Schizophrenia Research 60 2003 239 258 www elsevier com locate schres Review Childhood developmental abnormalities in schizophrenia evidence from high risk studies Laura T Niemi Jaana M Suvisaari Annamari Tuulio Henriksson Jouko K Lo nnqvist Department of Mental Health and Alcohol Research KTL National Public Health Institute Mannerheimintie 166 FIN 00300 Helsinki Finland Received 14 September 2001 accepted 13 February 2002 Abstract According to cohort studies individuals who develop schizophrenia in adulthood show developmental abnormalities in childhood These include delays in attainment of speech and motor milestones problems in social adjustment and poorer academic and cognitive performance Another method of investigating developmental abnormalities associated with schizophrenia is the high risk HR method which follows up longitudinally the development of children at high risk for schizophrenia Most HR studies have investigated children who have a parent with schizophrenia This review summarizes findings concerning childhood and adolescent development from 16 HR studies and compares them with findings from cohort conscript and family studies We specifically addressed two questions 1 Does the development of HR children differ from that of control children 2 Which developmental factors if any predict the development of schizophrenia spectrum disorders in adulthood While the answer to the first question is affirmative there may be other mechanisms involved in addition to having a parent with schizophrenia Factors which appear to predict schizophrenia include problems in motor and neurological development deficits in attention and verbal short term memory poor social competence positive formal thought disorder like symptoms higher scores on psychosis related scales in the MMPI and severe instability of early rearing environment D 2002 Elsevier Science B V All rights reserved Keywords Childhood developmental abnormalities Schizophrenia High risk method 1 Introduction The hypothesis that schizophrenia is a neurodevelopmental disorder is supported by several lines of evidence Weinberger 1995 Abnormalities in brain development and maturation seem to begin prenatally Corresponding author Tel 358 9 4744 8894 fax 358 94744 8478 E mail address laura niemi ktl fi L T Niemi but may continue throughout childhood Woods 1998 Minor physical anomalies manifesting as slight anatomical defects of the head hair eyes mouth hands and feet and thought to be caused by some injury during the first or second trimester of fetal life are more common among patients with schizophrenia than in their unaffected siblings or the general population Murphy and Owen 1996 Ismail et al 1998 Obstetric complications particularly hypoxicischemia related complications increase the risk for 0920 9964 02 see front matter D 2002 Elsevier Science B V All rights reserved doi 10 1016 S0920 9964 02 00234 7 240 L T Niemi et al Schizophrenia Research 60 2003 239 258 later development of schizophrenia Zornberg et al 2000 Geddes and Lawrie 1995 Neuropathological findings suggest abnormalities in brain development among patients with schizophrenia absence of gliosis suggests although does not prove that they may be of fetal origin Heckers 1997 Dwork 1997 Infections and malnutrition during pregnancy may also increase the risk for later developing schizophrenia Susser et al 1996 Mednick et al 1988 Barr et al 1990 Brown et al 2000 If schizophrenia is a consequence of abnormal neurodevelopment it seems reasonable to assume that abnormality in development would somehow manifest itself during childhood Follow back cohort and conscript studies have demonstrated associations between adult onset schizophrenia and delays or abnormalities in childhood or adolescent emotional cognitive motor and or social development These include delays in the attainment of early childhood motor milestones Jones et al 1994 problems in motor coordination Crow et al 1995 Rosso et al 2000 as well as other problems in neuromotor development Fish et al 1992 Walker et al 1999 Cannon et al 1999 Rosso et al 2000 worse performance in cognitive tests or lower IQ than among control children Crow et al 1995 David et al 1997 Kremen et al 1998 Davidson et al 1999 Cannon et al 2000 problems with speech DeLisi et al 1991 Jones et al 1994 Bearden et al 2000 and difficulties in social adjustment Walker et al 1993 Crow et al 1995 Malmberg et al 1998 Davidson et al 1999 Bearden et al 2000 However two Finnish cohort studies found no difference in school marks in academic subjects between children who later developed schizophrenia and other cohort members Isohanni et al 1998 Cannon et al 1999 the other even found that excellent school marks were more common among males who later developed schizophrenia than among males with no psychiatric disorders Isohanni et al 1999 There are certain weaknesses in these study designs Deficient data sampling problems and the different practices of doctors when examining patients and recording findings may have caused bias in follow back studies Although cohort and conscript studies are prospective and the data reliable they can never provide very detailed information because thousands of individuals are typically assessed As the morbidity of schizophrenia in the general population is quite low a study method has been developed to enrich the sample with individuals who later develop schizophrenia This method is called the High Risk HR method High Risk HR research refers to a method of studying the etiology of a disorder by investigating individuals who have an increased risk for developing it Cornblatt and Obuchowski 1997 The most important risk factors for schizophrenia are genetic heritability estimates from the most recent twin studies are as high as 83 Cannon et al 1998 Cardno et al 1999 Because conclusive evidence for any particular environmental factor being a risk factor for schizophrenia has been lacking it has not been possible to identify children with an increased risk of developing schizophrenia because of an exposure to an environmental risk factor and the only feasible method to identify such children has been to investigate those with a positive family history of the disorder HR studies of schizophrenia have typically followed up the offspring of an affected parent s because the risk of developing schizophrenia among such individuals is approximately 10 increasing to almost 50 if both parents are affected compared with 1 risk in