Acute-phase and 1-year follow-up results of a randomized controlled trial of CBT versus Befriending for first-episode psychosis: the ACE project.

BACKGROUND: The ACE project involved 62 participants with a first episode of psychosis randomly assigned to either a cognitive behaviour therapy (CBT) intervention known as Active Cognitive Therapy for Early Psychosis (ACE) or a control condition known as Befriending. The study hypotheses were that: (1) treating participants with ACE in the acute phase would lead to faster reductions in positive and negative symptoms and more rapid improvement in functioning than Befriending; (2) these improvements in symptoms and functioning would be sustained at a 1-year follow-up; and (3) ACE would lead to fewer hospitalizations than Befriending as assessed at the 1-year follow-up. METHOD: Two therapists treated the participants across both conditions. Participants could not receive any more than 20 sessions within 14 weeks. Participants were assessed by independent raters on four primary outcome measures of symptoms and functioning: at pretreatment, the middle of treatment, the end of treatment and at 1-year follow-up. An independent pair of raters assessed treatment integrity. RESULTS: Both groups improved significantly over time. ACE significantly outperformed Befriending by improving functioning at mid-treatment, but it did not improve positive or negative symptoms. Past the mid-treatment assessment, Befriending caught up with the ACE group and there were no significant differences in any outcome measure and in hospital admissions at follow-up. CONCLUSIONS: There is some preliminary evidence that ACE promotes better early recovery in functioning and this finding needs to be replicated in other independent research centres with larger samples.

Cognitively oriented psychotherapy for early psychosis (COPE): a 1-year follow-up.

OBJECTIVES: Cognitively oriented psychotherapy for early psychosis (COPE) is aimed at facilitating the adjustment of the person, and at preventing or alleviating secondary morbidity in the wake of the first psychotic episode. DESIGN: A total of 80 people participated in the initial trial and completed assessments on a range of outcome measures. Post-treatment assessment results from a non-randomized controlled trial of COPE have been previously reported. The present paper describes the results obtained from 51 patients who attended a follow-up assessment 1 year subsequent to the end-of-treatment assessment. METHOD: The 51 patients formed three groups: (1) those who were offered and accepted COPE; (2) those who were offered COPE but refused it, and continued to receive other services from the Early Psychosis Prevention and Intervention Centre (EPPIC) (refusal subjects); and (3) those who were offered neither COPE nor any other continuing treatment from EPPIC (control subjects). RESULTS: At 1-year follow-up, there was only one significant difference and this was between the COPE and refusal groups on the Integration/Sealing Over (I/SO) measure (p = .008). End-of-treatment differences were mostly sustained over the 1-year follow-up period. When the complete sample of 80 was considered, there were no differences between the three groups in terms of hospital admissions, community episodes, or time taken to first in-patient re-admission. CONCLUSIONS: The study was weakened by the poor follow-up rates in the two control groups. This reduced power to detect differences between groups on the seven major measures. However, the relapse data gathered on the complete set of 80 patients were discouraging and suggest that the present formulation of COPE does not confer any advantage to those patients receiving the therapy over those not receiving the therapy.

An optimized method for estimating intracranial volume from magnetic resonance images.

The accuracy and efficiency of protocols to measure intracranial volume (ICV) from volumetric magnetic resonance imaging (MRI) studies has not been formally analyzed. The ICV of 30 control participants was obtained by tracing every slice of a MRI data set on which the cranial cavity appeared, and compared with estimated ICVs calculated by progressively selecting one of every x slices (i.e., "1-in-x") as a sampling strategy. The reliability and precision of each sampling strategy was then determined. There was virtually no reduction in reliability at the 1-in-10 sampling strategy, with a reliability exceeding 0.999. ICV can be confidently traced using a 1-in-10 sampling strategy, which should result in significant time savings.

Hippocampal volume in first-episode psychoses and chronic schizophrenia: a high-resolution magnetic resonance imaging study.

BACKGROUND: It has been proposed that the hippocampus is a potential site for a neurodevelopmental lesion in schizophrenia. While smaller hippocampal volumes have been described in chronic schizophrenia, there have been few magnetic resonance imaging studies in first-episode psychosis. Furthermore, no studies have examined the specificity of this finding to first-episode schizophrenia, compared with first-episode affective psychosis. METHODS: Hippocampal and whole-brain volumes were estimated using high-resolution magnetic resonance imaging in 140 controls, 46 patients with chronic schizophrenia, and 32 patients with first-episode psychosis. RESULTS: Patients with chronic schizophrenia and first-episode psychosis had significantly smaller hippocampal volumes as compared with controls. Within the first-episode group, both patients with schizophrenia/schizophreniform psychosis and those with affective psychosis had smaller left hippocampal volumes as compared with controls. Smaller right hippocampal volumes were associated with age and illness duration in patients with chronic schizophrenia. Hippocampal volumes were not correlated with age of illness onset or medication dosage in either patient group. CONCLUSIONS: These data show that smaller hippocampal volumes are present from the onset of illness. While these findings would support the neurodevelopmental model of schizophrenia, the finding of smaller left hippocampal volume in patients with first-episode schizophrenia and affective psychosis does not support the prediction that smaller hippocampi are specific to schizophrenia. The association of smaller right hippocampal volumes with increased illness duration in chronic schizophrenia suggests either that there is further neurodegeneration after illness onset or that bilateral small hippocampi predict chronicity.

The effects of age and mood on saccadic function in older individuals.

To investigate the effect of age and mood on saccadic function, we recorded prosaccades, predictive saccades, and antisaccades from 238 cognitively normal, physically healthy volunteers aged 44 to 85 years old. Mood levels were measured using the State-Trait Anxiety Inventory and Center for Epidemiological Studies Depression Scale inventories. Small, but significant, positive relationships with age were observed for the mean latency and associated variability of latency for all types of saccades, as well as the antisaccade error rate. Saccade velocity or accuracy was unaffected by age. Increasing levels of depression had a minor negative influence on the antisaccade latency, whereas increasing levels of anxiety raised the antisaccade error rate marginally.

Cognitively-oriented psychotherapy for early psychosis (COPE). Preliminary results.

BACKGROUND: The present study describes the results of the pilot testing of a therapy we have developed for people with first-episode psychosis. Cognitively-oriented psychotherapy for early psychosis (COPE) is aimed at facilitating the adjustment of the person, and at preventing or alleviating secondary morbidity in the wake of the first psychotic episode. METHOD: Eighty people formed three groups: those who were offered and accepted COPE (COPE subjects); those who refused COPE (refusal subjects); and those who were offered neither COPE nor any other continuing treatment from our service (control subjects). The individuals were assessed prior to, and at the end of, COPE treatment (a 12-month period) on the Integration/Sealing Over, Explanatory Model, Scale for the Assessment of Negative Symptoms, Brief Psychiatric Rating Scale, Quality of Life, SCL-90-R, and Beck Depression Inventory measures. RESULTS: People who received COPE obtained significantly superior scores (P < 0.05) to the control group on four of the seven measures but only significantly out-performed the refusal group on one of the seven measures (P < 0.05). The COPE group performed significantly worse on the BDI than the refusal group (P < 0.05). Effect sizes are also provided for each measure. CONCLUSIONS: There seems to be a place for psychological therapy in this group of people but our results need to be replicated in a more definitive randomised controlled trial and such a study is now in progress.

The dimensional structure of first episode psychosis: an exploratory factor analysis.

BACKGROUND: Recent research has focused upon the subdiagnostic level in an effort to derive more valid domains of psychotic disorder. This has led to the influential positive-negative dichotomy in schizophrenia being superseded by a three-syndrome model. The strategy of looking for syndromes within poorly validated diagnostic categories, such as schizophrenia, has limitations, particularly since it originated in, and has been largely restricted to, the more chronic subsamples. METHOD: A representative sample of first episode psychosis (N = 509), which includes the full spectrum of functional psychosis, was utilized to re-examine the dimensional structure of functional psychosis from first principles. Patients were assessed with the Royal Park Multidiagnostic Instrument for Psychosis (MIP), a comprehensive procedure that documents the psychopathology of the first episode in a clinically valid manner. RESULTS: Principal axis factor analysis was carried out on the tetrachoric correlation matrix of 92 core psychopathological items. A robust and clinically valid four-factor solution was obtained, comprising depression, mania and only two other factors. The first was a Bleulerian blend of negative symptoms, catatonic/motor symptoms and disorganization. The second was a combination of Schneiderian first rank symptoms, and other hallucinations and delusions. The data thus failed to support the three-syndrome model for non-affective symptoms in this population. A six-factor solution, although partially consistent with other studies, represented a more complex and confusing elaboration of the more clinically valid four-factor solution. CONCLUSIONS: The findings have implications for the conceptualization of early psychosis, which need to be explored further in validation studies.

The dimensionality of schizophrenia concepts in first-episode psychosis.

This study aimed to determine the dimensionality of concepts of schizophrenia using 11 different diagnostic systems, and then to identify the nature of these dimensions by their relationship to a range of signs and symptoms. The sample consisted of 479 patients admitted with a first episode of functional psychosis. The underlying structure of the 11 diagnostic systems was best represented by an oblique 3-factor solution. Whereas the second and third factors could be meaningfully interpreted by their correlations with signs and symptoms, the first factor, anchored by 'modern' nosologies such as DSM-III-R, was more clearly specified by what it is not (the absence of affective symptoms) rather than by what it is (the presence of characteristic psychotic symptoms). A logistic regression of DSM-III-R diagnosis on to separate diagnostic components supports the contention that duration of illness and affective exclusion criteria discriminate the presence of DSM-III-R schizophrenia much better than the three characteristic psychotic symptom groupings.

Confirmatory factor analysis of the Wechsler Memory Scale-Revised in a sample of clients with alcohol dependency.

Previous analyses of the Wechsler Memory Scale-Revised (WMS-R; Wechsler, 1987) have reported one-, two-, and three-factor solutions and raised questions about the validity of the visual memory subtests. These various findings may stem in part from different methods of analysis, and from the study of different participant samples. To address these issues, we analysed data from the WMS-R and a spatial maze test administered to 154 participants with a history of alcohol dependence. Results from confirmatory factor analysis supported the interpretation of three factors underlying the WMS-R subtests and the spatial maze score in this sample, namely, attention-concentration, immediate memory, and delayed recall. This result held despite the inclusion of the maze score which is a well-validated measure of visuo-spatial memory.

Covariance structure analysis: statistical practice, theory, and directions.

Although covariance structure analysis is used increasingly to analyze nonexperimental data, important statistical requirements for its proper use are frequently ignored. Valid conclusions about the adequacy of a model as an acceptable representation of data, which are based on goodness-of-fit test statistics and standard errors of parameter estimates, rely on the model estimation procedure being appropriate for the data. Using analogies to linear regression and anova, this review examines conditions under which conclusions drawn from various estimation methods will be correct and the consequences of ignoring these conditions. A distinction is made between estimation methods that are either correctly or incorrectly specified for the distribution of data being analyzed, and it is shown that valid conclusions are possible even under misspecification. A brief example illustrates the ideas. Internet access is given to a computer code for several methods that are not available in programs such as EQS or LISREL.

Prodromal symptoms of schizophrenia in first-episode psychosis: prevalence and specificity.

Three hundred thirteen patients with first-episode psychosis were assessed using the Royal Park Multidiagnostic Instrument for Psychosis (RPMIP) to determine differences among seven DSM-III-R diagnoses in the comparative frequencies and diagnostic efficiencies of DSM-III-R schizophrenia prodromal symptoms. Patients with a diagnosis of schizophrenia and schizophreniform disorder were significantly more likely to evince prodromal symptoms. A multinomial logit model suggested that individual prodromal symptoms were relatively poor at distinguishing between diagnoses. This was confirmed when sensitivity, specificity, and positive (PPP) and negative (NPP) predictive power of individual prodromal symptoms were examined. Although DSM-III-R schizophrenia prodromal symptoms do occur more commonly in schizophrenia, they are by no means pathognomonic of that disorder.

Latent trait modelling of symptoms of schizophrenia.

Latent trait models were fitted to data for 149 schizophrenic or schizophreniform inpatients rated on the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) using the Rasch Extended Logistic Model. It was found that a reduction in the numbers of rating categories, from six to three or four led to consistencies in response while deletion of several items led to consistent scales of symptoms that accorded with an item response characterization. Behaviours included in the final scales varied in the numbers of categories, and in the range of symptom level covered by a category. Relationships between scores representing symptoms were found to be modelled better by a factor structure that included a third overlapping 'cognitive' factor in addition to the now traditional positive and negative factors, than by the original positive and negative factors alone.

Monitoring regional geriatric assessment teams: analysis of client flows and outcomes.

The Commonwealth Government funding of the Geriatric Assessment Program began in 1984. The Program included an evaluation component, and this paper reports findings for three Regional Geriatric Assessment Teams (RGATs) in Victoria focusing on (1) the identification of different starting points in the flow of clients to the RGATs, (2) the relationships between different starting points and (3) recommended care plans, and the relationships between (2) and final outcome, particularly whether or not this involved admission to nursing home care. The role performed by RGATs is reviewed in the context of introducing mandatory assessment, the success of which will depend on the effectiveness of RGATs not only in differentiating need for and securing admission to nursing home care but also in assessing for, accessing and initiating alternative services.

The investigation of the HCN derivative diiminosuccinonitrile as a prebiotic condensing agent. The formation of phosphate esters.

Diiminosuccinonitrile (DISN) is formed readily by the Fe3+ oxidation of diaminomaleonitrile, a tetramer of HCN. DISN effects the phosphorylation of uridine in 13% yield to a mixture of the isomers of UMP when the reaction is performed in dimethylformamide solution. A 4% yield of the UMP isomers is obtained in neutral aqueous solution using 2 times the DISN concentration and 7 times the phosphate concentration used in DMF. DISN did not effect the conversion of adenosine to AMP or 5'-AMP to 5'-ADP in aqueous solution. The cyclization of 3'-AMP and 3'-UMP to the corresponding 2'-3'-cyclic phosphates proceeds in yields as high as 40-50% at 60 degrees C in pH 6 aqueous solutions in the presence of divalent metal ions. Lower yields of the cyclic phosphate are observed when 2'-AMP is the starting material. Substitution of acetate buffer for imidazole buffer results in a decrease in the yield of cyclic phosphate, the extent of which depends on the metal ion used in the reaction. No 3'5'-cyclic AMP was detected as a reaction product with either 5'-AMP or 3'-AMP as the starting material except for a 2.4% yield from 3'-AMP in the presence of Zn2+. BrCN effects the conversion of 3'-AMP to the 2'-3'-cyclic AMP in 37-65% yield depending on the divalent cation used as catalyst. A mechanism has been proposed for these cyclization reactions and their potential significance to the prebiotic synthesis of ribonucleic acid derivatives is discussed.