Lack of an inverse relationship between duration of untreated psychosis and cognitive function in first episode schizophrenia

This study assessed the relationship between duration of untreated psychosis (DUP) and cognitive measures in order to assess if longer DUP was associated with worse performance. One hundred two patients with first episode schizophrenia or schizoaffective disorder were assessed on cognitive measures of speed of processing, episodic memory, executive function, and visual spatial processing at baseline (when patients were drug naive and after 16 weeks of olanzapine or risperidone treatment), so that a change score could be derived. DUP was defined by the emergence of psychiatric symptoms and the emergence of psychotic symptoms. Data were analyzed correlationally, parametrically (after the group was divided into long and short DUP by median split), and by regression. We found that DUP for psychotic symptoms in this group of patients was long, with a median of 46 weeks. Neither correlational, parametric analyses in which DUP served as a class variable, nor multiple regression indicated that longer DUP was associated with worse cognition at baseline or smaller magnitude of improvement in cognition. Our results suggest that while early intervention may be critical for symptom amelioration by shortening DUP, early intervention for treatment of psychiatric symptoms may have little or no impact on cognitive function. Furthermore, assuming that cognition is a core symptom of schizophrenia, the notion that ongoing psychosis is somehow toxic for a variety of information processing domains appears questionable.     

Correlates of cognitive deficits in first episode schizophrenia

OBJECTIVE: The presence of cognitive dysfunction in schizophrenia has been well documented, but questions remain about whether there are relationships between this dysfunction and clinical symptomatology. If present, such relationships should be most clearly observable in patients with first episode schizophrenia; that is, before the effects of chronic illness, institutionalization, or treatment might confound them. METHOD: 307 schizophrenia subjects in their first episode of illness were recruited to participate in a clinical trial comparing the long-term efficacy of haloperidol and risperidone. The psychopathology, cognitive functioning, early treatment history, and duration of untreated psychosis of these subjects were assessed prior to their assignment to randomized, double-blind treatment. Approximately two-thirds of the subjects were receiving antipsychotic treatment at the time of assessment; however, the duration of treatment was limited to 12 weeks or less. RESULTS: The severity of negative symptoms at the time of assessment was associated with deficits in memory, verbal fluency, psychomotor speed and executive function. Positive symptoms were not associated with cognitive deficits. Also, the duration of untreated illness (DUI) prior to assessment was not significantly associated with cognitive impairment. CONCLUSIONS: The results of this study of first episode schizophrenia patients suggest that a relationship exists between negative symptoms and cognitive dysfunction. However, that relationship accounts for only a minor portion of the variance (i.e., 10-15%) in the severity of cognitive dysfunction after controlling for a number of potentially confounding factors. This finding provides support for the theory that the neurobiological processes that give rise to symptomatology and cognitive dysfunction in schizophrenia are partially overlapping.     

Early course of illness in first episode schizophrenia with long duration of untreated illness - a comparative study

When a long duration of untreated illness (DUI) is correlated with an unfavourable progression of schizophrenia in the same way as that of a long duration of untreated psychosis (DUP), the characteristics of patients with a long DUI are of particular interest for early recognition and early intervention programmes. With this background, demographic data and early symptoms were collected from 82 first time in-patients with schizophrenia using the IRAOS (Interview for the Retrospective Assessment of the Onset of Schizophrenia). In the total sample, the average DUI was almost 5.9 years. On the basis of the DUI median (5.2 yrs), the random sample was divided into two groups: one with long (n = 41) and one with short (n = 41) DUI. When comparing both groups in terms of socio-demographic data, no significant differences could be found (with the exception of age at first admission: 28 - 32 yrs). On a psychopathological level, patients with long DUI were prone to depressive moods, anxiety, compulsive symptoms and showed early signs of disturbances in bodily perception. An educational campaign should sensitize both employees working in primary care and experts who diagnose and treat psychological illnesses, to the fact that these symptoms could point to a prodrome even when the patient has passed the typical age of being at risk from schizophrenia.     

Prolonged untreated illness duration from prodromal onset predicts outcome in first episode psychoses

Several, although not all, studies suggest that prolonged duration of untreated illness (DUI) predicts poor outcome in psychotic disorders such as schizophrenia. It is unclear whether this association can be explained by factors such as baseline deficits or poor premorbid adjustment. First episode psychotic patients were evaluated at 1 and 2 years following baseline evaluations. Predictive measures showing significant correlations with outcome were entered in multiple regression analyses with Strauss-Carpenter scale (SC) and Global Assessment of Functioning scale (GAF) outcome scores as dependent variables. Illness duration computed from the onset of the prodrome (DUI-pro), used both as a dichotomous and as a continuous measure, highly significantly predicted both GAF and SC scores at 2 years. On the other hand, baseline functioning significantly predicted the 1-year but not the 2-year outcome. When Premorbid Adjustment Scale (PAS) scores were additionally entered into the analyses in a smaller subset, the relation between DUI-pro and the 2-year outcome scores remained significant. Significant associations were also seen between outcome and baseline neuropsychological deficits involving attention and memory. Further research is needed to examine whether prolonged untreated illness is simply associated with poor outcome or plays a causal role in relation to outcome. The latter, if true, would strongly support therapeutic intervention efforts in the prodromal and early psychotic phases of schizophrenia.     

First rank symptoms in first episode psychosis and their relationship to the duration of untreated illness

Most studies of First Rank Symptoms (FRS) are based on cross-sectional inpatient samples of people with schizophrenia at various stages of illness. We sought to examine the prevalence of FRS in a representative sample of first episode psychosis patients and compare those with and without FRS clinically and in terms of duration of untreated illness. Information was gathered from 158 consecutive cases of first episode psychosis presenting in a defined geographical region through semi-structured interview tools. Of this sample, 40.5% of cases received a diagnosis of schizophrenia. The prevalence of FRS among the entire group was 52.5%. After controlling for multiple testing, no FRS contributed significantly to predicting a diagnosis of schizophrenia. There was no significant relationship between the duration of untreated illness and FRS.     

Reduced auditory evoked gamma band response and cognitive processing deficits in first episode schizophrenia

Objectives. Gamma-band oscillations (e.g., the early auditory evoked gamma-band response, aeGBR) have been suggested to mediate cognitive and perceptual processes by driving the synchronization of local neuronal populations. Reduced aeGBR is a consistent finding in patients with schizophrenia and high-risk subjects, and has been proposed to represent an endophenotype for the illness. However, it is still unclear whether this reduction represents a deficit in sensory or cognitive processes, or a combination of the two. The present study investigated this question by manipulating the difficulty of an auditory reaction task in patients with first-episode schizophrenia and healthy controls. Methods. A 64-channel EEG was recorded in 23 patients with first-episode schizophrenia and 22 healthy controls during two conditions of an auditory reaction task: an easy condition that merely required low-level vigilance, and a difficult condition that placed significant demands on attention and working memory. Results. In contrast to healthy controls, patients failed to increase aeGBR power and phase-locking in the difficult condition. In patients, aeGBR power and phase-locking indices were associated with working memory deficits. Conclusions. The observed results confirm the applicability of aeGBR disturbances as a stable endophenotype of schizophrenia, and suggest a cognitive, rather than sensory, deficit at their origin.     

Grey matter deficits and symptom profile in first episode schizophrenia

Several studies have investigated grey matter reductions in first episode schizophrenia (FES), but few have examined the relationship between grey matter reduction and clinical profile. A group of 31 patients with strictly defined FES and 30 healthy controls underwent T1-weighted magnetic resonance imaging (MRI) scan. Voxel-based morphometry in SPM99 was used to identify four distinct regions of grey matter reduction in the FES subjects. The regions of interest (ROIs) were in the left ventral prefrontal cortex (ROI 1), left parietal and temporal cortices (ROI 2), right cerebellum (ROI 3), and right frontal and parietal cortices (ROI 4). These regions of reduction were transformed into binary masks, which were convolved with patients' pre-processed grey matter images. Patients' grey matter volumes in these regions were correlated with their composite scores on the following three symptom dimensions: Psychomotor Poverty, Disorganization and Reality Distortion. The volumes of ROIs 1, 2 and 4 were found to be significantly correlated with the Reality Distortion syndrome score. Our findings indicate that distinct, widespread grey matter reductions are present very early in the course of schizophrenia. The results also suggest a possible structural underpinning for the abnormal brain activity typically associated with symptoms of Reality Distortion.     

精神分裂症首次发病未治疗患者静息态下局部脑区自发活动的研究

目的探讨精神分裂症首次发病未治疗患者静息态下局部脑区自发活动的情况:方法:利用低频振幅(ALFF)方法,对27例首次发病未治疗的精神分裂症患者(患者组)进行静息状态下功能磁共振(fMRI)扫描,对影像学数据进行ALFF方法处理,结果与22名年龄、性别及受教育程度相匹配的健康对照者(正常对照组)比较。结果:与正常对照组相比,患者组ALFF显著增高的脑区是运动前区、辅助运动区和眶额回;ALFF显著降低的脑区是楔前叶、后扣带回、内侧前额叶和角回(P0.05,Alphaism矫正)。结论:精神分裂症首次发病未治疗患者在静息态下运动前区、辅助运动区、眶额回、楔前叶、后扣带回、内侧前额叶和角回的局部脑区自发活动异常,这些异常脑区可能有助于解释精神分裂症的病理机制。     

Shortened duration of untreated first episode of psychosis: changes in patient characteristics at treatment.

OBJECTIVE: This study examined whether duration of untreated psychosis can be shortened in patients with first episodes of DSM-IV schizophrenia spectrum disorders and whether shorted duration alters patient appearance at treatment. METHOD: Two study groups were ascertained in the same Norwegian health care sector: one from 1993-1994 with usual detection methods and one from 1997-1998 with early detection strategies that included education about psychosis. RESULTS: Patients with early detection had a shorter median duration of untreated psychosis by 21.5 weeks than patients with usual detection. The number with psychosis was greater in the early detection group; the number with schizophrenia was less. Early detection patients had more substance abuse and were younger, better adjusted premorbidly, and less ill. CONCLUSIONS: Early detection can shorten duration of untreated psychosis and help more patients when they are less severely ill. Given the devastation of psychosis, this is a significant treatment advance.     

精神分裂症认知功能损害与病程的关系

目的：探讨精神分裂症认知功能损害的程度与病程关系。方法;分别用韦氏记忆测验,数字划销测验和威斯康星卡片分类测验评估27例急性精神分裂症病人和31例慢性精神分裂症病人的记忆、注意和执行功能。结果：注意损害随病程的延长而加重,记忆和执行功能损害与病程无关。     

Course of cognitive functioning in first episode schizophrenia spectrum disorders

Studies of cognitive functioning in patients with first episode schizophrenia spectrum disorders can be particularly informative. Through the use of electronic- and bibliography-based searches, the authors identified studies examining the course of cognitive functioning in first episode patients. The results of this review indicated that first episode patients at presentation for treatment often show compromised cognitive functioning, particularly in the domains of verbal learning and memory, psychomotor speed and attention. However, in comparison with patients with a longer illness history, first episode patients demonstrate significantly superior performance. In longitudinal studies of first episode patients, cognitive functioning generally remained static, suggesting limited change in performance over the first several years of the illness. The implications of these findings for future research are discussed.     

首发精神分裂症患者血清GFAP与认知功能的研究

目的 研究首发精神分裂症患者血清中胶质纤维酸性蛋白(Glial Fibrillary Acidic Protein,GFAP)水平的变化与认知功能障碍之间的关系.方法 用酶联免疫吸附技术(Enzyme-linked Immunoadsordent Assay,ELISA)测定48例精神分裂症患者(患者组)和42例正常对照者(对照组)血清GFAP的浓度,并用威斯康星卡片分类测验(Wisconsin Cord Sorting Test,WCST)检测首发精神分裂症患者和正常人的认知功能.比较两组血清GFAP浓度,同时探讨GFAP浓度的变化与认知功能的关系.结果 (1)患者组血清浓度高于对照组(P＜0.01);(2)患者组WCST成绩低于对照组(P＜0.01),表明首发精神分裂症患者认知功能及执行能力比正常人差;(3)相关分析表明WCST中错误应答数、持续性错误数与患者血清GFAP浓度呈正相关,完成分类个数与患者血清GFAP浓度呈负相关(P＜0.05).结论 首发精神分裂症患者存在认知功能障碍和神经胶质细胞损害,且代表神经胶质细胞损害的血清GFAP浓度与认知功能障碍程度呈正相关.     

Lack of association between prepulse inhibition and antisaccadic deficits in chronic schizophrenia: implications for identification of schizophrenia endophenotypes

Individuals with schizophrenia, compared to healthy individuals, are known to exhibit deficient prepulse inhibition (PPI) of the startle response as well as reduced performance on the antisaccade task. There is evidence for genetic transmission of both PPI and antisaccadic abnormalities in schizophrenia. It has been suggested that PPI and antisaccade measures identify separate endophenotypes, on the basis of a lack of relationship between PPI and antisaccade deficits in patients with schizotypal personality disorder. However, given that patients with schizotypal personality disorder are unlikely to manifest all the abnormalities associated with schizophrenia, it is important to determine that there is no relationship present between these two abnormalities in people affected with schizophrenia. The main objective of this investigation therefore was to establish the lack of the association between PPI and antisaccade deficits in schizophrenia in two independent studies. Study 1 involved 39 patients with schizophrenia and 14 healthy controls and study 2 involved 35 patients with schizophrenia and 22 healthy controls. PPI (uninstructed paradigm) of the acoustically elicited startle (eye blink) was measured electromyographically. Antisaccadic eye movements (standard, non-overlap version) were measured using infrared oculography. Patients displayed reduced PPI and a lower percentage of correct antisaccades relative to healthy controls in both studies. As expected, no relationship occurred between PPI and the percentage of correct antisaccade responses in either group. It is concluded that PPI and antisaccade abnormalities in schizophrenia represent separate endophenotypes, reflecting the functions of different genetic aetiologies and different or only partially overlapping neural systems.     

Relationship between premorbid functioning and symptom severity as assessed at first episode of psychosis

OBJECTIVE: Investigating the relationship between premorbid and prodromal status and the clinical manifestations of the first psychotic episode is relevant for understanding the pathophysiology of psychosis and for improving management of the disease. This study examined patterns of premorbid functioning of persons interviewed during their first episode of psychotic illness and examined the relationship of premorbid characteristics with symptom severity and cognitive functioning during the first illness episode. METHOD: The data were derived from the baseline assessments of a multicenter international drug trial that enrolled 535 patients in their first episode of psychosis. Subjects' scores on the Premorbid Adjustment Scale were used to assign them to groups according to whether their premorbid functioning was stable-good, stable-poor, or deteriorating. The three groups' scores on the Positive and Negative Syndrome Scale, Clinical Global Impression (CGI) severity scale, and a cognitive battery were compared. RESULTS: Almost half of the patients (47.5%) had stable-good premorbid functioning, 37.3% had stable-poor premorbid functioning, and 15.1% had initially good, but later deteriorating, premorbid functioning. Compared to the stable-poor and deteriorating groups, the stable-good group had lower (better) negative syndrome and general psychopathology scores on the Positive and Negative Syndrome Scale and a lower CGI severity scale score. Differences between the stable-poor and stable-good groups were also found on some cognitive measures and on the positive syndrome subscale of the Positive and Negative Syndrome Scale. CONCLUSIONS: More than half of the subjects, who were interviewed during their first episode of psychotic disorder, had evident premorbid behavioral disturbances. Poor premorbid functioning before onset of psychosis was associated with more severe symptoms and more severe cognitive manifestations of illness during the first illness episode.     

Genetic and perinatal determinants of structural brain deficits in schizophrenia

Using a subsample from the Copenhagen schizophrenia high-risk project, we examined the contributions of schizophrenic genetic liability and perinatal complications to computed tomographic (CT) measurements of ventricular enlargement and cortical and cerebellar abnormalities. A factor analysis of six CT measurements yielded two significant factors. One factor reflected multisite neural deficits as evidenced by abnormality of the cerebellar vermis and widening of the sylvian and interhemispheric fissures and cortical sulci. The other factor reflected periventricular damage as evidenced by enlargement of the third and lateral ventricles. Because all of the subjects had schizophrenic mothers, the major source of genetic variation is contributed by the diagnostic status of their fathers. In a stepwise multiple-regression analysis, it was determined that the multisite neural deficits factor was significantly related to genetic risk for schizophrenia (as measured by schizophrenia spectrum illness in the subjects' fathers) but was unrelated to pregnancy or delivery complications or to weight at birth. Periventricular damage was highly and significantly correlated with the number of complications suffered at delivery, but only among subjects with an elevated genetic risk. Although limited by a small sample size, these results suggest that the two types of CT abnormalities in schizophrenia may reflect partially independent processes based on different combinations of genetic and perinatal influences.