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Identifying dynamic functional connectivity biomarkers using GIG-ICA: Application to schizophrenia, schizoaffective disorder, and psychotic bipolar disorder.

ABSTRACT: Functional magnetic resonance imaging (fMRI) studies have shown altered brain dynamic functional connectivity (DFC) in mental disorders. Here, we aim to explore DFC across a spectrum of symptomatically-related disorders including bipolar disorder with psychosis (BPP), schizoaffective disorder (SAD), and schizophrenia (SZ). We introduce a group information guided independent component analysis procedure to estimate both group-level and subject-specific connectivity states from DFC. Using resting-state fMRI data of 238 healthy controls (HCs), 140 BPP, 132 SAD, and 113 SZ patients, we identified measures differentiating groups from the whole-brain DFC and traditional static functional connectivity (SFC), separately. Results show that DFC provided more informative measures than SFC. Diagnosis-related connectivity states were evident using DFC analysis. For the dominant state consistent across groups, we found 22 instances of hypoconnectivity (with decreasing trends from HC to BPP to SAD to SZ) mainly involving post-central, frontal, and cerebellar cortices as well as 34 examples of hyperconnectivity (with increasing trends HC through SZ) primarily involving thalamus and temporal cortices. Hypoconnectivities/hyperconnectivities also showed negative/positive correlations, respectively, with clinical symptom scores. Specifically, hypoconnectivities linking postcentral and frontal gyri were significantly negatively correlated with the PANSS positive/negative scores. For frontal connectivities, BPP resembled HC while SAD and SZ were more similar. Three connectivities involving the left cerebellar crus differentiated SZ from other groups and one connection linking frontal and fusiform cortices showed a SAD-unique change. In summary, our method is promising for assessing DFC and may yield imaging biomarkers for quantifying the dimension of psychosis. Hum Brain Mapp 38:2683-2708, 2017. © 2017 Wiley Periodicals, Inc.

SUBMITTER: Du Y

PROVIDER: S-EPMC5399898 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background To compare estimated 10-year and 30-year cardiovascular risk in primary care patients with and without serious mental illness (SMI; bipolar disorder, schizophrenia, or schizoaffective disorder). Methods and Results All patients aged 18 to 75 years with a primary care visit in January 2016 to September 2018 were included and were grouped into those with and without SMI using diagnosis codes. Ten-year cardiovascular risk was estimated using atherosclerotic cardiovascular disease scores for patients aged 40 to 75 years without cardiovascular disease; 30-year cardiovascular risk was estimated using Framingham risk scores for patients aged 18 to 59 years without cardiovascular disease. Demographic, vital sign, medication, diagnosis, and health insurance data were collected from the electronic health record by a clinical decision support system. Descriptive statistics examined unadjusted differences, while general linear models examined differences for continuous variables and logistic regression models for categorical variables. Models were then adjusted for age, sex, race, ethnicity, and insurance type. A total of 11 333 patients with SMI and 579 924 patients without SMI were included. After covariate adjustment, 10-year cardiovascular risk was significantly higher in patients with SMI (mean, 9.44%; 95% CI, 9.29%-9.60%) compared with patients without SMI (mean, 7.99%; 95% CI, 7.97-8.02). Similarly, 30-year cardiovascular risk was significantly higher in those with SMI (25% of patients with SMI in the highest-risk group compared with 11% of patients without SMI; P<0.001). The individual cardiovascular risk factors contributing most to increased risk for those with SMI were elevated body mass index and smoking. Among SMI subtypes, patients with bipolar disorder had the highest 10-year cardiovascular risk, while patients with schizoaffective disorder had the highest 30-year cardiovascular risk. Conclusions The significantly increased cardiovascular risk associated with SMI is evident even in young adults. This suggests the importance of addressing uncontrolled major cardiovascular risk factors in those with SMI at as early an age as possible. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02451670.

Project description:Neuropsychological impairment is heterogeneous in psychosis. The association of intracranial volume (ICV) and total brain volume (TBV) with cognition suggests brain structure abnormalities in psychosis will covary with the severity of cognitive impairment. We tested the following hypotheses: (1) brain structure abnormalities will be more extensive in neuropsychologically impaired psychosis patients; (2) psychosis patients with premorbid cognitive limitations will show evidence of hypoplasia (ie, smaller ICV); and (3) psychosis patients with evidence of cognitive decline will demonstrate atrophy (ie, smaller TBV, but normal ICV).One hundred thirty-one individuals with psychosis and 97 healthy subjects underwent structural magnetic resonance imaging and neuropsychological testing. Patients were divided into neuropsychologically normal and impaired groups. Impaired patients were further subdivided into deteriorated and compromised groups if estimated premorbid intellect was average or below average, respectively. ICV and TBV were compared across groups. Localized brain volumes were qualitatively examined using voxel-based morphometry.Compared to healthy subjects, neuropsychologically impaired patients exhibited smaller TBV, reduced grey matter volume in frontal, temporal, and subcortical brain regions, and widespread white matter volume loss. Neuropsychologically compromised patients had smaller ICV relative to healthy subjects, and neuropsychologically normal and deteriorated patient groups, but relatively normal TBV. Deteriorated patients exhibited smaller TBV compared to healthy subjects, but relatively normal ICV. Unexpectedly, TBV, adjusted for ICV, was reduced in neuropsychologically normal patients.Patients with long-standing cognitive limitations exhibit evidence of early cerebral hypoplasia, whereas neuropsychologically normal and deteriorated patients show evidence of brain tissue loss consistent with progression or later cerebral dysmaturation.

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Identifying dynamic functional connectivity biomarkers using GIG-ICA: Application to schizophrenia, schizoaffective disorder, and psychotic bipolar disorder.

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