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2015 Volume 27 Issue 5
In this issue
Systematic review and meta-analysis
Meta-analysis of the relationship of peripheral retinal nerve fiber layer thickness to Alzheimer’s disease and mild cognitive impairment Meijuan WANG, Yingbo ZHU, Zhongyong SHI, Chunbo LI, Yuan SHEN Background: Previous studies report that the thickness of the peripheral retinal nerve fiber layer (RNFL) in individuals with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) is significantly thinner than in normal controls (NC), but RNFL thickness in different quadrants of the optic nerve remains unclear. 
Aim: Conduct a systematic review of studies that assess peripheral RNFL thickness in AD and MCI. 
Methods: Based on pre-defined criteria, studies in English or Chinese were identified from PubMed, Embase, ISI web of knowledge, Ovid/Medline, Science Direct, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chongqing VIP database, WANFANG DATA, and the China BioMedical Literature Service System (SinoMed). Review Manager 5.3 was used for analysis. 
Results: The 19 cross-sectional studies identified had a pooled sample of 1455 individuals. There was substantial heterogeneity between studies that compared RNFL in AD or MCI to normal controls, but this heterogeneity was primarily restricted to low-quality studies. Combining 6 high-quality studies (n=578) indicated that total RNFL thickness and the thickness of superior and inferior RNFL quadrants in AD were significantly thinner than in normal controls. Similarly, combining 5 high-quality studies (n=541) indicated significantly thinner total RNFL thickness in MCI than in controls. Six studies (n=589) found thinner RNFL in the superior and inferior quadrants in MCI than in controls; and 6 studies (n=487) found thinner RNFL in the temporal quadrant in MCI than in controls. Finally, 7 studies (n=432) indicated that total RNFL was thinner in AD than in MCI, and 6 studies (n=364) indicated thinner RNFL in the superior and inferior quadrants in AD than in MCI. 
Conclusions: Much of the heterogeneity in results from previous studies may be due to poor methodology. Peripheral RNFL thicknesses, particularly in the superior and inferior quadrants, becomes progressively thinner as cognitive function declines, so this could be a candidate biomarker for early identification of AD. Methodologically rigorous studies in large population-based cohort studies that follow elderly individuals over time and that simultaneously collect information on potential mediating factors (such as blood pressure, blood glucose, and lipid levels) are needed to confirm or disprove the potential predictive value of RNFL. 
Keywords: Alzheimer’s disease; mild cognitive impairment; retinal nerve fiber layer; meta-analysis [Shanghai Arch Psychiatry. 2015, 27(5): 263-279. doi: http://dx.doi.org/10.11919/j.issn.1002-0829.215100]
Original research article
Assessment of a six-week computer-based remediation program for social cognition in chronic schizophrenia Linda K BYRNE, Lingyi PAN, Marita McCABE, David MELLOR, Yifeng XU Background: Programs to remediate cognitive deficits have shown promising results in schizophrenia, but remediation of social cognition deficits is less well understood. Social cognitive deficits may cause more disability than the widely recognized neurocognitive deficits, suggesting that this is an area worthy of further investigation. 
Aim: Implement and evaluate a brief computerized cognitive remediation program designed to improve memory, attention, and facial affect recognition (FAR) in outpatients with chronic schizophrenia. 
Methods: Baseline assessments of FAR and of clinical, cognitive, and psychosocial functioning were completed on 20 males with schizophrenia enrolled in an outpatient rehabilitation program at the Shanghai Mental Health Center (the intervention group) and on 20 males with schizophrenia recruited from among regular outpatients at the Center (the control group). Both groups received treatment as usual, but the intervention group also completed an average of 12.7 sessions of a computer-based remediation program for neurocognitive, social, and FAR functioning over a 6-week period. The baseline measures were repeated in both groups at the end of the 6-week trial. 
Results: There were no statistically significant differences in the changes in clinical symptoms (assessed by the Positive and Negative Syndrome Scale, PANSS) or cognitive measures (assessed using the Hong Kong List Learning Test and the Letter-Number Sequencing Task) between the intervention and control groups over the 6-week trial, but there were modest improvements on the PANSS for the intervention group between baseline and after the intervention. There was a significantly greater improvement in the social functioning measure (the Personal and Social Performance scale, PSP) in the intervention group than in the control group. The pre-post change in the total facial recognition score in the intervention group was statistically significant (paired t-test=-2.60, p=0.018), and there was a statistical trend of a greater improvement in facial recognition in the intervention group than in the control group (F(1,37)=2.93; p=0.092). 
Conclusions: Integration of FAR training with a short, computer-administrated cognitive remediation program may improve recognition of facial emotions by individuals with schizophrenia, and, thus, improve their social functioning. But more work on developing the FAR training modules and on testing them in larger, more diverse samples will be needed before this can be recommended as a standard part of cognitive remediation programs. 
Keywords: schizophrenia; cognitive rehabilitation; working memory; social cognition; facial affect recognition; controlled trial; China [Shanghai Arch Psychiatry. 2015, 27(5): 296-306. doi: http://dx.doi.org/10.11919/j.issn.1002-0829.215095]
Adjunctive treatment with high frequency repetitive transcranial magnetic stimulation for the behavioral and psychological symptoms of patients with Alzheimer’s disease:a randomized, double-blind, sham-controlled study Yue WU1,2*, Wenwei XU1,2, Xiaowei LIU1,2 Qing XU1,2, Li TANG1,2 Shuyan WU1,2 Background: Behavioral and psychological symptoms of dementia (BPSD) occur in 70-90% of patients at different stages of Alzheimer’s Disease (AD), but the available methods for managing these problems are of limited effectiveness. 
Aim: Assess the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS), applied over the left dorsolateral prefrontal cortex (DLPFC), on BPSD and cognitive function in persons with AD. 
Methods: Fifty-four patients with AD and accompanying BPSD were randomly divided into an intervention group (n=27) and a control group (n=27). In addition to standard antipsychotic treatment, the intervention group was treated with 20Hz rTMS five days a week for four weeks, while the control group was treated with sham rTMS. The Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD), the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog), and the Treatment Emergent Symptom Scale (TESS) were administered by raters who were blind to the group assignment of patients before and after four weeks of treatment. 
Results: Twenty-six subjects from each group completed the study. After four weeks of antipsychotic treatment with adjunctive real or sham rTMS treatment, the mean (sd) total BEHAVE-AD scores and mean total ADAS-Cog scores of both groups significantly decreased from baseline. After adjusting for baseline values, the intervention group had significantly lower scores (i.e., greater improvement) than the control group on the BEHAVE-AD total score, on five of the seven BEHAVE-AD factor scores (activity disturbances, diurnal rhythm, aggressiveness, affective disturbances, anxieties and phobias), on the ADAS-Cog total score, and on all four ADAS-Cog factor scores (memory, language, constructional praxis, and attention). The proportion of individuals whose behavioral symptoms met a predetermined level of improvement (i.e., a drop in BEHAVE-AD total score of > 30% from baseline) in the intervention group was greater than that in the control group (73.1% vs. 42.3%, X2=5.04, p=0.025). 
Conclusion: Compared to treatment of AD with low-dose antipsychotic medications alone, the combination of low-dose antipsychotic medication with adjunctive treatment with high frequency rTMS can significantly improve both cognitive functioning and the behavioral and psychological symptoms that often accompany AD. 
Keywords: Alzheimer’s disease; behavioral and psychological symptoms; cognitive function; transcranial magnetic stimulation; China [Shanghai Arch Psychiatry. 2015, 27(5): 280-288. doi: http://dx.doi.org/10.11919/j.issn.1002-0829.215107]
Effectiveness of Traditional Chinese Medicine (TCM) treatments on the cognitive functioning of elderly persons with mild cognitive impairment associated with white matter lesions Songming HE, Lijun LI, Juying HU, Qiaoli CHEN, Weiqun SHU Background: Cerebral white matter lesion (WML) is a pathological change of the white matter which is considered an early sign of brain impairment in elderly individuals, so it is reasonable to administer early dementia prevention programs to individuals with WML. Traditional Chinese Medicine (TCM) has developed several approaches to prevent or delay the onset of dementia that have, as yet, not been formally tested. 
Aim: Evaluate the effects of a 6-month TCM intervention for elderly persons with mild cognitive impairment and WML. 
Methods: Eighty individuals 65 years of age or older with radiological evidence of WML and mild cognitive impairment based on the Montreal Cognitive Assessment (MoCA) were classified into the four main TCM constitutional types (qi deficiency, yang deficiency, phlegm dampness, or blood stasis) and randomly assigned to a treatment group or a treatment-as-usual control group. The treatment group participated in training focused on diet, lifestyle, exercises, and emotional regulation adjustment; they also received six monthly courses of moxibustion (heating acupoints by burning the moxa of dried mugwort), each of which involved 10 daily 15-minute sessions focused on three targeted acupoints (one of which was specific to the constitutional type). Changes in the MoCA and in the score of each of the four constitutional types were the main outcomes assessed. 
Results:Two participants dropped out of each group over the 6 months, leaving 38 in each group. Based on repeated measures analysis of variance, the total MoCA score, four of the six MoCA subscales scores (visual space and executive function, naming, attention and calculation, and delayed memory), and all four of the TCM constitution type scores showed significantly greater improvement over the 6 months in the treatment group than in the control group. 
Conclusions: This study shows that TCM interventions can improve both the cognitive functioning and the severity of symptoms considered in the TCM assessment of constitutional types among elderly individuals with mild cognitive impairment and WML. Long-term follow-up studies that use blinded evaluation of the outcome are needed to determine whether or not constitution-specific TCM treatments can prevent the onset of dementia. 
Keywords: Traditional Chinese Medicine; white matter lesion; mild cognitive impairment; dementia; moxibustion; China [Shanghai Arch Psychiatry. 2015, 27(5): 289-295. doi: http://dx.doi.org/10.11919/j.issn.1002-0829.215109]
Forum
Heredity in comorbid bipolar disorder and obsessive-compulsive disorder patients Andrea AMERIO, Matteo TONNA, Anna ODONE, Brendon STUBBS, S. Nassir GHAEMI
Decreasing antipsychotic polypharmacy: ‘Less is more’ in the Chinese context Yifeng XU Summary: Excessive polypharmacy is a common problem around the world, particularly in the treatment of psychiatric disorders. In mainland China use of out-of-date treatment strategies by psychiatric professionals is one of the reasons; others include unrealistically high expectations about the effectiveness of medications, the dominant role of the doctor in doctor-patient negotiations about treatment, the practice of polypharmacy in Traditional Chinese Medicine (TCM), the profit-driven nature of medical institutions and individuals, the infiltration of pharmaceutical marketing, and a critical lack of relevant research. This commentary considers the cultural factors that need to be addressed when trying to reduce polypharmacy in psychiatry in China. 
Keywords: polypharmacy; doctor-patient relationship; TCM; pharmaceutical companies; clinical guidelines; China [Shanghai Arch Psychiatry. 2015; 27(6): 371-373. Epub 2015 Nov 10. doi: http://dx.doi.org/10.11919/ j.issn.1002-0829.215106]
Case report
Infanticide by a mother with untreated schizophrenia Rahul SAHA, Shubh Mohan SINGH, Anil NISCHAL Summary: This case report describes a 30-year-old mother of four with a 6-year history of obvious paranoia and psychosis from a poor rural farming community in India. Her symptoms and social functioning deteriorated over time, but the family did not seek medical care until she killed her 3-month-old daughter while under the influence of command hallucinations. Subsequent treatment with antipsychotic medication resulted in control of her psychotic symptoms and greatly improved psychosocial functioning. This case is an example of one of the many negative consequences of a community’s failure to recognize and treat mental illnesses. The patient had severe symptoms that were obvious to all for 6 years prior to the infanticide, but the family’s lack of basic knowledge about mental illness, the lack of locally available mental health care, and the relatively high cost of care prevented family members from obtaining the treatment that almost certainly would have prevented the tragic death of her infant. Changing these three factors in poor rural communities of low- and middle-income countries is the challenge we must work together to address. Infanticide secondary to untreated mental illness is a glaring reminder of how urgent this task is. 
Keywords: schizophrenia; infanticide; at-risk mothers; India [Shanghai Arch Psychiatry. 2015; 27(5): 311-314. doi: http://dx.doi.org/10.11919/j.issn.1002-0829.215058]
Sudden cardiac death after modified electroconvulsive therapy Zhihui WANG, Jiyu WANG Summary: Sudden deaths associated with the use of electroconvulsive therapy are rare. In this case report a 58-year-old male with a 20-year history of bipolar disorder and no history or signs of cardiac illness died from cardiac arrest within one hour of receiving an initial session of modified electroconvulsive therapy (MECT) to treat a recurrent episode of non-psychotic mania. The patient regained consciousness and was medically stable immediately after the MECT session (which did not produce a convulsion) but deteriorated rapidly after transfer to the recovery room. It was not possible to conduct an autopsy, but the authors surmise that the most probable cause was that the use of haloperidol 17 hours prior to MECT exacerbated the cardiac effects of nonconvulsive MECT. The case highlights the need for a thorough cardiac work-up on patients being considered for MECT (possibly including assessment of cardiac enzymes in older individuals) and careful consideration of the concurrent use of antipsychotic medications and MECT. 
Keywords: electroconvulsive therapy; sudden death; antipsychotic medication; bipolar disorder; China [Shanghai Arch Psychiatry. 2015; 27(5): 315-318. doi: http://dx.doi.org/10.11919/j.issn.1002-0829.214169]
Biostatistics in psychiatry
The effect of simple imputation on inferences about population means when data are missing in biomedical research due to detection limits Hongyue WANG, Guanqing CHEN, Xiang LU, Hui ZHANG, Changyong FENG Summary: The sample geometric mean has been widely used in biomedical and psychosocial research to estimate and compare population geometric means. However, due to the detection limit of measurement instruments, the actual value of the measurement is not always observable. A common practice to deal with this problem is to replace missing values by small positive constants and make inferences based on the imputed data. However, no work has been carried out to study the effect of this naïve imputation method on inference. In this report, we show that this simple imputation method may dramatically change the reported outcomes of a study and, thus, make the results uninterpretable, even if the detection limit is very small. 
Keywords: sample geometric mean; population geometric mean; two-sample test [Shanghai Arch Psychiatry. 2015; 27(5): 319-325. doi: http://dx.doi.org/10.11919/j.issn.1002-0829.215121]
Correspondence
Persistent mental symptoms and rabies Hasan Tahsin GOZDAS, Mustafa HATIPOGLU