Chaohua Huang

Changes of brain morphometry in first-episode, drug-naïve, non-late-life adult patients with major depression: an optimized voxel-based morphometry study.

BACKGROUND Previous structural imaging studies found evidence of brain morphometric changes in major depression (MD) patients, but they rarely excluded compounding effects of some important factors, such as medication and brain degeneration. This study sought to explore the brain morphometric changes of first-episode, drug-naïve, non-late-life adult MD patients with optimized voxel-based morphometry (VBM) method. METHODS Twenty-three first-episode, drug-naïve, non-late-life adult depressed patients and 23 healthy control subjects were enrolled in this study. Subjects underwent high-resolution magnetic resonance imaging, and optimized VBM was performed to analyze the morphometric data. A partial correlation model was used to analyze associations of morphometric changes with Hamilton Depression Rating Scale scores and illness duration. RESULTS Depressed patients showed significant gray matter volume reduction in the bilateral limbic system, especially in hippocampus. These changes did not significantly correlate with symptom severity or illness duration. CONCLUSIONS Our findings provided new evidence of gray matter deficits in first-episode, drug-naïve, non-late-life adult MD patients. It supported that the reduction of hippocampal volume is a trait for MD patients and further highlighted the important role of the limbic system, particularly hippocampus in the pathophysiology of MD.

Aberrant intrinsic brain activity and cognitive deficit in first-episode treatment-naive patients with schizophrenia

BACKGROUND Given the important role of the default mode network (DMN) in cognitive function and the well-known neurocognitive deficit in schizophrenia, it is intriguing to examine systematically the relationship between neurocognitive dysfunction and aberrant intrinsic activities, and also functional connectivity, of the DMN in patients with schizophrenia. Method First-episode, treatment-naive patients with schizophrenia (FES) (n = 115) and healthy controls (n = 113) underwent resting-state functional magnetic resonance imaging (fMRI) scans and neurocognitive tests. Intrinsic neural activities evaluated by using the fragment amplitude of low-frequency fluctuations (fALFF) and the resting-state functional connectivity assessed by seed-based correlational analysis were compared between patients and controls. Aberrant intrinsic activities and DMN connectivity in patients were then correlated to neurocognitive performance and clinical symptoms. RESULTS Compared to controls, patients with FES showed decreased fALFF in the bilateral medial prefrontal cortex (MPFC) and the orbitofrontal cortex (OFC), and increased fALFF in the bilateral putamen. Increased functional connectivity with the DMN was observed in the left insula and bilateral dorsolateral PFC (DLPFC) in patients with FES. In patients, aberrant fALFF in the bilateral OFC were correlated with cognitive processing speed; fALFF in the left OFC and right putamen were correlated with the clinical factors excited/activation and disorganization; and increased DMN functional connectivity in the left insula was correlated with the clinical factors positive, excited/activation, disorganization and neurocognitive deficit in the domain of sustained attention. CONCLUSIONS These associations between neurocognitive dysfunction and aberrant intrinsic activities, and also functional connectivity, of the DMN in patients with schizophrenia may provide important insights into the neural mechanism of the disease.

Assessment of white matter abnormalities in paranoid schizophrenia and bipolar mania patients

White matter abnormalities have been repeatedly reported in both schizophrenia and bipolar disorder (BD) in diffusion tensor imaging (DTI) studies, but the empirical evidence about the diagnostic specificity of white matter abnormalities in these disorders is still limited. This study sought to investigate the alterations in fractional anisotropy (FA) in white matter throughout the entire brain of patients from Chengdu, China with paranoid schizophrenia and bipolar mania. For this purpose, DTI was used to assess white matter integrity in patients with paranoid schizophrenia (n=25) and psychotic bipolar mania (n=18) who had been treated with standard pharmacotherapy for fewer than 5 days at the time of study, as well as in normal controls (n=30). The differences in FA were measured by use of voxel-based analysis. The results show that reduced FA was found in the left posterior corona radiata (PCR) in patients with psychotic bipolar mania and paranoid schizophrenia compared to the controls. Patients with psychotic bipolar mania also showed a significant reduction in FA in right posterior corona radiata and in right anterior thalamic radiation (ATR). A direct comparison between the two patient groups found no significant differences in any regions, and none of the findings were associated with illness duration. Correlation analysis indicated that FA values showed a significant negative correlation with positive symptom scores on the Positive and Negative Syndrome Scale in the left frontal-parietal lobe in the paranoid schizophrenia. It was concluded that common abnormalities in the left PCR might imply an overlap in white matter pathology in the two disorders and might be related to shared risk factors for the two disorders.

Voxel based morphometric and diffusion tensor imaging analysis in male bipolar patients with first-episode mania.

OBJECTIVES Structural abnormality of both gray and white matter has been detected in patients with bipolar disorder (BD). But results were greatly inconsistent across studies which were most likely attributed to heterogeneous populations as well as processing techniques. The present study aimed to investigate brain structural and microstructural alterations in a relative homogenous sample of bipolar mania. METHODS 3D T1-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were conducted in 18 patients with BD and 27 healthy volunteers. Gray matter (GM) and white matter (WM) differences were evaluated using voxel-based morphometry (VBM) and voxel-based analysis of fractional anisotropy (FA) maps derived from DTI, respectively. RESULTS Patients with BD had a larger volume of GM in the left thalamus and bilateral basal ganglia, including the bilateral putamen and extending to the left claustrum, as well as reduced FA values in the left posterior corona radiata. CONCLUSIONS By combined analysis, alterations in subcortical GM areas and part of the corresponding association fiber area were detected. Compared with observations in homogeneous samples, our findings indicate that disruption of the limbic network may be intrinsic to BD.

Abnormalities in connectivity of white-matter tracts in patients with familial and non-familial schizophrenia

BACKGROUND Abnormalities in the connectivity of white-matter (WM) tracts in schizophrenia are supported by evidence from post-mortem investigations, functional and structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). The aims of this study were to explore the microstructural changes in first-episode schizophrenia in a Han Chinese population and to investigate whether a family history of psychiatric disorder is related to the severity of WM tract integrity abnormalities in these patients. METHOD T1-weighted MR and DT images were collected in 68 patients with first-episode schizophrenia [22 with a positive family history (PFH) and 46 with a negative family history (NFH)] and 100 healthy controls. Voxel-based analysis was performed and WM integrity was quantified by fractional anisotropy (FA). Cluster- and voxel-level analyses were performed by using two-sample t tests between patients and controls and/or using a full factorial model with one factor and three levels among the three sample groups (patients with PFH or NFH, and controls), as appropriate. RESULTS FA deficits were observed in the patient group, especially in the left temporal lobe and right corpus callosum. This effect was more severe in the non-familial schizophrenia than in the familial schizophrenia subgroup. CONCLUSIONS Overall, these findings support the hypothesis that loss of WM integrity may be an important pathophysiological feature of schizophrenia, with particular implications for brain dysmaturation in non-familial and familial schizophrenia.

Overlapping clusters of gray matter deficits in paranoid schizophrenia and psychotic bipolar mania with family history

The purpose of this study was to assess volumetric abnormalities of gray matter throughout the entire brain in patients with paranoid schizophrenia or with bipolar mania compared with control groups. We obtained weighted 3D T1 magnetic resonance images from 23 patients with paranoid schizophrenia, 24 patients with psychotic bipolar mania, and 36 healthy controls. Gray matter volume differences were assessed using optimized volumetric voxel-based morphometry (VBM). Both paranoid schizophrenia and bipolar mania group showed reduction of gray matter volume in the superior temporal gyrus (STG) (Brodmann Area, BA 22 areas), and the inferior parietal lobule, and enlargement of putamen, although different sides of the inferior parietal lobule and putamen were affected in the groups. Our findings showed the presence of overlapping clusters of gray matter deficits in paranoid-type schizophrenia and psychotic bipolar mania. The overlap in gray matter pathology between the two disorders may be attributed to risk factors common to both disorders.

Voxel-based morphometric analysis on the volume of gray matter in bipolar I disorder.

A number of previous studies have found that bipolar disorder is associated with abnormalities of brain structure. In this study we used optimized voxel-based morphometry (VBM) to compare gray matter volume between patients with bipolar I disorder and healthy controls. Twenty-four bipolar I patients (15 males and nine females) and 36 healthy controls (21 males and 15 females), who were well matched for age and gender, were scanned using structural magnetic resonance imaging. Gray matter volume was assessed and compared using optimized VBM, and the correlation between duration of illness/number of episodes and regional volumes was analyzed. There was no difference in whole-brain gray matter volume between the two groups. Optimized vVBM showed that subjects with bipolar I disorder had smaller volumes in the left inferior parietal lobule, right superior temporal gyrus, right middle frontal gyrus and left caudate. Only the volume of the right middle frontal gyrus was correlated with duration of illness and number of episodes in patients. These results suggest widespread gray matter defects in bipolar I disorder, which may play an important role in onset of the illness.

A splitting brain: Imbalanced neural networks in schizophrenia

Dysconnectivity between key brain systems has been hypothesized to underlie the pathophysiology of schizophrenia. The present study examined the pattern of functional dysconnectivity across whole-brain neural networks in 121 first-episode, treatment-naïve patients with schizophrenia by using resting-state functional magnetic resonance imaging (rsfMRI). Group independent component analysis (ICA) was first applied to rsfMRI data to extract 90 functional components of the brain. The functional connectivity between these ICA components was then evaluated and compared between the patient and control groups. To examine the functional roles of significantly altered between-component connections in patients, each ICA component was ascribed to one of 10 previously well-defined brain networks/areas. Relative to findings in healthy controls (n=103), 29 altered functional connections including 19 connections with increased connectivity and 10 connections with decreased connectivity in schizophrenia patients were found. Increased connectivity was mainly within the default mode network (DMN) and between the DMN and cognitive networks, whereas decreased connectivity was predominantly associated with sensory networks. Given the key roles of the DMN in internal mental processes and sensory networks in inputs from the external environment, these patterns of altered brain network connectivity could suggest imbalanced neural processing of internal and external information in schizophrenia.

Contrasting and convergent patterns of amygdala connectivity in mania and depression: a resting-state study.

BACKGROUND wMania and depression in bipolar disorder (BP) manifest two extremes of aberrant emotional, physiologic and behavioral arousal states despite similarities in treatment response and neurocognitive deficits. We used resting-state functional magnetic resonance imaging (rsfMRI) to explore the common and unique abnormal functional connectivity underlying acute manic or depressed state in BP. METHODS 18 Patients with bipolar mania (BM), 10 patients with bipolar depression (BD) and 28 healthy controls underwent resting-state functional magnetic resonance imaging scanning. Left and right amygdala seed-to-voxel based functional connectivity were assessed and compared among the three groups. The relationships between aberrant functional connectivity and the severity of clinical symptoms, number of episodes, illness duration were investigated. RESULTS Compared to healthy controls, both BM and BD groups showed reduced functional connectivity between bilateral amygdala and inferior frontal gyrus (orbital), striatum, right lingual gyrus and posterior cerebellar lobe. Furthermore right amygdala-hippocampal connectivity was decreased in BD but increased in BM. No significant correlations were found between strength of abnormal functional connectivity and clinical characteristic in BD or BM. LIMITATIONS No euthymic subjects were recruited, and the patients in current study were all on medication. CONCLUSIONS The presence of substantial overlap in the pattern of disturbed connectivity between amygdala and frontal, striatal, lingual and cerebellar regions suggests mood state-independent dysconnectivity. The contrasting pattern of functional connectivity between right amygdala and hippocampus in BD and BM provides a novel lead to the probable mechanistic differences in these two extremes of mood states.

Extensive brain structural network abnormality in first-episode treatment-naive patients with schizophrenia: morphometrical and covariation study

BACKGROUND Alterations in gray matter (GM) are commonly observed in schizophrenia. Accumulating studies suggest that the brain changes associated with schizophrenia are distributed rather than focal, involving interconnected networks of areas as opposed to single regions. In the current study we aimed to explore GM volume (GMV) changes in a relatively large sample of treatment-naive first-episode schizophrenia (FES) patients using optimized voxel-based morphometry (VBM) and covariation analysis. METHOD High-resolution T1-weighted images were obtained using 3.0-T magnetic resonance imaging (MRI) from 86 first-episode drug-naive patients with schizophrenia and 86 age- and gender-matched healthy volunteers. Symptom severity was evaluated using the Positive and Negative Syndrome Scale (PANSS). GMV was assessed using optimized VBM and in 16 regions of interest (ROIs), selected on the basis of a previous meta-analysis. The relationships between GMVs in the ROIs were examined using an analysis of covariance (ANCOVA). RESULTS The VBM analysis revealed that first-episode patients showed reduced GMV in the hippocampus bilaterally. The ROI analysis identified reductions in GMV in the left inferior frontal gyrus, bilateral hippocampus and right thalamus. The ANCOVA revealed different patterns of regional GMV correlations in patients and controls, including of inter- and intra-insula, inter-amygdala and insula-postcentral gyrus connections. CONCLUSIONS Schizophrenia involves regional reductions in GMV and changes in GMV covariance in the insula, amygdala and postcentral gyrus. These findings were evident at the onset of the disorder, before treatment, and therefore cannot be attributable to the effects of chronic illness progression or medication.