Aetiology of Depression: Insights from epidemiological and genetic research

This thesis includes several population-based studies that explore the aetiology of depression, with a specific interest on biological factors, genetics and epigenetics, and physical health factors for depression. Unravelling the aetiology of depression could potentially answer some remaining questions about depression, and finally may explain why we consistently fail to develop effective management and treatment tools for depression. Therefore, this thesis aims to apply advanced epidemiological studies and to extend the existing knowledge on the aetiology of depression. Using population- based data, the studies described in this thesis examine several risk factors and predictors that may enlighten the pathophysiological mechanism that underlie the development of depression. Specifically, Chapter 2 of this thesis presents longitudinal studies that examine the impact of potential biomarkers, such as vitamin D (Chapter 2.1), and inflammatory markers (Chapter 2.2) on the occurrence of depression. Chapter 3 of this thesis presents two studies which apply advanced genetic epidemiological methods to study the genetics of depression. Chapter 4 focuses on the epigenetics of depression and presents the largest epigenome wide association population-based study so far. Moreover, we dedicated a chapter to the impact of physical health conditions such as myocardial infarct on depression (Chapter 5.1) as well as one to the physical consequences of depression such as cognitive decline (Chapter 5.2). Finally, Chapter 6 provides a more general discussion of the main findings in this thesis and addresses several methodological considerations of the studies. Clinical implications of the results in this thesis, and future directions are also presented

Business Corporation Law in Changing Society

Evidence suggests that depression is cross-sectionally and longitudinally associated with activation of inflammatory response system. A few studies, however, have investigated the longitudinal relationship between raised inflammatory biomarkers and persistence of depressive symptoms. We examined the temporal relationship between serum levels of inflammatory biomarkers and persistence of depressive symptoms among older participants

Influence of socioeconomic factors on pregnancy outcome in women with structural heart disease

OBJECTIVE: Cardiac disease is the leading cause of indirect maternal mortality. The aim of this study was to analyse to what extent socioeconomic factors influence the outcome of pregnancy in women with heart disease.  METHODS: The Registry of Pregnancy and Cardiac disease is a global prospective registry. For this analysis, countries that enrolled ≥10 patients were included. A combined cardiac endpoint included maternal cardiac death, arrhythmia requiring treatment, heart failure, thromboembolic event, aortic dissection, endocarditis, acute coronary syndrome, hospitalisation for cardiac reason or intervention. Associations between patient characteristics, country characteristics (income inequality expressed as Gini coefficient, health expenditure, schooling, gross domestic product, birth rate and hospital beds) and cardiac endpoints were checked in a three-level model (patient-centre-country).  RESULTS: A total of 30 countries enrolled 2924 patients from 89 centres. At least one endpoint occurred in 645 women (22.1%). Maternal age, New York Heart Association classification and modified WHO risk classification were associated with the combined endpoint and explained 37% of variance in outcome. Gini coefficient and country-specific birth rate explained an additional 4%. There were large differences between the individual countries, but the need for multilevel modelling to account for these differences disappeared after adjustment for patient characteristics, Gini and country-specific birth rate.  CONCLUSION: While there are definite interregional differences in pregnancy outcome in women with cardiac disease, these differences seem to be mainly driven by individual patient characteristics. Adjustment for country characteristics refined the results to a limited extent, but maternal condition seems to be the main determinant of outcome

The genetic history of the Southern Arc: a bridge between West Asia and Europe

By sequencing 727 ancient individuals from the Southern Arc (Anatolia and its neighbors in Southeastern Europe and West Asia) over 10,000 years, we contextualize its Chalcolithic period and Bronze Age (about 5000 to 1000 BCE), when extensive gene flow entangled it with the Eurasian steppe. Two streams of migration transmitted Caucasus and Anatolian/Levantine ancestry northward, and the Yamnaya pastoralists, formed on the steppe, then spread southward into the Balkans and across the Caucasus into Armenia, where they left numerous patrilineal descendants. Anatolia was transformed by intra–West Asian gene flow, with negligible impact of the later Yamnaya migrations. This contrasts with all other regions where Indo-European languages were spoken, suggesting that the homeland of the Indo-Anatolian language family was in West Asia, with only secondary dispersals of non-Anatolian Indo-Europeans from the steppe

Hydrogeological characteristics of the alluvial sediments of the river Bregalnica at the Fortuna locality water supply, Stip

The total water capacity of the Fortuna wll system which uses the groundwater for the water supply for the town of Stip amounts to 171 l/s, but today this system yields only 50 l/s. The capacity of individual wells ranges frm 10 to 27 l/s with level variations ranging from 2,5 to 5.87 m. Water layers thickness is from 6 to 7 m. Mean filtration coefficient after test pumping is 0.4655 sm./s and after the granulometric sampling 0.2 sm./s. Mn content in the water is about 250 times higher than the maximum allowed

Humoral and cell-mediated immune responses following lesions of the nucleus basalis magnocellularis in the rat

The present study was undertaken to elucidate whether electrolytic lesions of nucleus basalis magnocellularis-NBM (an animal model of Alzheimer's disease-AD) may influence humoral and cellular immune responses in adult male Wistar rats. For this purpose intact control (IC), sham-operated (SO) and NBM-lesioned rats were divided into two main groups: (1) rats immunized with sheep red blood cells (SRBC) for plaque-forming cell (PFC) response and anti-SRBC agglutinins, and (2) rats immunized with bovine serum albumin in complete Freund's adjuvant (BSA-CFA) for anti-BSA antibody production, Arthus and delayed hypersensitivity skin reaction to BSA. PFC responses and anti-SRBC agglutinins as well as diameter and expression of edema/induration of Arthus/delayed skin reaction and titer of anti-BSA antibody were significantly lower in NBM lesioned rats (compared to IC and SO). The results showed that in NBM-lesioned rats both the humoral and cellular immune responses were suppressed

Exome-sequencing in a large population-based study reveals a rare Asn396Ser variant in the LIPG gene associated with depressive symptoms

Functional Genomics of Systemic Disorder