· In this issue ·

The current issue starts with a review by Professors Wang and Guo[1]on the long history of research in China on event-related potentials (ERPs) in patients with schizophrenia, with a particular focus on P300 and auditory P50 inhibition. This method for assessing the underlying pathophysiological mechanisms of schizophrenia is relatively simple and inexpensive so it flourished among researchers in China who were not as well resourced as their colleagues in highincome countries. A substantial body of literature has developed that finds correlates between specific ERP indicies and different types of cognitive deficits in schizophrenia. Some of these indices change with treatment and some do not; some are seen in firstdegree relatives of patients with schizophrenia and others are not. There is increasing optimism that specific ERP indicies will be identified that can be used in the diagnosis and clinical prognosis of schizophrenia. The recent rapid development of fMRI studies in China as research budgets have increased has, to some extent, eclipsed studies on ERPs. But, unlike neuroimaging studies, electrophysiological measures can provide temporal resolution in milliseconds—similar to the speed of neural processes—so Wang and Guo strongly recommend undertaking studies that integrate ERP and neuroimaging techniques.

The first research paper[2]is an example of the literature described in the review of ERP studies. This study uses event-related brain potential (ERP) topographic mapping techniques to characterize the location and intensity of cognitive activity during mental rotation tasks (i.e., mental rotation of two-dimensional and three-dimensional objects) in patients with schizophrenia. Like previous studies, they find impaired performance on mental rotation tasks by patients versus controls, right hemispheric dominance during mental rotation tasks in both patients and controls, and a much weaker contribution from the left hemisphere in the patient group than in the control group. Unlike most other studies, they also found a much faster reaction time in the patient group and a differential response to normally oriented images versus mirror images that was not found in the control group. This unique pattern of deficits in the mental rotation task reveals several potential electrophysiological biomarkers that might identify individuals at high risk of schizophrenia. Further studies with larger, more representative samples that follow changes in the proposed biomarkers over time and that assess them in first-degree family members of patients are needed.

The second research paper[3]assesses the crosssectional relationship between functional status, clinical symptoms and neurocognitive variables in hospitalized patients during an acute episode of schizophrenia. The study had two unexpected findings. First, unlike most studies on functional determinants in schizophrenia, they found that their measure of social functioning (the Personal and Social Performance Scale, PSP) was strongly correlated with clinical measures derived from the Positive and Negative Symptom Scale (PANSS) but not with their measures of cognitive functioning (the Letter-Numbering Sequencing Task and the Hong Kong List Learning Test). Second, they failed to replicate the common finding of a close relationship between the severity of negative symptoms and cognitive functioning. It is, of course, notoriously difficult to reliably assess patients’ social functioning while on an inpatient ward because the structured environment and rigid social roles are so different from what patients experience in the community. This and the relatively simple measures of neurocognitive functioning employed in the study may have been a factor in these negative findings. But it is also possible that the relative importance of neurocognitive factors and clinical symptoms on the functional status of a patient with schizophrenia changes over the course of the illness and as the severity of clinical symptoms waxes and wanes. Longitudinal studies that make repeated assessments of these three classes of variables (i.e., symptoms, cognition and functioning) in both inpatient and community settings are needed to resolve this issue.

The third research paper[4]addresses an important problem in the management of patients with schizophrenia: the relationship between insight and internalized stigma. Internalization of stigmatizing attitudes about mental illness is believed to be a major factor limiting patients’ adherence with treatment so understanding the mechanisms that influence this process may help to identify interventions that can improve adherence. The findings from western studies in the area suggest that patients with poor insight have relatively little internalized stigma but as their insight improves with treatment the intensity of the internalized stigma increases. The current crosssectional study categorized inpatients and outpatients with schizophrenia to ‘lacking insight into their illness’and ‘having insight into their illness’ based on one item in the Chinese version of the Brief Psychiatric Rating Scale (BPRS), evaluated the severity of their clinical symptoms using PANSS, and then administered two self-completion instruments about stigma (Internalized Stigma of Mental Illness; and Modified Consumer Experiences of Stigma Questionnaire). The results did not confirm previous studies showing higher levels of internalized stigma in individuals with better insight; on logistic regression analysis the only factor that was significantly associated with lack of insight was inpatient (versus outpatient) status. These findingssuggest that internalized stigma and insight may have different determinants cross culturally, so some of the conventional wisdom about them based on western studies may need to be reconsidered. But a basic problem in such studies is that insight into the illness can fluctuate rapidly with fluctuations in the clinical symptoms of the illness while internalized stigma typically changes over a much longer timeframe; so longitudinal studies will be needed to provide a more realistic assessment of the relationship between these two aspects of schizophrenia.

The fourth research paper[5]is about internet addiction in university students, a topic of considerable public concern in China. The authors used the Tridimensional Personality Questionnaire (TPQ) to compare the personality characteristics of a representative sample of 697 students from universities in Wenzhou who did and did not meet criteria for internet addition as assessed by a self-report measure (the Chen Internet Addiction Scale). The cross-sectional prevalence of internet addiction in the students was 6.9% (95% CI=5.1-9.1%), which is within the range of prevalences reported elsewhere in China (4.5-15.0%). The univariate analysis confirmed previous reports from Taiwan about a strong relationship between personality characteristics and internet addiction. Compared to those without internet addiction students with internet addiction had higher scores on the novelty-seeking and harmavoidance subscales of the TPQ but lower scores on the reward-dependence subscale. Multivariate logistic regression analysis found that internet addiction was independently associated with male gender, Han (versus minority) ethnicity, and substance use (i.e., tobacco or alcohol use). After adjustment for these demographic variables the relationship between personality characteristics and internet addiction disappeared. This result highlights the importance of adjusting results from cross-sectional studies for potential confounding factors. The conclusions of the many previous studies from China and Taiwan about the relationship of personality traits to internet addiction that have not adjusted for demographic factors need to be reconsidered.

The forum[6-8]and the case report[9]in this issue are about clozapine, a medication that has had a very different history in China than in the United States. In China clozapine was first approved for use in 1976 and was clinically available in an inexpensive generic form by the mid-1980s. Its use increased rapidly during the 1990’s because it was cheap, highly effective, and had relatively few side effects compared to the firstgeneration antipsychotics. For many years it was the only second-generation antipsychotic available, but with the introduction of other second-generation antipsychotics that were patent protected in China (staring with risperidone), the higher profit-margins for hospitals of the new drugs and their lower risk of serious side-effects led to a rapid decline in the use of monotherapy clozapine. Nevertheless, it remains the most commonly used antipsychotic in many parts of the country, often as an adjunctive treatment to other antipsychotics—despite the lack of evidence that this type of polypharmacy is effective. In the United States clozapine was introduced in 1989; it was widely recognized as more effective than any other available agent for treatment-resistant patients with schizophrenia. But its risk of severe side-effects such as potentially fatal agranulocytosis severely restricted it use despite evidence that careful monitoring could greatly reduce the likelihood of these serious outcomes. As a result, there are large numbers of treatmentresistant patients in the United States who are being inadequately treated with multiple antipsychotic medications because their clinicians are unwilling to try clozapine. Thus clozapine is seriously under-utilized in the United States and often inappropriately used in China. The 2009 eleven-year follow-up study of patients with schizophrenia in Finland[10]found that clozapine use was associated with significantly lower overall mortality than any other antipsychotic, so resolving the issue of the appropriate use of clozapine is not simply a problem in clinical pharmacology, it has serious public health consequences.

1. Wang JJ, Guo Q.Research in China on event-related potentials in patients with schizophrenia. Shanghai Arch Psychiatry 2012; 24 (2): 67-75.

2. Chen J, Yang L, Zhao J, Li L, Liu G, Ma W, Zhang Y, Wu X, Deng Z, Tuo R. Hemispheric dominance during the mental rotate task in patients with schizophrenia. Shanghai Arch Psychiatry 2012; 24 (2): 76-82.

3. Zuo S, Byrne LK, Peng D, Mellor D, McCabe M, Zhang J, Huang J, Xu Y. Symptom severity is more closely associated with social functioning status in inpatients with schizophrenia than cognitive deficits. Shanghai Arch Psychiatry 2012; 24 (2): 83-90.

4. Lu Y, Wang X. Correlation between insight and internalized stigma in patients with schizophrenia. Shanghai Arch Psychiatry 2012; 24 (2): 91-98.

5. Jiang D, Zhu S, Ye M, Lin C. Cross-sectional survey of prevalence and personality characteristics of college students with internet addiction in Wenzhou China. Shanghai Arch Psychiatry 2012; 24 (2): 99-107.

6. Wang C, Li L. Proper use of clozapine: experiences in China. Shanghai Arch Psychiatry 2012; 24 (2): 108-109.

7. Kelly DL, Wehring HJ, Vyas G. Current status of clozapine in the United States. Shanghai Arch Psychiatry 2012; 24 (2): 110-113.

8. Kane J. Clozapine is under-utilized. Shanghai Arch Psychiatry 2012; 24 (2): 114-115.

9. Wang Y, He R, Zhang H. Case report on clozapine-associated neuroleptic malignant syndrome. Shanghai Arch Psychiatry 2012; 24 (2): 116-117.

10. Tiihonen J, L?nnqvist J, Wahlbeck K, Klaukka T, Niskanen L, Tanskanen A, et al. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study. Lancet 2009; 374(9690): 620-627.