The New England family study high‐risk project: Neurological impairments among offspring of parents with schizophrenia and other psychoses

Department of Epidemiology, Brown University, Providence, Rhode Island.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics (Impact Factor: 3.42). 10/2013; 162(7):653-60. DOI: 10.1002/ajmg.b.32181
Source: PubMed


This manuscript presents the design and initial outcomes of the New England Family Study's (NEFS) High-Risk Project, one of the few epidemiologically representative cohorts that has prospectively followed a large sample of offspring of parents with both affective and non-affective psychotic disorders from the fetal period forward. The goals of this report are: (1) to describe in some detail the design, data collection methods, and resulting sample of this project; and (2) to prospectively identify and compare rates of childhood neurological impairments among offspring of psychotic and nonpsychotic parents, with a particular emphasis on offspring risk in relation to specific classes of parental psychosis (i.e., affective vs. non-affective psychosis). The investigators identified a pool of 755 parents with potential psychotic disorders, located over 80% of these and confirmed psychotic diagnoses for 212 affected parents and 132 unaffected control parents. At birth, the 259 offspring of parents with psychosis had approximately a twofold increased risk of abnormal neurological functioning compared to offspring of families with no psychotic history. This was most pronounced among the 58 offspring of parents with schizophrenia. Similar trends were observed at ages 1 and 7 years although these did not reach statistical significance. Neither at birth nor at any of the follow-up assessments were the 157 offspring of parents with affective psychosis found to be at elevated risk of neurological impairment. Implications for future research and potential preventive interventions for at-risk individuals are discussed. © 2013 Wiley Periodicals, Inc.

14 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Identifying early developmental indicators of risk for schizophrenia is important for prediction and possibly illness prevention. Disturbed intermodality has been proposed as one important neurodevelopmental risk for schizophrenia. Early intermodal integration (EII) is the infant's ability to link motility and perception and to relate perception across modalities. We hypothesized that infants of parents with schizophrenia would have more EII abnormalities than infants of healthy parents and that infants of parents with affective psychosis would be intermediate in severity. The New England Family Study high-risk sample, ascertained from community populations, was utilized. Eight-month-old infants of parents with schizophrenia (n = 58), affective psychoses (n = 128), and healthy controls (n = 174) were prospectively assessed. Diagnoses of parents were determined 30 years later blind to offspring data. EII measures were grouped into 3 domains characterizing different aspects of infant development: (1) one's own body, (2) objects, and (3) social interactions. Results demonstrated that body- and object-related EII abnormalities were significantly increased for infants of parents with schizophrenia compared with control infants and not significantly increased for infants of parents with affective psychoses. EII abnormalities in relation to social interactions were significantly increased in infants of parents with schizophrenia and affective psychoses. Thus, body- and object-related EII abnormalities were most severe in infants of parents with schizophrenia, supporting the importance of intermodality dysfunction as an early indicator of the vulnerability to schizophrenia. Future research should evaluate how this dysfunction evolves with development and its associations with other psychopathological and neurodevelopmental deficits in youth at risk for psychosis.
    Schizophrenia Bulletin 08/2013; 40(5). DOI:10.1093/schbul/sbt111 · 8.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The 22q11.2 deletion syndrome (22q11DS) presents with medical and neuropsychiatric manifestations including neurocognitive deficits. Quantitative neurobehavioral measures linked to brain circuitry can help elucidate genetic mechanisms contributing to deficits. To establish the neurocognitive profile and neurocognitive 'growth charts', we compared cross-sectionally 137 individuals with 22q11DS ages 8-21 to 439 demographically matched non-deleted individuals with developmental delay (DD) and medical comorbidities and 443 typically developing (TD) participants. We administered a computerized neurocognitive battery that measures performance accuracy and speed in executive, episodic memory, complex cognition, social cognition and sensorimotor domains. The accuracy performance profile of 22q11DS showed greater impairment than DD, who were impaired relative to TD. Deficits in 22q11DS were most pronounced for face memory and social cognition, followed by complex cognition. Performance speed was similar for 22q11DS and DD, but 22q11DS individuals were differentially slower in face memory and emotion identification. The growth chart, comparing neurocognitive age based on performance relative to chronological age, indicated that 22q11DS participants lagged behind both groups from the earliest age assessed. The lag ranged from less than 1 year to over 3 years depending on chronological age and neurocognitive domain. The greatest developmental lag across the age range was for social cognition and complex cognition, with the smallest for episodic memory and sensorimotor speed, where lags were similar to DD. The results suggest that 22q11.2 microdeletion confers specific vulnerability that may underlie brain circuitry associated with deficits in several neuropsychiatric disorders, and therefore help identify potential targets and developmental epochs optimal for intervention.Molecular Psychiatry advance online publication, 21 January 2014; doi:10.1038/mp.2013.189.
    Molecular Psychiatry 01/2014; 19(11). DOI:10.1038/mp.2013.189 · 14.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Schizophrenia and affective psychoses are debilitating disorders that together affect 2%-3% of the adult population. Approximately 50%-70% of the offspring of parents with schizophrenia manifest a range of observable difficulties including socioemotional, cognitive, neuromotor, speech-language problems, and psychopathology, and roughly 10% will develop psychosis. Despite the voluminous work on premorbid vulnerabilities to psychosis, especially on schizophrenia, the work on premorbid intervention approaches is scarce. While later interventions during the clinical high-risk (CHR) phase of psychosis, characterized primarily by attenuated positive symptoms, are promising, the CHR period is a relatively late phase of developmental derailment. This article reviews and proposes potential targets for psychosocial interventions during the premorbid period, complementing biological interventions described by others in this Special Theme issue. Beginning with pregnancy, parents with psychoses may benefit from enhanced prenatal care, social support, parenting skills, reduction of symptoms, and programs that are family-centered. For children at risk, we propose preemptive early intervention and cognitive remediation. Empirical research is needed to evaluate these interventions for parents and determine whether interventions for parents and children positively influence the developmental course of the offspring. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email:
    Schizophrenia Bulletin 04/2015; 41(4). DOI:10.1093/schbul/sbv047 · 8.45 Impact Factor