Benjamin Wiffen

Abnormal cortisol awakening response predicts worse cognitive function in patients with first-episode psychosis

BACKGROUND Cognitive impairment, particularly in memory and executive function, is a core feature of psychosis. Moreover, psychosis is characterized by a more prominent history of stress exposure, and by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. In turn, stress exposure and abnormal levels of the main HPA axis hormone cortisol are associated with cognitive impairments in a variety of clinical and experimental samples; however, this association has never been examined in first-episode psychosis (FEP). METHOD In this study, 30 FEP patients and 26 controls completed assessment of the HPA axis (cortisol awakening response and cortisol levels during the day), perceived stress, recent life events, history of childhood trauma, and cognitive function. The neuropsychological battery comprised general cognitive function, verbal and non-verbal memory, executive function, perception, visuospatial abilities, processing speed, and general knowledge. RESULTS Patients performed significantly worse on all cognitive domains compared to controls. In patients only, a more blunted cortisol awakening response (that is, more abnormal) was associated with a more severe deficit in verbal memory and processing speed. In controls only, higher levels of perceived stress and more recent life events were associated with a worse performance in executive function and perception and visuospatial abilities. CONCLUSIONS These data support a role for the HPA axis, as measured by cortisol awakening response, in modulating cognitive function in patients with psychosis; however, this association does not seem to be related to the increased exposure to psychosocial stressors described in these patients.

Correlates, change and 'state or trait' properties of insight in schizophrenia.

BACKGROUND The associations of insight into illness and clinical and socio-demographic variables in schizophrenia have been examined, yet little attention has been given to premorbid functioning, insight change and outcomes. OBJECTIVES We examined these associations in a large cohort of recent onset schizophrenia spectrum disorder patients. METHODS This was a prospective 6-month, open-label, multicentre, phase IV trial in 303 subjects with recent onset (<or=2 years) schizophrenia treated with risperidone long-acting injection (RLAI). Insight (Schedule for the Assessment of Insight - Expanded), treatment efficacy (Positive and Negative Syndrome Scale, Clinical Global Impression) and quality of life (Short Form-36) were assessed at baseline and after 2, 4 and 6 months. The Premorbid Adjustment Scale was administered at baseline. RESULTS Insight was positively associated with better premorbid functioning, more education and schizoaffective disorder versus schizophrenia. Insight improved modestly, but significantly throughout treatment, particularly illness beliefs. Baseline insight was negatively correlated with quality of life and positive symptoms and positively correlated with anxiety/depression. It was not significantly associated with change in symptom severity or time in trial, but was positively associated with age. CONCLUSIONS Insight, at least in this stable, comparatively high-insight sample, improved during treatment but this is not closely related to improvement in psychotic symptoms. Insight appears to have trait-like qualities demonstrated by association with premorbid factors. While insight is generally a favorable attribute and is associated with fewer psychotic symptoms, it is also associated with increased depression and lower perceived quality of life. Some components of insight are more amenable to improvement; particularly the ability to adopt less fixed illness attributions.

Neuropsychological, clinical and cognitive insight predictors of outcome in a first episode psychosis study

The outcome of first episode psychosis (FEP) is highly variable and difficult to predict. We studied prospectively the impact of poor insight and neuropsychological deficits on outcomes in a longitudinal cohort of 127 FEP patients. Participants were assessed on 5 domains of cognitive function and 2 domains of insight (clinical and cognitive). At 12 months, patients were assessed again for symptom severity and psychosocial function. Regression analyses revealed that cognitive insight (a measure of self-reflectiveness and self-certainty) was the best baseline predictor of overall psychopathology at 12 months whereas executive function performance at admission to the study indicated later severity of negative symptoms. Other neuropsychological and insight measures were poor predictors of psychosocial function at 1 year. The results suggest that specific neuropsychological and insight factors have separate predictive capacities indicating that they are distinct psychological processes in psychosis. Cognitive insight proved to be a useful prognostic indicator, and should be considered for future studies and as a potential focus for treatment.

Insight: Demographic Differences and Associations with One-Year Outcome in Schizophrenia and Schizoaffective Disorder

BACKGROUND Insight is increasingly seen as an important variable for study in psychotic illness, particularly in relation to treatment adherence. This study aims to quantify the association of insight with outcome, sociodemographic variables and diagnosis in a large stable patient sample. METHOD Data are from a one-year, open-label, international, multicenter trial (n=670) of long-acting risperidone in adult symptomatically stable patients with schizophrenia or schizoaffective disorder. Psychopathology and insight were quantified using the Positive and Negative Syndrome Scale (PANSS). Patients were assessed at four time points over the year of the study. RESULTS 31.2% of the sample showed clinically significant deficits in insight at baseline. There were no differences based on sex, but significant differences in age and diagnosis, with oldest patients and schizophrenia patients (cf., schizoaffective disorder) showing more deficits. Baseline insight impairment was correlated with change in PANSS score at one year (r=-0.243, p<0.001). Recursive partitioning showed that, of those whose symptoms improved, those whose insight also improved were more likely to complete the trial. CONCLUSIONS Insight is important above and beyond the effects of symptoms for predicting continuation in drug trials. This may have implications for the design and analysis of such trials, as well as suggesting the importance of targeting insight in treatment to increase likelihood of adherence to treatment. There also appear to be small but significant differences in insight based on age and diagnosis within the schizophrenia spectrum.

Are there specific neuropsychological deficits underlying poor insight in first episode psychosis

Insight in psychosis is a multi-dimensional phenomenon, and has been hypothesised to have some sort of neuropsychological basis. It is unclear to what extent specific neuropsychological abilities are able to predict insight beyond the effect of generalised cognitive ability. We aimed to test this association, alongside the relationship of insight with illness duration and diagnosis, in a sample of first episode psychosis patients. 110 first episode psychosis patients were recruited and a comprehensive assessment was administered, including insight, symptoms, diagnosis and neuropsychological function. Low insight was related to worse performance in a variety of neuropsychological tasks. Regression analysis tested whether any specific tasks were related to insight (or dimensions of insight) beyond the effect of IQ. Verbal memory had an effect on total insight and all dimensions of insight (except compliance) beyond the effect of IQ. Insight appeared to vary with diagnosis, with those diagnosed with depressive affective psychoses having better insight than those with manic affective psychoses. There was no relationship between insight and DUP, but there was a relationship between time spent in treatment before assessment and insight, even after controlling for severity of symptoms. These results suggest a model of insight in early psychosis with a significant neuropsychological component, particularly with verbal memory but also with generalised cognitive ability. There is likely to be a social component to insight affected by initial time spent in contact with treatment, helping patients to understand and come to terms with their illness.

Failure to find association between childhood abuse and cognition in first-episode psychosis patients

This study investigated the relationship between severe childhood abuse and cognitive functions in first-episode psychosis patients and geographically-matched controls. Reports of any abuse were associated with lower scores in the executive function domain in the control group. However, in contrast with our hypothesis, no relationships were found amongst cases.

Insight and suicidality in first-episode psychosis: understanding the influence of suicidal history on insight dimensions at first presentation

Lack of insight is a cardinal feature of psychosis with crucial implications for outcome. Concerns have been raised regarding a link between insight and suicidality. This study aimed to test the relationship between suicidal behaviour preceding first‐episode psychosis (FEP) and insight dimensions at treatment onset.

Interaction between cannabis consumption and childhood abuse in psychotic disorders: preliminary findings on the role of different patterns of cannabis use

Several studies have suggested that lifetime cannabis consumption and childhood abuse synergistically contribute to the risk for psychotic disorders. This study aimed to extend existing findings regarding an additive interaction between childhood abuse and lifetime cannabis use by investigating the moderating role of type and frequency of cannabis use.

Interaction between cannabis consumption and childhood abuse in psychotic disorders

Several studies have suggested that lifetime cannabis consumption and childhood abuse synergistically contribute to the risk for psychotic disorders. This study aimed to extend existing findings regarding an additive interaction between childhood abuse and lifetime cannabis use by investigating the moderating role of type and frequency of cannabis use.

Can cognitive insight predict symptom remission in a first episode psychosis cohort

BackgroundThe outcome of first episode psychosis (FEP) is highly variable and difficult to predict. Cognitive insight measured at illness onset has previously been found to predict psychopathology 12-months later. The aims of this study were to examine whether the prospective relationship between cognitive insight and symptom severity is evident at four-years following FEP and to examine some psychological correlates of cognitive insight.MethodsFEP participants (n = 90) completed the Beck Cognitive Insight Scale (BCIS) at illness onset, and associations between BCIS scores with symptom severity outcomes (4-years after FEP) were assessed. The BCIS scales (self-reflectiveness and self-certainty) were examined as a composite score, and individually compared to other cognitive measures (IQ and jumping to conclusions (JTC) bias).ResultsRegression analyses revealed that the cognitive insight composite did not predict 4-year symptom remission in this study while the self-reflection subscale of the BCIS predicted severity of symptoms at 4-years. Self-certainty items of the BCIS were not associated with symptom severity. Significant correlations between the JTC bias, self-certainty and IQ were found, but self-reflection did not correlate with these other cognitive measures.ConclusionsSelf-reflective capacity is a more relevant and independent cognitive construct than self-certainty for predicting prospective symptom severity in psychosis. Improving self-reflection may be a useful target for early intervention research.