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Background: Psychotic disorders differ in their impact on psychosocial functioning. However, few studies have directly compared psychosocial functioning and its determinants between schizophrenia, schizoaffective disorder (SAD), bipolar disorder (BD), and major depressive disorder with psychotic features (psychotic MDD). Objective: We compared rates of independent living, employment, marriage, and having children between these diagnostic groups in a large national sample of participants with psychotic disorders in Finland. Methods: A cross-sectional substudy of participants (N = 9148) aged 18 to 65 years in the Finnish SUPER study, recruited nationwide from health- and social care settings and with advertisements. Psychosis diagnoses, age of onset, and hospitalizations were collected from healthcare registers. Participants were interviewed for psychosocial functioning. Associations of age of onset, hospitalizations, gender, and education with psychosocial functioning were analyzed using logistic regression models. Results: Of participants, 13.8% were employed or studying, 72.0% living independently and 32.5% had children. Overall, BD was associated with best, SAD and psychotic MDD with intermediate, and schizophrenia with worst level of psychosocial functioning. Greatest differences were found in independent living (OR 4.06 for BD vs. schizophrenia). In multivariate models, gender and number of hospitalizations predicted employment, marriage, and independent living in all diagnostic categories, and age of onset in some diagnostic categories. Conclusions: Level of functioning and psychosocial outcomes differed markedly between psychotic disorders, particularly in independent living. Outcomes were worst for schizophrenia and best for BD. Across all psychotic disorders, female gender and lifetime number of hospitalizations had strong independent associations with marriage, employment, and independent living. publishedVersion

The use of various digital health technologies is increasing in the treatment of psychotic disorders, as well as in psychiatry in general. In this review we present key studies on how technology is practically used to treat cognitive deficits, hallucinations and delusions of psychotic patients. The goal of this literature review is to provide the reader a comprehensive understanding on how technology is currently being utilized in the treatment of psychotic disorders, and to discuss how technology can pave the way towards a more integrative approach of treating psychotic disorders. The search for each symptom category was performed through PubMed and Google Scholar databases over the last 10-15 years. Computer-based cognitive rehabilitation seems to be as effective as the non-computerized equivalent, but has several additional advantages. AVATAR therapy and virtual reality-based treatments show promise in treating both hallucinations and delusions, but more research in this area is required. Digital solutions offer new ways to monitor and assess the different symptoms of psychotic disorders and to administer selfmanagement in the daily lives of patients. Digital health technology belongs to the treatment of psychotic disorders, but it should be further studied in order to more fully understand the underlying psychological mechanisms involved, and to further validate the approaches that will be the most beneficial for large scale clinical use.

The purpose of this study was to explore the association of cognition with hazardous drinking Polygenic Scores (PGS) in 2649 schizophrenia, 558 schizoaffective disorder, and 1125 bipolar disorder patients in Finland. Hazardous drinking PGS was computed using the LDPred program. Participants performed two computerized tasks from the Cambridge Automated Neuropsychological Test Battery (CANTAB) on a tablet computer: the 5-choice serial reaction time task, or Reaction Time (RT) test, and the Paired Associative Learning (PAL) test. The association between hazardous drinking PGS and cognition was measured using four cognition variables. Log-linear regression was used in Reaction Time (RT) assessment, and logistic regression was used in PAL assessment. All analyses were conducted separately for males and females. After adjustment of age, age of onset, education, household pattern, and depressive symptoms, hazardous drinking PGS was not associated with reaction time or visual memory in male or female patients with schizophrenia, schizoaffective, and bipolar disorder.

The purpose of this study was to explore the association of cognition with hazardous drinking Polygenic Scores (PGS) in 2649 schizophrenia, 558 schizoaffective disorder, and 1125 bipolar disorder patients in Finland. Hazardous drinking PGS was computed using the LDPred program. Participants performed two computerized tasks from the Cambridge Automated Neuropsychological Test Battery (CANTAB) on a tablet computer: the 5-choice serial reaction time task, or Reaction Time (RT) test, and the Paired Associative Learning (PAL) test. The association between hazardous drinking PGS and cognition was measured using four cognition variables. Log-linear regression was used in Reaction Time (RT) assessment, and logistic regression was used in PAL assessment. All analyses were conducted separately for males and females. After adjustment of age, age of onset, education, household pattern, and depressive symptoms, hazardous drinking PGS was not associated with reaction time or visual memory in male or female patients with schizophrenia, schizoaffective, and bipolar disorder. publishedVersion

Pre- and perinatal environmental factors have been associated with increased schizophrenia risk, particularly in combination with genetic liability. Both low and high birth weight have been associated with an increased risk of autism spectrum disorders and schizophrenia. The interaction of specific schizophrenia susceptibility genes and specified pre- and perinatal environmental factors have recently been described in relation to augmented schizophrenia risk. In this thesis, the relationship between birth weight and schizophrenia risk was investigated as part of a large Finnish schizophrenia family study sample based on the Genetic Epidemiology and Molecular Genetics of Schizophrenia in Finland study, in which genetic susceptibility for schizophrenia is known to be elevated relative to the general population (Study I). The study sample consisted of two subsamples having at least one sibling with a diagnosis of schizophrenia. The associations between birth weight and symptom severity of schizophrenia and psychotic disorders (Study II) and cognitive functioning in schizophrenia (Study III) were also characterized. A gene-environment interaction, focusing on birth weight and specific genes from the DISC1 network (Study IV), which had previously been found to be associated with increased schizophrenia risk in the same cohort, was also investigated in relation to schizophrenia risk. A 1.68-fold increase in schizophrenia risk was observed in subjects presenting with a high birth weight (>4000 g) relative to subjects with an intermediate birth weight of 3000-4000 g (Study I). In particular, schizophrenia risk was elevated among high birth weight individuals in combination with specific variants of the NDE1 gene (Study IV). Both low and high birth weight were found to be associated with increased severity of disorganized and negative symptom dimensions, whereas birth weight was not associated with symptoms of reality distortion (Study II). Both low and high birth weight, compared with the intermediate birth weight range, were associated with a slight decrease in cognitive performance among both subjects with schizophrenia and their unaffected first-degree relatives (Study III). The observations in the thesis corroborate existing findings describing an association between high birth weight and increased schizophrenia risk. An association between low birth weight and increased schizophrenia risk, a finding widely documented in the literature, was not seen here. Birth weight was found to influence both symptom severity and cognitive performance in schizophrenia. The findings also suggest that the functions of NDE1 during the early stages of neurodevelopment are vulnerable to the influence of pre- and perinatal environmental factors associated with high birth weight, with the propensity to augment subsequent schizophrenia susceptibility among offspring. The mechanisms underlying the association between high birth weight and schizophrenia risk are speculative, but may involve factors such as pre- or perinatal hypoxia, maternal metabolic and immunological mechanisms during pregnancy. Graviditets- och förlossningsfaktorer påverkar vår predisposition för schizofreni, framför allt i kombination med ett ärftligt anlag för sjukdomen. I denna doktorsavhandling undersöks sambandet mellan födelsevikten och risken för att utveckla schizofreni samt schizofrenisjukdomens kliniska symtombild i finländska familjer med ett känt anlag för schizofreni. Avhandlingen undersöker även hur DISC1-genvarianter, som deltar i utvecklingen av det centrala nervsystemet, tillsammans med födelsevikten påverkar predispositionen för schizofreni. Doktorsavhandlingen är en del av forskningsprojektet Genetisk epidemiologi och molekylärgenetisk bakgrund vid allvarliga psykiska störningar i regi av Institutet för hälsa och välfärd. Undersökningen påvisade förhöjd predisposition för schizofreni hos individer med hög födelsevikt (> 4000 g). Dessutom upptäcktes ett samband mellan hög och låg födelsevikt å ena sidan och svårare symtombild och en lägre kognitiv kapacitet å andra sidan, i jämförelse med normal födelsevikt. Förhöjd predisposition för schizofreni förelåg framför allt hos individer med vissa NDE1-genvarianter av DISC1-gentypen och hög födelsevikt. Födelsevikten anses avspegla graviditets- och förlossningsmiljöns inverkan på det växande fostret. Dessa forskningsrön stödjer uppfattningen om att födelsevikten har ett samband med utvecklingen av det centrala nervsystemet och med en förhöjd disposition för schizofreni samt bl.a. att NDE1-genen påverkas av graviditets- och förlossningsfaktorer. Även om denna avhandling inte undersökte de direkta förklaringarna bakom dessa observationer är det känt att födelsevikten har ett samband med metabola och immunologiska faktorer hos modern under graviditeten samt med syrebrist hos barnet i samband med förlossning. Detta är så vitt det är känt den mest omfattande undersökningen av sambanden mellan födelsevikten och en genetisk predisposition för schizofreni och det är en ny upptäckt att samspelet mellan graviditets- och förlossningsfaktorer och genen som deltar i utvecklingen av det centrala nervsystemet innebär en förhöjd predisposition för schizofreni. Dessa resultat bidrar till en ökad förståelse av schizofrenisjukdomens långsiktiga natur och utveckling där predisponerande biologiska faktorer för schizofreni aktiveras i ett mycket tidigt utvecklingsstadium. Dessa forskningsrön väcker frågor om huruvida graviditets- och förlossningsfaktorer bör uppmärksammas mer som en del av utvecklingen av mödra- och barnrådgivningsverksamheten för psykiatriska riskgrupper. Genetisk forskning kommer i framtiden att bidra med ökad kunskap om biologiska riskfaktorer för psykiatriska sjukdomar samtidigt som forskningen erbjuder utökade möjligheter för att undersöka sambanden mellan de genetiska och miljömässiga faktorer som ger upphov till psykiatriska sjukdomar.

Cannabis use is common in people with psychotic disorders. However, the effect of cannabis on cognition in psychosis remains unclear. Our study investigates relationships between the history of cannabis use and cognitive performance in patients with first-episode psychosis (FEP) during a one-year follow-up. The present study included FEP (N = 91) and control (N = 61) groups. Cannabis use was evaluated with a self-report questionnaire, clinical assessment, and medical records during a lifetime and 12 months prior to the treatment onset (recent). Symptoms of psychosis and anxiety were evaluated on the brief psychiatric rating scale. Negative symptoms were assessed using the scale for the assessment of negative symptoms. Cognitive tests were used to evaluate neurocognition (summarized in the g factor) and social cognition. Crude regression analyses for the g factor included variables of cannabis use as independent variables. Full regression models were controlled for gender, education, and clinical symptoms. In the FEP group, men used cannabis more frequently than women. In the crude regression model for FEP patients, never having used cannabis was associated with a better neurocognitive profile at 12 months. In the full model, more severe anxiety symptoms were associated with better neurocognition at two months, and less severe negative symptoms were associated with better neurocognition at 12 months. Cannabis use was not associated with social cognition. No associations between cognitive performance and cannabis use emerged in the controls. Negative and affective symptom severity in FEP was associated with cognitive performance to a greater degree than a lifetime history of cannabis use.

Cannabis use is common in people with psychotic disorders. However, the effect of cannabis on cognition in psychosis remains unclear. Our study investigates relationships between the history of cannabis use and cognitive performance in patients with first-episode psychosis (FEP) during a one-year follow-up. The present study included FEP (N = 91) and control (N = 61) groups. Cannabis use was evaluated with a self-report questionnaire, clinical assessment, and medical records during a lifetime and 12 months prior to the treatment onset (recent). Symptoms of psychosis and anxiety were evaluated on the brief psychiatric rating scale. Negative symptoms were assessed using the scale for the assessment of negative symptoms. Cognitive tests were used to evaluate neurocognition (summarized in the g factor) and social cognition. Crude regression analyses for the g factor included variables of cannabis use as independent variables. Full regression models were controlled for gender, education, and clinical symptoms. In the FEP group, men used cannabis more frequently than women. In the crude regression model for FEP patients, never having used cannabis was associated with a better neurocognitive profile at 12 months. In the full model, more severe anxiety symptoms were associated with better neurocognition at two months, and less severe negative symptoms were associated with better neurocognition at 12 months. Cannabis use was not associated with social cognition. No associations between cognitive performance and cannabis use emerged in the controls. Negative and affective symptom severity in FEP was associated with cognitive performance to a greater degree than a lifetime history of cannabis use.