Shôn Lewis

Prediction of Psychosis in Adolescents and Young Adults at High Risk: Results From the Prospective European Prediction of Psychosis Study

CONTEXT Indicated prevention is currently regarded as the most promising strategy to attenuate, delay, or even avert psychosis. Existing criteria need improvement in terms of specificity and individual risk assessment to allow for better targeted and earlier interventions. OBJECTIVE To develop a differential predictive clinical model of transition to first-episode psychosis. DESIGN Prospective multicenter, naturalistic field study with a total follow-up time of 18 months. SETTING Six early-detection outpatient centers in Germany, Finland, the Netherlands, and England. PARTICIPANTS Two hundred forty-five help-seeking patients in a putatively prodromal state of psychosis according to either ultra-high-risk (UHR) criteria or the basic symptom-based criterion cognitive disturbances (COGDIS). MAIN OUTCOME MEASURE Incidence of transition to psychosis. RESULTS At 18-month follow-up, the incidence rate for transition to psychosis was 19%. Combining UHR and COGDIS yielded the best sensitivity. A prediction model was developed and included positive symptoms, bizarre thinking, sleep disturbances, a schizotypal disorder, level of functioning in the past year, and years of education. With a positive likelihood ratio of 19.9, an area under the curve of 80.8%, and a positive predictive value of 83.3%, diagnostic accuracy was excellent. A 4-level prognostic index further classifying the general risk of the whole sample predicted instantaneous incidence rates of up to 85% and allowed for an estimation of time to transition. CONCLUSIONS The prediction model identified an increased risk of psychosis with appropriate prognostic accuracy in our sample. A 2-step risk assessment is proposed, with UHR and cognitive disturbance criteria serving as first-step criteria for general risk and the prognostic index as a second-step tool for further risk classification of each patient. This strategy will allow clinicians to target preventive measures and will support efforts to unveil the biological and environmental mechanisms underlying progression to psychosis.

Obstetric complications, neurodevelopmental deviance, and risk of schizophrenia

It is concluded from a review of the literature and a pilot survey that schizophrenic patients more frequently have a history of obstetric complications (OCs) than do other psychiatric patients and normal subjects. OCs are associated with increased cerebral ventricular size in both infancy and adulthood, and are more common among non-familial schizophrenic patients. Neonatal cerebrovascular events consequent upon OCs provide a mechanism to explain the increased risk of neurodevelopmental deviance and later schizophrenia.

Brain structure and neurocognitive and behavioural function in adolescents who were born very preterm

BACKGROUND Infants born very preterm (<33 weeks) are at increased risk of neurocognitive deficits. Their neurodevelopmental outcome up to age 8 years can be predicted by neonatal ultrasonography, but little is known of their later function. We investigated the effect of very preterm birth on brain structure and neurocognitive and behavioural functioning in adolescence. METHODS A cohort of 105 infants born before 33 weeks of gestation in 1979-80 had ultrasonographic scans at University College Hospital, London, and were prospectively examined at 1, 4, and 8 years. At age 14-15 years, 72 of those who remained in UK (cases) and 21 age-matched full-term controls underwent brain magnetic resonance imaging (MRI), as well as neurological, cognitive, and behavioural assessment. MRI images were assessed by two neuroradiologists unaware of ultrasonographic findings or case or control status. FINDINGS Of the 72 cases, 40 had unequivocally abnormal MRI and 15 had equivocal scans. Of the 21 controls, one had abnormal and five equivocal MRI. Abnormalities of ventricles, corpus callosum, and white matter were especially common in cases. More brain lesions were identified by MRI than by neonatal ultrasonography. The cases had significantly more reading, adjustment, and neurological impairments than controls, but their behaviour was significantly related to MRI abnormality. INTERPRETATION Individuals born very preterm show an excess of neurocognitive and behavioural problems in adolescence, and more than half have abnormal MRI brain scans.

Reduction of cortical volume in schizophrenia on magnetic resonance imaging

The MRI scans of 48 schizophrenic patients, fulfilling RDC criteria, were compared to those of 34 healthy controls matched for age, ethnicity and parental social class. The volume of the frontal and anterior parietal lobes was significantly reduced in the schizophrenic group as a result of a selective decrease in cortical volume, with a corresponding increase in the volume of sulcal fluid. Reduction in the volume of the temporal grey matter was more marked on the right, but was not in excess of the loss of volume observed in other areas of the cortex. MRI abnormalities correlated poorly with clinical parameters, although both unemployment and poor pre-morbid adjustment predicted reduced cerebral volume and increased sulcal volume. These results question whether the medial temporal lobes are the only site of structural pathology in schizophrenia.

Psychopathological syndromes in the functional psychoses : associations with course and outcome

The aim of this study was to identify underlying dimensions of psychopathology in a cohort of patients with functional psychosis of recent onset, and to examine their prognostic value. Factor analysis of the psychopathological features of 166 consecutively admitted patients with functional psychosis of recent onset revealed seven psychopathological dimensions, which explained 63% of the variance. Five of these seven syndromes bore differential associations with subsequent treatment and illness course, independent of: (i) associations with DSM-III-R diagnosis; (ii) associations with other prognostic factors; and (iii) associations with the baseline values of outcome variables. The most striking associations were shown for an early and insidious onset syndrome with affective flattening, which predicted a more disabled course of illness on three of four outcome dimensions, and which was more common in males and unmarried individuals. A second syndrome, characterized by bizarre behaviour, inappropriate affect, catatonia, and poor rapport showed similar, slightly less striking, associations with illness course, as well as with poor pre-morbid social functioning. A third syndrome, characterized by positive psychotic symptoms was to a lesser degree associated with poorer outcome, whereas a fourth syndrome distinguished by manic symptomatology predicted a more benign illness course. A fifth syndrome identified by lack of insight predicted more time in hospital and admission under a section of the Mental Health Act during the follow-up period. A further finding was that dimensional representations of psychopathological features were considerably more useful than categorical representations (DSM-III-R and ICD-10) as predictors of illness course and treatment decisions.

The evolution of insight, paranoia and depression during early schizophrenia

BACKGROUND How insight, paranoia and depression evolve in relation to each other during and after the first episode of schizophrenia is poorly understood but of clinical importance. METHOD Serial assessments over 18 months were made using multiple instruments in a consecutive sample of 257 patients with first episode DSM-IV non-affective psychosis. Repeated measures of paranoia, insight, depression and self-esteem were analysed using structural equation modelling, to examine the direction of relationships over time after controlling for confounds. RESULTS Depression was predicted directly by greater insight, particularly at baseline, and by greater paranoia at every stage of follow-up. Neither relationship was mediated by self-esteem, although there was a weak association of lower self-esteem with greater depression and better insight. Paranoia was not strongly associated with insight. Duration of untreated psychosis and substance use at baseline predicted depression at 18 months. CONCLUSIONS In first-episode psychosis, good insight predicts depression. Subsequently, paranoia is the strongest predictor. Neither effect is mediated by low self-esteem. Effective treatment of positive symptoms is important in preventing and treating low mood in early schizophrenia.

Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial

Objective To determine whether cognitive therapy is effective in preventing the worsening of emerging psychotic symptoms experienced by help seeking young people deemed to be at risk for serious conditions such as schizophrenia. Design Multisite single blind randomised controlled trial. Setting Diverse services at five UK sites. Participants 288 participants aged 14-35 years (mean 20.74, SD 4.34 years) at high risk of psychosis: 144 were assigned to cognitive therapy plus monitoring of mental state and 144 to monitoring of mental state only. Participants were followed-up for a minimum of 12 months and a maximum of 24 months. Intervention Cognitive therapy (up to 26 (mean 9.1) sessions over six months) plus monitoring of mental state compared with monitoring of mental state only. Main outcome measures Primary outcome was scores on the comprehensive assessment of at risk mental states (CAARMS), which provides a dichotomous transition to psychosis score and ordinal scores for severity of psychotic symptoms and distress. Secondary outcomes included emotional dysfunction and quality of life. Results Transition to psychosis based on intention to treat was analysed using discrete time survival models. Overall, the prevalence of transition was lower than expected (23/288; 8%), with no significant difference between the two groups (proportional odds ratio 0.73, 95% confidence interval 0.32 to 1.68). Changes in severity of symptoms and distress, as well as secondary outcomes, were analysed using random effects regression (analysis of covariance) adjusted for site and baseline symptoms. Distress from psychotic symptoms did not differ (estimated difference at 12 months −3.00, 95% confidence interval −6.95 to 0.94) but their severity was significantly reduced in the group assigned to cognitive therapy (estimated between group effect size at 12 months −3.67, −6.71 to −0.64, P=0.018). Conclusions Cognitive therapy plus monitoring did not significantly reduce transition to psychosis or symptom related distress but reduced the severity of psychotic symptoms in young people at high risk. Most participants in both groups improved over time. The results have important implications for the at risk mental state concept. Trial registration Current Controlled Trials ISRCTN56283883.

Neurocognitive function and outcome in first-episode schizophrenia: a 10-year follow-up of an epidemiological cohort

The natural history of neurocognitive impairments in schizophrenia is unclear. We aimed to characterise this in an epidemiological first-episode cohort and relate it to long-term outcome. All but 1 of 112 first-episode psychosis cases ascertained from a geographical catchment area were traced at 10-12 years. Neurocognitive and multi-dimensional outcome assessments were made at interview in 49 cases with schizophrenia and related disorders. Twenty-four of these had completed the same neurocognitive battery at index admission. Comparisons with normative data showed impaired executive function in a proportion of the first episode (FE) sample at baseline. Significant deterioration was seen over the follow-up period in three of nine sub-tests: object assembly, picture completion and memory for designs. Neurocognitive impairments at outcome, but not baseline, correlated with clinical outcome. Poor outcome was associated with a decline in performance on visuo-spatial tasks and a failure to improve on frontal-temporal tasks during the follow-up period. Executive deficits may be present in the FE, but do not progress over 10-12 years. Visuo-spatial function is spared in the FE but may deteriorate over time. Changes in both these patterned deficits are predictive of clinical outcome.

Integrated motivational interviewing and cognitive behavioural therapy for people with psychosis and comorbid substance misuse: randomised controlled trial

Objectives To evaluate the effectiveness of integrated motivational interviewing and cognitive behavioural therapy in addition to standard care for patients with psychosis and a comorbid substance use problem. Design Two centre, open, rater blind randomised controlled trial. Setting Secondary care in the United Kingdom. Participants 327 patients with a clinical diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder and a diagnosis of dependence on or misuse of drugs, alcohol, or both according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Intervention The intervention was integrated motivational interviewing and cognitive behavioural therapy plus standard care, which was compared with standard care alone. Phase one of therapy—“motivation building”—concerns engaging the patient, then exploring and resolving ambivalence for change in substance use. Phase two—“action”—supports and facilitates change using cognitive behavioural approaches. Up to 26 therapy sessions were delivered over one year. Main outcome measures The primary outcome was death from any cause or admission to hospital in the 12 months after completion of therapy. Secondary outcomes were frequency and amount of substance use (assessed using the timeline followback method), readiness to change, perceived negative consequences of use, psychotic symptom ratings, number and duration of relapses, and global assessment of functioning and deliberate self harm at 12 and 24 months, with additional timeline followback assessments at 6 and 18 months. Analysis was by intention to treat and robust treatment effect estimates were produced. Results 327 participants were randomly allocated to either the intervention (n=164) or treatment as usual (n=163). At 24 months, 326 (99.7%) were assessed on the primary outcome and 246 (75.2%) on the main secondary outcomes. Treatment had no beneficial effect on hospital admissions or death during follow-up, with 23.3% (38/163) of the therapy group and 20.2% (33/163) of controls deceased or admitted (adjusted odds ratio 1.16, 95% confidence interval 0.68 to 1.99; P=0.579). Therapy had no effect on the frequency of substance use or the perceived negative consequences of misuse, but did have a statistically significant effect on amount used per substance using day (adjusted ORs for main substance 1.50, 95% CI 1.08 to 2.09; P=0.016; and all substances 1.48, 95% CI 1.07 to 2.05; P=0.017). Treatment had a statistically significant effect on readiness to change use at 12 months (adjusted OR 2.05, 95% CI 1.26 to 3.31; P=0.004) that was not maintained at 24 months (0.78, 95% CI 0.48 to 1.28; P=0.320). There were no effects of treatment on clinical outcomes such as relapses, psychotic symptoms, functioning, and self harm. Conclusions Integrated motivational interviewing and cognitive behavioural therapy for people with psychosis and substance misuse do not improve outcome in terms of hospitalisation, symptom outcomes, or functioning. This approach does reduce the amount of substance used for at least one year after completion of therapy. Trial registration Current Controlled Trials: ISRCTN14404480.

Insight and neurocognition in schizophrenia

The relationship between neurocognitive impairments in schizophrenia remains unclear. Recent literature was reviewed and the most consistent finding was an association between perseverative errors on the Wisconsin Card Sort Test (WCST) and poor insight. The aim was to confirm and extend this finding using a range of assessments relevant to perseveration, and different dimensions of insight, in a sample of 33 acutely psychotic subjects within 5 years of onset of schizophrenia and related disorders. Results showed a correlation (r=-0.59) between insight and perseverative errors, rather than more general measures of abstraction. A factor representing relabelling symptoms, derived from insight scale items, correlated even more strongly; however, other insight factors correlated more weakly, suggesting they are less dependent on neuropsychological deficits. The ability to monitor output and correct errors appears to be closely related to the core features of insight in psychosis.