Skip to main content

Both low birthweight and high birthweight are associated with cognitive impairment in persons with schizophrenia and their first-degree relatives

  • M. Torniainen (a1) (a2), A. Wegelius (a1) (a3), A. Tuulio-Henriksson (a1) (a2) (a4), J. Lönnqvist (a1) (a2) (a5) and J. Suvisaari (a1) (a6)...

Both low birthweight and high birthweight have been associated with an increased risk for schizophrenia and cognitive impairments in the general population. We assessed the association between birthweight and cognitive performance in persons with schizophrenia and their unaffected first-degree relatives.


We investigated a population-based family sample comprising persons with schizophrenia (n = 142) and their unaffected first-degree relatives (n = 277). Both patients and relatives were interviewed with the Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV) and a comprehensive neuropsychological test battery was administered. Information on birthweight was obtained from obstetric records. We used generalized estimating equation (GEE) models to investigate the effect of birthweight, as a continuous variable, on cognitive functioning, adjusting for within-family correlation and relevant covariates.


Both low birthweight and high birthweight were associated with lower performance in visuospatial reasoning, processing speed, set-shifting and verbal and visual working memory among persons with schizophrenia and their unaffected first-degree relatives compared to individuals with birthweight in the intermediate range. The group × birthweight interactions were non-significant.


Both low birthweight and high birthweight are associated with deficits in cognition later in life. Schizophrenia does not seem to modify the relationship between birthweight and cognition in families with schizophrenia.

Corresponding author
*Address for correspondence: M. Torniainen, M.Psych., Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, PO Box 30, 00271 Helsinki, Finland. (Email:
Hide All
Aarnoudse-Moens CS, Weisglas-Kuperus N, van Goudoever JB, Oosterlaa J (2009). Meta-analysis of neurobehavioral outcomes in very preterm and/or very low birth weight children. Pediatrics 124, 717728.
Abel KM, Wicks S, Susser ES, Dalman C, Pedersen MG, Mortensen PB, Webb RT (2010). Birth weight, schizophrenia, and adult mental disorder: is risk confined to the smallest babies? Archives of General Psychiatry 67, 923930.
Allin MP, Kontis D, Walshe M, Wyatt J, Barker GJ, Kanaan RA, McGuire P, Rifkin L, Murray RM, Nosarti C (2011). White matter and cognition in adults who were born preterm. PLoS One 6, e24525.
APA (2000). Diagnostic and Statistical Manual of Mental Disorders, 4th edn, text revision (DSM-IV-TR). American Psychiatric Association: Washington, DC.
Arajärvi R, Haukka J, Varilo T, Suokas J, Juvonen H, Suvisaari J, Muhonen M, Suominen K, Tuulio-Henriksson A, Schreck M, Hovatta I, Partonen T, Lönnqvist J (2004). Clinical phenotype of schizophrenia in a Finnish isolate. Schizophrenia Research 67, 195205.
Barker DJ (1995). Fetal origins of coronary heart disease. British Medical Journal 311, 171174.
Baron IS, Litman FR, Ahronovich MD, Baker R (2012). Late preterm birth: a review of medical and neuropsychological childhood outcomes. Neuropsychology Review 22, 438450.
Cannon M, Moffitt TE, Caspi A, Murray RM, Harrington H, Poulton R (2006). Neuropsychological performance at the age of 13 years and adult schizophreniform disorder: prospective birth cohort study. British Journal of Psychiatry 189, 463464.
Cannon TD, van Erp TG, Rosso IM, Huttunen M, Lönnqvist J, Pirkola T, Salonen O, Valanne L, Poutanen VP, Standertskjold-Nordenstam CG (2002). Fetal hypoxia and structural brain abnormalities in schizophrenic patients, their siblings, and controls. Archives of General Psychiatry 59, 3541.
Cohen J (1988). Power Analysis for the Behavioral Sciences, 2nd edn. Lawrence Erlbaum Associates: Hillsdale, NJ.
Delis DC, Kramer JH, Kaplan E, Ober BA (1987). California Verbal Learning Test: Manual. Research Edition. The Psychological Corporation/Harcourt Brace & Company: San Antonio, TX.
Dickinson D, Ramsey ME, Gold JM (2007). Overlooking the obvious: a meta-analytic comparison of digit symbol coding tasks and other cognitive measures in schizophrenia. Archives of General Psychiatry 64, 532542.
First MB, Spitzer RL, Gibbon M, Williams JBW (1996). Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV). American Psychiatric Press, Inc., Washington, DC.
Fowden AL, Giussani DA, Forhead AJ (2006). Intrauterine programming of physiological systems: causes and consequences. Physiology (Bethesda) 21, 2937.
Freedman D, Bao Y, Kremen WS, Vinogradov S, McKeague IW, Brown AS (2012). Birth weight and neurocognition in schizophrenia spectrum disorders. Schizophrenia Bulletin. Published online: 29 February 2012. doi: 10.1093/schbul/sbs008.
Golden C (1978). Stroop Color and Word Test: Manual for Clinical and Experimental Uses. Stoelting: Chicago, IL.
Gunnell D, Rasmussen F, Fouskakis D, Tynelius P, Harrison G (2003). Patterns of fetal and childhood growth and the development of psychosis in young males: a cohort study. American Journal of Epidemiology 158, 291300.
Henriksen T (2008). The macrosomic fetus: a challenge in current obstetrics. Acta Obstetricia et Gynecologica Scandinavica 87, 134145.
Hoti F, Tuulio-Henriksson A, Haukka J, Partonen T, Holmström L, Lönnqvist J (2004). Family-based clusters of cognitive test performance in familial schizophrenia. BioMed Central Psychiatry 4, 20.
Hovatta I, Terwilliger JD, Lichtermann D, Mäkikyrö T, Suvisaari J, Peltonen L, Lönnqvist J (1997). Schizophrenia in the genetic isolate of Finland. American Journal of Medical Genetics 74, 353360.
Jolly MC, Sebire NJ, Harris JP, Regan L, Robinson S (2003). Risk factors for macrosomia and its clinical consequences: a study of 350,311 pregnancies. European Journal of Obstetrics, Gynecology, and Reproductive Biology 111, 914.
Karilampi U, Helldin L, Archer T (2011). Cognition and global assessment of functioning in male and female outpatients with schizophrenia spectrum disorders. Journal of Nervous and Mental Disease 199, 445448.
Kelleher I, Clarke MC, Rawdon C, Murphy J, Cannon M (2012). Neurocognition in the extended psychosis phenotype: performance of a community sample of adolescents with psychotic symptoms on the MATRICS neurocognitive battery. Schizophrenia Bulletin. Published online: 4 September 2012. doi: 10.1093/schbul/sbs086.
Kirkegaard I, Obel C, Hedegaard M, Henriksen TB (2006). Gestational age and birth weight in relation to school performance of 10-year-old children: a follow-up study of children born after 32 completed weeks. Pediatrics 118, 16001606.
Koskela O (1965). Large fetus; a geographic modification. Annales Chirurgiae et Gynaecologiae Fenniae 54, 461471.
Leonard H, Nassar N, Bourke J, Blair E, Mulroy S, de Klerk N, Bower C (2008). Relation between intrauterine growth and subsequent intellectual disability in a ten-year population cohort of children in Western Australia. American Journal of Epidemiology 167, 103111.
MacLeod CM (1991). Half a century of research on the Stroop effect: an integrative review. Psychological Bulletin 109, 163203.
Morgan VA, Croft ML, Valuri GM, Zubrick SR, Bower C, McNeil TF, Jablensky AV (2012). Intellectual disability and other neuropsychiatric outcomes in high-risk children of mothers with schizophrenia, bipolar disorder and unipolar major depression. British Journal of Psychiatry 200, 282289.
Morgane PJ, Austin-LaFrance R, Bronzino J, Tonkiss J, Diaz-Cintra S, Cintra L, Kemper T, Galler JR (1993). Prenatal malnutrition and development of the brain. Neuroscience and Biobehavioral Reviews 17, 91128.
Reichenberg A, Harvey PD (2007). Neuropsychological impairments in schizophrenia: integration of performance-based and brain imaging findings. Psychological Bulletin 133, 833858.
Reitan RM, Wolfson D (1985). The Halstead Reitan Neuropsychological Test Battery. Neuropsychology Press: Tuscon, AZ.
Rifkin L, Lewis S, Jones P, Toone B, Murray R (1994). Low birth weight and schizophrenia. British Journal of Psychiatry 165, 357362.
Shenkin SD, Starr JM, Deary IJ (2004). Birth weight and cognitive ability in childhood: a systematic review. Psychological Bulletin 130, 9891013.
Silva A, Metha Z, O'Callaghan FJ (2006). The relative effect of size at birth, postnatal growth and social factors on cognitive function in late childhood. Annals of Epidemiology 16, 469476.
Sitskoorn MM, Aleman A, Ebisch SJ, Appels MC, Kahn RS (2004). Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis. Schizophrenia Research 71, 285295.
Skranes J, Vangberg TR, Kulseng S, Indredavik MS, Evensen KA, Martinussen M, Dale AM, Haraldseth O, Brubakk AM (2007). Clinical findings and white matter abnormalities seen on diffusion tensor imaging in adolescents with very low birth weight. Brain 130, 654666.
Sorensen HJ, Mortensen EL, Reinisch JM, Mednick SA (2006). Height, weight and body mass index in early adulthood and risk of schizophrenia. Acta Psychiatrica Scandinavica 114, 4954.
Tanskanen P, Valkama M, Haapea M, Barnes A, Ridler K, Miettunen J, Murray GK, Veijola JM, Jones PB, Taanila AM, Isohanni MK (2011). Is prematurity associated with adult cognitive outcome and brain structure? Pediatric Neurology 44, 1220.
Torniainen M, Suvisaari J, Partonen T, Castaneda AE, Kuha A, Perälä J, Saarni S, Lönnqvist J, Tuulio-Henriksson A (2011). Sex differences in cognition among persons with schizophrenia and healthy first-degree relatives. Psychiatry Research 188, 712.
Turken A, Whitfield-Gabrieli S, Bammer R, Baldo JV, Dronkers NF, Gabrieli JD (2008). Cognitive processing speed and the structure of white matter pathways: convergent evidence from normal variation and lesion studies. NeuroImage 42, 10321044.
Tuulio-Henriksson A, Arajärvi R, Partonen T, Haukka J, Varilo T, Schreck M, Cannon T, Lönnqvist J (2003). Familial loading associates with impairment in visual span among healthy siblings of schizophrenia patients. Biological Psychiatry 54, 623628.
Van Lieshout RJ, Boyle MH (2011). Is bigger better? Macrosomia and psychopathology later in life. Obesity Reviews 12, e405e411.
Van Lieshout RJ, Voruganti LP (2008). Diabetes mellitus during pregnancy and increased risk of schizophrenia in offspring: a review of the evidence and putative mechanisms. Journal of Psychiatry and Neuroscience 33, 395404.
Videman T, Heikkilä J (1978). Frequent users of doctor services in a small rural community. Scandinavian Journal of Social Medicine 6, 3741.
Volpe JJ (2009). Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances. Lancet Neurology 8, 110124.
Wechsler D (1981). WAIS-R: Manual: Wechsler Adult Intelligence Scale – Revised. The Psychological Corporation: Cleveland, OH.
Wechsler D (1987). WMS-R: Wechsler Memory Scale – Revised, Manual. The Psychological Corporation: San Antonio, TX.
Wegelius A, Tuulio-Henriksson A, Pankakoski M, Haukka J, Lehto U, Paunio T, Lönnqvist J, Suvisaari J (2011). An association between high birth weight and schizophrenia in a Finnish schizophrenia family study sample. Psychiatry Research 190, 181186.
Zeger SL, Liang KY (1986). Longitudinal data analysis for discrete and continuous outcomes. Biometrics 42, 121130.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Type Description Title
Supplementary materials

Torniainen Supplementary Material

 PDF (111 KB)
111 KB


Altmetric attention score

Full text views

Total number of HTML views: 1
Total number of PDF views: 21 *
Loading metrics...

Abstract views

Total abstract views: 200 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 25th February 2018. This data will be updated every 24 hours.