Changqing Xiao

Abnormal neural activities in first-episode, treatment-naïve, short-illness-duration, and treatment-response patients with major depressive disorder: A resting-state fMRI study

BACKGROUND Abnormality of limbic-cortical networks was postulated in depression. Using a regional homogeneity (ReHo) approach, we explored the regional homogeneity (ReHo) of the brain regions in patients with first-episode, treatment-naïve, short-illness-duration, and treatment-response depression in resting state to test the abnormality hypothesis of limbic-cortical networks in major depressive disorder (MDD). METHODS Seventeen patients with treatment-response MDD and 17 gender-, age-, and education-matched healthy subjects participated in the resting-state fMRI scans. RESULTS CONCLUSIONS Our findings suggested the abnormality of limbic-cortical networks in first-episode, treatment-naïve, short-illness-duration, and treatment-response MDD patients, and added an expanding literature to the abnormality hypothesis of limbic-cortical networks in MDD.

Decreased interhemispheric resting-state functional connectivity in first-episode, drug-naive major depressive disorder

BACKGROUND Major depressive disorder (MDD) is shown to have structural and functional abnormalities in specific brain areas and connections by recent neuroimaging studies. However, little is known about the alterations of the interhemispheric resting-state functional connectivity (FC) in patients with MDD. In the present study, we used a newly developed voxel-mirrored homotopic connectivity (VMHC) method to investigate the interhemispheric FC of the whole brain in patients with MDD at rest. METHODS Twenty-four first-episode, drug-naive patients with MDD and 24 age-, gender-, and education-matched healthy subjects underwent a resting-state functional magnetic resonance imaging (fMRI). An automated VMHC approach was used to analyze the data. RESULTS Patients with MDD showed lower VMHC than healthy subjects in the medial prefrontal cortex (MPFC) and the posterior cingulate cortex/precuneus (PCC/PCu), two core regions within default mode network (DMN). Both left and right MPFC showed reduced FC with the other frontal areas and with right anterior cingulate gyrus (ACC), while PCC/PCu exhibited abnormal FC with the frontal areas and thalamus in patient group. Significant positive correlation was observed between VMHC in MPFC and persistent error response of Wisconsin Card Sorting Test (WCST-Pre) in patients. Further ROC analysis revealed that VMHC in the MPFC and PCC/PCu could be used to differentiate the patients from healthy subjects with relatively high sensitivity and specificity. CONCLUSIONS Our results suggest that decreased VMHC in brain regions within DMN may underlie the pathogenesis of MDD.

Alterations of the amplitude of low-frequency fluctuations in treatment-resistant and treatment-response depression: A resting-state fMRI study

BACKGROUND Patients with treatment-resistant depression (TRD) and those with treatment-response depression (TSD) respond to antidepressants differently and previous studies have commonly reported different brain networks in resistant and nonresistant patients. Using the amplitude of low-frequency fluctuations (ALFF) approach, we explored ALFF values of the brain regions in TRD and TSD patients at resting state to test the hypothesis of the different brain networks in TRD and TSD patients. METHODS Eighteen TRD patients, 17 TSD patients and 17 gender-, age-, and education-matched healthy subjects participated in the resting-state fMRI scans. RESULTS There are widespread differences in ALFF values among TRD patients, TSD patients and healthy subjects throughout the cerebellum, the visual recognition circuit (middle temporal gyrus, middle/inferior occipital gyrus and fusiform), the hate circuit (putamen), the default circuit (ACC and medial frontal gyrus) and the risk/action circuit (inferior frontal gyrus). The differences in brain circuits between the TRD and TSD patients are mainly in the cerebellum, the visual recognition circuit and the default circuit. CONCLUSIONS The affected brain circuits of TRD patients might be partly different from those of TSD patients.

Abnormal resting-state cerebellar-cerebral functional connectivity in treatment-resistant depression and treatment sensitive depression.

BACKGROUND Previous studies have commonly shown that patients with treatment-resistant depression (TRD) and treatment-sensitive depression (TSD) demonstrate a different cerebellar activity. No study has yet explored resting-state cerebellar-cerebral functional connectivity (FC) in these two groups. Here, seed-based FC approach was employed to test the hypothesis that patients with TRD and TSD had a different cerebellar-cerebral FC. The identified FC might be used to differentiate TRD from TSD. METHODS Twenty-three patients with TRD, 22 patients with TSD, and 19 healthy subjects (HS) matched with age, gender, and education level participated in the scans. Seed-based connectivity analyses were performed by using cerebellar seeds. RESULTS Relative to HS, both patient groups showed significantly decreased cerebellar-cerebral FC with the prefrontal cortex (PFC) (superior, middle, and inferior frontal gyrus) and default mode network (DMN) [superior, middle, and inferior temporal gyrus, precuneus (PCu), and inferior parietal lobule (IPL)], and increased FC with visual recognition network (lingual gyrus, middle occipital gyrus, and fusiform) and parahippocampal gyrus. However, the TRD group exhibited a more decreased FC than the TSD group, mainly in connected regions within DMN [PCu, angular gyrus (AG) and IPL]. Further receiver operating characteristic curves (ROC) analyses showed that cerebellar-DMN couplings could be applied as markers to differentiate the two subtypes with relatively high sensitivity and specificity. CONCLUSIONS Both patient groups demonstrate similar pattern of abnormal cerebellar-cerebral FC. Decreased FC between the cerebellum and regions within DMN might be used to separate the two patient groups.

Right lateralized white matter abnormalities in first-episode, drug-naive paranoid schizophrenia

Numerous studies in first-episode schizophrenia suggest the involvement of white matter (WM) abnormalities in multiple regions underlying the pathogenesis of this condition. However, there has never been a neuroimaging study in patients with first-episode, drug-naive paranoid schizophrenia by using tract-based spatial statistics (TBSS) method. Here, we used diffusion tensor imaging (DTI) with TBSS method to investigate the brain WM integrity in patients with first-episode, drug-naive paranoid schizophrenia. Twenty patients with first-episode, drug-naive paranoid schizophrenia and 26 healthy subjects matched with age, gender, and education level were scanned with DTI. An automated TBSS approach was employed to analyze the data. Voxel-wise statistics revealed that patients with paranoid schizophrenia had decreased fractional anisotropy (FA) values in the right superior longitudinal fasciculus (SLF) II, the right fornix, the right internal capsule, and the right external capsule compared to healthy subjects. Patients did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain regions and patient demographics and the severity of illness. Our findings suggest right-sided alterations of WM integrity in the WM tracts of cortical and subcortical regions may play an important role in the pathogenesis of paranoid schizophrenia.

Abnormal default-mode network homogeneity in first-episode, drug-naive schizophrenia at rest.

BACKGROUND Dysconnectivity hypothesis posits that schizophrenia relates to abnormal resting-state connectivity within the default-mode network (DMN) and this aberrant connectivity is considered as contribution of difficulties in self-referential and introspective processing. However, little is known about the alterations of the network homogeneity (NH) of the DMN in schizophrenia. In the present study, we used an automatic NH method to investigate the NH of the DMN in schizophrenia patients at rest. METHODS Forty-nine first-episode, drug-naive schizophrenia patients and 50 age-, gender-, and education-matched healthy controls underwent a resting-state functional magnetic resonance imaging (fMRI). An automated NH approach was used to analyze the data. RESULTS Patients exhibited lower NH than controls in the left medial prefrontal cortex (MPFC) and the right middle temporal gyrus (MTG). Significantly higher NH values in the left posterior cingulate cortex (PCC) and the right cerebellum Crus I were found in the patient group than in the control group. No significant correlation was found between abnormal NH values and Positive and Negative Symptom Scale (PANSS) scores, duration of untreated psychosis (DUP), age or years of education in the patient group. CONCLUSIONS Our findings suggest that abnormal NH of the DMN exists in first-episode, drug-naive schizophrenia and further highlight the importance of the DMN in the pathophysiology of schizophrenia.

Altered white matter integrity in young adults with first-episode, treatment-naive, and treatment-responsive depression

Abnormalities of the white matter (WM) tracts integrity in brain areas involved in emotional regulation have been postulated in major depressive disorder (MDD). However, there is no diffusion tensor imaging (DTI) study in patients with treatment-responsive MDD at present. DTI scans were performed on 22 patients with treatment-responsive MDD and 19 well-matched healthy subjects. Tract-based spatial statistics (TBSS) approach was employed to analyze the scans. Voxel-wise statistics revealed four brain WM tracts with lower fractional anisotropy (FA) in patients compared to healthy subjects: the bilateral internal capsule, the genu of corpus callosum, the bilateral anterior corona radiata, and the right external capsule. FA values were nowhere higher in patients compared to healthy subjects. Our findings demonstrate that the abnormalities of the WM tracts, major in the projection fibers and corpus callosum, may contribute to the pathogenesis of treatment-responsive MDD.

Decreased resting-state interhemispheric coordination in first-episode, drug-naive paranoid schizophrenia

BACKGROUND Dysconnectivity hypothesis posits that schizophrenia relates to abnormalities in neuronal connectivity. However, little is known about the alterations of the interhemispheric resting-state functional connectivity (FC) in patients with paranoid schizophrenia. In the present study, we used a newly developed voxel-mirrored homotopic connectivity (VMHC) method to investigate the interhemispheric FC of the whole brain in patients with paranoid schizophrenia at rest. METHODS Forty-nine first-episode, drug-naive patients with paranoid schizophrenia and 50 age-, gender-, and education-matched healthy subjects underwent a resting-state functional magnetic resonance imaging (fMRI) scans. An automated VMHC approach was used to analyze the data. RESULTS Patients exhibited lower VMHC than healthy subjects in the precuneus (PCu), the precentral gyrus, the superior temporal gyrus (STG), the middle occipital gyrus (MOG), and the fusiform gyrus/cerebellum lobule VI. No region showed greater VMHC in the patient group than in the control group. Significantly negative correlation was observed between VMHC in the precentral gyrus and the PANSS positive/total scores, and between VMHC in the STG and the PANSS positive/negative/total scores. CONCLUSIONS Our results suggest that interhemispheric resting-state FC of VMHC is reduced in paranoid schizophrenia with clinical implications for psychiatric symptomatology thus further contribute to the dysconnectivity hypothesis of schizophrenia.

Early and late onset, first-episode, treatment-naive depression: same clinical symptoms, different regional neural activities

BACKGROUND Patients with early onset depression (EOD) and late onset depression (LOD) have distinctive risk factors and clinical pictures. Using regional homogeneity (ReHo) approach, we were to test the hypothesis of the different abnormal neural activity between patients with EOD or LOD. METHODS Fifteen patients with EOD, 15 patients with LOD, 15 young healthy subjects (HS) and 15 old HS participated in the study. ReHo approach was employed to analyze the scans. RESULTS ANOVA analysis revealed widespread differences in ReHo values among the four groups throughout frontal, parietal, temporal, occipital cortex, cerebellum and limbic regions. Compared to LOD group, EOD group had higher ReHo in right precuneus (PCu) and bilateral superior frontal gyrus, and lower ReHo in left superior temporal gyrus. Compared to young HS, lower ReHo in left parahippocampal gyrus and higher ReHo in left fusiform gyrus and bilateral superior frontal gyrus were seen in EOD group; in contrast, in LOD group, lower ReHo in right PCu and higher ReHo in left superior temporal gyrus and left Crus I of the cerebellum were observed. Further ROC analysis suggested that the mean ReHo values in right PCu and bilateral superior frontal gyrus could serve as markers to identify patients with EOD from individuals with LOD. LIMITATION The large age gap may limit the translational value of our findings. CONCLUSIONS Patients with EOD and those with LOD have abnormal neural activities in different brain regions, although the two groups share the same symptoms.

Is there a cerebellar compensatory effort in first-episode, treatment-naive major depressive disorder at rest?

BACKGROUND This study was undertaken to explore whether there is a cerebellar compensatory response in patients with first-episode, treatment-naive major depressive disorder (MDD). The cerebellar compensatory response is defined as a cerebellar hyperactivity which would be inversely correlated with both the activation of the functionally connected cerebral regions and the depression severity. METHODS Resting-state functional magnetic resonance imaging (fMRI) data of 24 patients with MDD and 24 healthy subjects were analyzed with the fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity (FC) methods. The structural images were processed with the voxel-based morphometry (VBM) method. RESULTS Compared to healthy controls, depressed patients had significantly increased fALFF in the left Crus I and the left cerebellar lobule VI. FC analysis of these two seeded regions found that depressed patients had increased FC between the left Crus I and the right hippocampus, but had decreased FC between the left Crus I and the left inferior parietal lobule (IPL), and between the left cerebellar lobule VI and bilateral inferior temporal gyrus. No correlation was observed between the abnormal fALFF of the seeds and their connected regions and the depression severity or the executive function. The VBM results did not show significant reduction in gray or white matter volume in any above-mentioned region. CONCLUSIONS Our findings suggest that increased cerebellar activity at resting state may be a disease state phenomenon but not a compensatory response to the dysfunction of the default mode network (DMN) in MDD.