Aiai CAO, Ting SHEN, Haibin LI, Chuangxin WU, Marita MCCABE, David MELLOR, Linda BYRNE, Jie ZHANG, Jia HUANG, Daihui PENG,*, Yifeng XU*,5

Dysfunction of cognition patterns measured by MATRICS Consensus Cognitive Battery (MCCB) among first episode schizophrenia patients and their biological parents

Aiai CAO1,2#, Ting SHEN1,#, Haibin LI1, Chuangxin WU1, Marita MCCABE3, David MELLOR4, Linda BYRNE4, Jie ZHANG1, Jia HUANG1, Daihui PENG1,*, Yifeng XU*1,5

first-episode schizophrenia, cognitive function, biological parents, MCCB

1. Background

Cognitive dysfunction is acknowledged to be one of the most significant symptoms of schizophrenia[1], and has a predominant role in the functional outcomes of the illness.[2]Although the mechanisms underlying this dysfunction remain unclear, prefrontal cortical dysfunction is considered to be a specific pathological basis of abnormality in logical thinking and problem solving[3]and executive impairment.[4,5]Thus, relative to controls, patients with schizophrenia have significantly increased errors on the Wisconsin Card Sorting Test[6],and this may be attributable to difficulties in problem solving rather than physical distractibility.[6]

Interestingly, patients with schizophrenia exhibit cognitive impairment not only in the acute phase of the illness but also in the stable phase[1], and many studies show that the healthy first-degree relatives of patients with schizophrenia also suffer from cognitive deficits[7],suggesting that there is genetic susceptibility for cognitive deficits among patients with schizophrenia.[8]Cognitive features of patients with schizophrenia might be affected by the cognition mode of patients’biological parents. However, there are few studies to test the issue.[9]In this study, we explored the patterns of cognition among both schizophrenia patients and their biological parents using the Chinese version of MATRICS Consensus Cognitive Battery (MCCB).

2. Methods

2.1 Subjects

Thirty patients with schizophrenia and both of their parents (n=60) were recruited from the inpatient clinics at Shanghai Mental Health Centre, China. In addition, sixty healthy subjects, matched with to the parent group according to age, gender, and education level, were recruited from the general population via advertisement. Written informed consent was obtained from all subjects prior to their participation in the study. All participants were interviewed independently by two psychiatrists to confirm their psychiatric status.Inclusion criteria for schizophrenia were as followed: 1)satisfying DSM-IV diagnosis criteria of schizophrenia,first episode, 2) duration of episode was less than two weeks, 3) aged from17-45 years, 4) being able to understand and read Chinese, and comprehend test procedures, 5) at least 5-years of schooling, 6) had not completed MCCB or similar cognitive assessments within the previous six months. Exclusion criteria were:1) more than 2-years course of illness, 2) alcohol and/or psychoactive substance abuse or use, 3) clinical neurological diseases or medical conditions which currently impact the efficacy of assessment.

Inclusion criteria for biological parents of the patients with schizophrenia were: 1) no psychiatric illness identified when screened with the structured Clinical Interview for DSM-IV, 2) aged between 40 and 70 years, 3) at least 5-years education, 4) being able to understand and read Chinese. Exclusion criteria for biological parents were: 1) suffering from schizophrenia, or other psychotic disorders or pervasive developmental disability, 2) suffering any neurological disorder, loss of consciousness, brain trauma time exceeding one hour, 3) alcohol and/or drug abuse, or use of any psychoactive substance.

Inclusion criteria for the control group matched to the parent participants were: 1) no disorder identified when screened with the SCID, 2) aged from 17-70 years old, 3) at least 5-years education, 4) able to understand and read Chinese. Exclusion criteria were the same as those applied for the biological parents group.

2.2 Assessment Tools

2.2.1 Neuropsychological assessment

The Chinese version of the MATRICS Consensus Cognitive Battery (MCCB) was used in this study.Developed by the U.S. National Institute of Mental Health (NIMH), this test has been found to have good psychometric properties in China. It assesses seven dimensions of cognitive function, including the speed of processing, attention/vigilance, working memory,verbal learning and memory, visual learning and memory, reasoning and problem-solving skills and social cognition. In this study, speed of processing was tested by the Trail Making Test A, attention/vigilance was assessed with Continuous Performance Testing(CPT), working memory was assessed with Spatial Span, verbal learning and memory was assessed with HVLT and BVMT was used to assess visual learning and memory. We used the Mazes Test to assess reasoning and problem-solving ability and the Emotional Test assessed social cognition.

2.2.2 Statistical Analysis

The independent-samples t-tests were used to investigate any differences in the age and length of education of the groups. All the raw scores for the cognitive tests were converted to T-score based on the guidelines of MCCB. First, raw scores on the individual tests were placed on a common metric (normally distributed scaled scores, which have a mean of 10 and a standard deviation of 3 in the Chinese normative group). The scaled scores were then converted into T-scores: the demographic data (age, education, and gender) were used to generate fractional polynomial regression equations to optimally predict the scaled scores. To determine the optimal fractional polynomial equation, the method of Royston and Altman (1994)was employed using the statistical package. The residuals from optimal regression equations were then converted to T-scores with a mean of 50 and a standard deviation of 10.[10,11]Cognitive index were tested by analysis of covariance.

3. Results

3.1 Demographic data

Due to some missing data on the MCCB measures(two parents) and refusal to complete the MCCB (14 controls and one patient), the final sample used in the analyses consisted of 29 patients with first episode schizophrenia and 58 parents, and 46 healthy controls.Of the 29 patients with schizophrenia, 13 were male and 16 were female. Their mean age was 26.24 years(SD=5.87), and the mean number of years of education was 12.93 (SD=3.21). The parent group consisted of 30 fathers and 28 mothers with mean age of 50.50 years(SD=7.06) and 9.90 years of education (SD=3.65).Of the 46 healthy participants as the control group of patients’ parents: 22 are males and 24 are females at the age of 50.50 (7.06). The demographic details of the three groups are summarized in Table 1. There were no significant differences in the age or education level of the non-patient groups.

3.2 Assessment of Neuropsychological test

3.2.1 Comparison of cognition between schizophrenia patients and control group

To explore the differences in the cognitive functioning of the patient and control groups, we compared scores on the seven psychological dimensions of cognitive function. As shown in Table 2, there were differences in mean scores on the visual learning, reasoning and problem solving, and social cognition tasks, however they were not significant. However, the patient group scored significantly lower than the control group in speed processing, attention, working memory and verbal learning.

3.2.2 Comparison between patients’ and control group As shown in Table 3, the mean scores of patients and their parents differed significantly on only two domains of the MCCB, speed processing and attention.

3.2.3 Comparison between patients’ parents and the control group.

As shown in Table 4, patients’ parents scored lower than the control group on only one MCCB domains:verbal learning.

4. Discussion

4.1 Main findings

Schizophrenia is likely to have a potential genetic effect. Interestingly, some research showed that social cognitive dysfunction was one of the endophenotypes for schizophrenia and appeared among schizophrenia patients’ first grading kinship.[12]It remains unclear if some domains of cognitive deficits also exist in the first grading kinship of patients with schizophrenia or not.

Previous studies had proved that there is a certain correlation between the negative symptoms of schizophrenia and verbal working memory.[13,14,15]Some studies showed that even if psychotic symptoms disappear, the impairment of verbal memory still exists. Moreover, the impairment also exists in their first grading kinship. In order to explore whether there were differences between schizophrenia patients, their first grading kinship and normal controls in verbal working memory, Sonia investigated 197 cases of schizophrenia, 197 cases of their first-grading relatives,and 200 normal controls by Trail Matching Test. The study showed that the Trail Matching Test level of patients with schizophrenia was lower than that of their first-grading relatives and normal control group.While, there were differences between first-grading relatives and normal control group too. The studysuggested that verbal working memory might be one of endophenotype manifestations for schizophrenia.[16]

Figure 1. The flowchart of the study

Table 1. Comparison of general information between patients' parents and control group

Table 2. Comparison of seven psychological dimensions between patients and control group

Table 3. Comparison across seven psychological dimensions between patients and their parents

Table 4. Comparison of seven psychological dimensions between patients’ parents and control group

Electrophysiological studies found that the abnormality of P300 was one index of the cognitive dysfunctions for patients with schizophrenia during the stable period of drug withdrawal. The P300 in frontal brain regions of the patients’ healthy relatives dropped,which also suggested that the amplitude of P300 could be used as the endogenous EEG physiological signs to schizophrenia’s relatives[17]. Iconography studies showed that the reduced grey matter on the frontal lobe of the patients with schizophrenia was associated with the impairment of cognitive function. One fMRI study found that the abnormal activation in ventral anteriornucleus and dorsomedial nucleus decreased for schizophrenia group.[18]Another study on late-onset schizophrenia explored the relative characteristics between rCBF and cognitive impairment, which displayed the relationship between the left frontal lobe dysfunction and memory impairment in lateonset schizophrenia.[19]These studies demonstrated that there were potential biological mechanisms of cognitive deficits in patients with schizophrenia,relatively independent of clinical symptoms.

4.2 Limitations

The sample size is small, but the disease of the firstepisode patients is representative. We hope to increase the sample size in subsequent studies and demonstrate the above result.

4.3 Implications

Based on the current findings, the study tested the cognitive patterns of first-episode patients with schizophrenia and their biological parents using a novel cognition measurement battery. The cognitive assessment tool is the Chinese version of cognitive test battery of schizophrenia (MCCB) developed by the United States MATRICS company. The first interesting result showed that male patients with schizophrenia had obvious cognitive defects in six domains of cognitive function by MCCB tools except the social cognition domain. This result confirmed that social cognition may be one of the endophenotypes for schizophrenia and schizophrenia patients’ first grading kinship.[20]Meanwhile, the female patients showed lower ability on both working memory and problem reasoning than their female parents. The statistically significant differences also existed between the patients’ fathers and healthy controls. But the patients’ mothers didn’t show any significant difference of reasoning problem domain compared with healthy control. Abnormal visual learning domain appeared in patients’ mothers compared with healthy controls.Thus, both the first-episode schizophrenia patients and their biological parents have defects in working memory. The function defect is more significant in the schizophrenia patient group. The genetic susceptibility may be useful to explain the cognitive dysfunction exisisting in both the schizophrenia patients and their biological parents, especially for domains of verbal learning and reasoning problems.

There are six dimensions of cognitive impairments in both first-episode schizophrenia patients and their biological parents, including speed of processing,attention, working memory, verbal learning, visual learning, and problem reasoning as well. Compared to healthy controls, their biological parents have significant defects in domains of working memory,problem reasoning and visual learning as well.Undoubtedly, the small sample limited the current meaning of this study. However, patients with schizophrenia have significant cognitive dysfunctions,which may be affected by the course of disease,medications, etc. This study analyzed the cognitive patterns in patients with first-episode schizophrenia so as to minimize the effects of medication and course of disease. Future studies need to explore the underlying mechanisms of similar cognitive dysfunction between patients with first-episode schizophrenia and their biological parents.

Funding statement

Funding was provided by Shanghai Health Bureau scientific research grant (2010086, 2011-2013)

Conflict of interest statement

The authors declare no conflict of interest related to this manuscript.

Informed consent

All participants and their legal guardians provided signed informed consent to participate this study

Ethical approval

The ethics committee of the Sixth People’s Hospital of Peking University approved this study

Authors’ contributions

Cao A, Shen T, and Peng DH chose the study topic and wrote the draft.

Cai A, Li HB, and Wu CX performed the data analysis.

McCabe M and Mellor D provided guidance on data analysis.

Zhang J and Huang J collected cases

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MCCB測定首發(fā)精神分裂癥患者及其生物學(xué)父母存在認(rèn)知功能障礙

Cao A, Shen T, Li H, Wu C, McCabe M, Mellor D, Byrne L, Zhang J, Huang J, Peng D, Xu Y

首發(fā)精神分裂癥；認(rèn)知功能；生物學(xué)父母；認(rèn)知功能成套測驗(yàn)共識(shí)版（M CCB ）

Background: Schizophrenia is characterized by abnormal perception, thinking, emotions, and behaviors.Cognitive dysfunction is acknowledged as one of the most pivotal symptoms in schizophrenia. In addition to positive or negative symptoms, which had been proposed by Gallhofer in the early 1970s, schizophrenia patients suffered from cognitive impairments as well. Many studies show that there is genetic susceptibility in the first grading kinship of patients with schizophrenia. Patients with schizophrenia have cognitive impairment not only in the acute phase but also in the stable phase. Studies also show that the healthy first-grading relatives of patients with schizophrenia suffer from cognitive defects. However, there is still a lack of studies about the cognitive features of biological parents of those with schizophrenia. In this study,we speculate the biological parents of schizophrenia patients have specific cognitive dysfunction. And we explore the patterns of cognition among both schizophrenia patients and their biological parents using the Chinese version of MATRICS Consensus Cognitive Battery (MCCB).

Aims: Cognitive features of patients with schizophrenia might be affected by the cognition mode of patients' biological parents. The dysfunctional cognitive patterns need to be characterized among the patients with schizophrenia and their parents.

Methods: We applied the MATRICS Consensus Cognitive Battery (MCCB, a novel measurement tool)to evaluate the cognitive function of 29 first-episode patients with schizophrenia (meeting ICD-10 diagnostic criteria for schizophrenia, aged between 17-45 years old), 58 cases of biological parents of schizophrenia patients (aged between 40-70 years old) and 46 healthy controls (aged between 40-70 years old). Furthermore, we explored the relationship between the cognitive dysfunction in patients with schizophrenia and their biological parents. All data were analyzed using SPSS18.0 statistical software.

Results: 1) Male patients with schizophrenia had obvious cognitive defects in six domains of cognitive function as measured by the MCCB (all except the social cognition domain) compared to their male parents.Female patients showed lower ability on both working memory and problem reasoning than their female parents. 2) The significant differences of both working memory and reasoning problems also existed between the patients' fathers and matched healthy controls. 3) Patients' mothers didn't show any significant difference on the problem reasoning domain compared with healthy controls. However, the visual learning domain appeared abnormal in patients' mothers compared with healthy controls.

Conclusion: There are six dimensions of cognitive impairments in both first-episode schizophrenia patients and their biological parents. Compared with healthy controls, patients’ biological parents have conspicuous dysfunction in domains of working memory, problem reasoning and visual learning as well. Further study is needed to explore the underlying mechanisms of similar cognitive dysfunction between first-episode schizophrenia patients and their biological parents.

[Shanghai Arch Psychiatry. 2017; 29(3): 154-160.

http://dx.doi.org/10.11919/j.issn.1002-0829.216117]

1Shanghai Mental Health Centre, Shanghai Jiaotong University, Shanghai, China

2Shanghai Changning Mental Health Centre, Shanghai, China

3Institute for Health & Ageing, Australian Catholic University, Melbourne, Australia

4School of Psychology, Deakin University, Melbourne, Australia

5Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China

# joint first author

*joint correspondencing author

*correspondence: Daihui Peng. Mailing address: 600 South Wanping RD, Shanghai, China, Postcode: 200030. E-Mail: pdhsh@126.com; Yifeng Xu. Mailing address: 600 South Wanping RD, Shanghai, China, Postcode: 200030. E-Mail: hyyyyb@gmail.com

背景：精神分裂癥的臨床表現(xiàn)為特征性的知覺、思維、情感和行為等障礙。認(rèn)知障礙也是精神分裂癥核心癥狀之一。20世紀(jì)70年代早期Gallhofer曾提出過，精神分裂癥除有陽性或陰性癥狀，也存在認(rèn)知障礙。許多研究表明，精神分裂癥的一級(jí)親屬中存在遺傳易感性。認(rèn)知障礙不僅急性期存在，維持鞏固期也會(huì)有。有研究還顯示，精神分裂癥健康的一級(jí)親屬亦存在認(rèn)知缺陷。但對(duì)精神分裂癥及其生物學(xué)父母的認(rèn)知特征研究仍缺乏。本研究，我們假設(shè)精神分裂癥及其生物學(xué)父母存在特定的認(rèn)知功能障礙，擬采用認(rèn)知功能成套測驗(yàn)共識(shí)版（MATRICS Consensus Cognitive Battery,MCCB)中文版，以探討精神分裂癥患者及其生物學(xué)父母的認(rèn)知模式。

目的：精神分裂癥的認(rèn)知特征可能受到其生物學(xué)父母認(rèn)知模式的影響。研究旨在描繪精神分裂癥患者與其父母之間的功能失調(diào)的認(rèn)知模式。

方法：采用認(rèn)知功能成套測驗(yàn)共識(shí)版(MCCB,一種新的測量工具)評(píng)估29例首發(fā)精神分裂癥(符合ICD-10精神分裂癥診斷標(biāo)準(zhǔn)，年齡17-45歲)，58例精神分裂癥患者的生物學(xué)父母(年齡40 - 70歲)和46例健康對(duì)照(年齡40-70歲)的認(rèn)知功能，以探討精神分裂癥患者及其生物學(xué)父母之間的認(rèn)知功能障礙之間的關(guān)系。所有數(shù)據(jù)使用SPSS18.0統(tǒng)計(jì)軟件進(jìn)行分析。

結(jié)果：1)男性精神分裂癥患者與其父親相比在MCCB認(rèn)知功能測定的6個(gè)維度有明顯認(rèn)知缺陷(除社會(huì)認(rèn)知功能外)。女性患者的工作記憶和問題推理能力都低于其母親。2)患者父親和健康對(duì)照組之間的工作記憶和推理問題也存在顯著差異。3)與健康對(duì)照組相比，患者母親在問題推理方面沒有明顯的差異，但視覺記憶有異常。

結(jié)論：首發(fā)精神分裂癥患者及其生物學(xué)父母在6個(gè)維度存在認(rèn)知功能障礙?；颊吒改冈诠ぷ饔洃洝栴}推理和視覺記憶等方面也存在明顯功能障礙。仍需深入研究以揭示首發(fā)精神分裂癥及其生物學(xué)父母存在認(rèn)知功能障礙的潛在機(jī)制。

Aiai Cao graduated from Shanghai Jiaotong University School of Medicine in 2010 with her bachelors of medicine and in 2013 with a masters of medicine. Since 2013 she has been working in Shanghai at the women’s psychiatric unit of Changning District Mental Health Center. Her research interests include inflammatory factors, cognitive function and genetics of schizophrenia and affective disorders.

Dr. Ting Shen is currently working as a deputy director of physician in the department of emergency and severe case in Shanghai Mental Health Center. She has been engaged in clinical and research work in psychiatry for 18 years. Her research interest is the clinical research of schizophrenia.