Short-term Effects of Antipsychotic Treatment on Cerebral Function in Drug-Naive First-Episode Schizophrenia Revealed by “Resting State” Functional Magnetic Resonance Imaging

Lui, Su; Li, Tao; Deng, Wei; Jiang, Lijun; Wu, Qisong; Tang, Hehan; Yue, Qiang; Huang, Xiaoqi; Chan, Raymond C.K.; Collier, David; Meda, Shashwath A.; Pearlson, Godfrey D.; Mechelli, Andrea; Sweeney, John A.; Gong, Qiyong

doi:10.1001/archgenpsychiatry.2010.84

Cited by 336 publications

(296 citation statements)

References 65 publications

(71 reference statements)

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“…We tried to address this issue by testing for functional differences in relatives who, by definition, carry higher genetic risk for the disease but are not on antipsychotic medications. Two recent studies (54,90) noted decreased DMN connectivity within MPFC regions in drug-naive SZ patients, and their findings are consistent with our data. One of these studies (90) showed that bilateral prefrontal cortex, parietal, caudate, and superior temporal regions had increased regional connectivity 6 wk after antipsychotic treatment.…”

Section: Ica Derived Dmnssupporting

confidence: 93%

“…Ceramides (composed of sphingosines and fatty acids) regulate cellular differentiation, proliferation, and apoptosis. Recent research implicates abnormal sphingolipid metabolism through alterations in peripheral ceramide levels in first-episode SZ (90), and abnormal plasma ceramide levels are reported in affective disorders, mild cognitive impairment, and memory disturbances (87,91 Fig. 4.…”

Section: Ica Derived Dmnsmentioning

confidence: 99%

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Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia

Meda

Ruaño

Windemuth

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The brain's default mode network (DMN) is highly heritable and is compromised in a variety of psychiatric disorders. However, genetic control over the DMN in schizophrenia (SZ) and psychotic bipolar disorder (PBP) is largely unknown. Study subjects (n = 1,305) underwent a resting-state functional MRI scan and were analyzed by a two-stage approach. The initial analysis used independent component analysis (ICA) in 324 healthy controls, 296 SZ probands, 300 PBP probands, 179 unaffected first-degree relatives of SZ probands (SZREL), and 206 unaffected first-degree relatives of PBP probands to identify DMNs and to test their biomarker and/ or endophenotype status. A subset of controls and probands (n = 549) then was subjected to a parallel ICA (para-ICA) to identify imaging-genetic relationships. ICA identified three DMNs. Hypoconnectivity was observed in both patient groups in all DMNs. Similar patterns observed in SZREL were restricted to only one network. DMN connectivity also correlated with several symptom measures. Para-ICA identified five sub-DMNs that were significantly associated with five different genetic networks. Several top-ranking SNPs across these networks belonged to previously identified, well-known psychosis/mood disorder genes. Global enrichment analyses revealed processes including NMDA-related long-term potentiation, PKA, immune response signaling, axon guidance, and synaptogenesis that significantly influenced DMN modulation in psychoses. In summary, we observed both unique and shared impairments in functional connectivity across the SZ and PBP cohorts; these impairments were selectively familial only for SZREL. Genes regulating specific neurodevelopment/transmission processes primarily mediated DMN disconnectivity. The study thus identifies biological pathways related to a widely researched quantitative trait that might suggest novel, targeted drug treatments for these diseases.genetics | BSNIP | architecture | molecular S chizophrenia (SZ) and psychotic bipolar disorder (PBP) are common, serious, heritable, genetically complex illnesses, sharing multiple characteristics, including risk genes and abnormalities in cognition, neural function, and brain structure (1-4). However, despite recent advances, their underlying biological mechanisms are largely undetermined and may be shared across the two diagnostic groups. Recent large-scale analyses have used various statistical informatics strategies to dissect these biological underpinnings better (5, 6). A recent study using a pathwayenrichment strategy showed that genes involved in neuronal cell adhesion, synaptic formation, and cell signaling are overrepresented in SZ and bipolar disorder (BP) (6). Another study using an informatics-based approach identified several cohesive genetic networks related to axon guidance, neuronal cell mobility, and synaptic functioning as key players in schizophrenia (5).Although risk for psychotic illnesses is driven in small part by highly penetrant, often private mutations such as copy number variants, substantial...

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Section: Ica Derived Dmnssupporting

confidence: 93%

Section: Ica Derived Dmnsmentioning

confidence: 99%

Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia

Meda

Ruaño

Windemuth

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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209

158

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“…In addition, higher LFO magnitudes in the precuneus node of the DMN are associated with stronger negative connectivity between DMN and task-positive networks (Di et al, 2013). Schizophrenia-related LFO alterations reported in the literature (He et al, 2013;Hoptman et al, 2010;Huang et al, 2010;Lui et al, 2010;Turner et al, 2013;Yu et al, 2013Yu et al, , 2014, as well as findings from our study linking lower LFO regional magnitudes to poorer cognitive task performance, may therefore reflect dysfunction of an important mechanism for gating functional neural connectivity. This speculation is consistent with conceptual accounts of schizophrenia as a disease predominantly of network dysconnectivity (Andreasen, 1999;Friston, 1998).…”

Section: Discussionsupporting

confidence: 68%

“…Measures of LFO amplitude have received relatively little attention in the schizophrenia literature, despite demonstration of regionally specific LFO differences between schizophrenia patients and healthy controls (He et al, 2013;Hoptman et al, 2010;Huang et al, 2010;Lui et al, 2010;Turner et al, 2013;Yu et al, 2013Yu et al, , 2014. A large sample study from the multi-site fMRI Biomedical Informatics Network (FBIRN) (Turner et al, 2013) reported widespread regions of decreased fractional ALFF (fALFF) in schizophrenia, including posterior cortex.…”

Section: Introductionmentioning

confidence: 99%

Relating Intrinsic Low-Frequency BOLD Cortical Oscillations to Cognition in Schizophrenia

Fryer

Roach

Ford

et al. 2015

Neuropsychopharmacol

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The amplitude of low-frequency fluctuations (ALFF) in the blood oxygenation level-dependent (BOLD) signal during resting-state fMRI reflects the magnitude of local low-frequency BOLD oscillations, rather than interregional connectivity. ALFF is of interest to studies of cognition because fluctuations in spontaneous intrinsic brain activity relate to, and possibly even constrain, task-evoked brain responses in healthy people. Lower ALFF has been reported in schizophrenia, but the cognitive correlates of these reductions remain unknown. Here, we assess relationships between ALFF and attention and working memory in order to establish the functional relevance of intrinsic BOLD oscillatory power alterations with respect to specific cognitive impairments in schizophrenia. As part of the multisite FBIRN study, restingstate fMRI data were collected from schizophrenia subjects (SZ; n = 168) and healthy controls (HC; n = 166). Voxelwise fractional ALFF (fALFF), a normalized ALFF measure, was regressed on neuropsychological measures of sustained attention and working memory in SZ and HC to identify regions showing either common slopes across groups or slope differences between groups (all findings po0.01 height, po0.05 family-wise error cluster corrected). Poorer sustained attention was associated with smaller fALFF in the left superior frontal cortex and bilateral temporoparietal junction in both groups, with additional relationships in bilateral posterior parietal, posterior cingulate, dorsal anterior cingulate (ACC), and right dorsolateral prefrontal cortex (DLPFC) evident only in SZ. Poorer working memory was associated with smaller fALFF in bilateral ACC/mPFC, DLPFC, and posterior parietal cortex in both groups. Our findings indicate that smaller amplitudes of low-frequency BOLD oscillations during rest, measured by fALFF, were significantly associated with poorer cognitive performance, sometimes similarly in both groups and sometimes only in SZ, in regions known to subserve sustained attention and working memory. Taken together, these data suggest that the magnitude of resting-state BOLD oscillations shows promise as a biomarker of cognitive function in health and disease.

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“…Dopamine receptor antagonist has been shown to reduce global and local network efficiency in healthy adult brains (Achard and Bullmore, 2007). After short-term antipsychotic treatment, first-episode schizophrenia patients showed decreased functional connectivity across brain regions compared with pretreatment (Lui et al, 2010). However, the patient groups in our study showed increased connectivity compared with healthy controls.…”

Section: Discussionmentioning

confidence: 45%

Abnormal Medial Prefrontal Cortex Resting-State Connectivity in Bipolar Disorder and Schizophrenia

Chai

Whitfield-Gabrieli

Shinn

et al. 2011

Neuropsychopharmacol

283

202

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Bipolar disorder and schizophrenia overlap in symptoms and may share some underlying neural substrates. The medial prefrontal cortex (MPFC) may have a crucial role in the psychophysiology of both these disorders. In this study, we examined the functional connectivity between MPFC and other brain regions in bipolar disorder and schizophrenia using resting-state functional magnetic resonance imaging (fMRI). Resting-state fMRI data were collected from 14 patients with bipolar disorder, 16 patients with schizophrenia, and 15 healthy control subjects. Functional connectivity maps from the MPFC were computed for each subject and compared across the three groups. The three groups showed distinctive patterns of functional connectivity between MPFC and anterior insula, and between MPFC and ventral lateral prefrontal cortex (VLPFC). The bipolar disorder group exhibited positive correlations between MPFC and insula, and between MPFC and VLPFC, whereas the control group exhibited anticorrelations between these regions. The schizophrenia group did not exhibit any resting-state correlation or anticorrelation between the MPFC and the VLPFC or insula. In contrast, neither patient group exhibited the significant anticorrelation between dorsal lateral prefrontal cortex (DLPFC) and MPFC that was exhibited by the control group. The decoupling of DLPFC with MPFC in bipolar disorder and schizophrenia is consistent with the impaired executive functioning seen in these disorders. Functional connectivity between MPFC and insula/VLPFC distinguished bipolar disorder from schizophrenia, and may reflect differences in the affective disturbances typical of each illness.

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Short-term Effects of Antipsychotic Treatment on Cerebral Function in Drug-Naive First-Episode Schizophrenia Revealed by “Resting State” Functional Magnetic Resonance Imaging

Cited by 336 publications

References 65 publications

Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia

Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia

Relating Intrinsic Low-Frequency BOLD Cortical Oscillations to Cognition in Schizophrenia

Abnormal Medial Prefrontal Cortex Resting-State Connectivity in Bipolar Disorder and Schizophrenia

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