Psychotic experiences (PEs) occur in the general population, beyond psychotic disorders. PEs are a risk factor for mental ill health in young people but can occur benignly in selected samples of adults. Environmental factors predispose to PEs but their underlying mechanisms are not well-understood. Progress in understanding PEs may be limited by diverse conceptualisations, imprecise measurement and a lack of explanatory frameworks that can bridge the gaps between aetiological factors, their effects on the brain and their behavioural manifestations. In this thesis, I undertook a comprehensive investigation of the measurement, health implications, aetiology and computational mechanisms of PEs in adolescents and young adults using data from two large cohort samples, supplemented with smaller-scale behavioural studies. I first investigated the measurement of PEs. I assessed and optimised the measurement of PEs in young people by two self-report instruments. I then used latent variable modelling to show that a self-report and interview instrument measured the same underlying psychotic phenomena. Both instruments were able to measure severe PEs, while the self-report questionnaire also measured more mild psychotic phenomena. I then investigated the health implications of PEs. Using cluster analysis in both cohorts, I found replicable patterns of PEs at similar levels of intensity and persistence but with and without depressive symptoms and with varying risk of mental disorder. Paranoid ideation was more associated with depressive symptoms than non-paranoid unusual perceptions and beliefs. Childhood adversity was associated with both PE-prone groups, but later social support from family and friends was far higher in those with PEs and low depressive symptoms than those with PEs and high depressive symptoms. Subsequently, I investigated the role of the social environment in the development of PEs and psychopathology using longitudinal structural equation modelling. I found that asocial dispositions increased or preceded increase in PEs over one year, mediated by detriment to social support. Conversely, PEs did not precede or increase asociality. I then showed that dimensions of PEs and depressive symptoms were promoted by childhood adversity but differentially affected by later social support, with paranoid ideation being more influenced by support than non-paranoid unusual perceptions/beliefs. Finally, I investigated specific mechanisms of PEs in two behavioural studies. In the seventh study, I used computational modelling of reward learning to link PEs to reduced ability to modulate learning by confidence, replicating computational effects of a pharmacological model of psychosis. I also used a novel visual task to show that the manifestation of PEs as anomalous perceptions versus anomalous beliefs might be explained by over-reliance on different types of prior knowledge in perceptual inference. These results suggest that different conceptual approaches to PEs might be synthesised despite issues with their measurement. PEs in young people, while not entirely benign, are heterogeneously associated with psychopathology. Importantly, they characterise a minority of young people who are at very high transdiagnostic risk of mental illness but also occur without distress in young people, often in the context of a supportive social environment. Health outcomes in young people with PEs are predicted and potentially modified by social functioning and social relationships. PEs might arise from atypicalities in how the influences of information sources on perception and belief-updating are modulated according to their reliabilities.

Psychotic-like experiences (PLEs) are prevalent occurrences deemed comparable with the symptoms of psychosis, but not sufficiently severe to warrant a diagnosis upon clinical presentation. Their presence is associated with several adverse clinical outcomes: the onset of various common mental health disorders (e.g. anxiety, mood, substance abuse), poorer functioning, non-remission and relapse. Sleep and circadian rhythm disruption (SCRD) is observed in 30-80% of patients with psychosis. The omnipotence of SCRD across all phases of the disorder (including the prodromal, acute, chronic and residual phases) raises the question as to whether SCRD may directly contribute to the development of psychosis. Assuming that PLEs are along the same continuum to developing psychosis, a logical next step to further disentangle the sleep-psychosis relationship is to examine whether SCRD relates to the experience of PLEs and whether this relationship is bi-directional. This thesis begins by examining the core predictions made by a continuum model of understanding psychosis and how specific parameters of sleep may influence PLEs. A smaller high-definition cross-sectional study follows, examining biological underpinnings (electroencephalography (EEG), electrocardiography (ECG), endogenous melatonin rhythms and actigraphy) of a complaint of poor sleep and their relation to the occurrence of PLEs. We then refocus on which parameters of sleep are most integral to the sleep-PLE relationship and close with an investigation of how Hypothalamic Pituitary Adrenal (HPA) axis activity may further our knowledge of this relationship. The findings of this thesis demonstrate specificity in the parameters of sleep shown to impact certain PLEs. The importance of objective sleep and biologically driven measures in this line of research are underscored, with group differences in EEG, ECG and melatonin. This thesis also highlights dissociative symptomatology as a candidate mediator for the sleep-psychosis relationship, and emphasises the ties between paranoia and negative affect. Finally, this thesis also illuminates the challenges of examining the relationship between sleep and PLEs in isolation, and suggests that they must be considered within the broader framework of co-existing mental health problems.

Abstract The aim of this study was to investigate the association between adolescent substance use and psychosis in later life, after taking into account a wide range of known confounders, using data from the Northern Finland Birth Cohort 1986 (N = 9432). Adolescence is a vulnerable neurodevelopmental period, during which many brain maturation processes take place. Substance use during this critical period may disrupt these processes, ultimately leading to mental health problems. Several meta-analyses have demonstrated associations between cannabis use and tobacco smoking and increased risk of psychotic disorders. However, lack of data on the temporal order of the association and uncertainty in relation to the role of confounding factors warranted further studies. Furthermore, there are no longitudinal studies on the association between adolescent inhalant use and psychotic disorders. The study sample consisted of the Northern Finland Birth Cohort 1986. There were 7344 adolescents who participated in the follow-up study in 2001-2002, when they were aged 15-16 years. Adolescents who answered the questions on substance use and psychotic experiences (PROD-screen) were included in the present study. The final sample included 6542 subjects. In this study, an increased risk of psychosis was found in those subjects who had used cannabis five times or more, smoked 10 or more cigarettes daily or had used inhalants 2-4 times or more. Each of these substances were associated with psychosis in a dose-response manner, even after adjustments for confounders. In addition, initiation of daily smoking at 13 years of age or earlier was associated with increased risk of psychosis compared to later initiation. In this comprehensive longitudinal population-based study, frequent cannabis use, daily tobacco smoking and frequent inhalant use in adolescence were independently associated with increased risk of incident psychosis, even after adjusting for confounders such as baseline psychotic experiences, other substance use and history of parental psychosis and substance abuse disorder. The results supply yet another reason to implement effective prevention strategies. / Tiivistelmä Väitöstutkimuksen tarkoituksena oli selvittää, onko teini-iän päihteidenkäytöllä yhteyttä psykoosiin sairastumiseen senkin jälkeen, kun sekoittavat tekijät on huomioitu. Aineistona käytettiin vuoden 1986 Pohjois- Suomen syntymäkohorttia (N = 9 432). Teini-iässä aivot muovautuvat ja kypsyvät nopeasti, minkä vuoksi se on erityisen herkkää aikaa päihteiden haitallisille vaikutuksille. Nuorena aloitettu päihteidenkäyttö saattaa häiritä aivojen kypsymistä, ja kehityksen häiriintyminen voi myöhemmin altistaa mielenterveysongelmille. Aiempien tutkimusten pohjalta tiedetään, että kannabiksen käyttö ja tupakointi ovat yhteydessä korkeampaan riskiin sairastua psykoosiin. Päihteidenkäytön ja psykoosiin sairastumisen välistä ajallista yhteyttä ei olla kuitenkaan aiemmin kyetty tutkimaan vakuuttavasti, eikä huomioon ole otettu nuoruuden aikaisia psykoottisia kokemuksia. Inhalanttien käytön eli imppaamisen yhteydestä psykoosiriskiin ei ole julkaistu yhtään pitkittäistutkimusta. Tutkimusaineisto koostui Pohjois-Suomen syntymäkohortista vuodelta 1986. Vuosina 2001–2002 järjestettyyn seurantatutkimukseen osallistui 7344 15–16- vuotiasta nuorta. Lopullisessa otoksessa (n=6542) huomioitiin henkilöt, jotka vastasivat kysymyksiin psykoottisista kokemuksista ja päihteidenkäytöstä. Kannabiksen käyttö 5 kertaa tai enemmän, päivittäinen tupakointi 10 savuketta tai enemmän ja inhalanttien käyttö 2-4 kertaa tai enemmän olivat yhteydessä korkeampaan riskiin sairastua psykoosiin seurannan aikana sekoittavien tekijöiden huomioimisenkin jälkeen. Tutkittujen päihteiden käyttö kasvatti psykoosiin sairastumisen riskiä päihteen käyttömäärän mukaan. Lisäksi päivittäisen tupakoinnin aloittaminen 13-vuotiaana tai aiemmin oli yhteydessä korkeampaan psykoosiriskiin tupakoinnin myöhemmin aloittaneisiin verrattuna. Tässä suuressa pitkittäisessä, yleisväestöön perustuvassa tutkimuksessa havaittiin, että toistuva kannabiksen käyttö, päivittäinen ja runsas tupakointi sekä toistuva inhalanttien käyttö teini-iässä olivat itsenäisesti yhteydessä kohonneeseen psykoosiriskiin, vaikka aiemmat psykoottiset kokemukset, muu päihdekäyttö, vanhempien psykoosisairaudet ja päihdeongelmat otettiin huomioon. Tulosten perusteella nuorten runsaan päihteidenkäytön ennaltaehkäisy on tärkeää ja sillä on todennäköisesti positiivisia vaikutuksia nuorten mielenterveyteen.