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.     

A meta-analysis of blood and salivary cortisol levels in first-episode psychosis and high-risk individuals

Dysregulated cortisol responses and glucose metabolism have been reported in psychosis. We performed a random-effects meta-analysis of cortisol responses in first-episode psychosis (FEP) and psychosis risk states, taking into consideration glucose metabolism. A total of 47 studies were included. Unstimulated blood cortisol levels were significantly higher (g = 0.48, 95 %CI: 0.25–0.70, p < 0.001) in FEP, but not in psychosis risk states (g = 0.39, 95 %CI: −0.42–1.21, p = 0.342), compared to controls. Cortisol awakening response (CAR) was attenuated in FEP (g = −0.40, 95 %CI: −0.68 - −0.12, p = 0.006), but not in psychosis risk states (p = 0.433). Glucose and insulin levels were positively correlated with unstimulated blood cortisol levels in FEP. Our meta-analysis supports previous findings of elevated blood cortisol levels and attenuated CAR in FEP. Future research should focus on identifying the common denominators for alterations in stress hormones and glucose metabolism.     

Predictors of functional outcome in individuals at high clinical risk for psychosis at six years follow-up

BackgroundThe long-term functional status of subjects at ultra high risk for psychosis (HR) is relatively under investigated. This study explores baseline predictors of long-term functional outcome in HR subjects who did not convert to psychosis during a 6 years follow-up period.MethodsA total of 154 HR were followed up for an average of 6 years. The primary outcome variable was global assessment of functioning at the last follow-up visit as assessed with the Global Assessment of Functioning tool. A multinomial logistic regression was performed to identify potential predictors of functional outcome.ResultsBaseline and follow-up data on functioning was available for 92 HR. Twenty-four (43%) individuals who did not convert to psychosis reported poor functioning at follow-up. Baseline scores in the GAF (Exp(b) = 0.857; 95% CIs: 0.75/0.97), employment status (Exp(b) = 0.029; 95% CIs: 0.00/0.268), and CAARMS total scores (Exp(b) = 1.976; 95% CIs: 1.00/1.14) predicted functional outcome in HR subjects at 6 years.ConclusionsDespite the preventive treatments received, many individuals who did not convert to full-blown psychosis in the longer term do not functionally remit. These individuals are lower functioning, unemployed and have higher symptom loading at the time of their presentation to the prodromal clinic. Our study suggests the need for innovative treatments targeting long term functional status beyond the prevention of psychosis onset in the HR population.     

Duration of untreated psychosis predicts functional and clinical outcome in children and adolescents with first-episode psychosis: A 2-year longitudinal study

Longer duration of untreated psychosis (DUP) in adult patients with first-episode psychosis (FEP) has been associated with poor clinical and social outcomes. We aimed to estimate the influence of DUP on outcome at 2-year follow-up in subjects with an early-onset (less than 18 years of age) FEP of less than 6 months' duration. A total of 80 subjects (31.3% females, mean age 16.0 ± 1.8 years) were enrolled in the study. The influence of DUP on outcome was estimated using multiple regression models (two linear models for influence of DUP on the C-GAF at 2 years and C-GAF change through the follow-up period, and a logistic model for influence of DUP on 41 PANSS remission at 2 years in schizophrenia patients (n = 47)). Mean DUP was 65.3 ± 54.7 days. Median DUP was 49.5 days. For the whole sample (n = 80), DUP was the only variable significantly related to C-GAF score at 2-year follow-up (Beta = − 0.13, p < 0.01), while DUP and premorbid adjustment (Beta = − 0.01, p < 0.01; and Beta = − 0.09, p = 0.04, respectively) were the only variables significantly related to C-GAF change. In schizophrenia patients, DUP predicted both C-GAF score at 2 years and C-GAF change, while in patients with affective psychosis (n = 22), DUP was unrelated to outcome. Lower baseline C-GAF score (OR = 0.91, p < 0.01) and shorter DUP (OR = 0.98, p = < 0.01) were the only variables that significantly predicted clinical remission in schizophrenia patients. In conclusion, longer DUP was associated with lower C-GAF at 2 years, less increase in C-GAF, and lower rates of clinical remission in early-onset FEP. Our findings support the importance of early detection programs, which help shorten DUP.     

Prognosis and outcome in a cohort of patients with non-affective functional psychosis

Summary Over a period of 3 years since the first in a lifetime onset of an episode of non-affective functional psychosis a cohort of 82 Dutch patients was studied at set intervals with regard to prognosis and outcome. Prognostic statements on remission, relapse, duration of episode, length of stay in hospital, and occupational, family and overall social adjustment were checked against actual outcome after I year. In general, the research team of three psychiatrists, a psychologist and a sociologist began quite optimistically, but became slightly more pessimistic with time. However, their predictions proved hardly better than chance statements. The team appeared to be more pessimistic about the diagnosis of schizophrenia than about that of reactive psychosis, although they were not correct with one diagnostic category more often than with the other.     

Impact of duration of untreated psychosis on pre-treatment, baseline, and outcome characteristics in an epidemiological first-episode psychosis cohort

INTRODUCTION: To assess the impact of duration of untreated psychosis (DUP) on baseline and 18-month follow-up characteristics controlling for relevant confounders in an epidemiological first-episode psychosis (FEP) cohort. METHOD: The Early Psychosis Prevention and Intervention Centre (EPPIC) in Australia admitted 786 FEP patients from January 1998 to December 2000. Data were collected from medical files using a standardized questionnaire. Data from 636 patients were analyzed. RESULTS: Median DUP was 8.7 weeks. Longer DUP was associated with worse premorbid functioning (p<0.001), higher rate of schizophrenia-spectrum disorders (p<0.001), and younger age at onset of psychosis (p=0.004). Longer DUP was not associated with baseline variables but with a lower rate of remission of positive symptoms (p<0.001) and employment/occupation (p<0.001), a higher rate of persistent substance use (p=0.015), worse illness severity (p<0.001) and global functioning (p<0.001) at follow-up after controlling for relevant confounders, explaining approximately 5% of variance of remission of positive symptoms (p<0.001) in the total sample and 3% in schizophrenia-spectrum disorders excluding bipolar I disorder (p=0.002). Outcome was significantly worse when DUP exceeded 1-3 months. CONCLUSION: Avoiding pitfalls of non-epidemiological studies, DUP appears to be a modest independent predictor of prognosis in the medium-term. Results support the need for assertive early detection strategies.     

The relationship of early premorbid adjustment with negative symptoms and cognitive functions in first-episode schizophrenia: A prospective three-year follow-up study

Premorbid adjustment is an important prognostic factor of schizophrenia. The relationships between sub-components of premorbid adjustment and outcomes on symptoms and cognition in first-episode schizophrenia were under-studied. In the current study, we prospectively followed up 93 patients aged 18–55 years presenting with first-episode schizophrenia-spectrum disorder. Psychopathological and cognitive assessments were conducted at baseline, clinical stabilization, 12, 24 and 36 months. Premorbid adjustment was sub-divided into discrete functional domains, developmental stages and premorbid-course types based on ratings of the Premorbid Adjustment Scale (PAS). The study focused on early developmental stages to minimize contamination by prodromal symptoms. Results indicated that gender differences in premorbid functioning were primarily related to early-adolescence adjustment and academic domain. Social domain was more strongly related to negative symptoms, while academic domain was more consistently linked to cognitive outcome (Wisconsin Card Sorting test and verbal fluency). Patients with stable-poor premorbid course had more severe negative symptoms and cognitive impairment. In conclusion, in a Chinese cohort of first-episode schizophrenia-spectrum disorder, sub-components of early premorbid adjustment were shown to be differentially related to clinical and cognitive measures. The results highlighted the importance of applying a more refined delineation of premorbid functioning in studying illness outcome.     

Inflammatory and cardiometabolic markers at presentation with first episode psychosis and long-term clinical outcomes: A longitudinal study using electronic health records

Approximately one third of patients presenting with a first episode of psychosis need long-term support, but there is a limited understanding of the sociodemographic or biological factors that predict this outcome. We used electronic health records from a naturalistic cohort of consecutive patients referred to an early intervention in psychosis service to address this question. We extracted data on demographic (age, sex, ethnicity and marital status), immune (differential cell count measures and C-reactive protein (CRP)) and metabolic (cholesterol, triglycerides, glucose, glycated haemoglobin, blood pressure, body mass index (BMI)) factors at baseline, and subsequent need for long-term secondary (specialist) psychiatric care. Of 749 patients with outcome data available, 447 (60%) had a good outcome and were discharged to primary care, while 302 (40%) required follow-up by secondary mental health services indicating a worse outcome. The need for ongoing secondary mental healthcare was associated with high triglyceride levels (adjusted odds ratio/OR = 7.32, 95% CI 2.26–28.06), a low basophil:lymphocyte ratio (adjusted OR = 0.14, 95% CI 0.02–0.58), and a high monocyte count (adjusted OR = 2.78, 95% CI 1.02–8.06) at baseline. The associations for baseline basophil (unadjusted OR = 0.27 per SD, 95% CI 0.10–0.62) and platelet counts (unadjusted OR = 2.88, 95% CI 1.29–6.63) attenuated following adjustment for BMI. Baseline CRP levels or BMI were not associated with long-term psychiatric outcomes. In conclusion, we provide evidence that triglyceride levels and several blood cell counts measured at presentation may be clinically useful markers of long-term prognosis for first episode psychosis in clinical settings. These findings will require replication.     

Duration of attenuated positive and negative symptoms in individuals at clinical high risk: Associations with risk of conversion to psychosis and functional outcome

Research in individuals at clinical high-risk (CHR) for psychosis has focused on subjects with no more than 12 months of present or worsened attenuated positive symptoms. However, the impact of long duration attenuated positive and/or negative prodromal symptoms on outcomes is unclear. Seventy-six CHR subjects with attenuated positive symptoms and at least moderate severity level negative symptoms rated on the Scale of Prodromal Symptoms (SOPS) were prospectively followed for a mean of 3.0 ± 1.6 years. Social and Role functioning was assessed with the Global Functioning: Social and Role scales. Correlations between attenuated positive and negative symptom duration and severity and conversion to psychosis and functional outcomes were analyzed. The average onset of SOPS rated negative symptoms (M = 53.24 months, SD = 48.90, median = 37.27) was approximately twelve months prior to the emergence of attenuated positive symptom (M = 40.15 months, SD = 40.33, median = 24.77, P < 0.05). More severe positive symptoms (P = 0.004), but not longer duration of positive (P = 0.412) or negative (P = 0.754) symptoms, predicted conversion to psychosis. Neither positive symptom duration (P = 0.181) nor severity (P = 0.469) predicted role or social functioning at study endpoint. Conversely, longer negative symptom duration predicted poor social functioning (P = 0.004). Overall, our findings suggest that the severity of attenuated positive symptoms at baseline may be more important than symptom duration for determining individuals at increased risk of developing psychosis. In contrast, long-standing negative symptoms may be associated with persistent social difficulties and therefore have an important position in the treatment of disability.     

IQ as a predictor of functional outcome in schizophrenia: a longitudinal, four-year study of first-episode psychosis

Studies of established schizophrenia have consistently found that cognitive function predicts social and clinical outcomes. The findings from first-episode studies have been more variable, with only some studies reporting predictive relationships. We tested the possibility that an index of general cognitive ability, IQ, may be a more sensitive and reliable predictor of outcome in first-episode schizophrenia than specific measures of memory and executive function. Fifty-four patients with first-episode schizophrenia or schizoaffective disorder were assessed for cognitive and social function as well as symptoms at three time points over the four years following first presentation of their psychotic illness. Regression analyses were performed to determine whether IQ and specific neuropsychological measures at first episode and one-year follow-up predicted four-year social function and residual symptoms. The effects of premorbid and concurrent IQ on outcome were also assessed. Premorbid IQ and IQ at each assessment significantly predicted social function at four-year follow-up. This relationship remained significant after the social function or symptom scores at first presentation were accounted for in the regression. Specific measures predicted certain domains of social function, but these were weaker and less consistent than IQ. The predictive values of cognition on residual symptoms were less strong; the most consistent finding was a relationship between IQ and the negative syndrome. This study suggests that early in the course of schizophrenia, general cognitive ability, as measured by IQ, is a more sensitive and reliable predictor of functional outcome than measures of specific ability.     

Predictors of acute treatment response in patients with a first episode of non-affective psychosis: sociodemographics, premorbid and clinical variables

Approximately 60% of patients with a first episode of psychosis will significantly reduce the severity of their positive symptomatology with antipsychotic drugs. The aim of this study was to investigate predictors of response to antipsychotic treatment during the first episode of non-affective psychosis. 172 patients (107 male) with a diagnosis of schizophreniform, schizophrenia, schizoaffective, brief reactive psychosis, schizotypal personality disorder or psychosis non-otherwise specified entered the study. Sociodemographic, premorbid and clinical data at baseline were evaluated. Unpaired t-test for continuous and chi2 for categorical data, respectively, were used to compare responders and non-responders selected variables. Multivariate logistic regression was used to establish a prediction model. 57.6% of study subjects (99 of 172) responded to antipsychotic treatment. The following variables were significantly associated with less likelihood of response: 1.--lower severity of general psychopathology, positive symptoms and disorganized symptoms at baseline; 2.--earlier age of onset; 3.--diagnosis of schizophrenia; 4.--longer DUP; 5.--poorer premorbid adjustment during adolescence, and 6.--hospitalization. Multivariate logistic regression demonstrated that differences between responders and non-responders were largely accounted for by BPRS total score, age of onset, premorbid adjustment at early adolescence, and diagnosis. Patients with an early age of onset of schizophrenia, a poor premorbid adolescent functioning, and with a lower severity of psychopathology at intake seem to have a decrease likelihood of responding to antipsychotic treatment. Helping clinicians to identify non-responders is meant as a first step to optimise therapeutic effort to benefit individuals in this vulnerable group.     

Association between duration of untreated psychosis, premorbid functioning, and cognitive performance and the outcome of first-episode schizophrenia in Japanese patients: prospective study

OBJECTIVE: The aim of the present study was to identify the relationship between duration of untreated psychosis (DUP), premorbid functioning, and cognitive dysfunction and the outcome of first-episode schizophrenia. METHOD: Thirty-four neuroleptic-na?ve patients who consulted hospitals in Tokyo and who were treated by psychiatrists for the first time were evaluated with regard to DUP, premorbid functioning, psychiatric symptoms, and global functioning. The neuropsychological test battery consisted of the Letter Cancellation Test, Trail-Making Test, Digit Span and Verbal Fluency Test. One year later, 24 of the subjects were reassessed for psychiatric symptoms, global functioning, and social functioning, and the relationships between DUP, premorbid functioning, and cognitive performance and the outcome was investigated. RESULTS: Short DUP, good premorbid functioning, and good Letter Cancellation Test, Digit Span and Verbal Fluency Test scores were significantly associated with good outcome. CONCLUSIONS: The present results in a Japanese sample are consistent with previous international evidence that delay of initial treatment, premorbid functioning, and cognitive deficits are associated with outcome. A major limitation of the present study was the small size of the subject group. But because the subjects were relatively homogeneous and not influenced by psychoactive substances, the results reflect the essence of the disorder.     

The negative and positive self: a longitudinal study examining self-esteem, paranoia and negative symptoms in individuals with first-episode psychosis

Aim: Self‐esteem has been implicated in the development of psychotic phenomena, especially paranoia. Recent findings suggest that it may be useful to assess the instability of self‐esteem instead of the mean score. We examined this construct as two separate factors: positive beliefs about the self (PBS) and negative beliefs about the self (NBS). Theoretical models have implicated NBS in the development of paranoia, whereas research studies have sometimes found an association between PBS and negative symptoms. The first aim of this study was to investigate associations between change in PBS and NBS, and subsequent change in paranoia and negative symptoms. The second aim was to examine whether fluctuations in PBS and NBS predicted mean paranoia levels. Methods: Data from a large sample of individuals with first‐episode psychosis (n = 256) assessed at baseline, 6 weeks, 3 months and 18 months was analysed. Results: The data suggest that changes in both PBS and NBS in the early stages of disorder are related to change in negative symptoms, but not paranoia. PBS variability and NBS mean scores significantly predicted average paranoia levels when taken from across all four time points, suggesting potential differences in the associations with psychosis of these two constructs. Conclusion: Self‐esteem boosting interventions administered in the first 6 weeks after admission to healthcare services may improve the subsequent course of negative symptoms.     

Psychiatric comorbidity in first episode schizophrenia: a 2 year, longitudinal outcome study

OBJECTIVE: We have previously documented a high prevalence of Axis I psychiatric comorbidity in our patients with first episode psychosis. This study sought to determine the longitudinal impact of Axis I psychiatric comorbidity on patients with first episode schizophrenia (FES) and we hypothesised that patients with psychiatric comorbidity were associated with poorer clinical and functional outcomes. METHOD: One hundred and forty two consecutively hospitalized FES patients were included. Socio-demographic information was obtained and the PANSS, SUMD, GAF, WHOQOL-Bref were used to assess psychopathology, insight, social/occupational functioning and quality of life respectively at baseline and at 6, 12, 18 and 24 months after discharge. RESULTS: Over time and compared with baseline scores, patients with Axis I psychiatric comorbidity (n=46, 32.4%) had significantly less reduction of their PANSS total and subscale scores, less improvement in their awareness of their psychiatric illnesses and symptoms at 12, 18 and 24 months and poorer insight into the consequences of their illness at 18 and 24 months. Poor insight at baseline was correlated positively with PANSS negative symptom subdomain, and negatively with GAF at 24 months. CONCLUSION: Axis I Psychiatric comorbidity was associated with worse prospective outcomes in hospitalized patients with first episode schizophrenia, and this highlights a greater need towards the early recognition and management of these conditions.     

Neurocognition and occupational functioning in patients with first-episode psychosis: a 2-year follow-up study

Neurocognitive deficits are a core feature of schizophrenia that is associated with poor occupational functioning. Few studies have investigated this relationship in patients with first-episode psychosis. The current study examined the characteristics of employed and unemployed patients with first-episode psychosis at baseline and 2-year follow-up, and the predictive value of neurocognition on employment status. One-hundred and twenty-two first-episode psychosis patients were assessed with clinical and neurocognitive measures at baseline. Occupational status was assessed at baseline and 2-year follow-up. Those unemployed at baseline were rated lower on global functioning and were more likely to have a schizophrenia spectrum disorder. Total employment rates were 41% at baseline and 38% at 2-year follow-up. Four employment paths emerged at follow-up, defined as persistently employed, becoming unemployed, entering employment and persistently unemployed. The persistently employed group had the highest global functioning score. For the total sample, baseline employment status and sustained attention predicted employment status at follow-up. For those employed at baseline, better sustained attention, higher global functioning, more positive symptoms and less alcohol use predicted persistent employment at follow-up. For those unemployed at baseline, none of the variables predicted change in employment status. Implications of these results are discussed.     

Neurocognitive dysfunction in first-episode psychosis: correlates with symptoms, premorbid adjustment, and duration of untreated psychosis

OBJECTIVE: The authors examined the relationship of neurocognitive function with duration of untreated psychosis, premorbid illness factors, and clinical symptoms to determine whether long duration of untreated psychosis independently compromises cognitive function. METHOD: Patients recruited to a study of the effect of an early detection program on the duration of untreated first-episode psychosis in two catchment areas were compared to patients in a similar treatment program in two other catchment areas without an early detection program. The median duration of untreated psychosis was 10.5 weeks for all patients. A total of 301 patients entered the study, and 207 completed a comprehensive neuropsychological test battery that assessed working memory/fluency, executive function, verbal learning, impulsivity, and motor speed. The median time from start of treatment to neuropsychological testing was 108 days; all patients were tested within 9 months. RESULTS: No significant association was found between duration of untreated psychosis and any of the cognitive measures. Strong associations were demonstrated between poorer premorbid school functioning and neurocognitive deficits, especially in verbal learning and working memory. No relationship was found between neurocognitive functions and clinical measures, except for an inverse correlation of Positive and Negative Syndrome Scale negative symptoms and working memory and a positive correlation between positive symptoms and motor speed. CONCLUSIONS: The data contribute to a disconfirmation of the hypothesis of an association between duration of untreated psychosis and neurocognitive performance at baseline.     

Neurocognitive attention and behavior outcome of school-age children with a history of febrile convulsions: a population study

PURPOSE: A prospective population-based case-control study was performed to ascertain whether febrile convulsion (FC) in early childhood is associated with neurocognitive attention deficits in school age. METHODS: A total of 103 children, confirmed to have FC by age 3 years from a population survey of 4,340 live-birth newborns in Tainan City, Taiwan, was followed up until at least age 6 years. An achievement test, behavioral ratings, and computerized neurocognitive battery assessing various subcomponents of attention were given to 87 FC children (FC group) and 87 randomly selected population-matched control (CC group). RESULTS: Compared with the CC group, the FC group did not have scholastic performance or behavioral outcome disadvantage. Overall FC group performance was distinguished by significantly higher scores in the achievement test and fewer missing errors (p < 0.005) and commission errors (p < 0. 05), less variability in reaction time (p < 0.005), and a nonsignificant trend of impulsivity. Attention performance of the FC and CC groups were comparable. Within the FC group, age at onset, complex FC, recurrence of FC, development of unprovoked seizures, or prior use of phenobarbital had no adverse effects on neurocognitive attention outcome. CONCLUSIONS: This population study suggests that FC in early childhood does not have adverse effects on behavior, scholastic performance, and neurocognitive attention. On the contrary, the FC group demonstrated significantly better control of distractibility and attention at school age.     

精神病临床高危综合征与首发精神分裂症患者的神经认知功能比较研究

目的 探讨精神病临床高危综合征人群和首发未服药精神分裂症（First-episode Drug-naive Schizophrenia,FES）患者的神经认知功能特征.方法 应用中文版精神病高危综合征定式访谈（SIPS）收集精神病高危综合征人群46例,采用Matrics成套认知功能测试（MCCB）中文版评估认知功能,并与20例FES患者和37例健康对照进行比较分析.结果 除情绪管理分测验外,MCCB的其他8项分测验结果在三组之间差异均有统计学意义,包括连线（F=5.76,P=0.00）、符号编码（F=19.82,P=0.00）、词语学习（F=10.20,P=0.00）、空间广度（F=5.30,P=0.01）、迷宫（Hc=16.97,P=0.00）、空间记忆（Hc=19.07,P=0.00）、语义流畅（F=9.99,P=0.00）以及持续操作（Hc=15.46,P=0.00）.两两比较发现：两组患者的成绩均显著差于健康对照组;精神病临床高危综合征人群与FES患者相比,词语学习测验分较高（LSD-t=2.60,P=0.01）.结论 精神病临床高危综合征的神经认知功能明显受损,其特征与首发精神分裂症相似.词语学习测验,对于区分精神病临床高危综合征和已经发病的精神分裂症患者,可能具有参考价值.