Dysconnectivity in schizophrenia: Where are we now?

Pettersson-Yeo, William; Allen, Paul; Benetti, Stefania; McGuire, Philip; Mechelli, Andrea

doi:10.1016/j.neubiorev.2010.11.004

Cited by 633 publications

(506 citation statements)

References 150 publications

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“…Our results are also in line with studies demonstrating altered brain network connectivity under the influence of drugs that induce psychotic symptoms (Diaconescu et al, 2010;Esposito et al, 2013;Pujol et al, 2013) and studies demonstrating altered connectivity in different stages of schizophrenia (Pettersson-Yeo et al, 2011). This may suggest that altered functional connectivity under the influence of delta-9-THC might be a plausible mechanism through which regular cannabis consumption increases the risk of development of schizophrenia.…”

Section: Discussionsupporting

confidence: 91%

Cannabinoid Modulation of Functional Connectivity within Regions Processing Attentional Salience

Bhattacharyya

Falkenberg

Martín‐Santos

et al. 2014

Neuropsychopharmacol

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103

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There is now considerable evidence to support the hypothesis that psychotic symptoms are the result of abnormal salience attribution, and that the attribution of salience is largely mediated through the prefrontal cortex, the striatum, and the hippocampus. Although these areas show differential activation under the influence of delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD), the two major derivatives of cannabis sativa, little is known about the effects of these cannabinoids on the functional connectivity between these regions. We investigated this in healthy occasional cannabis users by employing event-related functional magnetic resonance imaging (fMRI) following oral administration of delta-9-THC, CBD, or a placebo capsule. Employing a seed cluster-based functional connectivity analysis that involved using the average time series from each seed cluster for a whole-brain correlational analysis, we investigated the effect of drug condition on functional connectivity between the seed clusters and the rest of the brain during an oddball salience processing task. Relative to the placebo condition, delta-9-THC and CBD had opposite effects on the functional connectivity between the dorsal striatum, the prefrontal cortex, and the hippocampus. Delta-9-THC reduced fronto-striatal connectivity, which was related to its effect on task performance, whereas this connection was enhanced by CBD. Conversely, mediotemporal-prefrontal connectivity was enhanced by delta-9-THC and reduced by CBD. Our results suggest that the functional integration of brain regions involved in salience processing is differentially modulated by single doses of delta-9-THC and CBD and that this relates to the processing of salient stimuli.

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Section: Discussionsupporting

confidence: 91%

Cannabinoid Modulation of Functional Connectivity within Regions Processing Attentional Salience

Bhattacharyya

Falkenberg

Martín‐Santos

et al. 2014

Neuropsychopharmacol

Self Cite

103

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“…It was first proposed in 19th century highlighting that reduced interactions of brain regions could arise from abnormal axonal connectivity (for a review see [14]). The concept re-emerged with the seminal contribution of Friston and colleagues [15] who re-examined the evidence from the emerging fMRI-literature which indicated reduced functional interactions between brain regions identified through BOLDsignal correlations [16]. Importantly, the authors modified the original term disconnection (''dis'' = ''apart,'') to dysconnectivity to highlight that functional and anatomical connectivity is not generally reduced but may also involve abnormal increases in schizophrenia (dys = bad or ill).…”

Section: Disconnection and Dysconnectivity In Schizophreniamentioning

confidence: 99%

Dysconnectivity, large-scale networks and neuronal dynamics in schizophrenia

Uhlhaas

2013

Current Opinion in Neurobiology

154

143

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“…In a review of investigations that did compare FE and chronic stages of schizophrenia, it was concluded that schizophrenia is associated with dysconnectivity that is particularly evident in the connections involving the frontal lobe, and that this applies across all stages of the disorder. 2 There are additional studies that have focused on the early changes in schizophrenia, including. 6,12,15,[29][30][31][32] Another important factor in the heterogeneity of the findings may be that many studies have focused on functional connectivity between regions specified a priori, rather than adopting a whole-brain analysis.…”

Section: Introductionmentioning

confidence: 99%

Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia

Wang

Zhang

et al. 2016

SCHBUL

132

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Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functionalconnectivity differences in prodromal, FE (mostly drug naïve), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients). Brain-wide functional-connectivity analysis was performed in different datasets and the results from the datasets of the same stage were then integrated by meta-analysis, with Bonferroni correction for multiple comparisons. Prodromal patients differed from controls in their pattern of functionalconnectivity involving the inferior frontal gyri (Broca's area). In FE patients, 90% of the functional-connectivity changes involved the frontal lobes, mostly the inferior frontal gyrus including Broca's area, and these changes were correlated with delusions/blunted affect. For chronic patients, functionalconnectivity differences extended to wider areas of the brain, including reduced thalamo-frontal connectivity, and increased thalamo-temporal and thalamo-sensorimoter connectivity that were correlated with the positive, negative, and general symptoms, respectively. Thalamic changes became prominent at the chronic stage. These results provide evidence for distinct patterns of functional-dysconnectivity across FE and chronic stages of schizophrenia. Importantly, abnormalities in the frontal language networks appear early, at the time of disease onset. The identification of stage-specific pathological processes may help to understand the disease course of schizophrenia and identify neurobiological markers crucial for early diagnosis.

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Dysconnectivity in schizophrenia: Where are we now?

Cited by 633 publications

References 150 publications

Cannabinoid Modulation of Functional Connectivity within Regions Processing Attentional Salience

Cannabinoid Modulation of Functional Connectivity within Regions Processing Attentional Salience

Dysconnectivity, large-scale networks and neuronal dynamics in schizophrenia

Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia

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