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 not 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.

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.

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.

Functional Characterization of Six SLCO1B1 (OATP1B1) Variants Observed in Finnish Individuals with a Psychotic Disorder.

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.

Effectiveness of Antipsychotic Use for Reducing Risk of Work Disability: Results From a Within-Subject Analysis of a Swedish National Cohort of 21,551 Patients With First-Episode Nonaffective Psychosis.

OBJECTIVE: The authors sought to determine whether antipsychotic use, compared with nonuse, is associated with lower work disability in first-episode nonaffective psychosis, and if so, for how long. METHODS: A within-subject design was used to study the risk of sickness absence or disability pension during antipsychotic use compared with nonuse during a maximum of 11 years of follow-up (2006-2016) in a Swedish nationwide cohort of patients with first-episode nonaffective psychosis (N=21,551; age range, 16-45 years). The within-subject analyses were conducted with stratified Cox regression models, adjusted for time-varying factors, using each individual as her or his own control to eliminate selection bias. The primary outcome was work disability (sickness absence or disability pension). RESULTS: Overall, 45.9% of first-episode patients had work disability during the median length of follow-up of 4.8 years. The risk of work disability was lower during use compared with nonuse of any antipsychotic (adjusted hazard ratio [aHR]=0.65, 95% CI=0.59-0.72). The lowest adjusted hazard ratios emerged for long-acting injectable antipsychotics (aHR=0.46, 95% CI=0.34-0.62), oral aripiprazole (aHR=0.68, 95% CI=0.56-0.82), and oral olanzapine (aHR=0.68, 95% CI=0.59-0.78). Long-acting injectables were associated with lower risk than olanzapine, the most commonly used oral antipsychotic (aHR=0.68, 95% CI=0.50-0.94). Adjusted hazard ratios were similar during the periods of <2 years, 2-5 years, and >5 years since diagnosis. CONCLUSIONS: Among individuals with first-episode nonaffective psychosis, antipsychotic treatment (with long-acting injectables in particular) was associated with about 30%-50% lower risk of work disability compared with nonuse of antipsychotics in the same individuals, which held true beyond 5 years after first diagnosis. These findings are informative regarding the important topic of early discontinuation of antipsychotic treatment after a first episode of nonaffective psychosis, but they need replication.

Extrapyramidal symptoms predict cognitive performance after first-episode psychosis.

Extrapyramidal (EP) symptoms such as tremor, rigidity, and bradykinesia are common side effects of most antipsychotics, and may associate with impaired performance in neurocognitive testing. We studied EP symptoms in first-episode psychosis (FEP; n = 113). Cognitive testing and EP symptoms (three items of the Simpson-Angus Scale) were assessed at baseline and follow-up (mean follow-up time 12 months). Mild EP symptoms were present at treatment onset in 40% of the participants. EP symptoms were related with lower performance in neurocognitive testing at baseline and at follow-up, especially among those with nonaffective psychotic disorder, and especially in tasks requiring speed of processing. No associations between EP symptoms and social cognition were detected. In linear regression models, when positive and negative symptom levels and chlorpromazine equivalents were accounted for, baseline EP symptoms were associated with worse baseline global neurocognition and visuomotor performance. Baseline EP symptoms also longitudinally predicted global, verbal, and visuomotor cognition. However, there were no cross-sectional associations between EP symptoms and cognitive performance at follow-up. In sum, we found both cross-sectional and longitudinal associations between EP symptoms and neurocognitive task performance in the early course of psychosis. Those without EP symptoms at the start of treatment had higher baseline and follow-up neurocognitive performance. Even mild EP symptoms may represent early markers of long-term neurocognitive impairment.

Lifetime psychiatric diagnoses among adolescents with severe conduct problems - A register-based follow-up study.

BACKGROUND: Both delinquency and out-of-home care (OOHC) are associated with a wide spectrum of psychiatric disorders. Reform schools (RS) are Finnish OOHC institutions for adolescents with severe conduct problems. OBJECTIVE: We investigated the prevalence of psychiatric diagnoses among individuals with a history of RS placement. PARTICIPANTS AND SETTING: The data consisted of individuals placed in a RS on the last day of the years 1991, 1996, 2001, 2006 or 2011 (N = 1074) and a matched comparison group (N = 5313). METHODS: Information on lifetime psychiatric diagnoses, grouped into eight categories, was collected from the nationwide health care registry. The follow-up time ranged from 17 to 44 years. RESULTS: Among RS population, 59.5 % had some psychiatric diagnosis, which was 12-fold compared to general population peers (hazard ratio HR = 12.4). The most prevalent categories were Conduct disorders and/or ADHD (30.7 %, HR = 41.5), Substance use disorders (29.3 %, HR = 16.8,), Other childhood disorders (8.6 %, HR = 11.9) and Personality disorders (10.9 %, HR = 11.6) followed by Mental retardation (6.4 %, HR = 8.4), Schizophrenia spectrum disorders (9.7 %, HR = 7.9), Affective disorders (17.9 %, HR = 7.3), and Disorders of psychological development (6.1 %, HR = 4.4). All differences were statistically significant (p < .001). CONCLUSIONS: RS background associates with an excess of psychiatric disorders, which adds to the burden of other known risk factors for adult age well-being. Effective screening and intervention for psychiatric problems should be available both during the RS placement and after-care.

Differences in psychosocial functioning between psychotic disorders in the Finnish SUPER study.

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.

Psychotic-like experiences of young adults in the general population predict mental disorders.

Psychotic-like experiences (PLEs) have been identified as risk markers for psychotic disorders and may indicate an individual's susceptibility to mental disorders in general. We examined whether 23 PLEs (assessed with M-CIDI questionnaire) reported in young adulthood (n = 1313) predict subsequent psychotic or any mental disorders in the general population. We also investigated whether these possible associations are explained by general psychological distress assessed with the General Health Questionnaire-12 (GHQ-12). The register follow-up period spanned 10-12 years. In Cox regression models, PLEs predicted subsequent psychotic disorders (n = 12) when the effects of age, sex, education, and marital status were adjusted for, but not when general psychological distress was added to the model. Having any mental disorders during follow-up (n = 91) was predicted by PLEs reported at a younger age, when controlling for age, sex, education, marital status, and general psychological distress. In line with earlier results in other age groups, PLEs can be seen as a sign of vulnerability to not just psychotic but all mental disorders during the following years also among young adults in the general population. PLEs were a predictive marker of general psychopathology independently from general psychological distress.

Antidepressant use among immigrants with depressive disorder living in Finland: A register-based study.

BACKGROUND: The aim of this study was to examine differences in the initiation and discontinuation of antidepressants between immigrants and the Finnish-born population diagnosed with depression in specialized health care. METHODS: The study utilized register-based data, which includes all immigrants living in Finland at the end of 2010 and matched Finnish-born controls. For this study, we selected individuals who had received a diagnosis of depression during 2011-2014 (immigrants n = 2244, Finnish-born n = 2773). Their antidepressant use was studied for a one-year period from initiation. A logistic regression was used to predict initiation and a Cox regression was used to predict discontinuation. RESULTS: Immigrants were more likely to initiate the use of antidepressants than the Finnish-born controls (adjusted OR = 1.25, 95% CI = 1.07-1.46), but they also discontinued the medication earlier than the Finnish-born controls (adjusted HR = 1.48, 95% CI = 1.31-1.68). Immigrants from Sub Saharan Africa, the Middle East and Northern Africa were most likely to discontinue antidepressants earlier. More severe depression, a longer length of residence in Finland and more intensive psychiatric treatment were associated with decreased risk of discontinuation. LIMITATIONS: The registers do not provide information on the perceived reasons for the discontinuation. CONCLUSIONS: Immigrants with depression initiate antidepressants more often than the Finnish-born population, but they also discontinue them earlier. Early discontinuation may be a sign of insufficient treatment suggesting that there could be a need for improvement in mental health care for immigrants in Finland.

Reaction Time and Visual Memory in Connection to Hazardous Drinking Polygenic Scores in Schizophrenia, Schizoaffective Disorder 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.

Reaction Time and Visual Memory in Connection to Alcohol Use in Persons with Bipolar Disorder.

The purpose of this study was to explore the association of cognition with hazardous drinking and alcohol-related disorder in persons with bipolar disorder (BD). The study population included 1268 persons from Finland with bipolar disorder. Alcohol use was assessed through hazardous drinking and alcohol-related disorder including alcohol use disorder (AUD). Hazardous drinking was screened with the Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) screening tool. Alcohol-related disorder diagnoses were obtained from the national registrar data. 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. Depressive symptoms were assessed with the Mental Health Inventory with five items (MHI-5). However, no assessment of current manic symptoms was available. Association between RT-test and alcohol use was analyzed with log-linear regression, and eß with 95% confidence intervals (CI) are reported. PAL first trial memory score was analyzed with linear regression, and ß with 95% CI are reported. PAL total errors adjusted was analyzed with logistic regression and odds ratios (OR) with 95% CI are reported. After adjustment of age, education, housing status and depression, hazardous drinking was associated with lower median and less variable RT in females while AUD was associated with a poorer PAL test performance in terms of the total errors adjusted scores in females. Our findings of positive associations between alcohol use and cognition in persons with bipolar disorder are difficult to explain because of the methodological flaw of not being able to separately assess only participants in euthymic phase.

Reaction Time and Visual Memory in Connection with Alcohol Use in Schizophrenia and Schizoaffective Disorder.

The purpose of this study was to explore the association between cognition and hazardous drinking and alcohol use disorder in schizophrenia and schizoaffective disorder. Cognition is more or less compromised in schizophrenia, and schizoaffective disorder and alcohol use might aggravate this phenomenon. The study population included 3362 individuals from Finland with diagnoses of schizophrenia or schizoaffective disorder. Hazardous drinking was screened with the AUDIT-C (Alcohol Use Disorders Identification Test for Consumption) screening tool. Alcohol use disorder (AUD) diagnoses were obtained from national registrar data. Participants performed two computerized tasks from the Cambridge Automated Neuropsychological Test Battery (CANTAB) on a tablet computer: The Five-Choice Serial Reaction Time Task (5-CSRTT) or the reaction time (RT) test and the Paired Associative Learning (PAL) test. The association between alcohol use and the RT and PAL tests was analyzed with log-linear regression and logistic regression, respectively. After adjustment for age, education, housing status, and the age at which the respondents had their first psychotic episodes, hazardous drinking was associated with a lower median RT in females and less variable RT in males, while AUD was associated with a poorer PAL test performance in terms of the total errors adjusted scores (TEASs) in females. Our findings of positive associations between alcohol and cognition in schizophrenia and schizoaffective disorder are unique.

Post-traumatic stress disorder among immigrants living in Finland: Comorbidity and mental health service use.

The aim of this study was to compare differences in comorbidity between immigrants and Finnish-born controls, and to examine the treatment received by immigrants with PTSD. Our original data included all the immigrants living in Finland by the end of 2010 and matched controls. For this study, we selected individuals who had received a diagnosis of PTSD during 2010-2015 (immigrants: n = 754, Finnish-born controls: n = 311). We compared the frequency of different comorbid conditions between immigrants and natives. Multinomial logistic regression was used to predict categorized treatment intensity with the region of origin and length of residence among the immigrants. Psychiatric comorbidity was much more extensive among the Finnish-born controls than among immigrants. Immigrants from Africa and the Middle East more often received treatment of low intensity compared with immigrants from Western countries. The length of residence was associated with more frequent treatment. The important differences in comorbidity and background characteristics between immigrants and natives should be taken into account in planning treatment guidelines for PTSD. The disparities in treatment intensity across different immigrant groups indicate a need to improve the services for immigrants with PTSD.

Depression and anxiety disorders among immigrants living in Finland: Comorbidity and mental health service use.

BACKGROUND: The aims of this study were to (1) compare differences in psychiatric comorbidity of depression and anxiety disorders between immigrants and native Finns and to (2) compare differences in the intensity of psychiatric care received by different immigrant groups and Finnish-born controls with depression and/or anxiety disorders. METHODS: The study uses registered-based data, which includes all immigrants living in Finland at the end of 2010 and matched Finnish-born controls. For this study, we selected individuals who had received a diagnosis of depression and/or an anxiety disorder during the follow-up (2011-2015) (immigrants n = 6542, Finnish-born controls n = 9281). We compared differences in comorbidity between the immigrants and the Finnish-born controls using chi-squared tests. Multinomial logistic regression was used to predict psychiatric treatment intensity by immigrant status, region of origin, and other background factors. RESULTS: In both diagnosis groups, Finnish-born participants exhibited greater comorbidity of other psychiatric disorders. Immigrants more often received lower intensity treatment and less often higher intensity treatment. These differences were most striking among those from Eastern Europe, the Middle East, and Africa. LIMITATIONS: We did not have the information on the perceived need for the services, which limits us from drawing further conclusions about the mechanisms behind the observed patterns. CONCLUSIONS: Immigrants in Finland receive less intensive treatment for depression and anxiety disorders compared to the Finnish-born population. Since lower symptom levels can unlikely alone explain these differences, they could reflect a need for improvement in the psychiatric services for immigrants.

Variants in regulatory elements of PDE4D associate with major mental illness in the Finnish population.

We have previously reported a replicable association between variants at the PDE4D gene and familial schizophrenia in a Finnish cohort. In order to identify the potential functional mutations underlying these previous findings, we sequenced 1.5 Mb of the PDE4D genomic locus in 20 families (consisting of 96 individuals and 79 independent chromosomes), followed by two stages of genotyping across 6668 individuals from multiple Finnish cohorts for major mental illnesses. We identified 4570 SNPs across the PDE4D gene, with 380 associated to schizophrenia (p ≤ 0.05). Importantly, two of these variants, rs35278 and rs165940, are located at transcription factor-binding sites, and displayed replicable association in the two-stage enlargement of the familial schizophrenia cohort (combined statistics for rs35278 p = 0.0012; OR = 1.18, 95% CI: 1.06-1.32; and rs165940 p = 0.0016; OR = 1.27, 95% CI: 1.13-1.41). Further analysis using additional cohorts and endophenotypes revealed that rs165940 principally associates within the psychosis (p = 0.025, OR = 1.18, 95% CI: 1.07-1.30) and cognitive domains of major mental illnesses (g-score p = 0.044, ß = -0.033). Specifically, the cognitive domains represented verbal learning and memory (p = 0.0091, ß = -0.044) and verbal working memory (p = 0.0062, ß = -0.036). Moreover, expression data from the GTEx database demonstrated that rs165940 significantly correlates with the mRNA expression levels of PDE4D in the cerebellum (p-value = 0.04; m-value = 0.9), demonstrating a potential functional consequence for this variant. Thus, rs165940 represents the most likely functional variant for major mental illness at the PDE4D locus in the Finnish population, increasing risk broadly to psychotic disorders.

Employment among people with schizophrenia or bipolar disorder: A population-based study using nationwide registers.

OBJECTIVE: To assess the employment rate and the related background factors among people with schizophrenia or bipolar disorder. METHODS: We identified all people in Sweden aged 18-64 years diagnosed with schizophrenia or bipolar disorder in nationwide registers in the years 2006-2013. The identified individuals were grouped by main activity or source of income. The association between background factors and employment was analyzed with generalized estimating equations (GEE). RESULTS: Three years before the first psychosis or bipolar disorder diagnosis, 24% of the individuals with schizophrenia and 45% of the individuals with bipolar disorder were employed. However, the employment rate dropped around the time of the first diagnosis. Five years later, 10% of the individuals with schizophrenia and 34% of the individuals with bipolar disorder were employed. The most important factors associated with employment after diagnosis were a high level of education, older age at the first registered diagnosis, no substance use disorder, and a low number of previous hospitalizations. Marriage or cohabiting, higher level of education, and higher age at the first diagnosis were associated with an increased employment rate especially among people with schizophrenia, and substance use was associated with a lower employment rate, especially among people with bipolar disorder. Men with bipolar disorder had a higher employment rate than women. CONCLUSION: The employment rate is low among people with schizophrenia and higher among people with bipolar disorder. The association of background characteristics with employment was mostly in the same direction both in schizophrenia and in bipolar disorder.