Hai-Chen Yang

Abnormalities of cortical-limbic-cerebellar white matter networks may contribute to treatment-resistant depression: a diffusion tensor imaging study.

BackgroundWhite matter abnormalities can cause network dysfunction that underlies major depressive disorder (MDD). Diffusion tensor imaging (DTI) is used to examine the neural connectivity and integrity of the white matter. Previous studies have implicated frontolimbic neural networks in the pathophysiology of MDD. Approximately 30% of MDD patients demonstrate treatment-resistant depression (TRD). However, the neurobiology of TRD remains unclear.MethodsWe used a voxel-based analysis method to analyze DTI data in young patients with TRD (n = 30; 19 males, 11 females) compared with right-handed, age- and sex-matched healthy volunteers (n = 25; 14 males, 11 females).ResultsWe found a significant decrease in fractional anisotropy (FA) (corrected, cluster size >50) in the left middle frontal gyrus (peak coordinates [−18 46–14]), left limbic lobe uncus (peak coordinates [−18 2–22]), and right cerebellum posterior lobe (peak coordinates [26–34 -40]). There was no increase in FA in any brain region in patients. We also found a significant negative correlation between mean regional FA values in the three areas and Beck Depression Inventory symptom scores.ConclusionsWe found significant differences in white matter FA in the frontal lobe, limbic lobe and cerebellum between TRD patients and controls. These data suggest that abnormalities of cortical-limbic-cerebellar white matter networks may contribute to TRD in young patients.

High-frequency rTMS treatment increases white matter FA in the left middle frontal gyrus in young patients with treatment-resistant depression

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for treatment-resistant depression (TRD), but its therapeutic mechanisms are unclear. White matter abnormalities are thought to cause network dysfunction underlying TRD. Diffusion tensor imaging (DTI) is an ideal tool for examining neural connections and the integrity of white matter. Few studies have used DTI to investigate the impact of rTMS on alterations of whiter matter in TRD. METHOD 30 young treatment-resistant unipolar depression patients (19 males and 11 females) were enrolled in a double-blind, randomized high-frequency (15 Hz) rTMS treatment study. Seventeen patients were treated with real stimulation, and 13 were treated with sham stimulation. White-matter fractional anisotropy (FA) was evaluated using voxel-based analysis (VBA) of FA maps derived from DTI before and after treatment. Twenty-five age- and gender-matched subjects were examined as a control group. RESULTS In an exploratory VBA method, clusters of fifty voxels or greater that survived a family-wise error (FWE)-corrected threshold of p<0.05 were considered significant. The results revealed significantly reduced FA in the left middle frontal gyrus, with peak coordinates [-18 46 -14] in TRD patients. This reduced FA was significantly improved after active rTMS treatment, but not sham stimulation. FA increases were correlated with decreased depressive symptoms. LIMITATIONS This study requires replication and further clarification in a larger patient population, and optimization of stimulation locations and methods. CONCLUSIONS These results suggest that the efficacy of rTMS on TRD is related to increased white-matter FA in the left middle frontal gyrus.

Validity of the 32-item Hypomania Checklist (HCL-32) in a clinical sample with mood disorders in China

BackgroundThe 32-item Hypomania Checklist (HCL-32), a questionnaire for screening bipolar disorders, has been utilised in several countries, but it unclear if the Chinese version of the HCL-32 is valid.MethodsConsecutive patients with bipolar disorders (BP, N = 300) and unipolar major depression (UP, N = 156) completed the Chinese version of the HCL-32. The subjects underwent a structured clinical interview for DSM-IV Axis-I disorders (SCID).ResultsThe eigenvalues for the first three factors in the HCL-32 were calculated as 5.16 (active/elated), 2.72 (risk-taking) and 2.48 (irritable) using factor analysis. Cronbachs alpha for the HCL-32 was calculated to be 0.88. Positive responses to twenty-eight items were significantly more frequent by patients with BP than those with UP, and the other four items (7th, 21st, 25th and 32nd) showed no such trend. Fourteen was the optimal cut-off for discriminating between BP and UP. The HCL-32 distinguished between BP-II and UP, with 13 being the optimal cut-off. A cut-off of 13 yielded a sensitivity of 0.77 and a specificity of 0.62 between BP and UP.ConclusionsThis study demonstrated that the simplified Chinese version of HCL-32 was valid for patients with mood disorders. The optimal cut-off of 13 for distinguishing between BP-II and UP was valid and could be used to improve the sensitivity of screening BP-II patients when the HCL-32 is used in psychiatric settings in China.

Sociodemographic and clinical features of bipolar disorder patients misdiagnosed with major depressive disorder in China

Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD), which may lead to inappropriate treatment and poor outcomes. This study aimed to compare demographic and clinical features between patients with MDD and those with BD, but being misdiagnosed as MDD, in China.

Validity of the Chinese version Mood Disorder Questionnaire (MDQ) and the optimal cutoff screening bipolar disorders.

To investigate the validity of the Chinese version of Mood Disorder Questionnaire (C-MDQ) in China. Patients with bipolar disorders (BP, N=284) and patients with unipolar depressive disorder (UP, N=134) were assessed with the C-MDQ. The Eigenvalues of the first two factors were 3.15 and 2.09, respectively. The Cronbachs alpha of the C-MDQ was 0.79. The frequency of positive responses of UP patients was significantly lower than those of BP patients for 12 items except the seventh item. A C-MDQ screening score of seven or more was the best cutoff between BP and UP. The C-MDQ could distinguish between bipolar II disorder (BP-II) and UP, and the best cutoff was five. A cutoff of five had a sensitivity of 0.80 and a specificity of 0.54 between BP and UP. This study demonstrated the good validity of C-MDQ in China. The best cutoff between BP-II and UP can be regarded as the optimal cutoff between BP and UP to improve the sensitivity of screening for BP-II. Five should be the optimal cutoff between the BP and UP when only the 13 items of the questionnaire are used in China.

Hypomanic symptoms assessed by the HCL-32 in patients with major depressive disorder: A multicenter trial across China

AIM To investigate the results of the Hypomania Checklist-32 (HCL-32) administered as a screening instrument in clinical settings to mood disorders patients in the depressive phase. METHODS A total of 1487 patients diagnosed and being treated for major depressive disorder (MDD) in 13 mental health centers across China were self-rated by the HCL-32 and independently examined by the Mini International Neuropsychiatric Interview (MINI). RESULTS After examination by the MINI, 309 (20.8%) of the 1487 patients clinically diagnosed as having MDD satisfied DSM-IV criteria for bipolar disorder (BD): 118 (7.9%) for bipolar I disorder (BD-I) and 191 (12.8%) for bipolar II disorder (BD-II). The mean HCL-32 score of the BD patients was statistically higher than that of patients with unipolar depression (UD, major depressive disorder), BD-II higher than UD, while no significant difference between BD-I and BD-II. The HCL-32 distinguished between BD and UD (best cutoff score 14), between BD-II and UD (best cutoff 12). At the optimum cutoff of 12 between BD and UD, the sensitivity was 0.86, specificity 0.69. LIMITATIONS No standardized instruments were used to measure the severity of depressive symptoms. Depressed patients with a previous history of BD were excluded from this study. CONCLUSIONS The HCL-32 results in this multicenter study of patients in the depressive phase were similar to those of earlier, generally smaller-scale studies which subjects could be in any mood phases. A score of 12 could be used as the optimum cutoff between BD and UD to improve screening for BD-II if the HCL-32 was applied in clinical settings in China.

White-matter density abnormalities in depressive patients with and without childhood neglect: A voxel-based morphometry (VBM) analysis

Childhood maltreatment (abuse or neglect) can result in changes to the brain structures and functions that underlie adult depression. Few studies have explored the impact of childhood maltreatment on white-matter microstructure, especially for childhood neglect. Nineteen depressive patients who experienced childhood neglect, 21 depressive patients who did not experience childhood neglect, and 20 healthy control subjects were compared in this study. The Childhood Trauma Questionnaire (CTQ), Hamilton Depressive Rating Scale (HAMD), Self-Rating Depression Scale (SDS), and Dysfunctional Attitude Scale (DAS) were used to evaluate each subject. High-resolution T1-weighted 3T magnetic resonance imaging scans and a whole-brain optimized voxel-based morphometry (VBM) approach were also used. Compared with healthy controls, the depressive group of subjects with childhood neglect showed significantly lower white-matter densities in the bilateral inferior parietal lobe (IPL) [43 -32 24] [-42 -42 25], whereas the depressive group without childhood neglect showed significantly lower densities in bilateral sub-lobar extra-nuclear white matter [27 -15 16] [-27 32 4]. White-matter densities in the bilateral sub-lobar extra-nuclear [-25 -17 18] [27 -13 20] and right brainstem midbrain [9 -34 -13] regions were higher in the depressive patients with childhood neglect than in the depressive patients without childhood neglect. White-matter densities in the bilateral inferior parietal lobe were negatively correlated with neglect total scores on the CTQ and with HAMD and DAS scores. White-matter densities in the bilateral sub-lobar extra-nuclear region were only negatively correlated with HAMD scores. Subjects that have depression with or without childhood neglect show different white-matter microstructural abnormalities.

Demographic and clinical features and prescribing patterns of psychotropic medications in patients with the melancholic subtype of major depressive disorder in China.

Background Little has been known about the demographic and clinical features of the melancholic subtype of major depressive disorder (MDD) in Chinese patients. This study examined the frequency of melancholia in Chinese MDD patients and explored its demographic and clinical correlates and prescribing patterns of psychotropic drugs. Methods A consecutively collected sample of 1,178 patients with MDD were examined in 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide. The cross-sectional data of patients’ demographic and clinical characteristics and prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. The diagnosis of the melancholic subtype was established using the Mini International Neuropsychiatric Interview (MINI). Medications ascertained included antidepressants, mood stabilizers, antipsychotics and benzodiazepines. Results Six hundred and twenty nine (53.4%) of the 1,178 patients fulfilled criteria for melancholia. In multiple logistic regression analyses, compared to non-melancholic counterparts, melancholic MDD patients were more likely to be male and receive benzodiazepines, had more frequent suicide ideations and attempts and seasonal depressive episodes, while they were less likely to be employed and receive antidepressants and had less family history of psychiatric disorders and lifetime depressive episodes. Conclusions The demographic and clinical features of melancholic MDD in Chinese patients were not entirely consistent with those found in Western populations. Compared to non-melancholic MDD patients, melancholic patients presented with different demographic and clinical features, which have implications for treatment decisions.

Alterations in regional homogeneity of resting-state brain activity in patients with major depressive disorder screening positive on the 32-item hypomania checklist (HCL-32)

BACKGROUND Bipolar disorder (BD) is difficult to diagnose in the early stages of the illness, with the most frequent misdiagnosis being major depressive disorder (MDD). We aimed to use a regional homogeneity (ReHo) approach with resting-state functional magnetic resonance imaging (rs-fMRI) to investigate the features of spontaneous brain activity in MDD patients screening positive on the 32-item Hypomania Checklist (HCL-32). METHODS Nineteen MDD patients screening positive (HCL-32(+); 9 males; 24.9±5.7 years) and 18 patients screening negative (HCL-32(-); 9 males; 27.1±6.7 years), together with 24 healthy controls (HC; 11 males; 26.4±3.9 years) were studied. ReHo maps were compared and an receiver operating characteristic (ROC) analysis was conducted to confirm the utility of the identified ReHo differences in classifying the patients. RESULTS The MDD versus HC showed different ReHo in many brain areas, especially in the frontal and parietal cortex. The HCL-32(+) versus HCL-32(-) showed significant increase of ReHo in the right medial superior frontal cortex, left inferior parietal cortex and middle/inferior temporal cortex, and decrease of ReHo in the left postcentral cortex and cerebellum. ROC analysis showed good sensitivity and specificity for distinguishing these two subgroups of MDD. LIMITATIONS Recruited patients were all on antidepressants and standard mania rating scales were not performed to assess their hypomanic symptoms. CONCLUSIONS The rs-fMRI measurement of ReHo in distributed brain regions may be putative biomarkers which could differentiate subthreshold BD from MDD.

Evaluation of Mood Disorder Questionnaire (MDQ) in Patients with Mood Disorders: A Multicenter Trial across China

Background The aim of this study was to test the ability of the Chinese version of the Mood Disorder Questionnaire (MDQ) to identify Bipolar Disorders (BD) in patients diagnosed with Major Depressive Disorder (MDD) or Unipolar Disorder (UD) in the clinical setting. Methods 1,487 being treated for MDD or UD at 12 mental health centers across China, completed the MDQ and subsequently examined by the Mini International Neuropsychiatric Interview (MINI). Receiver Operating Characteristic(ROC) curves were used to determine the ability of the MDQ to differentiate between BD (BD, BD-I and BD-II) and MDD or UD and patients with BD-I from patients with BD-II. Results Of the 1,487 patients, 309 (20.8%) satisfied the DSM-IV criteria for BD: 118 (7.9%) for BD-I and 191 (12.8%) for BD-II. When only part one of the MDQ was used, the best cutoff was 7 between BD and UD (sensitivity 0.66, specificity 0.88, positive predictive value 0.59, negative predictive value 0.91), 6 between BD-II and UD, and 10 between BD-I and BD-II. If all three parts of the MDQ were used, the MDQ could not distinguish between BD and UD at a cutoff of 7 (or 6), and the sensitivity was only 0.22 (or 0.24). Conclusion The Chinese version of the MDQ had good psychometric features in screening bipolar disorders from depressive patients with mood disorders when part two and part three of the MDQ were ignored.