Browsing by Subject "SCHIZOPHRENIA"

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  • Rikandi, Eva; Mantyla, Teemu; Lindgren, Maija; Kieseppa, Tuula; Suvisaari, Jaana; Raij, Tuukka T. (2018)
    Background: Functional connectivity is altered in psychotic disorders. Multiple findings concentrate on the default mode network, anchored on the precuneus-posterior cingulate cortex (PC-PCC). However, the nature of the alterations varies between studies and connectivity alterations have not been studied during an ecologically valid natural stimulus. In the present study, we investigated the functional and structural connectivity of a PC-PCC region, where functioning differentiated first-episode psychosis patients from control subjects during free viewing of a movie in our earlier study. Methods: 14 first-episode psychosis patients and 12 control subjects were imaged with GE 3T, and 29 patients and 19 control subjects were imaged with a Siemens Skyra 3T scanner while watching scenes from the movie Alice in Wonderland. Group differences in functional connectivity were analysed for both scanners separately and results were compared to identify any overlap. Diffusion tensor measures of 26 patients and 19 control subjects were compared for the related white matter tracts, identified by deterministic tractography. Results: Functional connectivity was increased in patients across scanners between the midline regions of the PC-PCC and the anterior cingulate cortex-medial prefrontal cortex (ACC-mPFC). We found no group differences in any of the diffusion tensor imaging measures. Conclusions: Already in the early stages of psychosis functional connectivity between the midline structures of the PC-PCC and the ACC-mPFC is consistently increased during naturalistic stimulus. (c) 2018 Elsevier B.V. All rights reserved.
  • Kurki, Mitja I.; Saarentaus, Elmo Christian; Pietiläinen, Olli; Gormley, Padraigh; Lal, Dennis; Kerminen, Sini; Torniainen-Holm, Minna; Hämäläinen, Eija; Rahikkala, Elisa; Keski-Filppula, Riikka; Rauhala, Merja; Korpi-Heikkila, Satu; Komulainen-Ebrahim, Jonna; Helander, Heli; Vieira, Päivi; Männikkö, Minna; Peltonen, Markku; Havulinna, Aki; Salomaa, Veikko; Pirinen, Matti; Suvisaari, Jaana; Moilanen, Jukka S.; Körkkö, Jarmo; Kuismin, Outi; Daly, Mark; Palotie, Aarno (2019)
    The contribution of de novo variants in severe intellectual disability (ID) has been extensively studied whereas the genetics of mild ID has been less characterized. To elucidate the genetics of milder ID we studied 442 ID patients enriched for mild ID (>50%) from a population isolate of Finland. Using exome sequencing, we show that rare damaging variants in known ID genes are observed significantly more often in severe (27%) than in mild ID (13%) patients. We further observe a significant enrichment of functional variants in genes not yet associated with ID (OR: 2.1). We show that a common variant polygenic risk significantly contributes to ID. The heritability explained by polygenic risk score is the highest for educational attainment (EDU) in mild ID (2.2%) but lower for more severe ID (0.6%). Finally, we identify a Finland enriched homozygote variant in the CRADD ID associated gene.
  • Boku, Shuken; Takeshi, Izumi; Abe, Seiji; Takahashi, Tomohisa; Nishi, Akira; Nomaru, Hiroko; Naka, Yasuhiko; Kang, Gina; Nagashima, Masako; Hishimoto, Akitoyo; Hishimoto, Akitoyo; Enomoto, Shingo; Duran Torres, Gilberto; Tanigaki, Kenji; Zhang, Jinghang; Ye, Kenny; Kato, Shigeki; Männistö, Pekka Topias; Kobayashi, Kazuto; Hiroi, Noboru (2018)
    Working memory capacity, a critical component of executive function, expands developmentally from childhood through adulthood. Anomalies in this developmental process are seen in individuals with autism spectrum disorder (ASD), schizophrenia and intellectual disabilities (ID), implicating this atypical process in the trajectory of developmental neuropsychiatric disorders. However, the cellular and neuronal substrates underlying this process are not understood. Duplication and triplication of copy number variants of 22q11.2 are consistently and robustly associated with cognitive deficits of ASD and ID in humans, and overexpression of small 22q11.2 segments recapitulates dimensional aspects of developmental neuropsychiatric disorders in mice. We capitalized on these two lines of evidence to delve into the cellular substrates for this atypical development of working memory. Using a region- and cell-type-selective gene expression approach, we demonstrated that copy number elevations of catechol-O-methyl-transferase (COMT) or Tbx1, two genes encoded in the two small 22q11.2 segments, in adult neural stem/progenitor cells in the hippocampus prevents the developmental maturation of working memory capacity in mice. Moreover, copy number elevations of COMT or Tbx1 reduced the proliferation of adult neural stem/progenitor cells in a cell-autonomous manner in vitro and migration of their progenies in the hippocampus granular layer in vivo. Our data provide evidence for the novel hypothesis that copy number elevations of these 22q11.2 genes alter the developmental trajectory of working memory capacity via suboptimal adult neurogenesis in the hippocampus.
  • Appenzeller, Silke; Balling, Rudi; Barisic, Nina; Baulac, Stephanie; Caglayan, Hande; Craiu, Dana; De Jonghe, Peter; Depienne, Christel; Dimova, Petia; Djemie, Tania; Gormley, Padhraig; Guerrini, Renzo; Helbig, Ingo; Hjalgrim, Helle; Hoffman-Zacharska, Dorota; Jaehn, Johanna; Klein, Karl Martin; Koeleman, Bobby; Komarek, Vladimir; Krause, Roland; Kuhlenbaeumer, Gregor; Leguern, Eric; Lehesjoki, Anna-Elina; Lemke, Johannes R.; Lerche, Holger; Linnankivi, Tarja; Marini, Carla; May, Patrick; Moller, Rikke S.; Muhle, Hiltrud; Pal, Deb; Palotie, Aarno; Pendziwiat, Manuela; Robbiano, Angela; Roelens, Filip; Rosenow, Felix; Selmer, Kaja; Serratosa, Jose M.; Sisodiya, Sanjay; Stephani, Ulrich; Sterbova, Katalin; Striano, Pasquale; Suls, Arvid; Talvik, Tiina; von Spiczak, Sarah; Weber, Yvonne; Weckhuysen, Sarah; Zara, Federico; Abou-Khalil, Bassel; Alldredge, Brian K.; EuroEPINOMICS-RES Consortium; Epilepsy Phenome Genome Project; Epi4K Consortium (2014)
  • Mikkonen, Kasperi; Wegelius, Asko; Salmijärvi, Laura; Paunio, Tiina; Kieseppä, Tuula (2020)
  • Tomppo, Liisa; Ekelund, Jesper; Lichtermann, Dirk; Veijola, Juha; Jaervelin, Marjo-Riitta; Hennah, William (2012)
  • Soininen, Paivi; Putkonen, Hanna; Joffe, Grigori; Korkeila, Jyrki; Puukka, Pauli; Pitkanen, Anneli; Valimaki, Maritta (2013)
  • Laurikainen, Heikki; Vuorela, Arja; Toivonen, Anna; Reinert-Hartwall, Linnea; Trontti, Kalevi; Lindgren, Maija; Keinanen, Jaakko; Mäntylä, Teemu; Paju, Janina; Ilonen, Tuula; Armio, Reetta-Liina; Walta, Maija; Tuisku, Jouni; Helin, Semi; Marjamäki, Päivi; Hovatta, Iiris; Therman, Sebastian; Vaarala, Outi; Linnaranta, Outi; Kieseppä, Tuula; Salokangas, Raimo K. R.; Honkanen, Jarno; Hietala, Jarmo; Suvisaari, Jaana (2020)
    Several lines of research support immune system dysregulation in psychotic disorders. However, it remains unclear whether the immunological marker alterations are stable and how they associate with brain glial cell function. This longitudinal study aimed at investigating whether peripheral immune functions are altered in the early phases of psychotic disorders, whether the changes are associated with core symptoms, remission, brain glial cell function, and whether they persist in a one-year follow-up. Two independent cohorts comprising in total of 129 first-episode psychosis (FEP) patients and 130 controls were assessed at baseline and at the one-year follow-up. Serum cyto-/chemokines were measured using a 38-plex Luminex assay. The FEP patients showed a marked increase in chemokine CCL22 levels both at baseline (p <0.0001; Cohen's d = 0.70) and at the 12-month follow-up (p = 0.0007) compared to controls. The group difference remained significant (p = 0.0019) after accounting for relevant covariates including BMI, smoking, and antipsychotic medication. Elevated serum CCL22 levels were significantly associated with hallucinations (rho = 0.20) and disorganization (rho = 0.23), and with worse verbal performance (rho = -0.23). Brain glial cell activity was indexed with positron emission tomography and the translocator protein radiotracer [C-11]PBR28 in subgroups of 15 healthy controls and 14 FEP patients with serum CCL22/CCL17 measurements. The distribution volume (V-T) of [C-11]PBR28 was lower in patients compared to controls (p = 0.026; Cohen's d = 0.94) without regionally specific effects, and was inversely associated with serum CCL22 and CCL17 levels (p = 0.036). Our results do not support the over-active microglia hypothesis of psychosis, but indicate altered CCR4 immune signaling in early psychosis with behavioral correlates possibly mediated through cross-talk between chemokine networks and dysfunctional or a decreased number of glial cells.
  • Hakulinen, Christian; Elovainio, Marko; Arffman, Martti; Lumme, Sonja; Suokas, Kimmo; Pirkola, Sami; Keskimäki, Ilmo; Manderbacka, Kristiina; Böckerman, Petri (2020)
    Objective: Individuals with severe mental disorders have an impaired ability to work and are likely to receive income transfer payments as their main source of income. However, the magnitude of this phenomenon remains unclear. Using longitudinal population cohort register data, the authors conducted a case-control study to examine the levels of employment and personal income before and after a first hospitalization for a serious mental disorder. Methods: All individuals (N=50,551) who had been hospitalized for schizophrenia, other nonaffective psychosis, or bipolar disorder in Finland between 1988 and 2015 were identified and matched with five randomly selected participants who were the same sex and who had the same birth year and month. Employment status and earnings, income transfer payments, and total income in euros were measured annually from 1988 to 2015. Results: Individuals with serious mental disorders had notably low levels of employment before, and especially after, the diagnosis of a severe mental disorder. Their total income was mostly constituted of transfer payments, and this was especially true for those diagnosed as having schizophrenia. More than half of all individuals with a serious mental disorder did not have any employment earnings after they received the diagnosis. Conclusions: The current study shows how most individuals in Finland depend solely on income transfer payments after an onset of a severe mental disorder.
  • Psychiat Genomics Consortium; Lönnqvist, Jouko; Paunio, Tiina (2018)
    Genetic correlation is a key population parameter that describes the shared genetic architecture of complex traits and diseases. It can be estimated by current state-of-art methods, i.e., linkage disequilibrium score regression (LDSC) and genomic restricted maximum likelihood (GREML). The massively reduced computing burden of LDSC compared to GREML makes it an attractive tool, although the accuracy (i.e., magnitude of standard errors) of LDSC estimates has not been thoroughly studied. In simulation, we show that the accuracy of GREML is generally higher than that of LDSC. When there is genetic heterogeneity between the actual sample and reference data from which LD scores are estimated, the accuracy of LDSC decreases further. In real data analyses estimating the genetic correlation between schizophrenia (SCZ) and body mass index, we show that GREML estimates based on similar to 150,000 individuals give a higher accuracy than LDSC estimates based on similar to 400,000 individuals (from combinedmeta-data). A GREML genomic partitioning analysis reveals that the genetic correlation between SCZ and height is significantly negative for regulatory regions, which whole genome or LDSC approach has less power to detect. We conclude that LDSC estimates should be carefully interpreted as there can be uncertainty about homogeneity among combined meta-datasets. We suggest that any interesting findings from massive LDSC analysis for a large number of complex traits should be followed up, where possible, with more detailed analyses with GREML methods, even if sample sizes are lesser.
  • Salmela, Elina; Renvall, Hanna; Kujala, Jan; Hakosalo, Osmo; Illman, Mia; Vihla, Minna; Leinonen, Eira; Salmelin, Riitta; Kere, Juha (2016)
    Several functional and morphological brain measures are partly under genetic control. The identification of direct links between neuroimaging signals and corresponding genetic factors can reveal cellular-level mechanisms behind the measured macroscopic signals and contribute to the use of imaging signals as probes of genetic function. To uncover possible genetic determinants of the most prominent brain signal oscillation, the parieto-occipital 10-Hz alpha rhythm, we measured spontaneous brain activity with magnetoencephalography in 210 healthy siblings while the subjects were resting, with eyes closed and open. The reactivity of the alpha rhythm was quantified from the difference spectra between the two conditions. We focused on three measures: peak frequency, peak amplitude and the width of the main spectral peak. In accordance with earlier electroencephalography studies, spectral peak amplitude was highly heritable (h(2)>0.75). Variance component-based analysis of 28000 single-nucleotide polymorphism markers revealed linkage for both the width and the amplitude of the spectral peak. The strongest linkage was detected for the width of the spectral peak over the left parieto-occipital cortex on chromosome 10 (LOD=2.814, nominal P
  • Vaissiere, James; Thorp, Jackson G.; Ong, Jue-Sheng; Ortega-Alonzo, Alfredo; Derks, Eske M. (2020)
    There is a well-established relationship between cannabis use and psychosis, although the exact nature of this relationship is not fully understood. Recent studies have observed significant genetic overlap between a diagnosis of schizophrenia and lifetime cannabis use. Expanding on this work, the current study aimed to examine whether genetic overlap also occurs for subclinical psychosis (schizotypy) and cannabis use, as well as examining the phenotypic association between the traits. Phenotypic correlations were calculated for a variety of schizotypy and cannabis phenotypes in the UK Biobank (UKB), and single nucleotide polymorphism (SNP)-based heritability estimates and genetic correlations were calculated for these UKB phenotypes as well as for several other variables taken from recent genomewide association studies. Positive phenotypic correlations were observed between 11 out of 12 pairs of the cannabis use and schizotypy phenotypes (correlation range .05-.18), indicating a robust association between increased symptoms of schizotypy and cannabis use. SNP-based heritability estimates for two schizotypy phenotypes remained significant after multiple testing correction:social anhedonia(h(SNP)(2)= .08,SE= .02,N= 4025) andever seen an unreal vision(h(SNP)(2)= .35,SE= .10,N= 150,717). Finally, one significant genetic correlation was observed between schizotypy and cannabis use, a negative correlation betweensocial anhedoniaandnumber of times used cannabis(r(g)= -.30,p= .012). The current study suggests the relationship between cannabis use and psychosis is also seen in subclinical symptoms of psychosis, but further research with larger samples is needed to determine the biological mechanisms underlying this association.
  • Lindgren, Maija; Holm, Minna; Markkula, Niina; Härkänen, Tommi; Dickerson, Faith; Yolken, Robert H.; Suvisaari, Jaana (2020)
    Common infectious agents, such as Toxoplasma gondii (T. gondii) and several human herpes viruses, have been linked to increased risk of self-harm. The aim of this study was to investigate the associations between self-harm and seropositivity to T. gondii, Epstein-Barr virus (EBV), Herpes Simplex virus Type 1 (HSV-1), and Cytomegalovirus (CMV). IgM and IgG antibodies to these infections were measured in the Health 2000 project nationally representative of the whole Finnish adult population, and 6250 participants, age 30 and over, were followed for 15 years via registers. In addition, lifetime suicidal ideation and suicide attempts based on medical records and interview were assessed within a subsample of 694 participants screened to a substudy for possible psychotic symptoms or as controls. Among the 6250 participants, 14 individuals died of suicide and an additional 4 individuals had a diagnosis of intentional self-harm during follow-up. Serological evidence of lifetime or acute infections was not found to be associated with these suicidal outcomes. However, in the subsample, those seropositive for CMV had fewer suicide attempts compared to those seronegative, adjusting for gender, age, educational level, childhood family size, regional residence, CRP, and screen status (OR for multiple attempts = 0.40, 95% confidence interval 0.20-0.83, p = 0.014). To conclude, common infections were not associated with risk of death by suicide or with self-harm diagnoses at a 15-year follow-up in the general population sample. Our finding of an increased number of suicide attempts among persons seronegative for CMV calls for further research.
  • Thomson, Annika; Tiihonen, Jari; Miettunen, Jouko; Virkkunen, Matti; Lindberg, Nina (2018)
    The rate of criminal reoffending among firesetters varies greatly. Our aim was to investigate firesetting and general criminal recidivism in a consecutive sample of Finnish males who were sent for a forensic psychiatric examination (FPE)(1) after committing firesetting offenses. We also wanted to evaluate the relationships between psychopathy and criminal recidivism, and between schizophrenia-spectrum disorders and criminal recidivism. The sample comprised 113 firesetters with a mean age of 32.8 years, and the average follow-up time was 16.9 years. The FPE statements of the firesetters were reviewed and psychiatric diagnoses were collected. The psychopathy assessments were based on the 20-item Hare Psychopathy Checklist-Revised (PCL-R). Information on reoffending was gathered from the Finnish National Police Register. During the follow-up 20 (18%) persons were registered for a new firesetting and 84 (74%) for any new offense. Firesetters with high traits (PCL-R 25) of psychopathy were more likely than those with low traits (PCL-R <25) to reoffend with any crime during the follow-up. The risk of general criminal recidivism was lower among firesetters with a schizophrenia-spectrum disorder than among those with non-psychotic disorders. Conclusively, both firesetting and general criminal recidivism rates were high in this sample of offenders.
  • Bosqui, Tania; O'Reilly, Dermot; Vaananen, Ari; Patel, Kishan; Donnelly, Michael; Wright, David; Close, Ciara; Kouvonen, Anne (2019)
    PurposeThere is a recent and growing migrant population in Northern Ireland. However, rigorous research is absent regarding access to mental health care by different migrant groups. In order to address this knowledge gap, this study aimed to identify the relative use of psychotropic medication between the largest first generation migrant groups in Northern Ireland and the majority population.MethodsCensus (2011) data was linked to psychotropic prescriptions for the entire enumerated population of Northern Ireland using data linkage methodology through the Administrative Data Research Centre Northern Ireland (ADRC-NI).ResultsLower prescription dispensation for all psychotropic medication types, particularly antidepressants (OR=0.35, CI 95% 0.33-0.36) and anxiolytics (OR=0.42, CI 95% 0.40-0.44), was observed for all migrant groups with the exception of migrants from Germany.ConclusionsIt is likely that the results reflect poorer access to services and indicate a need to improve access and the match between resources, services and the health and social care needs of migrants. Further research is required to identify barriers to accessing primary care and mental health services.
  • Seppänen, Allan; Joelsson, Petteri; Ahlgren-Rimpiläinen, Aulikki; Repo-Tiihonen, Eila (2020)
    Despite a recent contrary trend, Finland has been for decades one of the most violent countries in Western Europe. Also, Finland has had one of the highest number of psychiatric beds per capita in Europe, although this, too, has seen a sharp decline. Against this background, among other national idiosyncrasies, Finland has developed its forensic psychiatric services. Here, we describe the legal, organizational and clinical structure of these services, and outline the historical and current issues that have shaped them. Finally, we consider future challenges facing the Finnish forensic service system, as part of wider European and global trends.
  • Weizmann-Henelius, Ghitta; Grönroos, Matti; Putkonen, Hanna; Eronen, Markku; Lindberg, Nina; Hakkanen-Nyholm, Helinä (2012)
  • Rautiainen, M-R; Paunio, T.; Repo-Tiihonen, E.; Virkkunen, M.; Ollila, H. M.; Sulkava, Sonja; Jolanki, O.; Palotie, A.; Tiihonen, J. (2016)
    The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N = 370, N = 5850 for controls, GWAS; N = 173, N = 3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR) = 2.19 (1.53-3.14), P = 1.9 x 10(-5)). Two polymorphisms at 6p21.2 LINC00951-LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR = 1.59 (1.37-1.85), P = 1.6 x 10(-9)) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (beta = 0.68, P = 0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder.
  • Ukkola-Vuoti, Liisa; Kanduri, Chakravarthi; Oikkonen, Jaana; Buck, Gemma; Blancher, Christine; Raijas, Pirre; Karma, Kai; Lahdesmaki, Harri; Järvelä, Irma (2013)
  • Kerminen, Sini; Martin, Alicia R.; Koskela, Jukka; Ruotsalainen, Sanni E.; Havulinna, Aki S.; Surakka, Ida; Palotie, Aarno; Perola, Markus; Salomaa, Veikko; Daly, Mark J.; Ripatti, Samuli; Pirinen, Matti (2019)
    Polygenic scores (PSs) are becoming a useful tool to identify individuals with high genetic risk for complex diseases, and several projects are currently testing their utility for translational applications. It is also tempting to use PSs to assess whether genetic variation can explain a part of the geographic distribution of a phenotype. However, it is not well known how the population genetic properties of the training and target samples affect the geographic distribution of PSs. Here, we evaluate geographic differences, and related biases, of PSs in Finland in a geographically well-defined sample of 2,376 individuals from the National FINRISK study. First, we detect geographic differences in PSs for coronary artery disease (CAD), rheumatoid arthritis, schizophrenia, waist-hip ratio (WHR), body-mass index (BMI), and height, but not for Crohn disease or ulcerative colitis. Second, we use height as a model trait to thoroughly assess the possible population genetic biases in PSs and apply similar approaches to the other phenotypes. Most importantly, we detect suspiciously large accumulations of geographic differences for CAD, WHR, BMI, and height, suggesting bias arising from the population's genetic structure rather than from a direct genotype-phenotype association. This work demonstrates how sensitive the geographic patterns of current PSs are for small biases even within relatively homogeneous populations and provides simple tools to identify such biases. A thorough understanding of the effects of population genetic structure on PSs is essential for translational applications of PSs.