首发精神病患者快感缺失水平与认知功能的关系

目的 探讨首发精神病患者快感缺失水平及其与认知功能的关系,分析其认知功能的影响因素.方法 选取2016年12月-2019年3月在广州医科大学附属脑科医院就诊的符合《精神障碍诊断与统计手册(第5版)》(DSM-5)诊断标准的首发精神病患者143例.采用阳性和阴性症状量表(PANSS)评定患者的精神症状,以其中N2情绪退缩...     

Association of a risk allele of ANK3 with cognitive performance and cortical thickness in patients with first-episode psychosis

Background

The gene ANK3 is implicated in bipolar disorder and schizophrenia. The present study investigated the influence of this gene on cognitive performance and brain structure among individuals with first-episode psychosis (FEP). The brief illness duration of an FEP sample makes it well suited for studying the effects of genetic variation.

Methods

We genotyped 2 single nucleotide polymorphisms (SNPs; rs1938526 and rs10994336) in ANK3 in patients with FEP. Multivariate analysis of variance compared risk allele carriers and noncarriers on 6 domains of cognition consistent with MATRICS consensus. A subsample of 82 patients was assessed using magnetic resonance imaging. We compared brain structure between carriers and noncarriers using cortical thickness analysis and voxel-based morphometry on white matter.

Results

In the 173 patients with FEP included in our study, rs1938526 and rs10994336 were in very high linkage disequilibrium (d′ = 0.95), and analyses were therefore only carried out on the SNP (rs1938526) with the highest minor allele frequency (G). Allele G of rs1938526, was associated with lower cognitive performance across domains (F_6,164 = 2.38, p = 0.030) and significantly lower scores on the domains of verbal memory (p = 0.015), working memory (p = 0.006) and attention (p = 0.019). The significant effects of this SNP on cognition were not maintained when controlling for IQ. Cortical thinning was observed in risk allele carriers at diverse sites across cortical lobes bilaterally at a threshold of p < 0.01, false discovery rate–corrected. Risk-allele carriers did not show any regions of reduced white matter volume.

Limitations

The sample size is modest given that a low-frequency variant was being examined.

Conclusion

The ANK3 risk allele rs1938526 appears to be associated with general cognitive impairment and widespread cortical thinning in patients with FEP.     

1-year follow-up study of cognitive function in first-episode non-affective psychosis

The longitudinal course of primary cognitive dysfunction seen in schizophrenia has yet to be fully clarified. Whereas some studies in chronic patients have revealed a progressive decline in cognitive abilities, those studies with first-episode patients have indicated that initial cognitive deficits might remain stable over time. The aim of this study was to examine the longitudinal course of cognitive functioning in patients with a first episode of schizophrenia. 112 patients with a first episode of schizophrenia-spectrum disorders and 22 healthy controls completed clinical and cognitive evaluations at baseline and again after 1 year. An extensive neuropsychological battery that comprised seven cognitive domains was used. Patients and controls improved their cognitive performance in virtually all the cognitive domains after one year. However, patients continued to show marked cognitive deficits after one year, unlike healthy volunteers. The longitudinal cognitive changes were similar in patients and controls in all domains except Verbal Memory (F = 11.67; df = 1; P = 0.001). The increase in cognitive scores found during early phases of the illness seems to be associated to practice-related changes and would not reflect a real cognitive enhancement but rather stability of deficit. Patients' deficits remained stable over time in all cognitive domains except Verbal Memory, in which less performance improvement was found. Further investigations are warranted to discern the variability in patterns of specific cognitive deficits over time.     

Neurological abnormalities and cognitive ability in first-episode psychosis

BACKGROUND: It remains unclear if the excess of neurological soft signs, or of certain types of neurological soft signs, is common to all psychoses, and whether this excess is simply an epiphenomenon of the lower general cognitive ability present in psychosis. AIMS: To investigate whether an excess of neurological soft signs is independent of diagnosis (schizophrenia v. affective psychosis) and cognitive ability (IQ). METHOD: Evaluation of types of neurological soft signs in a prospective cohort of all individuals presenting with psychoses over 2 years (n=310), and in a control group from the general population (n=239). RESULTS: Primary (P<0.001), motor coordination (P<0.001), and motor sequencing (P<0.001) sign scores were significantly higher in people with any psychosis than in the control group. However, only primary and motor coordination scores remained higher when individuals with psychosis and controls were matched for premorbid and current IQ. CONCLUSIONS: Higher rates of primary and motor coordination signs are not associated with lower cognitive ability, and are specific to the presence of psychosis.     

Duration of untreated psychosis and cognitive deterioration in first-episode schizophrenia

Cognitive impairment is an important clinical feature in many individuals with schizophrenia. Factors associated with cognitive deficit are not well established. Duration of untreated psychosis (DUP) has recently gained interest as a prognostic factor in schizophrenia. This study reports on the association between DUP and cognitive function. Subjects comprised 42 individuals (30 males, 12 females) who experienced a first-episode of DSM-III-R schizophrenia or schizophreniform disorder. Cognitive function was determined at clinical stabilization using the WAIS-R. An estimate of cognitive deterioration was based on the WAIS-R subtest profile. Longer DUP, male gender, higher premorbid IQ and younger age at admission independently predicted cognitive deterioration. Poorer performance on Digit Symbol and Comprehension subtests was associated with longer DUP. The findings suggest that untreated psychosis compromises some aspects of cognitive function. Studies investigating the association between DUP and outcome should control for potentially confounding variables. Early treatment of psychosis could help to reduce the prominent cognitive deficit in first-episode schizophrenia.     

Differential associations of cognitive insight components with pretreatment characteristics in first-episode psychosis

An increasing number of studies have focused on cognitive insight (i.e. awareness of one's own thinking) in psychotic disorders. However, little is known about the premorbid and pretreatment correlates of cognitive insight in the early course of psychosis. One hundred and three patients experiencing first-episode psychosis (FEP) were assessed shortly after treatment initiation for cognitive insight. Pretreatment and baseline clinical, functional and neurocognitive characteristics were examined. The self-reflectiveness dimension of cognitive insight was independently associated with clinical insight and executive functioning, whereas self-certainty was associated with premorbid IQ, premorbid academic adjustment and clinical insight. The amount of variance explained by the independent variables was small to moderate. Self-reflectiveness and self-certainty have differential pretreatment correlates in FEP and may reflect separate cognitive processes which require targeted interventions.     

The differential effect of illicit drug use on cognitive function in first-episode psychosis and healthy controls

Donoghue K, Mazzoncini R, Hart J, Zanelli J, Morgan C, Dazzan P, Morgan KD, Murray RM, Jones PB, Doody GA. The differential effect of illicit drug use on cognitive function in first‐episode psychosis and healthy controls. Objective:: Illicit drug use can result in impairment in cognitive function in healthy individuals. Individuals with a psychotic disorder also show a deficit in cognitive function. Drug use may simply contribute to the characteristic cognitive deficit found in psychosis or alternatively result in a ‘double deficit’. This study aims to investigate the association between drug use and cognitive function at the first‐episode of psychosis and in community‐matched controls. Method:: One hundred and seventy‐seven patients at the first episode of psychosis completed a battery of neuropsychological tests. Those that had used drugs in the previous year (n = 80) were compared with those who had not used drugs in the previous year (n = 97). A subsample of the first‐episode psychosis patients were compared with community‐matched controls (n = 110) according to drug‐use status. Results:: Patients with a first episode of psychosis who had used drugs performed equally to those who had not used drugs on neuropsychological tests. In contrast, healthy controls who had used drugs in the previous year performed worse on tests of executive function and working memory compared with those controls that had not used drugs. Conclusion:: There are differential associations of illicit drug misuse with cognitive function for first‐episode psychosis patients and healthy controls.     

Association of Parkinson disease age of onset with DRD2, DRD3 and GRIN2B polymorphisms

IntroductionDopamine and glutamate are crucial neurotransmitters in Parkinson disease (PD). While recent large meta-analyses reported that genetic variation of dopamine (DRD2, DRD3) and glutamine (NMDA, GRIN2B) neurotransmitter receptors was not associated with PD risk, they could conceivably influence PD phenotype. We studied the association of these receptor polymorphisms relating to PD age of onset.MethodsThere were 664 PD patients and 718 controls, all Caucasian, with stored DNA at Mayo Clinic, Jacksonville, Florida. Genotyping was performed for DRD2 (Taq 1A, rs1800497), DRD3 (rs6280), and NMDA (GRIN2B, rs7301328) polymorphisms with ABI Taqman assays. Single nucleotide polymorphism associations with age of onset were evaluated using dominant, recessive, and additive genotypic models.ResultsDRD3 variant carriers had an approximate 4.4-year decrease in mean age of onset when both copies of the minor allele were present (P = 0.0034) and an approximate 1.5-year decrease in mean age at onset for every additional minor allele (P = 0.023) (recessive and additive models, respectively). There was no association with age of onset for DRD2 or GRIN2B under any statistical model (all P ≥ 0.22).ConclusionsThe DRD3 (rs6280) polymorphism, but not DRD2 (Taq1A) or GRIN2B, influences younger PD age of onset in the US Caucasian population. Validation of these findings in larger studies with other ethnic groups is indicated.     

Dysregulated peripheral endocannabinoid system signaling is associated with cognitive deficits in first-episode psychosis

Among etiological explanations for psychosis, several hypotheses involving alterations on the immune/inflammatory system have been proposed. The endocannabinoid system (ECS) is an endogenous neuroprotective, anti-inflammatory system that modulates cognitive processes. Its altered expression has been associated with psychotic disorders. 73 patients with a first episode of psychoses (FEP) and 67 healthy controls were recruited in 5 university centers in Spain. The protein expression of the main peripheral ECS components was determined in peripheral blood mononuclear cells. The cognition function was assessed following the MATRICS consensus. After controlling for potential confounding factors, working memory statistically correlated to the peripheral N-acyl phosphatidylethanolamine phospholipase expression (p = 0.039). The short-term verbal memory correlated to the Diacylglycerol lipase (p = 0.043) and the fatty acid amide hydrolase (p = 0.026) expression. Finally, attention measures correlated to the Monoacylglycerol lipase expression, by means of the CPT-II commissions (p = 0.036) and detectability (p = 0.026) scores. The ECS may regulate the activation of key mediators in immune and inflammatory responses that may be involved in the primary neuronal stress phenomenon that occurs from the onset of psychotic illness. This study points a relationship between the ECS and the cognitive function in early psychosis and suggests the use of some of the ECS elements as biomarkers and/or pharmacological targets for FEP.     

奎硫平对首发精神分裂症认知功能的影响

目的:探讨奎硫平对首发精神分裂症患者认知功能的影响。方法:将71例精神分裂症患者随机分为两组,分别给予奎硫平和氯丙嗪治疗8周。于治疗前、治疗8周末分别用阳性与阴性症状量表(PANSS)评定疗效,用威斯康星卡片分类测验(WCST)、数字划消测验(CT)、修订韦氏成人记忆量表(WMS-RC)评定认知功能。结果:两组PANSS分值治疗前后差异均有显著性(P<0.01);但两组之间比较,差异无显著性(P>0.05)。治疗8周末奎硫平组WCST总测验次数、持续错误数、非持续错误数,CT,WMS-RC测验成绩均显著提高(P<0.05~0.01);而氯丙嗪组则无明显变化(P>0.05)。结论:奎硫平与氯丙嗪对首发精神分裂症患者疗效相当,但奎硫平对首发精神分裂症患者认知功能改善明显。     

首发精神分裂症患者认知功能研究

目的:了解首发精神分裂症患者认知功能损害特点以及治疗对认知功能的影响。方法:对37例符合中国精神障碍分类与诊断标准第3版首发精神分裂症诊断标准的患者于治疗前及治疗8周后采用华文认知能力量表(CCAS)、阳性与阴性症状量表(PANSS)进行评定;同时调查患者的临床特征。结果:精神分裂症患者治疗后CCAS工作记忆(t=3.315,P<0.01)、学习能力(t=4.726,P<0.01)、推理能力(t=4.209,P<0.01)、加工速度(t=6.253,P<0.01)、空间/计算(t=5.111,P<0.01)等认知功能和言语智商(t=3.769,P<0.01)、操作智商(t=3.552,P<0.01)以及总智商(t=3.972,P<0.01)均较治疗前有不同程度提高;治疗前后比较差异均有统计学意义。经Pearson相关分析,治疗前后总智商的差值与PANSS总分及阳性总分差值具有相关性(r分别=0.564、0.756,P<0.05)。结论:首发精神分裂症患者在发病初期就存在认知功能损害;奥氮平等药对精神分裂症的认知损害具有一定改善作用,短时记忆某些成份的改善与精神症状(阳性症状)的好转具有相关性。     

首次发病的强迫症患者认知功能的研究

目的:探讨首次发病的强迫症(OCD)患者认知功能的特点及相关影响因素。方法:采用逻辑记忆、视觉再生记忆、连线测验、数字广度、Stroop测验及威斯康星卡片分类测验分别对35例首次发病的OCD患者(OCD组)及30名健康对照者(HC组)进行神经心理学测评;应用Yale-Brown强迫量表(Y-BOCS)、抑郁自评量表(SDS)、状态-特质焦虑问卷(STAI)评定患者的病情及抑郁、焦虑程度。结果:OCD组的逻辑延迟记忆、视觉再生记忆、连线测验A、B时间、数字广度倒背、Stroop测验字色阅读时间、威斯康星卡片分类测验成绩较明显差于健康对照组(P均<0.05)。OCD患者的病程与其视觉延迟记忆、数字广度倒背分呈负相关(r=-0.39,P=0.024;r=-0.38,P=0.027),SDS分与Stroop测验字色阅读时间正相关(r=0.37,P<0.05),Y-BOCS分、SAI分及TAI分与各神经心理学指标的相关性无统计学意义(P均>0.05)。结论:首次发病的OCD患者存在记忆、注意和执行功能损害。     

Association of grey matter volume deviation with insight impairment in first-episode affective and non-affective psychosis

The neurobiological correlates of impaired insight in psychotic illness remain uncertain and may be confounded by factors such as illness progression and medication use. Our study consisted of two separate experiments. In the first experiment, we examined the association between measures of insight and regional brain volume in thirty-two patients with first-episode psychosis. In the second experiment, we looked at similar associations in thirty individuals with chronic schizophrenia. Detailed measures of symptom awareness and symptom attribution were obtained using the Scale to assess Unawareness of Mental Disorder. MRI scans were acquired and analysed using Statistical Non-Parametric Mapping for voxel-based analyses of grey matter maps. Regression models were used to assess the relationship between insight and grey matter volume in both the first-episode psychosis and the chronic schizophrenia experiments whilst controlling for potential confounds. In first-episode psychosis patients, symptom misattribution was associated with increased grey matter in the right and left caudate, right thalamus, left insula, putamen and cerebellum. In the chronic schizophrenia study, there were no significant associations between regional grey matter volume and measures of insight. These findings suggest that neuroplastic changes within subcortical and frontotemporal regions are associated with impaired insight in individuals during their first episode of psychosis.     

Aggression in Asian patients with first-episode psychosis

AIMS: The aims of this study were to examine the prevalence and severity of aggression in patients with first-episode psychosis and to identify the association between aggression and sociodemographic and clinical factors. METHODS: Consecutive patients with first-episode psychosis admitted to the Early Psychosis Intervention Programme, Singapore, were assessed for a history of aggressive acts. Diagnosis was confirmed using the Structured Clinical Interview for DSM-IV and psychopathology was assessed using PANSS. RESULTS: Of the 146 patients, 63.0% had no history of aggressive acts, 13.7% demonstrated severe aggression (defined as weapon use, sexual assault or victim injury) and 23.3% had lesser aggression (all other acts of aggression). Patients with aggression had a significantly longer duration of untreated psychosis (DUP) than those with no history of aggression (p = .01). The mean total PANSS scores did not differ significantly among the three groups. However, the General Psychopathology scores and the scores for 'hostility', 'poor impulse control', 'lack of insight and judgement' and 'somatic concern' were all significantly elevated in patients with aggression (p < .05). CONCLUSION: The significant association between aggression and longer DUP once again reiterates the need for early detection and effective management of first-episode psychosis.     

Patient satisfaction with treatment in first-episode psychosis

Purpose: To examine first-episode psychotic patients' satisfaction with elements of a comprehensive 2-year treatment program. Subjects and method: The TIPS (Early Treatment and Intervention in Psychosis) project provided a 2-year treatment program consisting of milieu therapy (inpatient), individual psychotherapy, family intervention and medication. Of 140 patients at baseline, 112 were included at 2-year follow-up. Eighty-four participants were interviewed using a questionnaire eliciting levels of satisfaction with different treatment elements at two of the four sites. Results: Participants and non-participants did not differ on demographic or clinical data at baseline. Of those participating, 75% were satisfied with treatment in general. Individual and milieu therapy received higher rating than medication or family intervention. No predictors of general satisfaction with treatment were found, but continuously psychotic patients were the least satisfied with medication treatment. Discussion: As in most patient satisfaction studies within mental health treatment networks, there was high level of general satisfaction with the total package of treatment but considerable variation in satisfaction for specific interventions. In this sample of first-episode psychosis patients, there was general satisfaction with treatments based on one-to-one relationships while multi-family group intervention was consistently valued less enthusiastically.     

精神分裂症患者认知功能与精神症状相关性研究

目的：探讨精神分裂症患者认知功能与精神症状的相关性。方法：对40例精神分裂症患者于治疗前、治疗12周末分别进行韦氏成人智力量表（WAIS-R）、韦氏记忆量表（WMS）、H—R神经心理成套测验（HRB）中的连线测验A、威斯康星卡片分类测验（WCST）及言语流利性测验及简明精神病评定量表（BPRS）评定。结果：治疗前焦虑抑郁因子分与总记忆商数（MQ）分显著相关,迟滞因子分与WCST完成类别数、智力显著相关;治疗12周末焦虑抑郁因子分与总智商（IQ）显著相关,迟滞因子分与WCST持续反应数、言语IQ、操作IQ显著相关,猜疑因子分与WCST持续反应数显著相关。结论：精神分裂症患者部分认知功能与精神症状显著相关。     

Untreated initial psychosis: relation to cognitive deficits and brain morphology in first-episode schizophrenia

OBJECTIVE: Studies of patients experiencing their first episode of psychosis have demonstrated that they typically remain undiagnosed and untreated for 1-2 years. It has been postulated that prolonged untreated psychosis may have serious effects: poor response to neuroleptic medications, poor clinical outcomes, and direct neurotoxicity. This study investigated the relationships between duration of untreated initial psychosis and neurocognitive functioning and high-resolution imaging brain measurements. METHOD: A total of 156 subjects with DSM-IV schizophrenia, schizophreniform disorder, or schizoaffective disorder were evaluated during their first episode of psychosis. Measurements included nine domains of neurocognitive functioning, volumetric measures of total brain tissue, gray and white matter, and CSF, and measures of brain surface anatomy. RESULTS: The mean duration of untreated initial psychosis was 74.3 weeks. Correlations between neurocognitive functioning, brain volumetric measurements, and surface anatomy measurements with duration of untreated initial psychosis were weak; none reached statistical significance. When the group was divided on the basis of median duration of untreated initial psychosis, there were again no significant differences between the groups with long and short duration of untreated initial psychosis except on two measures (verbal memory and cortical sulcal depth). CONCLUSIONS: The absence of strong correlations suggests that untreated initial psychosis has no direct toxic neural effects. These results suggest that large-scale initiatives designed to prevent neural injury through early intervention in the prepsychotic or early psychosis phase may be based on incorrect assumptions that neurotoxicity or cognitive deterioration may be avoided. Nevertheless, early treatment is justified because it reduces suffering.