Risk factors for schizophrenia and affective disorders in the Northern Finland Birth Cohort studies

Schizophrenia and psychotic and nonpsychotic affective disorders are a major public health problem, affecting over 10% of the population. Risk factors for these disorders are for instance genetic factors, complications of pregnancy and childbirth, substance use, poor school success, life events, somatic illness, and socioeconomic factors. Many of these potential risk factors may be pluripotent, resulting in risk for diverse mental health outcomes. It is also likely that risk factors differ between psychotic and nonpsychotic affective disorders, but research on this is quite scarce. The research project aims to study extensively biological and environmental risk factors, their specificity, and interactions and causal pathways in schizophrenia, psychotic and nonpsychotic affective disorders in two large birth cohorts. Regarding interactions of risk factors, we study especially mechanisms, how genetic risk (estimated with polygenic risk scores) associate with early life risk factors or substance use in onset of these disorders. A survey related to the effects of the COVID-19 pandemic will be used to study if earlier vulnerability affects the risk of increased depressive symptoms as a consequence of the pandemic.

The study is based on the Northern Finland Birth Cohorts 1966 (n = 11647) and 1986 (n = 9340), which are two population-based studies where data on individuals have been collected progressively since pregnancy. There are currently 1,345 (11.9%) people in the 1966 birth cohort and 1,168 (12.5%) people in the 1986 birth cohort with schizophrenia or affective disorder. In addition to traditional epidemiological methods, structural equation modeling and machine learning methods are used to analyze data. In sensitivity analyses, we can replicate analyses using depressive symptoms instead of diagnoses.

The innovative methodological approaches hold promise for scientifically and clinically significant findings. Some of the potential risk factors are modifiable, finding these may renew the knowledge on aetiology of schizophrenia and affective disorders. These birth cohorts offer a unique opportunity to study the interactions of risk factors and possible pragmatic causal pathways to disease onset in two unique datasets. Research findings can be used to more effectively design interventions to reduce and alleviate these serious and critical illnesses with public health impact.


Earlier work

I have been involved in work relating to the risk of psychosis and affective disorders since year 2000, below a list of previous studies (updated 15.6.2022):

Choudhary P, Ronkainen J, Nedelec R, Tolvanen M, Lowry E, Miettunen J, Jarvelin M-R, Sebert S.  The relationship of life-course patterns of adiposity with type 2 diabetes, depression, and their comorbidity in the Northern Finland Birth Cohort 1966.  Int J Obes, in press. (IF = 5.095, JUFO = 3)

Denissoff A, Mustonen A, Alakokkare A-E, Scott JG, Musa S, Miettunen J, Niemelä S.  Is early exposure to cannabis associated with bipolar disorder? results from a Finnish birth-cohort study.  Addiction, in press. (IF = 6.526, JUFO = 3)

Filatova S , Koivumaa-Honkanen H, Khandaker GM, Lowry E, Nordström T, Hurtig T, Moilanen K, Miettunen J Early motor developmental milestones and schizotypy in the Northern Finland Birth Cohort 1966 Schizophr Bull 2018; 44:1151-8

Filatova S , Marttila R, Koivumaa-Honkanen H, Nordström T, Veijola J, Mäki P, Khandaker GM, Isohanni M, Jääskeläinen E, Moilanen K, Miettunen J A comparison of the cumulative incidence and early risk factors for psychotic disorder in young adults in the Northern Finland Birth Cohorts 1966 and 1986 Epidemiol Psychiatr Sci 2017; 26:314-24

Filatova S, Koivumaa-Honkanen H, Hirvonen N, Freeman A, Ivandic I, Hurtig T, Khandaker G, Jones PB, Moilanen K, Miettunen J Early motor developmental milestones and schizophrenia: a systematic review and meta-analysis Schizophr Res 2017; 188:13-20

Herva A, Laitinen J, Miettunen J, Veijola J, Karvonen JT, Läksy K, Joukamaa M Obesity and depression: Results from the longitudinal Northern Finland 1966 Birth Cohort Study Int J Obes 2006; 30:520-7

Hurtig T, Taanila A, Veijola J, Ebeling H, Mäki P, Miettunen J, Kaakinen M, Joukamaa M, Therman S, Heinimaa M, Järvelin M-R, Moilanen I Associations between psychotic-like symptoms and inattention/hyperactivity symptoms Soc Psychiatry Psychiatr Epidemiol 2011; 46:17-27

Ikonen H, Palaniswamy S, Nordström T, Järvelin M-R, Herzig K-H, Jääskeläinen E, Seppälä J, Miettunen J, Sebert S Vitamin D status and correlates of low vitamin D in schizophrenia, other psychoses and non-psychotic depression – The Northern Finland Birth Cohort 1966 study Psychiatry Res 2019; 279:186-94. doi:10.1016/j.psychres.2019.02.060 (IF = 2.223, JUFO = 1)

Immonen J, Jääskeläinen E, Korpela H, Miettunen J Age at onset and the outcomes of schizophrenia: systematic review and meta-analysis Early Interv Psychiatry 2017; 11:453-60

Isohanni M, Isohanni I, Koponen H, Koskinen J, Laine P, Lauronen E, Miettunen J, Mäki P, Riala K, Räsänen S, Saari K, Tienari P, Veijola J, Murray G Developmental precursors of psychosis Curr Psychiatry Rep 2004; 6:168-75

Isohanni M, Lauronen E, Moilanen K, Isohanni I, Kemppainen L, Koponen H, Miettunen J, Mäki P, Räsänen S, Veijola J, Tienari P, Wahlberg K-E, Murray G Predictors of schizophrenia. Evidence from the Northern Finland 1966 Birth Cohort and other sources Br J Psychiatry Suppl 2005; 187:s4-s7

Isohanni M, Löhönen J, Tamminga C, Ivleva E, Koponen H, Tanskanen P, Mäki P, Peltonen L, Paunio T, Ghose S, Jääskeläinen E, Isohanni I, Alaräisänen A, Miettunen J, Lehtonen J, Moilanen J, Mäkinen J, Penttilä M, McGrath J Developmental pathways of schizophrenia: a system theoretical view and proposal of a system model Psychiatria Fennica 2009; 40:14-32.

Jääskeläinen E, Juola T, Korpela H, Lehtiniemi H, Nietola M, Korkeila J, Miettunen J Epidemiology of psychotic depression – a systematic review and meta-analysis Psychol Med 2018; 48:905-18

Karjula S, Arffman R, Morin-Papunen L, Franks S, Järvelin M-R, Tapanainen JS, Miettunen J, Piltonen TT.  A population-based follow-up study shows high psychosis risk in women with PCOS.  Arch Womens Ment Health, in press. (IF = 3.633, JUFO = 1)

Kehusmaa J, Ruotsalainen H, Männikkö N, Alakokkare A-E, Niemelä M, Jääskeläinen E, Miettunen J.  The association between the social environment of childhood and adolescence and depression in young adulthood- a prospective cohort study.  J Affect Disord 2022; 305:37-46 (IF = 4.839, JUFO = 1)

Keskinen E, Marttila A, Marttila R, Jones PB, Murray GK, Moilanen K, Koivumaa-Honkanen H, Mäki P, Isohanni M, Jääskeläinen E, Miettunen J Interaction between parental psychosis and early motor development and the risk of Schizophrenia in a general population birth cohort Eur Psychiatry 2015; 30:719-26

Keskinen E, Marttila R, Koivumaa-Honkanen H, Moilanen K, Keinänen-Kiukaanniemi S, Timonen M, Isohanni M, McGrath J, Miettunen J, Jääskeläinen E Search for protective factors for psychosis – A population based sample with special interest in unaffected individuals with parental psychosis Early Interv Psychiatry 2018; 12:869-78

Keskinen E, Miettunen J, Koivumaa-Honkanen H, Mäki P, Isohanni M, Jääskeläinen E Interaction between parental psychosis and risk factors during pregnancy and birth for schizophrenia – The Northern Finland 1966 Birth Cohort study Schizophr Res 2013; 145:56-62

Kinnunen L, Nordström T, Niemelä M, Räsänen S, Whittle S, Miettunen J.  Parental physical illnesses and their association with subsequent externalizing and internalizing symptoms in children.  J Child Fam Stud, in press. (IF = 2.278, JUFO = 1)

Kinnunen L, Nordström T, Niemelä M, Räsänen S, Whittle S, Sawyer M, Miettunen J.  Parental somatic illnesses and their association with prodromal symptoms of psychosis among offspring.  Schizophr Res 2020; 224:190-2. (IF = 3.759, JUFO = 2)

Koskinen J, Löhönen J, Koponen H, Isohanni M, Miettunen J Rate of cannabis use disorders in clinical samples of patients with schizophrenia: a meta-analysis Schizophr Bull 2010; 36:1115-30

Lahti J, Räikkönen K, Sovio U, Miettunen J, Hartikainen A-L, Pouta A, Taanila A, Joukamaa M, Järvelin M-R, Veijola J Early life origins of schizotypal traits in the 1966 Northern Finland Birth Cohort Br J Psychiatry 2009; 195:132-37

Lassila M, Nordström T, Hurtig T, Mäki P, Jääskeläinen E, Oinas E, Miettunen J School success in childhood and subsequent prodromal symptoms and psychoses in the Northern Finland Birth Cohort 1986 Psychol Med 2020; 50:948-55.

Metcalf SA, Jones PB, Nordström T, Timonen M, Mäki P, Miettunen J, Jääskeläinen E, Järvelin M-R, Stochl J, Murray GK, Veijola J, Khandaker G Serum C-reactive protein in adolescence and risk of schizophrenia in adulthood: a prospective birth cohort study Brain Behav Immun 2017; 59:253-9

Metsänen M, Wahlberg K-E, Saarento O, Tarvainen T, Miettunen J, Koistinen P, Läksy K, Tienari P Early presence of thought disorder as a prospective sign of mental disorder Psychiatry Res 2004; 125:193-203

Miettunen J Environmental epidemiology of psychoses in Nottingham – social deprivation and incidence of psychoses in 1992-94 and 1997-99 Master of Philosophy -thesis, 20033

Miettunen J, Immonen J, McGrath J, Isohanni M, Jääskeläinen E The age of onset of schizophrenia spectrum disorders In: Age of Onset of Mental Disorders

Miettunen J, Isohanni M, Paunio T, Freimer N, Taanila A, Ekelund J, Järvelin M-R, Joukamaa M, Lichtermann D, Koivumaa-Honkanen H, Veijola J Predicting depression with psychopathology and temperament traits – the Northern Finland 1966 Birth Cohort Depress Res Treat 2012; 2012:160905

Miettunen J, Murray GK, Jones PB, Mäki P, Ebeling H, Taanila A, Joukamaa M, Savolainen J, Törmänen S, Järvelin M-R, Veijola J, Moilanen I Longitudinal associations between childhood and adulthood externalizing and internalizing psychopathology and adolescent substance use Psychol Med 2014; 44:1727-38

Miettunen J, Törmänen S, Murray GK, Jones PB, Mäki P, Ebeling H, Moilanen I, Taanila A, Heinimaa M, Joukamaa M, Veijola J Association of cannabis use with prodromal symptoms of psychosis in adolescence Br J Psychiatry 2008; 192: 470-1

Miettunen J, Veijola J, Isohanni M, Paunio T, Freimer N, Jääskeläinen E, Taanila A, Ekelund J, Järvelin M-R, Peltonen L, Joukamaa M, Lichtermann D Identifying schizophrenia and other psychoses with psychological scales in the general population J Nerv Ment Dis 2011; 199:230-8

Miller B, Alaräisänen A, Miettunen J, Järvelin M-R, Koponen H, Räsänen P, Isohanni M, Kirkpatrick B Advanced paternal age, suicide, and all-cause mortality in the general population J Nerv Ment Dis 2010; 198:404-11

Miller B, Messias E, Miettunen J, Alaräisänen A, Järvelin M-R, Koponen H, Räsänen P, Isohanni M, Kirkpatrick B Meta-analysis of paternal age and schizophrenia risk in male versus female offspring Schizophr Bull 2011; 37: 1039-47

Miller B, Suvisaari J, Miettunen J, Järvelin M-R, Haukka J, Tanskanen A, Lönnqvist J, Isohanni M, Kirkpatrick B Advanced paternal age and parental history of schizophrenia Schizophr Res 2011; 133:125-32

Mustonen A, Ahokas T, Nordström T, Murray GK, Mäki P, Jääskeläinen E, Heiskala A, McGrath JJ, Scott JG, Miettunen J, Niemelä S Smokin’ hot: adolescent tobacco smoking and the risk of psychosis adolescent tobacco smoking and the risk of psychosis Acta Psychiatr Scand 2018; 138:5-14

Mustonen A, Hielscher E, Miettunen J, Denissoff A, Alakokkare A-E, Scott JG, Niemelä S.  Adolescent cannabis use, depression and anxiety disorders in Northern Finland Birth Cohort 1986.  BJ Psych Open 2021; 7: e137. (No IF, no JUFO)

Mustonen A, Niemelä S, McGrath JJ, Murray GK, Nordström T, Mäki P, Miettunen J, Scott JG Adolescent inhalant use and psychosis risk – a prospective longitudinal study Schizophr Res 2018; 201:360-366

Mustonen A, Niemelä S, Nordström T, Murray GK, Mäki P, Jääskeläinen E, Miettunen J Adolescent cannabis use, baseline prodromal symptoms and the risk of psychosis Br J Psychiatry 2018; 212:227-33

Mäki P, Koskela S, Murray GK, Nordström T, Miettunen J, Jääskeläinen E, Veijola JM Difficulty in making contact with others and social withdrawal as early signs of psychosis in adolescents – the Northern Finland Birth Cohort 1986 Eur Psychiatry 2014; 29:345-51

Mäki P, Riekki T, Miettunen J, Isohanni M, Jones PB, Murray GK, Veijola J Schizophrenia in the offspring of antenatally depressed mothers in the Northern Finland 1966 Birth Cohort – relationship to family history of psychosis Am J Psychiatry 2010; 167:170-7

Mäki P, Veijola J, Jones PB, Murray GK, Koponen H, Tienari P, Miettunen J, Tanskanen P, Wahlberg K-E, Koskinen J, Lauronen E, Isohanni M Predictors of schizophrenia – a review Br Med Bull 2005; 73:1-15

Nietola M, Huovinen H, Heiskala A, Nordström T, Miettunen J, Korkeila J, Jääskeläinen E.  Early childhood and adolescent risk factors for psychotic depression in a general population birth cohort sample.  Soc Psychiatry Psychiatr Epidemiol 2020; 55:1179-86. (IF = 3.152, JUFO = 2)

Nyman E, Miettunen J, Freimer N, Joukamaa M, Mäki P, Ekelund J, Peltonen L, Järvelin M-R, Veijola J, Paunio T Impact of temperament on depression and anxiety symptoms and depressive disorder in a population-based birth cohort J Affect Disord 2011; 131:393-7

Nyman ES, Sulkava S, Soronen P, Miettunen J, Loukola A, Leppä V, Joukamaa M, Mäki P, Järvelin M-R, Freimer N, Peltonen L, Veijola J, Paunio T Interaction of early environment, gender and genes of monoamine neurotransmission in the etiology of depression in a large population-based Finnish birth cohort BMJ Open 2011; 1:e000087

Ortega-Alonso A, Ekelund J, Sarin A-P, Miettunen J, Veijola J, Järvelin M-R, Hennah W Genome-wide association study of psychosis proneness in the Finnish population Schizophr Bull 2017; 43:1304-14

Patwardhan I, Mason WA, Chmelka B, Savolainen J, Miettunen J, Järvelin MR Prospective Relations between Alexithymia, Substance Use and Depression: Findings from a National Birth Cohort Nord J Psychiatry 2019; 73:340-8

Patwardhan I, Mason WA, Savolainen J, Chmelka MB, Miettunen J, Järvelin M-R Childhood cumulative contextual risk and depression diagnosis among young adults: The mediating roles of adolescent alcohol use and perceived social support J Adolesc 2017; 60:16-26

Rautio N, Filatova S, Lehtiniemi H, Miettunen J Living environment and its relationship to depressive mood: A systematic review Int J Soc Psychiatry 2018; 64:92-103

Räsänen S, Niemelä M, Nordström T, Hakko H, Haapea M, Marshall CA, Miettunen J Parental hospital-treated somatic illnesses and psychosis of the offspring – the Northern Finland Birth Cohort 1986 Study, Early Interv Psychiatry 2019; 13:290-6 doi:10.1111/eip.12479 (IF = 1.950, JUFO = 1)

Sarala M, Mustonen A, Alakokkare A-E, Salom C, Miettunen J, Niemelä S.  Maternal smoking during pregnancy and paternal smoking before pregnancy: Associations with young adult offspring psychosis, internalizing disorders and substance use disorder.  Eur J Publ Health, in press. (IF = 3.367, JUFO = 2)

Scott JG, Matuschka L, Niemelä S, Miettunen J, Emmerson B, Mustonen A Evidence of a causal relationship between smoking tobacco and schizophrenia spectrum disorders Front Psychiatry 2018; 9:607

Siira V, Wahlberg K-E, Miettunen J, Läksy K, Tienari P MMPI measures as a signs of predisposition to mental disorder among adoptees at high risk for schizophrenia Psychiatry Res 2008; 158:278-86

Siira V, Wahlberg K-E, Miettunen J, Tienari P, Läksy K Differentiation of adoptees at high versus low genetic risk for schizophrenia by adjusted MMPI indices Eur Psychiatry 2006; 21:245-50

Solje E, Miettunen J, Marttila R, Helisalmi S, Laitinen M, Koivumaa-Honkanen H, Isohanni M, Hiltunen M, Jääskeläinen E, Remes AM The C9ORF72 expansion sizes in patients with psychosis –a population based study on the Northern Finland Birth Cohort 1966 Psychiatr Genet 2016; 26:92-4

Stochl J, Whittier A, Wagner AP, Veijola J, Jääskeläinen E, Miettunen J, Khandaker GM, Jones PB Association between developmental milestones and age of schizophrenia onset: Results from the Northern Finland Birth Cohort 1966 Schizophr Res 2019; 208:228-34

Tienari P, Wynne LC, Sorri A, Lahti I, Läksy K, Moring J, Naarala M, Nieminen P, Wahlberg K-E, Miettunen J Genotype-environment interaction in the Finnish Adoptive Family Study, Interplay between genes and environment? In: Risk and Protective Factors in Schizophrenia (Eds. Häfner H, an der Heiden W, Resch F, Schröder J), Springer, Steinkopff Verlag, Betz-Druck, Darmstadt, Germany, 2002

Timonen M, Hakko H, Miettunen J, Koskinen O, Zitting P, Karvonen JT, Herva A, Räsänen P Association between atopic disorders and depression: Findings from the Northern Finland 1966 Birth Cohort Study Am J Med Genet B Neuropsychiatr Genet 2001; 105:216-7

Tomppo L, Hennah W, Miettunen J, Järvelin M-R, Veijola J, Ripatti S, Lahermo P, Palotie A, Lichtermann D, Peltonen L, Ekelund J Association of variants in DISC1 with psychosis related traits in a large population cohort Arch Gen Psychiatry 2009;66:134-41

Wahlberg K-E, Wynne LC, Hakko H, Läksy K, Moring J, Miettunen J, Tienari P Interaction of genetic risk and adoptive parent communication deviance: Longitudinal prediction of adoptee psychiatric disorders Psychol Med 2004; 34:1531-42