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Using Multivariate Statistics

Introduction: The Danish Civil Registration System (CRS) was established in 1968, and all persons alive and living in Denmark were registered for administrative use. Content: CRS includes individual information on the unique personal identification number, name, gender, date of birth, place of birth, citizenship, identity of parents and continuously updated information on vital status, place of residence and spouses. Validity and coverage: Since 1968, CRS has recorded current and historical information on all persons living in Denmark. Among persons born in Denmark in 1960 or later it contains complete information on maternal identity. For women born in Denmark in April 1935 or later it contains complete information on all their children. CRS contains complete information on immigrations and emigrations from 1969 onwards, permanent residence in a Danish municipality from 1971 onwards, and full address in Denmark from 1977 onwards. Conclusion: CRS in connection with other registers and biobanks will continue to provide the basis for significant knowledge relevant to the aetiological understanding and possible prevention of human diseases.

https://journals.sagepub.com/doi/pdf/10.1177/1403494810387965

The Danish civil registration system

The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies

The dopamine hypothesis of schizophrenia has been one of the most enduring ideas in psychiatry. Initially, the emphasis was on a role of hyperdopaminergia in the etiology of schizophrenia (version I), but it was subsequently reconceptualized to specify subcortical hyperdopaminergia with prefrontal hypodopaminergia (version II). However, these hypotheses focused too narrowly on dopamine itself, conflated psychosis and schizophrenia, and predated advances in the genetics, molecular biology, and imaging research in schizophrenia. Since version II, there have been over 6700 articles about dopamine and schizophrenia. We selectively review these data to provide an overview of the 5 critical streams of new evidence: neurochemical imaging studies, genetic evidence, findings on environmental risk factors, research into the extended phenotype, and animal studies. We synthesize this evidence into a new dopamine hypothesis of schizophrenia-version III: the final common pathway. This hypothesis seeks to be comprehensive in providing a framework that links risk factors, including pregnancy and obstetric complications, stress and trauma, drug use, and genes, to increased presynaptic striatal dopaminergic function. It explains how a complex array of pathological, positron emission tomography, magnetic resonance imaging, and other findings, such as frontotemporal structural and functional abnormalities and cognitive impairments, may converge neurochemically to cause psychosis through aberrant salience and lead to a diagnosis of schizophrenia. The hypothesis has one major implication for treatment approaches. Current treatments are acting downstream of the critical neurotransmitter abnormality. Future drug development and research into etiopathogenesis should focus on identifying and manipulating the upstream factors that converge on the dopaminergic funnel point.

/pdf/the-dopamine-hypothesis-of-schizophrenia-version-iii-the-3pqlczm8om.pdf

The Dopamine Hypothesis of Schizophrenia: Version III—The Final Common Pathway

A review of MRI findings in schizophrenia

OBJECTIVE: The authors synthesize findings of previous studies implicating migration as a risk factor for the development of schizophrenia and provide a quantitative index of the associated effect size. METHOD: MEDLINE was searched for population-based incidence studies concerning migrants in English-language publications appearing between the years 1977 and 2003. Article bibliographies and an Australian database were cross-referenced. Studies were included if incidence reports provided numerators and denominators and if age correction was performed or could be performed by the authors. Relative risks for migrant groups were extracted or calculated for each study. Significant heterogeneity across studies indicated the need for a mixed-effects meta-analytic model. RESULTS: The mean weighted relative risk for developing schizophrenia among first-generation migrants (40 effect sizes) was 2.7 (95% confidence interval [CI]=2.3–3.2). A separate analysis performed for second-generation migrants (seven effect siz...

https://ajp.psychiatryonline.org/doi/pdf/10.1176/appi.ajp.162.1.12

Schizophrenia and migration: a meta-analysis and review.

The hypothesis that chronic and long-term experience of 'social defeat' may increase the risk for schizophrenia is proposed. This increased risk may result from sensitisation of the mesolimbic dopamine system and/or increased baseline activity of this system. Data supporting the social defeat hypothesis are presented.

/pdf/social-defeat-risk-factor-for-schizophrenia-4l4a4ckwwz.pdf

Social defeat: Risk factor for schizophrenia?

Psychological distress among AIDS orphans in rural Uganda.

According to the social defeat (SD) hypothesis, published in 2005, long-term exposure to the experience of SD may lead to sensitization of the mesolimbic dopamine (DA) system and thereby increase the risk for schizophrenia. The hypothesis posits that SD (ie, the negative experience of being excluded from the majority group) is the common denominator of 5 major schizophrenia risk factors: urban upbringing, migration, childhood trauma, low intelligence, and drug abuse. The purpose of this update of the literature since 2005 is to answer 2 questions: (1) What is the evidence that SD explains the association between schizophrenia and these risk factors? (2) What is the evidence that SD leads to sensitization of the mesolimbic DA system? The evidence for SD as the mechanism underlying the increased risk was found to be strongest for migration and childhood trauma, while the evidence for urban upbringing, low intelligence, and drug abuse is suggestive, but insufficient. Some other findings that may support the hypothesis are the association between risk for schizophrenia and African American ethnicity, unemployment, single status, hearing impairment, autism, illiteracy, short stature, Klinefelter syndrome, and, possibly, sexual minority status. While the evidence that SD in humans leads to sensitization of the mesolimbic DA system is not sufficient, due to lack of studies, the evidence for this in animals is strong. The authors argue that the SD hypothesis provides a parsimonious and plausible explanation for a number of epidemiological findings that cannot be explained solely by genetic confounding.

/pdf/the-social-defeat-hypothesis-of-schizophrenia-an-update-3d46i6kx92.pdf

Elizabeth Cantor-Graae

Papers

Schizophrenia and migration: a meta-analysis and review.

Social defeat: Risk factor for schizophrenia?

Psychological distress among AIDS orphans in rural Uganda.

The Social Defeat Hypothesis of Schizophrenia: An Update

Substance abuse in schizophrenia: a review of the literature and a study of correlates in Sweden