<p>There are several traditions of conceptualizing and measuring harm from drinking. Two main approaches are considered in the introduction – the psychiatric epidemiology and the social survey research traditions. The present thesis adopts the latter, although, as discussed, on the empirical level there is no sharp borderline between the two perspectives, as there is not between personal (i.e. physical and psychological) and social harm from drinking as such. But while methods for studying personal harm are fairly well developed, social harm, i.e. adverse consequences of alcohol that involve social interaction, has received less attention. One of the aims of the thesis has been to explore different dimensions of harm from drinking, identify different harm areas and develop and apply area-specific measures using general population survey data.</p><p>Two papers examine psychometric properties of a widely used screening instrument, the AUDIT (Alcohol Use Disorder Identification Test). While the first paper is concerned with the validity of the AUDIT, testing it against different criteria, the second paper focuses on the test-retest reliability of the instrument. In the third paper, a number of summary measures of different areas of alcohol-related harm are constructed using factor analysis. These measures are then, in the last paper, applied to estimate prevalence and risk of alcohol-related harm in the Swedish general population. The analyses are based on data from a national survey on drinking problems in Sweden collected in 2001-2002.</p><p>It is concluded that the AUDIT screens well for both impaired self-control and social harm from drinking (as well as for high volume drinking), but performs less well when screening for health problems. The test-retest reliability of the AUDIT is relatively high. In the other two papers, constructing new summary measures and applying them to estimate prevalence of harm, it is concluded that, except for being young, no particular sociodemographic risk groups can be identified for different areas of harm from the same level and pattern of drinking. To what extent this reflects reality or is an effect of the methods we use and kind of population we reach in surveys is discussed.</p>

<p>Kidney dysfunction increases cardiovascular disease (CVD) risk. The mechanisms for the risk increase seem to involve a combination of traditional and non-traditional CVD risk factors.</p><p>We studied renal dysfunction as CVD and mortality risk factor in middle-aged men free from diabetes and CVD. The risk for myocardial infarction (MI) and CVD mortality was increased by ~40% in the 16.5% of men with worse renal function, independent of other CVD risk factors.</p><p>Renal transplant dysfunction as CVD and mortality risk factor was also studied. Renal transplant dysfunction was a risk factor for mortality and for combined CVD endpoint. The risk by renal transplant dysfunction was independent of traditional CVD risk factors as well as transplantation-specific risk factors. Only moderate increase in serum creatinine resulted in mortality and CVD risk comparable to diabetes, older age and higher low density lipoprotein levels.</p><p>In haemodialysis patients, the effects of a dialysis session on non-traditional CVD risk factors were studied. A HD session reduced asymmetric dimethylarginine (ADMA) and homocysteine levels, as well as augmentation index (AIx). The change in AIx was related to ADMA plasma level change.</p><p>In patients with stage 3-5 chronic kidney disease (CKD), endothelium dependent vasodilation (EDV) was studied together with markers of oxidative stress and C-reactive protein (CRP). CRP was related to lipid peroxidation, while EDV was related to intracellular antioxidative capacity measured by reduced glutathione levels.</p><p>These studies demonstrate that mild to moderate renal dysfunction is independently associated with increased CVD risk in apparently healthy people, as well as in renal transplant recipients. The mechanisms by which renal dysfunction increases CVD risk are yet to be elucidated. We suggest that arterial stiffness could be reduced in haemodialysis patients by increasing nitric oxide bioavailability. In stage 3-5 CKD patients, improving intracellular antioxidative capacity may result in endothelial function improvement.</p>

There are several traditions of conceptualizing and measuring harm from drinking. Two main approaches are considered in the introduction – the psychiatric epidemiology and the social survey research traditions. The present thesis adopts the latter, although, as discussed, on the empirical level there is no sharp borderline between the two perspectives, as there is not between personal (i.e. physical and psychological) and social harm from drinking as such. But while methods for studying personal harm are fairly well developed, social harm, i.e. adverse consequences of alcohol that involve social interaction, has received less attention. One of the aims of the thesis has been to explore different dimensions of harm from drinking, identify different harm areas and develop and apply area-specific measures using general population survey data. Two papers examine psychometric properties of a widely used screening instrument, the AUDIT (Alcohol Use Disorder Identification Test). While the first paper is concerned with the validity of the AUDIT, testing it against different criteria, the second paper focuses on the test-retest reliability of the instrument. In the third paper, a number of summary measures of different areas of alcohol-related harm are constructed using factor analysis. These measures are then, in the last paper, applied to estimate prevalence and risk of alcohol-related harm in the Swedish general population. The analyses are based on data from a national survey on drinking problems in Sweden collected in 2001-2002. It is concluded that the AUDIT screens well for both impaired self-control and social harm from drinking (as well as for high volume drinking), but performs less well when screening for health problems. The test-retest reliability of the AUDIT is relatively high. In the other two papers, constructing new summary measures and applying them to estimate prevalence of harm, it is concluded that, except for being young, no particular sociodemographic risk groups can be identified for different areas of harm from the same level and pattern of drinking. To what extent this reflects reality or is an effect of the methods we use and kind of population we reach in surveys is discussed.

Kidney dysfunction increases cardiovascular disease (CVD) risk. The mechanisms for the risk increase seem to involve a combination of traditional and non-traditional CVD risk factors. We studied renal dysfunction as CVD and mortality risk factor in middle-aged men free from diabetes and CVD. The risk for myocardial infarction (MI) and CVD mortality was increased by ~40% in the 16.5% of men with worse renal function, independent of other CVD risk factors. Renal transplant dysfunction as CVD and mortality risk factor was also studied. Renal transplant dysfunction was a risk factor for mortality and for combined CVD endpoint. The risk by renal transplant dysfunction was independent of traditional CVD risk factors as well as transplantation-specific risk factors. Only moderate increase in serum creatinine resulted in mortality and CVD risk comparable to diabetes, older age and higher low density lipoprotein levels. In haemodialysis patients, the effects of a dialysis session on non-traditional CVD risk factors were studied. A HD session reduced asymmetric dimethylarginine (ADMA) and homocysteine levels, as well as augmentation index (AIx). The change in AIx was related to ADMA plasma level change. In patients with stage 3-5 chronic kidney disease (CKD), endothelium dependent vasodilation (EDV) was studied together with markers of oxidative stress and C-reactive protein (CRP). CRP was related to lipid peroxidation, while EDV was related to intracellular antioxidative capacity measured by reduced glutathione levels. These studies demonstrate that mild to moderate renal dysfunction is independently associated with increased CVD risk in apparently healthy people, as well as in renal transplant recipients. The mechanisms by which renal dysfunction increases CVD risk are yet to be elucidated. We suggest that arterial stiffness could be reduced in haemodialysis patients by increasing nitric oxide bioavailability. In stage 3-5 CKD patients, improving intracellular antioxidative capacity may result in endothelial function improvement.

This study examined the hypothesis that developmental expression of psychometric risk in the form of subclinical psychotic experiences in the general population is usually transitory but in some instances may become abnormally persistent and progress to a clinical psychotic state. A prospective cohort study was conducted in a general population sample of 845 adolescents, aged 14–17 years, in Munich, Germany (Early Developmental Stages of Psychopathology Study). Expression of psychosis was assessed 4 times (T0–T3) over a period of 8.4 years. Transition from subclinical psychosis at T0–T2 to clinical psychosis in terms of impairment at T3 was examined as a function of the level of prior persistence of subclinical psychosis (present never, once, twice, or thrice). The more the subclinical psychosis persisted over the period T0–T2, the greater the risk of transition to clinical psychosis at T3 in a dose-response fashion (subclinical psychosis expression once over T0–T2: odds ratio [OR] = 1.5 [95% confidence interval {CI} = 0.6–3.7], posttest probability [PP] = 5%; twice: OR = 5.0 [95% CI = 1.6–15.9], PP = 16%; at all 3 measurements: OR = 9.9 [95% CI = 2.5–39.8], PP = 27%). Of all clinical psychosis at T3, more than a third (38.3%) was preceded by subclinical psychotic experiences at least once and a fifth (19.6%) at least twice. Consequently, a significant proportion of psychotic disorder may be conceptualized as the rare poor outcome of a common developmental phenotype characterized by persistence of psychometrically detectable subclinical psychotic experiences. This may be summarized descriptively as a psychosis proneness-persistence-impairment model of psychotic disorder.

Aim: To examine prospectively over a period of 4 years the profile of cannabis dependence and the risk of specific dependence criteria in a community sample of adolescents. Methods: A representative community sample of 2446 young adults aged 14–24 years at baseline was followed up over a period of 4 years. Frequency of use measures and of criteria for DSM-IV dependence were assessed by standardized diagnostic interview measures (CIDI). To explore the nature of this association, frequency of use and concomitant use of other psychoactive substances was considered. Results: 30% of the sample were cannabis users. Among all users 35% met at least one dependence criterion. Most frequently reported dependence criteria among all users were withdrawal (17%), tolerance (15%), loss of control (14%) and continued use despite a health problem (13%). Even without concomitant use of other illicit drugs, 22% of low frequency users and 81% of high frequency users met at least one dependence criterion. Symptom patterns were similar in high and low frequency users. The occurrence of a dependence syndrome or of specific dependence criteria could not be attributed to the use of other illicit drugs or to comorbid nicotine and alcohol dependence. Conclusions: Regular cannabis use in adolescence is associated with the development of a dependence syndrome. This association cannot be explained by the concomitant use of other illicit substances or by comorbid nicotine and alcohol dependence.

Die klinische Forschung zu Häufigkeit und Krankheitslast psychischer Störungen ist meist in mehrerer Hinsicht nicht repräsentativ. Insbesondere die Tatsache, dass die untersuchten Patienten sich von sich aus in Behandlung begeben, bedeutet eine gewisse Selektion (z.B. überdurchschnittlich motivierte). Mit wie vielen Fällen haben wir es aber zu tun, wenn man auch diejenigen berücksichtigt, die kein aktives Hilfesuch-Verhalten zeigen? Und wie hoch ist die in klinischen Stichproben offensichtliche individuelle Krankheitslast psychischer Störungen auf einer gesellschaftlichen Ebene – auch im Vergleich mit körperlichen Erkrankungen – einzuschätzen? Ansätze für solche Hochrechnungen und die Abschätzung von Häufigkeit, Störungskosten und Behandlungsbedarf psychischer Störungen müssen epidemiologisch anhand von Daten aus der Allgemeinbevölkerung geklärt werden. Die vorliegende Habilitationsschrift basiert auf Publikationen, die in meiner Arbeitsgruppe „Epidemiologie und Versorgungsforschung“ am Lehrstuhl für Klinische Psychologie und Psychotherapie zwischen 2001 und 2006 entstanden sind. Die entsprechenden Befunde und Implikationen wurden und werden nicht nur in der Klinischen Psychologie, sondern auch in Nachbardisziplinen (z.B. Psychiatrie, Epidemiologie, Occupational Health Psychology, Gesundheitsökonomie, Versorgungsforschung) sowie in der nicht-wissenschaftlichen Öffentlichkeit (z.B. Gesundheitsberichterstattung, Versorgungsplanung) zur Kenntnis genommen und zitiert. In den vorgestellten Arbeiten habe ich zunächst – erstmals für Deutschland – auf der Grundlage bevölkerungsbezogener Daten bundesrepräsentative Befunde zur Verbreitung psychischer Störungen herausgestellt (z.B. Jacobi, Wittchen et al., 2004; Jacobi, Hoyer &amp;amp; Wittchen, 2004; Jacobi, Klose &amp;amp; Wittchen, 2004). Zum zweiten beschäftigte ich mich mit der internationalen Befundlage, indem ich mich an der Koordination eines internationalen und multidisziplinären Forscher-Netzwerkes beteiligte, das eine umfassende Abschätzung der Größenordnung im Sinne von Verbreitung und Kosten für die EU vorgenommen hat (Wittchen &amp;amp; Jacobi, 2005). Vor diesem Hintergrund habe ich zum dritten ausgewählte Fragestellungen zum Zusammenhang zwischen psychischen Störungen und körperlichen Erkrankungen bzw. zur Stärke und zu Konsequenzen solcher Komorbidität verfolgt (z.B. Goodwin, Jacobi &amp;amp; Thefeld, 2003; Sareen, Jacobi et al., 2006). Die Habilitationsschrift verdeutlicht nicht nur die eminente Größenordnung und Krankheitslast psychischer Störungen (z.B. reduzierte Lebensqualität, Beeinträchtigungen, Krankheitskosten, Verschlechterung des gesundheitlichen Outcomes bei körperlichen Erkrankungen). Sie eröffnet auch neue wissenschaftliche Perspektiven ihrer Erforschung, z.B. im Hinblick auf Prävention und Behandlungsbedarf, oder hinsichtlich der Verschränkungen mit Prozessen körperlicher Morbidität. / This Habilitation-Thesis, based on 10 peer-reviewed publications (2001-2006), presents findings on size and burden of mental disorders in the community. First, following an introductory discussion of methodological aspects in epidemiological studies, an overview of the prevalence of mental disorders in Germany and Europe is given (Part A). As Examples for socio-economic determinants of mental disorders, some analyses on gender differences and a comparison between West and East Germany are presented (Part B). Further, it is shown that mental disorders are costly (in terms of disability adjusted life years as well as in terms of direct and indirect monetary burden) (Part C). This refers also to the interplay between mental disorders and somatic conditions: comorbid cases show significantly poorer outcomes (reduced health related quality of life, work loss and disability, help-seeking behaviour) (Part D).

OBJETIVO: Confirmar, em uma amostra de jovens provenientes da população geral, achados recentes em relação à fisiopatologia do transtorno bipolar. Foi escopo desta investigação avaliar diferenças em uma neurotrofina, dois marcadores de dano oxidativo, duas citocinas pró-inflamatórias e uma antiinflamatória entre grupos de participantes com transtorno bipolar, depressão maior e também pessoas sem quaisquer episódios de humor. Nominalmente, foram elas o fator neurotrófico derivado do cérebro (brain-derived neurotrophic factor, BDNF), conteúdo de substâncias reativas ao ácido tiobarbitúrico (thiobarbituric acid reactive substances, TBARS), o conteúdo de proteína carbonil (protein carbonyl content, PCC), o fator de necrose tumoral-alfa (tumor necrosis factor-alpha, TNF-α), a interleucina-6 (IL-6) e a interleucina-10 (IL-10). MÉTODO: Indivíduos provenientes da população geral, que haviam participado de um estudo transversal (n=1560), com um rastreamento positivo para o transtorno bipolar foram recrutados, bem como dois grupos de controles. O primeiro tinha apenas episódios depressivos e o segundo não tinha história de episódios de humor. Isso levou a uma amostra de 231 participantes que passou por confirmação diagnóstica com a Entrevista Clínica Estruturada para o DSM-IV. Todas as análises incluíram avaliação de associações bivariadas. Um modelo a priori que incluía sexo, classe social, estado atual de humor, uso de substâncias e grupo diagnóstico como preditores foi utilizado. RESULTADOS: A amostra final foi composta por 55 participantes com transtorno bipolar, 82 com depressão maior e 95 controles. Uma minoria (9,6%) utilizava medicações psiquiátricas quando da entrevista. O transtorno bipolar foi associado a níveis circulantes elevados de PCC e TNF-α quando comparado com o grupo controle. A depressão maior também foi associada a níveis elevados de PCC quando comparada com o grupo sem episódios de humor. O uso de medicações psiquiátricas se associou com níveis mais baixos de TNF-α. As correlações entre os marcadores não foram tão fortes quanto em amostras clínicas anteriores. CONCLUSÕES: Os resultados encontrados apontam para duas conclusões mais amplas. Primeiramente, o transtorno bipolar se associa com um estado pró-oxidante e pró-inflamatório desde fases iniciais. Em segundo lugar, essas alterações parecem mais sutis que as observadas em amostras clínicas compostas por pessoas com doença crônica, o que reforçaria a idéia da ocorrência de algum tipo de progressão da doença. O principal cuidado com esses resultados é que provêm de amostras transversais, não longitudinais. Isso faz com que causalidade não possa ser inferida, e permanece a possibilidade que outros fatores além da doença bipolar sejam responsáveis pela toxicidade sistêmica observada. / OBJECTIVE: The aim of this study was to confirm, in a sample of young adults from the general population, recent findings regarding the pathophysiology of bipolar disorder. The focus of this investigation was finding group differences in one neurotrophin, two markers of oxidative damage, two pro-inflammatory cytokines and one anti-inflammatory cytokine in participants with bipolar disorder, major depression and people without any mood episodes. Markers assessed here were brain-derived neurotrophic factor (BDNF), thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). METHOD: Individuals from the general population, previously included in a cross-sectional study (n=1560), with a positive screen for bipolar disorder were recruited, as well as two groups of controls. One had only depressive episodes and the other had no history of mood episodes. This yielded a sample of 231 participants that further underwent diagnostic confirmation with the Structured Clinical Interview for DSM-IV (SCID). All analyses included a check for bivariate associations as well as an a priori multivariate model with sex, social class, current mood state, use of substances and SCID diagnoses as predictors. RESULTS: The final sample included 55 participants with bipolar disorder, 82 with major depression and 95 healthy controls. Only a minority was using any psychiatric medications (9.6%). Bipolar disorder was associated with higher PCC and TNF-α levels when compared to the control group. Major depression was also associated with higher PCC levels when compared to the control condition. Use of psychiatric medication was associated with lower TNF-α levels. Correlations between the same markers were not as strong as in clinical samples. CONCLUSIONS Two broad conclusions are called for from these results. The first is that early-stage bipolar disorder is already associated with a pro-oxidant, pro-inflammatory state. The second is that these changes appear more subtle than those observed in typical late-stage, chronic patients, supporting the notion that a form of illness progression takes place. The main caveat is that this data is cross-sectional, not longitudinal. This precludes causal inferences as factors other than the bipolar illness can conceivably induce systemic toxicity.

Background: Smokingprevalencein Serbiaishighbothamonggeneralandvulnerable populations.Interventionsshouldbeevidencebasedandinlinewithneedsofeachpopulation group. Thehighestprevalenceofsmokingisamongvulnerablegroups,whereinterventions beyondthoseaimedatgeneralpopulationarerequired.Aims: Toanalyzeandcompare smokingprevalenceanditspatterns,exposuretotobaccosmokeandtheircorrelatesamong generalpopulationandvulnerablegroupsandtoidenitfygapsandneedsformonitoringand policy.Materialandmethods:Secondaryanalysisofdataobtainedthroughdifferentsurveys implementedin2013and2014wasconducted. Databasesfromthreegeneralpopulation surveysandsixsurveysamongselectedvulnerablegroups(prisoners, menhavingsexwith men,sexworkers,peoplelivingwithHIV,Romayouth,institutionalizedchildren)wereused. Results:Datashowhighsmokingprevalenceamongadults(34.7%)withgenderdifferences. Lowersocioeconomicstatusisthestrongestfactorassociatedwithsmokingamongadults. Smokingprevalenceisthehighestintheagegroup35-45years(47.0%).AmongSerbian youth,perceivedavailabilityandbeingtaughtinschoolabouttobaccoareimportantcorrelates ofsmoking. Morethanhalfofadultsandyouthareexposedtotobaccosmokeatvarious places.SmokingissociallyhighlyacceptableinSerbiansocietyandriskperceptionisatlow level....

OBJETIVO: Confirmar, em uma amostra de jovens provenientes da população geral, achados recentes em relação à fisiopatologia do transtorno bipolar. Foi escopo desta investigação avaliar diferenças em uma neurotrofina, dois marcadores de dano oxidativo, duas citocinas pró-inflamatórias e uma antiinflamatória entre grupos de participantes com transtorno bipolar, depressão maior e também pessoas sem quaisquer episódios de humor. Nominalmente, foram elas o fator neurotrófico derivado do cérebro (brain-derived neurotrophic factor, BDNF), conteúdo de substâncias reativas ao ácido tiobarbitúrico (thiobarbituric acid reactive substances, TBARS), o conteúdo de proteína carbonil (protein carbonyl content, PCC), o fator de necrose tumoral-alfa (tumor necrosis factor-alpha, TNF-α), a interleucina-6 (IL-6) e a interleucina-10 (IL-10). MÉTODO: Indivíduos provenientes da população geral, que haviam participado de um estudo transversal (n=1560), com um rastreamento positivo para o transtorno bipolar foram recrutados, bem como dois grupos de controles. O primeiro tinha apenas episódios depressivos e o segundo não tinha história de episódios de humor. Isso levou a uma amostra de 231 participantes que passou por confirmação diagnóstica com a Entrevista Clínica Estruturada para o DSM-IV. Todas as análises incluíram avaliação de associações bivariadas. Um modelo a priori que incluía sexo, classe social, estado atual de humor, uso de substâncias e grupo diagnóstico como preditores foi utilizado. RESULTADOS: A amostra final foi composta por 55 participantes com transtorno bipolar, 82 com depressão maior e 95 controles. Uma minoria (9,6%) utilizava medicações psiquiátricas quando da entrevista. O transtorno bipolar foi associado a níveis circulantes elevados de PCC e TNF-α quando comparado com o grupo controle. A depressão maior também foi associada a níveis elevados de PCC quando comparada com o grupo sem episódios de humor. O uso de medicações psiquiátricas se associou com níveis mais baixos de TNF-α. As correlações entre os marcadores não foram tão fortes quanto em amostras clínicas anteriores. CONCLUSÕES: Os resultados encontrados apontam para duas conclusões mais amplas. Primeiramente, o transtorno bipolar se associa com um estado pró-oxidante e pró-inflamatório desde fases iniciais. Em segundo lugar, essas alterações parecem mais sutis que as observadas em amostras clínicas compostas por pessoas com doença crônica, o que reforçaria a idéia da ocorrência de algum tipo de progressão da doença. O principal cuidado com esses resultados é que provêm de amostras transversais, não longitudinais. Isso faz com que causalidade não possa ser inferida, e permanece a possibilidade que outros fatores além da doença bipolar sejam responsáveis pela toxicidade sistêmica observada. / OBJECTIVE: The aim of this study was to confirm, in a sample of young adults from the general population, recent findings regarding the pathophysiology of bipolar disorder. The focus of this investigation was finding group differences in one neurotrophin, two markers of oxidative damage, two pro-inflammatory cytokines and one anti-inflammatory cytokine in participants with bipolar disorder, major depression and people without any mood episodes. Markers assessed here were brain-derived neurotrophic factor (BDNF), thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). METHOD: Individuals from the general population, previously included in a cross-sectional study (n=1560), with a positive screen for bipolar disorder were recruited, as well as two groups of controls. One had only depressive episodes and the other had no history of mood episodes. This yielded a sample of 231 participants that further underwent diagnostic confirmation with the Structured Clinical Interview for DSM-IV (SCID). All analyses included a check for bivariate associations as well as an a priori multivariate model with sex, social class, current mood state, use of substances and SCID diagnoses as predictors. RESULTS: The final sample included 55 participants with bipolar disorder, 82 with major depression and 95 healthy controls. Only a minority was using any psychiatric medications (9.6%). Bipolar disorder was associated with higher PCC and TNF-α levels when compared to the control group. Major depression was also associated with higher PCC levels when compared to the control condition. Use of psychiatric medication was associated with lower TNF-α levels. Correlations between the same markers were not as strong as in clinical samples. CONCLUSIONS Two broad conclusions are called for from these results. The first is that early-stage bipolar disorder is already associated with a pro-oxidant, pro-inflammatory state. The second is that these changes appear more subtle than those observed in typical late-stage, chronic patients, supporting the notion that a form of illness progression takes place. The main caveat is that this data is cross-sectional, not longitudinal. This precludes causal inferences as factors other than the bipolar illness can conceivably induce systemic toxicity.