Influence of TAAR6 polymorphisms on response to aripiprazole

Background

There is some evidence suggesting a role of TAAR6 in schizophrenia. The aim of the present study is to investigate possible influences of a panel of markers in TAAR6 (rs8192625, rs4305745, rs4305746, rs6903874, rs6937506) on clinical outcomes and side effects in a sample of Korean schizophrenic aripiprazole treated patients.

Methods

Efficacy was assessed at baseline and weeks 1, 2, 4, 6, 8 using CGI-S, CGI-I, BPRS and SANS. Side effects were evaluated through SAS, BAS and AIMS. Multivariate analysis of covariance (MANCOVA) was used to test possible influences of single SNPs on clinical and safety scores. Tests for associations using multi-marker haplotypes were performed using the statistics environment “R”.

Results

A significant time per genotype interaction was found between rs4305746 in repeated measures of ANOVA on BPRS scores (F = 2.45, df = 10,365, p = 0.008). In particular G/A and A/A genotype patients were more likely to improve over time as compared to carriers of the G/G genotype. Permutation analysis confirmed a significant effect of rs4305746 on course of BPRS scores over time (p = 0.007). Haplotype analysis did not reveal any significant association with clinical and safety scores at any time.

Conclusion

A possible association could exist between some genotypes in TAAR6 and response to aripiprazole. However, several limitations characterize the present work, such as small sample size, the finding related to a single scale and the possibility of false positive findings, thus further investigation is required.     

Lack of association of GPX1 and MnSOD genes with symptom severity and response to clozapine treatment in schizophrenia subjects

Abnormal activities of critical antioxidant enzymes and other indices of lipid peroxidation in plasma and red blood cells were detected in patients with schizophrenia. Other results have shown that oxidative stress may be modulated by clozapine. Based on that and some studies already found different clinical relations between reactive oxygen species and negative and positive symptoms, we evaluated association between clinical response and the polymorphism in the human glutathione peroxidase (GPX1) (Pro200Leu, rs1050450) and manganese SOD (MNSOD) (Ala16Val, rs4880) gene in 216 clozapine‐treated patients with schizophrenia. No association was found with these two functional polymorphisms and clozapine response and symptom change after 6 months. No correlations were found between positive/negative symptoms score and both polymorphisms. Our results present that GPX1 (Pro200Leu) and MNSOD (Ala16Val) polymorphisms seem do not play a central role in the clozapine response, although studies in larger and independent samples are necessary to confirm our findings. Copyright © 2009 John Wiley & Sons, Ltd.     

Association study between Disrupted-in-Schizophrenia-1 (DISC1) and Japanese patients with treatment-resistant schizophrenia (TRS)

Treating the 20-30% of patients with schizophrenia whose symptoms are resistant to antipsychotic treatment, a condition known as treatment-resistant schizophrenia (TRS), can be problematic. Recently, an association between Disrupted-in-Schizophrenia-1 (DISC1), a candidate susceptibility gene for schizophrenia, and TRS was reported. Associations between three missense SNPs, rs3738401 (Q264R), rs6675281 (L607F), and rs821616 (S704C) in DISC1, especially rs3738401, showed strong significance. Thus, the main aim of our current study was to examine if the reported possible functional polymorphisms in DISC1 were related to Japanese TRS. First, DISC1 was re-investigated in 485 Japanese patients with schizophrenia and 660 healthy controls with a case-control study using four candidate SNPs, rs751229, rs3738401, rs821597, and rs821616. DISC1 was not associated with schizophrenia in the Japanese population. Second, we investigated whether these SNPs contributed to TRS in 127 inpatients with schizophrenia (35 patients; TRS and 92 patients; non-TRS). The genotypic distributions of these four SNPs were not significantly different between TRS and non-TRS in either genotypic or recessive models of minor alleles. In addition, clinical variables, such as improvement in clinical symptoms, duration of hospitalization, and total antipsychotics dose amounts, were not different among the genotypes of these SNPs. Taken together, results showed that DISC1 had no apparent degree of association with Japanese patients with schizophrenia as a candidate susceptibility gene for disease per se or TRS.     

中山市住院流浪精神病患者现状分析

目的 了解中山市住院流浪精神病患者的现状,为制定政策、采取有效救治和管理措施提供依据.方法 对中山市第三人民医院收治的316例流浪精神病患者,采用自拟住院精神病患者调查表统计临床资料,采用肇事肇祸危险性5级评定法评估肇事肇祸危险性,采用临床总体印象量表、简明精神病量表、护士用住院病人观察量表评定疾病状况.结果 住院流浪精神病患者以未婚青年男性为主,籍贯以省内及邻近省份为主,肇事肇祸危险性评估1级以上占58.72%,以脏臭流浪(24.68%)、影响社会治安(44.30%)入院为主,54.81%既往有精神病史,49.68%诊断为精神分裂症者,21.52%合并内科疾病,91.14%使用典型抗精神病药物治疗,全院年平均床位占有率23.27%.结论 住院流浪精神病患者的救治工作关系到社会和谐稳定,患者长期滞留医院是当前亟待解决的问题.     

Left orbitofrontal and superior temporal gyrus structural changes associated to suicidal behavior in patients with schizophrenia

Suicidal attempts are relatively frequent and clinically relevant in patients with schizophrenia. Recent studies have found gray matter differences in suicidal and non-suicidal depressive patients. However, no previous neuroimaging study has investigated possible structural abnormalities associated to suicidal behaviors in patients with schizophrenia. A whole-brain magnetic resonance voxel-based morphometric examination was performed on 37 male patients meeting the DSM-IV criteria for schizophrenia. Thirteen (35.14%) patients had attempted suicide. A non-parametric permutation test was computed to perform the comparability between groups. An analysis of covariance (AnCova) model was constructed with a statistical threshold of p<0.05 corrected for multiple comparisons. After controlling for age and severity of illness, results showed significant gray matter density reduction in left superior temporal lobe (p=0.03) and left orbitofrontal cortex (p=0.04) in patients who had attempted suicide when comparing with non-suicidal patients. Although sample size limitations and potential clinical heterogeneity preclude definitive conclusions, these data point to structural differences in key cerebral areas. Neuroimaging studies are necessary to expand our knowledge of biological mechanisms underlying suicide in schizophrenia.     

Acute antipyschotic efficacy and side effects in schizophrenia: association with serotonin transporter promoter genotypes

BACKGROUND: The serotonin transporter (5-HTT) plays an important role in serotonergic neurotransmission. In the present study, we investigated the effects of the 44 bp insertion/deletion polymorphism in the promoter region of 5-HTT gene (5-HTTLPR) on symptomatology of psychosis and clinical response to antipsychotic drugs. METHODS: In total 56 patients acutely treated with haloperidol or risperidone either for the first episode of schizophrenia, schizophreniform or schizoaffective disorders, or for the relapse of these psychotic disorders after tapering their maintenance treatment, were genotyped for the 5-HTTLPR L and S alleles and for the new A/G functional variant within the L alelle (La/g). Psychopathological symptoms were assessed with the Brief Psychiatric Rating Scale (BPRS) and with Clinical Global Impression (CGI) twice: at 8-12 days after the first dose of antipsychotic and after 4 weeks. Extrapyramidal side effects were assessed with the Simpson-Angus Extrapyramidal Side Effects Scale (EPS), the Barnes Akathisia Scale (BARS) and the Abnormal Involuntary Movement Scale (AIMS). RESULTS: Age, body mass index (BMI), illness duration, drug type and dosage were considered as covariates when analysing association with genetic variants as they were associated with baseline or final BPRS and CGI scores and/or extrapyramidal side effects. 5-HTTLPR was not associated with baseline and final BPRS and CGI scores or with the CGI% reduction. However, the 5-HTTLPR S allele was associated with a lower improvement in BPRS scores (P=0.022) and this effect was even stronger after pooling subjects with S or Lg containing alleles (P=0.006). We did not observe any effect of 5-HTTLPR on acute antipsychotics side effects. CONCLUSION: Present result supports a contribution of serotonin system to neuroleptics efficacy for the treatment of schizophrenia. The analysis of the La/g functional variant may significantly improve the predictive power of 5-HTTLPR genotyping and represent a step further towards the development of the personalized antipsychotic treatment.     

Hallucinatory disorder,an original clinical picture? Clinical and imaging data

OBJECTIVE: The aim of this study was to verify the existence of areas of clinical and neurofunctional homogeneity in a group of patients with auditory verbal hallucinations (AVHs) as an isolated symptom, attributable to what we have called "Hallucinatory Disorder" (HD) in an attempt to propose a clinical picture that is distinct from Schizophrenia. METHOD: Nine patients clinically characterised by chronic AVHs were compared with nine schizophrenic patients using the Structured Clinical Interview for DSM-III-R, BPRS, PANSS, SAPS, SANS, HRS-A, HRS-D, CDSS, MMSE, CGI and PSYRATS. Both groups of patients and nine healthy subjects underwent EEG and SPECT examinations. RESULTS: Considering the psychopathological dimensions of Schizophrenia, in the HD patients clinical evaluations revealed a mono-dimensional clinical profile, whereas all these dimensions contributed to the clinical picture of the schizophrenic patients. The SPECT data showed that the schizophrenic patients had a reduced rCBF in some areas of the right frontal lobe, while the HD patients did not show any area of hypoperfusion. The SPECT hyperperfusion data showed an activation pattern in the HD patients that was characterised by the involvement of various cortical and subcortical cerebral areas, similar to those found in studies of inner speech and auditory verbal imagery. CONCLUSIONS: The two groups of patients present significant differences that seem capable of supporting the proposed hypothesis that HD may be an independent nosographical entity.     

电休克应用于精神分裂症患者护理的效果观察

目的 探讨电休克应用于精神分裂症患者护理的效果。方法 回顾性分析2019 年1～12 月我院治疗的70 例精神分裂症患者,根据护理模式分为传统护理干预组及综合护理干预组。所有患者实施电休克治疗,传统护理干预组采取普通护理,综合护理干预组采取心理、治疗准备等综合护理。比较简明精神病评定量表（BPRS）及PANSS 量表评分、护理满意度问卷调查评分、住院时间、并发症发生率。结果 综合护理干预组护理满意度问卷调查评分高于传统护理干预组,差异有统计学意义（P＜0.05）。护理后,综合护理干预组BPRS 评分及PANSS 量表评分为（23.21±3.05）分、（71.93±10.61）分,低于传统护理干预组的（36.19±6.79）分、（95.29±11.71）分,差异有统计学意义（P＜0.05）。综合护理干预组患者护理满意度问卷调查评分高于传统护理干预组（P＜0.05）。综合护理干预组住院时间为（7.78±1.82）d,短于传统护理干预组的（9.97±1.86）d,差异有统计学意义（P＜0.05）。综合护理干预组并发症总发生率为2.86%,低于传统护理干预组的20.00%,差异有统计学意义（P＜0.05）。结论 电休克治疗的精神分裂症患者采用综合护理干预,可更好地促进患者康复、改善患者病情、减少并发症发生、缩短住院时间,并提高患者对护理的满意度。     

Norsk rapport

Nils Retterstôl (bilden) är sedan 1969 professor i psykiatri vid universitefet i Bergen, tillika styresman och överläkare vid Neevengården sykehus.