Tina-Marie Proffitt

Cognition at illness onset as a predictor of later functional outcome in early psychosis: systematic review and methodological critique.

BACKGROUND Cognitive deficits occur early in the course of psychosis, are mostly stable, and have been identified as potential functional prognostic markers. Previous reviews of chronic schizophrenia have concluded that specific cognitive deficits are strongly associated with poorer functional outcomes. However, results of schizophrenia studies may be influenced by the effects of long-term illness or treatment or be biased toward individuals with poorer outcomes and may not be relevant to early psychosis (EP). This review aimed to systematically examine the evidence regarding general and social cognitive predictors of later functional outcome in EP and critique the methodology of the studies reviewed. A final aim was to conduct a meta-analysis of the studies reviewed, but methodological reasons precluded this. METHOD A comprehensive search of PsycINFO and MEDLINE databases identified 15 relevant articles and 7 further articles following a reference list search, totaling 22 included articles. RESULTS Most studies found at least one cognitive domain predicted functional outcome, but examination of separate cognitive domains revealed there were more null than significant associations between cognition and functional outcome across every cognitive domain. No study examined social cognition as a predictor of outcome. The frequency with which different cognitive domains predicted outcome varied depending on study methodology and this was most noticeable when studies with short-term follow-up were compared with longer-term follow-up studies. CONCLUSIONS Due to the methodological variability and limitations of the studies reviewed, firm conclusions regarding the relationship between cognition and functional outcomes in EP cannot be made. Tentatively, cognition may be prognostic in EP, especially for longer-term outcomes. However, further research that addresses the methodological issues identified, including examination of social cognition and other non-cognitive predictors, is needed.

The reliability and validity of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) in first-episode psychosis

AIMS The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) is a brief, easily administered, valid and reliable screening instrument for all psychoactive substances in drug treatment and primary care settings. This study aims to determine the reliability and validity of the ASSIST for detecting substance use disorders in first-episode psychosis. PARTICIPANTS Participants were 214 first-episode psychosis patients attending the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne, Australia. MEASUREMENTS Participants were administered the ASSIST, Alcohol Use Disorders Identification Test (AUDIT), the Severity of Dependence Scale (SDS) and the Brief Psychiatric Rating Scale (BPRS). Presence of DSM-IV substance abuse and dependence disorders in the previous 12 months was assessed using the Structured Clinical Interview for DSM-IV (SCID-IV). FINDINGS The ASSIST total substance involvement (TSI) score and specific substance involvement (SSI) scores for cannabis, alcohol and amphetamine use demonstrated high levels of internal consistency and acceptable levels of concurrent and discriminative validity. Individuals with cutoff scores of >/=2, 4 and 1 on the ASSIST cannabis, alcohol and amphetamine SSI scores were 5 to 6 times more likely to meet the diagnostic criteria for these substance use disorders. CONCLUSIONS The ASSIST is a psychometrically sound measure of cannabis, alcohol and amphetamine use disorders in first-episode psychosis.

The relative contribution of neurocognition and social cognition to 6-month vocational outcomes following Individual Placement and Support in first-episode psychosis

AIMS To examine whether baseline neurocognition and social cognition predict vocational outcomes over 6 months in patients with first-episode psychosis (FEP) enrolled in a randomised controlled trial of Individual Placement and Support (IPS) versus treatment as usual (TAU). METHODS 135 FEP participants (IPS n=69; TAU n=66) completed a comprehensive neurocognitive and social cognitive battery. Principal axis factor analysis using PROMAX rotation was used to determine the underlying cognitive structure of the battery. Setwise (hierarchical) logistic and multivariate linear regressions were used to examine predictors of: (a) enrolment in education and employment; and (b) hours of employment over 6 months. Neurocognition and social cognition factors were entered into the models after accounting for premorbid IQ, baseline functioning and treatment group. RESULTS Six cognitive factors were extracted: (i) social cognition; (ii) information processing speed; (iii) verbal learning and memory; (iv) attention and working memory; (v) visual organisation and memory; and (vi) verbal comprehension. Enrolment in education over 6 months was predicted by enrolment in education at baseline (p=.002) and poorer visual organisation and memory (p=.024). Employment over 6 months was predicted by employment at baseline (p=.041) and receiving IPS (p=.020). Better visual organisation and memory predicted total hours of paid work over 6 months (p<.001). CONCLUSIONS Visual organisation and memory predicted the enrolment in education and duration of employment, after accounting for premorbid IQ, baseline functioning and treatment. Social cognition did not contribute to the prediction of vocational outcomes. Neurocognitive interventions may enhance employment duration in FEP.

Grey and white matter abnormalities are associated with impaired spatial working memory ability in first-episode schizophrenia

Spatial working memory (SWM) dysfunction has been suggested as a trait marker of schizophrenia and implicates a diffuse network involving prefrontal, temporal and parietal cortices. However, structural abnormalities in both grey and white matter in relation to SWM deficits are largely unexplored. The current magnetic resonance imaging (MRI) study examined this relationship in a sample of young first-episode schizophrenia (FES) patients using a whole-brain voxel-based method. SWM ability of 21 FES patients and 41 comparable controls was assessed by the CANTAB SWM task. Using an automated morphometric analysis of brain MRI scans, we assessed the relationship between SWM abilities and both grey matter volume and white matter density in both groups. Our findings demonstrated the different directionality of the association between SWM errors and grey matter volume in left frontal regions and white matter tracts connecting these regions with temporal and occipital areas between FES patients and controls. This suggests that the substrate underpinning the normal variability in SWM function in healthy individuals may be abnormal in FES, and that the normal neurodevelopmental processes that drive the development of SWM networks are disrupted in schizophrenia.

Divergent effects of first-generation and second-generation antipsychotics on cortical thickness in first-episode psychosis

Background Whether there are differential effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) on the brain is currently debated. Although some studies report that FGAs reduce grey matter more than SGAs, others do not, and research to date is limited by a focus on schizophrenia spectrum disorders. To address this limitation, this study investigated the effects of medication in patients being treated for first-episode schizophrenia or affective psychoses. Method Cortical thickness was compared between 52 first-episode psychosis patients separated into diagnostic (i.e. schizophrenia or affective psychosis) and medication (i.e. FGA and SGA) subgroups. Patients in each group were also compared to age- and sex-matched healthy controls (n = 28). A whole-brain cortical thickness interaction analysis of medication and diagnosis was then performed. Correlations between cortical thickness with antipsychotic dose and psychotic symptoms were examined. Results The effects of medication and diagnosis did not interact, suggesting independent effects. Compared with controls, diagnostic differences were found in frontal, parietal and temporal regions. Decreased thickness in FGA-treated versus SGA-treated groups was found in a large frontoparietal region (p < 0.001, corrected). Comparisons with healthy controls revealed decreased cortical thickness in the FGA group whereas the SGA group showed increases in addition to decreases. In FGA-treated patients cortical thinning was associated with higher negative symptoms whereas increased cortical thickness in the SGA-treated group was associated with lower positive symptoms. Conclusions Our results suggest that FGA and SGA treatments have divergent effects on cortical thickness during the first episode of psychosis that are independent from changes due to illness.

A randomized controlled trial of vocational intervention for young people with first-episode psychosis: method

Young people who are experiencing first‐episode psychosis (FEP) are at increased risk of being unemployed compared to either their same age peers in the general population, or those with other mental illnesses. Significant research has been conducted examining employment interventions for those with chronic psychotic illness. This has yielded strong results in favour of an intervention called individual placement and support (IPS). However, significantly less work has examined the benefit of this approach to those in FEP when the potential for vocational rehabilitation is perhaps greater. This study adds to the knowledge of vocational intervention in first‐episode psychotic illness. Additionally, it expands this work into the areas of cognition, social cognition, social inclusion and economics.

The effect of atypical antipsychotics on pituitary gland volume in patients with first-episode psychosis: a longitudinal MRI study.

BACKGROUND Pituitary volume is currently measured as a marker of hypothalamic-pituitary-adrenal hyperactivity in patients with psychosis despite suggestions of susceptibility to antipsychotics. Qualifying and quantifying the effect of atypical antipsychotics on the volume of the pituitary gland will determine whether this measure is valid as a future estimate of HPA-axis activation in psychotic populations. AIMS To determine the qualitative and quantitative effect of atypical antipsychotic medications on pituitary gland volume in a first-episode psychosis population. METHOD Pituitary volume was measured from T1-weighted magnetic resonance images in a group of 43 first-episode psychosis patients, the majority of whom were neuroleptic-naïve, at baseline and after 3months of treatment, to determine whether change in pituitary volume was correlated with cumulative dose of atypical antipsychotic medication. RESULTS There was no significant baseline difference in pituitary volume between subjects and controls, or between neuroleptic-naïve and neuroleptic-treated subjects. Over the follow-up period there was a negative correlation between percentage change in pituitary volume and cumulative 3-month dose of atypical antipsychotic (r=-0.37), i.e. volume increases were associated with lower doses and volume decreases with higher doses. CONCLUSIONS Atypical antipsychotic medications may reduce pituitary gland volume in a dose-dependent manner suggesting that atypical antipsychotic medication may support affected individuals to cope with stress associated with emerging psychotic disorders.

Neuroprotective effects of ethyl-eicosapentaenoic acid in first episode psychosis: A longitudinal T2 relaxometry pilot study

We used magnetic resonance imaging to examine the effect of ethyl-eicosapentaenoic acid (E-EPA) on hippocampal T(2) relaxation time in first episode psychosis patients at baseline and after 12 weeks of follow-up. There was an increase in T(2) in the placebo group but not in the E-EPA group, suggesting a neuroprotective effect of E-EPA treatment. In addition, the smaller the increase in T(2), the greater the improvement in negative symptoms.

Vascular Endothelial Growth Factor and Brain-Derived Neurotrophic Factor in Quetiapine Treated First-Episode Psychosis

Objective. It has been suggested that atypical antipsychotics confer their effects via brain-derived neurotrophic factor (BDNF). We investigated the effect of quetiapine on serum levels of BDNF and vascular endothelial growth factor (VEGF) in drug-naive first-episode psychosis subjects. Methods. Fifteen patients drawn from a larger study received quetiapine treatment for twelve weeks. Baseline levels of serum BDNF and VEGF were compared to age- and sex-matched healthy controls and to levels following treatment. Linear regression analyses were performed to determine the relationship of BDNF and VEGF levels with outcome measures at baseline and week 12. Results. The mean serum BDNF level was significantly higher at week 12 compared to baseline and correlated with reductions in Brief Psychiatric Rating Scale (BPRS) and general psychopathology scores. Changes in serum VEGF levels also correlated significantly with a reduction in BPRS scores, a significant improvement in PANNS positive symptoms scores, and displayed a positive relationship with changes in BDNF levels. Conclusions. Our findings suggest that BDNF and VEGF are potential biomarkers for gauging improvement of psychotic symptoms. This suggests a novel neurotrophic-based mechanism of the drug effects of quetiapine on psychosis. This is the first report of VEGF perturbation in psychosis.

Phospholipase A2 activity in first episode schizophrenia: Associations with symptom severity and outcome at week 12

Abstract Objectives. Intracellular phospholipases A2 (inPLA2) are activated during monoaminergic neurotranismision and act as key enzymes in cell membrane repair and remodelling, neuroplasticity, neurodevelopment, apoptosis, synaptic pruning, neurodegenerative processes and neuroinflammation. Several independent studies found increased inPLA2 activity in drug-naïve first episode and chronic schizophrenia. This study investigates if inPLA2 activity is associated with symptoms severity and treatment response in first episode schizophrenia (FES). Methods. InPLA2 activity was measured in serum of 35 young FES patients (mean age: 19.36 ± 3.32, mean duration of illness: 7.53 ± 6.28 months, 16 neuroleptic-naïve) before and after 12 weeks of treatment with second-generation antipsychotic medications (olanzapine, quetiapine or risperidone), as well as in 22 healthy controls matched for age. Psychopathology and social functioning were assessed at the same time points. Results. Baseline inPLA2 activity was significantly increased in drug-naïve and treated FES patients compared to healthy controls. Baseline inPLA2 activity was also associated with severity of negative symptoms and lower functioning at baseline. Furthermore, baseline inPLA2 activity was associated with improvement in negative symptoms and functioning within the first 12 weeks of treatment. Conclusions. Intracellular PLA2 activity is increased in first episode schizophrenia and associated with symptom severity and outcome after 12 weeks of treatment. Future studies should investigate the implications of inPLA2 activity as a potential predictor of treatment response for different antipsychotic agents.