Research and publications

The research of the group Sleep and Health has focused on understanding the individual variation in susceptibility to disturbed sleep, emotions, and mental health, with the basic idea that only by understanding the basic mechanisms and inter-individual variation behind the reactivity of these mechanisms one can develop targeted, individualized tools to ameliorate sleep- and stress-related disturbances.

INVIDUAL VARIATION IN SUSCEPTIBILITY TO PSYCHIATRIC DISORDERS

We have identified genetic risk variants for major psychiatric diseases incl. schizophrenia and bipolar disorder in the Finnish population and as part of large international collaborative networks. This work has revealed how both common & low-risk, and rare & high variations contribute to the disease risk. The role of the rare & high-risk variations, such as those at RBM12, KCNB1, DISC1, or TOP3B, is particularly intruiging and prominent in the specific sub-isolate populations in Finland.

Selected references: 

  1. Schizophrenia Working Group of the Psychiatric Genomics Consortium. (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511(7510):421-7
  2. Soronen P, Ollila HM, Antila M, Silander K, Palo OM, Kieseppä T, Lönnqvist J, Peltonen L, Tuulio-Henriksson A, Partonen T, Paunio T (2010) Replication of GWAS of bipolar disorder: association of SNPs near CDH7 with bipolar disorder and visual processing.  Mol Psychiatry 15(1):4-
  3. Soronen P, Silander K, Antila M, Palo OM, Ellonen P, Wedenoja J, Turunen JA, Pietiläinen OPH, Hennah W, Tuulio-Henriksson A, Kieseppä T, Partonen T, Lönnqvist J, Peltonen L, Paunio T (2008) Association of a nonsynonymous variant of DAOA with visuospatial ability in a bipolar family sample. Biol Psychiatry.Sep 1;64(5):438-42. Epub May 7 ;
  4. Steinberg S, Gudmundsdottir S, Suvisaari J, Paunio T, Torniainen-Holm M, Sveinbjornsson G, Frigge MLÖ, Jonsdottir GA, Huttenlocher J, Arnardottir S, Ingimarsson O, Haraldsson M, Kong A, Norddahl GL, Gudbjartsson DF, Sigurdsson E, Stefansson H, Stefansson K. (2017) Truncating mutations in RBM12 cause psychosis. Nature Genetics, Nat Genet. 2017 Aug;49(8):1251-1254. doi: 10.1038/ng.3894;
  5. Peltola MA, Kuja-Panula J, Liuhanen J, Võikar V, Piepponen P, Hiekkalinna T, Taira T, Lauri SE, Suvisaari J, Kulesskaya N, Paunio T, Rauvala H. (2016) AMIGO-Kv2.1 Potassium Channel Complex is Associated With Schizophrenia-Related Phenotypes. Schizophr Bull. Jan;42(1):191-201. doi: 10.1093/schbul/sbv105; 6
  6. Stoll G, Pietiläinen OP, Linder B, Suvisaari J, Brosi C, Hennah W, Leppä V, Torniainen M, Ripatti S, Ala-Mello S, Plöttner O, Rehnström K, Tuulio-Henriksson A, Varilo T, Tallila J, Kristiansson K, Isohanni M, Kaprio J, Eriksson JG, Raitakari OT, Lehtimäki T, Jarvelin MR, Salomaa V, Hurles M, Stefansson H, Peltonen L, Sullivan PF, Paunio T, Lönnqvist J, Daly MJ, Fischer U, Freimer NB, Palotie A. (2013) Deletion of TOP3β, a component of FMRP-containing mRNPs, contributes to neurodevelopmental disorders. Nat Neurosci 16(9):1228-37

INDIVIDUAL VARIATION IN SUSCEPTIBILITY TO DISTURBED SLEEP AND ENVIRONMENTAL STRESS 

During the past 10 years, our main research focus has been on understanding indivdiual characteristics in regulation of sleep and emotions, and in tolerance to disrupted sleep and environmental stress. We identified genetic risk factors for emotional burnout in occupational cohorts in the UST and, under circadian stress (shift work), in melatonin receptor 1A genes by genome-wide association. The latter finding evidenced for the importance of intrinsic melatonin signaling in modulation of the capability to tolerate circadian stress. - In a national and international collaboration, we detected genetic risk variations for extreme impulsivity and violent behavior and antisocial personality.  The risk factors identified in the samples enriched for extreme phenotypes played also role in mediating susceptibility to substance use disorder or features of antisocial personality in general population, when there were environmental risk factors during the early development.

Selected references:

  1. Santangeli O, Lehtikuja H, Palomäki E, Wigren HK, Paunio T, Porkka-Heiskanen T. Sleep and Behavior in Cross-Fostering Rats: Developmental and Sex Aspects. Sleep. 2016 Dec 1;39(12):2211-2221.
  2. Kantojärvi K, Liuhanen J, Saarenpää-Heikkilä O, Satomaa AL, Kylliäinen A, Pölkki P, Jaatela J, Toivola A, Milani L, Himanen SLk, Porkka-Heiskanen T, Paavonen J, Paunio T. Variants in calcium voltage-gated channel subunit Alpha1 C-gene (CACNA1C) are associated with sleep latency in infants. PLoS One. 2017 Aug 9;12(8:e0dgcc180652.
  3. Utge S, Kronholm E, Partonen T, Soronen P, Ollila HM, Loukola A, Perola M, Salomaa V, Porkka-Heiskanen T, Paunio T. Shared genetic background for regulation of mood and sleep: association of GRIA3 with sleep duration in healthy Finnish women. Sleep. 2011 Oct 1;34(10):1309-16.
  4. Tiihonen J, Rautiainen MR, Ollila HM, Repo-Tiihonen E, Virkkunen M, Palotie A, Pietiläinen O, Kristiansson K, Joukamaa M, Lauerma H, Saarela J, Tyni S, Vartiainen H, Paananen J, Goldman D, Paunio T. Genetic background of extreme violent behavior. Mol Psychiatry. 2015 Jun;20(6):786-92.
  5. Bevilacqua L, Doly S, Kaprio J, Yuan Q, Tikkanen R, Paunio T, Zhou Z, Wedenoja J, Maroteaux L, Diaz S, Belmer A, Hodgkinson CA, Dell'osso L, Suvisaari J, Coccaro E, Rose RJ, Peltonen L, Virkkunen M, Goldman D. (2010) A population-specific HTR2B stop codon predisposes to severe impulsivity. Nature 468(7327):1061-6. Erratum in: Nature. 2011 Feb 17;470(7334):424 
  6. Sulkava S, Ollila HM, Ahola K, Partonen T, Viitasalo K, Kettunen J, Lappalainen M, Kivimäki M, Vahtera J, Lindström J, Härmä M, Puttonen S, Salomaa V, Paunio T. Genome-wide scan of job-related exhaustion with three replication studies implicate a susceptibility variant at the UST gene locus. Hum Mol Genet.  2013 Aug 15;22(16):3363-72.
  7. Sulkava S, Ollila HM, Alasaari J, Puttonen S, Härmä M, Viitasalo K, Lahtinen A, Lindström J, Toivola A, Sulkava R, Kivimäki M, Vahtera J, Partonen T, Silander K, Porkka-Heiskanen T, Paunio T. Common Genetic Variation Near Melatonin Receptor 1A Gene Linked to Job-Related Exhaustion in Shift Workers. Sleep. 2017 Jan 1;40(1). 
  8. Alasaari JS, Lagus M, Ollila HM, Toivola A, Kivimäki M, Vahtera J, Kronholm E, Härmä M, Puttonen S, Paunio T. (2012) Environmental stress affects DNA methylation of a CpG rich promoter region of serotonin transporter gene in a nurse cohort. PLoS One 7(9):e45813

SLEEP & HEALTH - TOOLS FOR CARE

One major line of our research has been to discover the relation of sleep and environmental stress for health, and to develop research-based, targetted tools to ameliorate sleep- and stress-related disturbances. The interest on searching for connections between stress, disturbed sleep and depression origins from our milestone publication in 2009, where we showed the temporally unidirectional relationship of poor sleep quality, depressed mood and, eventually, work disability due to depressive disorder in a comprehensive sample of twins. In another large epidemiological study, we were able to link the core feature of depression, negative attitude towards self, to frequent nightmares, suggesting for their intimate connection via disturbed REM sleep processes.

The ultimate goal of our research is to find tools to improve methods for prevention and individual care. Meanwhile we are looking for specific biomarkers for risk detection, there has been important work which has taken advantage of the research on sleep medicine and resulted in recommendations for health practices in the common population as well as for patients with insomnia.

Selected references

  1. Paunio T, Korhonen T, Hublin C, Partinen M, Koskenvuo K, Koskenvuo M, Kaprio J. Poor sleep predicts symptoms of depression and disability retirement due to depression. J Affect Disord. 2015;172:381-9
  2. Paunio T, Korhonen T, Hublin C, Partinen M, Kivimäki M, Koskenvuo M, Kaprio J. Longitudinal study on poor sleep and life dissatisfaction in a nationwide cohort of twins. Am J Epidemiol. 2009 Jan 15;169(2):206-13
  3. Sandman N, Valli K, Kronholm E, Revonsuo A, Laatikainen T, Paunio T. Nightmares: risk factors among the Finnish general adult population. Sleep. 2015  Apr 1;38(4):507-14.
  4. Ollila HM, Kronholm E, Kettunen J, Silander K, Perola M, Porkka-Heiskanen T, Salomaa V, Paunio T. Insomnia does not mediate or modify the association between MTNR1B risk variant rs10830963 and glucose levels. Diabetologia. 2016 May;59(5):1070-2.
  5. Ollila HM, Utge S, Kronholm E, Aho V, Van Leeuwen W, Silander K, Partonen T,  Perola M, Kaprio J, Salomaa V, Sallinen M, Härmä M, Porkka-Heiskanen T, Paunio T. TRIB1 constitutes a molecular link between regulation of sleep and lipid metabolism in humans. Transl Psychiatry. 2012 Mar 20;2:e97.
  6. Leminen MM, Virkkala J, Saure E, Paajanen T, Zee PC, Santostasi G, Hublin C, Müller K, Porkka-Heiskanen T, Huotilainen M, Paunio T. Enhanced Memory Consolidation Via Automatic Sound Stimulation During Non-REM Sleep. Sleep. 2017 Mar 1;40(3). doi: 10.1093/sleep/zsx003. PubMed PMID: 28364428.

  7. Santangeli O, Porkka-Heiskanen T, Virkkala J, Castaneda AE, Marttunen M, Paunio T, Urrila AS. Sleep and slow-wave activity in depressed adolescent boys: a preliminary study. Sleep Med. 2017 Oct;38:24-30

  8. Riemann D, Baglioni C, Bassetti C, Bjorvatn B, Dolenc Groselj L, Ellis JG, Espie CA, Garcia-Borreguero D, Gjerstad M, Gonçalves M, Hertenstein E, Jansson-Fröjmark M, Jennum PJ, Leger D, Nissen C, Parrino L, Paunio T, Pevernagie D, Verbraecken J, Weeß HG, Wichniak A, Zavalko I, Arnardottir ES, Deleanu OC, Strazisar B, Zoetmulder M, Spiegelhalder K. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017 Dec;26(6):675-700

  9. https://www.aarp.org/content/dam/aarp/health/healthy-living/2017/01/gcbh...