Changlian Tan

Abnormal amplitude low-frequency oscillations in medication-naive, first-episode patients with major depressive disorder: A resting-state fMRI study

BACKGROUND Recent resting-state fMRI studies on major depressive disorder (MDD) have found altered temporal correlation between low-frequency oscillations (LFOs). However, changes on the amplitudes of these LFOs remain largely unknown. METHODS Twenty-two medication-naive, first-episode patients with MDD and 19 age-, sex-, education-matched healthy controls were recruited. Resting-state fMRI was obtained by using an echo-planar imaging sequence and the fractional amplitude of low-frequency fluctuations (fALFF) was calculated to investigate the amplitude of LFOs in the resting state. RESULTS Compared with control subjects, patients with MDD showed significantly decreased fALFF in right cerebellum posterior lobe, left parahippocampal gyrus and right middle frontal gyrus and increased fALFF in left superior occipital gyrus/cuneus (p<0.05, corrected for multiple comparisons). Further receiver operating characteristic curves (ROC) analyses suggested that the alterations of fALFF in these regions might be used as markers to classify patients with MDD from healthy controls. CONCLUSIONS These findings indicated LFOs abnormalities in MDD and the fALFF analysis might be a potential approach in further exploration of this disorder.

Classification of Different Therapeutic Responses of Major Depressive Disorder with Multivariate Pattern Analysis Method Based on Structural MR Scans

Background Previous studies have found numerous brain changes in patients with major depressive disorder (MDD), but no neurological biomarker has been developed to diagnose depression or to predict responses to antidepressants. In the present study, we used multivariate pattern analysis (MVPA) to classify MDD patients with different therapeutic responses and healthy controls and to explore the diagnostic and prognostic value of structural neuroimaging data of MDD. Methodology/Principal Findings Eighteen patients with treatment-resistant depression (TRD), 17 patients with treatment-sensitive depression (TSD) and 17 matched healthy controls were scanned using structural MRI. Voxel-based morphometry, together with a modified MVPA technique which combined searchlight algorithm and principal component analysis (PCA), was used to classify the subjects with TRD, those with TSD and healthy controls. The results revealed that both gray matter (GM) and white matter (WM) of frontal, temporal, parietal and occipital brain regions as well as cerebellum structures had a high classification power in patients with MDD. The accuracy of the GM and WM that correctly discriminated TRD patients from TSD patients was both 82.9%. Meanwhile, the accuracy of the GM that correctly discriminated TRD or TSD patients from healthy controls were 85.7% and 82.4%, respectively; and the WM that correctly discriminated TRD or TSD patients from healthy controls were 85.7% and 91.2%, respectively. Conclusions/Significance These results suggest that structural MRI with MVPA might be a useful and reliable method to study the neuroanatomical changes to differentiate patients with MDD from healthy controls and patients with TRD from those with TSD. This method might also be useful to study potential brain regions associated with treatment response in patients with MDD.

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.

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 neural activity of brain regions in treatment-resistant and treatment-sensitive major depressive disorder: A resting-state fMRI study

BACKGROUND Patients with treatment-resistant depression (TRD) and those with treatment-sensitive depression (TSD) responded to antidepressants differently. Previous studies have commonly shown that patients with TRD or TSD had abnormal neural activity in different brain regions. In the present study, we used a coherence-based ReHo (Cohe-ReHo) approach to test the hypothesis that patients with TRD or TSD had abnormal neural activity in different brain regions. METHODS Twenty-three patients with TRD, 22 with TSD, and 19 healthy subjects (HS) matched with gender, age, and education level participated in the study. RESULTS ANOVA analysis revealed widespread differences in Cohe-ReHo values among the three groups in different brain regions which included bilateral superior frontal gyrus, bilateral cerebellum, left inferior temporal gyrus, left occipital cortex, and both sides of fusiform gyrus. Compared to HS, lower Cohe-ReHo values were observed in TRD group in bilateral superior frontal gyrus and left cerebellum; in contrast, in TSD group, lower Cohe-ReHo values were mainly found in bilateral superior frontal gyrus. Compared to TSD group, TRD group had lower Cohe-ReHo in bilateral cerebellum and higher Cohe-ReHo in left fusiform gyrus. There was a negative correlation between Cohe-ReHo values of the left fusiform gyrus and illness duration in the pooled patients (r = 0.480, p = 0.001). The sensitivity and specificity of cerebellar Cohe-ReHo values differentiating TRD from TSD were 83% and 86%, respectively. CONCLUSIONS Compared to healthy controls, both TRD and TSD patients shared the majority of brain regions with abnormal neural activity. However, the lower Cohe-ReHo values in the cerebellum might be as a marker to differentiate TRD from TSD with high sensitivity and specificity.

Aberrant default mode functional connectivity in early onset schizophrenia.

Background The default mode network (DMN) has been linked to a number of mental disorders including schizophrenia. However, the abnormal connectivity of DMN in early onset schizophrenia (EOS) has been rarely reported. Methods Independent component analysis (ICA) was used to investigate functional connectivity (FC) of the DMN in 32 first-episode adolescents with EOS and 32 age and gender-matched healthy controls. Results Compared to healthy controls, patients with EOS showed increased FC between the medial frontal gyrus and other areas of the DMN. Partial correlation analyses showed that the FC of medial frontal gyrus significantly correlated with PANSS-positive symptoms (partial correlation coefficient  = 0.538, Bonferoni corrected P = 0.018). Limitations Although the sample size of participants was comparable with most fMRI studies to date, it was still relatively small. Pediatric brains were registered to the MNI adult brain template. However, possible age-specific differences in spatial normalization that arise from registering pediatric brains to the MNI adult brain template may have little effect on fMRI results. Conclusion This study provides evidence for functional abnormalities of DMN in first-episode EOS. These abnormalities could be a source of abnormal introspectively-oriented mental actives.

A resting-state functional magnetic resonance imaging study on the first-degree relatives of persons with schizophrenia

In this study, resting state fMRI images and BOLD signals were recorded from 13 first-degree relatives of schizophrenic patients and 13 healthy controls. The data were analyzed with the ReHo approach after realignment, registration, and normalization in statistical parametric mapping 2 (SPM2). A two-sample t-test was used to analyze the ReHo differences between first-degree relatives and healthy controls in a voxel by voxel manner. A combined threshold of p < 0.005 and number of voxels >5 was designated as statistically significant. To evaluate cognitive deficits in first-degree relatives, attention/vigilance and verbal/visual memory were measured. Significant impairments in attention were observed in first-degree relatives compared to healthy controls. Significant abnormalities in ReHo were observed in resting brain in first-degree relatives. Decreased ReHo was found to be distributed over the bilateral middle frontal, middle temporal, cingulate gyrus and cerebellar tonsil; the left inferior frontal gyrus, inferior parietal lobule and dorsolateral prefrontal cortex; the right superior frontal gyrus and dorsolateral prefrontal cortex. Increased ReHo was found to be distributed in the right precuneus and superior temporal gyrus. These changes in ReHo suggest abnormality in the resting state brain function of first-degree relatives of schizophrenic patients and may be early signs for the development of schizophrenia.

A Voxel-Based Morphometric MRI Study in Young Adults with Borderline Personality Disorder

Background Increasing evidence has documented subtle changes in brain morphology and function in patients with borderline personality disorder (BPD). However, results of magnetic resonance imaging volumetry in patients with BPD are inconsistent. In addition, few researchers using voxel-based morphometry (VBM) have focused on attachment and childhood trauma in BPD. This preliminary study was performed to investigate structural brain changes and their relationships to attachment and childhood trauma in a homogenous sample of young adults with BPD. Method We examined 34 young adults with BPD and 34 healthy controls (HCs) to assess regionally specific differences in gray matter volume (GMV) and gray matter concentration (GMC). Multiple regressions between brain volumes measured by VBM and attachment style questionnaire (ASQ) and childhood trauma questionnaire (CTQ) scores were performed. Results Compared with HCs, subjects with BPD showed significant bilateral increases in GMV in the middle cingulate cortex (MCC)/posterior cingulate cortex (PCC)/precuneus. GMC did not differ significantly between groups. In multiple regression models, ASQ insecure attachment scores were correlated negatively with GMV in the precuneus/MCC and middle occipital gyrus in HCs, HCs with more severe insecure attachment showed smaller volumes in precuneus/MCC and middle occipital gyrus, whereas no negative correlations between insecure attachment and GMV in any region were found in BPD group. In addition, CTQ total scores were not correlated with GMV in any region in the two groups respectively. Conclusions Our findings fit with those of previous reports of larger precuneus GMV in patients with BPD, and suggest that GMV in the precuneus/MCC and middle occipital gyrus is associated inversely with insecure attachment style in HCs. Our finding of increased GMV in the MCC and PCC in patients with BPD compared with HCs has not been reported in previous VBM studies.

Abnormal white matter structural connectivity in adults with obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a complex and severe psychiatric disorder whose pathogenesis is not fully understood. Recent studies have shown white matter (WM) alterations in adults with OCD, but the results have been inconsistent. The present study investigated WM structure in OCD patients with the hypothesis that large-scale brain networks may be disrupted in OCD. A total of 24 patients with OCD and 23 healthy controls (HCs) were scanned with diffusion tensor imaging. A tract-based spatial statistics (TBSS) approach was used to detect differences across the whole brain in patients with OCD vs HCs; post hoc fiber tractography was applied to characterize developmental differences between the two groups. Relative to HCs, patients with OCD had lower fractional anisotropy (FA) values in the corpus callosum (CC), left anterior corona radiata (ACR), left superior corona radiata (SCR) and left superior longitudinal fasciculus (SLF), and higher radial diffusivity in the genu and body of CC. Among the TBSS de-projected region of interest results, compared with HCs, patients with OCD showed lower of the mean FA values of fiber bundles passing though the SLF, and shorter lengths of ACR, SCR and CC. In conclusion, this study provides novel evidence of widespread microstructural alterations in OCD and suggests that OCD may involve abnormalities affecting a broader network of regions than commonly believed.

Spontaneous neural activity in the right superior temporal gyrus and left middle temporal gyrus is associated with insight level in obsessive-compulsive disorder

BACKGROUND Insight into illness is an important issue for psychiatry disorder. Although the existence of a poor insight subtype of obsessive-compulsive disorder (OCD) was recognized in the DSM-IV, and the insight level in OCD was specified further in DSM-V, the neural underpinnings of insight in OCD have been rarely explored. The present study was designed to bridge this research gap by using resting-state functional magnetic resonance imaging (fMRI). METHODS Spontaneous neural activity were examined in 19 OCD patients with good insight (OCD-GI), 18 OCD patients with poor insight (OCD-PI), and 25 healthy controls (HC) by analyzing the amplitude of low-frequency fluctuation (ALFF) in the resting state. Pearson correlation analysis was performed between regional ALFFs and insight levels among OCD patients. RESULTS OCD-GI and OCD-PI demonstrated overlapping and distinct brain alterations. Notably, compared with OCD-GI, tOCD-PI had reduced ALFF in left middle temporal gyrus (MTG) and right superior temporal gyrus (STG), as well as increased ALFF in right middle occipital gyrus. Further analysis revealed that ALFF values for the left MTG and right STG were correlated negatively with insight level in patients with OCD. LIMITATIONS Relatively small sample size and not all patients were un-medicated are our major limitations. CONCLUSIONS Spontaneous brain activity in left MTG and right STG may be neural underpinnings of insight in OCD. Our results suggest the great role of human temporal brain regions in understanding insight, and further underscore the importance of considering insight presentation in understanding the clinical heterogeneity of OCD.