Failure of deactivation in the default mode network: a trait marker for schizophrenia?

TLDR: Both schizophrenic patients and their relatives show altered task-related deactivation in the medial frontal cortex, which suggests that default mode network dysfunction may function as a trait marker for schizophrenia.

Abstract: Background. Functional imaging studies in relatives of schizophrenic patients have had inconsistent findings, particu-larly with respect to altered dorsolateral prefrontal cortex activation. Some recent studies have also suggested that failureof deactivation may be seen.Method. A total of 28 patients with schizophrenia, 28 of their siblings and 56 healthy controls underwent functionalmagnetic resonance imaging during performance of the n-back working memory task. An analysis of variance wasfitted to individual whole-brain maps from each set of patient–relative–matched pair of controls. Clusters of significantdifference among the groups were then used as regions of interest to compare mean activations and deactivations amongthe groups.Results. In all, five clusters of significant differences were found. The schizophrenic patients, but not the relatives,showed reduced activation compared with the controls in the lateral frontal cortex bilaterally, the left basal gangliaand the cerebellum. In contrast, both the patients and the relatives showed significant failure of deactivation comparedwith the healthy controls in the medialfrontal cortex, with the relatives also showing less failure than the patients. Failureof deactivation was not associated with schizotypy scores or presence of psychotic-like experiences in the relatives.Conclusions. Both schizophrenic patients and their relatives show altered task-related deactivation in the medial frontalcortex. This in turn suggests that default mode network dysfunction may function as a trait marker for schizophrenia.Received 29 April 2013; Revised 4 September 2014; Accepted 9 September 2014Key words: Default mode network, endophenotype, fMRI, schizophrenia, working memory.