Imaging genetic liability to schizophrenia

Systematic review of fMRI studies of patients' nonpsychotic relatives

Angus MacDonald, Heidi W. Thermenos, Deanna M. Barch, Larry J. Seidman

    Research output: Contribution to journalReview article

    103 Citations (Scopus)

    Abstract

    There is a growing literature on brain activity in the nonpsychotic first-degree relatives of patients with schizophrenia as measured using functional imaging. This systematic review examined 20 studies in 4 domains of cognition, including cognitive control (7 samples), working memory (5 samples), long-term memory (4 samples), and language (4 samples). While the literature was widely divergent, these studies did consistently find activation differences between patients' relatives and controls. The most consistent increases in activation within hemisphere were found in right ventral prefrontal cortex (PFC) and right parietal cortex. Abnormal activity, defined as significant increases or decreases in activation relative to controls irrespective of hemisphere, was found in about two-thirds of contrasts in the cerebellum, dorsal prefrontal, lateral temporal, and parietal cortices, and thalamus, with basal ganglia and ventral PFC showing abnormalities in approximately half of those contrasts. Anterior cingulate was generally spared in patients' relatives. The diversity of findings in studies of patients' relatives may derive from differences between the cognitive demands across studies. We identify avenues for building a more accurate and cumulative literature, including symmetrical inclusion criteria for relatives and controls, recording in-scanner responses, using both a priori and whole-brain tests, explicitly reporting threshold values, reporting main effects of task, reporting effect sizes, and quantifying the risk of false negatives. While functional imaging in the relatives of schizophrenia patients remains a promising methodology for understanding the impact of the unexpressed genetic liability to schizophrenia, no single region or mechanism of abnormalities has yet emerged.

    Original languageEnglish (US)
    Pages (from-to)1142-1162
    Number of pages21
    JournalSchizophrenia Bulletin
    Volume35
    Issue number6
    DOIs
    StatePublished - Nov 1 2009

    Fingerprint

    Schizophrenia
    Magnetic Resonance Imaging
    Parietal Lobe
    Prefrontal Cortex
    Long-Term Memory
    Gyrus Cinguli
    Brain
    Temporal Lobe
    Basal Ganglia
    Thalamus
    Short-Term Memory
    Cerebellum
    Cognition
    Language

    Keywords

    • cognitive control
    • fMRI
    • family study
    • language
    • memory
    • neuroimaging
    • relatives
    • review
    • schizophrenia
    • working memory

    Cite this

    Imaging genetic liability to schizophrenia : Systematic review of fMRI studies of patients' nonpsychotic relatives. / MacDonald, Angus; Thermenos, Heidi W.; Barch, Deanna M.; Seidman, Larry J.

    In: Schizophrenia Bulletin, Vol. 35, No. 6, 01.11.2009, p. 1142-1162.

    Research output: Contribution to journalReview article

    MacDonald, Angus ; Thermenos, Heidi W. ; Barch, Deanna M. ; Seidman, Larry J. / Imaging genetic liability to schizophrenia : Systematic review of fMRI studies of patients' nonpsychotic relatives. In: Schizophrenia Bulletin. 2009 ; Vol. 35, No. 6. pp. 1142-1162.
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