• DOI:10.1093/schbul/sbx001
• Corpus ID: 24459302

Altered DLPFC–Hippocampus Connectivity During Working Memory: Independent Replication and Disorder Specificity of a Putative Genetic Risk Phenotype for Schizophrenia

@article{Schneider2017AlteredDC,
  title={Altered DLPFC–Hippocampus Connectivity During Working Memory: Independent Replication and Disorder Specificity of a Putative Genetic Risk Phenotype for Schizophrenia},
  author={Michael Schneider and Henrik Walter and Carolin Moessnang and Axel Sch{\"a}fer and Susanne Erk and Sebastian Mohnke and Lydia Romund and Maria Garbusow and Luanna Dixson and Andreas Heinz and Nina Romanczuk-Seiferth and Andreas Meyer-Lindenberg and Heike Tost},
  journal={Schizophrenia Bulletin},
  year={2017},
  volume={43},
  pages={1114–1122}
}

• Michael Schneider, H. Walter, +10 authors H. Tost
• Published 1 September 2017
• Psychology, Biology, Medicine
• Schizophrenia Bulletin

Altered connectivity of dorsolateral prefrontal cortex (DLPFC) and hippocampus during working memory is considered an intermediate phenotype for schizophrenia (SCZ), but the relevance for other mental disorders with shared genetic background remains unknown. Here we investigated its presence in unaffected first-degree relatives of patients with bipolar disorder (BD) or major depressive disorder (MDD). Furthermore, we aimed to provide an independent replication of this phenotype in first-degree relatives of SCZ patients. We acquired functional magnetic resonance imaging (fMRI) data from 309 healthy controls and 218 healthy first-degree relatives of index patients with SCZ (n = 62), BD (n = 66) and MDD (n = 90), who completed the n-back working memory paradigm. We observed a significant group effect on DLPFC-hippocampus coupling (PFWE = .031, all P-values region of interest [ROI] corrected). Post hoc comparisons revealed that this effect was driven by the SCZ relatives, who showed a significant increase in the negative functional connectivity of the DLPFC and right hippocampus compared to controls (PFWE = .001), BD relatives (PFWE = .015) and trend-wise also MDD relatives (PFWE = .082). Comparison of BD and MDD relatives to the controls revealed no difference (PFWE-values > .451). Supplementary analyses suggested that the SCZ relatives finding is robust to a range of potential confounds, including structural differences. Our data further support altered DLPFC-hippocampus connectivity during working memory as an intermediate phenotype for SCZ. This suggests that this phenotype is relatively specific to SCZ and does not translate to other genetically related disorders in the mood-psychosis spectrum.