Shared intermediate phenotypes for schizophrenia and bipolar disorder: neuroanatomical features of subtypes distinguished by executive dysfunction

Shepherd, Alana M.; Quidé, Yann; Laurens, Kristin R.; O’Reilly, Nicole; Rowland, Jesseca E.; Mitchell, Philip B.; Carr, Vaughan J.; Green, Melissa

doi:10.1503/jpn.130283

Cited by 29 publications

(15 citation statements)

References 78 publications

(69 reference statements)

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“…Previous studies have found gray matter volume reductions in the frontal lobe and increased gray matter volume in caudate and thalamus, which may be related with cognitive deficits shared across patients with schizophrenia and bipolar disorder [33,34]. These results validate the possibility that patients with bipolar disorder and schizophrenia suffer from a cortical–subcortical imbalance [33,34]. A genome‐wide association study found that there are three regions—CACNA1C, ANK3, and ITIH3–ITIH4—affecting the risk of both schizophrenia and bipolar disorder [35].…”

Section: Discussionsupporting

confidence: 71%

“…However, some researchers have suggested that susceptibility genes and gray matter abnormalities have a critical effect on brain function [31–33]. Previous studies have found gray matter volume reductions in the frontal lobe and increased gray matter volume in caudate and thalamus, which may be related with cognitive deficits shared across patients with schizophrenia and bipolar disorder [33,34]. These results validate the possibility that patients with bipolar disorder and schizophrenia suffer from a cortical–subcortical imbalance [33,34].…”

Section: Discussionmentioning

confidence: 62%

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Neurocognitive function in clinically stable individuals with long‐term bipolar I disorder: Comparisons with schizophrenia patients and controls

Lin¹,

Wang²,

Chen³

et al. 2017

The Kaohsiung J of Med Scie

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This study compared the levels of the five domains of neurocognitive function-executive function, attention, memory, verbal comprehension, and perceptual organization-among clinically stable individuals with long-term bipolar I disorder, individuals with long-term schizophrenia, and a group of controls. We recruited a total of 93 clinically stable individuals with bipolar I disorder, 94 individuals with schizophrenia, and 106 controls in this study. Their neurocognitive function was measured using a series of neurocognitive function tests: the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), Line Cancellation Test, Visual Form Discrimination, Controlled Oral Word Association Test, Wisconsin Card Sorting Test, Continuous Performance Task, and Wechsler Memory Scale-Third Edition. Neurocognitive function was compared among the three groups through a multivariate analysis of variance. The results indicated that when the effect of age was controlled, clinically stable individuals with bipolar I disorder and those with schizophrenia demonstrated poor neurocognitive function on all tests except for the WAIS-III Similarity and Information and the Line Cancellation Test. The individuals with bipolar I disorder had similar levels of neurocognitive function compared with the schizophrenia group, but higher levels of neurocognitive function on the WAIS-III Comprehension, Controlled Oral Word Association Test, and Wechsler Memory Scale-Third Edition Auditory Immediate and Delayed Index and Visual Immediate and Delayed Index. The conclusions of this study suggest that compared with controls, individuals with long-term bipolar I disorder and those with long-term schizophrenia have poorer neurocognitive function, even when clinically stable. Individuals with long-term bipolar I disorder and those with long-term schizophrenia have similar levels of deficits in several domains of neurocognitive function.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 62%

Neurocognitive function in clinically stable individuals with long‐term bipolar I disorder: Comparisons with schizophrenia patients and controls

Lin¹,

Wang²,

Chen³

et al. 2017

The Kaohsiung J of Med Scie

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“…This finding is intriguing as BP and SZ may share familial and genetic risk factors (Berrettini, 2003, Kim et al, 2015, Purcell et al, 2009, Shepherd et al, 2015) including miRNAs (Kim, Reimers, 2010, Miller, Zeier, 2012, Walker, Rybka, 2015) and, given the seed sequences of miR-132 and miR-212 are identical, these miRNAs may share a number of targets. Additionally, as miR-34a expression levels are dysregulated in cohorts of both SZ and BP patients (in DLPFC and cerebellum, respectively) (Bavamian, Mellios, 2015, Kim, Reimers, 2010), our finding that miR-34a is significantly differentially expressed in a cohort of patients with MDD identifies miR-34a as the first miRNA to be differentially expressed in the CNS across 3 psychiatric illnesses—BP, MDD and SZ.…”

Section: Discussionmentioning

confidence: 99%

The microRNA network is altered in anterior cingulate cortex of patients with unipolar and bipolar depression

Azevedo

Carter

Meng

et al. 2016

Journal of Psychiatric Research

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MicroRNAs (miRNAs) are small, non-coding RNAs acting as post-transcriptional regulators of gene expression. Though implicated in multiple CNS disorders, miRNAs have not been examined in any psychiatric disease state in anterior cingulate cortex (AnCg), a brain region centrally involved in regulating mood. We performed qPCR analyses of 29 miRNAs previously implicated in psychiatric illness (major depressive disorder (MDD), bipolar disorder (BP) and/or schizophrenia (SZ)) in AnCg of patients with MDD and BP versus controls. miR-132, miR-133a and miR-212 were initially identified as differentially expressed in BP, miR-184 in MDD and miR-34a in both MDD and BP (although none survived multiple correction testing and must be considered preliminary). In silico target prediction algorithms identified putative targets of differentially expressed miRNAs. Nuclear Co-Activator 1 (NCOA1), Nuclear Co-Repressor 2 (NCOR2) and Phosphodiesterase 4B (PDE4B) were selected based upon predicted targeting by miR-34a (with NCOR2 and PDE4B both targeted by miR-184) and published relevance to psychiatric illness. Luciferase assays identified PDE4B as a target of miR-34a and miR-184, while NCOA1 and NCOR2 were targeted by miR-34a and 184, respectively. qPCR analyses were performed to determine whether changes in miRNA levels correlated with mRNA levels of validated targets. NCOA1 showed an inverse correlation with miR-34a in BP, while NCOR2 demonstrated a positive correlation. In sum, this is the first study to demonstrate miRNA changes in AnCg in psychiatric illness and validate miR-34a as differentially expressed in CNS in MDD. These findings support a mechanistic role for miRNAs in the regulation of stress-responsive genes disrupted in psychiatric illness.

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“…Recent studies have shown dysfunction of the precentral gyrus (PreCG) has long been thought to play a role in the impairments of voluntary movement associated with Schizophrenia and it has significantly reduced functional activity (FC) in patients with schizophrenia [3,4] . Also, schizophrenia is associated with volume deficits in PreCG [5] . Another research indicates the patients with schizophrenia showed lower activation in left PreCG than right PreCG [6] and a regional homogeneity (ReHo) study showed decreased ReHo in right precentral gyrus [7] .…”

Section: Introductionmentioning

confidence: 97%

Precentral gyrus abnormal connectivity in male and female patients with schizophrenia

Zarei¹

2018

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Aim: Dysfunction of the precentral gyrus plays a role in the impairments of voluntary movement associated with schizophrenia and it has significantly reduced functional activity in patients with schizophrenia. The aim of this study was to demonstrate the precentral gyrus alteration and its abnormal connectivity in schizophrenia. Methods:The region of interest-based analysis method was used to investigate the precentral gyrus connectivity alteration in schizophrenia. The resting-state functional magnetic resonance imaging data of healthy control subjects and patients with schizophrenia (Centers of Biomedical Research Excellence data set) was used to examine the aberrant functional brain connectome in schizophrenia. This data set contains raw anatomical and functional magnetic resonance data from 72 patients with schizophrenia and 75 healthy controls, ranging in age from 18 to 65 years old. Results:Our results show precentral gyrus has abnormal communication with thalamus, hippocampus, parahippocampal gyrus, posterior division of supramarginal gyrus and medial prefrontal cortex (pFDR = 0.05). This information is expected to provide a better understanding of altered functional connectivity of the precentral gyrus in the male and female patients with schizophrenia. Conclusion:Collectively, these findings support the hypothesis that precentral gyrus has an abnormal connectivity in schizophrenia and this alteration is not the same in the male and female patients with schizophrenia.

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Shared intermediate phenotypes for schizophrenia and bipolar disorder: neuroanatomical features of subtypes distinguished by executive dysfunction

Cited by 29 publications

References 78 publications

Neurocognitive function in clinically stable individuals with long‐term bipolar I disorder: Comparisons with schizophrenia patients and controls

Neurocognitive function in clinically stable individuals with long‐term bipolar I disorder: Comparisons with schizophrenia patients and controls

The microRNA network is altered in anterior cingulate cortex of patients with unipolar and bipolar depression

Precentral gyrus abnormal connectivity in male and female patients with schizophrenia

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