Task and resting-state fMRI studies in first-episode schizophrenia: A systematic review

Mwansisya, Tumbwene E.; Hu, Aimin; Li, Yihui; Chen, Xudong; Wu, Guowei; Huang, Xiaojun; Lv, Dongsheng; Zhou, Li; Liu, Chang; Zhang, Xue; Feng, Jianfeng; Liu, Zhening

doi:10.1016/j.schres.2017.02.026

Cited by 111 publications

(79 citation statements)

References 88 publications

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“…Despite several decades of extensive research, it has been challenging to define the key molecular pathways and corresponding etiologies of these diseases. During the last two decades, the use of advanced imaging techniques such as functional magnetic resonance imaging (fMRI), gamma synchrony, and mapping of scalp electrical activity have helped to identify SCZ and BD endophenotypes, including atrophy of the cingulate gyrus and dorsolateral prefrontal cortex, mainly in the left brain hemisphere (Bangalore et al, 2009;Bleich-Cohen et al, 2012;Cullen et al, 2006;Li et al, 2016;Mahon et al, 2015;Meda et al, 2008;Mwansisya et al, 2017;Narayanaswamy, Kalmady, Venkatasubramanian, & Gangadhar, 2015;Prasad & Keshavan, 2008;Rockstroh et al, 1998;Venkatasubramanian, Jayakumar, Gangadhar, & Keshavan, 2008a, 2008bWalter et al, 2003;Weiss et al, 2004;Williams et al, 2009). In fact, the loss or reversal of brain asymmetry/laterality is one of the most consistent observations that have eluded an understanding in neurodevelopmental diseases like SCZ and BD (Ho et al, 2017;Wang et al, 2014;Williams et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Aberrant transcriptomes and DNA methylomes define pathways that drive pathogenesis and loss of brain laterality/asymmetry in schizophrenia and bipolar disorder

Abdolmaleky

Gower

Wong

et al. 2018

American J of Med Genetics Pt B

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Although the loss of brain laterality is one of the most consistent modalities in schizophrenia (SCZ) and bipolar disorder (BD), its molecular basis remains elusive. Our limited previous studies indicated that epigenetic modifications are key to the asymmetric transcriptomes of brain hemispheres. We used whole-genome expression microarrays to profile postmortem brain samples from subjects with SCZ, psychotic BD [BD[+]] or non-psychotic BD [BD(−)], or matched controls (10/group) and performed whole-genome DNA methylation (DNAM) profiling of the same samples (3-4/group) to identify pathways associated with SCZ or BD[+] and genes/sites susceptible to epigenetic regulation. qRT-PCR and quantitative DNAM analysis were employed to validate findings in larger sample sets (35/group). Gene Set Enrichment Analysis (GSEA) demonstrated that BMP signaling and astrocyte and cerebral cortex development are significantly (FDR q < 0.25) coordinately upregulated in both SCZ and BD[+], and glutamate signaling and TGFβ signaling are significantly coordinately upregulated in SCZ. GSEA also indicated that collagens are downregulated in right versus left brain of controls, but not in SCZ or BD[+] patients. IngenuityPathway Analysis predicted that TGFB2 is an upstream regulator of these genes (p = .0012).While lateralized expression of TGFB2 in controls (p = .017) is associated with a corresponding change in DNAM (p ≤ .023), lateralized expression and DNAM of TGFB2 are absent in SCZ or BD. Loss of brain laterality in SCZ and BD corresponds to aberrant epigenetic regulation of TGFB2 and changes in TGFβ signaling, indicating potential avenues for disease prevention/ treatment. K E Y W O R D Sbrain asymmetry, DNA methylation, NR2E1, schizophrenia, TGFB2

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Section: Introductionmentioning

confidence: 99%

Aberrant transcriptomes and DNA methylomes define pathways that drive pathogenesis and loss of brain laterality/asymmetry in schizophrenia and bipolar disorder

Abdolmaleky

Gower

Wong

et al. 2018

American J of Med Genetics Pt B

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“…Furthermore, human-derived neural cultures have shown elevated, complement-dependent elimination of synaptic structures 25 , lower neurite number and neuronal connectivity 26 and synaptic vesicle release deficits 27 in schizophrenia relative to healthy controls. Further, albeit indirect, evidence for altered synaptic function comes from in vivo neuroimaging studies which show lower brain volumes 28 and altered functional connectivity in schizophrenia relative to controls 29 , which may reflect altered synaptic density and/or function in schizophrenia (although there are other potential explanations for these findings). Thus, there are converging lines of evidence implicating synaptic dysfunction in the pathophysiology of schizophrenia, and specifically for lower levels of synaptic proteins.…”

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confidence: 99%

Synaptic density marker SV2A is reduced in schizophrenia patients and unaffected by antipsychotics in rats

et al. 2020

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Synaptic dysfunction is hypothesised to play a key role in schizophrenia pathogenesis, but this has not been tested directly in vivo. Here, we investigated synaptic vesicle glycoprotein 2A (SV2A) levels and their relationship to symptoms and structural brain measures using [ 11 C]UCB-J positron emission tomography in 18 patients with schizophrenia and 18 controls. We found significant group and group-by-region interaction effects on volume of distribution (V T). [ 11 C]UCB-J V T was significantly lower in the frontal and anterior cingulate cortices in schizophrenia with large effect sizes (Cohen's d = 0.8-0.9), but there was no significant difference in the hippocampus. We also investigated the effects of antipsychotic drug administration on SV2A levels in Sprague-Dawley rats using western blotting, [ 3 H]UCB-J autoradiography and immunostaining with confocal microscopy, finding no significant effects on any measure. These findings indicate that there are lower synaptic terminal protein levels in schizophrenia in vivo and that antipsychotic drug exposure is unlikely to account for them.

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“…What might this mean in terms of our understanding of the neurocognitive mechanisms that may underlie the association between cannabis use and schizophrenia? Impairments in verbal learning and memory have long been associated with schizophrenia (Aleman et al 1999), as well as structural (Nenadic et al 2015) and functional changes (Mwansisya et al 2017) in a number of neural substrates linked to verbal memory (Guimond et al 2016). Abnormal medial temporal function especially during memory tasks is one of the key alterations reported in schizophrenia (Heckers 2001) and onset of psychosis has been linked to alterations in medial temporal structure (Mechelli et al 2011) and function (Allen et al 2017;Allen et al 2016;Allen et al 2012) and abnormal dopamine function in the midbrain.…”

Section: Discussionmentioning

confidence: 99%

Disrupted parahippocampal and midbrain function underlie slower verbal learning in adolescent-onset regular cannabis use

et al. 2019

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Rationale Prolonged use of cannabis, the most widely used illicit drug worldwide, has been consistently associated with impairment in memory and verbal learning. Although the neurophysiological underpinnings of these impairments have been investigated previously using functional magnetic resonance imaging (fMRI), while performing memory tasks, the results of these studies have been inconsistent and no clear picture has emerged yet. Furthermore, no previous studies have investigated trial-by-trial learning. Objectives We aimed to investigate the neural underpinnings of impaired verbal learning in cannabis users as estimated over repeated learning trials. Methods We studied 21 adolescent-onset regular cannabis users and 21 non-users using fMRI performed at least 12 h after last cannabis use, while they performed a paired associate verbal learning task that allowed us to examine trial-by-trial learning. Brain activation during repeated verbal encoding and recall conditions of the task was indexed using the blood oxygen level-dependent haemodynamic response fMRI signal. Results There was a significant improvement in recall score over repeated trials indicating learning occurring across the two groups of participants. However, learning was significantly slower in cannabis users compared to non-users (p = 0.032, partial eta-squared = 0.108). While learning verbal stimuli over repeated encoding blocks, non-users displayed progressive increase in recruitment of the midbrain, parahippocampal gyrus and thalamus (p = 0.00939, partial eta-squared = 0.180). In contrast, cannabis users displayed a greater but disrupted activation pattern in these regions, which showed a stronger correlation with new word-pairs learnt over the same blocks in cannabis users than in non-users. Conclusions These results suggest that disrupted medial temporal and midbrain function underlie slower learning in adolescentonset cannabis users. Keywords Verbal learning. Memory. Cannabis use. fMRI. Midbrain. Parahippocampal gyrus. BOLD This article belongs to a Special Issue on Imaging for CNS drug development and biomarkers.

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Task and resting-state fMRI studies in first-episode schizophrenia: A systematic review

Cited by 111 publications

References 88 publications

Aberrant transcriptomes and DNA methylomes define pathways that drive pathogenesis and loss of brain laterality/asymmetry in schizophrenia and bipolar disorder

Aberrant transcriptomes and DNA methylomes define pathways that drive pathogenesis and loss of brain laterality/asymmetry in schizophrenia and bipolar disorder

Synaptic density marker SV2A is reduced in schizophrenia patients and unaffected by antipsychotics in rats

Disrupted parahippocampal and midbrain function underlie slower verbal learning in adolescent-onset regular cannabis use

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