TY - JOUR
T1 - Functional neuroimaging and schizophrenia
T2 - A view towards effective connectivity modeling and polygenic risk
AU - Birnbaum, Rebecca
AU - Weinberger, Daniel R.
PY - 2013/9
Y1 - 2013/9
N2 - We review critical trends in imaging genetics as applied to schizophrenia research, and then discuss some future directions of the field. A plethora of imaging genetics studies have investigated the impact of genetic variation on brain function, since the paradigm of a neuroimaging intermediate phenotype for schizophrenia first emerged. It was initially posited that the effects of schizophrenia susceptibility genes would be more penetrant at the level of biologically based neuroimaging intermediate phenotypes than at the level of a complex and phenotypically heterogeneous psychiatric syndrome. The results of many studies support this assumption, most of which show single genetic variants to be associated with changes in activity of localized brain regions, as determined by select cognitive controlled tasks. From these basic studies, functional neuroimaging analysis of intermediate phenotypes has progressed to more complex and realistic models of brain dysfunction, incorporating models of functional and effective connectivity, including the modalities of psycho-physiological interaction, dynamic causal modeling, and graph theory metrics. The genetic association approaches applied to imaging genetics have also progressed to more sophisticated multivariate effects, including incorporation of two-way and three-way epistatic interactions, and most recently polygenic risk models. Imaging genetics is a unique and powerful strategy for understanding the neural mechanisms of genetic risk for complex CNS disorders at the human brain level.
AB - We review critical trends in imaging genetics as applied to schizophrenia research, and then discuss some future directions of the field. A plethora of imaging genetics studies have investigated the impact of genetic variation on brain function, since the paradigm of a neuroimaging intermediate phenotype for schizophrenia first emerged. It was initially posited that the effects of schizophrenia susceptibility genes would be more penetrant at the level of biologically based neuroimaging intermediate phenotypes than at the level of a complex and phenotypically heterogeneous psychiatric syndrome. The results of many studies support this assumption, most of which show single genetic variants to be associated with changes in activity of localized brain regions, as determined by select cognitive controlled tasks. From these basic studies, functional neuroimaging analysis of intermediate phenotypes has progressed to more complex and realistic models of brain dysfunction, incorporating models of functional and effective connectivity, including the modalities of psycho-physiological interaction, dynamic causal modeling, and graph theory metrics. The genetic association approaches applied to imaging genetics have also progressed to more sophisticated multivariate effects, including incorporation of two-way and three-way epistatic interactions, and most recently polygenic risk models. Imaging genetics is a unique and powerful strategy for understanding the neural mechanisms of genetic risk for complex CNS disorders at the human brain level.
KW - Effective connectivity
KW - Functional connectivity
KW - Functional neuroimaging
KW - Intermediate phenotype
KW - Polygenic risk score
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=84888021526&partnerID=8YFLogxK
U2 - 10.31887/dcns.2013.15.3/rbirnbaum
DO - 10.31887/dcns.2013.15.3/rbirnbaum
M3 - Article
C2 - 24174900
AN - SCOPUS:84888021526
SN - 1294-8322
VL - 15
SP - 279
EP - 289
JO - Dialogues in Clinical Neuroscience
JF - Dialogues in Clinical Neuroscience
IS - 3
ER -