Chuan-Yue Wang

Effect of Antipsychotic Medication Alone vs Combined With Psychosocial Intervention on Outcomes of Early-Stage Schizophrenia: A Randomized, 1-Year Study

CONTEXT Antipsychotic drugs are limited in their ability to improve the overall outcome of schizophrenia. Adding psychosocial treatment may produce greater improvement in functional outcome than does medication treatment alone. OBJECTIVE To evaluate the effectiveness of antipsychotic medication alone vs combined with psychosocial intervention on outcomes of early-stage schizophrenia. DESIGN Randomized controlled trial. SETTING Ten clinical sites in China. PARTICIPANTS Clinical sample of 1268 patients with early-stage schizophrenia treated from January 1, 2005, through October 31, 2007. Intervention Patients were randomly assigned to receive antipsychotic medication treatment only or antipsychotic medication plus 12 months of psychosocial intervention consisting of psychoeducation, family intervention, skills training, and cognitive behavior therapy administered during 48 group sessions. MAIN OUTCOME MEASURES The rate of treatment discontinuation or change due to any cause, relapse or remission, and assessments of insight, treatment adherence, quality of life, and social functioning. RESULTS The rates of treatment discontinuation or change due to any cause were 32.8% in the combined treatment group and 46.8% in the medication-alone group. Comparisons with medication treatment alone showed lower risk of any-cause discontinuation with combined treatment (hazard ratio, 0.62; 95% confidence interval, 0.52-0.74; P < .001) and lower risk of relapse with combined treatment (0.57; 0.44-0.74; P < .001). The combined treatment group exhibited greater improvement in insight (P < .001), social functioning (P = .002), activities of daily living (P < .001), and 4 domains of quality of life as measured by the Medical Outcomes Study 36-Item Short Form Health Survey (all P < or = .02). Furthermore, a significantly higher proportion of patients receiving combined treatment obtained employment or accessed education (P = .001). CONCLUSION Compared with those receiving medication only, patients with early-stage schizophrenia receiving medication and psychosocial intervention have a lower rate of treatment discontinuation or change, a lower risk of relapse, and improved insight, quality of life, and social functioning. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00654576.

Abnormal baseline brain activity in bipolar depression: A resting state functional magnetic resonance imaging study

We examined resting state brain activity in the depressive phase of bipolar disorder (BD) by measuring the amplitude of low-frequency fluctuations (ALFF) in the functional magnetic resonance imaging (fMRI) signal. Unlike functional connectivity, the ALFF approach reflects local properties in specific regions and provides direct information about impaired foci. Groups of 26 patients with BD depression and 26 gender-, age-, and education-matched healthy subjects participated in fMRI scans. We examined group differences in ALFF findings as well as correlations between clinical measurements and ALFF in the regions showing significant group differences. Our results showed that patients with BD depression had significantly increased ALFF in the left insula, the right caudate nucleus, the temporal gyrus, the bilateral inferior frontal gyrus, and the posterior lobe of the cerebellum. They also had decreased ALFF in the left postcentral gyrus, the left parahippocampal gyrus, and the cerebellum. Moderate negative correlations were found between the Hamilton Depression Rating Scale score and ALFF in the left insular cortex in the patient group. These results support a model of BD that involves dysfunction in the prefrontal-limbic networks and associated striatal systems. We also demonstrated the feasibility of ALFF as a technique to investigate persistent cerebral dysfunction in BD.

Regional homogeneity within the default mode network in bipolar depression: a resting-state functional magnetic resonance imaging study.

Aim We sought to use a regional homogeneity (ReHo) approach as an index in resting-state functional magnetic resonance imaging (fMRI) to investigate the features of spontaneous brain activity within the default mode network (DMN) in patients suffering from bipolar depression (BD). Methods Twenty-six patients with BD and 26 gender-, age-, and education-matched healthy subjects participated in the resting-state fMRI scans. We compared the differences in ReHo between the two groups within the DMN and investigated the relationships between sex, age, years of education, disease duration, the Hamilton Rating Scale for Depression (HAMD) total score, and ReHo in regions with significant group differences. Results Our results revealed that bipolar depressed patients had increased ReHo in the left medial frontal gyrus and left inferior parietal lobe compared to healthy controls. No correlations were found between regional ReHo values and sex, age, and clinical features within the BD group. Conclusions Our findings indicate that abnormal brain activity is mainly distributed within prefrontal-limbic circuits, which are believed to be involved in the pathophysiological mechanisms underlying bipolar depression.

A randomized, crossover comparison of herbal medicine and bromocriptine against risperidone-induced hyperprolactinemia in patients with schizophrenia.

Hyperprolactinemia is a common adverse effect that occurs as a result of antipsychotic therapies, which often results in discontinuation. Empirical evidence has shown that some herbal medicines have suppressive effects on prolactin (PRL) hyperactivities. This study was designed to compare the herbal preparation called Peony-Glycyrrhiza Decoction (PGD) with bromocriptine (BMT), a dopamine agonist widely used for PRL-secreting disorders, in the treatment of risperidone-induced hyperprolactinemia. Twenty schizophrenic women who were under risperidone maintenance treatment, diagnosed with hyperprolactinemia (serum PRL levels >50 &mgr;g/L), and currently experiencing oligomenorrhea or amenorrhea were selected for the study. Subjects were randomized to additional treatment with PGD (45 g/d) followed by BMT (5 mg/d) or BMT followed by PGD at the same doses for 4 weeks each, with an interval of 4-week washout period between 2 treatment sessions. The severity of psychotic symptoms, adverse events, serum PRL, estradiol, testosterone, and progesterone levels were examined at baseline and end point. Peony-Glycyrrhiza Decoction treatment produced a significant baseline-end point decrease in serum PRL levels, without exacerbating psychosis and changing other hormones, and the decreased amplitudes were similar to those of BMT (24% vs 21%-38%). Moreover, there was a significantly greater proportion of patients during PGD treatment than BMT treatment showing improvements on adverse effects associated with hyperprolactinemia (56% vs 17%, P = 0.037). These results suggest that the herbal therapy can yield additional benefits while having comparable efficacy in treating antipsychotic-induced hyperprolactinemia in individuals with schizophrenia.

Resting-state abnormal baseline brain activity in unipolar and bipolar depression

In the present study, we investigated differences in resting-state brain activity in patients with bipolar depression (BD) and unipolar depression (UD) by measuring the amplitude of low-frequency fluctuation (ALFF) of functional magnetic resonance imaging (fMRI) signals. Twenty-one BD and 21 gender-, age-, and education-matched UD patients participated in the fMRI analysis. We compared the differences in the ALFF between the two groups and investigated the correlation between clinical measurements and ALFF in the regions displaying significant group differences. BD subjects displayed significantly decreased ALFF in the left superior parietal lobule and the left posterior insula (l-PI). They also displayed increased ALFF in the right dorsal anterior insula (r-dAI) when compared to the UD group. Moderate negative correlations were found between the Hamilton Depression Rating Scale score (HAMD) and the ALFF in the l-PI for the BD (r=-0.44, P=0.02) and UD (r=-0.45, P=0.02) groups. Our results support the notion that insular subregions may contribute to the precise differentiation between BD and UD.

Clozapine in China.

Clozapine remains one of the most commonly used antipsychotic medications in China. As China has the largest population internationally on clozapine treatment, its experience and research findings are of keen interest to Western psychiatrists. However, most of the related papers have hitherto been published only in Chinese language journals. Here we review mainly Chinese-language publications on the use of clozapine in China. A descriptive study based on literature identified from searches of Medline and the China National Knowledge Infrastructure (CNKI) databases (1979-2007), and other hand-picked references. Unlike the situation in other countries, clozapine is still widely used for a number of psychiatric disorders in China, though the prescription of other second-generation antipsychotics (SGAs) is also increasing. About 25-60% of all treated patients with schizophrenia receive clozapine; and clozapine is preferred by some as a first-line treatment for schizophrenia. Clozapine is also used for other conditions such as mania, treatment-resistant depression and drug abuse. The average daily dose is between 200 and 400 mg. The incidence of leukopenia is 3.92% and agranulocytosis 0.21% in China, with about one third of reported cases of patients with agranulocytosis dying. Weight gain and clozapine-associated diabetes are also commonly reported in the Chinese population. Clozapine is currently the most commonly used treatment for schizophrenia in China. Chinese psychiatrists need to pay more attention to its potential toxic side effects when they make drug choices.

Prevalence and socio-demographic correlates of major depressive episode in rural and urban areas of Beijing, China

OBJECTIVE This study aimed to determine the 12-month and lifetime prevalence of major depressive episode (MDE) and their socio-demographic correlates in both the urban and rural areas of Beijing, China. METHODS A total of 4767 adults were randomly selected and interviewed in Beijing using the Composite International Diagnostic Interview (CIDI 1.0). Basic socio-demographic and clinical data were collected during the interviews. RESULTS The overall 12-month prevalence of MDE was 3.2%; 2.8% and 3.8% for men and women, respectively. The overall lifetime prevalence of MDE was 5.3%; 4.4% and 6.3% for men and women, respectively. Being older than 25 years of age was independently associated with increased risk of MDE. Sixteen point three percent of the subjects with lifetime MDE attempted suicide while the rate of suicide attempts was only 0.2% in subjects without MDE. The percentage of subjects with MDE who received any type of treatment from medical practitioners was 33.1%; of them, only 5.4% sought help from mental health professionals. CONCLUSIONS National epidemiologic surveys are needed to further explore the prevalence of MDE in China. The low percentage of subjects treated for MDE constitutes a major public health problem that should be urgently addressed.

Risperidone Maintenance Treatment in Schizophrenia: A Randomized, Controlled Trial

OBJECTIVE Prevention of relapse is the crucial task in the maintenance treatment of schizophrenia. The investigators in this study sought to determine the duration of maintenance treatment needed with the initial therapeutic dose, in contrast to a reduced dose. METHOD In a multicenter open-label, randomized, controlled study, patients with schizophrenia who were clinically stabilized following an acute episode were randomly assigned to a no-dose-reduction group (initial optimal therapeutic dose continued throughout the study), a 4-week group (initial optimal therapeutic dose continued for 4 weeks, followed by a 50% dose reduction that was maintained until the end of the study), or a 26-week group (initial optimal therapeutic dose continued for 26 weeks, followed by a 50% dose reduction until the end of the study). All patients continued until the last recruited patient completed the 1-year follow-up. RESULTS Of the 404 patients who met the entry criteria and were randomly assigned, 374 completed the study. The estimated mean time from entry to relapse was 571 days in the 4-week group, 615 days in the 26-week group, and 683 days in the no-dose-reduction group, with estimated relapse rates of 30.5%, 19.5%, and 9.4%, respectively. Patients in the no-dose-reduction group experienced greater reduction in the severity of psychotic symptoms. CONCLUSIONS Patients who continued to receive the full risperidone dose used for their acute episode had fewer relapses than those who had dose reductions after 4 weeks or 26 weeks during the maintenance period. There was negligible difference in side effects among the three groups.

Regional homogeneity of resting-state brain abnormalities in bipolar and unipolar depression

OBJECTIVE Bipolar disorder patients experiencing a depressive episode (BD-dep) without an observed history of mania are often misdiagnosed and are consequently treated as having unipolar depression (UD), leading to inadequate treatment and poor outcomes. An essential solution to this problem is to identify objective biological markers that distinguish BD-dep and UD patients at an early stage. However, studies directly comparing the brain dysfunctions associated with BD-dep and UD are rare. More importantly, the specificity of the differences in brain activity between these mental disorders has not been examined. With whole-brain regional homogeneity analysis and region-of-interest (ROI) based receiver operating characteristic (ROC) analysis, we aimed to compare the resting-state brain activity of BD-dep and UD patients. Furthermore, we examined the specific differences and whether these differences were attributed to the brain abnormality caused by BD-dep, UD, or both. METHODS Twenty-one bipolar and 21 unipolar depressed patients, as well as 26 healthy subjects matched for gender, age, and educational levels, participated in the study. We compared the differences in the regional homogeneity (ReHo) of the BD-dep and UD groups and further identified their pathophysiological abnormality. In the brain regions showing a difference between the BD-dep and UD groups, we further conducted receptive operation characteristic (ROC) analyses to confirm the effectiveness of the identified difference in classifying the patients. RESULTS We observed ReHo differences between the BD-dep and UD groups in the right ventrolateral middle frontal gyrus, right dorsal anterior insular, right ventral anterior insular, right cerebellum posterior gyrus, right posterior cingulate cortex, right parahippocampal gyrus, and left cerebellum anterior gyrus. Further ROI comparisons and ROC analysis on these ROIs showed that the right parahippocampal gyrus reflected abnormality specific to the BD-dep group, while the right middle frontal gyrus, the right dorsal anterior insular, the right cerebellum posterior gyrus, and the right posterior cingulate cortex showed abnormality specific to the UD group. CONCLUSIONS We found brain regions showing resting state ReHo differences and examined their sensitivity and specificity, suggesting a potential neuroimaging biomarker to distinguish between BD-dep and UD patients. We further clarified the pathophysiological abnormality of these regions for each of the two patient populations.

Voxel-based morphometry study of the insular cortex in female patients with current and remitted depression

OBJECTIVE Women are more prone to major depressive disorders (MDDs) and the incidence of MDD in women is almost twice that of men. Insular cortex abnormalities are a common finding in neuroanatomical studies of patients with MDD. However, it remains largely unclear whether female MDD patients at different clinical stages show morphologic changes in a specific subregion of the insular cortex. Additionally, it is not understood if any subregion changes can be used as a state or trait marker of MDD, and whether the diagnostic performance of any marker is sufficient to identify MDD. METHODS Nineteen right-handed current MDD (cMDD) female patients and 19 remitted MDD (rMDD) patients, as well as 19 healthy controls matched for age and educational level, were recruited into the study. By means of voxel-based morphometry (VBM), we investigated gray matter volume abnormalities in insular subregions among the three groups and further conducted region-of-interest (ROI)-based receiver operating characteristic (ROC) analyses. The data from these investigations were correlated with clinical data to confirm the effectiveness of the identified changes in the subregions in differentiating the three groups. RESULTS Both the cMDD and rMDD groups showed significantly decreased gray matter volumes in the left dorsal anterior insula compared to the healthy controls. The cMDD groups also showed decreased gray matter volumes in the right dorsal anterior insula relative to healthy controls. Further ROC comparisons demonstrated that the left dorsal anterior insula can effectively differentiate cMDD and rMDD groups from healthy controls. CONCLUSIONS Our findings suggest that the volume changes in the left dorsal anterior insular cortex may be a trait-related marker of vulnerability to MDD and that the right dorsal anterior insular cortex may involve pathological changes of MDD.