Long-term antipsychotic use and its association with outcomes in schizophrenia - the Northern Finland Birth Cohort 1966

Peer reviewe

Predictors of long-term change in adult cognitive performance: systematic review and data from the Northern Finland Birth Cohort 1966

Objective: Several social life events and challenges have an impact on cognitive development. Our goal was to analyze the predictors of change in cognitive performance in early midlife in a general population sample. Additionally, systematic literature review was performed. Method: The study sample was drawn from the Northern Finland Birth Cohort 1966 at the ages of 34 and 43 years. Primary school performance, sociodemographic factors and body mass index (BMI) were used to predict change in cognitive performance measured by the California Verbal Learning Test, Visual Object Learning Test, and Abstraction Inhibition and Working Memory task. Analyses were weighted by gender and education, and p-values were corrected for multiple comparisons using Benjamini–Hochberg procedure (B–H). Results: Male gender predicted decrease in episodic memory. Poor school marks of practical subjects, having no children, and increase in BMI were associated with decrease in episodic memory, though non-significantly after B–H. Better school marks, and higher occupational class were associated with preserved performance in visual object learning. Higher vocational education predicted preserved performance in visual object learning test, though non-significantly after B-H. Likewise, having children predicted decreased performance in executive functioning but non-significantly after B-H. Conclusions: Adolescent cognitive ability, change in BMI and several sociodemographic factors appear to predict cognitive changes in early midlife. The key advantage of present study is the exploration of possible predictors of change in cognitive performance among general population in the early midlife, a developmental period that has been earlier overlooked

Defective WNT signaling may protect from articular cartilage deterioration - a quantitative MRI study on subjects with a heterozygous WNT1 mutation

Objective: WNT signaling is of key importance in chondrogenesis and defective WNT signaling may contribute to the pathogenesis of osteoarthritis and other cartilage diseases. Biochemical composition of articular cartilage in patients with aberrant WNT signaling has not been studied. Our objective was to assess the knee articular cartilage in WNT1 mutation-positive individuals using a 3.0T MRI unit to measure cartilage thickness, relaxation times, and texture features. Design: Cohort comprised mutation-positive (N = 13; age 17-76 years) and mutation-negative (N = 13; 16-77 years) subjects from two Finnish families with autosomal dominant WNT1 osteoporosis due to a heterozygous missense mutation c.652T>G (p.C218G) in WNT1. All subjects were imaged with a 3.0T MRI unit and assessed for cartilage thickness, T2 and T1 rho relaxation times, and T2 texture features contrast, dissimilarity and homogeneity of T2 relaxation time maps in six regions of interest (ROIs) in the tibiofemoral cartilage. Results: All three texture features showed opposing trends with age between the groups in the medial tibiofemoral cartilage (P = 0.020-0.085 for the difference of the regression coefficients), the mutation-positive individuals showing signs of cartilage preservation. No significant differences were observed in the lateral tibiofemoral cartilage. Cartilage thickness and means of T2 relaxation time did not differ between groups. Means of T1r relaxation time were significantly different in one ROI but the regression analysis displayed no differences. Conclusions: Our results show less age-related cartilage deterioration in the WNT1 mutation-positive than the mutation-negative subjects. This suggests, that the WNT1 mutation may alter cartilage turnover and even have a potential cartilage-preserving effect. (C) 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.Peer reviewe

3D morphometric analysis of calcified cartilage properties using micro-computed tomography

Objective: Our aim is to establish methods for quantifying morphometric properties of calcified cartilage (CC) from micro-computed tomography (mu CT). Furthermore, we evaluated the feasibility of these methods in investigating relationships between osteoarthritis (OA), tidemark surface morphology and open subchondral channels (OSCCs). Method: Samples (n = 15) used in this study were harvested from human lateral tibial plateau (n = 8). Conventional roughness and parameters assessing local 3-dimensional (3D) surface variations were used to quantify the surface morphology of the CC. Subchondral channel properties (percentage, density, size) were also calculated. As a reference, histological sections were evaluated using Histopathological osteoarthritis grading (OARSI) and thickness of CC and subchondral bone (SCB) was quantified. Results: OARSI grade correlated with a decrease in local 3D variations of the tidemark surface (amount of different surface patterns (r(s) = -0.600, P = 0.018), entropy of patterns (EP) (r(s) = -0.648, P = 0.018), homogeneity index (HI) (r(s) = 0.555, P = 0.032)) and tidemark roughness (TMR) (r(s) = -0.579, P = 0.024). Amount of different patterns (ADP) and EP associated with channel area fraction (CAF) (r(p) = 0.876, P <0.0001; r(p) = 0.665, P = 0.007, respectively) and channel density (CD) (r(p) = 0.680, P = 0.011; r(p) = 0.582, P = 0.023, respectively). TMR was associated with CAF (r(p) = 0.926, P <0.0001) and average channel size (r(p) = 0.574, P = 0.025). CC topography differed statistically significantly in early OA vs healthy samples. Conclusion: We introduced a mu-CT image method to quantify 3D CC topography and perforations through CC. CC topography was associated with OARSI grade and OSCC properties; this suggests that the established methods can detect topographical changes in tidemark and CC perforations associated with OA. (c) 2018 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Lifetime antipsychotic medication and cognitive performance in schizophrenia at age 43 years in a general population birth cohort

This naturalistic study analysed the association between cumulative lifetime antipsychotic dose and cognition in schizophrenia after an average of 16.5 years of illness. Sixty participants with schizophrenia and 191 controls from the Northern Finland Birth Cohort 1966 were assessed at age 43 years with a neurocognitive test battery. Cumulative lifetime antipsychotic dose-years were collected from medical records and interviews. The association between antipsychotic dose-years and a cognitive composite score based on principal component analysis was analysed using linear regression. Higher lifetime antipsychotic dose-years were significantly associated with poorer cognitive composite score, when adjusted for gender, onset age and lifetime hospital treatment days. The effects of typical and atypical antipsychotics did not differ. This is the first report of an association between cumulative lifetime antipsychotic dose and global cognition in midlife schizophrenia. Based on these data, higher lifetime antipsychotic dose-years may be associated with poorer cognitive performance at age 43 years. Potential biases related to the naturalistic design may partly explain the results; nonetheless, it is possible that large antipsychotic doses harm cognition in schizophrenia in the long-term.Peer reviewe

3D morphometric analysis of calcified cartilage properties using micro-computed tomography

OBJECTIVE: Our aim is to establish methods for quantifying morphometric properties of calcified cartilage (CC) from micro-computed tomography (muCT). Furthermore, we evaluated the feasibility of these methods in investigating relationships between osteoarthritis (OA), tidemark surface morphology and open subchondral channels (OSCCs). METHOD: Samples (n = 15) used in this study were harvested from human lateral tibial plateau (n = 8). Conventional roughness and parameters assessing local 3-dimensional (3D) surface variations were used to quantify the surface morphology of the CC. Subchondral channel properties (percentage, density, size) were also calculated. As a reference, histological sections were evaluated using Histopathological osteoarthritis grading (OARSI) and thickness of CC and subchondral bone (SCB) was quantified. RESULTS: OARSI grade correlated with a decrease in local 3D variations of the tidemark surface (amount of different surface patterns (rs = -0.600, P = 0.018), entropy of patterns (EP) (rs = -0.648, P = 0.018), homogeneity index (HI) (rs = 0.555, P = 0.032)) and tidemark roughness (TMR) (rs = -0.579, P = 0.024). Amount of different patterns (ADP) and EP associated with channel area fraction (CAF) (rp = 0.876, P < 0.0001; rp = 0.665, P = 0.007, respectively) and channel density (CD) (rp = 0.680, P = 0.011; rp = 0.582, P = 0.023, respectively). TMR was associated with CAF (rp = 0.926, P < 0.0001) and average channel size (rp = 0.574, P = 0.025). CC topography differed statistically significantly in early OA vs healthy samples. CONCLUSION: We introduced a mu-CT image method to quantify 3D CC topography and perforations through CC. CC topography was associated with OARSI grade and OSCC properties; this suggests that the established methods can detect topographical changes in tidemark and CC perforations associated with OA

Non-response and information bias in population-based psychiatric research:the Northern Finland 1966 Birth Cohort study

Abstract Study samples in medical research are selected according to the objectives of the studies. Researchers seek to collect data as extensively and reliably as possible. In practice, however, data are often missing or may be incorrect. This thesis covers some of the problems concerning missing data and data collection in psychiatric research. Methods for adjusting for missing data and for evaluating the reliability of data are presented. The data originate from the Northern Finland 1966 Birth Cohort (N = 12058). This study explored how participation in an epidemiologic study that includes questionnaires and a clinical examination is affected by mental health (N = 11540), and whether non-participants experience more severe clinical symptoms than participants in a psychiatric field study (N = 145) among subjects with a psychosis. Inverse probability weighting (IPW) was used to adjust for non-participation in comparisons of brain volumes between schizophrenia and control groups. The precision of self-reported medication use was also explored (N = 7625). In an epidemiologic study of all cohort members, subjects with a psychiatric disorder participated less actively than those without one. In the psychiatric field study, non participants were more often patients with schizophrenia than other psychoses. The psychiatric symptoms of non-participants were more severe and they needed more hospital care than participants. The use of IPW led to higher estimates of cerebrospinal fluid volume and lower estimates of grey and white matter volumes in schizophrenia patients, and increased the statistical significance of the differences in brain volume estimates between the schizophrenia and control groups. The precision of self-reported data on psychoactive medication use was substantial. Due to non-participation, the true prevalence of psychiatric disorders is probably higher than the prevalence estimates from field studies that are based on data provided by participants only. In order to reflect the true differences in the target population, weighting methods can be used to improve estimates affected by non-participation. Regarding psychoactive medication use, data collected by postal questionnaire can be assumed accurate enough for study purposes. However, it may underestimate the prevalence of medication use due to non-participation.Abstract Tutkimusaineisto valitaan tutkimuksen tavoitteiden perusteella. Tavoitteena on kerätä kattava ja virheetön aineisto. Käytännössä kuitenkin osa tiedoista voi puuttua tai olla virheellistä. Tässä väitöskirjassa esitellään yleisesti menetelmiä huomioida puuttuva tieto analyyseissä ja arvioida aineistojen luotettavuutta psykiatrisessa tutkimuksessa. Aineisto perustuu Pohjois-Suomen vuoden 1966 syntymäkohorttiin (N = 12058). Väitöskirjassa tutkittiin, miten psykiatrinen sairastavuus vaikuttaa osallistumiseen epidemiologisessa tutkimuksessa, joka sisälsi kyselyitä ja terveystutkimuksen (N = 11540), sekä erosiko psykiatriseen kenttätutkimukseen osallistuneiden ja osallistumattomien psykoosipotilaiden kliininen taudinkuva toisistaan (N = 145). Käänteisen todennäköisyyden painotusmenetelmää käytettiin korjaamaan puuttuvan tiedon aiheuttamaa virhettä aivovolyymien estimaateissa skitsofreniapotilailla. Lisäksi arvioitiin itse ilmoitetun lääkekäyttötiedon luotettavuutta (N = 7625). Epidemiologisessa tutkimuksessa ne kohortin jäsenet, joilla oli jokin psykiatrinen sairaus, osallistuivat passiivisemmin kuin ne, joilla ei ollut psykiatrista sairautta. Psykoosipotilaat, jotka eivät osallistuneet psykiatriseen kenttätutkimukseen, sairastivat tutkimukseen osallistuneita useammin skitsofreniaa kuin muita psykooseja ja heidän taudinkuvansa oli vakavampi. Painottaminen kasvatti aivonesteen ja alensi harmaan ja valkean aineen tilavuuksien estimaatteja skitsofreniapotilailla, ja lisäsi aivovolyymien erojen tilastollista merkitsevyyttä skitsofreniapotilaiden ja vertailuhenkilöiden välillä. Itse ilmoitetun psykoaktiivisten lääkkeiden käyttötiedon luotettavuus oli merkittävä. Kadosta johtuen psykiatristen sairauksien todellinen vallitsevuus on todennäköisesti korkeampi kuin vallitsevuuden estimaatit, jotka on laskettu tutkimukseen osallistuneiden tiedoista. Painotusmenetelmiä voidaan käyttää parantamaan puuttuvan tiedon vääristämiä estimaatteja, koska painottamalla huomioidaan todellisia eroja kohdeväestössä. Tutkittaessa lääkekäyttötietoa postikyselyillä kerätyn aineiston voidaan olettaa olevan laadultaan riittävä tutkimustarpeisiin