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Background: Evidence on the role of co-occurring psychiatric disorders in mortality associated with psychotic depression is limited. Aims: To estimate the risk of cause-specific mortality in psychotic depression compared with severe non-psychotic depression while controlling for comorbid psychiatric disorders. Method: This cohort study used routine data from nationwide health registers in Finland. Eligible participants had their first diagnosis for psychotic depression or for severe non-psychotic depression between the years 2000 and 2018, had no pre-existing diagnoses for schizophrenia spectrum disorders or bipolar disorder, and were aged 18–65 years at the index diagnosis. Causes of death were defined by ICD-10 codes. The follow-up time was up to 18 years. Results: We included 19 064 individuals with incident psychotic depression and 90 877 individuals with incident non-psychotic depression. Half (1199/2188) of the deaths in those with psychotic depression occurred within 5 years from the index diagnosis and the highest relative risk was during the first year after the diagnosis. Compared with individuals with non-psychotic depression, those with psychotic depression had a higher risk of all-cause mortality (adjusted hazard ratio, aHR = 1.59, 95% CI 1.48–1.70), suicides (aHR = 2.36, 95% CI 2.11–2.64) and fatal accidents (aHR 1.63, 95% CI 1.26–2.10) during the subsequent 5-year period after the index diagnosis. Conclusions: Psychotic symptoms markedly added to the mortality risk associated with severe depression after controlling for psychiatric comorbidity. Prompt treatment and enhanced monitoring for psychotic symptoms is warranted in all patients with severe depression to prevent deaths because of suicides and other external causes. [ABSTRACT FROM AUTHOR]

Background: Long-term 'not in education, employment or training' (NEET) status is an important indicator of youth marginalisation.Aims: To carry out a comprehensive overview of the associations between different psychiatric illnesses and long-term NEET status.Method: We used the register-based 1987 Finnish Birth Cohort study, which includes all live births in Finland during that year. The analyses comprised 55 273 individuals after exclusions for intellectual disability, death or emigration. We predicted that psychiatric disorders, diagnosed by specialist services between 1998 and 2007 when the cohort were 10-20 years of age, would be associated with subsequent long-term NEET (defined as NEET for at least 5 years between 2008 and 2015, when they were 20-28 years of age).Results: In total, 1438 individuals (2.6%) were long-term NEET during follow-up and the associations between long-term NEET and the 11 diagnostic categories we studied were statistically significant (P < 0.001). In multivariate models we included sociodemographic characteristics and upper secondary education as covariates, and the highest effect sizes, measured by odds ratios (OR) with 95% confidence intervals (CI), were found for psychosis (OR = 12.0, 95% CI 9.5-15.2) and autism spectrum disorder (OR = 17.3, 95% CI 11.5-26.0). If individuals had not successfully completed this education, 70.6% of those with autism spectrum disorder and 48.4% of those with psychosis were later long-term NEET.Conclusions: Adolescents who receive treatment for psychiatric disorders, particularly autism spectrum disorder or psychosis, need support to access education and employment. This could help to prevent marginalisation in early adulthood. [ABSTRACT FROM AUTHOR]

Through copy number variations, the 16p13.11 locus has been consistently linked to mental disorders. This locus contains the NDE1 gene, which also encodes microRNA- 484. Both of them have been highlighted to play a role in the etiology of mental illness. A 4-SNP haplotype spanning this locus has been shown to associate with schizophrenia in Finnish females. Here we set out to identify any functional variations implicated by this haplotype. We used a sequencing and genotyping study design to identify variations of interest in a Finnish familial cohort ascertained for schizophrenia. We identified 295 variants through sequencing, none of which were located directly within microRNA-484. Two variants were observed to associate with schizophrenia in a sex-dependent manner (females only) in the whole schizophrenia familial cohort (rs2242549 P = .00044; OR = 1.20, 95% CI 1.03-1.40; rs881803 P = .00021; OR = 1.20, 95% CI 1.02-1.40). Both variants were followed up in additional psychiatric cohorts, with neuropsychological traits, and gene expression data, in order to further examine their role. Gene expression data from the familial schizophrenia cohort demonstrated a significant association between rs881803 and 1504 probes (FDR q < 0.05). These were significantly enriched for genes that are predicted miR-484 targets (n = 54; P = .000193), and with probes differentially expressed between the sexes (n = 48; P = .000187). While both SNPs are eQTLs for NDE1, rs881803 is located in a predicted transcription factor binding site. Based on its location and association pattern, we conclude that rs881803 is the prime functional candidate under this locus, affecting the roles of both NDE1 and miR-484 in psychiatric disorders. [ABSTRACT FROM AUTHOR]

Large amount of data have been published on non-psychotic depression (NPD), schizophrenia (SZ), and bipolar disorder, while psychotic depression (PD) as an own entity has received much smaller attention. We performed a systematic review and meta-analyses on epidemiology, especially incidence and prevalence, risk factors, and outcomes of PD. A systematic search to identify potentially relevant studies was conducted using four electronic databases and a manual search. The search identified 1764 unique potentially relevant articles, the final study included 99 articles. We found that the lifetime prevalence of PD varies between 0.35% and 1%, with higher rates in older age. Onset age of PD was earlier than that of NPD in younger samples, but later in older samples. There were no differences in gender distribution in PD v. NPD, but higher proportion of females was found in PD than in SZ or in psychotic bipolar disorder (PBD). Risk factors have rarely been studied, the main finding being that family history of psychosis and bipolar disorder increases the risk of PD. Outcomes of PD were mostly worse when compared with NPD, but better compared with SZ and schizoaffective disorder. The outcome compared with PBD was relatively similar, and somewhat varied depending on the measure of the outcome. Based on this review, the amount of research on PD is far from that of NPD, SZ, and bipolar disorder. Based on our findings, PD seems distinguishable from related disorders and needs more scientific attention. [ABSTRACT FROM AUTHOR]

Objectives: We conducted a population based study aiming at finding predictors of mortality in psychotic disorders and evaluating the extent to which sociodemographic, lifestyle and health-related factors explain the excess mortality.Methods: In a nationally representative sample of Finns aged 30-70years (n=5642), psychotic disorders were diagnosed using structured interviews and medical records in 2000-2001. Information on mortality and causes of death was obtained of those who died by the end of year 2013. Cox proportional hazards models were used to investigate the mortality risk.Results: No people with affective psychoses (n=36) died during the follow-up, thus the analysis was restricted to non-affective psychotic disorders (NAP) (n=106). Adjusting for age and sex, NAP was statistically significantly associated with all-cause mortality (hazard ratio (HR) 2.99, 95% CI 2.03-4.41) and natural-cause mortality (HR 2.81, 95% CI 1.85-4.28). After adjusting for sociodemographic factors, health status, inflammation and smoking, the HR dropped to 2.11 (95% CI 1.10-4.05) for all-cause and to 1.98 (95% CI 0.94-4.16) for natural-cause mortality. Within the NAP group, antipsychotic use at baseline was associated with reduced HR for natural-cause mortality (HR 0.25, 95% CI 0.07-0.96), and smoking with increased HR (HR 3.54, 95% CI 1.07-11.69).Conclusions: The elevated mortality risk in people with NAP is only partly explained by socioeconomic factors, lifestyle, cardio-metabolic comorbidities and inflammation. Smoking cessation should be prioritized in treatment of psychotic disorders. More research is needed on the quality of treatment of somatic diseases in people with psychotic disorders. [ABSTRACT FROM AUTHOR]

Purpose: Migrants appear to have a higher risk of mental disorders, but findings vary across country settings and migrant groups. We aimed to assess incidence and prevalence of mental disorders among immigrants and Finnish-born controls in a register-based cohort study.Methods: A register-based cohort study of 184.806 immigrants and 185.184 Finnish-born controls (1.412.117 person-years) was conducted. Information on mental disorders according to ICD-10 was retrieved from the Hospital Discharge Register, which covers all public health care use.Results: The incidence of any mental disorder was lower among male (adjusted HR 0.82, 95% CI 0.77-0.87) and female (aHR 0.76, 95% CI 0.72-0.81) immigrants, being lowest among Asian and highest among North African and Middle Eastern immigrants. The incidence of bipolar, depressive and alcohol use disorders was lower among immigrants. Incidence of psychotic disorders was lower among female and not higher among male immigrants, compared with native Finns. Incidence of PTSD was higher among male immigrants (aHR 4.88, 95% CI 3.38-7.05).Conclusions: The risk of mental disorders varies significantly across migrant groups and disorders and is generally lower among immigrants than native Finns. [ABSTRACT FROM AUTHOR]

Background: A text messaging service (short message service [SMS]) has the potential to target large groups of people with long-term illnesses such as serious mental disorders, who may have difficulty with treatment adherence. Robust research on the impact of mobile technology interventions for these patients remains scarce.Objective: The main objective of our study was to investigate the impact of individually tailored short text messages on the rate of psychiatric hospital readmissions, health care service use, and clinical outcomes. In addition, we analyzed treatment costs.Methods: Between September 2011 and November 2012, we randomly assigned 1139 people to a tailored text message intervention (n=569) or usual care (n=570). Participants received semiautomated text messages for up to 12 months or usual care. The primary outcome, based on routinely collected health register data, was patient readmission into a psychiatric hospital during a 12-month follow-up period. Secondary outcomes were related to other service use, coercion, medication, adverse events, satisfaction, social functioning, quality of life, and economic factors (cost analysis).Results: There was 98.24% (1119/1139) follow-up at 12 months. Tailored mobile telephone text messages did not reduce the rate of hospital admissions (242/563, 43.0% of the SMS group vs 216/556, 38.8% of the control group; relative risk 1.11; 95% CI 0.92-1.33; P=.28), time between hospitalizations (mean difference 7.0 days 95% CI -8.0 to 24.0; P=.37), time spent in a psychiatric hospital during the year (mean difference 2.0 days 95% CI -2.0 to 7.0; P=.35), or other service outcomes. People who received text messages were less disabled, based on Global Assessment Scale scores at the time of their readmission, than those who did not receive text messages (odds ratio 0.68; 95% CI 0.47-0.97; P=.04). The costs of treatment were higher for people in the SMS group than in the control group (mean €10,103 vs €9210, respectively, P<.001).Conclusions: High-grade routinely collected data can provide clear outcomes for pragmatic randomized trials. SMS messaging tailored with the input of each individual patient did not decrease the rate of psychiatric hospital visits after the 12 months of follow-up. Although there may have been other, more subtle effects, the results of these were not evident in outcomes of agreed importance to clinicians, policymakers, and patients and their families.Trial Registration: International Standard Randomized Controlled Trial Number (ISRCTN): 27704027; http://www.isrctn.com/ISRCTN27704027 (Archived by WebCite at http://www.webcitation.org/6rVzZrbuz). [ABSTRACT FROM AUTHOR]

Variants in the SLCO1B1 (solute carrier organic anion transporter family member 1B1) gene encoding the OATP1B1 (organic anion transporting polypeptide 1B1) protein are associated with altered transporter function that can predispose patients to adverse drug effects with statin treatment. We explored the effect of six rare SLCO1B1 single nucleotide variants (SNVs) occurring in Finnish individuals with a psychotic disorder on expression and functionality of the OATP1B1 protein. The SUPER-Finland study has performed exome sequencing on 9381 individuals with at least one psychotic episode during their lifetime. SLCO1B1 SNVs were annotated with PHRED-scaled combined annotation-dependent (CADD) scores and the Ensembl variant effect predictor. In vitro functionality studies were conducted for the SNVs with a PHRED-scaled CADD score of >10 and predicted to be missense. To estimate possible changes in transport activity caused by the variants, transport of 2',7'-dichlorofluorescein (DCF) in OATP1B1-expressing HEK293 cells was measured. According to the findings, additional tests with rosuvastatin and estrone sulfate were conducted. The amount of OATP1B1 in crude membrane fractions was quantified using a liquid chromatography tandem mass spectrometry-based quantitative targeted absolute proteomics analysis. Six rare missense variants of SLCO1B1 were identified in the study population, located in transmembrane helix 3: c.317T>C (p.106I>T), intracellular loop 2: c.629G>T (p.210G>V), c.633A>G (p.211I>M), c.639T>A (p.213N>L), transmembrane helix 6: 820A>G (p.274I>V), and the C-terminal end: 2005A>C (p.669N>H). Of these variants, SLCO1B1 c.629G>T (p.210G>V) resulted in the loss of in vitro function, abolishing the uptake of DCF, estrone sulfate, and rosuvastatin and reducing the membrane protein expression to 31% of reference OATP1B1. Of the six rare missense variants, SLCO1B1 c.629G>T (p.210G>V) causes a loss of function of OATP1B1 transport in vitro and severely decreases membrane protein abundance. Carriers of SLCO1B1 c.629G>T might be susceptible to altered pharmacokinetics of OATP1B1 substrate drugs and might have increased likelihood of adverse drug effects such as statin-associated musculoskeletal symptoms.

Abstract: We investigated the prevalence of coronary heart disease (CHD) and myocardial infarction (MI) in persons with DSM-IV psychotic disorders. We also examined cardiac conduction abnormalities, and the role of antipsychotic medication in them. The study was based on a nationally representative survey of 8028 persons aged 30 years or over from Finland. Diagnoses of CHD and MI were based on electrocardiographic findings, health examination, and register information. QTc was calculated using the Bazett formula, and Minnesota classification was used for conduction abnormalities. We found that large Q-waves suggesting past MI were significantly more frequent in persons with schizophrenia, while the prevalence of CHD in persons with psychotic disorders did not differ significantly from the remaining study sample. Prevalence of prolonged QTc interval was significantly increased in persons with schizophrenia and in users of typical antipsychotics. However, low-potency antipsychotic use but not diagnosis of schizophrenia remained an independent predictor of prolonged QTc interval in a logistic regression. Low-potency antipsychotic use was associated with ventricular conduction defects, and high-potency antipsychotic use with premature beats. Symptoms and signs of CHD should be actively monitored patients with schizophrenia, and the electrocardiogram should be monitored for all types of changes in persons receiving antipsychotic medication. [Copyright &y& Elsevier]

Background: Persons with psychotic disorder may have poorer visual acuity (VA). The aim of the study is to investigate in a general population the prevalence of impaired habitual VA and self-reported difficulties in vision among persons with different psychotic disorders.Method: A nationally representative sample of 6,663 persons aged 30 or older whose binocular VA for distance and for near vision was measured with current spectacles, if any. Diagnostic assessment of DSM-IV psychotic disorders used both SCID interview and case note data. Life-time ever diagnoses of psychotic disorders were classified into schizophrenia, other non-affective psychotic disorders and affective psychoses.Results: After adjusting for age and sex, schizophrenia was associated with significantly increased odds of having visual impairment for distance (OR 5.04, P < 0.0001) and for near vision (OR 6.22, P < 0.0001), while other psychotic disorders were not. Self-reported problems in VA were more common in persons with schizophrenia and other non-affective psychotic disorders than in the remaining study sample. Only 43.9% of persons with schizophrenia, compared with 69.7% in the total sample (chi(2) = 13.79, d.f. 1, P = 0.0002), had had their vision examined during the 5 years before the VA measurement.Conclusions: Because persons with schizophrenia attend vision examinations substantially less frequently than others, and their vision is notably weaker, regular ocular evaluations should be included in physical health monitoring in psychotic disorders. [ABSTRACT FROM AUTHOR]

We report patterns of hospitalization in schizophrenic psychoses by age 34 in a longitudinal population-based cohort. We test the predictive ability of various demographic and illness-related variables on patterns of hospitalization, with a special focus on the length of the first psychiatric hospitalization. All living subjects of the Northern Finland 1966 Birth Cohort with DSM-III-R schizophrenia ( n =88) and other schizophrenia spectrum cases ( n =27) by the year 1997 in the Finnish Hospital Discharge Register were followed for an average of 10.5 years. Measures of psychiatric hospitalization included time to re-hospitalization (as continuous and as re-hospitalization within 2 years) and the number of hospital episodes. Length of the first hospitalization, other illness-related and various socio-demographic predictors were used to predict hospitalization patterns. After adjusting for gender, age at first admission and number of hospital days a short (1–14 days) first hospitalization (reference >30 days; adjusted odds ratio 6.39; 95% CI 2.00–20.41) and familial risk of psychosis (OR 3.36; 1.09–10.39) predicted re-hospitalization within 2 years. A short first hospitalization also predicted frequent psychiatric admissions defined as the first three admissions within 3 years (OR 13.77; 3.92–48.36). A short first hospitalization was linked to increased risk of re-hospitalizations. Although short hospitalization is recommended by several guidelines, there may be a group of patients with schizophrenic psychoses in which too short a hospitalization may lead to inadequate treatment response. [ABSTRACT FROM AUTHOR]

We demonstrate that CYP2D6 copy-number variation (CNV) can be imputed using existing imputation algorithms. Additionally, we report frequencies of key pharmacogenetic variants in individuals with a psychotic disorder from the genetically bottle-necked population of Finland. We combined GWAS chip and CYP2D6 CNV data from the Breast Cancer Pain Genetics study to construct an imputation panel (n = 902) for CYP2D6 CNV. The resulting data set was used as a CYP2D6 CNV imputation panel in 9262 non-related individuals from the SUPER-Finland study. Based on imputation of 9262 individuals we confirm the higher frequency of CYP2D6 ultrarapid metabolizers and a 22-fold enrichment of the UGT1A1 decreased function variant rs4148323 (UGT1A1*6) in Finland compared with non-Finnish Europeans. Similarly, the NUDT15 variant rs116855232 was highly enriched in Finland. We demonstrate that imputation of CYP2D6 CNV is possible and the methodology enables studying CYP2D6 in large biobanks with genome-wide data., (© 2022. The Author(s).)

The outcome of first-episode psychosis (FEP) varies and may be predicted by several baseline measures. In the Helsinki Early Psychosis Study, young adultswith FEP (n=97) fromtheHelsinki area in Finland were broadly assessed as soon as possible after first psychiatric contact for psychosis. Age- and gender-matched population controls were also assessed (n=62). The participants were followed up via appointments and medical records. We present both published and unpublished results on predictors of 12-month clinical, functional, and metabolic outcomes. More severe cognitive deficits at the beginning of treatment predicted several outcomes such as occupational status and functional level - beyond baseline positive and affective symptomlevels, but notwhen negative symptoms were accounted for. More severe baseline obsessive-compulsive symptoms were predictive of a lower rate of remission, whereas a higher level of anxiety symptoms predicted better functional outcome, when the severity of positive symptoms was adjusted for. Adverse childhood experiences measuring cumulating psychosocial stress did not predict occupational status or functional level when positive and negative symptoms and neurocognition were controlled for, whereas in controls having experienced school bullying was associated with lower functioning. Insulin resistance in early psychosis appeared as an early marker of increased vulnerability to weight gain and abdominal obesity in young adults with FEP. Further, increased waist circumference predicted worsening low-grade inflammation, increasing further the cardiovascular risk. In sum, we have found different types of prognostic markers in FEP. Identifying the individuals at risk of less favorable outcomes could affect treatment choices in FEP. [ABSTRACT FROM AUTHOR]

Background and Purpose- At acute phase and neurointensive care, patients with aneurysmal subarachnoid hemorrhage (aSAH) may become agitated or delirious. We found no previous studies on psychotic disorders or antipsychotic drug (APD) use by long-term aSAH survivors. We defined the APD use and its risk factors among 12-month survivors of aSAH in an Eastern Finnish population-based cohort with long-term follow-up. Methods- We analyzed APD use in 1144 consecutive patients with aSAH alive at 12 months of the Kuopio intracranial aneurysm patient and family database and their age, sex, and birth municipality matched controls (3:1; n=3432) from 1995 to 2013 and median follow-up of 9 years. Using the Finish nationwide health registries, we obtained drug purchase and hospital discharge data. Results- In total, 140 (12%) of the 1144 patients started APD use first time after aSAH (index date), in contrast to 145 (4%) of the 3432 matched population controls. The cumulative rate of starting APD was 6% at 1 year and 9% at 5 years, in contrast to 1% and 2% in the controls, respectively. The rates at 1 and 5 years were only 1% and 2% in the 489 patients with a good condition (modified Rankin Scale score, 0 or 1 at 12 months; no shunt, intracerebral hemorrhage, or intraventricular hemorrhage). Instead, the highest rate of APD use, 23% at 5 years was among the 192 patients shunted for hydrocephalus after aSAH. Eighty-eight (63%) of the 140 aSAH patients with APD use had also concomitant antidepressant or antiepileptic drug use. Conclusions- The 12-month survivors of aSAH were significantly more likely to be started on APD after aSAH than their matched population controls. These patients often used antidepressant and antiepileptic drugs concomitantly. The use of APDs strongly correlated with signs of brain injury after aSAH, with low use if no signs of significant brain injury were present.

After twenty years of transformation of Finnish mental health care, in the late 80s and early 90s of the last century, incidence of schizophrenia in Western Lapland dropped from 35/100,000 to 7/100,000. This phenomenon is linked with Yrjo O. Alanen et al. who investigated schizophrenia treatment outcomes and psychosocial rehabilitation of people with schizophrenia. Investigators focused on an individually tailored psychotherapeutic recovery plan during patient's hospitalization, including care for patients' families. Within the "Finnish National Schizophrenia Project" the principles of the Need-Adapted Treatment were created and 50% of Finland's country gained access to mobile crisis intervention teams. Further studies were continued within "Acute PsychosisIntegrated Treatment Project" (1992-1993) which locally, in Western Lapland, proceeded into "Open Dialogue in Acute Psychosis Project" (ODAP) (1994-1997). In this approach, all important decisions regarding the patient, including hospitalization or pharmacotherapy, are discussed not only with the entire therapeutic team, but also with the patient and his family members. Two - and five-year follow-ups demonstrated high treatment efficacy as well as important cost reduction in mental health care spending. First two"Open Dialogue Method" training courses for representatives of the medical, psychological, nursing and social care have been completed in Poland in October 2014. Studies evaluating the therapeutic effectiveness of the described approach are being planned.

Background: The Helsinki High-Risk Study monitors women treated for schizophrenia-spectrum disorders in Helsinki mental hospitals before 1975, their offspring, and controls., Aims: To compare the development of high-risk and control group children, and investigate which factors predicted future psychiatric disorders., Method: We examined information from childhood and school health record cards of 159 high-risk and 99 control group offspring. Logistic regression was used to assess whether developmental abnormalities predicted later mental disorders., Results: Compared with controls, children in the high-risk group had more emotional symptoms before school age, attentional problems and social inhibition at school age, and neurological soft signs throughout. In this group pre-school social adjustment problems (OR=9.7, 95% CI 1.8-51.8) or severe neurological symptoms (Fisher's test, P=0.006) predicted future schizophrenia-spectrum disorder. Social adjustment problems and emotional symptoms during school age predicted future non-psychotic psychiatric disorders., Conclusions: Our study supports the validity of neurological, emotional, social and behavioural markers as vulnerability indicators of psychotic and other mental disorders, particularly among children genetically at high risk of psychosis.