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.

Polymorphisms in ERBB4 and TACR1 associated with dry mouth in clozapine-treated patients.

BACKGROUND: Sialorrhea is a common and uncomfortable adverse effect of clozapine, and its severity varies between patients. The aim of the study was to select broadly genes related to the regulation of salivation and study associations between sialorrhea and dry mouth and polymorphisms in the selected genes. METHODS: The study population consists of 237 clozapine-treated patients, of which 172 were genotyped. Associations between sialorrhea and dry mouth with age, sex, BMI, smoking, clozapine dose, clozapine and norclozapine serum levels, and other comedication were studied. Genetic associations were analyzed with linear and logistic regression models explaining sialorrhea and dry mouth with each SNP added separately to the model as coefficients. RESULTS: Clozapine dose, clozapine or norclozapine concentration and their ratio were not associated with sialorrhea or dryness of mouth. Valproate use (p = 0.013) and use of other antipsychotics (p = 0.015) combined with clozapine were associated with excessive salivation. No associations were found between studied polymorphisms and sialorrhea. In analyses explaining dry mouth with logistic regression with age and sex as coefficients, two proxy-SNPs were associated with dry mouth: epidermal growth factor receptor 4 (ERBB4) rs3942465 (adjusted p = 0.025) and tachykinin receptor 1 (TACR1) rs58933792 (adjusted p = 0.029). CONCLUSION: Use of valproate or antipsychotic polypharmacy may increase the risk of sialorrhea. Genetic variations in ERBB4 and TACR1 might contribute to experienced dryness of mouth among patients treated with clozapine.

A retrospective analysis of iv ketamine outcome on hospitalisations in an unselected psychiatric sample.

OBJECTIVE: This study aims to explore the outcome with iv ketamine treatment in a real-world clinical setting, primarily measured as posttreatment days hospitalised. METHODS: The psychiatric medical records of 46 patients having received iv ketamine on a psychiatric treatment indication between 2015 and 2018 were retrospectively examined. Analysis comparing the number and duration of hospital admissions before and after ketamine treatment as well as logistic regression analysis to investigate clinical predictors of effectiveness, were performed. To assess patients' severity of depressed symptoms records were screened for MADRS-S scores. RESULTS: No significant difference between pre- and posttreatment hospital days (p = 0.170), or number of hospitalisations (p = 0.740) were found. The response rate was 31% and remission rate 21%. None of the predictors showed statistical significance in the logistic model. CONCLUSION: Iv ketamine treatment showed effectiveness in reducing depressive symptoms even with complex patients in a real-world clinical setting. However, this did not translate to a reduction in hospitalisation. Highlighting the multifaceted challenges posed when implementing iv ketamine treatment in clinical practice.

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.

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.

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.

Genetic risk scores associated with temperament clusters in Finnish depression patients.

OBJECTIVE: Cloninger's temperament dimensions have been studied widely in relation to genetics. In this study, we examined Cloninger's temperament dimensions grouped with cluster analyses and their association with single nucleotide polymorphisms (SNPs). This study included 212 genotyped Finnish patients from the Ostrobothnia Depression Study. METHODS: The temperament clusters were analysed at baseline and at six weeks from the beginning of the depression intervention study. We selected depression-related catecholamine and serotonin genes based on a literature search, and 59 SNPs from ten different genes were analysed. The associations of single SNPs with temperament clusters were studied. Using the selected genes, genetic risk score (GRS) analyses were conducted considering appropriate confounding factors. RESULTS: No single SNP had a significant association with the temperament clusters. Associations between GRSs and temperament clusters were observed in multivariate models that were significant after permutation analyses. Two SNPs from the DRD3 gene, two SNPs from the SLC6A2 gene, one SNP from the SLC6A4 gene, and one SNP from the HTR2A gene associated with the HHA/LRD/LP (high harm avoidance, low reward dependence, low persistence) cluster at baseline. Two SNPs from the HTR2A gene were associated with the HHA/LRD/LP cluster at six weeks. Two SNPs from the HTR2A gene and two SNPs from the COMT gene were associated with the HP (high persistence) cluster at six weeks. CONCLUSION: GRSs seem to associate with an individual's temperament profile, which can be observed in the clusters used. Further research needs to be conducted on these types of clusters and their clinical applicability.

Predictors of short-term response and the role of heavy alcohol use in treatment of depression.

BACKGROUND: Depression and alcohol use disorders frequently co-occur. However, research on psychosocial interventions for treating this dual pathology is limited. The Ostrobothnian Depression Study (ODS) aimed to increase the systematic use of evidence-based methods, particularly among patients with comorbid depression and substance use in a naturalistic setting. This is a secondary analysis of the ODS study. The aim of the present study was to explore the predictors of a response to treatment during the first six months of the ODS intervention with a specific focus on the role of comorbid heavy alcohol use. METHODS: The study sample (n = 242) comprised psychiatric specialist care patients with depression (Beck Depression Inventory score ≥ 17) at baseline. Patients with a baseline Alcohol Use Disorders Identification Test (AUDIT) score > 10 (n = 99) were assigned to the AUD (Alcohol Use Disorder) group in this study. The ODS intervention comprised behavioral activation (BA) for all and additional motivational interviewing (MI) for those in AUD group. The predictors of response to treatment (minimum of 50% reduction in depressive symptoms) during the first six months were analyzed with logistic regression models. RESULTS: In the total sample at six months (n = 150), predictors of response to treatment were more severe depression (OR 1.10, CI 1.02-1.18), larger amounts of alcohol consumed (OR = 1.16, CI 1.03-1.31) and antipsychotic medication "not in use" (OR = 0.17, CI 0.07-0.44). In the non-AUD group (n = 100), more severe depression (OR 1.12, CI 1.01-1.25) and antipsychotics "not in use" (OR 0.20, CI 0.06-0.67) also predicted a positive response. Among AUD group patients (n = 50), larger amounts of alcohol consumed (OR 1.54, CI 1.04-2.27) and antipsychotic medication "not in use" (OR 0.12, CI 0.02-0.60) predicted a response to the treatment intervention. CONCLUSIONS: The severity of symptoms and comorbid disorders were found to predict better treatment response, suggesting that the intervention was more effective in patients with severe symptoms. Patients with depression should be treated effectively regardless of having concomitant AUD. The results of this study suggest that BA combined with MI should be one of the treatment options for this dual pathology. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02520271 (11/08/2015).

Machine Learning Classification of Psychiatric Data Associated with Compensation Claims for Patient Injuries.

BACKGROUND: Adverse events are common in health care. In psychiatric treatment, compensation claims for patient injuries appear to be less common than in other medical specialties. The most common types of patient injury claims in psychiatry include diagnostic flaws, unprevented suicide, or coercive treatment deemed as unnecessary or harmful. OBJECTIVES: The objective was to study whether it is possible to form different categories of patient injury types associated with the psychiatric evaluations of compensation claims and to base machine learning classification on these categories. Further, the binary classification of positive and negative decisions for compensation claims was the other objective. METHODS: Finnish psychiatric specialist evaluations for the compensation claims of patient injuries were classified into six different categories called classes applying the machine learning methods of artificial intelligence. In addition, another classification of the same data into two classes was performed to test whether it was possible to classify data cases according to their known decisions, either accepted or declined compensation claim. RESULTS: The former classification task produced relatively good classification results subject to separating between different classes. Instead, the latter was more complex. However, classification accuracies of both tasks could be improved by using the generation of artificial data cases in the preprocessing phase before classifications. This preprocessing improved the classification accuracy of six classes up to 88% when the method of random forests was used for classification and that of the binary classification to 89%. CONCLUSION: The results show that the objectives defined were possible to solve reasonably.

Socioeconomic status, psychotherapy duration, and return to work from disability due to common mental disorders.

OBJECTIVE: Low socioeconomic status (SES) is a risk factor for work disability due to common mental disorders (CMDs), one possible reason being inequal use of services. Psychotherapy is an evidence-based treatment for CMDs. This study examines socioeconomic and sociodemographic differences in psychotherapy attendance and an association of psychotherapy duration with return to work (RTW). METHODS: The study subjects (N = 12,263) were all Finnish citizens granted a disability pension (DP) due to CMDs in 2010-2012. Numbers of psychotherapy sessions (maximum 200) were collected from the nine-year interval around the DP grant. Socioeconomic and sociodemographic differences in psychotherapy duration (dependent variable) among DP recipients were studied using multinomial logistic regression models, likewise, the association between psychotherapy duration and RTW (dependent variable) among temporary DP recipients was examined. RESULTS: Higher SES, female gender, and younger age were positively associated with attending longer psychotherapies and surpassing the early treatment termination level (>10 sessions). Attending 11-60 psychotherapy sessions was positively associated with full RTW and partial RTW, whereas longer psychotherapies were not. Early termination was positively associated with partial RTW only. CONCLUSION: This study demonstrates varying tendencies among CMD patients from different backgrounds to attend long rehabilitative psychotherapies, which may create inequalities in RTW.

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.

Socioeconomic factors and use of psychotherapy in common mental disorders predisposing to disability pension.

BACKGROUND: Research in high-income countries has identified low socioeconomic status as a risk factor for disability pension (DP) due to common mental disorders (CMDs). Psychotherapy is an evidence-based treatment for the majority of CMDs along with medication and it is often targeted to prevent work disability. This study examines socioeconomic differences in the use of rehabilitative psychotherapy in Finland, where citizens have universal health coverage, but psychotherapy is partly dependent on personal finance. METHODS: The study subjects (N = 22,501) were all the Finnish citizens granted a DP due to CMD between 2010 and 2015 and a comparison group (N = 57,732) matched based on age, gender, and hospital district. Socioeconomic differences in psychotherapy use were studied using logistic regression models. Socioeconomic status was defined by education, income, and occupation. Age, gender, and family status were also examined. RESULTS: A lower level of education, lower occupational status (blue-collar worker), male gender, and older age, were associated with less frequent psychotherapy use, in both groups. Education was the strongest component of socioeconomic status associated with psychotherapy use, but the role of income was not straightforward. Unemployment when approaching DP, but not otherwise, was a risk factor for not receiving rehabilitative psychotherapy. Socioeconomic disparities were not any smaller among CMD patients approaching DP than in the comparison group. CONCLUSION: This study demonstrates the disparity in the provision of psychotherapy for CMD patients, even on the verge of DP with an acute need for services. This disparity is partly related to a complex interplay of socioeconomic factors and the service system characteristics. Factors predisposing to unequal access to mental health services are presumably diverse and should be studied further.

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.

The role of alcohol use and adiposity in serum levels of IL-1RA in depressed patients.

BACKGROUND: The role of Interleukin-1 Receptor antagonist (IL-1Ra), an innate antagonist to pro-inflammatory cytokine IL-1, has attracted increasing attention due to its potential pathogenic and therapeutic implications in depression. However, the role of alcohol and adiposity in modulating IL-1Ra cytokine pathway in depressed patients has remainned unknown. The aim of this study was to follow the changes in IL-1Ra serum levels in depressed patients with or without simultaneous alcohol use disorder (AUD) and different degrees of adiposity during 6 months of follow-up. MATERIALS AND METHODS: A total of 242 patients with depression were followed for 6 months. At baseline 99 patients had simultaneous AUD. Levels of serum IL-1Ra and common mediators of inflammation (IL-6, hs-CRP) were measured. Clinical assessments included Body Mass Index (BMI), Montgomery-Asberg Depression Rating Scale (MADRS) and Alcohol Use Disorders Identification Test (AUDIT) scores. RESULTS: Significant reductions in clinical symptoms and IL-1Ra were observed during 6-month follow-up. In hierarchical linear regression analysis, the effect of MADRS score, age, gender, and smoking had a combined effect of 2.4% in the model. The effect of AUDIT score increased the effect to 4.2% of variance (p = 0.08), whereas adding BMI increased the effect to 18.5% (p <  0.001). CONCLUSION: Adiposity may influence the IL-1Ra anti-inflammatory response in depressed patients, whereas the effect of alcohol consumption in these patients seems insignificant. These findings should be considered in studies on the role of IL-1Ra in depression. TRIAL REGISTRATION: Ostrobothnia Depression Study in ClinicalTrials.gov , Identifier NCT02520271 .

Implementation of CYP2D6 copy-number imputation panel and frequency of key pharmacogenetic variants in Finnish individuals with a psychotic disorder.

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.

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.

Glucagon-like peptide-1 serum levels are associated with weight gain in patients treated with clozapine.

Metabolic syndrome and related cardiovascular risk factors are well-known comorbidities among patients with schizophrenia. Biomarkers of these antipsychotic-associated metabolic adverse effects and antipsychotic-induced weight gain are needed. Glucagon-like peptide-1 (GLP-1) is involved in insulin secretion, regulation of satiety, inhibition of food intake, and inhibition of gastric emptying. GLP-1 also induces reduction in body weight. Visfatin/ NAMPT/ PBEF is an adipocytokine secreted by several cells and tissues. Increased plasma visfatin levels have been associated with overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases, low grade inflammation, and proinflammatory markers. Associations between antipsychotic-induced weight gain and serum visfatin and GLP-1 levels have been little studied in patients with schizophrenia. The aim of the present study was to test the possible role of serum GLP-1 and visfatin level alterations as markers of weight gain in association with metabolic and inflammatory markers in 190 patients (109 male, 81 female) with schizophrenia on clozapine treatment. High serum levels of GLP-1 correlated significantly with higher levels of visfatin, leptin, insulin, HOMA-IR, higher BMI, and weight change among men. Associations between serum visfatin levels and BMI or weight change were not found in the present patients. Serum GLP-1 level seems to be a marker of metabolic risk factors among men with schizophrenia on clozapine treatment. Female patients may be more sensitive to suppressive effects of clozapine on GLP-1 secretion. Patients on clozapine would benefit from GLP-1 agonists as preventive treatment.