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2014 Volume 26 Issue 1
In this issue
Systematic review and meta-analysis
Recent research about mild cognitive impairment in China Yan CHENG, Shifu XIAO Summary: The rapid aging of the Chinese population has spurred interest in research about the cause and prevention of dementia and its precursor, mild cognitive impairment (MCI). This review summarizes the last decade of research in China about MCI. Extensive research about the epidemiology, neuropsychological characteristics, diagnosis, genetic etiology, neuroimaging and electrophysiological changes, and treatment of MCI has provided some new insights but few breakthroughs. Further advances in the prevention and treatment of MCI will require a greater emphasis on multi-disciplinary prospective studies with large, representative samples that use standardized methods to assess and monitor changes in cognitive functioning over time. 
Key words: mild cognitive impairment, dementia, research methodology, China
Original research article
Cross-sectional survey of the relationship of symptomatology, disability and family burden among patients with schizophrenia in Sichuan, China Zhuoqiu ZHANG, Hong DENG, Ying CHEN, Shuiying LI, Qian ZHOU, Hua LAI, Lifang LIU, Ling LIU, Wenwu SH Background: Schizophrenia is a chronic condition that leads to high rates of disability and high levels of family burden but the interactive relationship between these variables remains unclear, particularly in low- and middle-income countries where the vast majority of patients live with their families. 
Aim: Assess the symptom severity, level of disability, and family burden among clinically stable outpatients with schizophrenia in Sichuan, China. 
Methods: A total of 101 clinically stable outpatients with schizophrenia who had a median duration of illness of five years were assessed using the World Health Organization Disability Assessment Scale 2.0 (WHODAS II), the Positive and Negative Syndrome Scale (PANSS) and the Family Adaptation, Partnership, Growth, Affection and Resolve Index scale (APGAR); and their caregivers were surveyed using the Family Burden Interview Schedule (FBIS). 
Results: Among the 101 patients, 92 lived with their immediate family members, 74 had clinically significant disability, and 73 were unemployed. The level of disability was associated with the severity of symptoms (r=0.50, p
Conclusions: Even after adjusting for the severity of patients’ symptoms, patient disability is independently associated with family burden. This highlights the importance of targeting both symptoms and disability in treatment strategies for this severe, often lifelong, condition. In countries like China where most individuals with schizophrenia live with their families, family burden is an important component of the impact of the illness on the community that should be included in measures of the relative social and economic importance of the condition. 
Key words: schizophrenia, family relationships, burden of illness, disability evaluation, cross-sectional survey, China
Duration of untreated psychosis and clinical outcomes of first-episode schizophrenia: a 4-year follow-up study Hongyun QIN*, Jie ZHANG, Zhenping WANG, Haiying MIN, Caiying YAN, Fuzhen CHEN, Weizhong FU, Ming ZHA Background: The relationship between the duration of untreated psychosis and long-term clinical outcomes remains uncertain. 
Objective: Prospectively assess the relationship of the duration of untreated psychosis on clinical outcomes in a sample of individuals with first-onset schizophrenia treated at the Pudong Mental Health Center from January 2007 to December 2008. 
Methods: Information about general health, psychotic symptoms and social functioning were collected using the Brief Psychiatric Rating Scale (BPRS), Treatment Emergent Symptom Scale (TESS), Morningside Rehabilitation Status Scale (MRSS), and Social Disability Screening Schedule (SDSS) at baseline and in June 2010 and June 2012. 
Results: The 43 individuals with first-episode schizophrenia participating in the study were divided into short (≤24 weeks) and long (>24weeks) duration of untreated psychosis (DUP) groups. The mean (sd) duration of follow-up was 1197 (401) days in the short DUP group and 1412 (306) days in the long DUP group (t=9.98, p=0.055). Despite less prominent psychotic symptoms at the time of first diagnosis among patients who had a long DUP compared to those with a short DUP (BPRS mean scores, 42.5 [8.4] v. 50.0 [10.6], t=2.42, p=0.0210) and a similar number of clinical relapses (based on positive symptoms assessed by the BPRS), patients with a long DUP were more likely to require hospitalization at the time of first diagnosis (52% [11/21] v. 9% [2/22], χ2=9.55, p=0.002) and more likely to require re-hospitalization during the first two years of treatment (67% [14/21] v. 32% [7/22], χ2=5.22, p=0.022). Moreover, after four years of routine treatment, despite a similar severity of positive symptoms, patients who had had a long DUP prior to initiating treatment had significantly poorer social functioning than those who had had a short DUP (SDSS mean scores, 7.0 [5.2] v. 3.4 [4.9], t=2.20, p=0.035). 
Conclusions: These findings show that despite having a similar level of psychotic symptoms – as measured by the BPRS – compared to patients with a short DUP, patients with schizophrenia who have a long DUP prior to initial treatment have poorer long-term social functioning. This confirms the clinical importance of the early recognition and treatment of individuals with chronic psychotic conditions. 
Key words: schizophrenia, antipsychotic agents, treatment, follow-up studies, China
Five-year follow-up study of multi-domain cognitive training for healthy elderly community members Wei FENG, Chunbo LI, You CHEN, Yan CHENG, Wenyuan WU Background: Cognitive training, a safe non-pharmacological intervention, may help mitigate cognitive decline and prevent the development of dementia in elderly individuals. 
Objective: Evaluate the long-term effects of cognitive training among healthy elderly community members. 
Methods: Healthy individuals 70 years of age or older from one urban community in Shanghai were screened and the 151 individuals who met inclusion criteria were assigned either to an intervention group (n=90) or a control group (n=61). The intervention involved twice-weekly training in reasoning, memory, and strategy that continued for 12 weeks (a total of 24 sessions). Participants were assessed at baseline and at 12 weeks, and 5 years after enrollment using the Chinese versions of the Neuropsychological Test Battery for Elderly persons (NTBE), the Stroop Color-Word Test, and a general health questionnaire. 
Results: Forty-nine (54%) intervention group subjects and 33 (54%) control group subjects completed the 5-year follow-up. There were few differences in the baseline neurocognitive measures of those who did and did not complete the 5-year follow-up, and there were few differences between those who dropped out of the intervention group compared to those who dropped out of the control group. At the 5-year follow-up, individuals in the intervention group performed better than those in the control group on only 5 measures (in the Trails Making A Test and the Cancellation Test 3) of the 61 measures assessed by NTBE and the Stroop tests, but none of these differences met the pre-determined required level of statistical significance (p=0.0008). 
Conclusion: We do not confirm the results of previous studies that report long-term benefits of brief cognitive training courses for elderly community residents. Our failure to identify differences in cognitive functioning five years after cognitive training is not likely due to differential dropout between the intervention and control groups but may be related to the relatively small sample and the large number of measures being assessed. Future intervention studies for cognitive training in the elderly should be hypothesis driven (i.e., focused on a single outcome measure of interest), use much larger samples, and include regular booster sessions as part of the cognitive training package. 
Key words: aged, cognition, neuropsychological tests, follow up studies, neuropsychology, China
Randomized controlled trial of four protocols of repetitive transcranial magnetic stimulation for treating the negative symptoms of schizophrenia Suhua ZHAO*, Jiehua KONG, Shuling LI, Zishun TONG, Chanjuan YANG, Huaqing ZHONG Background: The negative symptoms of schizophrenia are not effectively treated with antipsychotic medications. Repetitive transcranial magnetic stimulation (rTMS) is an alternative approach that may be more effective in treating negative symptoms, but there has been little research comparing the effectiveness of different rTMS stimulation protocols. 
Objective: Compare the effect of four different rTMS protocols in the treatment of the negative symptoms of schizophrenia. 
Methods: Ninety-six patients with schizophrenia who had prominent negative symptoms were randomly assigned to four treatment groups: 10 Hz, 20 Hz, theta burst stimulation (TBS), and mock rTMS (i.e., the control group). In the first three groups, the left dorsolateral prefrontal cortex was stimulated at 80% of the motor threshold five times per week for four weeks. Before and after the treatment, evaluators who were blind to the group assignment of patients administered the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS) and the Treatment Emergent Symptom Scale (TESS). 
Results: Three of the 96 patients dropped out during the trial (two from the control group and one from the 20 Hz group). Compared to the control group, after 4 weeks of rTMS treatment all three treatment groups had lower scores on the PANSS negative symptom subscale, the PANSS general psychopathology subscale, and the SANS. The TBS group had significantly larger reductions in these scores than the 10 Hz group and the 20 Hz group, but there were no significant differences between the 10 Hz and 20 Hz groups. There were no pre- versus post-treatment differences in the PANSS positive symptom subscale scores between the four groups. No serious adverse events occurred and there were no statistically significant differences in the TESS scores across the four groups. 
Conclusions: We find that rTMS, particularly the TBS stimulation protocol for rTMS, is a safe and effective treatment method for patients with schizophrenia who have prominent negative symptoms. Longitudinal studies with large samples are needed to optimize the rTMS treatment, to identify the stimulation protocol, duration, intensity and treatment interval that provides the best therapeutic result at the lowest risk to the patient. 
Key words: repetitive transcranial magnetic stimulation, schizophrenia, randomized controlled trial, treatment, China
Forum
Challenges in the diagnosis and treatment of transsexualism in contemporary China
Case report
Case report of refractory tardive dystonia induced by olanzapine Zhenxiao SUN, Xiangli WANG Summary: Tardive dystonia (TDt), a cluster of extrapyramidal symptoms that are caused by long-term use of antipsychotic medication, is characterized by difficulty in autonomic movements of skeletal (voluntary) muscles and consequent deformations of the body. TDt is rarely seen among patients taking olanzapine, but olanzapine was the precipitating antipsychotic medication in this 22-year old male patient with schizophrenia who developed lip puckering, persistent involuntary torticollis, muscular pain, axial dystonia and unstable gait after taking a standard dose of olanzapine regularly for about one year. His symptoms did not resolve after his olanzapine was stopped. Four months of treatment with clozapine combined with magnesium valproate, vitamin E, tiapride, and lorazepam did not lead to any improvement in the dystonia. 
Key words: movement disorders/adverse effects, olanzapine, schizophrenia
Biostatistics in psychiatry
Establishing a data monitoring committee for clinical trials Julia Y. LIN, Ying LU Summary: A data monitoring committee (DMC) is a group of clinicians and biostatisticians appointed by study sponsors who provide independent assessment of the safety, scientific validity and integrity of clinical trials. In the United States, the Food and Drug Administration requires the formation of DMC in all trials that assess new interventions. DMC are also strongly recommended in other clinical studies that have substantial safety issues, that have double-blind treatment assignment or that are expected to have a major impact on clinical practice. They are important in clinical research in psychiatry because they provide an added layer of protection for the vulnerable populations that are often enrolled in such studies. This report describes the role, formation and operation of DMC. 
Key words: data monitoring committee, clinical trials, interim analysis, biostatistics