Syftet med föreliggande kvantitativa studie är att undersöka sambandet mellan socioekonomisk klassposition i vuxenlivet och risken att vårdas för schizofreni. Sambandet mellan klassposition och hälsa kan ta sig uttryck i två riktningar - något som avhandlas i kausalitetsteorin och selektionsteorin. Kausalitetsteorin utgår från att en individs klassposition påverkar ens framtida hälsa, där en lägre klassposition riskerar att leda till sämre hälsa. I kontrast till detta utgår selektionsteorin från att en individs hälsa påverkar klasspositionen, där ohälsa tenderar att leda till en lägre klassposition. Dessa teorier utgör föreliggande studies teoretiska utgångspunkt. Datamaterialet som används är “Stockholm Birth Cohort” (SBC), vilket är resultatet av en sannolikhetsmatchning mellan två avidentifierade material. Materialet består av longitudinell kohortdata som sträcker sig från år 1953 till år 2008. Analysmetoden i föreliggande studie är multipel logistisk regressionsanalys vilket är lämpligt då utfallsvariabeln har gjorts binär. Resultatet som nås är att det existerar ett signifikant samband mellan socioekonomisk klassposition i vuxenlivet och risken att vårdas för schizofreni, även när sambandet kontrollerats för föräldrarnas socioekonomiska klassposition, psykiska hälsa, utbildning, inkomst, alkoholmissbruk samt familjetyp och kohortmedlemmens kön. Då denna infallsvinkel är relativt outforskad är detta resultat därför ett relevant bidrag till forskningsfältet. Vidare har försök gjorts att undersöka riktningen på detta samband och utifrån genomförda tester verkar det som att både kausalitets- och selektionsteorin har ett förklaringsvärde beroende på ifall klassposition mäts utifrån föräldrarnas eller individens klassposition. Rimligtvis är socioekonomisk klassposition och schizofreni ömsesidigt sammanlänkande över individens livsförlopp.

Yes / Born in Bradford (BiB) is a prospective multi-ethnic pregnancy and birth cohort study that was established to examine determinants of health and development during childhood and, subsequently, adult life in a deprived multi-ethnic population in the north of England. Between 2007 and 2010, the BiB cohort recruited 12,453 women who experienced 13,776 pregnancies and 13,858 births, along with 3353 of their partners. Forty five percent of the cohort are of Pakistani origin. Now that children are at primary school, the first full follow-up of the cohort is taking place. The aims of the follow-up are to investigate the determinants of children's pre-pubertal health and development, including through understanding parents' health and wellbeing, and to obtain data on exposures in childhood that might influence future health. Methods: We are employing a multi-method approach across three data collection arms (community-based family visits, school based physical assessment, and whole classroom cognitive, motor function and wellbeing measures) to follow-up over 9000 BiB children aged 7-11 years and their families between 2017 and 2021. We are collecting detailed parent and child questionnaires, cognitive and sensorimotor assessments, blood pressure, anthropometry and blood samples from parents and children. Dual x-ray absorptiometry body scans, accelerometry and urine samples are collected on subsamples. Informed consent is collected for continued routine data linkage to health, social care and education records. A range of engagement activities are being used to raise the profile of BiB and to disseminate findings. Discussion: Our multi-method approach to recruitment and assessment provides an efficient method of collecting rich data on all family members. Data collected will enhance BiB as a resource for the international research community to study the interplay between ethnicity, socioeconomic circumstances and biology in relation to cardiometabolic health, mental health, education, cognitive and sensorimotor development and wellbeing. / BiB receives core infrastructure funding from the Wellcome Trust (WT101597MA) and the National Institute for Health Research (NIHR) under its Collaboration for Applied Health Research and Care (CLAHRC) for Yorkshire and Humber and Clinical Research Network (CRN) research delivery support. Further support for genome-wide and multiple ‘omics measurements is from the UK Medical Research Council (G0600705), National Institute of Health Research (NF-SI-0611-10196), US National Institute of Health (R01 DK10324), and the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013) / ERC grant agreement no 669545. The follow-up of BiB participants, which is the focus of this paper, is funded by a joint grant from the UK Medical Research Council and UK Economic and Social Science Research Council (MR/N024397/1) and a grant from the British Heart Foundation (CS/16/4/32482.) D.A.L. works in a unit that receives UK Medical Research Council funding (MC_UU_00011/6) and is a UK National Institute of Health Research senior investigator (NF-SI-0611-10196).

Mental health reflects an array of causal influences that span biological, psychological, and social circumstances, with resultant underlying causal pathways to poor mental health outcomes in childhood that are complex. Key features of this complexity are reciprocal interactions between person and environment that take place over time. The core of this thesis seeks to attend to the complexity of development to move the field of developmental health forward toward greater explanation, and more successful prediction and prevention. The focal point of the thesis is the psychosocial determinants of childhood mental health, the resource domain of the developing child, and the interplay between characteristics of the individual child, the family, and the community. The eventual goal is to better understand why and how socioeconomic circumstances impact on developmental health. One component of this thesis focuses on the expansion of extant developmental theory. The other component focuses on the development of an analytic strategy that more appropriately reflects the intricacies of this theoretical expansion. In the process, data are analysed, principally as a heuristic strategy, to illustrate the analytical approach needed to support the theoretical framework. The specification of a bioecological conceptual framework suitable to guide research and policy in developmental health is the first principal objective of the thesis. A critical examination of the resource framework proposed by Brooks-Gunn, Brown, Duncan, and Anderson Moore (1995) reveals it to be centred on family and community resources, but otherwise silent with respect to the physical and psychological resources of the child. The quintessential point of this thesis is that theory in developmental health must be able to account for the contribution individuals make to their own development. A modified resource framework is proposed that acknowledges financial, physical, human, and social capital, within the domains of the individual child, the family, and the community. The second principal objective of the thesis, the development of analytical methods that focus on the individual child and the complexity of data generated by this theoretical approach, is then introduced. Theory and method are thus integrated when comprehensive measures of characteristics in multiple domains across developmental periods are modeled using longitudinal data from the Western Australian Pregnancy Cohort (Raine) Study (Newnham, Evans, Michael, Stanley, & Landau, 1993). The mothers of 2,860 children were enrolled at 18 weeks in pregnancy and the children have been followed at birth, one, two, three, five, and eight years of age. Eighty-nine per cent (2,537 /2,860) of families were available for follow-up at eight and 74 per cent (2,126/2,860) of families responded. Extensive demographic, psychological, and developmental data were available for the children and their families and a limited amount of data were available for the communities in which they reside. A measure of mental health morbidity, the Child Behaviour Checklist (Achenbach, 1991), was available for the children at two, five, and eight years of age. In the first instance, dichotomous summary variables are derived for the demographic, psychological, and developmental variables of interest. Variables are then selected for inclusion in one of several explanatory models. To create a mathematical representation of resource characteristics, the information for each child is concatenated as a series of binary strings. Frequency tabulation is then used to aggregate the data and odds ratios are calculated to determine the degree of risk associated with each string of code, or pattern of factors relative to a nominated mental health outcome. The results provided a scaffold from which this theoretical and analytical approach is compared and contrasted with the reviewed literature. Two principal themes of investigation are pursued. The first theme to be examined is the interplay between characteristics of the child, family, and community and the contribution children make to their own development. The specific approach models the interaction between selected characteristics of the child, family and community in each of four developmentally significant time periods. The theoretical position adopted in the present study suggests that the effect of any personal or contextual factor on later development, if a relationship does truly exist, is most likely to be differential. That is, it is a combination of influences that determines developmental outcomes for children, not any single factor acting independently. The modelling process demonstrates that, for the children involved, personal and contextual factors impact mental health differentially depending on various other individual, family and/or community characteristics. The modelling process identifies patterns of factors that impact relatively small, but significant, numbers of children because the models focus on the effect for individual children rather than the effect for the group. For example, one model suggests that the effect of intra-uterine growth restriction for the group as a whole may be minimal, but the impact for some children could be critical depending on the combination of family and community influences, such as the mothers level of education, the family’s experience of significant life stress, and residence in a relatively disadvantaged community. The second theme to be examined is the possibility that the accumulation of resource deficits or risk characteristics, over time, amplifies the likelihood of mental health problems in childhood. The approach models selected characteristics of the child in each of the four periods of development collectively, and it also models selected characteristics spanning each of the four time periods discretely. The results suggest that latency, pathway, and recency effects may operate simultaneously, and that timing and accumulated burden may both be important determinants of risk. For example, with regard to children whose family experienced life stress, these three effects operated in a systematic way to increase the degree of risk of a mental health problem. In summary, the aggregation of data at the individual level is a productive approach in seeking to explain population level social phenomena. While seemingly paradoxical, the identification of the joint, interactive effects between individual, family, and community characteristics, better allows for the quantification of family and community characteristics operating through multiple causal pathways.

Abstract Schizophrenia and other psychotic disorders are severe and disabling mental disorders that break out during early adulthood, often when a person is in his/her early 20s. Furthermore, functional decline in many cognitive areas, including the ability to communicate in social interactions and impaired facial expression recognition, is typical to patients with schizophrenia. Understanding the risk factors of psychosis is essential as these disorders may be more amenable to treatment in their early stages. However, recognition of those at the highest risk of psychosis is challenging as no definitive biomarkers are available. Functional MRI is a promising tool that can potentially identify neural signals relating to the individual’s risk of psychosis onset. Psychotic disorders are etiologically heterogeneous disorders — both environmental and genetic factors have been linked to the onset of psychotic disorders. The most influential risk factor for a psychotic disorder is familial risk with genetic loading. The present study examines whether familial risk of psychosis (FR), the polygenic risk score for schizophrenia (PRS) and early adversity associate with brain response to faces. We used fMRI to measure blood oxygen level dependent (BOLD) response to faces. Our study showed that FR associated with deviant prefrontal cortex BOLD responses. In addition, we detected that interregional BOLD signal and grey matter volume varied as a function of PRS; the lowest functional and structural covariance was detected in individuals with high PRS. We also detected that early adversities associated with brain response to faces and that this association varied as a function of glucocorticoid receptor gene expression. Our findings indicate that the above risk factors of psychosis associate with brain response to faces. / Tiivistelmä Skitsofrenia ja muut psykoosisairaudet ovat vakavia mielenterveyden häiriöitä, jotka puhkeavat usein nuorella aikuisiällä. Eräs tyypillinen piirre psykoosisairauksille on vaikeus tunnistaa muiden ihmisten kasvonilmeitä. Psykoosisairauksien riskitekijöiden ymmärtäminen on tärkeää, sillä hoito tehoaa parhaiten sairastumisen alkuvaiheessa. Suurimmassa psykoosivaarassa olevien henkilöiden tunnistaminen on kuitenkin haastavaa, sillä luotettavia tautiin liittyviä biomarkkereita ei ole saatavilla. Toiminnallinen magneettikuvaus (fMRI) on lupaava työkalu, jolla saattaa olla tulevaisuudessa käyttöarvoa psykoosivaaraan liittyvien aivomuutosten tunnistamisessa. Etiologialtaan psyykoosisairaudet ovat heterogeenisiä: sekä ympäristö että perinnölliset tekijät vaikuttavat yksilön sairastumisriskiin. Voimakkain riskitekijä on suvullinen psykoosialttius. Tässä osajulkaisuväitöskirjassa tutkitaan suvullisen psykoosialttiuden, skitsofrenian polygeenisen riskipisteen (PRS) sekä varhaisten vastoinkäymisten yhteyttä aivojen kasvonilmeitä tulkitsevaan järjestelmään. Tutkimuksessa on hyödynnetty fMRI-kuvausta kasvonilmestimuluksen aikana. Tutkimuksessamme suvullinen psykoosialttius oli yhteydessä etuotsalohkon fMRI-signaalimuutoksiin. Tämän lisäksi havaitsimme, että kasvonilmejärjestelmän fMRI-signaalin ja harmaan aineen kovarianssi oli yhteydessä PRS:ään: matalin aivoalueiden välinen korrelaatio havaittiin henkilöillä, joiden PRS oli korkea. Havaitsimme myös, että varhaiset vastoinkäymiset ovat yhteydessä kasvonilmeiden aikaansaamiin aivovasteisiin. Tämä assosiaatio oli myös yhteydessä glukokortikoidireseptorin geenin ilmentymiseen. Väitöskirjan löydökset viittaavat siihen, että edellä mainitut psykoosin riskitekijät ovat yhteydessä kasvonilmeitä tulkitsevaan järjestelmään.

Abstract Recognition of individuals at highest risk for psychosis is challenging and no definitive biomarkers are yet available. Physical illnesses associated with a sedentary lifestyle are common in patients with severe mental illness. Both, bodyweight and risk for psychosis are associated with brain white matter (WM) abnormalities. There are several dysregulated pathways which are common in psychiatric illnesses and weight-related processes, but it is not known how weight and vulnerability for psychosis interact in the brain. The present study examines brain WM microstructure and its association to body mass index (BMI) in young adults with a familial risk for psychosis (FR). In addition, the level of physical activity and cardiorespiratory fitness in individuals vulnerable to psychosis was examined. Participants of the present study are members of the Northern Finland Birth Cohort 1986. Two separate clinical substudies were conducted. The first having been done when the participants were at age 15–16. At that time, physical activity was defined by postal questionnaire (n=6,987) and cardiorespiratory fitness was measured by a submaximal cycle ergometer test (n=4,803). Risk for psychosis was viewed from three perspectives, with possible overlap between groups: having familial risk for psychosis, existing prodromal symptoms at age 15–16, and development of hospital treated psychosis between the ages of 16 and 20 years. The latter substudy was conducted when the participants were aged between 20 and 25 years. Diffusion tensor imaging was performed on 108 participants. Our study showed that there was no difference in WM microstructure between FR and control groups suggesting that WM abnormalities are not a genetic feature for risk of psychosis in all populations. However, the association between BMI and WM microstructure differed significantly between the FR and control groups. We also demonstrated that the level of physical activity was lower before the onset of psychotic illness. Therefore, these results imply that it would be of great importance to consider weight and physical activity levels in subjects at risk for psychosis, in order to avoid the detrimental effects of a sedentary lifestyle on overall health. / Tiivistelmä Korkeimmassa psykoosiriskissä olevien tunnistaminen on haastavaa, eikä kunnollisia biomarkkereita ole käytettävissä. Vähäiseen liikunta-aktiivisuuteen liitetyt fyysiset sairaudet ovat yleisiä vakavaa mielenterveyshäiriötä sairastavilla. Sekä kehonpaino että psykoosialttius on yhdistetty aivojen valkean aineen rakenteen poikkeavuuksiin. Useat kehon säätelymekanismien poikkeavuudet liittyvät sekä psykiatrisiin sairauksiin että painoon liittyviin prosesseihin, mutta ei ole olemassa tutkimustietoa siitä, miten paino ja psykoosialttius vaikuttavat yhdessä aivojen rakenteeseen. Tässä osajulkaisuväitöskirjassa tutkitaan aivojen valkean aineen mikrorakennetta nuorilla aikuisilla, jotka ovat sukuriskissä sairastua psykoosiin, sekä painon vaikutusta valkean aineen rakenteeseen psykoosiriskissä. Lisäksi tutkitaan psykoosialttiiden nuorten liikunta-aktiivisuutta ja kuntoa. Tutkittavat kuuluvat Pohjois-Suomen vuoden 1986 syntymäkohorttiin. Kaksi osatutkimusta toteutettiin, joista aikaisempi kliininen tutkimus tutkittavien ollessa 15–16-vuotiaita. Tuolloin selvitettiin liikunta-aktiivisuus postikyselyn avulla (n=6,987) ja aerobinen kunto mittaamalla hapenottokyky polkupyöräergometrilla (n=4,803). Psykoosialttiutta tarkasteltiin kolmella tavalla, ja ryhmien välillä esiintyi osittaista päällekkäisyyttä: sukurasitus, 15–16 v. iässä raportoidut psykoosinkaltaiset oireet ja sairaalahoitoon johtanut psykoosi 16–20 v. iässä. Toinen kliininen osatutkimus toteutettiin tutkittavien ollessa 20–25-vuotiaita. Tutkimuksen yhteydessä tehtiin aivojen diffuusiotensorikuvaus 108 osallistuneelle. Aivojen valkean aineen mikrorakenteessa ei havaittu eroa sukuriskissä olevien ja kontrollien välillä viitaten siihen, että poikkeavuudet valkean aineen rakenteessa eivät olisi psykoosiriskin geneettinen piirre kaikissa populaatioissa. Havaitsimme kuitenkin, että assosiaatio painoindeksin ja valkean aineen rakenteen välillä oli erilainen sukuriski- ja kontrolliryhmissä. Tutkimus osoitti myös, että liikunta-aktiivisuus on alentunut jo ennen psykoosisairauden puhkeamista. Psykoosiriskissä olevien liikuntatottumuksiin ja painoon tulisi kiinnittää erityistä huomiota jo varhaisessa vaiheessa elimellisten sairauksien ehkäisemiseksi.