A etiologia da síndrome do desconforto respiratório (SDR) é considerada multifatorial e multigênica. A proteína B do surfactante (SP-B) é essencial para a função pulmonar normal. O gene responsável pela produção da SP-B está localizado no braço curto do cromossomo 2 (2p12->p11.2), estendendo-se por aproximadamente por 9.5 Kilobases e contém 11 exons. A presença de polimorfismos e mutações em genes dos componentes do surfactante, particularmente no gene da SP-B, parece estar associada à SDR. Objetivos: Determinar a freqüência de polimorfismos do gene que codifica a proteína B do surfactante no DNA de recém nascidos pré-termo portadores de SDR e de recémnascidos de termo sadios, comparar as freqüências desses polimorfismos entre os dois grupos e avaliar se existe alguma relação entre sexo, raça e SDR. Casuística e Métodos: Foram incluídos no estudo 150 RN, sendo 50 pré-termo portadores de SDR com idades gestacionais variando entre 28 e 33 semanas e 6 dias, e 100 RN de termo clinicamente sadios com idades gestacionais variando de 37 a 41 semanas e seis dias, no período de junho de 2001 a julho de 2004. Foram analisados quatro polimorfismos: A/C no nucleotídeo - 18; C/T no nucleotídeo 1580; A/G no nucleotídeo 9306 e G/C no nucleotídeo 8714. Os polimorfismos foram determinados através da amplificação dos segmentos de DNA genômico por reação em cadeia da polimerase e posterior genotipagem. Os genótipos foram definidos através da análise dos produtos obtidos a partir de reações com enzimas de S . 22 restrição [PCR-based converted restriction fragment length polymorphism (cRFLP)]. Resultados: O grupo controle foi constituído por 100 RN de termo aparentemente saudáveis; 42(42%) do sexo feminino e 58(58%) do sexo masculino; 39(39%) da raça branca e 61(61%) da raça não branca. O peso variou de 2280g a 4.740g (média de 3.239,9g), e a idade gestacional variou de 37 a 41 semanas e seis dias (média de 39 semanas e 3 dias). O grupo SDR foi composto por 50 RNPT, sendo 21(42%) do sexo feminino e 29(58%) do sexo masculino; 28(56%) eram da raça branca e 22(44%), não brancos. O peso variou de 640g a 2.080g (média de 1273g); a idade gestacional média foi de 31 semanas e dois dias, tendo variado de 28 semanas a 33 semanas e seis dias. Foi encontrada uma diferença estatisticamente significante quando comparados os dois grupos e a variável raça isoladamente no polimorfismo G/C 8714 (p=0,028). Quando a variável sexo foi analisada isoladamente, não houve diferença estatisticamente significante dos polimorfismos entre os dois grupos. As freqüências dos genótipos dos outros três polimorfismos estudados foram muito similares nos dois grupos, não tendo sido encontrada diferença estatisticamente significante quando as variáveis sexo e raça foram avaliadas conjuntamente. Conclusão: A análise do polimorfismo G/C 8714 mostrou que em indivíduos da raça branca, o genótipo GG foi apenas encontrado no grupo SDR, sugerindo que a sua presença possa se constituir em um possível fator de risco para a doença, enquanto que o genótipo GC foi mais prevalente no grupo controle indicando a possibilidade desse genótipo ser um fator protetor / The etiology of respiratory distress syndrome (RDS) is multifactorial and multigenic. Surfactant protein B (SP-B) is essential for normal lung function. The human SP-B gene is located on the short arm of chromosome 2 (2p12->p11.2), encompasses approximately 9.5 kilobases and have 11 exons. Polymorphisms and mutations in the genes that encode the surfactant components, particularly the SP-B gene, have been associated to the pathogenesis of RDS. Aims: To analyze SP-B gene polimorfisms frequencies in preterm babies with RDS and healthy term newborns, to compare the polymorphisms frequencies between both groups and to evaluate if there are differences related to sex, race and RDS. Material and Methods: We included 150 neonates, 50 preterm with RDS and gestational ages ranging from 28 weeks to 33 weeks and 6 days, and 100 healthy term newborns with gestational ages ranging from 37 weeks to 41 weeks and 6 days, during June 2001 to July 2004. Four SP-B gene polymorphisms were analyzed: A/C at - 18, C/T at 1580; A/G at 9306 and G/C at nucleotide 8714. The polymorphisms were detected by PCR amplification of genomic DNA and genotyping. The genotypes were determined using PCR-based converted restriction fragment length polymorphism (cRFLP). Results: The control group comprised 100 apparently healthy term newborns; 42(42%) were female and 58(58%) male; 39(39%) were Whites and 61(61%) non-Whites. Weight ranged from 2280g to 4.740g (mean 3.239,9g); gestational age ranged from 37 weeks to 41 weeks and six days (mean 39 weeks and 3 days). The RDS group comprised 50 preterm neonates, 21(42%) female and 29(58%) male; 28(56%) were Whites and 22(44%) non-Whites. Weight ranged from 640g to 2.080g (mean 1273g); mean gestational age was 31 weeks and two days (range, 28-33 weeks and six days). All genotypes frequencies were similar among both groups when sex and race were analyzed together. When race was analyzed separately, there was a statistically significant difference between both groups in the polymorphism G/C at 8714 (p=0,028). There was no difference between both groups in all polymorphisms when sex was analyzed separately. Conclusions: The analysis of the SP-B polymophism G/C 8714 showed that in white neonates the genotype GG was only found in the RDS group and the genotype GC was more frequently found in controls. This suggests that genotype GG could be a risk factor while GC might be a protective genotype for the development of the disease

A fertilização in vitro tem sido associada com um aumento na incidência das hipospádias, e alguns hormônios esteróides usados em seus protocolos têm sido implicados neste processo. Para testar essas hipóteses em um modelo animal, descrevemos neste trabalho as alterações morfológicas ocorridas no tubérculo genital de camundongos, expostos à progesterona durante a vida intrauterina. Foi administrado acetato de medroxiprogesterona por via subcutânea no período pré-natal em animais normais e animais desprovidos de receptores androgênicos (Tfm). A progesterona induziu a formação de hipospádia nos animais do sexo masculino, virilização nos do sexo feminino e não causou alterações nos animais Tfm / In vitro fertilization (IVF) has been associated with an increase incidence of hypospadias. IVF protocols require the maternal use of progesterone which may be a factor in causing hypospadias. To test these hypotheses in an animal model, we describe the effects of maternal progesterone exposure on genital development in mice. Medroxyprogesterone acetate (MPA) was administered by subcutaneous injection during the pre-natal period to wild type mice and animals knockout to androgen receptors (Tfm mice). Progesterone caused hypospadias in male mice fetuses, a virilizing effect in the female mice genitalia and didn't have any effect in Tfm animals

INTRODUÇÃO: Raramente os estudos populacionais sobre disfunção erétil (DE) incluem homens com menos de 40 anos de idade e, quando o fazem, não há detalhamento dos vários fatores e conseqüências potencialmente associados a esta condição. O objetivo deste estudo foi avaliar a prevalência da disfunção erétil e seus fatores associados em amostra da população brasileira de 18 a 40 anos. MÉTODOS: O Estudo da Vida Sexual do Brasileiro (EVSB) entrevistou 7.022 homens e mulheres em locais públicos de 18 grandes centros urbanos do Brasil por meio de um questionário auto-responsivo que abordava aspectos demográficos, de saúde, de hábitos e dificuldades sexuais, sendo a presença de disfunção erétil avaliada por questão única. De todo o grupo, 1.947 eram do sexo masculino e da faixa etária de 18 a 40 anos. RESULTADOS: Um total de 35% dos indivíduos do estudo tinha queixas de disfunção erétil (73,7% dos quais sendo DE mínima e 26,3% moderada/completa). O relato de DE foi mais freqüente na faixa etária mais jovem (18 a 25 anos), nos indivíduos da raça negra, parda ou amarela e no grupo que tinha menor escolaridade; na analise de regressão múltipla, porém, dentre esses fatores, somente o baixo grau de instrução permaneceu fortemente associado à presença de DE. Estado civil e situação empregatícia não influenciaram a prevalência de problemas de ereção. Não foi encontrada associação de maior freqüência de DE em homens com histórico de tabagismo, obesidade, diabetes, hipertensão, sedentarismo, cardiopatia, hiperlipidemia, depressão ou ansiedade. Orientação sexual não se relacionou com maior prevalência de DE, porém a falta de informações sobre sexo durante a vida, dificuldades no início da vida sexual e a ausência do hábito de masturbação correlacionaram-se com uma maior chance de queixas de DE. Para toda a população do estudo, as fontes recentes de informação sobre sexo foram principalmente os livros e revistas, seguidos pela conversa com a parceira e com amigos, sendo a orientação médica xvi menos citada pelo grupo. Outros problemas sexuais, como ejaculação precoce, retardada e diminuição de libido, foram mais freqüentes em homens com DE, em comparação aos homens sem esta disfunção. Menos de 10% dos homens com DE relataram já terem recebido tratamento para o problema e cerca de 3% de indivíduos sem queixas de DE declararam terem feito uso de medicações para melhora da ereção. A DE causou impacto negativo em várias áreas da vida dos portadores desta disfunção: no relacionamento com a parceira e amigos, no trabalho e lazer, além da auto-estima dos indivíduos com o problema, causando também auto-avaliação negativa quanto ao desempenho e a vida sexual. CONCLUSÕES: A prevalência de DE, mesmo na população abaixo de 40 anos, foi alta, com preponderância da forma leve. Baixa escolaridade e problemas na iniciação sexual associaram-se com a presença de DE e, provavelmente devido a pouca idade dos indivíduos da amostra, não foi encontrada associação de DE com problemas de saúde de causa orgânica. Ações nas áreas de educação e prevenção teriam um impacto positivo no controle de disfunção erétil na população / INTRODUCTION: Populational studies in erectile dysfunction (ED) rarely included subjects less than 40 years old and, when this was done, there were no information on the several factors and consequences potentially associated with this condition. The objective of this study was to evaluate the prevalence of erectile dysfunction (ED) and associated factors in a sample of Brazilian men aged 18 to 40 years old. METHODS: The Brazilian Sexual Life Study interviewed 7,022 men and women in public places of 18 major Brazilian cities using a self-administered questionnaire that investigated social-demographic and health aspects, life habits and sexual difficulties, including ED, which was assessed by a single question. From the whole group, 1,947 were men between 18 and 40 years old. RESULTS: Complaints of ED were found in 35.0% of the study subjects (73.7% had mild ED; 26.3% moderate/complete ED). Greater frequency of ED report was seen in younger subjects (18 to 25 years), in men of black, mixed or Asian races, and in the group with less education; in the multiple regression analyses, among these factors, only low level of education remained strongly associated with ED diagnosis. Employment and marital status didnt affect the prevalence of erection problems. No association was seen between ED report and medical history of smoking, obesity, diabetes, hypertension, sedentary lifestyle, cardiopathy, hyperlipidemia, depression or anxiety. Sexual orientation was not correlated to greater ED frequency, but the lack of information about sex, difficulties in the beginning of sexual life and absence of masturbation habit were related to an increased chance of ED diagnosis. Recent sources of information about sex were mainly books and magazines, followed by talking to the partner and friends, being medical advice less mentioned by the whole study population. Other sexual disorders such as premature or retarded ejaculation, and decreased libido were more frequent in men with ED, in comparison to men without this dysfunction. Less than 10% of men with ED xix reported that ever received treatment for this problem, and about 3% of subjects without ED complaints admitted the use of medications to improve erectile function. ED caused negative impact in several aspects of life: in the relationship with partner and friends, in work and leisure, besides mens self-esteem, causing also a negative self-evaluation of sexual life and performance. CONCLUSIONS: Prevalence of ED in this population below 40 years of age was high, mostly of mild severity. Low education and problems in sexual initiation correlated to ED occurrence and, probably due to the sample subjects young age, no association was found with health problems of organic causes. Measures in the fields of education and prevention would have a positive impact in the control of erectile dysfunction in the population

Bibliography: leaves 107-119.

Bibliography: leaves 107-119 / viii, 149 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--University of Adelaide, Dept. of Community Medicine, 1987

Background: Second to Finland, Sweden has the world’s highest incidence of type 1 diabetes. Experiences of serious life events have retrospectively been shown to constitute a risk factor for the development of this disease, probably via the biological stress response. Parenting stress and maternal attachment insecurity are other important sources of stress in early childhood. Psychological stress increases the need for insulin and may induce insulin resistance, which might add extra pressure on the insulin-producing beta cells in the pancreas (beta-cell stress). The aim of the current thesis was to propose and start investigating a stress hypothesis – namely that psychological stress may induce insulin resistance leading to beta-cell stress, which could trigger an autoimmune reaction towards beta-cells in genetically predisposed children. When all the beta cells have been destroyed, insulin can no longer be produced in the body and type 1 diabetes becomes manifest. Methods: Families from the prospective population-based ABIS-project, which follows approximately 17 000 children, participated in the empirical studies of the current thesis. The mothers completed questionnaires, including various measures of psychological stress (e.g. parenting stress and experiences of serious life events) and socio-demographic background, at the birth of the child and when the child was 1 as well as 2.5 years of age. Maternal attachment insecurity was assessed with the Adult Attachment Interview. Blood samples drawn from the children at 1 and 2.5 years of age were analyzed for type 1 diabetes-related autoantibodies towards Tyrosine phosphatase (IA-2) and Glutamic Acid Decarboxylase (GAD). Findings and Conclusions: Parenting stress and experiences of serious life events like divorce and maternal exposure to violence were associated with the induction of diabetes-related autoimmunity in early childhood, possibly via insulin resistance and beta-cell stress. The risk of developing diabetesrelated autoimmunity after parental divorce or mothers’ exposure to violence was about threefold. None of the results were explained by any of the potential confounding factors analyzed. These results support and strengthen the stress hypothesis, which warrants further investigation. Mothers’ attachment insecurity was not associated with the induction of diabetes-related autoimmunity in their infants. However, this lack of association was perhaps due to methodological constraints. The vast majority of the parents were calmed or unaffected concerning their participation in the ABIS-project, suggesting that large-scale medical screening-projects in the general population are not in themselves a cause for worry and can be performed without causing increased anxiety. / On the day of the public defence the working title of article III was: Psychosocial correlates of parenting stress, lack of support and lack of confidence – A study of all babies in Southeast Sweden (ABIS). The status of article IV was: Manuscript to be submitted shortly; the status of article V was: Manuscript in preparation.

It is now generally acknowledged that particulate air pollution can cause respiratory symptoms and that indoor dust particles may be associated with mucous membrane irritation and odour annoyance. One reason for this may be that dust particles adsorb large quantities of gases and other volatile compounds. It is therefore important to be able to determine the chemical compounds adsorbed onto indoor dust particles. In this thesis, a new technique was developed that can analyse chemical compounds in indoor dust particles in a simple yet accurate way. In its basic configuration, it comprises a one stage thermal desorption oven, a gas flow cell with a miniaturized GC column, and a nitrogen-flushed photo diode array (PDA) detector for fast UV spectra recording. The dust sample is thermally desorbed in the oven and the released compounds are flushed onto the GC column by means of a carrier gas stream; the separated compounds are then registered by the PDA detector and identified by their characteristic gas-phase UV spectra. Using this set-up, a number of volatile organic as well as inorganic compounds were identified in indoor dust particles, e.g. nitric oxide, ammonia, hydrogen sulphide, pyridine, 2-furaldehyde, 2-methylfuran, and isoprene. Moreover, acrylate monomers were identified in dust samples from a secondary school with problems due to powdering floor polish. An instrumental set-up with higher performance was achieved by interfacing the gas flow cell to a capillary GC column. When airborne indoor dust samples were analysed by this system and by GC-MS under similar conditions of thermal desorption (150 °C) and GC separation, the two analytical systems were found to be complementary. GC-UV together with GC-MS was thus demonstrated to be considerably more powerful than GC-MS alone for the analysis of volatile organic compounds (VOC) in indoor dust. When airborne dust samples from damp (n=9) and control (n=9) residences were analysed for VOC and microorganisms, identifications made by culture and microscopy of the major moulds found, i.e. Aspergillus, Cladosporium and Penicillum, coincided with the identification of VOC known to be produced by these species. A number of additional VOC were also found, some of which may be irritating to the skin, eyes or respiratory tract if present at higher concentrations. Quantitative GC-UV analysis of indoor dust from 389 residences in Sweden showed that the VOC found at the highest concentrations were saturated aldehydes (C5-C10), furfuryl alcohol, 2,6-di-tert-butyl-4-methylphenol, 2-furaldehyde, and benzaldehyde. Alkenals were also found, notably 2-butenal (crotonaldehyde), 2-methyl-propenal (methacrolein), hexenal, heptenal, octenal, and nonenal. GC-UV was also applied (together with GC-MS) to determine VOC in dust from residences of 198 children with symptoms of asthma and/or allergy (cases) and from residences of 202 children without symptoms (controls). The mean concentration of nicotine was found to be significantly higher in dust from case residences, while the mean concentrations of hexane, nonanal, octane, 2-pentylfuran and tridecanol were significantly higher in dust from control residences. In a stepwise logistic regression model, nicotine, hexanal, furfuryl alcohol, nonane, butanol, and octenal showed increased relative risks, expressed as odds ratios comparing cases with controls. By contrast, benzaldehyde, nonanal, butenal, hexane, tridecanol, and pentylfuran showed decreased relative risks. These findings point to the possibility that not only environmental tobacco smoke but also other emissions in the indoor environment may be linked to the increased prevalence of asthma and/or allergy in children. It is concluded that GC-UV may be used as an alternative or complement to GC-MS for measuring chemicals in indoor dust, thus improving the survey and control of human exposure to particle-bound toxicants and other chemicals. / Copyright Agreement: Figure 3 included in the PDF file abowe is the exclusive property of SAGE Publications (http://www.sagepublications.com/), or its licensors and is protected by copyright and other intellectual property laws. The download of the file(s) is intended for the User's personal and noncommercial use. Any other use of the download of the Work is strictly prohibited. User may not modify, publish, transmit, participate in the transfer or sale of, reproduce, create derivative works (including coursepacks) from, distribute, perform, display, or in any way exploit any of the content of the file(s) in whole or in part. Permission may be sought for further use from Sage Publications Ltd, Rights and Permissions Department, 1 Oliver's Yard, 55 City Road, London EC1Y 1SP Fax: +44 (020) 7324-8600. By downloading the file(s), the User acknowledges and agrees to these terms.

Urinary tract infection (UTIs) is an extremely common disease. Proteus mirabilis is a common cause of UTI in individuals with functional or structural abnormalities or with long-term catheterization, it forms bladder and kidney stones as a consequence of urease-mediated urea hydrolysis. Known virulence factors, besides urease, are flagella, fimbriae, outer membrane proteins, hemolysins, amino acid deaminase, protease, capsule and lipopolysaccharide (LPS). Study of LPS core is particularly relevant for several reasons: it is a conserved region, although it is increasingly clear that there is some variability at the genus or groups of similar genera, its chemical structure modulates the endotoxic activity of lipid A, alteration of the LPS core, which generates less virulent bacteria, encourages the search of substances that interfere with the biosynthesis of this region, and conserved regions of the core LPS could be useful as antigens in preventing diseases caused by pathogens that contain these conserved regions. The specific aims of this project have been to identify and functionally characterize genes involved in core LPS biosynthesis in P. mirabilis, to elucidate the mechanism of incorporation of galactosamine (GalN) to the core LPS, to identify genes coding for phosphoethanolamine (PEtN) modifications, and to characterize and to study the biological effects of the gene encoding the PEtN transferase involved in the modification of the second heptose residue (L,D-HepII). We found that P. mirabilis has most of the genes for the biosynthesis of LPS core grouped in the waa cluster in the chromosome. Despite this, additional genes required for core LPS biosynthesis are found outside the waa cluster. The pentasaccharide of the inner core, shared by all Enterobacteriaceae, is biosynthesized in P. mirabilis, by the sequential activity of a bifunctional transferase (WaaA) and three heptosyltransferases (WaaC, WaaF, and WaaQ). These enzymes are transcribed from genes located inside the waa cluster, and are conserved in P. mirabilis strains analyzed; for more, they show a high identity and similarity level to homologues proteins of Escherichia coli, Klebsiella penumoniae and Serratia marcescens. The waaL gene, coding for the O-antigen polymerase ligase, is found adjacent to the classic waa cluster. Downstream this gene, four genes encoding enzymes belonging to the 4 (walM, walN, and WalR), and 9 (walO) glycosyltransferase family were found. Even if members of these families were related to LPS core biosynthesis in several Gram-negative bacteria, in P. mirabilis they do not appear to be involved in the biosynthesis of the reported core LPS structures. The presence of the disaccharide hexosamine (HexN)-1,4-galacturonic acid (GalA) is a feature of P. mirabilis LPS outer core. Depending on the nature of the HexN outer core residue, two different homologues for N-acetyl-hexosamine transferases are present in the waa cluster: wabH or wabP. Altought the incorporation of glucosamine into LPS core requires an acetylglucosaminyltransferase (WabH) and a deacetilase (WabN), the incorporation of GalN requires three enzymes: an acetylgalactosaminyltransferase (WabP), a deacetilase (WabN) and an epimerase (gne). An amplification test with specific primers for this two different homologues can be used to predict the HexN nature in P. mirabilis LPS cores. The strain-specific genes wamB and wamC code for a galactosyltransferase and a heptosyltransferase respectively in strain R110 of P. mirabilis. The enzyme encoded by gene wamD is a N-acetylglucosaminyltransferase, and it is found in strain 51/57 of P. mirabilis. WamA, coded by wamA gene in the waa cluster of strains R110, 50/57, TG83 and HI4320, is a heptosyltransferase responsible for the incorporation of a quarter residue of heptose (Hep), in DD configuration, to the GalA II of the outer core. In P. mirabilis strain 51/57, a gene coding a protein of the Mig-14 family was identified inside the waa cluster, this localization appears to be an exception in the Enterobacteriaceae family. Inspection of the whole genome of P. mirabilis HI4320 did not allow the identification of a mig-14 similar gene. There are three putative PEtN transferases in the genome of P. mirabilis: PMI3040, PMI3576, and PMI3104. The gene identified as eptC (PMI3104) transfers the moiety of PEtN to the O-6 position of L,D-Hep II (HepII6PEtN). The absence of the positive charge due to PEtN residue doesn't affect the bacterial growth kinetics in lab conditions in rich or defined media, but causes a moderate destabilization of the outer-membrane. Despite the lack of the PEtN residue on the Hep II in P. mirabilis LPS core, has no statistically effects during urinary tract infection assays in mouse model, the absence of this modification causes an increase sensitivity to complement in non-immune human sera. / P. mirabilis no es una causa frecuente de infecciones urinarias en el huésped normal, más bien infecta el tracto urinario con alteraciones funcionales o anatómicas, o instrumentación crónica como el cateterismo. P. mirabilis está a menudo asociado con cálculos urinarios e incrustaciones de los catéteres y es, particularmente importante, en pacientes con cateterización prolongada. Las infecciones del tracto urinario asociadas a cateterización son mundialmente reconocidas como la causa más común de infección asociada a tratamientos en ambiente hospitalario. El LPS es un factor de virulencia importante en bacterias Gram negativas patógenas. También conocido como endotoxina, es una molécula glicolipídica que constituye la estructura mayoritaria de la cara externa de la membrana externa (OM). En Proteus mirabilis la mayoría de los genes responsables de la biosíntesis de núcleo de LPS están localizados en el cromosoma, en el agrupamiento génico waa. A pesar de esto, algunos genes adicionales, necesarios para la biosíntesis del núcleo de LPS, se encuentran ubicados fuera del agrupamiento génico waa. El pentasacárido del núcleo interno, común a todas las Enterobacteriáceae, se biosintetiza en P. mirabilis, por la actividad secuencial de una transferasa bifunciona (WaaA) y tres heptosiltransferasas (WaaC, WaaF, y WaaQ). La presencia del disacárido HexN‐1,4‐GalA es característica del núcleo externo de LPS en P. mirabilis. Dependiendo de la naturaleza del residuo de HexN, se encuentran, en el agrupamiento génico waa, dos HexNAc transferasas diferentes: wabH o wabP. El gen eptC (PMI3104) codifica para la enzima que transfiere el residuo de fosfoetanolamina a la posición O-6 de la L,D-Hep II (HepII6PEtN), en el núcleo de LPS de P. mirabilis. La ausencia de la carga positiva del residuo de fosfoetanolamina no afecta a la cinética de crecimiento de las bacterias en condiciones standard de laboratorio sea en medios ricos o definidos. La ausencia del residuo fosfoetanolamina provoca una desestabilización moderada de la membrana externa que se traduce en una disminución de la MIC para SDS.

Background: A younger age at onset of use of a specific substance is a well-documented risk-factor for a substance use disorder (SUD) related to that specific substance. However, the cross-substance relationship between a younger age at onset of alcohol use (AU) and nicotine use (NU) and the risk of cannabis use disorders (CUD) in adolescence and early adulthood remains unclear. Aims: To identify the sequence of and latency between initial AU/NU and initial cannabis use (CU). To investigate whether younger age at AU- and NU-onset is associated with any and earlier CU-onset and a higher risk of transition from first CU to CUD, taking into account externalizing disorders (ED) and parental substance use disorders as putative influential factors. Methods: Prospective-longitudinal community study with N = 3021 subjects (baseline age 14–24) and up to four assessment waves over up to ten years with additional direct parental and family history information. Substance use and CUD were assessed with the DSM-IV/M-CIDI. Results: Most subjects with CU reported AU (99%) and NU (94%). Among users of both substances, 93% reported AU prior to CU (87% for NU). After adjustment for ED and parental substance use disorders younger age at AU-onset was associated with any CU. Younger age at NU-onset was associated with earlier CU initiation. Younger age at AU- and NU-onset was not associated with a higher risk of CUD. Conclusions: The cross-substance relevance of younger age at first AU and NU for the risk of CUD is limited to early CU involvement.

Hintergrund. Angst- und depressive Störungen treten sehr häufig auf. Die Komorbidität zwischen beiden Störungsgruppen ist hoch. Quer- und Längsschnittstudien legen nahe, dass vorausgehende Angststörungen das Risiko sekundärer Depression erhöhen, wobei wenig zur Rolle klinischer Charakteristika von Angststörungen in diesem Zusammenhang bekannt ist. Es liegen eine Fülle von Befunden zu Risikofaktoren für Angst- und depressive Störungen vor, die bei genauerer Betrachtung allerdings eine Reihe methodischer Limitationen und offener Forschungsfragen aufweisen (z.B. viele Querschnittserhebungen, klinische Stichproben, keine vergleichenden Analysen der Risikofaktoren von Angststörungen versus Depression). Eine reliable Bewertung der diagnostischen Spezifität vs. Unspezifität von Vulnerabilitäts- und Risikofaktoren von Angst- und depressiven Störungen mit den bislang vorliegenden Ergebnissen schwer möglich ist. Fragestellungen. Es wurden Gemeinsamkeiten und Unterschieden hinsichtlich der Korrelate und Risikofaktoren von reinen Angst- versus reinen depressiven Störungen untersucht. Durch einen Vergleich reiner Angst- mit reinen depressiven Störungen sollte eine reliablere Einschätzung der Spezifität versus Unspezifität der untersuchten Vulnerabilitäts- und Risikofaktoren erfolgen. Der zweite Fokus lag in der Analyse der Rolle von primären Angststörungen und der mit ihnen assoziierten klinischen Merkmale bei der Entwicklung sekundärer Depressionen. Methoden. Die „Early Developmental Stages of Psychopathology (EDSP)“- Studie ist eine prospektive, longitudinale Studie. Eine repräsentative Bevölkerungsstichprobe von ursprünglich 3021 Jugendlichen und jungen Erwachsenen (zu Baseline 14-24 Jahre alt) wurde dreimal befragt (eine Baseline-Erhebung sowie zwei Folgebefragungen). Zusätzlich wurden die Eltern der Probanden, die am ersten Follow-Up teilgenommen hatten, in einem Elterninterview direkt interviewt. Von 2548 Probanden lagen diagnostische Informationen von der Basisbefragung und des Follow-Up-Zeitraumes vor. Psychische Störungen wurden mit Hilfe des M-CIDI nach DSM-IV Kriterien erfasst. Darüber hinaus wurden eine Vielzahl potenzieller Risikofaktoren (z.B. Behavioral Inhibition, kritische Lebensereignisse) erhoben. Ergebnisse. Die drei wichtigsten Ergebnisse dieser Arbeit waren: a)Es konnten gemeinsame, aber auch einige spezifische Risikofaktoren für Angststörungen versus depressive Störungen nachgewiesen werden. b)Die Angststörungen stellen eine heterogene Gruppe dar: Auch innerhalb der Gruppe der Angststörungen zeichnen sich spezifische Risikofaktoren für spezifische Angststörungen ab (d.h. es fanden sich Unterschiede zwischen Spezifischer und Sozialer Phobie). c)Es wurden starke Assoziationen zwischen Angststörungen sowie der mit ihnen assoziierten Merkmale (Beeinträchtigung, Komorbidität, Panikattacken) und der Entwicklung sekundärer depressiver Störungen gefunden. Im multiplen Modell, das alle klinischen Merkmale beinhaltete, stellte sich der Faktor schwere Beeinträchtigung als bedeutendster Prädiktor heraus. Diskussion und Schlussfolgerungen. Insgesamt befürworten die Befunde dieser Arbeit eher die sog. Splitters-Perspektive von zumindest teilweise unterschiedlichen Risikofaktoren für Angst- und depressive Störungen. Einer der potentesten Risikofaktoren für depressive Störungen scheinen vorausgehende Angststörungen zu sein, der Schweregrad der Beeinträchtigung durch die Angststörung spielt dabei eine entscheidende Rolle. Eine rechtzeitige, effektive Behandlung dieser Angststörungen könnte eine sehr erfolgversprechende Strategie in der Prävention depressiver Störungen sein. Der Beeinträchtigungsgrad durch die Angststörung kann dabei zur Identifizierung von sog. Hoch-Risiko-Personen genutzt werden. / Background. Anxiety disorders and depression are frequent mental disorders; comorbidity is high. Although cross-sectional and longitudinal studies suggest that anxiety disorders increase the risk of subsequent depression, little is known about the role of clinical characteristics of anxiety disorder in this association. Furthermore, there are a lot of studies investigating risk factors of anxiety disorders and depression. Most of these studies, however, have some substantial limitations (e.g., cross-sectional design, clinical samples, lack of analyses comparing risk factors of anxiety disorders versus depression) preventing a reliable assessment of the specificity of vulnerability and risk factors for anxiety disorders and depression. Aims. The first aim of the study was to examine common and specific correlates and risk factors of pure anxiety disorders versus pure depression. The second aim was to analyse the association between anxiety disorders and subsequent depression and the role of clinical characteristics of anxiety disorders in this associations. Methods. The data are from the Munich Early Developmental Stages of Psychopathology (EDSP) study. The EDSP study is a 4-year prospective-longitudinal community study, which includes both baseline and follow-up data on 2548 adolescents and young adults 14 to 24 years of age at baseline. Parents of those probands participated at the first follow-up of the study were also interviewed. DSM-IV diagnoses were made using the Munich-Composite International Diagnostic Interview (M-CIDI). A range of risk factors were assessed (e.g., behavioral inhibition, life events). Results. There were both common and specific risk factors of anxiety disorders and depression. Furthermore, specific risk factors for specific anxiety disorders could be identified (i.e. different risk factors of specific phobia versus social phobia were found). Anxiety disorders and their clinical characteristics (impairment, comorbidity, panic attacks) were significantly associated with the development of subsequent depression. In the final model, which included all clinical characteristics, severe impairment remained the only clinical feature that was an independent predictor of subsequent depression. Discussion and conclusions. The findings suggest that there are specific risk factors of anxiety disorders and depression. Anxiety disorders are a very powerful risk factor for subsequent depression whereas severe impairment seems to play a major role in this association. Effective treatment of anxiety disorders, specifically those associated with extreme disability, might be important for targeted primary prevention of depression. The degree of impairment of anxiety disorders could be used for the identification of individuals at highest risk for onset of depression.