Treatment with Olanzapine is Associated with Modulation of the Default Mode Network in Patients with Schizophrenia

Abstract

Earlier studies have shown widespread alterations of functional connectivity of various brain networks in schizophrenia, including the default mode network (DMN). The DMN has also an important role in the performance of cognitive tasks. Furthermore, treatment with second-generation antipsychotic drugs may ameliorate to some degree working memory (WM) deficits and related brain activity. The aim of this study was to evaluate the effects of treatment with olanzapine monotherapy on functional connectivity among brain regions of the DMN during WM. Seventeen patients underwent an 8-week prospective study and completed two functional magnetic resonance imaging (fMRI) scans at 4 and 8 weeks of treatment during the performance of the N-back WM task. To control for potential repetition effects, 19 healthy controls also underwent two fMRI scans at a similar time interval. We used spatial group-independent component analysis (ICA) to analyze fMRI data. Relative to controls, patients with schizophrenia had reduced connectivity strength within the DMN in posterior cingulate, whereas it was greater in precuneus and inferior parietal lobule. Treatment with olanzapine was associated with increases in DMN connectivity with ventromedial prefrontal cortex, but not in posterior regions of DMN. These results suggest that treatment with olanzapine is associated with the modulation of DMN connectivity in schizophrenia. In addition, our findings suggest critical functional differences in the regions of DMN.

Functional Genetic Variation of the Cannabinoid Receptor 1 and Cannabis Use Interact on Prefrontal Connectivity and Related Working Memory Behavior

“…This analysis generated three correlation coefficients (r 2 ) for every IC, one for each template. Components that scored a higher spatial correlation value with cerebrospinal fluid (r 2 40.05) and with white matter (r 2 40.02) maps and/or a lower spatial correlation value with gray CNR1 gene, cannabis use and working memory M Colizzi et al matter map (r 2 o0.01) were not considered to be meaningful activations in a manner similar to previous studies (Kim et al, 2009;Sambataro et al, 2010). Therefore, seven ICs (IC 1,3,4,5,7,8,14) were excluded from further analysis.…”

A Review of the Functional and Anatomical Default Mode Network in Schizophrenia

“…More compelling evidence about the mediating role of the DMN in antipsychotic medications comes from the work of Sambataro et al [58]. With the hypothesis that olanzapine (an atypical antipsychotic agent) may affect working memory by modulating functional connectivity in the DMN, Sambataro et al examined 19 schizophrenia patients (13 drug-naive and 6 drug-free), and 19 normal controls.…”

“…The olanzapine treatment effect is associated with increased connectivity in ventromedial PFC. Sambataro et al proposed that olanzapine treatment may influence functional connectivity within the DMN via modulating the dopaminergic pathway directly in the pCC/PCUN, or indirectly in the ventromedial PFC [58].…”

“…Second, in view of evidence for the role of genetics in the changed activity and connectivity of the DMN in schizophrenia [25,26], as well as the potential association between DA signaling and DMN modulation [4][5][6]58], the relationship between genetic variation and antipsychotic treatmentrelated regulation of the DMN should be explored further in longitudinal studies with large samples of treatmentnaïve FESPs. Third, the potential influence of environmental factors on the activity and connectivity of the DMN also needs consideration.…”

Mapping the brain correlates of borderline personality disorder: A functional neuroimaging meta-analysis of resting state studies

“…These regions are recruited during autobiographical memory, associative memory, semantic and conceptual knowledge, and spatial information that may be associated with altered "disturbed relatedness" factor as well as with the cognitive alterations of BPD (Ruocco, 2005). Altered engagement of the DMN has been reported not only in BPD (Wolf et al, 2011), but also in depression (Sambataro et al, 2014), bipolar disorders (Martino et al, 2016), and schizophrenia (Sambataro et al, 2010) that are disorders with clinical similarities with BPD.…”