Evaluating social support and health outcomes in diabetes: Associations in community-based. samples. Melanie Levy. Department of Psychiatry

Transcription

1 1 Evaluating social support and health outcomes in diabetes: Associations in community-based samples Melanie Levy Department of Psychiatry McGill University, Montreal June 2017 A thesis submitted to McGill University in partial fulfillment of the requirements of the degree of Masters of Science in Psychiatry Melanie Levy, 2017

2 2 Table of Contents ABSTRACT... 4 ABRÉGÉ... 6 ACKNOWLEDGEMENTS... 8 PREFACE AND CONTRIBUTION OF AUTHORS... 9 CHAPTER 1: INTRODUCTION RATIONALE OBJECTIVES CHAPTER 2: REVIEW OF THE LITERATURE DIABETES DEFINITION OF DIABETES DIABETES TREATMENT AND COMPLICATIONS MODIFIABLE RISK FACTORS FOR TYPE 2 DIABETES NON-MODIFIABLE RISK FACTORS FOR TYPE 2 DIABETES DIABETES AND FUNCTIONAL DISABILITY MENTAL DISORDERS: DEPRESSION AND ANXIETY DEFINITION OF DEPRESSION MEASURES OF DEPRESSION DEPRESSION IN PEOPLE WITH DIABETES DEFINITION OF ANXIETY ANXIETY IN PEOPLE WITH DIABETES IMPLICATIONS OF MENTAL DISORDERS FOR FUNCTIONAL DISABILITY SOCIAL SUPPORT DEFINITION OF SOCIAL SUPPORT MEASURES OF SOCIAL SUPPORT PERCEIVED SOCIAL SUPPORT IN PEOPLE WITH DIABETES TRAJECTORIES OF PERCEIVED SOCIAL SUPPORT PERCEIVED SOCIAL SUPPORT AND MENTAL DISORDERS IMPLICATIONS OF PERCEIVED SOCIAL SUPPORT FOR FUNCTIONAL DISABILITY ADDRESSING KNOWLEDGE GAPS IN THE LITERATURE CHAPTER 3: MANUSCRIPT 1, AS PUBLISHED IN PSYCHOSOMATICS ABSTRACT INTRODUCTION METHODS RESULTS... 39

3 3 DISCUSSION REFERENCES TABLE 1. DEMOGRAPHIC CHARACTERISTICS OF ADULTS WITH DIABETES BY MENTAL DISORDER (N = 1,764) TABLE 2. INTERACTION BETWEEN MDD AND SOCIAL SUPPORT ON FUNCTIONAL DISABILITY TABLE 3. INTERACTION BETWEEN GAD AND SOCIAL SUPPORT ON FUNCTIONAL DISABILITY APPENDIX A TABLE A. 1. INTERACTION BETWEEN MDD AND SOCIAL SUPPORT CATEGORIES ON FUNCTIONAL DISABILITY TABLE A.2. INTERACTION BETWEEN GAD AND SOCIAL SUPPORT CATEGORIES ON FUNCTIONAL DISABILITY APPENDIX B FIGURE B.1. PARTICIPANT FLOW DIAGRAM FOR THE 2012 CCHS-MH STUDY CHAPTER 4: BRIDGE BETWEEN MANUSCRIPTS CHAPTER 5: STUDY 2, IN PREPARATION TO BE SUBMITTED TO JOURNAL OF PSYCHOSOMATIC RESEARCH HIGHLIGHTS ABSTRACT INTRODUCTION METHODS FIGURE 1. PARTICIPANT FLOW DIAGRAM FOR THE EVALUATION OF DIABETES TREATMENT STUDY RESULTS TABLE 1. MODEL FIT STATISTICS FIGURE 2. LATENT TRAJECTORIES OF SOCIAL SUPPORT OVER 4 YEARS (N = 1,077) TABLE 2. SAMPLE CHARACTERISTICS BY LATENT TRAJECTORY OF SOCIAL SUPPORT (N = 1,077) TABLE 3. DEPRESSIVE SYMPTOMS AND FUNCTIONAL DISABILITY AT FINAL ASSESSMENT BY SOCIAL SUPPORT TRAJECTORY GROUP (N = 788) DISCUSSION REFERENCES CHAPTER 6: DISCUSSION RESTATEMENT OF OBJECTIVES AND SUMMARY OF FINDINGS CLINICAL IMPLICATIONS OF FINDINGS DIRECTIONS FOR FUTURE RESEARCH STRENGTHS AND LIMITATIONS CONCLUSION CHAPTER 7: REFERENCES... 99

4 4 Abstract Background: Diabetes is a severe chronic metabolic disorder. Adults with diabetes are more likely to have comorbid major depressive disorder (MDD) or generalized anxiety disorder (GAD) relative to the general population. Diabetes, MDD, and GAD are each related to increased functional disability, and may be particularly detrimental to functioning when individuals present with comorbidities. Social support has been proposed to buffer against the detrimental effects of both diabetes and these mental disorders on functioning. However, perceived social support has not been examined as a moderator of the relation between MDD and GAD and functional disability in adults with diabetes. Additionally, there is a dearth of studies examining longitudinal patterns of perceived social support in community-based sample of adults with type 2 diabetes (T2D). Aims: The aims of this thesis are: 1) to examine whether social support moderates the association between MDD, GAD, and functional disability in adults with diabetes; 2) to identify temporal trajectories of perceived social support in adults with T2D; and 3) to examine differences in depressive symptoms and functional disability across different social support trajectories. Methods: This thesis includes two manuscripts. The first study used data from the crosssectional 2012 Canadian Community Health Survey-Mental Health. The sample was restricted to adult participants with diabetes (n=1,764). Separate linear regression analyses were conducted to examine perceived social support as a moderator of the association between MDD or GAD and functional disability. Models were adjusted for demographic characteristics. The second study used data from the longitudinal Evaluation of Diabetes Treatment study, a community-based survey of insulin-naïve adults with type 2 diabetes in Quebec. Latent class growth model

5 5 analyses were conducted for all participants who completed at least 2 of 5 annual waves of assessment (n=1,077). Having identified distinct groups based on latent trajectories of perceived social support, separate analysis of variance models were then conducted to examine mean differences in levels of depressive symptoms and functional disability, respectively, across social support trajectory groups. Separate models were conducted for depressive symptoms and functional disability, adjusting for demographic and diabetes-related covariates, and baseline depressive symptoms and functional disability, respectively. Results: The first manuscript indicated that MDD, GAD, and perceived social support were each related to functional disability, such that adults with a mental disorder reported higher functional disability compared to those without a mental disorder. Participants with low perceived social support also showed higher functional disability relative to those with high social support. However, social support did not moderate the relation between mental disorders and functional disability. The second manuscript first identified four distinct groups based on latent trajectory of social support. However, each trajectory remained relatively stable over time. Moreover, there was a negative linear trend between social support and both depressive symptoms and functional disability, respectively. Specifically, as social support decreased, depressive symptoms and functional disability both increased. Conclusions: The findings of these two manuscripts indicate that cross-sectional and longitudinal assessments of perceived social support are negatively related to depression and functional disability in adults with diabetes. Health care providers may assess perceived social support when treating adults with diabetes, particularly those with comorbid MDD or GAD. Targeting and intervening in cases of low social support may be particularly important, in order to prevent the deterioration of functioning.

6 6 Abrégé Introduction: Les adultes atteints du diabète sont plus susceptibles à la dépression majeure (DM) et le trouble d anxiété généralisé (TAG) comparé à la population générale. Le diabète, la DM et le TAG sont chacun associés avec une augmentation d incapacité fonctionnelle (IF) et peuvent être particulièrement nuisible au fonctionnement si les individus ont des maladies comorbides. Le soutien social a été proposé comme étant un facteur protectif contre les effets négatifs du diabète et des troubles mentaux sur le fonctionnement. Cependant, le soutien social perçu n a pas été examiné comme modérateur de l association entre la DM, le TAG et l IF parmi les adultes atteints du diabète. De plus, il y a un manque d études examinant le soutien social perçu longitudinal parmi les adultes atteints du diabète de type 2 (DT2). Objectifs: Les objectifs sont de: 1) examiner si le soutien social est un modérateur de l association entre la DM, le TAG et l IF parmi les adultes atteints du diabète; 2) identifier les trajectoires prospectives de soutien social perçu parmi les adultes atteints du DT2; et 3) examiner ces trajectoires de soutien social perçu comme prédicteurs de la santé physique et mentale parmi les adultes atteints du DT2. Méthodes: Cette thèse est comprise de deux manuscrits. La première étude se sert des données provenant de l étude transversale Enquête sur la santé dans les collectivités canadiennes Santé mentale L échantillon consiste des participants adultes ans atteints du diabète (n=1764). Des analyses de régression linéaires séparées ont été menées pour examiner le soutien social perçu comme étant un modérateur de l association entre la DM ou le TAG et l IF. Les modèles ont ajusté pour les caractéristiques démographiques. La deuxième étude s est servi des données provenant de l étude longitudinale Évaluation des traitements du diabète parmi les adultes au Québec atteints du DT2, qui n utilisent pas de l insuline. Les modèles d analyse de structure

7 7 latente ont inclus tous les participants qui ont complété au moins 2 sur 5 évaluations annuelles (n=1077). Après avoir identifié de distincts groupes basés sur les trajectoires latentes de soutien social perçu, des modèles d analyses de la variance ont été utilisés pour examiner les différences entre les niveaux de symptômes dépressifs et de l IF, entre les groupes de soutien social. Des modèles séparés ont été utilisés pour les symptômes dépressifs et l IF, ajustant pour les caractéristiques démographiques et liées au diabète, et les symptômes dépressifs et l IF initiaux, respectivement. Résultats: Le premier manuscrit a indiqué que la DM, le TAG et le soutien social perçu ont tous été associés à l IF, tel que les adultes avec un trouble mental avaient plus d IF comparés aux adultes sans un trouble mental. Les participants avec de bas niveaux de soutien social perçu ont aussi eu plus d IF que les participants avec de haut niveau de soutien social. Cependant, le soutien social n a pas modéré l association entre ces troubles mentaux et l IF. La deuxième étude a identifié quatre distincts groupes basés sur les trajectoires latentes de soutien social. Cependant, chaque trajectoire est restée stable au cours de l étude. Les symptômes dépressifs et l IF ont été différents à travers ces groupes. De plus, le soutien social a été négativement associé avec les symptômes dépressifs et l IF. Spécifiquement, quand le niveau de soutien social diminue, le niveau des symptômes dépressifs et de l IF, respectivement, augmente. Conclusions: Les évaluations transversales et longitudinales de soutien social perçu sont associées négativement à la dépression et l IF parmi les adultes atteints du diabète. Les professionnels de la santé pourraient prendre en compte le soutien social perçu en traitant les adultes atteints du diabète, particulièrement ceux avec la DM ou le TAG. Cibler et intervenir dans les cas de soutien social de niveaux bas pourrait être important pour prévenir l IF.

8 8 Acknowledgements I would like to thank my supervisor, Dr. Norbert Schmitz, who has been incredibly supportive and encouraging over the past two years. I am also grateful for his generous support through a CIHR grant. Thank you, Norbert, for the opportunity to have been a member of such a welcoming and collaborative research lab. A special thank you to Dr. Sonya S. Deschênes & Dr. Rachel J. Burns for their guidance and patience throughout every step of this thesis. I appreciate the opportunity to have learned an immense amount from you both. To Randa Elgendy, a very special thank you for being unwaveringly supportive and encouraging, for motivating me to keep working, and for being the other me in the lab. Thank you to our lab members, Eva Graham and Sofia Danna, for their guidance and for introducing me to the world of epidemiology. Thank you also to Franz Veru for his encouragement, and for being patient with Randa and my chatter in the office. Thank you to Dr. David Dunkley and Dr. Robert Whitley, my thesis committee members, for their advice and suggestions with my thesis topic. Thank you to Statistics Canada for the use of the 2012 Canadian Community Health Survey Mental Health public use microdata file, as well as McGill University s Department of Psychiatry for an Excellence Award in Psychiatry. Finally, a sincere thank you to my family and friends for their continual support and advice. To my parents, Albert & Nicola Levy, thank you for being such inspirational models of the importance of hard work and community service. Thank you all for providing me with endless supplies of caffeine and accepting working on my thesis as response to every question. I am so grateful and could not have done this without any of you.

9 9 Preface and contribution of authors Melanie Levy, as first author, wrote this thesis and was the principal author for the first and second manuscripts. M. Levy was involved in reviewing the literature, formulating the study hypotheses, conducting statistical analyses, interpreting the findings, and drafting and revising each manuscript included in this thesis. Dr. Norbert Schmitz, as thesis supervisor, contributed to the conception, study design (EDIT study), interpretation of results, and review of this thesis, and is a co-author on both manuscripts. As primary investigator for the Evaluation of Diabetes Treatment (EDIT) study, Dr. Schmitz was responsible for the design and implementation of the study ( ). Dr. Sonya S. Deschênes and Dr. Rachel J. Burns, as co-authors on both manuscripts, were involved in the study conceptions, interpretation of findings, and critical review of both manuscripts. Dr. Burns was also involved in the data collection of the most recent wave of the EDIT study.

10 10 Chapter 1: Introduction Rationale Diabetes is a severe chronic metabolic disorder characterized by the inability to produce or effectively use insulin [1]. The current prevalence of diabetes is Canada is 9.3% [2], 90% of which is type 2 diabetes [1]. Diabetes self-management requires complex routines, such as medication or insulin adherence, frequent monitoring of blood glucose, frequent doctors appointments, a healthy diet, and physical activity [1,3]. If inadequately managed, diabetes may lead to poor physical and mental health outcomes, including disability in various domains of functioning. As diabetes progresses, individuals may develop diabetes-related micro- and macrovascular complications, as well as other physical health comorbidities [2,4]. These, in turn, may also increase the likelihood of impaired functioning [5,6,7,8]. Given that impaired functioning is associated with physical, mental, and healthcare burden among people with diabetes [9], it is thus important to identify factors that are associated with functional disability in the diabetes population. One factor that is also associated with functional disability among people with diabetes is the presence of comorbid mental disorders. People with diabetes are more likely to have major depressive disorder (MDD) and generalized anxiety disorder (GAD) relative to the general population [8,10,11,12,13,14]. Moreover, MDD, depressive symptoms, and anxiety have been reciprocally associated with functional disability among people with diabetes [15,16]. Specifically, MDD, depressive symptoms, or anxiety at one assessment predicted functional disability at the subsequent assessment, and functional disability at one assessment predicted MDD, depressive symptoms, or anxiety at the next assessment [15,16]. These mental disorders may be detrimental to functioning through biological mechanisms, such that prolonged

11 11 exposures to stress adversely impact the sympathetic nervous system and the hypothalamicpituitary-adrenal axis [17]. This, in turn, may lead to deteriorated functioning [17]. Depressive and anxiety symptoms are also associated with poor diabetes self-management [18], which increases the risk of developing diabetes-related complications and functional disability [2,4]. Optimal diabetes self-management occurs when the individual s social environment is supportive. Social support generally refers to the relationships an individual has with others, including family, friends, peers, healthcare professionals, and the community [19]. One aspect of social support, the perceived availability of social support, has implications for both diabetes self-management [19,20,21] and future mental and physical health outcomes in adults with diabetes [22,23,24,25]. Specifically, within adults with diabetes, MDD and GAD may be particularly detrimental to functioning depending on perceptions of availability of social support [26]. Low social support has been associated with increased functional disability among both people with diabetes [24] and those with mental disorders [27,28]. However, no study has examined the interaction between social support, MDD or GAD and functional disability in a nationally-representative sample of adults with diabetes. Moreover, although several hypotheses have been proposed to explain temporal trajectories of social support [29,30,31], the course of social support over time among people with diabetes has been little studied. Little is also known about how social support is related to physical and mental health outcomes over time in a diabetes population. Understanding how perceived social support is related to mental disorders among people with diabetes may provide information relevant to preventing further deterioration of functioning.

12 12 Objectives The aim of this thesis is to evaluate social support and mental and physical health outcomes in community-based samples of adults with diabetes. Specifically, this thesis aimed to: 1) examine social support as a moderator of the association between MDD and GAD and functional disability in a nationally-representative, community-based sample of adults with diabetes; 2) identify temporal trajectories of social support in adults with type 2 diabetes; 3) examine the associations between temporal trajectories and depressive symptoms and functional disability in adults with type 2 diabetes. This thesis contains six further chapters. Chapter 2 provides a review of the literature on the thesis topic. Chapter 3 includes the first manuscript, a cross-sectional study examining of the interaction of social support with MDD and GAD on functional disability in a Canadian sample of adults with diabetes. Chapter 4 contains a bridge between the two manuscripts. Chapter 5 contains the second manuscript, a longitudinal study examining temporal trajectories of social support, as well as their associations with depressive symptoms and functional disability at the final assessment. Chapter 6 presents a summary of the research findings, the strengths and limitations of this thesis, the clinical implications of the findings, as well as future research directions. Finally, Chapter 7 contains the thesis reference list, excluding the reference lists for the two manuscripts, which can be found directly following each manuscript.

13 13 Chapter 2: Review of the literature Diabetes Definition of diabetes Diabetes is a serious chronic illness characterized by the body s inability to either produce or use insulin [1,32]. The lack of insulin that is necessary to absorb sugar from the bloodstream results in hyperglycemia, or consistently high blood sugar. Type 1 diabetes (T1D) and type 2 diabetes (T2D) are the two most common types of this illness. The cause, age of onset, treatment, and complications generally differ between these two types of diabetes. T1D is an autoimmune disease in which the pancreas no longer produces insulin and the individual depends on external sources of insulin. The age of onset for T1D is typically during childhood or adolescence, but usually occurs before the age of 40. T2D is a metabolic disorder in which the pancreas does not produce enough insulin or this insulin is not properly used. T2D typically occurs in adulthood, but can develop in youth and adults under age 40 as well [1,32]. Currently, about 9.3% of Canadians have been diagnosed with diabetes [2]. Among Canadian adults diagnosed with diabetes, 90-95% are diagnosed witht2d, whereas 5-10% are diagnosed with T1D [1]. Diabetes treatment and complications As it is a chronic illness, diabetes requires rigorous self-management routines to prevent the deterioration of the individual s health. Optimal self-management includes behaviours such as medication adherence, insulin-treatment adherence, blood glucose monitoring, frequent medical appointments, physical activity, and following a diet [1,3,18]. If diabetes is not adequately managed, diabetes-related complications may develop. These include retinopathy

14 14 (vision loss), nephropathy (kidney failure), neuropathy (nerve damage), diabetic foot ulcers or amputations, cardiovascular disease, and stroke [1,32]. Modifiable risk factors for type 2 diabetes Whereas T1D is a non-preventable form of the disease, there are several modifiable factors that have been associated with increased risk of developing T2D. Modifiable risk factors include factors that may be changed to reduce an individual s risk of developing T2D [1]. The most important risk factor for developing T2D is obesity because excess body weight weakens the body s ability to effectively use insulin. As this persists, the effectiveness of the pancreas to produce insulin declines eventually leading to the development of T2D [1]. Thus, an unhealthy diet, given its link with overweight and obesity, is also a risk factor for developing T2D [1]. Lack of physical activity also contributes to the risk of T2D because when an individual does not expend energy via exercise, calories are stored as fat in the body, which increases the risk for obesity [1]. Tobacco smoking has also been repeatedly reported as a significant risk factor for T2D. Smoking is linked to T2D through several mechanisms, including the increase of glycemic levels, the impairment of insulin effectiveness, and obesity [1]. Heavy alcohol consumption has been linked to the risk of T2D [33] through biological mechanisms such as impaired glucose metabolism or decreased insulin sensitivity [34,35,36], or through lifestyle factors such as obesity [37], poor diet or smoking [38,39]. Finally, low socioeconomic status is associated with obesity and physical inactivity and therefore may be an indirect risk factor for T2D [40]. Non-modifiable risk factors for type 2 diabetes Other risk factors for T2D are non-modifiable and include individual characteristics that cannot be changed to reduce risk of T2D [1]. Non-modifiable risk factors include, in particular,

15 15 having a family history of diabetes [41]. Individuals are also at an increased risk for developing T2D based on age (highest for middle-aged adults), race or ethnicity [42,43], sex [44], low birth weight, and history of gestational diabetes [45]. Moreover, childhood adversity has been associated with lifetime obesity [46] and incident T2D [47]. Other cardiometabolic factors that contribute to T2D risk include abnormal lipid metabolism, inflammation, and hypertension [44]. Lastly, genome-wide association studies have also reported a genetic risk for developing T2D [48]. Diabetes and functional disability As diabetes progresses, it can become debilitating to the individual in various domains of daily functioning [49]. Functioning is a general construct that comprises all body functions, activities, and participation that a person with a given health condition can do [50]. Functional disability, alternatively, is a measure of the functioning and impairment of an individual in general domains of life. These domains include self-care (ability to maintain personal hygiene, dress, eat, live alone), mobility (ability to move and get around), cognition (ability to communicate and understand), life activities (ability to perform responsibilities at home and work), getting along with others (ability to interact with others), and participation in society (ability to engage in recreational and community activities) [51]. Diabetes symptoms and diabetes-related complications are positively associated with functional disability [7]. Specifically, complications such as retinopathy and neuropathy may cause impairment in the domains of self-care, mobility, and life activities [7]. Moreover, diabetes symptoms and diabetesrelated complications have also been significantly positively associated with interference with getting along with others and participation in society [7]. Furthermore, T2D has also been associated with cognitive deficits on various tasks, including focused attention and motor task

16 16 processing [52]. Functional disability is typically assessed in epidemiological studies using either the World Health Organization Disability Assessment Schedule 2.0 [51] or the Medical Outcomes Survey Short Form Health Survey-36 [53], both of which assess impaired functioning in the abovementioned domains. Mental disorders: Depression and anxiety Definition of depression Major depressive disorder (MDD), is the most common mental disorder among adults [54], and is therefore the focus of this thesis. According to the American Psychiatric Association s Diagnostic and Statistical Manual of Mental Disorders-IV-Text Revision (DSM- IV-TR), MDD is defined by the following criteria: 1) depressed mood or diminished interest or pleasure most of the day, nearly every day for at least 2 weeks; 2) the presence of 5 or more other symptoms (i.e., appetite disturbance or significant weight change (5%), sleep disturbance, fatigue or loss of energy, psychomotor retardation or agitation, feelings of excessive guilt or worthlessness, lack of concentration, recurrent thoughts of death or suicide); and 3) clinically significant distress or social or occupational impairment [55]. The DSM-V has since been released in May 2013 and the diagnostic criteria for MDD are slightly changed. The DSM-IV- TR criteria excluded the diagnosis of MDD during the period of bereavement, or the two months following the death of a loved one [55]. In the DSM-V, this bereavement exclusion criterion was removed, and replaced with a caution to differentiate between normal and pathological bereavement [56]. This thesis focuses on DSM-IV-TR diagnostic criteria for MDD because the measures used in both manuscripts are based on this version.

17 17 Measures of depression Various measures have been developed to assess MDD and depressive symptoms. The gold standard diagnostic assessment for MDD is the Structured Clinical Interview for DSM-IV axis I disorders (SCID) [57]. The SCID is a semi-structured interview that must be administered by a trained psychiatrist or psychologist [57]. However, because the SCID requires a trained clinician, it is expensive and often infeasible to administer. Alternatively, structured interviews, such as the World Health Organization Composite International Diagnostic Interview (WHO- CIDI), are designed to be administered by trained lay interviewers [58]. The WHO-CIDI shows good reliability and validity compared to the SCID [58,59]. Finally, brief self-report symptom scales for depression are typically used for screening in both healthcare and research settings [60]. Among these questionnaires, the Patient Health Questionnaire-9 (PHQ-9) assesses 9 symptoms, based on the diagnostic criteria for MDD, over the past 2 weeks [61]. Other symptom scales include the Center for Epidemiological Studies Depression Scale (CES-D), the Hospital Anxiety and Depression Scale (HADS), and the Beck Depression Inventory-II (BDI-II) [60]. Depression in people with diabetes In a given 12-month period, an estimated 4% of Canadians reportedly have MDD [62]. However, people with diabetes tend to report higher comorbid MDD relative to the general population [10,11,12,13,14,24]. Similarly, people with diabetes tend to report higher depressive symptoms than the general population [63]. Previous research suggests a bi-directional relation between diabetes and MDD, such that diabetes is a risk factor for developing MDD [64] and that MDD is a risk factor for developing diabetes [64,65,66,67]. There are various psychosocial and behavioural factors associated with both diabetes and MDD and depressive symptoms that may contribute to the association between diabetes and MDD and depressive symptoms. The

18 18 psychosocial burden of a diagnosis with diabetes, as well as the rigorous self-management routines required, may increase the risk for MDD [63] and elevated depressive symptoms [63, 68]. Conversely, people with MDD or depressive symptoms may engage in unhealthy lifestyle behaviours, such as unhealthy eating, lack of physical activity, smoking, and heavy alcohol consumption [63,68,69]. These lifestyle factors are pertinent risk factors leading to or exacerbating T2D [1]. The symptoms of MDD, including diminished interest, fatigue, lack of concentration, and sleep and diet dysregulation, may account for the difficulty people with MDD have in maintaining healthy lifestyle factors and treatment adherence [3,70], and people with diabetes and comorbid MDD or depressive symptoms show poorer self-management than those with diabetes alone [9,71]. For example, MDD or depressive symptoms in people with diabetes has been associated with increased medication nonadherence and poor diet [9,70,72]. Among people with diabetes, MDD and depressive symptoms are also associated with poor diabetes-related health outcomes, including risk of diabetes-related complications, increased functional impairment, and more frequent healthcare utilization [9]. Definition of anxiety Anxiety is defined as a typical stress response in anticipation of a future event [72]. However, when an individual s anxiety symptoms cause significant impairment, he or she may be diagnosed with an anxiety disorder. Although there are several types of anxiety disorders included in the DSM-IV-TR, one common type is generalized anxiety disorder (GAD). According to the DSM-IV-TR definition of GAD, an individual must meet the following criteria for diagnosis: 1) excessive anxiety and worry about several events or activities, occurring most of the day, nearly every day for a period of at least 6 months; 2) difficulty controlling the worry;

19 19 3) the presence of 3 or more other symptoms (i.e., restlessness, fatigue, difficulty concentrating, irritability, muscle tension, sleep disturbance); and 4) the anxiety, worry or symptoms must cause significant distress or social or occupational impairment [55]. The DSM-V has since been released in May 2013 and the diagnostic criteria for GAD are slightly changed. In the DSM-IV- TR, the diagnosis of GAD was excluded if the symptoms occurred exclusively during a mood disorder episode; in this case, an individual would be diagnosed with the appropriate mood disorder [55]. In the DSM-V, this exclusion criterion was removed [73]. This thesis focuses on DSM-IV-TR diagnostic criteria for GAD because the measure used in the first manuscript follows this version. Anxiety in people with diabetes The 12-month prevalence of GAD in Canada is an estimated 2.6%, and the lifetime prevalence is an estimated 8.7% [74]. Similarly to MDD, people with diabetes are more likely than the general population to report comorbid GAD [12,13,14,75]. People with diabetes are more likely to also have comorbid MDD-GAD versus either MDD or GAD alone [76]. The associations between diabetes and anxiety disorders have been less frequently studied, and the results of existing studies have been inconsistent. Some studies have found no association between anxiety and risk of diabetes [77], whereas others have found increased risk of diabetes in women with anxiety, but not in men [67]. Implications of mental disorders for functional disability MDD is one of the leading causes of burden, as well as years lived with disability and disability adjusted life years, worldwide [78,79]. Chronic conditions, including diabetes and MDD, have been associated with increased disability and increased length of disability,

20 20 particularly in older age [80]. MDD has also been associated with absenteeism from work, diminished work productivity, and mental health disability days [81,82], particularly in people with comorbid diabetes and MDD [83]. MDD, as well as comorbid MDD-GAD, has been associated with increased functional disability relative to the general population [76]. Among people with diabetes, MDD is positively associated with functional disability, social functioning, and days of reduced household work [7]. A recent study found reciprocal associations between depressive symptoms and functional disability in a community-based sample of adults with type 2 diabetes, such that elevated depressive symptoms at one assessment predicted higher functional disability at the subsequent assessment, and vice versa [84]. People with diabetes and MDD or elevated depressive symptoms are more likely to show poor self-management and noncompliance with medical treatment, such as medication nonadherence, relative to those with MDD or lower depressive symptoms [18,70,71]. Inadequate diabetes self-management may, in turn, lead to functional disability [5]. Additionally, MDD has been associated with micro- and macrovascular diabetes-related complications [85], which are also associated with increased risk of functional disability [7]. Anxiety disorders account for 2% of the health-related disability in Canada [74]. GAD, specifically, has been associated with increased disability compared to healthy adults [86] and significant impairment and disability [74,87]. Additionally, a recent study conducted with data from the 2012 Canadian Community Health Survey Mental Health found that GAD was associated with increased disability among adults with diabetes [76]. Reciprocal associations have also been reported between anxiety symptoms and functional disability in adults with diabetes, independent of depressive symptoms [16]. Given this, among people with diabetes,

21 21 depression and anxiety have important implications for functioning in various domains of daily life. Social support Definition of social support Social support can be defined as the informal and formal relationships one has with others, including family, friends, peers, healthcare professionals, and community organizations [19,20]. This may include the formal and informal relationships an individual has with other people, which can include family, friends, peers, healthcare professionals, or community organizations [19,20,88]. Social support is a complex construct, so clearly operationally defining different aspects of social support allows researchers to identify what specific types of support are most effective in promoting positive health outcomes [26,89]. One aspect of social support is the social network, which refers to an individual s web of social relationships and linkages [19,20]. Research examining the social network tends to be quantitative and assesses the social network size by enumerating the sources of support or people surrounding the individual [20]. Received, or enacted, social support has also been extensively studied. This is defined as the assistance that an individual actually receives from supporters [19,89]. Alternatively, perceived social support is an individual s perception of the availability of adequate assistance, care, and acceptance from supporters [19,89]. Perceived social support is also multifaceted, and is typically comprised of four distinct aspects. Emotional support is the expression of emotions, such as warmth and nurturance, that indicate the receiver is cared for and valued [19,20]. Tangible support is the provision of resources, such as material goods, services, or financial assistance [19,20]. Informational, or practical-instrumental, support includes the provision of

22 22 information, guidance, advice or suggestions to help the receiver resolve problems [19,20]. Finally, companionship support is the receiver s sense of social belonging, as well as his or her engagement in social activities with supporters [19]. Previous research has examined the relations between social network, received support, and perceived support and mental and physical health outcomes [26]. Social network has been inconsistently related to positive health outcomes because it provides only data about the number of people around the individual, rather than comprehensive information about support satisfaction or quality of interactions [26,90]. Perceived social support has been repeatedly linked to positive health outcomes, whereas the findings about received social support have been inconsistent [26]. Given this, the focus of this thesis is perceived social support. The buffering hypothesis of social support posits that social support acts as a protective factor against negative health outcomes when a person faces stressful circumstances [19,20,91], such as chronic illness or mental disorders. Specifically, people who perceive high availability of social support may be less negatively affected by stressful events and illness than people who perceive low availability of social support [19]. Therefore, the buffering hypothesis proposes that social support is expected to moderate the associations between stress and negative health outcomes [92]. Measures of social support There are various existing methods to assess different aspects of social support. For example, social network can be measured using questionnaires such as the Social Support Questionnaire-6, which assesses both the number of people available for support, as well as the individual s satisfaction with that support [93]. Other studies construct measures of social network size that identify the number of different relationship types (e.g., immediate family, extended family, friends) present in the individual s network [90]. Within the context of chronic

23 23 illness, received social support is often assessed using such measures as the Diabetes Family Behavior Checklist-II, which assesses how often family members assist with various activities [94]. Finally, perceived support may be assessed using validated measures such as the Social Provisions Scale (SPS) [95,96] or the Medical Outcomes Survey Social Support Instrument (MOS) [97], both of which are commonly used in epidemiological studies. The SPS, for example, has been used in several waves of the Canadian Community Health Survey [98]. The MOS was designed to assess perceived social support in people with chronic conditions, and is therefore used in several epidemiological studies [24,25]. Perceived social support in people with diabetes Diabetes management becomes more complex as the illness progresses, with the potential diagnosis of diabetes-related complications or other physical health problems [1]. As people age, self-management also occurs within the context of comorbid health conditions like cardiovascular disease or cognitive decline [99]. Thus, among adults with diabetes, there is variability in health status, ranging from healthy people to those requiring extensive assistance with daily functioning [7,99]. Within the context of diabetes, social support can include, for example, assistance with medication adherence, accompanying the individual to doctor s appointments, or help with healthy diet or exercise adherence [18,19,100]. Therefore, diabetes self-management occurs within the social context of the individual, and has been found to be most effective within a positive support environment [18,101]. Despite the importance of social support for people with diabetes, this population tends to report lower perceived social support levels relative to the general population [23]. Studies have reported that high perceived social support may buffer against negative diabetes-related outcomes, including medication nonadherence [71,100], poor self-management

24 24 [19,100], and depressive symptoms [22,100]. Conversely, low perceived social support has been associated with poor outcomes such as medication nonadherence [71] and mortality [102]. A meta-analysis of longitudinal cohort studies found that low social support was more strongly related to poor diabetes control compared to either stressful events or coping style [21]. Selfmanagement is demanding and ongoing, placing a burden on support providers coping and emotional resources as well [101,103]. Because of this, the nature of the patient s social relationships may change over time. The spouses of adults with diabetes have reported elevated depressive and anxiety symptoms [104], as well as lower daily interaction enjoyment and increased marital tension with their partner, particularly in the case of longer diabetes duration [103]. Trajectories of perceived social support Several theories exist to explain the course of social support over time within the context of chronic illness. The mobilization hypothesis posits that support providers mobilize in response to the support recipient s stress or distress, such as chronic illness [30,31]. The deterioration hypothesis proposes that, when an individual faces a severe life event, support providers may not be able to maintain social support over time, and thus support may erode [29,30]. Stability theories of social support posit that social support remains stable over time, as it tends to be a trait-like characteristic [26]. However, little research has examined temporal patterns of perceived social support in adults with diabetes to test these proposed hypotheses. Perceived social support and mental disorders High perceived social support is associated with positive outcomes in people with depressive symptoms and anxiety [25]. Among people with diabetes, perceived social support is

25 25 associated with positive diabetes-related clinical outcomes, including better treatment adherence, blood pressure, and HbA1c [19]. Despite this, people with MDD and GAD have reported lower perceived social support compared to people without these mental disorders [23,24]. A recent study that examined the bi-directional associations between perceived social support and depressive symptoms in people with diabetes indicated reciprocal associations, such that social support at one assessment predicted functional disability at the subsequent assessment, and vice versa [25]. These findings indicate that perceived social support may have strong implications for future depressive symptoms, and depressive symptoms for future perceptions of social support. MDD and GAD have been theorized to influence perceptions of social support through two processes: cognitive biases and specific interpersonal interactions. First, people with MDD or depressive symptoms tend towards negative cognitive distortions and views about the self and the world, including low self-esteem and negative expectations of their interactions with others [105,106]. Similarly, people with anxiety tend to report cognitive distortions, but instead persistently interpret situations and other people as threatening [106,107]. These cognitive distortions are due to selective and automatic attention to either negative stimuli in MDD or threatening stimuli in GAD [106,107]. Therefore, individuals with these mental disorders tend to perceive their social environment as negative and threatening, rather than positive and supportive [106]. People with these mental disorders may also exhibit certain interpersonal behaviours that do not foster positive social relationships. People with MDD or depressive symptoms may engage in isolating behaviours, for example because of a loss of interest or energy for social activities or persistent negative interpretations of their social interactions, and thus withdraw from social relationships [105,108]. They may also engage in excessive reassurance-seeking

26 26 behaviours that impact their relationships [105,108]. Given the tendency to interpret social interactions and other stimuli in the environment as threatening, people with anxiety tend to engage in avoidant and excessive reassurance-seeking behaviours as well [109]. These cognitive distortions and interpersonal behaviours may therefore lead to a decrease in perceptions of positive social support among people with these mental disorders. Implications of perceived social support for functional disability Perceived social support may have important implications for health outcomes, including functioning, in people with diabetes, particularly in individuals with comorbid mental disorders. Among people with diabetes, low perceived social support is associated with functional disability [24]. Similarly, low perceived social support is associated with functional disability in people with depressive or anxiety symptoms [110]. However, little is known about how perceived social support interacts with mental health on functional disability in people with diabetes. People with diabetes and comorbid mental disorders tend to report higher functional disability than those with diabetes alone [76]. Therefore, it is important to examine if perceived social support may be a relevant factor to prevent the deterioration of functioning. Given that social support is a modifiable factor [20], understanding how specific aspects of social support are related to diabetes-related clinical outcomes may inform public health initiatives targeting improved diabetes management. The findings of research into these associations may be incorporated into future interventions aimed at improving perceived social support among people with diabetes, such as self-help or diabetes-specific support groups.

27 27 Addressing knowledge gaps in the literature The role of social support in people with diabetes, particularly those with comorbid mental disorders, has been previously studied. However, there are certain knowledge gaps in the literature that should be addressed, in order to gain a complete understanding of the relations between perceived social support, mental disorders, and functional disability among adults with diabetes. First, the social support literature is inconsistent in both the definition and measurement of social support across studies [26,89]. For example, some studies examine received support [30,111,112], perceived support [71,113], social network [90,113], or diabetes-related support [18,111,113,114,115]. Many studies also do not use reliable or validated questionnaires to assess social support; instead, they use single questions or pick individual items from questionnaires [18,111,113,115,116]. Therefore, it is challenging to compare the findings of different studies and to make meaningful interpretations of the existing research, in order to make clinical recommendations. The manuscripts included in this thesis are therefore conducted using reliable and validated measures of perceived social support. These measures of perceived social support specifically define the type of social support being assessed and are comparable to other studies [22,24,25,71]. The relation between mental disorders and functional disability has been extensively studied in large, community-based samples [15,24,76,84]. However, social support has rarely been studied in large, community-based samples [25], and tends to be examined in smaller, convenience samples that may not be generalizable [30,112]. Furthermore, the relation between social support and MDD [25] has been more frequently studied than GAD. Given the high prevalence of GAD in people with diabetes [14], as well as the association between GAD and

28 28 functional disability [16,86], understanding the interaction between GAD and social support is important. Moreover, perceived social support has been mainly studied cross-sectionally among people with diabetes [24]. These studies provide the basis for identifying a link between social support and health outcomes in diabetes; however, further longitudinal research is necessary to determine how the associations between social support and these diabetes-related outcomes change over time. Therefore, this thesis aims to: 1) examine social support as a moderator of the relation between MDD and GAD and functional disability in a nationally-representative, communitybased sample of adults with diabetes; 2) identify temporal trajectories of social support in adults with T2D; 3) examine the associations between temporal trajectories and depressive symptoms and functional disability in adults with T2D.

29 29 Chapter 3: Manuscript 1, as published in Psychosomatics Does Social Support Moderate the Association Among Major Depression, Generalized Anxiety Disorder, and Functional Disability in Adults with Diabetes? Levy, M., Burns, R. J., Deschênes, S. S., & Schmitz, N. (2017). Does social support moderate the association among major depression, generalized anxiety disorder and functional disability in adults with diabetes? Psychosomatics, 58(4), Authors & Affiliations: Melanie Levy a,b, Rachel J. Burns a,b, Sonya S. Deschênes a,b, Norbert Schmitz a,b,c a Department of Psychiatry, McGill University Ludmer Research & Training Building 1033 Pine Avenue West Montreal, QC, Canada H3A 1A1 b Douglas Mental Health University Institute Frank B. Common Pavilion, F Boul. Lasalle Montreal, QC, Canada H4H 1R3 c Department of Epidemiology & Biostatistics, McGill University Purvis Hall 1020 Pine Avenue West Montreal, QC, Canada H3A 1A2

30 30 Abstract Background: Diabetes requires complex self-management routines to prevent the development of functional disability. Relative to people without diabetes, those with diabetes are more likely to have comorbid major depression (MDD) and generalized anxiety disorder (GAD), which also increase the likelihood of functional disability. Social support is associated with positive health outcomes in people with comorbid diabetes and mental disorders and may serve as a buffer against functional disability, though this possibility has yet to be examined. Objectives: This study examined whether social support moderates the association between MDD or GAD and functional disability in adults with diabetes. Adults with MDD or GAD were expected to report greater disability than those without MDD or GAD. This association was expected to be stronger in people reporting lower social support relative to those reporting higher social support. Methods: Data came from the cross-sectional 2012 Canadian Community Health Survey-Mental Health (n=1,764). Diabetes status, social support and functional disability were assessed via selfreport; past-year MDD and GAD were assessed with structured diagnostic interviews. Results: Linear regression analyses, conducted separately for MDD and GAD, indicated main effects of past-year MDD and GAD, such that those with a mental disorder reported greater functional disability than those without a mental disorder. Social support did not moderate the associations between either MDD and functional disability or GAD and functional disability. Conclusions: In this nationally-representative population study, both MDD and GAD predicted greater functional disability in adults with diabetes. Social support, however, did not moderate these associations.