Anatomical and Functional Brain Abnormalities in Drug-Naive First-Episode Schizophrenia

Ren, Wei; Lui, Su; Deng, Wei; Li, Fēi; Li, Mingli; Huang, Xiaoqi; Wang, Yuqing; Li, Tao; Sweeney, John A.; Gong, Qiyong

doi:10.1176/appi.ajp.2013.12091148

Cited by 137 publications

(109 citation statements)

References 50 publications

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“…[4][5][6][7][8][9][10]44,45 Part of the importance of the present investigation is that it shows that frontal functional connectivity changes involving the inferior frontal gyrus are present in FE, antipsychoticnaive patients. A recent review 2 of functional connectivity changes in schizophrenia involved typically much smaller sample sizes than those reported here, and reported typically altered functional connectivity in patients sometimes involving the frontal lobe, but without much emphasis on the thalamus, and with no marked stage-specific differences in functional connectivity.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Zhang

et al. 2016

SCHBUL

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130

129

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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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Section: Discussionmentioning

confidence: 99%

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

Wang

Zhang

et al. 2016

SCHBUL

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130

129

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“…Ren et al, (2013) reported group differences in gray matter volume mainly in thalamo-cortical networks, while alterations in the amplitude of low-frequency fluctuations were observed in fronto-parietal and default mode networks. In contrast, using voxel-based morphometry and rs-fMRI Lui et al, (2009) reported no rs-fMRI connectivity abnormalities within brain regions with less gray matter in patients compared with healthy volunteers, including the superior temporal gyrus, middle temporal gyrus, and anterior cingulate gyrus.…”

Section: Introductionmentioning

confidence: 97%

“…The use of different methods may contribute to inconsistent findings, and thus studies incorporating multiple approaches for rs-fMRI data analysis may shed light on abnormal circuits in the neurobiology of psychosis. Moreover, given that antipsychotics may potentially influence rs-fMRI measures (Lui et al, 2010), studies conducted early in the course of illness prior to extensive pharmacological intervention are of critical importance to the field, but findings have thus far been inconsistent (eg, Guo et al, 2014a,b;He et al, 2013;Lui et al, 2009Lui et al, , 2010Ren et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Abnormal Resting State fMRI Activity Predicts Processing Speed Deficits in First-Episode Psychosis

Gallego

Robinson

Ikuta

et al. 2015

Neuropsychopharmacol

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Little is known regarding the neuropsychological significance of resting state functional magnetic resonance imaging (rs-fMRI) activity early in the course of psychosis. Moreover, no studies have used different approaches for analysis of rs-fMRI activity and examined gray matter thickness in the same cohort. In this study, 41 patients experiencing a first-episode of psychosis (including N ¼ 17 who were antipsychotic drug-naive at the time of scanning) and 41 individually age-and sex-matched healthy volunteers completed rs-fMRI and structural MRI exams and neuropsychological assessments. We computed correlation matrices for 266 regions-of-interest across the brain to assess global connectivity. In addition, independent component analysis (ICA) was used to assess group differences in the expression of rs-fMRI activity within 20 predefined publicly available templates. Patients demonstrated lower overall rs-fMRI global connectivity compared with healthy volunteers without associated group differences in gray matter thickness assessed within the same regions-of-interest used in this analysis. Similarly, ICA revealed worse rs-fMRI expression scores across all 20 networks in patients compared with healthy volunteers, with posthoc analyses revealing significant (po0.05; corrected) abnormalities within the caudate nucleus and planum temporale. Worse processing speed correlated significantly with overall lower global connectivity using the region-of-interest approach and lower expression scores within the planum temporale using ICA. Our findings implicate dysfunction in rs-fMRI activity in first-episode psychosis prior to extensive antipsychotic treatment using different analytic approaches (in the absence of concomitant gray matter structural differences) that predict processing speed.

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“…23 Third, these hormones both regulate physiological activity in brain regions that have established functional and structural alterations in the disorder. [24][25][26][27][28] OT receptor concentrations are highest within the hippocampus, septum, and amygdala 29 and the highest level of brain AVP 1b receptor expression is in the hippocampus, 30 which is an important brain structure for memory 31 and is abnormal in schizophrenia. 25,32 In preclinical models, haploinsufficient reeler mice, an animal model of neural deficits in schizophrenia, show reductions in OT receptors especially in the hippocampus and piriform cortex.…”

Section: Introductionmentioning

confidence: 99%

Reduced Levels of Vasopressin and Reduced Behavioral Modulation of Oxytocin in Psychotic Disorders

Rubin

Carter

Bishop

et al. 2014

Schizophrenia Bulletin

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Oxytocin (OT) and arginine vasopressin (AVP) exert robust influence on social affiliation and specific cognitive processes in healthy individuals. Abnormalities in these neuroendocrine systems have been observed in psychotic disorders, but their relation to impairments in behavioral domains that these endocrines modulate is not well understood. We compared abnormalities of OT and AVP serum concentrations in probands with schizophrenia (n = 57), schizoaffective disorder (n = 34), and psychotic bipolar disorder (n = 75); their first-degree relatives without a history of psychosis (n = 61, 43, 91, respectively); and healthy controls (n = 66) and examined their association with emotion processing and cognition. AVP levels were lower in schizophrenia (P = .002) and bipolar probands (P = .03) and in relatives of schizophrenia probands (P = .002) compared with controls. OT levels did not differ between groups. Familiality estimates were robust for OT (h 2 = 0.79, P = 3.97e−15) and AVP (h 2 = 0.78, P = 3.93e−11). Higher levels of OT were associated with better emotion recognition (β = 0.40, P < .001) and general neuropsychological function (β = 0.26, P = .04) in healthy controls as expected but not in any proband or relative group. In schizophrenia, higher OT levels were related to greater positive symptom severity. The dissociation of OT levels and behavioral function in all proband and relative groups suggests that risk and illness factors associated with psychotic disorders are not related to reduced OT levels but to a disruption in the ability of physiological levels of OT to modulate social cognition and neuropsychological function. Decreased AVP levels may be a marker of biological vulnerability in schizophrenia because alterations were seen in probands and relatives, and familiality was high.

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Anatomical and Functional Brain Abnormalities in Drug-Naive First-Episode Schizophrenia

Cited by 137 publications

References 50 publications

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

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

Abnormal Resting State fMRI Activity Predicts Processing Speed Deficits in First-Episode Psychosis

Reduced Levels of Vasopressin and Reduced Behavioral Modulation of Oxytocin in Psychotic Disorders

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