Factors contributing to readmission in patients with psychotic disorders, with a special reference to first follow-up visit in outpatient care.

BACKGROUND: Timely outpatient follow-up and readmission after discharge are common quality indicators in psychiatric care, but their association varies in previous research. We aimed to examine whether the impact of outpatient follow-up and other factors on readmission risk evolves over time in people with non-affective psychotic disorder (NAP). METHODS: The Finnish Quality of Care Register includes all people diagnosed with NAP since January 2010. Here, we followed patients with a hospital discharge between 2017 and 2021 until readmission, death, or up to 365 days. Time of the first outpatient follow-up appointment, length of stay (LOS), number of previous hospitalizations, psychosis diagnosis, substance use disorder (SUD), residential status, economic activity, gender, age, year, and region were included. Follow-up time was divided into five periods: week 1, weeks 2-4, weeks 5-13, weeks 14-25, and weeks 26-52, and each period was analyzed separately with Cox regression. RESULTS: Of the 29 858 discharged individuals, 54.1% had an outpatient follow-up within a week. A total of 10 623 (35.6%) individuals were readmitted. Short LOS increased the readmission risk in the first four weeks, whereas lack of outpatient follow-up raised the risk (adjusted HRs between 1.15 (95% CI 1.04-1.26) and 1.53 (1.37-1.71) in weeks 5-52. The number of previous hospitalizations remained a consistent risk factor throughout the follow-up, while SUD increased risk after 4 weeks and living without family after 13 weeks. CONCLUSIONS: Risk factors of readmission vary over time. These temporal patterns must be considered when developing outpatient treatment programs.

Antipsychotic medications and sleep problems in patients with schizophrenia.

BACKGROUND: Sleep problems are common and related to a worse quality of life in patients with schizophrenia. Almost all patients with schizophrenia use antipsychotic medications, which usually increase sleep. Still, the differences in subjective sleep outcomes between different antipsychotic medications are not entirely clear. METHODS: This study assessed 5466 patients with schizophrenia and is part of the nationwide Finnish SUPER study. We examined how the five most common antipsychotic medications (clozapine, olanzapine, quetiapine, aripiprazole, and risperidone) associate with questionnaire-based sleep problems in logistic regression analyses, including head-to-head analyses between different antipsychotic medications. The sleep problems were difficulties initiating sleep, early morning awakenings, fatigue, poor sleep quality, short (≤6 h) and long sleep duration (≥10 h). RESULTS: The average number of antipsychotic medications was 1.59 per patient. Clozapine was associated with long sleep duration (49.0 % of clozapine users vs 30.2 % of other patients, OR = 2.05, 95 % CI 1.83-2.30, p < .001). Olanzapine and risperidone were in head-to-head analyses associated with less sleep problems than patients using aripiprazole, quetiapine, or no antipsychotic medication. Aripiprazole and quetiapine were associated with more insomnia symptoms and poorer sleep quality. Patients without antipsychotic medications (N = 159) had poorer sleep quality than patients with antipsychotic use, and short sleep duration was common (21.5 % of patients using antipsychotics vs 7.8 % of patients using antipsychotics, OR = 2.97, 95 % CI 1.98-4.44, p < .001). CONCLUSIONS: Prevalence of sleep problems is markedly related to the antipsychotic medication the patient uses. These findings underline the importance of considering and assessing sleep problems when treating schizophrenia patients with antipsychotics.

Criminal behavior in alcohol-related dementia and Wernicke-Korsakoff syndrome: a Nationwide Register Study.

BACKGROUND: Chronic heavy alcohol use may lead to permanent brain damage, cognitive impairment, and dementia. While the link between alcohol use and crime is strong, virtually no research exists on the criminal behavior of patients with the alcohol-related neurocognitive disorders of Wernicke-Korsakoff syndrome (WKS) and alcohol-related dementia (ARD). METHODS: The study population included all persons diagnosed with WKS (n = 1149) or ARD (n = 2432) in Finland in 1998-2015. Data on diagnoses, mortality, and crime were obtained from Finnish nationwide registers. Crime incidences were calculated 4 years before and after diagnosis. Crime types, incidences, and mortality were compared between disorders and with the general population. RESULTS: Altogether 35.6% of WKS patients and 23.6% of ARD patients had committed crimes in the 4 years preceding diagnosis, most commonly property and traffic crimes, followed by violent crimes. The incidence of criminal behavior decreased significantly after diagnosis; in WKS patients, the standardized criminality ratio (SCR), the ratio of observed to expected number of crimes (95% CI), was 3.91 (3.72-4.10) in 4 years before and 2.80 (2.61-3.00) in 4 years after diagnosis. Likewise, in ARD patients, the SCRs were 2.63 (2.51-2.75) before and 0.84 (0.75-0.92) after diagnosis. No significant difference emerged in mortality between persons with and without a criminal history. CONCLUSIONS: Persons with alcohol-related neurocognitive disorders frequently engage in criminal behavior prior to diagnosis, especially multiple offending. In the 4 years before and after diagnosis, crime rates declined in a linear fashion, with a marked reduction after diagnosis.

Genetic contribution to microglial activation in schizophrenia.

Several lines of evidence indicate the involvement of neuroinflammatory processes in the pathophysiology of schizophrenia (SCZ). Microglia are brain resident immune cells responding toward invading pathogens and injury-related products, and additionally, have a critical role in improving neurogenesis and synaptic functions. Aberrant activation of microglia in SCZ is one of the leading hypotheses for disease pathogenesis, but due to the lack of proper human cell models, the role of microglia in SCZ is not well studied. We used monozygotic twins discordant for SCZ and healthy individuals to generate human induced pluripotent stem cell-derived microglia to assess the transcriptional and functional differences in microglia between healthy controls, affected twins and unaffected twins. The microglia from affected twins had increased expression of several common inflammation-related genes compared to healthy individuals. Microglia from affected twins had also reduced response to interleukin 1 beta (IL1ß) treatment, but no significant differences in migration or phagocytotic activity. Ingenuity Pathway Analysis (IPA) showed abnormalities related to extracellular matrix signaling. RNA sequencing predicted downregulation of extracellular matrix structure constituent Gene Ontology (GO) terms and hepatic fibrosis pathway activation that were shared by microglia of both affected and unaffected twins, but the upregulation of major histocompatibility complex (MHC) class II receptors was observed only in affected twin microglia. Also, the microglia of affected twins had heterogeneous response to clozapine, minocycline, and sulforaphane treatments. Overall, despite the increased expression of inflammatory genes, we observed no clear functional signs of hyperactivation in microglia from patients with SCZ. We conclude that microglia of the patients with SCZ have gene expression aberrations related to inflammation response and extracellular matrix without contributing to increased microglial activation.

Genetic contribution to disease-course severity and progression in the SUPER-Finland study, a cohort of 10,403 individuals with psychotic disorders.

Genetic factors contribute to the susceptibility of psychotic disorders, but less is known how they affect psychotic disease-course development. Utilizing polygenic scores (PGSs) in combination with longitudinal healthcare data with decades of follow-up we investigated the contributing genetics to psychotic disease-course severity and diagnostic shifts in the SUPER-Finland study, encompassing 10 403 genotyped individuals with a psychotic disorder. To longitudinally track the study participants' past disease-course severity, we created a psychiatric hospitalization burden metric using the full-coverage and nation-wide Finnish in-hospital registry (data from 1969 and onwards). Using a hierarchical model, ranking the psychotic diagnoses according to clinical severity, we show that high schizophrenia PGS (SZ-PGS) was associated with progression from lower ranked psychotic disorders to schizophrenia (OR = 1.32 [1.23-1.43], p = 1.26e-12). This development manifested already at psychotic illness onset as a higher psychiatric hospitalization burden, the proxy for disease-course severity. In schizophrenia (n = 5 479), both a high SZ-PGS and a low educational attainment PGS (EA-PGS) were associated with increased psychiatric hospitalization burden (p = 1.00e-04 and p = 4.53e-10). The SZ-PGS and the EA-PGS associated with distinct patterns of hospital usage. In individuals with high SZ-PGS, the increased hospitalization burden was composed of longer individual hospital stays, while low EA-PGS associated with shorter but more frequent hospital visits. The negative effect of a low EA-PGS was found to be partly mediated via substance use disorder, a major risk factor for hospitalizations. In conclusion, we show that high SZ-PGS and low EA-PGS both impacted psychotic disease-course development negatively but resulted in different disease-course trajectories.

Evidence for the additivity of rare and common variant burden throughout the spectrum of intellectual disability.

Intellectual disability (ID) is a common disorder, yet there is a wide spectrum of impairment from mild to profoundly affected individuals. Mild ID is seen as the low extreme of the general distribution of intelligence, while severe ID is often seen as a monogenic disorder caused by rare, pathogenic, highly penetrant variants. To investigate the genetic factors influencing mild and severe ID, we evaluated rare and common variation in the Northern Finland Intellectual Disability cohort (n = 1096 ID patients), a cohort with a high percentage of mild ID (n = 550) and from a population bottleneck enriched in rare, damaging variation. Despite this enrichment, we found only a small percentage of ID was due to recessive Finnish-enriched variants (0.5%). A larger proportion was linked to dominant variation, with a significant burden of rare, damaging variation in both mild and severe ID. This rare variant burden was enriched in more severe ID (p = 2.4e-4), patients without a relative with ID (p = 4.76e-4), and in those with features associated with monogenic disorders. We also found a significant burden of common variants associated with decreased cognitive function, with no difference between mild and more severe ID. When we included common and rare variants in a joint model, the rare and common variants had additive effects in both mild and severe ID. A multimodel inference approach also found that common and rare variants together best explained ID status (ΔAIC = 16.8, ΔBIC = 10.2). Overall, we report evidence for the additivity of rare and common variant burden throughout the spectrum of intellectual disability.

Association of antidepressant and benzodiazepine use, and anticholinergic burden with cognitive performance in schizophrenia.

Schizophrenia is characterized by cognitive impairment affecting everyday functioning. Earlier research has hypothesized that antidepressants may associate with better cognitive functioning, but results are mixed. This study explored the association between antidepressant use and cognitive performance in terms of reaction time and visual learning in a clinical sample. In addition, we examined benzodiazepine use and anticholinergic burden. Study participants were drawn from the SUPER-Finland cohort, collected among patients with psychotic illnesses in 2016-2018 throughout Finland (n = 10,410). The analysis included adults with a schizophrenia diagnosis (F20) and results from a cognitive assessment (n = 3365). Information about medications and psychosocial factors were gathered through questionnaire and interview. Cognitive performance was assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB) with two subtests measuring reaction time and visual learning. Almost 36 % of participants used at least one antidepressant. The use of antidepressants in general was not associated with performance in the reaction time and visual learning tasks. However, the use of SNRI antidepressants was associated with a faster reaction time. Benzodiazepine use and a higher anticholinergic burden were associated with poorer performance in both tests. The results strengthen earlier findings that there is no association between antidepressant use in general and cognitive performance in schizophrenia. However, the association of SNRI medications with a faster reaction time warrants further research. Moreover, the results suggest that more attention should be paid to the anticholinergic burden of the medications used by patients with schizophrenia, as well as avoiding continuous benzodiazepine use.

Enhancing identification of nonaffective psychosis in register-based studies.

The Finnish Quality of Psychosis Care Register assesses nonaffective psychosis (NAP) care, acknowledging treatment outside specialized psychiatric services. This approach, while providing a holistic view, raises concerns about diagnostic inaccuracies. Here, we studied situations where the register-based diagnosis might be inaccurate, and whether the first episode can be reliably identified using a 14-year wash-out period. People with first register-based NAP (ICD-10 F20-F29) between years 2010 and 2018 and without NAP diagnoses in 1996-2009 were identified from the Care Register for Health Care. A diagnosis of NAP was deemed unreliable before age 7, when dementia preceded NAP diagnosis, and when a NAP diagnosis had been assigned at admission or during psychiatric hospitalization but was not confirmed by discharge diagnosis. Despite a 14-year follow-back the first register diagnosis may miss the first treatment episode in older patients. Register-based studies on psychotic disorders should pay attention to exclusion criteria and to the definition of treatment onset.

Suicides in degenerative neurocognitive disorders and traumatic brain injuries.

BACKGROUND: Neuropsychiatric symptoms in major neurocognitive disorders have been strongly associated with suicidality. METHODS: The objectives were to explore suicide rates in degenerative neurocognitive disorders (DNDs), alcohol-related neurocognitive disorders (ARNDs), and traumatic brain injuries (TBIs). Patients who received these diagnoses between 1998 and 2015 (N = 231,817) were identified from nationwide registers, and their mortality was followed up until December 31, 2018. We calculated incidences of suicides per 100,000 person-years, types of suicides, and suicide rates compared with the general population (standardized mortality ratio [SMR]). RESULTS: During the follow-up, 0.3% (95% confidence interval [95% CI]: 0.2-0.5) of patients with DNDs, 1.1% (0.7-1.8) with ARNDs, and 1.0% (0.7-1.3) with TBIs committed suicide. Suicide mortality rate was higher in men (58.9, 51.3, to 67.4 per 100,000) than in women (9.8, 7.5, to 12.5 per 100,000). The highest suicide rate was in ARNDs (98.8, 65.1, to 143.8 per 100,000), followed by TBIs (82.0, 62.4, to 105.8 per 100,000), and DNDs (21.2, 18.3, to 24.5 per 100,000). The SMRs (95% CI) were 3.69 (2.53-5.38), 2.99 (2.31-3.86), and 1.31 (1.13-1.51), respectively, and no sex difference emerged. The most common cause of death was self-inflicted injury by hanging or drowning (12.4, 10.3, to 14.8 per 100,000). CONCLUSIONS: Suicide rates were higher in all three patient groups than the general population. Suicide risk remained elevated for more than 10 years after diagnosis. The suicide methods were mostly violent.

Life course associations between smoking and depressive symptoms. A 30-year Finnish follow-up study.

INTRODUCTION: Relatively little is known whether the association between smoking and depressive symptoms changes with age and how the trajectories of smoking and depressive symptoms are intertwined during the life course. In this population-based study, these associations were examined from young adulthood to middle age. METHODS: Participants of a Finnish cohort study (N=1955) were assessed at the ages of 22, 32, 42, and 52 using questionnaires covering daily smoking (yes/no) and the short 13-item Beck Depression Inventory. Longitudinal latent class and longitudinal latent profile analyses were used identify life course trajectories of smoking and depressive symptoms. RESULTS: The proportions of daily smokers decreased, while levels of depressive symptoms increased among both females and males from age 22 to 52 years. Smoking was associated with higher levels of depressive symptoms from age 22 to 42, while not at 52. Associations among males prevailed when adjusting for education, marital status, and alcohol use. Four life course classes of daily smoking (non-smokers, decreasing prevalence of smoking, persistent smokers, and increasing prevalence of smoking) and four trajectories of depressive symptoms (low, increasing/moderate, decreasing/moderate, and high) were identified. In males, persistent daily smokers (RRR=4.5, 95% CI: 2.2-9.2) and those in the class with increasing smoking prevalence (RRR=3.2, 95% CI: 1.1-9.1) had an increased risk of belonging to the high depressive symptoms profile. In females these associations were non-significant. CONCLUSIONS: Compared to females, the relationship between smoking and depressive symptoms seems more robust among males during adulthood. Specifically, males smoking persistently from young adulthood to middle age have an increased risk of high depressive symptoms trajectory. IMPLICATIONS: This population-based cohort with 30 years of follow-up showed that the life course trajectories of daily smoking and depressive symptoms are associated. Persistent daily smokers and those starting late had an increased risk of belonging to the profile with constantly high levels of depressive symptoms during the life course. However, these associations were statistically significant only in males. Actions should be strengthened, especially in males, to prevent smoking initiation, to help smoking cessation and identify and treat depression in smokers with significant depressive symptoms.

Dysregulation of Microbiota in Patients With First-Episode Psychosis Is Associated With Symptom Severity and Treatment Response.

BACKGROUND: The gut microbiome has been implicated in the pathogenesis of mental disorders where the gut-brain axis acts as a bidirectional communication network. METHODS: Herein, we investigated the compositional and functional differences of gut microbiome between patients with first-episode psychosis (FEP) (n = 26) and healthy control participants (n = 22) using whole-genome shotgun sequencing. In addition, we assessed the oral microbiome in patients with FEP (n = 13) and listed their taxonomic diversity. RESULTS: Our findings suggest that there is a dysbiosis of gut microbiota in patients with FEP. Relative abundance of Bifidobacterium adolescentis, Prevotella copri, and Turicibacter sanguinis was markedly increased (linear discriminant analysis scores [log10] > 1, and Mann-Whitney U test; false discovery rate-adjusted p values < .05) in the FEP group compared with the healthy control participants. Pathway analysis indicated that several metabolic pathways, particularly deoxyribonucleotide biosynthesis, branched-chain amino acid biosynthesis, tricarboxylic acid cycle, and fatty acid elongation and biosynthesis, were dysregulated in the FEP group compared with the healthy control group. In addition, this preliminary study was able to identify specific gut microbes (at baseline) that were predictive of weight gain in the FEP group at a 1-year follow-up. Bacteroides dorei, Bifidobacterium adolescentis, Turicibacter sanguinis, Roseburia spp., and Ruminococcus lactaris were positively associated (eXtreme gradient boosting, XGBoost regression model, Shapley additive explanations, R2 = 0.82) with weight gain. CONCLUSIONS: Our findings may suggest the involvement of gut microbiota in the pathogenesis of psychosis. The benefit of modulation of the gut microbiome in the treatment of psychotic disorders should be explored further.

Geographical variation in treated psychotic and other mental disorders in Finland by region and urbanicity.

PURPOSE: In Finland, prevalence of schizophrenia is higher in the eastern and northern regions and co-occurs with the distribution of schizophrenia polygenic risk scores. Both genetic and environmental factors have been hypothesized to contribute to this variation. We aimed to examine the prevalence of psychotic and other mental disorders by region and degree of urbanicity, and the impacts of socio-economic adjustments on these associations. METHODS: Nationwide population registers from 2011 to 2017 and healthcare registers from 1975 to 2017. We used 19 administrative and three aggregate regions based on the distribution of schizophrenia polygenic risk scores, and a seven-level urban-rural classification. Prevalence ratios (PRs) were calculated by Poisson regression models and adjusted for gender, age, and calendar year (basic adjustments), and Finnish origin, residential history, urbanicity, household income, economic activity, and physical comorbidity (additional adjustments) on an individual level. Average marginal effects were used to visualize interaction effects between region and urbanicity. RESULTS: A total of 5,898,180 individuals were observed. All mental disorders were slightly more prevalent (PR 1.03 [95% CI, 1.02-1.03]), and psychotic disorders (1.11 [1.10-1.12]) and schizophrenia (1.19 [1.17-1.21]) considerably more prevalent in eastern and northern than in western coastal regions. After the additional adjustments, however, the PRs were 0.95 (0.95-0.96), 1.00 (0.99-1.01), and 1.03 (1.02-1.04), respectively. Urban residence was associated with increased prevalence of psychotic disorders across all regions (adjusted PR 1.21 [1.20-1.22]). CONCLUSION: After adjusting for socioeconomic and sociodemographic factors, the within-country distribution of mental disorders no longer followed the traditional east-west gradient. Urban-rural differences, on the other hand, persisted after the adjustments.

Sense of mastery in first-episode psychosis-a one-year follow-up study.

Introduction: A sense of mastery refers to beliefs about having control over one's life and has been found to protect health and buffer the effect of stressful experiences. Methods: We investigated sense of mastery in first-episode psychosis (FEP) patients and population controls at baseline and at one-year follow-up. Pearlin and Schooler's Sense of Mastery scale was completed by 322 participants at baseline and by 184 participants at follow-up. Results: People having experienced FEP reported lower mastery than controls at both time points, but a modest increase was seen in patients at follow-up. The strongest correlates of high baseline mastery in FEP were lower depressive symptoms and higher perceived social support, whereas positive or negative psychotic symptoms did not associate with mastery. Current depressive symptoms also correlated with mastery at the follow-up point, and change in depressive symptoms correlated with change in mastery. Higher mastery at treatment entry predicted remission of psychotic symptoms one year later. Sense of mastery was also found to mediate the association of perceived social support with depressive symptoms. Discussion: The usefulness of mastery measures should be further tested for estimations of patient prognosis in early psychosis.

FreeSurfer 7 quality control: Key problem areas and importance of manual corrections.

We have studied the effects of manual quality control of brain Magnetic Resonance Imaging (MRI) images processed with Freesurfer. T1 images of first episode psychosis patients (N = 60) and healthy controls (N = 41) were inspected for gray matter boundary errors. The errors were fixed, and the effects of error correction on brain volume, thickness, and surface area were measured. It is commonplace to apply quality control to Freesurfer MRI recordings to ensure that the edges of gray and white matter are detected properly, as incorrect edge detection leads to changes in variables such as volume, cortical thickness, and cortical surface area. We find that while Freesurfer v7.1.1. does regularly make mistakes in identifying the edges of cortical gray matter, correcting these errors yields limited changes in the commonly measured variables listed above. We further find that the software makes fewer gray matter boundary errors when processing female brains. The results suggest that manually correcting gray matter boundary errors may not be worthwhile due to its small effect on the measurements, with potential exceptions for studies that focus on the areas that are more commonly affected by errors: the areas around the cerebellar tentorium, paracentral lobule, and the optic nerves, specifically the horizontal segment of the middle cerebral artery.

Lack of guidelines and translational knowledge is hindering the implementation of psychiatric genetic counseling and testing within Europe - A multi-professional survey study.

Genetic research has identified a large number of genetic variants, both rare and common, underlying neurodevelopmental disorders (NDD) and major psychiatric disorders. Currently, these findings are being translated into clinical practice. However, there is a lack of knowledge and guidelines for psychiatric genetic testing (PsychGT) and genetic counseling (PsychGC). The European Union-funded COST action EnGagE (CA17130) network was started to investigate the current implementation status of PsychGT and PsychGC across 35 participating European countries. Here, we present the results of a pan-European online survey in which we gathered the opinions, knowledge, and practices of a self-selected sample of professionals involved/interested in the field. We received answers from 181 respondents. The three main occupational categories were genetic counselor (21.0%), clinical geneticist (24.9%), and researcher (25.4%). Of all 181 respondents, 106 provide GC for any psychiatric disorder or NDD, corresponding to 58.6% of the whole group ranging from 43.2% in Central Eastern Europe to 66.1% in Western Europe. Overall, 65.2% of the respondents reported that genetic testing is offered to individuals with NDD, and 26.5% indicated the same for individuals with major psychiatric disorders. Only 22.1% of the respondents indicated that they have guidelines for PsychGT. Pharmacogenetic testing actionable for psychiatric disorders was offered by 15%. Interestingly, when genetic tests are fully covered by national health insurance, more genetic testing is provided for individuals with NDD but not those with major psychiatric disorders. Our qualitative analyses of responses highlight the lack of guidelines and knowledge on utilizing and using genetic tests and education and training as the major obstacles to implementation. Indeed, the existence of psychiatric genetic training courses was confirmed by only 11.6% of respondents. The question on the relevance of up-to-date education and training in psychiatric genetics on everyday related practice was highly relevant. We provide evidence that PsychGC and PsychGT are already in use across European countries, but there is a lack of guidelines and education. Harmonization of practice and development of guidelines for genetic counseling, testing, and training professionals would improve equality and access to quality care for individuals with psychiatric disorders within Europe.

Antipsychotic Use and Mortality in Persons with Alcohol-Related Dementia or Wernicke-Korsakoff Syndrome: A Nationwide Register Study in Finland.

BACKGROUND: Research on the use of psychotropic drugs in people with alcohol-related neurocognitive disorders is virtually nonexistent. We examined the prevalence of antipsychotic drug use and its effect on mortality among patients with Wernicke-Korsakoff syndrome (WKS) or alcohol-related dementia (ARD). METHODS: In this nationwide register study, we collected data on the medication use and mortality of all persons aged ≥40 diagnosed with WKS (n = 1149) or ARD (n = 2432) between 1998 and 2015 in Finland. We calculated the prevalence of antipsychotic use within one year of diagnosis and the adjusted cumulative mortality of antipsychotic users versus non-users in relation to the age-, sex-, and calendar year-matched general population. RESULTS: Of the WKS and ARD patients, 35.9% and 38.5%, respectively, purchased one or more antipsychotic drugs in the year following diagnosis. The adjusted cumulative mortality of the antipsychotic users was significantly lower than that of non-users in both the WKS and ARD groups, where the adjusted hazard ratios (95% CI) were 0.85 (0.72-0.99) and 0.73 (0.65-0.81), respectively. WKS and ARD patients using antipsychotics were less likely to die of alcohol-related causes than antipsychotic non-users, but the difference was significant only in the ARD group. CONCLUSIONS: This population-based study shows that antipsychotic use is common in patients with WKS or ARD. In contrast to other dementia studies, our results indicate that the mortality of antipsychotic users is significantly lower than that of non-users. The lower mortality could be explained by decreased alcohol use and better healthcare coverage in antipsychotic users.

Hippocampus-Centered Network Is Associated With Positive Symptom Alleviation in Patients With First-Episode Psychosis.

BACKGROUND: Previous functional magnetic resonance imaging studies have reported widespread brain functional connectivity alterations in patients with psychosis. These studies have mostly used either resting-state or simple-task paradigms, thereby compromising experimental control or ecological validity, respectively. Additionally, in a conventional functional magnetic resonance imaging intrasubject functional connectivity analysis, it is difficult to identify which connections relate to extrinsic (stimulus-induced) and which connections relate to intrinsic (non-stimulus-related) neural processes. METHODS: To mitigate these limitations, we used intersubject functional connectivity (ISFC) to analyze longitudinal functional magnetic resonance imaging data collected while 36 individuals with first-episode psychosis (FEP) and 29 age- and sex-matched population control participants watched scenes from the fantasy movie Alice in Wonderland at baseline and again at 1-year follow-up. Furthermore, to allow unconfounded comparison and to overcome possible circularity of ISFC, we introduced a novel approach wherein ISFC in both the FEP and population control groups was calculated with respect to an independent group of participants (not included in the analyses). RESULTS: Using this independent-reference ISFC approach, we found an interaction effect wherein the independent-reference ISFC in individuals with FEP, but not in the control group participants, was significantly stronger at baseline than at follow-up in a network centered in the hippocampus and involving thalamic, striatal, and cortical regions, such as the orbitofrontal cortex. Alleviation of positive symptoms, particularly delusions, from baseline to follow-up was correlated with decreased network connectivity in patients with FEP. CONCLUSIONS: These findings link deviation of naturalistic information processing in the hippocampus-centered network to positive symptoms.

Temporal changes in the associations between diagnosed psychiatric disorders and dropping out of school early.

Psychiatric problems are risk markers for poor educational attainment. The number of adolescents receiving treatment has increased. We investigated whether the association between psychiatric problems in early adolescence and dropping out of school had changed. We used the register-based 1987 and 1997 Finnish Birth Cohort studies, which include all live births in Finland. Hospital districts with incomplete records were excluded, leaving 25,421 participants born in 1987 and 32,025 born in 1997. The main outcome was not having applied for secondary education by the year the cohort members turned 18. Our main predictors were psychiatric and neurodevelopmental disorders diagnosed by specialized services during 1998-2003 and 2008-2013, when the cohort members were 10-16 years old. We found that 511 (2.0) of subjects born in 1987 and 499 (1.6%) born in 1997 dropped out of school. Having any diagnosis at 10-16 of age was associated with dropping out of school early in both cohorts: 3.9% in 1987 and 4.8% in 1997. The highest proportions were in the subgroup with autism spectrum disorders (ASD), 19.4% in 1987 and 16.2% in 1997. Dropping out early increased among adolescents diagnosed with any psychiatric or neurodevelopmental disorder, from 3.9 to 4.8%, with the clearest increase for learning disabilities, from 3.4 to 9.0%. Dropping out decreased for those with depression, from 4.5 to 2.1%. Adolescents with psychiatric and especially neurodevelopmental disorders, need effective interventions to prevent them dropping out of school early. Increased detection of psychopathology did not result in decreased dropout rates.

Cohort profile: SUPER-Finland - the Finnish study for hereditary mechanisms of psychotic disorders.

PURPOSE: SUPER-Finland is a large Finnish collection of psychosis cases. This cohort also represents the Finnish contribution to the Stanley Global Neuropsychiatric Genetics Initiative, which seeks to diversify genetic sample collection to include Asian, Latin American and African populations in addition to known population isolates, such as Finland. PARTICIPANTS: 10 474 individuals aged 18 years or older were recruited throughout the country. The subjects have been genotyped with a genome-wide genotyping chip and exome sequenced. A subset of 897 individuals selected from known population sub-isolates were selected for whole-genome sequencing. Recruitment was done between November 2015 and December 2018. FINDINGS TO DATE: 5757 (55.2%) had a diagnosis of schizophrenia, 944 (9.1%) schizoaffective disorder, 1612 (15.5%) type I or type II bipolar disorder, 532 (5.1 %) psychotic depression, 1047 (10.0%) other psychosis and for 530 (5.1%) self-reported psychosis at recruitment could not be confirmed from register data. Mean duration of schizophrenia was 22.0 years at the time of the recruitment. By the end of the year 2018, 204 of the recruited individuals had died. The most common cause of death was cardiovascular disease (n=61) followed by neoplasms (n=40). Ten subjects had psychiatric morbidity as the primary cause of death. FUTURE PLANS: Compare the effects of common variants, rare variants and copy number variations (CNVs) on severity of psychotic illness. In addition, we aim to track longitudinal course of illness based on nation-wide register data to estimate how phenotypic and genetic differences alter it.