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Heart failure (HF) is a major public health problem throughout the world. It accounts for one death certificate among nine in the United States. Heart failure and sudden death combined are responsible for the largest number of deaths in America. The total costs of HF in the United States are estimated to be $37 billion each year. Despite substantial medical and surgical advances related to treatment of HF, it remains a very costly condition with high mortality and morbidity rates. Although biological factors contribute to high morbidity and mortality in HF, there are many unexplored psychosocial factors that also likely contribute to these rates. Thus, the purpose of this dissertation was to examine the association between some of the psychosocial factors (i.e. depression, anxiety, comorbid depression and anxiety, stress, cognitive appraisal, and coping) and health outcomes as defined by rehospitalisation and mortality among HF patients. The first paper is a report of longitudinal study of 1,260 patients with HF. The purpose of the study was to determine whether co-morbid symptoms of depression and anxiety are associated with all-cause mortality or rehospitalization for cardiac causes in patients with HF. Anxiety and depression were treated first as continuous level variables, then as categorical variables using standard published cut points. Patients were then divided into four groups based on the presence of symptoms of anxiety and depression. When depression and anxiety were treated as continuous level variables, both comorbid depression and anxiety, and depression alone were significant predictors of all-cause mortality. However, when depression and anxiety were treated as categorical variables, comorbid depression and anxiety was a predictor of all-cause mortality, while anxiety and depressive symptoms considered alone were not independent predictors of the same outcome. None of those variables were significant predictors of cardiac rehospitalization outcome, regardless of whether entered as continuous or categorical level variables. The second paper is a report of a study that was conducted to (1) examine the association of stress with 6-month cardiac event-free survival; (2) examine the relationship of stress with salivary cortisol; and (3) examine the association of salivary cortisol level with 6-month cardiac event-free survival. The study sample was 81 HF patients. A prospective design was used in which patients were followed for 6 months to determine occurrence of 6-month cardiac event-free survival, defined as time to the combined endpoint of cardiac rehospitalization or all-cause death. Stress was not a significant predictor of event-free survival in HF, salivary cortisol was a significant predictor of event-free survival in the unadjusted model, but not in the adjusted model, and stress was not a significant predictor of salivary cortisol level. The final paper is a report of prospective design study that aimed to describe self-reported stress level, cognitive appraisal and coping among patients with HF, and to examine the association of cognitive appraisal and coping strategies with event-free survival based on a proposed model of HF patients’ response to stressors that been suggested according to literature to date. The study sample consisted of 88 HF patients who been followed for 6 months to determine occurrence of the combined endpoint of rehospitalization for cardiac causes or all-cause death. The study showed that stress level was associated with harm and loss cognitive appraisal. Harm/loss and threat cognitive appraisals were associated with avoidant emotional coping. Furthermore, harm/loss cognitive appraisal was a significant predictor of avoidant emotional coping and event free survival. Finally avoidant emotional coping was a significant predictor of event free survival among HF patients in the unadjusted model, but not in the adjusted model. The findings from this dissertation provided further evidence of the importance of psychosocial factors to health outcomes in HF patients. It also filled important gaps in the body of knowledge related to health outcomes among those with HF by demonstrating the need for cognitive and behavioral therapy among HF patients who negatively appraise their health condition.

It is not uncommon for math difficulties and reading difficulties to occur simultaneously. Despite this, math and reading difficulties are thought to have different cognitive profiles where math difficulties are linked to number sense; an innate ability to understand, approximate and manipulate both quantities and numerical information, whereas reading difficulties are linked to phonological ability; an innate ability to understand, create representations of and manipulate phonological information. A possible link between the difficulties is that phonological abilities also could affect mathematical ability. Support for this comes from studies where comorbid math and reading difficulties are associated with more severe difficulties in arithmetic ability compared to those with isolated math difficulties. The purpose of this study is to examine whether isolated math difficulties, isolated reading difficulties and comorbid math and reading difficulties can be linked to deficits in number sense, phonological ability or both of these, and whether comorbid math and reading difficulties differ in performance in mathematical tasks compared to isolated math difficulties for children in second grade. The study was carried out by testing 161 second grade children in arithmetic performance, reading performance, number sense and phonological ability. Based on performance in arithmetic and reading participants were divided into four groups: math difficulties (MD), reading difficulties (LD), comorbid math and reading difficulties (MD/LD) and control group. Statistical comparisons between groups were calculated by use of ANCOVAs, with non-verbal intelligence as covariate, and by independent t-test. Results gave partial support for the proposed core deficits for math and reading difficulties respectively, mainly concerning math difficulties and number sense deficits. The MD group performed significantly poorer in the non-symbolic number sense test.The group LD did not perform significantly poorer in respect to any task. The group MD/LD performed significantly poorer regarding subtraction, symbolic number sense tests and phonological awareness. Based on these results it can be discussed whether a link between number sense deficits and phonological awareness deficits may cause difficulty with learning and manipulating symbolic digit number. / Det är inte ovanligt att matematiksvårigheter förekommer tillsammans med lässvårigheter. Däremot förefaller matematiksvårigheter och lässvårigheter ha skilda kognitiva profiler där matematiksvårigheter kopplas till bristande number sense; en medfödd förmåga för att förstå, approximera och manipulera kvantiteter och numerisk information, medan lässvårigheter kopplas till bristande fonologisk förmåga; en medfödd förmåga att förstå, skapa representationer för och manipulera fonologisk information. En möjlig länk mellan svårigheterna är att fonologisk förmåga även kan påverka den matematiska förmågan. Stöd för detta har framkommit i studier där komorbida matematik- och lässvårigheter kopplats till mer uttalade matematiksvårigheter i jämförelse med isolerade matematiksvårigheter. Syftet med föreliggande studie är att undersöka huruvida isolerade matematiksvårigheter, isolerade lässvårigheter samt komorbida matematik- och lässvårigheter kan kopplas till bristande number sense, bristande fonologisk förmåga eller båda samt huruvida komorbida matematik- och lässvårigheter skiljer sig gentemot isolerade matematiksvårigheter gällande matematiksvårigheternas omfattning hos barn i andra klass. För att besvara syftet testades 161 barn i andra klass gällande aritmetisk färdighet, läsfärdighet, number sense och fonologisk förmåga. Efter sin prestation i matematik och läsningdelades deltagarna in i fyra grupper; matematiksvårigheter (MS), lässvårigheter (LS), komorbida matematik- och lässvårigheter (MS/LS) samt kontrollgrupp. Statistiska jämförelser beräknades mellan grupperna genom kovariansanalyser (ANCOVA), med icke-verbal intelligens som kovariat, samt genom oberoende t-test. Resultatet gav delvis stöd för den tänkta kärnproblematiken för matematiksvårigheter respektive lässvårigheter, främst gällande matematiksvårigheter och bristande number sense. Gruppen MS var signifikant sämre på ett icke-symboliskt number sense-test. Gruppen LS var inte signifikant sämre gällande något test. Gruppen MS/LS var signifikant sämre gällande subtraktion och symboliska number sense-test samt gällande fonologisk medvetenhet. Utifrån resultatet diskuteras huruvida en länk mellan bristande number sense och bristande fonologisk medvetenhet kan orsaka svårigheter med inlärning och hantering av symboliska siffertal.

Information regarding symptoms of Attention Deficit Disorder (ADD) in adolescence is much less prevalent than information about symptoms of this disorder in childhood. Comorbid conditions of ADD such as substance abuse, depression, paranoia and conduct disorder have only been marginally addressed in the literature. Furthermore, these areas, when addressed, have typically been studied in clinical populations referred to practitioners because of severe problems in the home, school or community. It is therefore likely that clinical populations may not represent the incidence of symptoms of ADD and existing comorbid conditions that might be found in non-clinical populations. The present study constituted an examination of symptoms of ADD, substance abuse, and comorbid conditions in a nonreferred adolescent population. Subjects were from a freshman class in a rural mountain area. The 118 subjects that participated in this study were given the Substance Abuse Subtle Screening Inventory (SASSI), the Minnesota Multiphasic Personality Inventory Adolescent Version (MMPI-A) and the Brown ADD Scales. Subjects were chosen randomly from the first 20 subjects who evidenced elevated symptoms of ADD as indicated on the Brown ADD Scales. An additional 20 subjects who did not have elevated symptoms of ADD were randomly chosen as the control population. The comorbid constellation of symptoms addressed in this study were substance abuse, depression, paranoia and conduct disorder. The results indicated that symptoms of ADD were significantly associated with substance abuse, depression and paranoia in this non-clinical population. Of interest was that Conduct Disorder was not found to be significantly associated with ADD, in this “normal population” although it has been associated with ADD in referred clinical populations. This may point to an important difference in this regard between the general population and those referred for clinical services.

My thesis aims at identifying both genetic and environmental causes of major depressive disorder (MDD), using a large case-control study: 6,000 Chinese women with recurrent MDD and 6,000 controls. One of the major challenges for conducting genetic research on MDD is disease heterogeneity. The first question addressed is how different MDD is from highly comorbid anxiety disorders. I examine how anxiety disorders predict clinical features of depression and the degree of heterogeneity in their predictive pattern. The second question addressed is whether clinically defined MDD is a single disorder, or whether it consists of multiple subtypes. Results are then compared with and interpreted in the context of Western studies. Furthermore, latent class analysis and factor analysis results are also used in association analysis to explore more genetically homogeneous subtypes. Genetic data were derived using a novel strategy, low pass whole genome sequence analysis. Using genotypes imputed from the sequence data, I show that a cluster of single nucleotide polymorphisms (SNPs) is significantly associated with a binary disease phenotype including only cases with = 4 episodes of MDD, suggesting that recurrence might be an indication of genetic predisposition. The third issue examined is the contribution of rare variants to disease susceptibility. Again using sparse sequence data, I identified exonic sequence variants and performed gene-based analysis by comparing the number of variants between cases and controls in every gene. Furthermore I performed gene enrichment test by combining P values of SNP association tests at different minor allele frequency ranges. Overall, I did not find convincing evidence that rare variants aggregately contribute to disease susceptibility. However, the gene-based analysis resulted in an unexpected finding: cases have an excess of variants in all thirteen-protein coding mitochondrial genes, which was due to copy number differences in the mitochondrial genome. Both human phenotypic data as well as mice experimental data show that the increase in the mitochondrial copy number in cases is due to chronic stress.

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Le trouble déficitaire de l’attention avec ou sans hyperactivité (TDA/H) est une condition qui touche un nombre important d’enfants d’âge scolaire. Plusieurs d’entre eux sont également atteints d’un trouble concomitant, qu’il soit de nature anxieuse ou agressive. Les manifestations comportementales qui en découlent, ainsi que les conséquences qui y sont associées, ont une influence sur l’enfant, mais également sur son parent. Certaines études suggèrent que ces conditions sont associées chez les parents à un niveau de stress élevé, à un sentiment d’auto-efficacité (SAE) plus faible, à plus de symptômes dépressifs et à une satisfaction conjugale plus faible. D’autres résultats rapportent le contraire. Pourquoi ces résultats sont-il divergents? Cette étude a pour but, en premier lieu, d’examiner, dans un échantillon québécois de 110 parents d’enfants atteints de TDA/H, si les caractéristiques du TDA/H des enfants (sous-type de TDA/H et présence d’un trouble concomitant) influencent les caractéristiques personnelles de leur parent (stress parental, SAE, symptômes dépressifs et satisfaction conjugale). En deuxième lieu, nous examinerons si l’attachement adulte est lié à ces quatre caractéristiques personnelles parentales et s’il modère le lien entre les caractéristiques du TDA/H de l’enfant et celles du parent. Les résultats indiquent que le profil diagnostique de l’enfant est lié aux symptômes dépressifs des parents et que la présence d’un trouble concomitant chez l’enfant est liée à la satisfaction conjugale parentale. De plus, un effet d’interaction est observé entre le profil diagnostique et la présence d’un trouble concomitant chez l’enfant sur le niveau de stress du parent. Les résultats démontrent également un effet significatif du style d’attachement adulte sur le sentiment d’auto-efficacité des parents, les parents avec un attachement sécure-autonome ayant un sentiment d’auto-efficacité plus élevé que ceux avec un attachement de type insécure-ambivalent. Aucun effet modérateur de l’attachement adulte sur la relation entre les caractéristiques du TDA/H de l’enfant et les caractéristiques personnelles de son parent n’est observé. / Attention deficit/hyperactivity disorder (AD/HD) is present in a large number of school-aged children. Many of them are also suffering from comorbid agressive or anxious disorders. Behavioral manifestations and the consequences that arise, have not only an influence on the child, but also on the parent. Some studies suggest that, for those parents, these conditions are associated with a higher level of stress, a lower sense of self-efficacy, more depressive symptoms and lower marital satisfaction. Other findings relate the opposite. Why are these results in conflict? This study aims, firstly, to examine, in a Quebec sample of 110 parents of children with AD/HD, if the children’s characteristics of AD/HD (diagnostic profile and the presence of a comorbid disorder) are related to their parent’s personal characteristics (parental stress, sense of self-efficacy, depressive symptoms and marital satisfaction). Second, we examine whether adult attachment is linked with those four parental characteristics and if it moderates the relationship between children’s AD/HD characteristics and parent’s personal characteristics. Results indicate that the child’s diagnostic profile is related to parent’s depressive symptoms and that the presence of comorbid disorders is related with parent’s marital satisfaction. Also, an interaction effect between child’s diagnostic profile and presence of comorbid disorders is observed on parental stress level. In addition, results showed a significant relation between adult attachment style and parent’s sense of self-efficacy only, confirming that parents with a secure-autonomous attachment style have a higher sense of self-efficacy than those with an insecure-ambivalent attachment style. No moderating effect of adult attachment on the relationship between child’s AD/HD characteristics and parent’s personal characteristics is observed.