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.     

奎硫平与氯丙嗪对精神分裂症患者认知功能影响的研究

目的探讨奎硫平与氯丙嗪对精神分裂症患者认知功能损害的影响,同时研究精神分裂症,尤其是首发患者认知功能损害的特点及影响因素。方法符合ICD-10诊断标准的精神分裂症患者91例,随机分为奎硫平组（45例）与氯丙嗪组（46例）两治疗组,疗程8周。治疔前及8周末分别进行韦氏成人智力测验（WAIS—RC）、韦氏成人记忆测验（WMS—RC）、威斯康星卡片分类试验（WCST）测定。结果治疗前,患者包括首发患者均有认知功能损害。8周后,奎硫平与氯丙嗪两组患者成绩均明显提高,而奎硫平组的改善显著优于氯丙嗪组。结论认知功能损害是精神分裂症的原发症状之一,奎硫平对其的治疗作用优于氯丙嗪。     

首发精神分裂症利培酮治疗前后认知功能的比较研究

目的探讨首发精神分裂症患者利培酮治疗前后认知功能的变化。方法采用认知评估工具连线测验、简单视觉空间记忆测验（BVMT-R）、WMS-III空间广度测验、霍普金斯词语学习测验（HVLT-R）、定步调听觉连续加法测验（PASAT）和威斯康星卡片分类测验（WCST-64）对经利培酮治疗8周前后的89例首发精神分裂症患者和62例健康对照者进行神经心理测试。结果首发精神分裂症患者治疗前的神经心理测验成绩显著差于治疗后和健康对照组（P〈0.05）;经利培酮治疗8周后达到临床痊愈标准患者的神经心理测验成绩除WMS-III空间广度测验外,其它大部分测验测验成绩仍显著差于健康对照组（P〈0.05）。结论首发精神分裂症患者存在处理速度、工作记忆、言语记忆、空间记忆、注意警觉和执行功能广泛的认知功能损害,利培酮治疗可部分改善认知缺陷,但精神症状达到临床痊愈的患者仍然存在多个领域认知缺陷,提示认知缺陷是精神分裂症的内表型。     

Cognition in young schizophrenia outpatients: comparison of first-episode with multiepisode patients

Cognitive impairments are recognized as a central feature of schizophrenia (SZ), largely independent of other symptoms, and a major cause of poor functioning. Studies indicate cognitive deterioration in the first years after the onset of SZ. These studies, however, have been criticized for using a small sample size, for having limited monitoring of confounding variables, and for the inclusion of cohorts of different ages. The current study compared the cognitive profile of first-episode schizophrenia patients, multi-episode schizophrenia patients and healthy controls (n = 44, n = 39, and n = 44; respectively). The study focused on the early stages of the disorder, recruiting only young patients. All subjects underwent an extensively validated computerized cognitive assessment (Cambridge Neuropsychological Test Automated Battery). The results revealed widespread cognitive impairments in SZ patients, compared with healthy control subjects. The multiepisode SZ patients were significantly more impaired than the first-episode ones, with deficits mainly related to psychomotor speed, pattern memory, and executive functioning. The functioning in other cognitive domains (ie, attention and spatial memory) was deficient even at an early stage of the disorder. These findings can help clarify the course of cognitive decline in young-aged SZ patients and aid in the development of phase-appropriate interventions.     

Social Cognition Enhancement Training for Schizophrenia: A Preliminary Randomized Controlled Trial

The purpose of this study was to evaluate whether social cognition enhancement training (SCET) is effective in improving social context appraisal and perspective-taking abilities of patients with schizophrenia. A total of 34 patients were randomly assigned to receive SCET plus standard psychiatric rehabilitation training or standard psychiatric rehabilitation training only. SCET was conducted twice weekly on a group basis for 6 months. Some social cognitive abilities were improved rapidly after 2-month treatment whereas some improved only after 6-month treatment. These results show promise for the impact of SCET on the social cognitive functioning of individuals with chronic schizophrenia, and further investigation is merited.Kee-Hong Choi and Jung-Hye Kwon are affiliated with the Department of Psychology, Korea University, Seoul, Korea     

Cognitive functioning in stabilized first-episode psychosis patients.

This paper describes the cognitive functioning of a community cohort of individuals presenting with a first episode of a schizophrenia spectrum psychosis. Data were obtained for 107 patients (mean age 25 years) following stabilization of acute psychotic symptoms, mostly with the use of novel antipsychotics, on measures of intellectual, memory, attentional and executive functioning using a standardized battery of cognitive measures, including WAIS III and WMS III. While patients generally performed in the average range across the majority of measures, deficits (Z-scores >1.0 S.D.) were observed on measures of speed of information processing (PASAT, WAIS III) and executive functions (Stroop Test and Trails B), with the greatest deficits observed on tests of processing speed (PASAT). Discrepancy scores between the NART and the WAIS suggest subtle but statistically significant declines in full scale and performance IQ following onset of psychosis. Differences in cognitive functioning between diagnostic groups were not supported. Comparison of the highest and lowest functioning patients with respect to the cognitive measures also did not support any demographic or clinical differences between these two subgroups. Our results suggest a relatively benign cognitive profile in first-episode schizophrenia spectrum psychosis, regardless of diagnosis, when most potential incidence cases in the community are included. The most severe deficits reported were on measures of speeded information processing, and level of performance did not distinguish between patients demographically or clinically.     

Correlates of substance misuse in patients with first-episode schizophrenia and schizoaffective disorder.

OBJECTIVE: To identify factors associated with substance misuse in first-episode patients with schizophrenia or schizoaffective disorder. METHOD: Twenty-seven patients with a past or current history of substance misuse were compared with 91 patients with no history of misuse on demographic and psychopathological measures before being treated for their first episode of psychosis, and on cognitive measures after 6 months of treatment. RESULTS: There were no statistically significant differences between groups for sex, schizophrenia subtype, marital status, education, family history of schizophrenia, course of illness, age of onset, baseline symptoms, time to treatment response, medication side effects, attention span, memory and executive functioning. However, dual diagnosis patients were found to have a higher parental social class, better premorbid cognitive functioning, higher IQ and better language skills. CONCLUSION: First-episode patients with a history of substance misuse have higher intellectual functioning, which may be associated with higher premorbid socioeconomic status and cognitive functioning.     

A 3-year prospective study of neurological soft signs in first-episode schizophrenia

Neurological soft signs are biological traits that underlie schizophrenia and are found to occur at higher levels in at-risk individuals. The expression of neurological soft signs may be modifiable during the onset of the first psychotic episode and the subsequent evolution of the illness and its treatment. This study investigates neurological soft signs in 138 patients with first-episode schizophrenia and tracks the expression of motor soft signs in the following 3 years. For the 93 patients who have completed the 3-year follow-up, we find that neurological soft signs are stable in the 3 years that follow the first psychotic episode, and that neurological soft signs are already elevated at the presentation of first-episode psychosis in medication-naive subjects. The level of neurological soft signs at clinical stabilization is lower for patients with a shorter duration of untreated psychosis. Although the quantity of neurological soft signs does not significantly change in the 3 years that follow the first episode, the relationship between neurological soft signs and negative symptoms does not become apparent until 1 year after the initial episode. A higher level of neurological soft signs is related to a lower educational level and an older age at onset, but the level of neurological soft signs does not predict the outcome in terms of relapse or occupational functioning.     

Cognitive functioning in young people with first episode psychosis: relationship to diagnosis and clinical characteristics

OBJECTIVE: To examine the extent and nature of neuropsychological deficits in adolescents and young people with first episode psychosis (FEP), and to determine whether the pattern and extent of neuropsychological deficits varied according to diagnosis. METHOD: A total of 83 FEP subjects aged 13-25 years, and 31 healthy controls completed a comprehensive battery of neuropsychological tests, grouped into 10 cognitive domains. First episode psychosis subjects were stratified into three diagnostic groups (schizophrenia, affective disorders, substance-induced psychosis) and differences in cognitive profiles were examined. The contribution of demographic and clinical characteristics to cognitive performance was also explored. RESULTS: The schizophrenia group demonstrated significantly worse performance on tasks of verbal learning and memory than the affective disorders group. Compared to healthy controls, the schizophrenia group also demonstrated global impairment across the majority of cognitive domains. The substance-induced group's performance lay between that of the schizophrenia and affective disorders groups. Analyses of differential deficits revealed that verbal learning, verbal memory and current intellectual functioning were selectively impaired in the schizophrenia group, whereas the affective disorders group demonstrated a selective deficit in speeded processing. Premorbid intellectual functioning, negative symptomatology and medication levels were the strongest predictors of cognitive performance in FEP subjects. CONCLUSIONS: Verbal memory deficits differentiate individuals with schizophrenia from those with psychotic affective disorders. Although significant cognitive deficits are evident across all diagnostic FEP groups, individuals with schizophrenia appear to have more generalized impairment across a broad array of cognitive functions than other psychotic diagnoses. Lower premorbid intellectual functioning does not appear to contribute to greater cognitive deterioration following onset of psychosis, but severity of illness may be a more important factor than levels of mood disturbance.     

Prefrontal cognitive functions in stabilized first-episode patients with schizophrenia spectrum disorders: a dissociation between dorsolateral and orbitofrontal functioning

Specific prefrontal cognitive impairments have been reported in first-episode and chronic schizophrenia. We sought to investigate potential impairments in specific prefrontal cortical cognitive functions among stabilized patients with a first-episode of schizophrenia. A sample of 80 individuals with a first-episode of schizophrenia spectrum disorders and 22 healthy volunteers underwent a neurocognitive battery assessing orbitofrontal (OFC) [The Iowa Gambling Task (GT)], and dorsolateral prefrontal (DLPFC) functions (WAIS III Backward digits, verbal fluency test (FAS), and Trail Making Test). Cognitive data were obtained following stabilization of acute psychotic symptoms. Clinical symptoms after six weeks of treatment were assessed by using the SAPS and SANS scales. While there were no significant group differences in overall scores and in the profile of progress of performance along periods on the GT, patient group showed a significant impairment when performing DLPFC tasks. Only FAS score was correlated to the severity of negative symptomatology. The OFC functions are unimpaired at the early phases of psychosis and in contrast there is a significant deficit in DLPFC functions in first-episode of schizophrenia.     

Neurocognitive performances in participants of at-risk mental state for schizophrenia and in first-episode patients

As suggested by the neurodevelopmental model, neurocognitive disturbances are core features of schizophrenia spectrum disorders. The aim of the present study was to explore the neurocognitive performance of symptomatically defined high-risk participants as well as first-episode patients on tests of verbal memory, executive functioning, working memory, and attention. The sample consisted of 54 participants at risk for schizophrenia and 37 patients with a first episode of psychosis. The high-risk group exhibited a similar cognitive performance profile to that of the first-episode participants when compared with normative data. The neurocognitive functioning of both patient groups were within standard average range at most of the cognitive domains. Moreover the intellectual functioning of both groups was within higher average level, while decreased "hit rates" could be observed within both subtests "Figures" and "Symbols" of the Continuous Performance Test-Identical Pairs Version (CPT-IP) in the group of first-episode patients. Direct comparison between the clinical groups did show increasing impairments of these parameters in first-episode patients compared to high-risk participants. Results suggest that high-risk participants do perform at average neurocognitive performance levels at all tested domains compared with normative data. Compared to norm values first-episode patients showed decreased attention abilities.     

Cognitive dimensions in first-episode schizophrenia spectrum disorders

BACKGROUND: The severity and pattern of cognitive deficits in epidemiological cohorts of patients with first-episode schizophrenia spectrum disorders still remains unclear. We aimed to characterize the basic cognitive functioning of a representative sample of patients with a first-episode schizophrenia spectrum disorders. METHOD: One hundred thirty-one patients experiencing first-episode psychosis and 28 healthy volunteers were administered a comprehensive neuropsychological evaluation. To reduce the number of cognitive test measures into meaningful cognitive dimensions, before analyzing differences between patient and healthy volunteer samples, exploratory factor analysis was carried out on data collected in patients group. The method of extraction was Principal Components Analysis with oblique rotation. RESULTS: An eight-factor model including verbal learning/memory, verbal comprehensive abilities, speed of processing/executive functioning, motor dexterity, motor speed, sustained attention, and impulsivity emerged. A significant below average performance in all cognitive dimensions, except impulsivity, was found. Patient's performance in speed of processing/executive functioning, motor dexterity and sustained attention dimensions exceeded one standard deviation below healthy comparison subjects. CONCLUSIONS: At early stages of the illness, patients display a marked impairment in several functionally relevant cognitive domains.     

Prefrontal lobe dysfunction predicts treatment response in medication-naive first-episode schizophrenia

Dysfunction of the frontal lobe is considered to be central to the pathology of schizophrenia. However, the nature of these abnormalities is unclear, in particular whether they are affected by treatment. In an earlier functional MRI study of our group we found dorsolateral prefrontal lobe (DLPFC) dysfunction to be present in medication-naive first-episode patients. In this follow-up study, we investigated whether treatment with atypical antipsychotics had an effect on DLPFC functioning, and whether (change in) DLPFC functioning was related to treatment response. Twenty-three medication-naive, first-episode male schizophrenia patients and 33 matched healthy controls were scanned at baseline and were re-scanned after 10 weeks, while performing a modified Sternberg working-memory task. We specifically investigated the effect of practice on brain activation, defined as the signal change between a novel and practiced working-memory task. After the baseline scan, patients were treated with atypical antipsychotics. Based on their symptom change after ten weeks, patients were divided into responders and non-responders We found DLPFC function did not change after 10 weeks in healthy controls or in patients who received treatment. However, while patients who responded to treatment did not differ from controls, non-responders showed a reduced practice effect in the DLPFC that was present already at baseline, which did not change after treatment. A reduced practice effect in the DLFPC at baseline was found to be predictive of poor treatment response at 10 weeks. These results suggest that prefrontal lobe dysfunction reflects a distinct neuropathological substrate in a subgroup of treatment non-responsive schizophrenia patients.     

Premorbid IQ as a predictor for the course of IQ in first onset patients with schizophrenia: a 10-year follow-up study

The aim of the present study was to examine the longitudinal course of IQ and its heterogeneity in patients with schizophrenia, from the perspective of the two main "subtypes" of schizophrenia described in the literature: progressive cognitive deficit versus cognitive stabilisation or recovery. Premorbid IQ scores and WAIS IQ scores of 100 first onset patients were obtained at first hospitalization (T1) and after 10 years (T2). Significant changes in IQ over time were found, representing (i) at T1, a deterioration compared to premorbid intelligence (B=-6.3, 95% CI -9.5 to -3.0, p<0.0001), followed by (ii) a recovery at T2 where IQ matched premorbid intelligence again (B=0.5, 95% CI -3.1 to 4.0, p=0.79). In addition, a significant interaction was found between course of IQ over time and estimated premorbid IQ, demonstrating that subjects with lower premorbid IQ levels remained stable over time whereas in individuals with higher premorbid IQ levels a pattern of deterioration was evident at T1, followed by a recovery up to premorbid level at T2. The data confirm the importance of estimated premorbid IQ as an indicator of the longitudinal course of cognitive functioning in patients with schizophrenia and add evidence to the hypothesis of heterogeneity or "subtypes" of schizophrenia. The data, however, do not confirm the existence of progressive deterioration of cognitive functioning. Rather, catching up of cognitive function later in the course of the illness may take place in those whose deficits become apparent in the early phases of illness, whereas those with the most severe premorbid impairments remain stable.     

Cognitive functioning in first-episode schizophrenia

OBJECTIVE: To compare the cognitive functioning of a sample of patients experiencing their first episode of schizophrenia with that of patients with an established schizophrenia illness. DESIGN: Cross-sectional and longitudinal study. SETTING: The Calgary Early Psychosis Treatment and Prevention Program and an outpatient clinic in a department of psychiatry at a university-affiliated hospital. PARTICIPANTS: One hundred and eleven patients who were experiencing their first episode of schizophrenia and 76 outpatients with an established schizophrenia illness. MEASURES: The Positive and Negative Syndrome Scale for schizophrenia was administered to all subjects to determine levels of positive and negative symptoms. Executive functioning, information processing, visual memory, and immediate and delayed verbal memory were assessed. RESULTS: There were limited differences between the 2 groups in terms of cognitive functioning. Although the first-episode patients demonstrated generally superior scores, their performance was impaired. CONCLUSIONS: These results support the findings of previous studies suggesting that first-episode patients demonstrate cognitive impairments similar to those of patients with an established schizophrenia illness.     

Association of serum antibodies to herpes simplex virus 1 with cognitive deficits in individuals with schizophrenia

BACKGROUND: Cognitive deficits are a characteristic feature of schizophrenia and contribute to the profound disabilities associated with this illness. Some of the cognitive deficits that occur in individuals with schizophrenia are similar to those found in individuals who have recovered from central nervous system infections with human herpesviruses. METHODS: We measured cognitive functioning and serologic evidence of infection with human herpesviruses in 229 outpatients with schizophrenia. We evaluated cognitive functioning with the Repeatable Battery for the Assessment of Neuropsychological Status. For each patient, serum IgG class antibodies with specificities for the following potentially neurotropic human herpesviruses were measured by means of a solid-phase immunoassay: herpes simplex viruses 1 and 2, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, and varicella-zoster virus. We determined the association between serologic evidence of herpesviruses infection and cognitive functioning by univariate and multivariate analyses, including demographic and clinical factors associated with cognitive functioning. RESULTS: We found that serologic evidence of infection with herpes simplex virus 1 is an independent predictor of cognitive dysfunction in individuals with schizophrenia. Discriminant function analysis indicated that much of the difference in cognitive functioning could be attributed to immediate memory. We found no significant association between cognitive dysfunction and serologic evidence of infection with other human herpesviruses. CONCLUSION: Serologic evidence of herpes simplex virus 1 infection is associated with cognitive impairment in schizophrenia.     

Effects of cognitive remediation therapy versus other interventions on cognitive functioning in schizophrenia inpatients

Computerised cognitive remediation therapy (CCRT) has been shown to improve cognitive function in individuals with schizophrenia beyond effects of other forms of therapy. However, results vary between studies, and most are aimed at individuals who are living in the community. Very few studies have investigated its efficacy in psychiatric wards in order to assess whether or not this is a suitable site to start the therapy. This study evaluated CCRT efficacy among schizophrenia inpatients who received a broad range of therapeutic interventions in a psychiatric ward. A randomised controlled trial of CCRT versus an active control in 66 young inpatients with a diagnosis of schizophrenia was conducted. The intervention lasted for 6 weeks and its efficacy was assessed with the composite score of the MATRICS Consensus Cognitive Battery. Both groups improved similarly in cognitive function and psychopathological symptoms. However, the CCRT group improved more than the controls in negative symptoms. This result shows that providing a drill and practice cognitive remediation to inpatients does not produce benefits for cognitive functioning substantially greater than other forms of therapy provided in a ward, but it is more efficient in reduction of negative symptoms. Our results suggest that CRT might be considered as a promising intervention for reducing negative symptoms in schizophrenia individuals.     

Neurocognitive and social cognitive predictors of interpersonal skill in schizophrenia

Social dysfunction is among the major criteria for receiving a diagnosis of schizophrenia, and research indicates that the impairments in social functioning experienced by individuals with schizophrenia are strongly related to deficits in interpersonal skills. In turn, these deficits in interpersonal skills have been linked to impairments in general cognitive abilities and impairments in social cognition. This study explored the relationship between neurocognition, social cognition, and interpersonal skills in 49 outpatients with schizophrenia and 44 non-clinical control participants. Results indicate that individuals with schizophrenia demonstrated impaired performance across several domains of neurocognitive and social cognitive functioning as well as interpersonal skills. In addition, among the participants with schizophrenia, social cognition significantly contributed unique variance to interpersonal skill beyond that of neurocognition. This pattern was not observed in the non-clinical control sample. These findings have implications for the treatment of the disorder and represent an important step in understanding the role of social cognition in schizophrenia.     

Frequency and predictive values of first rank symptoms at baseline among 362 young adult patients with first-episode schizophrenia Results from the Danish OPUS study

AIM: To investigate the frequency of the Schneiderian First Rank Symptoms (FRSs) in a representative group of patients with first-episode schizophrenia and to analyse the predictive value of these symptoms in relation to psychopathology, work situation, depression, dependency and admission after 2 years of treatment. METHOD: 547 patients were included in the Danish OPUS trial. A subgroup of these, namely the 388 patients who fulfilled the diagnostic criteria for schizophrenia (ICD-10), was included in this study. Data from SCAN interviews were used to describe the frequency of the different first rank symptoms and to compare the characteristics of the patients with and without FRSs. RESULTS: FRSs were very common among these patients with first-episode schizophrenia. Only 16% reported no FRSs at all. Almost half of the patients had experienced commenting or discussing voices, and more than 40% had experienced loud thoughts. More patients with than without FRSs had some kind of substance abuse. FRSs at baseline did not predict the level of scores in the psychotic, negative or disorganized dimension after 2 years. Having FRSs at baseline was related to a significantly lower number of days of admission during the two-year period, but was not associated with antipsychotic medication or depression after 2 years. CONCLUSION: FRSs are very common among first-episode psychosis patients, but their predictive value seems to be limited with respect to outcome measures like psychopathology, work or substance abuse. However, FRSs did predict a lower mean of days of admission.     

Meta-analysis of Cognitive Deficits in Ultra-high Risk to Psychosis and First-Episode Psychosis: Do the Cognitive Deficits Progress Over,or After,the Onset of Psychosis?

Cognitive dysfunction is a well-established feature of schizophrenia, and there is evidence suggesting that cognitive deficits are secondary to abnormal neurodevelopment leading to problems in acquiring such abilities. However, it is not clear whether there is also a decline in cognitive performance over, or after, the onset of psychosis. Our objective was to quantitatively examine the longitudinal changes in cognitive function in patients who presented with first-episode psychosis (FEP), ultra-high risk (UHR) for psychosis, and controls. Electronic databases were searched for the studies published between January 1987 and February 2013. All studies reporting longitudinal cognitive data in FEP and UHR subjects were retrieved. We conducted meta-analyses of 25 studies including 905 patients with FEP, 560 patients at UHR, and 405 healthy controls. The cognitive performances of FEP, UHR, and healthy controls all significantly improved over time. There was no publication bias, and distributions of effect sizes were very homogenous. In FEP, the degree of improvement in verbal working memory and executive functions was significantly associated with reduction in negative symptoms. There was no evidence of cognitive decline in patients with UHR and FEP. In contrast, the cognitive performances of both groups improved at follow-up. These findings suggest that cognitive deficits are already established before the prodromal phases of psychosis. These data support the neurodevelopmental model rather than neurodegenerative and related staging models of schizophrenia.Key words: schizophrenia, psychosis, cognition, neuropsychology, longitudinal