Clinical, Cognitive, and Neuroimaging Evidence of a Neurodevelopmental Continuum in Offspring of Probands With Schizophrenia and Bipolar Disorder.
Studies in child and adolescent offspring of patients with schizophrenia or bipolar disorders may help understand the influence of neurodevelopmental factors on the premorbid phenotype of these disorders.



To assess whether a combination of neurodevelopmental factors discriminates between young offspring of patients with schizophrenia (SzO) or bipolar disorder (BpO) and community controls (CcO). To assess the association between these factors and rates of psychiatric diagnoses in high risk (HR) youth.



One hundred thirty-three HR offspring (47 SzO and 86 BpO) and 84 CcO, aged 6-17, underwent cross-sectional clinical, neurocognitive, and structural neuroimaging assessment. Information on perinatal events and early childhood development was also obtained. General linear mixed models were performed to assess group discrimination and association with lifetime axis I psychiatric disorders.



Multivariate analyses revealed that greater neurological soft signs (NSS), less total grey matter volume (GMV) and a higher frequency of obstetric complications discriminated HR offspring from CcO. When comparing each group individually, greater NSS and a higher frequency of obstetric complications discriminated SzO from CcO, and BpO from CcO, while lower intelligence also discriminated SzO from CcO and from BpO. Within HR offspring, lower intelligence and less total GMV were associated with lifetime incidence of psychiatric disorders.



Both SzO and BpO showed evidence of neurodevelopmental insult, although this may have a greater impact in SzO. Lower intelligence and less total GMV hold potential as biomarkers of risk for psychiatric disorders in HR youth.
Department of Child and Adolescent Psychiatry and Psychology, 2014SGR489, Institut Clinic de Neurociències, Hospital Clínic i Provincial, Barcelona, Spain.|Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
Gisela
G
Sugranyes
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
Elena
E
de la Serna
Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Roger
R
Borras
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.|Early Intervention Team, Pere Mata Institute of Reus, Health Research Institute Pere Virgili (IISPV), Reus, Spain.
Vanessa
V
Sanchez-Gistau
Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Jose C
JC
Pariente
Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
Soledad
S
Romero
Department of Child and Adolescent Psychiatry and Psychology, 2014SGR489, Institut Clinic de Neurociències, Hospital Clínic i Provincial, Barcelona, Spain.|Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
Inmaculada
I
Baeza
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.|Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain.
Covadonga M
CM
Díaz-Caneja
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.|Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain.
Elisa
E
Rodriguez-Toscano
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.|Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain.
Carmen
C
Moreno
Department of Child and Adolescent Psychiatry and Psychology, 2014SGR489, Institut Clinic de Neurociències, Hospital Clínic i Provincial, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.|Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain.|Department of Psychiatry and Psychology, Hospital Clinic, Barcelona, Spain.
Miguel
M
Bernardo
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.|Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain.
Dolores
D
Moreno
Department of Child and Adolescent Psychiatry and Psychology, 2014SGR489, Institut Clinic de Neurociències, Hospital Clínic i Provincial, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.|Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain.|Department of Psychiatry and Psychology, Hospital Clinic, Barcelona, Spain.
Eduard
E
Vieta
Department of Child and Adolescent Psychiatry and Psychology, 2014SGR489, Institut Clinic de Neurociències, Hospital Clínic i Provincial, Barcelona, Spain.|Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.|Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain.
Josefina
J
Castro-Fornieles
D000293:Adolescent; D001714:Bipolar Disorder / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology; D002648:Child; D016241:Child of Impaired Parents / Q000706:statistics & numerical data; D003430:Cross-Sectional Studies; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D007360:Intelligence / Q000502:physiology*; D008297:Male; D059906:Neuroimaging; D007744:Obstetric Labor Complications / Q000453:epidemiology; D011247:Pregnancy; D012559:Schizophrenia / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology
bipolar disorder; neurodevelopmental disorders; neuroimaging; relatives; schizophrenia