scholarly journals Sex-dependent effect on the association of COMT Val158Met polymorphism with schizophrenia clinical symptoms and cognitive impairment

Author(s):  
Hang Xu ◽  
Yongjie Zhou ◽  
Jiesi Wang ◽  
Meihong Xiu ◽  
Dachun Chen ◽  
...  

Abstract Catechol-O-methyltransferase (COMT) Val158Met (rs4680) polymorphism is thought to be involved in the pathogenesis of schizophrenia, which is related to the regulation of dopamine transmission in the prefrontal cortex. Recent studies have shown that the influence of COMT Val158Met variation is sexually dimorphic. This study aims to explore the possible effect of the interaction between COMT Val158Met polymorphism and sex on patients’ clinical characteristics and cognitive function. 367 inpatients with chronic schizophrenia (246 males and 121 females) and 419 healthy controls (172 males and 247 females) are recruited. The cognitive performances are assessed by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the COMT Val158Met polymorphism is genotyped. The psychopathological symptoms of the patients are assessed by the Positive and Negative Syndrome Scale (PANSS). We find that: 1) sex difference in the allele frequency and genotype distribution of COMT Val158Met are found only in schizophrenia patients; 2) there is sex × COMT genotype interaction in positive symptoms, immediate memory, attention, and RBANS total score indexes in patients with schizophrenia; 3) mainly in the male patients’ sample, Val/Val carriers exhibit more positive symptoms and more severe cognitive impairment than Met carriers. These findings suggest that COMT Val158Met polymorphism is associated with the risk and severity of schizophrenia in a sexually dimorphic way, which is helpful to understand the factors that may lead to different manifestations of male and female patients with schizophrenia.

2020 ◽  
Vol 46 (6) ◽  
pp. 1498-1510 ◽  
Author(s):  
Mei Hong Xiu ◽  
Zezhi Li ◽  
Da Chun Chen ◽  
Song Chen ◽  
Maile E Curbo ◽  
...  

Abstract The pathogenesis and etiology of schizophrenia (SCZ) remains unclear. Accumulating studies showed that complex interrelationships between brain-derived neurotrophic factor (BDNF) and an imbalanced redox system has a crucial role in the psychopathology of SCZ. However, the influence of the interrelationships of BDNF and superoxide dismutase (SOD) on cognitive impairment and clinical symptomatology in drug-naive first-episode (DNFE) SCZ patients has not been studied thoroughly. Serum BDNF levels, plasma total SOD, manganese-SOD (Mn-SOD), copper/zinc-containing SOD (CuZn-SOD) activities, and malondialdehyde (MDA) levels were measured in 327 DNFE patients with SCZ and 391 healthy controls. Cognitive functions were measured using the Repeatable Battery for the Assessment of Neuropsychological status (RBANS) and clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). Compared with the controls, the DNFE patients had increased activities of total SOD and CuZn-SOD, and reduced levels of BDNF and MDA. BDNF levels were positively correlated with CuZn-SOD activity in patients. In addition, we found that elevated Mn-SOD and CuZn-SOD activities were related to PANSS depression factor. Moreover, an interactive effect of BDNF levels and Mn-SOD activity was associated with attentional index score in the patients. Therefore, our findings suggested that interrelationships between BDNF and antioxidant mechanisms might underlie the pathological mechanisms of cognitive impairments and symptomatology in the DNFE patients with SCZ.


2019 ◽  
Vol 53 (01) ◽  
pp. 21-29 ◽  
Author(s):  
Martin Schaefer ◽  
Susanne Sarkar ◽  
Ines Theophil ◽  
Karolina Leopold ◽  
Andreas Heinz ◽  
...  

Abstract Introduction Patients with schizophrenia are mainly characterized by negative symptoms and cognitive dysfunction. In this proof-of-concept study we tested effects on cognition and negative symptoms of a 6- or 24-week memantine add-on treatment to risperidone in patients with acute or chronic schizophrenia. Materials and Methods Patients with an acute episode of schizophrenia (n=11) and predominating positive symptoms were randomized to a 6-week add-on treatment with memantine (10 mg twice a day) versus placebo and patients with chronic schizophrenia (n=13) and negative symptoms were randomized to a 24-week add-on treatment with memantine (10 mg twice a day) versus placebo. All patients received antipsychotic medication with risperidone (2–8 mg/day). Psychopathological changes were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and after 2, 4, 6, 12, and 24 weeks. Cognitive function was measured at baseline, after 6 weeks, and 24 weeks. Results Patients with acute schizophrenia who received add-on treatment with memantine showed a significantly higher performance in attention intensity (p=0.043), problem-solving (p=0.043), verbal learning (p=0.050), and flexibility (p=0.049). Patients with chronic schizophrenia showed a significantly higher immediate memory in the memantine group compared to the placebo group (p=0.033) and a significantly greater reduction of the PANSS sum score if compared to the placebo group. Discussions Our study gives further evidence that memantine add-on treatment to risperidone may have neuroprotective effects and improve cognitive function in patients with schizophrenia. ClinicalTrials.gov Number: NCT00148590 and NCT00148616.


2021 ◽  
Vol 12 ◽  
Author(s):  
Qiaoling Sun ◽  
Jiansong Zhou ◽  
Huijuan Guo ◽  
Ningzhi Gou ◽  
Ruoheng Lin ◽  
...  

Schizophrenia is a complex and devastating disorder with unclear pathogenesis. Electroencephalogram (EEG) microstates have been suggested as a potential endophenotype for this disorder. However, no clear dynamic pattern of microstates has been found. This study aims to identify the dynamics of EEG microstates in schizophrenia and to test whether schizophrenia patients with altered clinical symptoms severity showed different microstates abnormalities compared with healthy controls. Resting-state EEG data in 46 individuals who met the ICD-10 diagnostic criteria for schizophrenia and 39 healthy controls was recorded. The patients with schizophrenia were divided into subgroups based on the level of their negative or positive symptoms assessed using the Positive and Negative Syndrome Scale. Microstate parameters (contribution, occurrence, and duration) of four prototypical microstate classes (A–D) were investigated. Compared with healthy controls, individuals with schizophrenia showed increased duration and contribution of microstate class C, decreased contribution and occurrence of microstate class B. Different microstate patterns were found between subgroups and healthy controls. Results in this study support the consistent observation of abnormal EEG microstates patterns in patients with schizophrenia and highlight the necessity to divide subjects into subgroups according to their clinical symptoms.


1993 ◽  
Vol 162 (6) ◽  
pp. 744-750 ◽  
Author(s):  
D. A. Kibel ◽  
I. Laffont ◽  
P. F. Liddle

The clinical features of patients who satisfy a variety of criteria for the negative syndrome can be arranged in five groups of phenomena: (a) poverty of thought and speech, (b) blunted affect, (c) decreased motor activity, (d) apathy and avolition, and (e) diminished interpersonal interaction. We have shown that depressed mood and depressive cognition are not related to the negative syndrome, but there is some overlap between the specific phenomena of depressive illness and negative symptoms in schizophrenia. Items measuring cognitive impairment have a moderate correlation with the negative syndrome, but the negative syndrome accounts for less than half of the variance of cognitive performance. These items that define the negative syndrome can be as reliably measured as depressive and positive symptoms.


2021 ◽  
Vol 12 ◽  
Author(s):  
Lijuan Huo ◽  
Zhiwei Zheng ◽  
Xiaobing Lu ◽  
Fengchun Wu ◽  
Yuping Ning ◽  
...  

Objectives: There are relatively few studies on mechanisms of cognitive deficits in late-life schizophrenia (LLS). Brain-derived neurotrophic factor (BDNF), as an important neuroplastic molecule, has been reported to be involved in neurocognitive impairment in schizophrenia. This study aimed to examine whether peripheral BDNF levels were associated with cognitive deficits in LLS, which has not been explored yet.Methods: Forty-eight LLS patients and 45 age-matched elderly controls were recruited. We measured all participants on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) for cognition and serum BDNF levels. Psychopathological symptoms in patients were assessed by the Positive and Negative Syndrome Scale (PANSS).Results: The levels of BDNF in LLS patients were significantly lower than those in healthy controls (8.80 ± 2.30 vs. 12.63 ± 5.08 ng/ml, p < 0.001). The cognitive performance of LLS patients was worse than that of the controls on RBANS total score and scores of immediate memory, attention, language, and delayed memory (all p ≤ 0.005). BDNF was positively associated with attention in LLS patients (r = 0.338, p = 0.019).Conclusion: Our findings suggest that older patients with schizophrenia exhibit lower BDNF levels and more cognitive deficits than older controls, supporting the accelerated aging hypothesis of schizophrenia. Moreover, decreased BDNF is related to attention deficits, indicating that BDNF might be a candidate biomarker of cognitive impairments in LLS patients.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dandan Li ◽  
Fengyan Zhang ◽  
Lu Wang ◽  
Yifan Zhang ◽  
Tingting Yang ◽  
...  

Abstract Objective Numerous studies have identified impaired decision making (DM) under both ambiguity and risk in adult patients with schizophrenia. However, the assessment of DM in patients with adolescent-onset schizophrenia (AOS) has been challenging as a result of the instability and heterogeneity of manifestations. The Iowa Gambling Task (IGT) and Game of Dice Task (GDT), which are frequently used to evaluate DM respectively under ambiguity and risk, are sensitive to adolescents and neuropsychiatric patients. Our research intended to examine the performance of DM in a relatively large sample of patients with AOS using the above-mentioned two tasks. We also aimed to take a closer look at the relationship between DM and symptom severity of schizophrenia. Methods We compared the performance of DM in 71 patients with AOS and 53 well-matched healthy controls using IGT for DM under ambiguity and GDT for DM under risk through net scores, total scores and feedback ration. Neuropsychological tests were conducted in all participants. Clinical symptoms were evaluated by using Positive and Negative Syndrome Scale (PANSS) in 71 patients with AOS. Pearson’s correlation revealed the relationship among total score of DM and clinical and neuropsychological data. Results Compared to healthy controls, patients with AOS failed to show learning effect and had a significant difference on the 5th block in IGT and conducted more disadvantageous choices as well as exhibited worse negative feedback rate in GDT. Apart from DM impairment under risk, diminished DM abilities under ambiguity were found related to poor executive function in AOS in the present study. Conclusions Our findings unveiled the abnormal pattern of DM in AOS, mainly reflected under the risky condition, extending the knowledge on the performance of DM under ambiguity and risk in AOS. Inefficient DM under risk may account for the lagging impulse control and the combined effects of developmental disease. In addition, our study demonstrated that the performance on IGT was related to executive function in AOS.


1992 ◽  
Vol 160 (2) ◽  
pp. 253-256 ◽  
Author(s):  
Elizabeth J. B. Davis ◽  
Milind Borde ◽  
L. N. Sharma

Cognitive impairment, negative and positive symptoms, primitive release reflexes, and age/temporal disorientation were assessed in 20 male patients meeting the DSM–III–R criteria for chronic schizophrenia and Schooler & Kane's criteria for TD. The control group comprised 20 age-matched male chronic schizophrenic patients without TD. Significant associations were found between TD, cognitive impairment, some negative symptoms, and formal thought disorder. These associations were independent of other illness and treatment variables. The severity of TD correlated significantly with that of cognitive impairment.


2015 ◽  
Vol 27 (4) ◽  
pp. 221-227 ◽  
Author(s):  
Li Su ◽  
Jianxiong Long ◽  
Runde Pan ◽  
Xinfeng Xie ◽  
Xixiang Mao ◽  
...  

BackgroundNRGNis one of the most promising candidate genes for schizophrenia based on function and position. Therefore, this study aimed to examine the genetic association of this polymorphism with schizophrenia in the Zhuang and Han populations of south China.Subjects and methodsA total of 282 patients (188 Han and 94 Zhuang) and 282 healthy subjects (188 Han and 94 Zhuang) were recruited. Of these, 246 schizophrenia patients underwent an assessment of psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS). A TaqMan genotyping assay method was used to determine the genotypes.ResultsWe did not find a significant association of rs12807809 polymorphism with schizophrenia in the total pooled samples, or in the separate ethnic groups. However, in Han schizophrenia patients, quantitative data analyses showed that the CC genotype of the rs12807809 polymorphism was associated with PANSS aggression subscale score and activation subscale score. Furthermore, carriers of the C allele of rs12807809 polymorphism among Han schizophrenia patients had higher scores of general, activation, depression, aggression, and global symptoms than the T allele carriers.ConclusionIn conclusion rs12807809 polymorphism may not contribute to the risk of schizophrenia but influence the clinical symptoms of schizophrenia in the Han population.


2012 ◽  
Vol 201 (4) ◽  
pp. 306-312 ◽  
Author(s):  
Rajeev Krishnadas ◽  
Sameer Jauhar ◽  
Susan Telfer ◽  
Somashekara Shivashankar ◽  
Robin G. McCreadie

BackgroundReasons for the increased prevalence of cigarette smoking in schizophrenia are unclear. Studies assessing clinical symptoms have sampled heterogeneous populations, with discrepant findings.AimsTo examine the relationship between clinical features, social adjustment and nicotine dependence in a geographically defined population of people with schizophrenia.MethodCross-sectional clinical study of 131 people with schizophrenia in Nithsdale, Scotland.ResultsSmokers were younger, mostly males and three times more likely to be unemployed. Those with severe nicotine dependence had greater scores on the positive subscale of the Positive and Negative Syndrome Scale (PANSS), and were prescribed higher doses of antipsychotic. Those with mild–moderate dependence had greater scores on the PANSS negative subscale. Greater symptom severity was associated with poorer social adjustment. Psychopathology and social adjustment were similar in quitters and never-smokers.ConclusionsOur findings indicate an association between nicotine dependence, clinical symptoms and social adjustment in schizophrenia. Although causal links cannot be inferred, identifying the relationship between nicotine dependence and psychopathology may have some value in the management of smoking in schizophrenia. Further longitudinal studies are required to explore this relationship.


2011 ◽  
Vol 26 (S2) ◽  
pp. 1502-1502
Author(s):  
A. Schreiner ◽  
D. Hoeben ◽  
C. Tessier ◽  
M. Lahaye ◽  
J. Turczynski ◽  
...  

ObjectiveTo explore tolerability and treatment response in adult patients with recently diagnosed (<5 years) and chronic (>5 years) schizophrenia treated with flexible doses of paliperidone ER.MethodsInternational prospective open-label 6-month study. Endpoints were the Positive and Negative Syndrome Scale (PANSS), patient functioning and treatment-emergent adverse events (TEAEs).ResultsOf 713 recently diagnosed patients, most were male (60.9%), mean age was 33.6 ± 11.2 years and mean time since diagnosis was 2.3 ± 1.7 years. Chronic patients (n = 1003) were predominantly male (59.2%) with a mean age of 43.8 ± 11.4 and mean time since diagnosis of 15.6 ± 9.2 years. 70.4% and 71.7% of patients completed the study, respectively. Mean mode doses of paliperidone ER were similar between recently diagnosed and chronic patients (7.0 ± 2.9 mg/day and 7.2 ± 2.9 mg/day). 63.1% of recently diagnosed and 60.8% of chronic patients switching due to lack of efficacy with their previous antipsychotic had a >20% improvement in PANSS total score at endpoint, and improvement with other switching reasons was consistently numerically higher in recently diagnosed patients. The rate of patients with mild or no functional impairment increased from 17.7% to 39.8% in recently diagnosed and from 14.4% to 32.9% in chronic patients. TEAEs reported in >5% were insomnia (10.7% and 8.1%), anxiety (8.6% and 6.0%) and somnolence (5.8% and 3.4%), respectively.ConclusionThese data suggest that both recently diagnosed and chronic patients previously unsuccessfully treated with other oral antipsychotics may benefit from paliperidone ER, with a tendency for recently diagnosed patients showing some higher treatment response in psychotic symptoms and patient functioning.


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