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Systematic review and meta-analysis

Huperzine A for treatment of cognitive impairment in major depressive disorder: a systematic review of randomized controlled trials

Wei ZHENG, Ying-Qiang XIANG, Gabor S. UNGVARI, Helen F.K. CHIU, Chee H. NG, Ying WANG, Yu-Tao XIANG

Background: Acetylcholinesterase (AChE) inhibitors have been shown to be effective in treating cognitive impairment in animal models and in human subjects with major depressive disorder (MDD). Huperzine A (HupA), a Traditional Chinese Medicine derived from a genus of clubmosses known as Huperzineserrata, is a powerful AChE inhibitor that has been used as an adjunctive treatment for MDD, but no meta-analysis on HupA augmentation for MDD has yet been reported.
Aim: Conduct a systematic review and meta-analysis of randomized controlled trials (RCTS) about HupA augmentation in the treatment of MDD to evaluate its efficacy and safety.
Methods: Two evaluators independently searched nine English-language and Chinese-language databases, selected relevant studies that met pre-determined inclusion criteria, extracted data about outcome and safety, and conducted quality assessments and data synthesis.
Results: Three low-quality RCTs (pooled n=238) from China were identified that compared monotherapy antidepressant treatment for depression versus combined treatment with antidepressants and HupA. Participants in the studies ranged from 16 to 60 years of age. The average duration of adjunctive antidepressant and HupA treatment in the studies was only 6.7 weeks. All three studies were open label and non-blinded, so their overall quality was judged as poor. Meta-analysis of the pooled sample found no significant difference in the improvement in depressive symptoms between the two groups (weighted mean difference: -1.90 (95%CI: -4.23, 0.44), p=0.11). However, the adjunctive HupA group did have significantly greater improvement than the antidepressant only group in cognitive functioning (as assessed by the Wisconsin Card Sorting Test and the Wechsler Memory Scale-Revised) and in quality of life. There was no significant difference in the incidence of adverse drug reactions between groups.
Conclusions: The data available on the effectiveness and safety of adjunctive treatment using HupA in patients with MDD who are receiving antidepressants is insufficient to arrive at a definitive conclusion about its efficacy and safety. Pooling of the data from three low-quality RCTs from China found no advantage of adjunctive HupA in the treatment of depressive symptoms, but adjunctive treatment with HupA was associated with a faster resolution of the cognitive symptoms that frequently accompany MDD. Trial registration number: CRD42015024796 (
Key words: depression; meta-analysis; cognitive function; huperzine A; adjunctive treatment

Original research article

Clinical investigation of speech signal features among patients with schizophrenia

Jing ZHANG, Zhongde PAN, Chao GUI, Jie ZHU, Donghong CUI

Background: A new area of interest in the search for biomarkers for schizophrenia is the study of the acoustic parameters of speech called ‘speech signal features’. Several of these features have been shown to be related to emotional responsiveness, a characteristic that is notably restricted in patients with schizophrenia, particularly those with prominent negative symptoms.
Aim: Assess the relationship of selected acoustic parameters of speech to the severity of clinical symptoms in patients with chronic schizophrenia and compare these characteristics between patients and matched healthy controls.
Methods: Ten speech signal features – six prosody features, formant bandwidth and amplitude, and two spectral features – were assessed using 15-minute speech samples obtained by smartphone from 26 inpatients with chronic schizophrenia (at enrollment and 1 week later) and from 30 healthy controls (at enrollment only). Clinical symptoms of the patients were also assessed at baseline and 1 week later using the Positive and Negative Syndrome Scale, the Scale for the Assessment of Negative Symptoms, and the Clinical Global Impression-Schizophrenia scale.
Results: In the patient group the symptoms were stable over the 1-week interval and the 1-week test-retest reliability of the 10 speech features was good (intraclass correlation coefficients [ICC] ranging from 0.55 to 0.88). Comparison of the speech features between patients and controls found no significant differences in the six prosody features or in the formant bandwidth and amplitude features, but the two spectral features were different: the Mel-frequency cepstral coefficient (MFCC) scores were significantly lower in the patient group than in the control group, and the linear prediction coding (LPC) scores were significantly higher in the patient group than in the control group. Within the patient group, 10 of the 170 associations between the 10 speech features considered and the 17 clinical parameters considered were statistically significant at the p<0.05 level.
Conclusions: This study provides some support for the potential value of speech signal features as indicators (i.e., biomarkers) of the severity of negative symptoms in schizophrenia, but more detailed studies using larger samples of more diverse patients that are followed over time will be needed before the potential utility of such acoustic parameters of speech can be fully assessed.
Keywords: schizophrenia; speech; speech signal features; biomarkers; negative symptoms; China


A community-based controlled trial of a comprehensive psychological intervention for community residents with diabetes or hypertension

Qingzhi ZENG, Yanling HE, Zhenyu SHI, Weiqing LIU, Hua TAO, Shiming BU, Donglei MIAO, Ping LIU, Xuan

Background: Depression and anxiety often occur in persons with chronic physical illnesses and typically magnify the impairment caused by these physical conditions, but little attention has been paid to this issue in low- and middle-income countries.
Aim: Evaluate the effectiveness of a community-based psychological intervention administered by nonspecialized clinicians and volunteers for alleviating depressive and anxiety symptoms in individuals with chronic physical illnesses.
Methods: A total of 10,164 community residents receiving treatment for diabetes or hypertension in Shanghai were arbitrarily assigned to a treatment-as-usual condition (n=2042) or an intervention condition (n=8122) that included community-wide psychological health promotion, peer support groups, and individual counseling sessions. The self-report Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder scale (GAD-7), and 12-item Short-Form Health Survey (SF-12) assessed depressive symptoms, anxiety symptoms, and quality of life at baseline and after the 6-month intervention.
Results: Among the 8813 individuals who completed the baseline assessment, 16% had mild or more severe depressive or anxiety symptoms (PHQ-9 or GAD-7 >5) and 4% had moderate or severe depressive or anxiety symptoms (PHQ-9 or GAD-7 >10). The education component of the intervention was effectively implemented, but only 31% of those eligible for peer-support groups and only 9% of those eligible for individual counseling accepted these interventions. The dropout rate was high (51%), and there were significant differences between those who did and did not complete the follow-up assessment. After adjusting for these confounding factors, the results in individuals who completed both assessments indicated that the intervention was associated with significant improvements in depressive symptoms (F=9.98, p<0.001), anxiety symptoms (F=12.85, p<0.001), and in the Mental Component Summary score of the SF-12 (F=16.13, p<0.001). There was, however, no significant change in the self-reported rates of uncontrolled diabetes or hypertension.
Conclusions: These results support the feasibility of implementing community-based interventions to reduce the severity of depressive and anxiety symptoms in persons with chronic medical conditions in lowand middle-income countries where psychiatric manpower is very limited. However, there are substantial methodological challenges to mounting such interventions that need to be resolved in future studies before the widespread up-scaling of this approach will be justified.
Keywords: depression; anxiety; community intervention; diabetes; hypertension; community medical service; China


Disability, psychiatric symptoms, and quality of life in infertile women: a cross-sectional study in Turkey


Background: Infertility is a major life crisis which can lead to the development of psychiatric symptoms and negative effects on the quality of life of affected couples, but the magnitude of the effects may vary depending on cultural expectations.
Aim: We compare the level of psychiatric symptoms, disability, and quality of life in fertile and infertile women in urban Turkey.
Methods: This cross-sectional study enrolled 100 married women being treated for infertility at the outpatient department of the Obstetrics and Gynecology Department of the Rize Education and Research Hospital and a control group of 100 fertile married women. All study participants were evaluated with a socio-demographic data screening form, the Hospital Anxiety and Depression Scale (HADS), the Brief Disability Questionnaire (BDQ), and the Short Form Health Survey (SF-36).
Results: The mean anxiety subscale score and depression subscale score of HADS were slightly higher in the infertile group than in controls, but the differences were not statistically significant. The proportion of subjects with clinically significant anxiety (i.e., anxiety subscale score of HADS >11) was significantly higher in infertile women than in fertile women (31% v. 17%, X2=5.37, p=0.020), but the proportion with clinically significant depressive symptoms (i.e., depression subscale score of HADS >8) was not significantly different (43% v. 33%, X2=2.12, p=0.145). Self-reported disability over the prior month was significantly worse in the infertile group than in the controls, and 4 of the 8 subscales of the SF-36 – general health, vitality, social functioning, and mental health – were significantly worse in the infertile group. Compared to infertile women who were currently working, infertile women who were not currently working reported less severe depression and anxiety and better general health, vitality, and mental health.
Conclusions: Married women from urban Turkey seeking treatment for infertility do not have significantly more severe depressive symptoms than fertile married controls, but they do report greater physical and psychological disability and a poorer quality of life. The negative effects of infertility were more severe in infertile women who were employed than in those who were not employed. Larger follow-up studies are needed to assess the reasons for the differences between these results and those reported in western countries which usually report a higher prevalence of depression and anxiety in infertile patients.
Keywords: infertility; quality of life; disability; psychiatric symptoms; cross-sectional study; Turkey


Is the DSM-5 hoarding disorder diagnosis valid in China?

Zhen WANG, Yuan WANG, Qing ZHAO, Kaida JIANG

Summary: Hoarding disorder, newly included as a separate diagnostic entity in the Obsessive-Compulsive and Related Disorders section of DSM-5, has been reported to have significantly different symptoms and etiology than obsessive-compulsive disorder (OCD). However, the validity of this new diagnosis in China – where the storing of possessions is sanctioned and normalized – remains to be proven. We considered available data about pathological hoarding in East Asia and found the condition to be relatively common and symptomatically similar to that reported in western countries. We conclude that the ‘Hoarding Disorder’ diagnosis defined in DSM-5 is a valid clinical entity in China, though when making the diagnosis clinicians must take care to differentiate pathological hoarding that is distressing to the individual and significantly interferes with social and occupational functioning from culturally sanctioned thriftiness that is not associated with either distress or social dysfunction.
Keywords: hoarding disorder; DSM-5; cross-cultural validity; case report; China

Case report

Behavioral and emotional manifestations in a child with

Satyakam MOHAPATRA, Udit Kumar PANDA

Summary: Prader-Willi syndrome is a neurodevelopmental disorder characterized by mental retardation and distinct physical, behavioral, and psychiatric features. Maladaptive behaviours, cognitive impairment, and impediments in speech and language seriously affect the early development and long-term functioning of individuals affected by the illness. We present a case of a 9-year-old child with Prader-Willi syndrome whose behavioural symptoms were treated with low-dose antipsychotic medications.
Keywords: Prader-Willi Syndrome; psychiatric symptoms; childhood disorders; case report; India


Treatment resistant depression or dementia: a case report

Zhongyong SHI, Shifu XIAO, Xia LI

Summary: The co-occurrence of depression and dementia is increasingly common in the elderly. The current case describes a 78-year-old female with two previous episodes of major depression who presented with both symptoms of depression (amotivation and flattened affect) and typical symptoms of dementia (impaired memory and executive functioning). Even after a detailed clinical exam and neuropsychiatric testing, it remained difficult to definitively classify the diagnosis as either treatment-resistant depression or old-age dementia. After 8 weeks of inpatient treatment, including changing her reserpine-based antihypertensive medication, adjusting her antidepressants, and providing psychotherapy, her depressive and anxiety symptoms improved, but most of her cognitive symptoms persisted. Her symptoms did not change over 7 months of post-hospitalization follow-up. She subsequently developed advanced breast cancer and started chemotherapy; at this point her depressive and cognitive symptoms became more pronounced. We conclude that it will take two-tothree years of follow-up to determine whether the cognitive symptoms are residual to her depression or a newly emerging dementia (or both). This case shows that for elderly patients who have symptoms of both depression and dementia, detailed clinical examination and neuropsychiatric testing may need to be combined with longitudinal assessment of their responsiveness to treatment before a definitive diagnosis can be assigned.
Keywords: depression; dementia; pseudo-dementia; case report; China

Biostatistics in psychiatry

Correlation and agreement: overview and clarification of competing concepts and measures

Jinyuan LIU, Wan TANG, Guanqin CHEN, Yin LU, Changyong FENG, Xin M. TU

Summary: Agreement and correlation are widely-used concepts that assess the association between variables. Although similar and related, they represent completely different notions of association. Assessing agreement between variables assumes that the variables measure the same construct, while correlation of variables can be assessed for variables that measure completely different constructs. This conceptual difference requires the use of different statistical methods, and when assessing agreement or correlation, the statistical method may vary depending on the distribution of the data and the interest of the investigator. For example, the Pearson correlation, a popular measure of correlation between continuous variables, is only informative when applied to variables that have linear relationships; it may be non-informative or even misleading when applied to variables that are not linearly related. Likewise, the intraclass correlation, a popular measure of agreement between continuous variables, may not provide sufficient information for investigators if the nature of poor agreement is of interest. This report reviews the concepts of agreement and correlation and discusses differences in the application of several commonly used measures.
Keywords: concordance correlation; intraclass correlation; Kendall’s tau; non-linear association; Pearson’s correlation; Spearman’s rho