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.

Visual memory and alcohol use in a middle-aged birth cohort.

Light and moderate alcohol use has been reported to be associated with both impaired and enhanced cognition. The purpose of this study was to explore whether there was a linear relationship between visual memory and alcohol consumption in males and females in a large middle-aged birth cohort population in cross-sectional and longitudinal settings. Data were collected from 5585 participants completing 31-year (1997-1998) and 46-year (2012-2014) follow-ups including Paired Associate Learning (PAL) test at 46-years follow-up. The participants were originally from 12,231 study population of the Northern Finland Birth Cohort 1966 (NFBC1966). The PAL test was conducted to assess visual memory. Reported alcohol use was measured as total daily use of alcohol, beer, wine, and spirits converted into grams and as frequency and amount of use of beer, wine, and spirits. The total daily alcohol use was not associated with reduced visual memory. The frequency of use of beer and wine in males was associated with better visual memory in cross-sectional and longitudinal settings. Using six or more servings of spirits was associated with worse visual memory in males in cross-sectional and longitudinal settings. Using six or more servings of spirits was associated with worse visual memory in males in cross-sectional and longitudinal setting. The study suggested a lack of a linear association between drinking and visual memory in the middle-aged population.

The bidirectional relationships of optimism and pessimism with depressive symptoms in adulthood - A 15-year follow-up study from Northern Finland Birth Cohorts.

BACKGROUND: Low optimism and high pessimism have predicted depressive symptoms in several studies, but the associations in the other direction, from depressive symptoms to future optimism and pessimism, have been unexplored. We examined bidirectional associations of optimism and pessimism with depressive symptoms in adulthood. METHODS: A population-based sample of 4011 Finnish adults (55 % women) was analyzed with a 15-year prospective follow-up period from age 31 to age 46. Optimism and pessimism were measured with the Life Orientation Test-Revised, and depressive symptoms were measured with the Symptom Checklist-25. Temporal associations were investigated with cross-lagged panel models. RESULTS: According to the model fit indices (RMSEA < 0.04, CFI ≥ 0.97) optimism and pessimism had bidirectional relationships with depressive symptoms: optimism predicted lower depressive symptoms (ß = -0.09, p < .001), and depressive symptoms predicted lower optimism (ß = -0.10, p < .001) in the follow-up. Also, pessimism predicted higher depressive symptoms (ß = 0.08, p < .001), and depressive symptoms predicted higher pessimism (ß = 0.09, p < .001) in the follow-up. In the participants with clinically high depressive symptoms at age 31, the predictive associations from optimism and pessimism to depressive symptoms remained, but associations in the other direction were attenuated. LIMITATIONS: The follow-up study included only two time points with a 15-year time gap, which does not consider the possible fluctuation in the study variables between the measured times. CONCLUSION: Dispositional optimism and pessimism may have bidirectional relationships with depressive symptoms in adulthood when the baseline depressive symptoms are below the clinical level.

The relative brain signal variability increases in the behavioral variant of frontotemporal dementia and Alzheimer's disease but not in schizophrenia.

Overlapping symptoms between Alzheimer's disease (AD), behavioral variant of frontotemporal dementia (bvFTD), and schizophrenia (SZ) can lead to misdiagnosis and delays in appropriate treatment, especially in cases of early-onset dementia. To determine the potential of brain signal variability as a diagnostic tool, we assessed the coefficient of variation of the BOLD signal (CVBOLD) in 234 participants spanning bvFTD (n = 53), AD (n = 17), SZ (n = 23), and controls (n = 141). All underwent functional and structural MRI scans. Data unveiled a notable increase in CVBOLD in bvFTD patients across both datasets (local and international, p < 0.05), revealing an association with clinical scores (CDR and MMSE, r = 0.46 and r = -0.48, p < 0.0001). While SZ and control group demonstrated no significant differences, a comparative analysis between AD and bvFTD patients spotlighted elevated CVBOLD in the frontopolar cortices for the latter (p < 0.05). Furthermore, CVBOLD not only presented excellent diagnostic accuracy for bvFTD (AUC 0.78-0.95) but also showcased longitudinal repeatability. During a one-year follow-up, the CVBOLD levels increased by an average of 35% in the bvFTD group, compared to a 2% increase in the control group (p < 0.05). Our findings suggest that CVBOLD holds promise as a biomarker for bvFTD, offering potential for monitoring disease progression and differentiating bvFTD from AD and SZ.

Substance Use and Sleep Problems in Patients With Psychotic Disorders.

Background: Substance use and sleep problems are common in patients with psychotic disorders, but their associations in these patients have not been evaluated. We aimed to investigate associations between substance use and sleep problems in a large nationwide cohort of patients with a psychotic disorder. Study Design: This study is part of the Finnish SUPER study, which belongs to the Stanley Global Neuropsychiatric Genomics Initiative. In this cross-sectional, multicenter study, participants (N = 8616) were recruited from primary and specialized healthcare. Patients with schizophrenia, schizoaffective disorder, bipolar disorder, and psychotic depression were included. Information on current alcohol (Alcohol Use Disorders Identification Test-Concise) and cigarette use as well as on lifetime illicit drug use, including cannabis, benzodiazepines, amphetamines, and opioids, was collected using questionnaires. The sleep outcomes in our logistic regression analysis were short (≤6 h) and long sleep (≥10 h) duration, difficulties initiating asleep, early morning awakenings, fatigue, and poor sleep quality (SQ). Results: Self-reported substance use was associated with a higher prevalence of sleep problems. After adjustments with age, gender, diagnostic group, and living status, hazardous alcohol use (eg, poor SQ odds ratio [OR] = 1.80, 95% CI: 1.49 to 2.16, P < .001), current smoking (short sleep duration OR = 1.28, 95% CI: 1.08 to 1.52, P = .005), and lifetime benzodiazepine misuse (difficulties initiating sleep OR = 2.00, 95% CI: 1.55 to 2.48, P < .001) were associated with sleep problems. Conclusions: Substance use was associated with sleep problems. Our findings underline the potential benefits of screening substance use when treating sleep problems in patients with psychotic disorders.

Sleep in Psychotic Disorders: Results From Nationwide SUPER Finland Study.

Objective: Characterizing sleep in patients with schizophrenia, schizoaffective disorder, bipolar disorder, and psychotic depression. Methods: This cross-sectional questionnaire study is based on the SUPER study sample, which is part of the Stanley Global Neuropsychiatric Genomics Initiative. The study is a multicentre, nationwide Finnish study consisting of patients (N = 8 623) both in primary and specialized health care. The main measurements were sleep duration, difficulties initiating sleep, early morning awakenings, and fatigue. These results were compared with a nationally representative sample of the Finnish population from the Health 2000 survey (N = 7 167) with frequency and logistic regression analyses. Results: Patients had more sleep problems compared with the general population, especially young and middle-aged patients (Difficulties initiating sleep in young patients odds ratio = 12.3, 95% CI 9.8-15.4). Long sleep duration was the most deviating property of the sleep characteristics, being particularly common among young patients with schizophrenia (odds ratio = 27.9, 95% CI 22.1-35.2, 47.4% vs 3.3% prevalence). All sleep problems were associated with worse subjective health. We also conducted a latent class analysis, resulting in a cluster relatively free of sleep problems (58% of patients), an insomnia symptom cluster (26%), and a hypersomnia symptom cluster (15%). Conclusions: In our sample, patients with psychotic disorders have more sleep problems-especially long sleep duration but also insomnia symptoms-compared with the general population. The patients can in a latent class analysis of their sleep symptoms be divided into groups with differing sleep profiles.