TY - JOUR
T1 - The impact of psychosis genome-wide associated ZNF804A variation on verbal fluency connectivity
AU - Tecelão, Diogo
AU - Mendes, Ana
AU - Martins, Daniel
AU - Bramon, Elvira
AU - Toulopoulou, Timothea
AU - Kravariti, Eugenia
AU - Murray, Robin
AU - Prata, Diana
PY - 2017/12/9
Y1 - 2017/12/9
N2 - Schizophrenia (SCZ) and bipolar disorder (BD) have high heritability. Genome-wide association studies (GWAS) have identified ZNF804A as a significant risk gene for both illnesses. A validation of this finding at the brain systems-level is imperative as there is still little understanding of how it heightens risk. Based in part on our recent findings of an effect on widespread decreased white matter microstructural fractional anisotropy (putatively a proxy of its integrity), particularly strong in SCZ, we asked whether the risk allele has a detrimental effect on regional brain activation and functional connectivity during a type of cognitive processing which is, together with its neural correlates, impaired in BD and SCZ: verbal fluency. Functional MRI and genotype data was collected from 80 healthy volunteers, and 54 SCZ and 40 BD patients. A standard multifactorial analysis of variance using statistical parametric mapping and significance correction of FWE p < 0.05 was used. We found the GWAS risk allele A was associated with decreased positive functional coupling between the left precentral gyrus/inferior frontal gyrus (i.e. the most highly recruited area for the task) and: 1) the left inferior frontal gyrus, and 2) the left posterior cingulate gyrus, encompassing the precuneus; both as a main effect across controls and psychosis patients. Such association of the risk allele with reduced functional connectivity (with no area where the opposite main effect was detected), converges with findings in other tasks, our previous finding of its widespread impact on brain white matter microstructure, and with the dysconnectivity hypothesis of SCZ.
AB - Schizophrenia (SCZ) and bipolar disorder (BD) have high heritability. Genome-wide association studies (GWAS) have identified ZNF804A as a significant risk gene for both illnesses. A validation of this finding at the brain systems-level is imperative as there is still little understanding of how it heightens risk. Based in part on our recent findings of an effect on widespread decreased white matter microstructural fractional anisotropy (putatively a proxy of its integrity), particularly strong in SCZ, we asked whether the risk allele has a detrimental effect on regional brain activation and functional connectivity during a type of cognitive processing which is, together with its neural correlates, impaired in BD and SCZ: verbal fluency. Functional MRI and genotype data was collected from 80 healthy volunteers, and 54 SCZ and 40 BD patients. A standard multifactorial analysis of variance using statistical parametric mapping and significance correction of FWE p < 0.05 was used. We found the GWAS risk allele A was associated with decreased positive functional coupling between the left precentral gyrus/inferior frontal gyrus (i.e. the most highly recruited area for the task) and: 1) the left inferior frontal gyrus, and 2) the left posterior cingulate gyrus, encompassing the precuneus; both as a main effect across controls and psychosis patients. Such association of the risk allele with reduced functional connectivity (with no area where the opposite main effect was detected), converges with findings in other tasks, our previous finding of its widespread impact on brain white matter microstructure, and with the dysconnectivity hypothesis of SCZ.
KW - Neuroimaging genetics
KW - Schizophrenia
KW - Bipolar disorder
KW - Psychosis
KW - Genome-wide association
KW - ZNF804A
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85038002790&origin=inward&txGid=34ed5eff40aaf2b013dec4d7a329f4b5
U2 - 10.1016/j.jpsychires.2017.12.005
DO - 10.1016/j.jpsychires.2017.12.005
M3 - Article
SN - 0022-3956
VL - 98
SP - 17
EP - 21
JO - Journal of psychiatric research
JF - Journal of psychiatric research
ER -