Value of early intervention in psychosis.
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Humans↗
Biomedical subjects
P D McGorry
Publications and source records attributed to P D McGorry.
Does treatment delay in first-episode psychosis really matter?
BACKGROUND: Relatively few predictors of outcome in first-episode psychosis are potentially malleable and duration of untreated psychosis (DUP) is one. However, the degree to which DUP is mediated by other predictors of outcome is unclear. This study examines the specific effects of DUP on 12-month outcome after adjusting for effects of potential confounders and moderating variables. METHOD: The sample comprised 354 first-episode psychosis patients followed up 12-months after remission/stabilization of their psychotic symptoms. Outcome measures included functional outcome, severity of positive symptoms and negative symptoms. Hierarchical multiple regression assessed whether DUP significantly predicted 12-month outcome after adjusting for other predictors. Contrast analysis further clarified the differential effects of DUP on 12-month outcome. RESULTS: DUP remained a significant predictor of outcome after adjusting for the effects of other variables. This finding remained robust for the subset of patients with schizophrenia or schizophreniform disorder. Functional outcome appeared to decline substantially even after very short treatment delays (> 7 days), with more gradual deterioration in functioning until very long DUP (> 1 year). Good outcome was variably associated with good pre-morbid adjustment, female gender, diagnosis of affective disorder, short duration of prodromal symptoms, and treatment within the Early Psychosis Prevention and Intervention model in contrast to other models of care. CONCLUSIONS: DUP consistently predicts outcome independently of other variables, and is not simply a proxy for other factors. As one of the few potentially malleable factors influencing outcome, DUP could prove to be a target for secondary preventive efforts in early psychosis.
Adolescent↗
Spatial working memory ability is a marker of risk-for-psychosis.
BACKGROUND: Working memory has been identified as a core cognitive deficit in schizophrenia that is associated with negative symptoms, but it is unclear whether it is impaired prior to onset of psychosis in symptomatic patients. METHOD: Thirty-eight young people at ultra high-risk (UHR) of developing psychosis (of whom nine later became psychotic) were compared with 49 healthy controls on tests of spatial working memory (SWM) and delayed matching-to-sample (DMTS). RESULTS: Both SWM and DMTS performance was significantly poorer in the UHR groups. Those who later became psychotic generally performed more poorly than those who did not, although this did not reach significance for any measure. A significant association between SWM errors and negative symptoms was seen in the later-psychotic group only (P = 0.02). CONCLUSIONS: Spatial working memory abilities are impaired in those at high-risk for psychosis. The relationship between working memory and negative symptoms may be useful as a predictive tool.
Adolescent↗
Suicide prevention in first episode psychosis: the development of a randomised controlled trial of cognitive therapy for acutely suicidal patients with early psychosis.
BACKGROUND: Young people with early psychosis are at particularly high risk of suicide. However, there is evidence that early intervention can reduce this risk. Despite these advances, first episode psychosis patients attending these new services still remain at risk. To address this concern, a program called LifeSPAN was established within the Early Psychosis Prevention and Intervention Centre (EPPIC). The program developed and evaluated a number of suicide prevention strategies within EPPIC and included a cognitively oriented therapy (LifeSPAN therapy) for acutely suicidal patients with psychosis. We describe the development of these interventions in this paper. METHOD: Clinical audit and surveys provided an indication of the prevalence of suicidality among first episode psychosis patients attending EPPIC. Second, staff focus groups and surveys identified gaps in service provision for suicidal young people attending the service. Third, a suicide risk monitoring system was introduced to identify those at highest risk. Finally, patients so identified were referred to and offered LifeSPAN therapy whose effectiveness was evaluated in a randomised controlled trial. RESULTS: Fifty-six suicidal patients with first episode psychosis were randomly assigned to standard clinical care or standard care plus LifeSPAN therapy. Forty-two patients completed the intervention. Clinical ratings and measures of suicidality and risk were assessed before, immediately after the intervention, and 6 months later. Benefits were noted in the treatment group on indirect measures of suicidality, e.g., hopelessness. The treatment group showed a greater average improvement (though not significant) on a measure of suicide ideation. CONCLUSIONS: Early intervention in psychosis for young people reduces the risk of suicide. Augmenting early intervention with a suicide preventative therapy may further reduce this risk.
Acute Disease↗
Duration of untreated psychosis and cognitive deterioration in first-episode schizophrenia.
Cognitive impairment is an important clinical feature in many individuals with schizophrenia. Factors associated with cognitive deficit are not well established. Duration of untreated psychosis (DUP) has recently gained interest as a prognostic factor in schizophrenia. This study reports on the association between DUP and cognitive function. Subjects comprised 42 individuals (30 males, 12 females) who experienced a first-episode of DSM-III-R schizophrenia or schizophreniform disorder. Cognitive function was determined at clinical stabilization using the WAIS-R. An estimate of cognitive deterioration was based on the WAIS-R subtest profile. Longer DUP, male gender, higher premorbid IQ and younger age at admission independently predicted cognitive deterioration. Poorer performance on Digit Symbol and Comprehension subtests was associated with longer DUP. The findings suggest that untreated psychosis compromises some aspects of cognitive function. Studies investigating the association between DUP and outcome should control for potentially confounding variables. Early treatment of psychosis could help to reduce the prominent cognitive deficit in first-episode schizophrenia.
Adolescent↗
Estimating cognitive deterioration in schizophrenia.
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Adult↗
Visuospatial memory and learning in first-episode schizophreniform psychosis and established schizophrenia: a functional correlate of hippocampal pathology?
BACKGROUND: Despite a number of studies that have indicated impaired memory function in patients with schizophrenia, there have been few that have used a sensitive measure of right medial temporal lobe pathology. Given the reported findings of reduced hippocampal volume in schizophrenia, we used a theoretically sensitive test of the right medial temporal lobe to determine the nature of the visuospatial memory deficit in the disorder. METHODS: Seventy-six patients (37 with a first-episode schizophreniform psychosis, and 39 with established schizophrenia) were compared with 41 comparison subjects on a number of tests of visuospatial memory. These included spatial working memory, spatial and pattern recognition memory and a pattern-location associative learning test. RESULTS: Both patient groups displayed recognition memory deficits when compared to the comparison group. However, only those patients with established schizophrenia (of 9 years duration on average) were impaired on the associative learning test. CONCLUSIONS: The results indicate either a progressive decline in visuospatial associative learning ability over the course of the disorder, or that poor visuospatial associative learning is a marker for poor prognosis. In addition, these results have implications for our understanding of the role of the right medial temporal lobe in the pathophysiology of schizophrenia.
Adolescent↗
Incidental radiological findings on brain magnetic resonance imaging in first-episode psychosis and chronic schizophrenia.
OBJECTIVE: To investigate whether patients with first-episode psychosis or chronic schizophrenia have an increased incidence of magnetic resonance imaging (MRI) brain abnormalities compared with control subjects. METHOD: Totally 340 clinical MRI reports [Controls (n=98), first-episode psychoses (n=152), chronic schizophrenia (n=90)] were reported by a neuroradiologist blind to diagnosis and subsequently categorized using referral criteria (immediate, urgent, routine or no referral). RESULTS: Thirty percent of all scans were reported by a neuroradiologist as abnormal, but the majority required no referral. Patients with chronic schizophrenia were more likely to have clinically significant abnormal scans than patients with first episode psychosis or control subjects. In four patients the MRI findings led to the discovery of previously unsuspected pathology. CONCLUSION: Patients with chronic schizophrenia have an increased prevalence of incidental brain abnormalities. A small proportion of patients with chronic schizophrenia and first-episode psychosis benefitted directly from MRI scanning.
Adult↗
A longitudinal study of hippocampal volume in first episode psychosis and chronic schizophrenia.
Brain abnormalities have been identified in patients with schizophrenia, but what is unclear is whether these changes are progressive over the course of the disorder. In this longitudinal study, hippocampal and temporal lobe volumes were measured at two time points in 30 patients with first episode psychosis (mean follow-up interval=1.9 years, range 0.54-4.18 years) and 12 with chronic schizophrenia (mean follow-up interval=2.3 years, range 1.03-4.12 years) and compared to 26 comparison subjects (mean follow-up interval 2.2 years, range 0.86-4.18 years). Hippocampal, temporal lobe, whole-brain and intracranial volumes (ICV) were estimated from high-resolution magnetic resonance images. Only whole-brain volume showed significant loss over the follow-up interval in both patient groups. The rate of this volume loss was not different in the first episode group compared to the chronic group. There were no changes in either hippocampal or temporal lobe volumes. The negative findings for the hippocampus and temporal lobes may mean that the abnormalities in these regions are stable features of schizophrenia. Alternatively, the period before the onset of frank psychotic symptoms may be the point of greatest risk for progressive change.
Adolescent↗
Preventing severe mental illnesses--new prospects and ethical challenges.
We review some exciting recent developments in studies of psychoses in general and schizophrenia in particular that offer hope such illnesses can be identified and treated early. Early treatment promises better outcomes for both the affected individuals and their families, and perhaps even the prospect of true prevention. But testing such interventions in vulnerable patients can raise ethical difficulties that if not adequately addressed may harm patients and hamper the development of these interventions. We believe there are appropriate ways of dealing with the ethical problems in the early intervention field, though we also suggest that additional work on both scientific and ethical fronts will need to be done to make these ways real. As a start toward that end, we have summarized a number of the debates in the field and from the following articles, and have distilled five 'points to consider' that interested parties will need to take into account.
Clinical Trials as Topic↗
Ethics and early intervention in psychosis: keeping up the pace and staying in step.
The intense clinical and research interest in early psychosis in recent years has highlighted a range of ethical issues which need to be considered carefully. Our perspective is based on 16 years of clinical and research experience with young people at this phase of illness as well as the research contributions of many others. We discuss the ethical dilemmas in relation to the three key foci, which make up the early psychosis paradigm. These are the pre-psychotic or prodromal phase, the period of untreated psychosis and the first psychotic episode and the critical period of recovery, which follows this. Most attention is devoted to the pre-psychotic period, however ethical considerations related to research in the other two clinical foci are briefly covered as well. Our contention is that the ethical issues are essentially identical to those arising in early intervention research in mainstream medicine. This has been concealed by inconsistency and emotion, which has great potential to confuse, politicize and derail rational debate. The legacy of the isolation of psychiatry from medicine and consequent prejudice and stigma in the professional as well as the public mind seems to be fueling a tendency in some societies to view psychiatric research as qualitatively different from other medical research. Sound clinical research data should be allowed to illuminate the options for potential consumers across all phases of illness. The alternative is research paralysis, which would force clinical practice to expand blindly without an evidence base.
Clinical Trials as Topic↗
Failure to confirm the 3 domains model of psychosis.
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Delusions↗
Stability of olfactory identification deficits in neuroleptic-naive patients with first-episode psychosis.
OBJECTIVE: Olfactory identification deficits and their relationship to negative symptoms in patients with schizophrenia were examined in patients with recent-onset psychosis, the majority of whom were neuroleptic naive. METHOD: Seventy-four inpatients with a first episode of psychosis (27 with schizophrenia or schizophreniform disorder, nine with schizoaffective disorder, 17 with affective psychoses, and 21 with other psychoses), 49 of whom had not received antipsychotic medication, were compared to 38 age- and gender-matched normal subjects. Olfactory identification ability was assessed with the University of Pennsylvania Smell Identification Test. Forty patients and 13 comparison subjects were reassessed at 6 months to examine whether olfactory deficits were specific to schizophrenia or schizophreniform disorder and were stable over time. RESULTS: At baseline, the patients had significant impairment in olfactory identification ability compared to the normal subjects. This difference persisted after controlling for gender, premorbid or current IQ, smoking history, cannabis use, or the effects of medication. Diagnostic subgroups did not differ in olfactory identification ability. The deficits remained stable at 6-month follow-up and were associated with negative symptoms at both time points. No relationship was found between olfactory identification ability and length of either untreated psychosis or illness prodrome. CONCLUSIONS: Impairment in olfactory identification ability was apparent from the outset of psychotic illness and was not specific to schizophrenia or schizophreniform disorder. No change in the degree of this deficit was found after patients were stabilized and had responded to medication. The deficit could not be explained by peripheral factors that might contribute to olfactory identification ability, suggesting that it reflects central mechanisms.
Adolescent↗
Untreated initial psychosis.
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Adaptation, Psychological↗
Can we improve the diagnostic efficiency and predictive power of prodromal symptoms for schizophrenia?
Prodromal symptoms and other variables for a sample of 200 young people who had experienced a first-onset functional psychosis, were analyzed to examine their diagnostic efficiency and predictive power in relation to a diagnosis of schizophrenia. Two different techniques were utilized to generate optimal cut-off points for a number of prodromal symptoms, and optimal decision rules to maximize diagnostic efficiency. The product of the chance-corrected sensitivity and specificity, or the area under the QROC curve, was used to assess the predictive efficiency of a number of prodromal variables, DSM-III-R prodromal variables, pre-psychotic deterioration, pre-morbid functioning, and prodromal duration. The SPAN technique generated a decision rule that performed equivalently to the single variable 'duration of prodrome'. Implications of these results for future research are discussed.
Adolescent↗
The nature of schizophrenia: signposts to prevention.
OBJECTIVE: To describe the characteristics of schizophrenia relevant to conducting indicated preventive interventions. METHOD: A systematic review of the literature informed by experiences at the Personal Assistance and Crisis Evaluation (PACE) clinic. RESULTS: Primary prevention requires a sophisticated knowledge of key causal risk factors relevant to the expression of a disorder. The causal risk factors most useful from an intervention standpoint may turn out to be somewhat removed from the neurobiology of the disorder and may even be relatively non-specific, so that tackling them could reduce the risks for a range of mental disorders. The frontier for more specific prevention in schizophrenia and related psychosis is currently represented by indicated preventive interventions for subthreshold symptoms. Again, these may be relatively broad spectrum early in the prepsychotic phase but more proximal to onset, greater treatment specificity can be explored. However, this can be viewed more as preventively orientated treatment rather than primary prevention per se. Early detection of first episode psychosis and optimal intensive treatment of first episodes and the critical early years after diagnosis also represent increasingly attractive preventive foci in psychotic disorders. CONCLUSION: As evidence accumulates, implementation of evidence-based practice in real work settings is a major challenge as it is throughout the mental health service system. The momentum of preventively orientated treatment must be maintained through the 2nd National Mental Health Strategy and in the face of recent misleading polemic regarding the treatability of psychotic disorders, especially schizophrenia. The evidence demonstrates that schizophrenia and related disorders have never been more treatable.
Australia↗
Evidence for progression of brain structural abnormalities in schizophrenia: beyond the neurodevelopmental model.
OBJECTIVE: Clinical, neuroimaging, neuropathological and neuropsychological evidence suggests that, in schizophrenia, there is structural and functional disturbance of the hippocampus. The purpose of this paper is to present published findings concerning the nature, timing and course of these putative disturbances of hippocampal function and the pathophysiological mechanisms involved, and to explore whether schizophrenia is a disorder of neurodevelopment, neurodegeneration or a combination of both processes. METHOD: The available cross-sectional and longitudinal evidence for hippocampal involvement in schizophrenia is reviewed and a model of hippocampal involvement in this disorder, which derives from our own cross-sectional and longitudinal hippocampal imaging data, is described. RESULTS: We propose a three-hit model in which an early neurodevelopmental lesion renders the hippocampus vulnerable to further insult later in life during the transition phase to active illness. The available evidence suggests that the left hippocampus is particularly vulnerable during these early stages, while further insult involving the hippocampus bilaterally occurs in those who develop a chronic form of the illness. CONCLUSIONS: Intervention strategies should target the most vulnerable stages of the illness, in particular the transition phase to psychosis, when novel treatments may prevent the illness or ameliorate its effects.
Brain↗
Evaluating the importance of reducing the duration of untreated psychosis.
OBJECTIVE: The concept of duration of untreated psychosis or DUP has been a strong candidate for intervention as part of the early intervention paradigm. However, its importance has been questioned. This paper aims to present selected issues concerning attempts to reduce DUP and evaluate the impact of these attempts. METHOD: Current research designs are critiqued and alternatives considered. RESULTS: Evidence suggests that it is difficult to design studies that are both ethical and potent enough to determine the contribution of treatment delay to outcome. CONCLUSIONS: Further research is justified but this should not obstruct common-sense service reforms.
Cost of Illness↗