The further potential for childhood emotional abuse to also impact how individuals cope and respond to chronic pain will be explored in depth in the following chapter (Chapter Four). 43 Current clinical treatment approaches for chronic pain focus on the use of prescription opioids. While prescription opioids may be effective for a limited set of acute pain scenarios and cancer-related pain, there remains a lack of evidence to support their effectiveness for long-term treatment of chronic pain, except in the case of some cancers (129). Alternatives to prescription opioids include cognitive behavioural therapy, exercise, yoga, acupuncture, and massage therapy which have been shown to decrease chronic pain in patients (129, 130). In addition, previously identified pathways between childhood emotional abuse and chronic pain represent potential vulnerabilities that may be amenable to treatment. For example, interventions addressing psychosocial impacts, including improving emotion regulation, self-awareness, and social functioning, have demonstrated a promising first-step in ameliorating previous harms and an area for further research (131). Another approach involves tampering the overactive stress responses, through relaxation techniques and cognitive therapy (132). Further, utilizing multidisciplinary trauma-informed treatment approaches to chronic pain have demonstrated effectiveness in reducing chronic pain in patients (133). Addressing the chronic pain among populations of PWID is particularly essential, as pain is known to drive individuals to use riskier consumption methods and drug sources to obtain pain relief, including injecting illicit heroin (115). Reducing chronic pain may also be an effective intervention to address the increased risk of overdose and transmission of infectious agents resulting from self-management of pain through illicit opioid injection. This study has several limitations to note, which are shared with the following data-driven study (Chapter Four). First, the VIDUS and ACCESS cohorts are not random samples and therefore generalizability of the findings may be limited. Second, data used in the study were mostly based on self-report and thus could be subject to reporting bias, including socially 44 desirable responses. Although self-reported behavioural data has been shown to be largely accurate among adult drug-using populations (134), childhood emotional abuse in particular may date back a few decades, and therefore concerns with recall bias and socially desirable responding remain. Lastly, as with any observational research, unmeasured confounders may exist, although we sought to reduce this bias through adjustment of regression models using key predictors of chronic pain. As this was an observational study, we cannot infer causation between childhood emotional abuse and adult chronic pain. In summary, the present study observed high rates of experiencing childhood emotional abuse and chronic pain among adult PWID. It was also found that childhood emotional abuse remained independently associated with adult chronic pain after adjusting for other forms of childhood maltreatment and relevant socio-demographic and drug using confounders. These findings demonstrate the need to expand on interventions focusing on improving parenting to decrease child maltreatment as well as those aimed at children identified as exposed to emotional abuse to prevent future health impacts. Finally, these findings also emphasize the importance of adopting trauma-informed approaches to pain treatment among this population. 45 Table 3.1: Baseline sample characteristics, stratified by reporting chronic pain in the past six months among people who inject drugs in Vancouver, Canada (n = 1,459) Characteristic Reporting chronic pain * p - value Yes n (%) 760 (52.1) No n (%) 699 (47.9) Childhood emotional abuse 330 (43.4) 261 (37.3) 0.015 Childhood physical abuse 273 (35.9) 206 (29.5) 0.006 Childhood sexual abuse 239 (31.4) 190 (27.2) 0.046 Childhood physical neglect 226 (29.7) 189 (27.0) 0.181 Childhood emotional neglect 356 (46.8) 328 (46.9) 0.819 Age (median, IQR) 49 (42-54) 46 (38-53) <0.001 Female Sex 280 (36.8) 238 (34.0) 0.260 White 433 (57.0) 387 (55.4) 0.476 Homelessness* 143 (18.8) 138 (19.7) 0.662 DTES residency* 451 (59.3) 395 (56.5) 0.273 Low educational attainment 373 (49.1) 355 (50.8) 0.400 Daily heroin use*† 163 (21.4) 150 (21.5) 0.996 Daily prescription opioid use*† 57 (7.5) 22 (3.1) <0.001 Daily cocaine use*† 44 (5.8) 36 (5.2) 0.592 Daily crack cocaine use*† 102 (13.4) 91 (13.0) 0.829 Daily crystal methamphetamine use*† 98 (12.9) 87 (12.4) 0.797 Heavy alcohol use*† 111 (14.6) 112 (16.0) 0.465 Mental health diagnosis ever 517 (68.0) 422 (60.4) 0.002 Engaged in OAT treatment* 431 (56.7) 349 (49.9) 0.009 HIV positive 338 (44.5) 266 (38.1) 0.013 IQR: interquartile range; DTES: Downtown Eastside; OAT: opioid agonist therapy * Denotes activities in the previous six months † Refers to any route of consumption (i.e., sniffing, snorting, smoking or injecting) 46 Table 3.2: Extent of overlap with additional maltreatment categories among people who inject drugs who reported childhood emotional abuse in Vancouver, Canada (n = 591) Child maltreatment category Number of those who reported % of overlap Childhood Physical Abuse 418 70.7 Childhood Sexual Abuse 328 55.5 Childhood Physical Neglect 297 50.3 Childhood Emotional Neglect 450 76.1 47 Table 3.3: Bivariable and multivariable GEE analysis of reporting chronic pain among people who inject drugs in Vancouver, Canada (n = 1,459) Unadjusted Adjusted Characteristic Odds Ratio (95% CI) p - value Odds Ratio (95% CI) p - value Childhood emotional abuse (Moderate/extreme vs. none/low) 1.38 (1.16-1.63) <0.001 1.25 (1.01-1.53) 0.037 Childhood physical abuse (Moderate/extreme vs. none/low) 1.44 (1.21-1.72) <0.001 Childhood sexual abuse (Moderate/extreme vs. none/low) 1.32 (1.10-1.58) 0.002 1.18 (0.95-1.46) 0.127 Childhood physical neglect (Moderate/extreme vs. none/low) 1.25 (1.04-1.50) 0.017 1.09 (0.89-1.35) 0.388 Childhood emotional neglect (Moderate/extreme vs. none/low) 1.05 (0.89-1.24) 0.567 Age (per year older) 1.03 (1.02-1.04) <0.001 1.04 (1.03-1.05) <0.001 Sex (Female vs. male) 1.09 (0.92-1.29) 0.332 Ancestry (White vs. other) 1.12 (0.95-1.33) 0.166 Homelessness* (yes vs. no) 1.08 (0.92-1.27) 0.333 DTES residency* (yes vs. no) 1.10 (0.97-1.25) 0.143 Educational attainment (Less than high school vs. 0.94 (0.80-1.12) 0.503 High school diploma or higher) Daily heroin use*† (yes vs. no) 1.09 (0.94-1.26) 0.247 Daily prescription opioid use*† (yes vs. no) 1.49 (1.16-1.91) 0.002 Daily cocaine use*† (yes vs. no) 0.85 (0.66-1.11) 0.235 Daily crack cocaine use*† (yes vs. no) 1.07 (0.89-1.27) 0.473 Daily crystal methamphetamine use*† (yes vs. no) 0.90 (0.75-1.08) 0.269 Heavy alcohol use*† (yes vs. no) 0.94 (0.80-1.09) 0.415 48 Unadjusted Adjusted Characteristic Odds Ratio (95% CI) p - value Odds Ratio (95% CI) p - value Mental health diagnosis ever (yes vs. no) 1.49 (1.26-1.77) <0.001 1.50 (1.25-1.80) <0.001 Engaged in OAT* (yes vs. no) 1.19 (1.03-1.37) 0.020 1.26 (1.08-1.47) 0.003 HIV Serostatus (positive vs. negative) 1.29 (1.09-1.52) 0.003 GEE: generalized estimating equations; CI: confidence interval; DTES: Downtown Eastside; OAT: opioid agonist therapy * Denotes activities in the previous six months. † Refers to any route of consumption (i.e., sniffing, snorting, smoking or injecting). 49 CHAPTER 4. THE IMPACT OF CHILDHOOD EMOTIONAL ABUSE ON PAIN INTERFERENCE AMONG PEOPLE WITH CHRONIC PAIN WHO INJECT DRUGS 4.1 INTRODUCTION In addition to the potential for childhood emotional abuse to impact the occurrence of chronic pain, as investigated in the previous study (Chapter Three), there is also potential for childhood emotional abuse to impact how individuals respond, cope, and deal with chronic pain. Pain interference, or the extent to which chronic pain hinders daily activities such as walking, mood, social relationships, sleep, and enjoyment of life is an under-researched but essential measure to understand, due to its impact on a patients’ physical recovery and quality of life (135-137). Even among individuals with similar levels of pain intensity, there are often vast differences in the corresponding level of pain interference (138). There is also evidence suggesting initial decreases in pain interference following chronic pain treatment frequently occur independently of changes in pain intensity, suggesting a larger role for psychosocial factors in how pain is managed than originally thought (139, 140). Previously identified psychosocial factors known to be associated with reporting high levels of pain interference include catastrophizing, low self-efficacy for dealing with pain, low social support, psychiatric comorbidities, and fear of movement (139, 141). Additional risk factors include older age, female gender, smoking, and low educational attainment (141-145). Socially marginalized individuals, including people who inject drugs (PWID), commonly exhibit many of these risk factors for pain interference, leading to a concentration of harmful pain outcomes among this vulnerable sub-population. 50 While childhood emotional abuse has been associated with poor mental health status in adults, evidence of the direction of the relationship between mental health and pain interference has been mixed (146). Previous research has identified pain interference as increasing the likelihood of mental illness, especially depression and anxiety (147). However, there is now increasing evidence that mental illness increases pain interference (148-150). One explanation for these results could be a vicious cycle in which mental illness increases pain interference, which increases the severity of mental illness, further increasing pain interference (151). While mental illness has previously been identified as a factor connecting childhood abuse and pain interference, there are likely many other psychosocial factors involved, including maladaptive coping skills and decreased interpersonal skills (152, 153). Given the harmful impact of high levels of pain interference, examining the potential influence from childhood emotional abuse on pain interference is essential to designing interventions to improve quality of life. Further, identifying potential mediators can provide insight into early interventions before pain is able to interfere with daily life activities. To my knowledge, no studies have investigated the impact of childhood exposures on chronic pain interference among PWID. This is despite the fact that individuals with substance use disorders report higher rates of both childhood emotional abuse and chronic pain than the general population, and pain interference is known to inhibit substance use treatment initiation (154). Also, as current chronic pain treatment is usually inadequate in completely eliminating pain, identifying potential approaches reducing pain interference is of significance. Drawing on data from long-running prospective cohorts of people who use drugs in Vancouver, Canada, the present study sought to determine if experiencing childhood emotional 51 abuse was associated with an increased likelihood of reporting pain interference. In addition, to examine whether having a history of mental health disorder diagnosis may mediate this relationship. 4.2 METHODS 4.2.1 Study Procedures This study included participants from the VIDUS and ACCESS cohorts, which were described in detail in Chapter 1, Section 3. All VIDUS and ACCESS participants who completed at least one study visit questionnaire between June 1, 2014 and November 30, 2016, and reported ever injecting drugs preceding the baseline interview were included in the present analysis. Additionally, at each follow-up, the sample was restricted to individuals who reported chronic pain in the previous six months. Consistent with Chapter 3, Section 2.2 of this thesis, chronic pain was defined as pain lasting longer than 3 months and beyond normal tissue healing time. 4.2.2 Study Variables The primary outcome variable of interest was reporting moderate to severe pain interference in the previous six months, as measured by the Brief Pain Inventory – Pain Interference subscale. The validated 6-item subscale measures the level at which pain has interfered with general activity, walking, mood, enjoyment of life, relations with other people, and sleep during the past 24 hours, using numeric scales (pain does not interfere = 0 to pain completely interferes = 10) (155). The item on the subscale referring to normal work interference was removed due to the majority of study participant’s lack of employment. We used recommended and pre-determined mean cut-off scores to translate the pain interference subscale score into one of four levels of pain interference: none or minimal (0.0), low (0.1 – 52 3.9), moderate (4.0 – 5.9), and severe (6.0 – 10.0) (156). For this analysis, we chose to collapse these four pain interference levels into two: none/low and moderate/severe. The primary explanatory variable of interest was moderate to extreme emotional abuse during childhood, measured exactly the same as previously described in Chapter 3, section 2.2. Secondary explanatory variables that might confound the relationship between childhood emotional abuse and adult pain interference were also considered, based on previous research (136, 156, 157). These included socio-demographic characteristics, including: age (per year older); biological sex at birth (female vs. male); ancestry (white vs. non-white); homelessness in the previous six months, defined as having no fixed address, sleeping on the street, or staying in a shelter or hostel (yes vs. no); and educational attainment (less than High school diploma vs. High school diploma or higher). Drug-use variables referred to behaviours in the previous six months, and included: ≥ daily heroin use (yes vs. no); ≥ daily prescription opioid use (yes vs. no); ≥ daily cocaine use (yes vs. no); ≥ daily crack cocaine use (yes vs. no); ≥ daily crystal methamphetamine use (yes vs. no); and heavy alcohol use, defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) as more than 3 drinks per day or more than 7 drinks per week for females and more than 4 drinks per day or more than 14 drinks per week for males (yes vs. no) (124). Other exposures included: childhood physical abuse (moderate/extreme vs. none/low); childhood sexual abuse (moderate/extreme vs. none/low); childhood physical neglect (moderate/extreme vs. none/low); childhood emotional neglect (moderate/extreme vs. none/low); engagement in opioid agonist therapy (yes vs. no); and HIV serostatus (positive vs. negative). 4.2.3 Statistical Analysis 53 Initially, the baseline sample characteristics stratified by the dichotomized pain interference, using the Pearson’s Chi-squared test (for binary variables) and Wilcoxon Rank Sum test (for continuous variables) were examined. Fisher’s exact test was used when one or more of the cells contained expected values less than or equal to five. Since the analysis of pain interference included serial measures for each participant, we used generalized estimating equations (GEE) with logit link, which provided standard errors adjusted by multiple observations per person using an exchangeable correlation structure. We first used bivariable GEE analyses to examine the association between each explanatory variable and reporting moderate to severe pain interference. To examine the relationship between emotional abuse and pain interference, we fit multivariable GEE models using a conservative confounding model selection approach. We included all variables that were associated with reporting moderate to severe pain interference in unadjusted analyses at p < 0.10 in a full multivariable model, and used a stepwise approach to fit a series of reduced models. After comparing the value of the coefficient of emotional abuse in each reduced model, we dropped the secondary variable associated with the smallest relative change. We continued this iterative process until the minimum change exceeded 5 %. We also quantified the severity of multicollinearity using the variance inflation factor (VIF). Subsequently, methods developed to explore whether the association of interest was mediated by ever being diagnosed with a mental health disorder (yes vs. no) were implemented (158). Because the values of the mediator variable did not change throughout the study period, conducting a cross-sectional mediation analysis was deemed appropriate. As such, the outcome measure of pain interference was transformed into rounded frequencies. Therefore, if an individual reported “moderate/severe” to pain interference for 3 or more of the 5 follow-ups 54 they were classified as overall “moderate/severe” to pain interference, while someone who reported “moderate/severe” to pain interference at 2 or less of the 5 follow-ups would be classified as overall “none/low” to pain interference. Parameters of interest included: the Average Casual Mediation Effect (ACME), defined as the average mediated effect between the predictor (childhood emotional abuse) and the outcome via mediator (mental health disorder diagnosis); the Average Direct Effect (ADE), defined as the average direct effect of the predictor on the outcome; the Total Effect (TE), which was the entire effect the predictor had on the outcome (i.e., ACME + ADE); and the Proportion Mediated (PM), which was the proportion of the causal effect of independent variable that was mediated by the mediator (i.e., ACME / TE). Averaged effects were calculated over 50 iterations. All p-values are two sided and tests were considered statistically significant at p<0.05. All statistical analyses were performed using R software version 3.2.4 (R Foundation for Statistical Computing, Vienna, Austria [2016]), with the R Mediation Package used to perform the mediation analysis (159). 4.3 RESULTS In total, 822 participants were eligible for the present study. Among this sample, 280 (34.1%) were women, 479 (58.3%) self-reported white ancestry and the median age at baseline was 49.8 years (IQR = 43.3–55.3). Overall, the 822 individuals contributed 2363 observations to the analysis and the median number of follow-up visits was 3 (IQR: 1-4) per person. The baseline characteristics of all participants stratified by reporting moderate to severe pain interference are presented in Table 4.1. As shown, among the 822 individuals included in the study 341 (41.5%) reported moderate to extreme childhood emotional abuse and 600 (74.8%) reported moderate to severe pain interference in the previous six months at baseline. 55 The results of the bivariable and multivariable GEE analyses of reporting moderate to severe pain interference are presented in Table 4.2. The four other childhood trauma variables (childhood physical abuse, childhood sexual abuse, childhood emotional neglect, and childhood physical neglect) were removed from the multivariable model due to the collinearity with childhood emotional abuse. As shown, in the final multivariable model after adjusting for a range of potential confounders, experiencing childhood emotional abuse remained independently and positively associated with reporting moderate to severe pain interference (AOR = 1.33; 95% CI: 1.05-1.70). In total, 539 (65.6%) participants reported a history of mental health disorder diagnosis with the most common diagnosis being depression reported by 425 (78.8%) participants, followed by anxiety reported by 247 (45.8%), and post-traumatic stress disorder reported by 109 (20.2%) participants. Mediation analysis yielded a statistically significant ACME (β = 0.01; 95% [CI]: 0.001-0.02), ADE (β = 0.08; 95% [CI]: 0.01-0.13) and TE (β = 0.09; 95% [CI]: 0.02-0.14), suggesting that for participants who experienced childhood emotional abuse, having a history of mental health disorder diagnosis resulted in a higher likelihood of reporting moderate to severe pain interference, as compared to those who were not emotionally abused. Approximately 12% of the effect was attributable to mediation. 4.4 DISCUSSION This study demonstrates that among PWID with chronic pain there are high rates of moderate to extreme childhood emotional abuse (41.5%) and moderate to severe pain interference (74.8%) at baseline. In the multivariable analysis, childhood emotional abuse was independently and positively associated with reporting moderate to severe adult pain 56 interference. In addition, these findings suggest that a history of mental health disorder diagnosis mediated this relationship. The analysis revealed a significant positive relationship between reporting childhood emotional abuse and experiencing current pain interference. Furthermore, like another study, this study found evidence to show that emotional abuse can result in a decreased ability to manage chronic pain effectively (157). Given the potential for childhood emotional abuse to increase not only the risk of chronic pain, as demonstrated in the previous chapter (Chapter Three), but also chronic pain interference, effective early interventions are needed to address this problem. This could take the form of programs aimed at preventing childhood abuse by providing parents with supportive parenting environments or intervening shortly after abuse has been documented to ameliorate or reverse risks of the long-term damage (160, 161). These results also suggest a previous mental health disorder diagnosis is a significant mediator in the relationship between childhood emotional abuse and pain interference, a finding previously noted on other studies (148, 149, 162, 163). There is some evidence to suggest that this relationship may be linked with biological pathways (e.g., neurotransmitters serotonin and norepinephrine) (148, 164, 165). Other work implies that psychosocial and behavioural factors are involved (e.g., reduced the likelihood of exercise and increased likelihood of bed rest, both of which are important to modify to improve recovery and decrease pain disability). There also may be connections with increased sleep disturbance, which has been associated with increased pain severity, sensitivity to pain, and pain interference (164). Finally, depression also has been shown to affect cognitive processes, including information processing, potentially leading to a higher likelihood of anticipating pain and over-estimating previous pain (165). This finding underscores the importance of concurrently treating mental 57 health disorders and chronic pain, which may also have the potential to address dangerous drug consumption methods and overdose risks for PWID, as pain is known to be a factor in illicit drug use. Further, promising results indicate treatment for depression, either pharmacotherapy or psychotherapy, reduces overall pain disability and interference among arthritic patients (166). In addition to mental illness acting as a mediator, there are various other potential pathways connecting childhood emotional abuse and pain interference, including maladaptive coping skills and decreased social relationships. Coping strategies for chronic pain can generally be classified as either adaptive or maladaptive. Adaptive strategies, including self-efficacy in coping and ignoring pain, help decrease negative pain outcomes, while maladaptive strategies, including catastrophizing, over-reliance on medications, and activity avoidance, increase negative outcomes (167). Emotional abuse has been associated with over-utilizing maladaptive pain coping techniques and under-utilizing adaptive ones, thus increasing the likelihood of reporting pain interference (139, 153, 164, 168). Finally, childhood emotional abuse impacts interpersonal relationships, leading to a decreased ability to develop and maintain relationships, and has been identified as an important factor in the experience of pain interference (152). Addressing pain interference through effective psychosocial treatments, such as improving emotional awareness, improving perceived control over pain, and reducing catastrophizing represent opportunities to improve quality of life and functioning (169, 170). Increased access to these effective programs is desperately needed, especially among marginalized populations, including PWID, as they are known to disproportionately experience the most negative pain outcomes. 58 The inability to adjust for other child maltreatment categories, including physical abuse, sexual abuse, physical neglect, and emotional neglect, is likely explained by the large overlap frequently demonstrated between maltreatment types. Emotional abuse does occur independent of other maltreatment types; however, the majority of emotional abuse cases demonstrate signs of other maltreatment exposures (7). Therefore, to reduce the occurrence of emotional abuse, interventions should address overall childhood abuse risk factors. In addition to the shared limitations with the previous data-driven chapter discussed in Chapter 3, Section 4, this study has several additional limitations to note. Due to issues related to collinearity, there was an unable to adjust for other trauma and neglect variables, and the exposure measure of childhood emotional abuse may be indicative of overall childhood trauma. The true prevalence of the mental health disorder variable may also be underestimated as it only captured participants with a diagnosis and was not able to account for participants with mental health concerns who did not access clinics or ever receive a diagnosis; additionally the variable only measured lifetime diagnosis and not current mental illness. In summary, high rates of experiencing childhood emotional abuse and pain interference were observed among this sample of PWID with chronic pain. It was also found that childhood emotional abuse remained independently associated with adult moderate to severe pain interference after adjusting for relevant socio-demographic and behavioural confounders. Further, having history of a mental health disorder diagnosis was found to mediate this relationship. These findings demonstrate the need to ensure PWID with chronic pain are provided with appropriate mental health treatment if needed, in order to reduce pain interference and potentially substance use. Finally, it highlights the potential for psychosocial interventions, including improving coping skills and interpersonal skills, to decrease pain 59 interference and improve quality of life for chronic pain patients who report childhood emotional abuse. 60 Table 4.1: Baseline sample characteristics, stratified by reporting moderate to severe pain interference in the past six months among people who inject drugs with chronic pain in Vancouver, Canada (n = 822) Characteristic Reporting pain interference * p - value Moderate/severe n (%) 600 (74.8) None/low n (%) 222 (25.2) Childhood emotional abuse 267 (44.5) 74 (33.3) 0.003 Childhood physical abuse 225 (37.5) 64 (28.8) 0.013 Childhood sexual abuse 204 (34.0) 53 (23.9) 0.004 Childhood physical neglect 197 (32.8) 53 (23.9) 0.007 Childhood emotional neglect 299 (49.8) 97 (43.7) 0.127 Age (median, IQR) 50 (44-55) 51 (44-56) 0.163 Female Sex 222 (37.0) 58 (26.1) 0.003 White 342 (57.0) 137 (61.7) 0.217 Homelessness* 83 (13.8) 29 (13.1) 0.769 Low educational attainment 313 (52.2) 108 (48.6) 0.324 Daily heroin use*† 132 (22.0) 32 (14.4) 0.016 Daily prescription opioid use*† 42 (7.0) 13 (5.9) 0.560 Daily cocaine use*† 32 (5.3) 12 (5.4) 0.968 Daily crack cocaine use*† 79 (13.2) 26 (11.7) 0.579 Daily crystal methamphetamine use*† 71 (11.8) 17 (7.7) 0.086 Heavy alcohol use*† 94 (15.7) 36 (16.2) 0.863 Engaged in OAT treatment* 335 (55.8) 120 (54.1) 0.632 HIV positive 281 (46.8) 89 (40.1) 0.085 IQR: interquartile range; OAT: opioid agonist therapy * Denotes activities in the previous six months. † Refers to any route of consumption (i.e., sniffing, snorting, smoking or injecting) 61 Table 4.2: Bivariable and multivariable GEE analysis of reporting moderate to severe pain interference among people who inject drugs with chronic pain in Vancouver, Canada (n = 822) Unadjusted Adjusted Characteristic Odds Ratio (95% CI) p - value Odds Ratio (95% CI) p - value Childhood emotional abuse (Moderate/extreme vs. none/low) 1.49 (1.18-1.88) <0.001 1.33 (1.05-1.70) 0.020 Childhood physical abuse (Moderate/extreme vs. none/low) 1.46 (1.15-1.85) 0.002 Childhood sexual abuse (Moderate/extreme vs. none/low) 1.52 (1.19-1.94) <0.001 Childhood physical neglect (Moderate/extreme vs. none/low) 1.59 (1.24-2.03) <0.001 Childhood emotional neglect (Moderate/extreme vs. none/low) 1.51 (1.19-1.91) <0.001 Age (per year older) 0.99 (0.98-1.00) 0.104 Sex (Female vs. male) 1.71 (1.30-2.19) <0.001 1.62 (1.24-2.11) <0.001 Ethnicity (White vs. other) 0.91 (0.72-1.14) 0.398 Homelessness* (yes vs. no) 1.45 (1.06-1.97) 0.019 Educational attainment (Less than high school vs. 1.25 (1.00-1.56) 0.053 High school diploma or higher) Daily heroin use*† (yes vs. no) 1.62 (1.26-2.08) <0.001 Daily prescription opioid use*† (yes vs. no) 1.43 (1.02-2.00) 0.036 Daily cocaine use*† (yes vs. no) 1.00 (0.62-1.59) 0.984 Daily crack cocaine use*† (yes vs. no) 1.22 (0.90-1.66) 0.192 Daily crystal methamphetamine use*† (yes vs. no) 1.42 (1.04-1.95) 0.028 Heavy alcohol use*† 62 Unadjusted Adjusted Characteristic Odds Ratio (95% CI) p - value Odds Ratio (95% CI) p - value (yes vs. no) 1.03 (0.79-1.36) 0.807 Engaged in OAT* (yes vs. no) 1.15 (0.94-1.42) 0.179 HIV positive (yes vs. no) 1.19 (0.95-1.49) 0.127 GEE: generalized estimating equations; CI: confidence interval; OAT: opioid agonist therapy * Denotes activities in the previous six months. † Refers to any route of consumption (i.e., sniffing, snorting, smoking or injecting). 63 CHAPTER 5. SUMMARY OF FINDINGS AND FUTURE DIRECTIONS 5.1 SUMMARY OF FINDINGS Childhood emotional abuse has historically been under-researched, but an emergent body of evidence points to its detrimental impact on adult health. As such, I undertook my thesis research to empirically examine potential connections between childhood emotional abuse, injection drug use, and chronic pain. I began with a review of existing research (Chapter Two) on the impact of childhood abuse on the risk of injection drug use, which informed my empirical investigation of the relationship between childhood emotional abuse and chronic pain among PWID (Chapter Three), as well as the relationship between childhood emotional abuse and pain interference among PWID with chronic pain (Chapter Four). Chapter Two summarized the evidence for the impact of childhood abuse on adult injection drug use through systematically searching high-quality original quantitative reports. Through data extraction conducted on the 17 included studies, several trends were outlined: the majority of the research conducted has investigated the impact of sexual abuse, compared with physical or emotional abuse; there is strong evidence for physical abuse increasing the risk of injection drug use; and research indicates there is likely an increased risk from sexual and emotional abuse on injection drug use, although current evidence is mixed, potentially due to vast differences in how researchers measured childhood sexual and/or emotional abuse. Chapter Three aimed to examine the potential impact of childhood emotional abuse on chronic pain among the VIDUS and ACCESS cohort participants. The multivariable GEE analysis revealed that those who experienced childhood emotional abuse had an increased likelihood of reporting chronic pain in the past six months, after adjusting for relevant socio- 64 demographic, drug-use, health related, and other childhood abuse confounders. These results aligned with previous analyses conducted within the general population, which identified an increased risk of chronic pain among those who experienced childhood sexual and physical abuse. Chapter Four aimed to explore the relationship between childhood emotional abuse and pain interference among PWID who reported chronic pain in the past six months. In addition, the potential for a history of mental health disorder diagnosis to mediate this relationship was examined. For this analysis, a model adjustment for other types of childhood abuse was not possible due to collinearity with childhood emotional abuse. The multivariable GEE analysis revealed that those who experienced childhood emotional abuse had an increased likelihood of reporting moderate to severe pain interference after adjusting for relevant socio-demographic, drug-use, and health related confounders. Further, it was found that approximately 12% of the effect was due to mediation from a history of mental health disorder diagnosis. 5.2 STUDY STRENGTHS AND SIGNIFICANT CONTRIBUTIONS My thesis has several strengths and significant contributions. First, as indicated in Chapter Two the majority of research investigating the long-term impacts of childhood abuse has focused on sexual abuse, with many not including a multivariable analysis and the majority relying on cross-sectional study designs. The ability to draw upon multiple years of rich longitudinal data from the VIDUS and ACCESS cohorts for Chapters Three and Four is a unique and specific strength of this thesis. Analysing 2.5 years of data served to ensure the precision of the study results as evidenced by the extensive model adjustments with a range of potential confounders. Second, the addition of a second reviewer in Chapter Two who 65 independently screened the full-text articles and reviewed the accuracy of extracted data measures was paramount to ensure a high level of confidence in the inclusion of all relevant research studies. Third, studying the impacts of childhood abuse is critical, however, populations of PWID have been largely excluded from research in this area. The findings of the current thesis contribute to a growing body of evidence pertaining to the specific needs of PWID. The importance of understanding the needs of PWID cannot be overstated – PWID not only experience higher rates of childhood emotional abuse compared with the general population, but also disproportionately experience worse health outcomes due to complex social-structural vulnerabilities, stigma, and reduced availability of health services. While injection drug use is well known to be associated with a range of health harms, the literature on the association with childhood abuse had yet to be systematically reviewed. I addressed this gap by conducting the systematic review. Chronic pain and related outcomes among this population is a further concern, as inadequate pain control is known to contribute to riskier drug use. By focusing Chapters Three and Four on populations of PWID important relationships were identified between childhood abuse and chronic pain. Fourth, the focus on childhood emotional abuse addresses the identified lack of studies investigating the long-term impacts of this abuse form. Chapter Three is one of the only empirical studies to identify links with childhood emotional abuse and reporting adult chronic pain. It is also, to my knowledge, the only study to investigate this relationship among PWID. Also, I believe Chapter Four is the first study to investigate potential relationships between childhood emotional abuse and pain interference, among PWID with chronic pain. Given the complexity of treating chronic pain, these findings indicate potential alternative approaches to 66 prevent and appropriately treat chronic pain and provide a foundation to build future research upon. 5.3 IMPLICATIONS FOR POLICY AND PRACTICE Identifying early-life experiences that contribute to an increased risk of injection initiation opens up an important avenue for prevention programs. To date, the majority of prevention programs have focused on preventing PWID from assisting in injection initiation for naïve participants (171, 172). While these are essential, they are unable to prevent injection naïve individuals from seeking out injection assistance. Multiple social influences impacting injection initiation have been identified, which provide insight into earlier prevention approaches. Having a strong supportive social network is one identified deterrent to injection initiation (173, 174). As childhood abuse is often associated with weakened social ties, one such approach to increase resiliency among abuse survivors is to facilitate peer support programs for those impacted to increase levels of social support (173). The high prevalence of childhood emotional abuse, identified in this thesis, signifies the continued urgent need to reduce rates of abuse. Household caregivers are the primary perpetrators of childhood emotional abuse, followed by non-household authority figures (e.g. teachers and sport coaches), as such these two groups are the focus for the ongoing prevention programs (1-3, 175). While some household risk factors for childhood abuse have been identified (e.g. parental substance use disorders and parental unemployment), the reality is that abuse can occur in any family, as such providing universally available programs supporting families beginning at their first prenatal appointment can aid in preventing emotional abuse from occurring (17, 176). In addition, for vulnerable families in need of additional help, targeted programs providing parents with a safe and supportive non-judgmental environment 67 to obtain parenting advice are desperately needed, such as the use of home nurse visitation programs beginning in pregnancy (160, 176). Further, increasing funding for programs targeting children known to be at a high risk for emotional abuse, including mentorship programs, are essential and likely cost-effective given the long-term health costs of chronic illnesses (161). Meanwhile, a complementary and potentially more impactful approach is to move beyond focusing on individuals and address the broader social factors that contribute to the high rates of childhood abuse, including income inequity, unstable employment options, and the lack of affordable permanent housing (177, 178). Large-scale broad policy changes are needed to address these contextual factors appropriately. Finally, non-household authority figures are also common perpetrators of childhood emotional abuse and should be targeted for abuse prevention. Introducing age appropriate personal rights and safety training in classrooms to increase children’s ability to recognize abuse and to increase disclosure of inappropriate behaviour to a trusted adult, in conjuncture with implementing standardized stress management training for educational professionals working with children are needed (175, 179-181). However, clear mechanisms for children reporting abuse is required for these to be effective. Within athletic organizations ensuring recommended safeguarding policies have been implemented and followed is essential for widespread abuse reduction (182, 183). These safeguarding policies include ensuring children are aware of their personal rights, minimizing risk through assessing space/staffing requirements, training for staff to recognize signs of abuse, clear boundaries when travelling for competitions, and having a clear protocol when responding to allegations of abuse (182). This thesis also adds to the body of research investigating early life experiences that may increase the risk of adult chronic pain and pain interference, and points to the complexity 68 of treating chronic pain. Undeniably, health professionals would benefit from more training regarding the importance of assessing life-course vulnerabilities that may impact treatment effectiveness, and much more needs to be done to provide them with appropriate support and resources to implement trauma-informed approaches to pain management. It is imperative that treatment approaches consider potential childhood influences on the experience of pain. There is also a significant lack of funding and support for approaches that are known to decrease the occurrence and negative outcomes of chronic pain including counselling, yoga, acupuncture, and massage therapy, in addition to trauma-informed care. Providing individuals with alternative approaches to prevent and cope with chronic pain is an important avenue for improvements in overall quality of life and mental wellbeing. 5.4 DIRECTIONS FOR FUTURE RESEARCH Research in this thesis sheds light on the complex relationships between childhood emotional abuse, injection drug use, and chronic pain. While an important gap was addressed through the systematic review in Chapter Two, areas for future research were identified. Specifically, the need for the increased use of prospective cohort studies identifying long-term impacts of childhood abuse, as well as the need to identify the most damaging aspects of childhood abuse, so as to improve existing interventions. The prevention of childhood abuse remains paramount. However, it will be difficult to develop and implement appropriate supports without accurate and reliable methods for identifying children who are most in need of supports. However, the notion of screening tools should be pursued with caution in light of the potential pitfalls and challenges (e.g., exacerbation of stigma) associated with conventional use of screening tools. While a lack of appropriate screening for adverse childhood experiences has been identified as a pressing need 69 by some (184, 185), much more work needs to be done to ensure that their use does not unintentionally result in exacerbation of stigma and stereotypes amongst an already highly marginalized population. In addition to ensuring that the principles and practices associated with Wilcox’s framework are addressed, any ‘screening approach’ would also need to be evaluated from a population health ethics perspective, ensuring that individual rights and freedoms are respected (186, 187). Further research may lead to the development of valid and helpful tools and approaches (e.g., a screening tool) to assist with targeting and tailoring interventions. As PWID exhibit markedly higher rates of chronic pain and pain interference than the general population, more research is also needed on effective chronic pain treatments among this population. Further, as every individual experiences childhood abuse differently, creating tailored individual approaches is necessary for the most effective health improvements. Future research may also explore the cost savings of providing increased access to approaches that are known to decrease the occurrence and negative outcomes of chronic pain, such as trauma-informed care, as a further incentive for policymakers. Finally, as inadequate pain treatment is known to contribute to individual’s use of riskier drugs and consumption methods, the potential to partially address the current overdose crisis through addressing and reducing pain concerns among PWID should be further explored (115). 5.5 CONCLUSIONS While the understanding of the impact of childhood abuse exposures on adult health outcomes has recently increased, the impacts of emotional abuse remain less explored, especially among marginalized populations, including PWID. My thesis found: that there is strong evidence for childhood physical abuse increasing the risk of adult injection drug use, 70 with mixed results for sexual and emotional abuse; that experiencing childhood emotional abuse was significantly and positively associated with experiencing chronic pain during adulthood among PWID after adjusting for relevant confounders; and that childhood emotional abuse remained significantly and positively associated with pain interference among PWID with chronic pain after adjusting for relevant confounders, with a history of mental illness diagnosis partially mediating this association. These results further strengthen the rationale for expanding trauma-informed care approaches for chronic pain management and for preventing and ameliorating the impacts of mental illness. Going forward, it is crucial that health professionals and policy makers consider the potential impact of childhood abuse on adult health. For this to occur, it is critical for clinicians to receive additional training on utilizing trauma-informed care approaches for their patients. This may be especially important for chronic pain among PWID, given the high rates of both emotional abuse and chronic pain among this marginalized population. Finally, the continued high rates of childhood abuse signify the urgent need to optimize a variety of abuse prevention approaches, including universally available programs for all families, targeted programs for families in need of additional support, and implementing safeguarding recommendations for professions working with children. 71 REFERENCES 1. Norman RE, Byambaa M, De R, Butchart A, Scott J, Vos T. The long-term health consequences of child physical abuse, emotional abuse, and neglect: a systematic review and meta-analysis. PLoS Med. 2012;9(11):e1001349. 2. Kairys SW, Johnson CF. The psychological maltreatment of children--technical report. Pediatrics. 2002;109(4):e68. 3. 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(2017) Yes Yes Yes Yes Yes No Yes Yes Quinn et al. (2016) Yes Yes Yes No Yes No Yes No Roy et al. (2011) No Yes Yes Yes Yes No Yes No Cross-sectional study design Author (Year) Selection Comparability Outcome Representative Respondents and non-respondents analysis Validated exposure tool Comparability Outcome assessment Statistical test is appropriate Bartholow et al. (1994) No Yes No No No Yes Holmes (1997) No No No Yes No Yes Holmes (2010) Yes No No No No Yes 97 Author (Year) Selection Comparability Outcome Representative Respondents and non-respondents analysis Validated exposure tool Comparability Outcome assessment Statistical test is appropriate Ibanez et al. (2005) No No No No No Yes Kerr et al. (2009) No No Yes Yes No Yes Marotta (2017) Yes No No Yes No Yes Mullings et al. (2000) Yes No No No No Yes Schwartz et al. (2014) No No No Yes No Yes Stevens et al. (1995) No No No No No Yes Tomori et al. (2016) Yes No No No No Yes Wickersham et al. (2016) No No No No No Yes Zierler et al. (1991) No No No No No Yes
Thesis/Dissertation
Downtown-Eastside (Vancouver, B.C.)
eng
Population and Public Health
Vancouver : University of British Columbia Library
Attribution-NonCommercial-NoDerivatives 4.0 International
Graduate
Childhood emotional abuse : relationships with injection drug use and chronic pain
Text