PubMed Health⌕ Search

Biomedical subjects

Patrick D McGorry

Publications and source records attributed to Patrick D McGorry.

At least 55 records · Page 3Linked to original sources

Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial.

OBJECTIVE: The first episode of psychotic illness is a key intervention point. The initial experience with medication can affect willingness to accept treatment. Further, relapse prevention is a treatment cornerstone during the first years of illness because active psychotic illness may affect lifetime outcomes. Thus, initial treatment of active symptoms and subsequent relapse prevention are central goals of pharmacotherapy. This study compared long-term effectiveness of risperidone versus haloperidol in first-episode psychosis patients. METHOD: First-episode psychosis patients (N=555, mean age=25.4 years) participated in a double-blind, randomized, controlled flexible-dose trial that compared risperidone (mean modal dose=3.3 mg) and haloperidol (mean modal dose=2.9 mg). The median treatment length was 206 days (maximum=1,514). RESULTS: Positive and Negative Syndrome Scale scores and Clinical Global Impression ratings improved significantly relative to baseline, with no significant differences between groups. Three-quarters of the patients achieved initial clinical improvement, defined as >20% reduction in total Positive and Negative Syndrome Scale score. However, among those who achieved clinical improvement, 42% of the risperidone group experienced a relapse compared with 55% of the haloperidol group. The median time to relapse was 466 days for risperidone-treated subjects and 205 days for those given haloperidol. These differences were statistically significant based on Kaplan-Meier survival analysis. Adverse effects distinguished the treatments: there were significantly more extrapyramidal signs and symptoms and adjunctive medication use in the haloperidol group and greater prolactin elevation in the risperidone group. There was less weight gain with haloperidol initially but no significant differences between groups at endpoint. CONCLUSIONS: Relatively low doses of antipsychotic drugs lead to significant symptom amelioration in the majority of first-episode psychosis patients. In the long term, risperidone prevents relapse in more patients and for a longer time and also induces less abnormal movements than haloperidol.

Adult↗

Early intervention in psychotic disorders: beyond debate to solving problems.

The challenges of early diagnosis are similar in psychiatry to the rest of medicine. For potentially severe and persistent disorders there is great value in early diagnosis, however, only under certain conditions. Early diagnosis would not be justified if there were no efficacious treatments or if such treatments provided earlier would do more harm than good for those exposed. There is growing evidence that earlier and sustained intervention improves at least short-term outcomes. However, early intervention may be iatrogenic where systems of care are poor in quality. One thing is clear, the general pattern of care is still "too little, too late" even in the most affluent countries. Consistent and extensive reform of health systems, with recognition of early intervention as an increasingly evidence-based "best buy", represents one of the key priorities in international mental health.

Humans↗

Prepsychotic phase of schizophrenia and related disorders: recent progress and future opportunities.

BACKGROUND: Clinical and research focus has recently shifted from established psychotic disorders to first-episode psychosis and the prepsychotic phase of illness. AIMS: To describe the principles, progress and dilemmas associated with the prospective detection, engagement and treatment of young people at risk of developing a psychotic disorder. METHOD: Strategies to identify young people at heightened risk of a psychotic disorder are described. Preventive interventions and results of their evaluation are provided. RESULTS: Well-validated criteria for identifying young people at heightened risk of psychosis have been developed, evidence of the efficacy of various psychological and pharmacological interventions in preventing progression has accumulated and progress towards the identification of clinical and neurobiological predictors of transition to acute psychosis has been made. CONCLUSIONS: The detection, monitoring and treatment of young people in the prepsychotic phase is a growth area in psychiatry. The ethical considerations about treatment options, treatment of minors and provision of information about risk status must be treated with sensitivity if the potential benefit to many young people and their families is to be realised.

Adolescent↗

Diagnostic stability 18 months after treatment initiation for first-episode psychosis.

OBJECTIVES: (1) Assessment of diagnostic stability of psychotic disorders or psychotic mood disorders from 6 weeks to 18 months after initiation of treatment in a representative first-episode psychosis (FEP) sample. (2) Comparison between those patients who shifted from DSM-IV schizophreniform disorder to schizophrenia or schizo-affective disorder and those whose diagnosis of schizophreniform disorder remained stable. METHOD: The Early Psychosis Prevention and Intervention Centre (EPPIC) in Australia admitted 786 FEP patients from January 1998 to December 2000. Data were collected from patients' medical records (MRs) using a standardized questionnaire. Seven hundred four MRs were available, 36 of which were excluded owing to nonpsychotic diagnoses or a psychotic disorder due to a general medical condition. Of the remaining 668 patients, 176 (26.3%) were lost to follow-up. Four hundred ninety-two subjects were analyzed. Strategies to assure validity and reliability of diagnoses were applied. RESULTS: The same diagnosis was made at baseline (< or = 6 weeks after admission into EPPIC) and 18 months for 69.9% of the patients. Among the most consistent diagnoses were schizophrenia (97.3%), schizoaffective disorder (94.1%), and bipolar disorder (83.2%); the least stable, as expected, was schizophreniform disorder (40.0%). In subjects with schizophreniform disorder at baseline, the best predictors of a shift from schizophreniform disorder to schizophrenia or schizoaffective disorder were a higher baseline Clinical Global Impressions-Severity of Illness scale score and lower premorbid Global Assessment of Functioning score, although the variance accounted for was small (R2 = .07). CONCLUSIONS: A longitudinally based diagnostic process in FEP samples is needed, especially in schizophreniform disorder and bipolar disorder. However, a thorough initial assessment of patient and family by a specialized team of investigators regarding the kind and duration of patient symptoms may lead to high diagnostic stability, especially in schizophrenia and schizoaffective disorder, even in a FEP sample with a relatively short duration of untreated psychosis.

Adult↗

Risk factors for psychosis in an ultra high-risk group: psychopathology and clinical features.

The identification of individuals at high risk of developing a psychotic disorder has long been a goal of clinicians because it is thought that early treatment of this group may prevent onset of the disorder. However, little is known of predictive factors of psychosis, even within a high-risk group. This study followed up 104 young people thought to be at 'ultra high risk' for schizophrenia and other psychotic disorders by virtue of having a family history of psychotic disorder combined with some functional decline or the presence of subthreshold or self-limiting psychotic symptoms. All subjects were therefore symptomatic, but not psychotic, at intake. Thirty-six subjects (34.6%) developed frank psychotic symptoms within 12 months. Measures of symptom duration, functioning, disability and psychopathology were made at intake, 6 and 12 months. Poor functioning, long duration of symptoms, high levels of depression and reduced attention were all predictors of psychosis. A combination of family history of psychosis, a recent significant decrease in functioning and recent experience of subthreshold psychotic symptoms was also predictive of psychosis. Combining highly predictive variables yielded a method of psychosis prediction at 12 months with good positive predictive value (80.8%), negative predictive value (81.8%) and specificity (92.6%) and moderate sensitivity (60.0%). Within our symptomatic high-risk group, therefore, it appears possible to identify those individuals who are at particularly high risk of developing a psychotic disorder such as schizophrenia. Given the very high PPV and low false positive rate with this two-step process, it may be justifiable to target these individuals for intensive monitoring of mental state and even low-dose neuroleptic medication or other biological and psychosocial treatments depending on clinical condition. This indicated prevention approach could be further developed and preventive strategies in the psychoses refined.

Adolescent↗

Early intervention in first-episode psychosis--the impact of a community development campaign.

OBJECTIVE: Substantial delays in providing access to treatment in first-episode psychosis have been well documented. The present study examines the impact of strategies aimed at improving access and reducing delays. METHOD: A pilot community education campaign was conducted with the aim of reducing the duration of untreated psychosis (DUP) in a geographically defined intervention sector located in the northwestern region of Melbourne, Australia. Utilising a quasi-experimental design, a comparison sector with similar demographics was selected from another part of the north-western region. A mobile early detection team and the same treatment system served both sectors. RESULTS: While there was no significant difference between the mean DUP for intervention and comparison sectors, the distributional features of DUP between the two regions were significantly different. In the intervention sector, disproportionately more cases with very long DUP were detected. When a small number of outliers were removed, the mean and median DUP in the intervention sector was reduced. CONCLUSION: These findings highlight the complexity of treatment access and delay and suggest that efforts to reduce DUP may have two effects, not one. Firstly, a different sample of cases is treated through the detection of hidden "long DUP" cases that otherwise may have remained untreated. Secondly, the DUP for the remainder may indeed be reduced. More research with larger samples and more potent campaign strategies is clearly required. It may also be worth considering whether there is a safe and ethical way to undertake a RCT of early versus delayed antipsychotic treatment to perhaps settle the DUP debate once and for all.

Adolescent↗

Schneiderian first rank symptoms predict poor outcome within first episode manic psychosis.

BACKGROUND: The validity of a sub-classification of affective psychosis according to the mood congruence of psychotic features has been questioned in the literature. While some authors have found a correlation between such symptoms and outcome, their predictive value was rather limited in these studies. METHOD: Prospective study of 108 subjects presenting with a first DSM-III-R manic episode with psychotic features to determine the frequency of different types of psychotic symptoms and to measure the predictive utility of mood incongruent psychotic symptoms (MIPS) and first-rank Schneiderian symptoms (FRSS) during the first episode for a 12-month outcome. Outcome was measured by the level of positive, negative, depressive symptoms, and psychosocial functioning. Duration of affective and psychotic symptoms was also assessed. RESULTS: Patients presented with a wide variety of psychotic symptoms. The presence of MIPS at baseline was significantly correlated with a longer persistence of psychotic symptoms, but not with poorer outcome at 12 months. By contrast, the presence of FRSS at baseline was significantly associated with earlier onset of psychosis as well as increased severity of negative symptoms and poorer psychosocial functioning after 12 months. CONCLUSION: The presence of FRSS during a first manic episode with psychotic features identifies a sub-group of patients with more severe presentation and poorer short-term outcome. These results question the prognostic utility of MIPS. LIMITATIONS: Despite the relatively large number of subjects compared with other studies, the statistical power to detect all but large effect sizes is limited by the sample size.

Adult↗

Pituitary volume in psychosis.

BACKGROUND: Patients with psychosis have activation of the hypothalamic-pituitary-adrenal (HPA) axis during the acute phase of the psychosis. Whether this has any morphological consequences for the pituitary gland is currently unknown. AIMS: To examine pituitary volume variation in people at different stages of psychotic disorder. METHOD: Pituitary volume was measured using 1.5 mm, coronal magnetic resonance images in 24 people with first-episode psychosis, 51 with established schizophrenia and 59 healthy controls. RESULTS: Compared with the control group, the people with first-episode psychosis had pituitary volumes that were 10% larger, whereas those with established schizophrenia had pituitary volumes that were 17% smaller. In both of the groups with psychosis, there was no difference in pituitary volume between those receiving typical antipsychotic drugs and those receiving atypical antipsychotics. CONCLUSIONS: The first episode of a psychosis is associated with a larger pituitary volume, which we suggest is due to activation of the HPA axis. The smaller pituitary volume in the group with established schizophrenia could be the consequence of repeated episodes of HPA axis hyperactivity.

Acute Disease↗

Two-year stability of personality disorder in older adolescent outpatients.

The 2-year stability of categorical and dimensional personality disorder (PD) in an older adolescent psychiatric outpatient sample was examined. One hundred and one 15-18-year-old participants were assessed using the Structured Clinical Interview for DSM Axis II Disorders (SCID-II) at baseline and 97 were re-interviewed, face-to-face, at 2 years. Of those with a categorical PD diagnosis at baseline, 74% still met criteria for a PD at follow-up, with marked gender differences (83% of females and 56% of males). Kappa for specific PDs was low for all except antisocial. Rank order and mean level dimensional stability ranged from high (antisocial, schizoid) to moderate (borderline, histrionic, schizotypal) to low (other PDs), with no decline in PD scores over the 2 years. There was no substantial influence upon stability of dimensional PD from the presence of Axis I disorder at baseline or from outpatient or inpatient treatment. However, categorical PD endured in 100% of those receiving inpatient care. The study supports that, in late teenage outpatients, the 2-year stability of the global category of PD is high and the stability of dimensionally rated PD appears to be similar to that found in young adults in a variety of settings, especially for some cluster A and B PDs. Diagnosis and early intervention appears to be justified in this age group.

Adolescent↗

Recovery style and outcome in first-episode psychosis.

Our study aimed to investigate how recovery styles influence 12-month clinical outcome in first-episode psychosis patients. We hypothesised that patients who use an integrative recovery style would have better outcome than those who seal over. A total of 196 first-episode psychosis patients from the Early Psychosis Intervention Centre (EPPIC) participated in the study. Each patient was interviewed at stabilization of their acute psychotic episode, and then again 12 months later, using an Integration/Sealing-over measure. Our results suggest that recovery style may be a useful predictor of outcome. Integrative patients had better outcome and functioning at 12 months. These results were influenced by diagnosis and, unlike previous studies, recovery style changed over time, suggesting it was not a stable trait. The capacity for recovery style to change challenges the suggestion it is a personality trait and raises the need for psychoeducation and other psychological interventions that could improve outcome.

Adolescent↗

Psychosis prediction: 12-month follow up of a high-risk ("prodromal") group.

Intervention in the prodromal phase of schizophrenia and related psychoses may result in attenuation, delay or even prevention of the onset of psychosis in some individuals. However, a "prodrome" is difficult to recognise prospectively because of its nonspecific symptoms. This study set out to recruit and follow up subjects at high risk of transition to psychosis with the aim of examining the predictive power for psychosis onset of certain mental state and illness variables.Symptomatic individuals with either a family history of psychotic disorder, schizotypal personality disorder, subthreshold psychotic symptoms or brief transient psychotic symptoms were assessed and followed up monthly for 12 months or until psychosis onset. Twenty of 49 subjects (40.8%) developed a psychotic disorder within 12 months. Some highly significant predictors of psychosis were found: long duration of prodromal symptoms, poor functioning at intake, low-grade psychotic symptoms, depression and disorganization. Combining some predictive variables yielded a strategy for psychosis prediction with good sensitivity (86%), specificity (91%) positive predictive value (80%) and negative predictive value (94%) within 6 months. This study illustrates that it is possible to recruit and follow up individuals at ultra high risk of developing psychosis within a relatively brief follow-up period. Despite low numbers some highly significant predictors of psychosis were found. The findings support the development of more specific preventive strategies targeting the prodromal phase for some individuals at ultra high risk of schizophrenia.

Adolescent↗

Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison.

BACKGROUND: Psychotic disorders, such as schizophrenia, are associated with neuroanatomical abnormalities, but whether these predate the onset of symptoms or develop progressively over the course of illness is unclear. We investigated this issue with MRI to study people with prodromal symptoms who are at ultra high-risk for the development of psychosis. METHODS: We did two comparisons, cross-sectional and longitudinal. For the cross-sectional comparison, 75 people with prodromal signs of psychosis were scanned with MRI. After at least 12 months of follow-up, 23 (31%) had developed psychosis and 52 (69%) had not. Baseline MRI data from these two subgroups were compared. For the longitudinal comparison, 21 of the ultra high-risk individuals were scanned again with MRI after at least 12 months. Ten of these had developed psychosis and 11 had not. MRI data from baseline and follow-up were compared within each group of people. FINDINGS: In the cross-sectional comparison, compared with people who did not develop psychosis, those who did develop the disorder had less grey matter in the right medial temporal, lateral temporal, and inferior frontal cortex, and in the cingulate cortex bilaterally. In the longitudinal comparison, when re-scanned, individuals who had developed psychosis showed a reduction in grey matter in the left parahippocampal, fusiform, orbitofrontal and cerebellar cortices, and the cingulate gyri. In those who had not become psychotic, longitudinal changes were restricted to the cerebellum. INTERPRETATION: Some of the grey-matter abnormalities associated with psychotic disorders predate the onset of frank symptoms, whereas others appear in association with their first expression.

Adult↗

The initial prodrome to bipolar affective disorder: prospective case studies.

BACKGROUND: The initial prodrome to bipolar disorder has received very little attention to date, with most of the available data only addressing the prodrome to relapse. This study presents several prospective case studies of the initial prodrome to bipolar affective disorder. METHODS: Three patients are presented who developed bipolar disorder during their treatment at the Personal Assessment and Crisis Evaluation Clinic (PACE). They were prospectively interviewed over a 12-month period using standard clinical research interviews. RESULTS: These patients met the criteria for bipolar disorder by the end of the treatment period. Depressive symptoms were the main reason for their first clinical presentation, with mania developing at a later date. Other comorbidities were observed before they were diagnosed with bipolar disorder. LIMITATIONS: The generalisability of our findings was constrained because of the small sample size. Furthermore, our findings are likely to be influenced by the intake criteria used at PACE, a clinic that primarily aims at identifying patients at risk of psychosis rather than bipolar disorder. CONCLUSION: Our study provides information about the initial prodrome to bipolar disorder, which has previously been neglected in research studies. We found there were no prodrome features that clearly distinguished between patients who go on to develop bipolar disorder and those who develop schizophrenia. We hope our prospective data will be the starting point for subsequent studies, with the aim of applying these findings to developing suitable preventative interventions for bipolar disorder.

Adolescent↗

Seasonality of symptom onset in first-episode schizophrenia.

BACKGROUND: There have been numerous reports of seasonal trends in psychotic illnesses. In schizophrenia, seasonal trends in incidence have been shown to be especially apparent in first-episode cases. Most previous research has used date of admission as a proxy for date of incidence of disorder; we present results of an investigation into seasonal trends in dates of onset of symptoms in a group of 295 first-episode cases of schizophrenia and schizophreniform disorder. METHOD: Data were analysed using statistical methods appropriate for detecting seasonal trends in pooled data over 6 years. RESULTS: Only male cases of schizophrenia and schizophreniform disorder showed a significant seasonal distribution to dates of onset of symptoms, with a peak in August (winter). CONCLUSION: True seasonal patterns are present in schizophrenia incidence, but their consistency with other published studies and wider significance, is difficult to ascertain because of different methods used in dating incidence of disorder.

Adolescent↗

Early intervention in psychosis: an overdue reform.

OBJECTIVE: To discuss the rationale for early intervention in psychotic disorders and to explore why the widespread implementation of early intervention services has stalled. METHOD: Four central questions are explored regarding early intervention in psychosis: (i) what is the rationale for early intervention services in psychosis and is it justified? (ii) what are the obstacles to the implementation of early intervention services throughout Australia? (iii) how could some of these obstacles be overcome? and (iv) what else needs to occur? RESULTS: Early intervention in psychosis aims to improve recognition and access, promote recovery from the initial psychotic episode, minimize secondary morbidity and reduce collateral damage. It may also prevent some brain dysfunction and damage, which may otherwise occur later in the illness. Despite the now growing body of evidence supporting the idea of early intervention, obstacles remain to its widespread adoption in policy and implementation, principally related to chronic under-funding of the public mental health system. Among the solutions proposed is the need to develop services with a youth focus, able to cater for young people with both psychotic and non-psychotic psychiatric disorders. These services should be well integrated with primary care and other youth orientated agencies. CONCLUSIONS: We are hopeful that strong investment in early intervention and better services for young people will be among the highest priorities of the Third National Mental Health Plan. This is not only where the greatest public health burden lies, but also where cost-effectiveness of intervention is likely to be maximal.

Adolescent↗

Early and late neurodevelopmental disturbances in schizophrenia and their functional consequences.

OBJECTIVE: The evidence from structural imaging studies supports the notion that schizophrenia arises from an early abnormality in brain development. In this paper we review the timing of structural changes in schizophrenia and argue that schizophrenia is a neuro-developmental disorder with limited progressive brain changes occurring during the evolution and early phase of psychosis. METHOD: The available cross-sectional and longitudinal studies are reviewed, along with data from our own research. RESULTS: The current literature, including our own data, suggests that structural brain changes are apparent premorbidly, consistent with a neurodevelopmental lesion. These are prominent in frontal and cingulate regions, and appear related to premorbid neuropsychological deficits in executive function. However, there appear to be additional brain changes over the transition to illness and beyond. CONCLUSIONS: We propose first, that an early neurodevelopmental insult interacts with either normal or abnormal postpubertal brain maturation to produce further (late neurodevelopmental) brain structural and functional changes; and second, that the effect of such neurodevelopmental lesions will have different consequences for functions that normally develop early in life, such as memory, compared with functions developing later, such as executive functions. A model is presented suggesting that the structural and functional abnormalities in schizophrenia can be understood as a consequence of the neurodevelopmental stage at which brain changes occur.

Brain↗

The "close-in" or ultra high-risk model: a safe and effective strategy for research and clinical intervention in prepsychotic mental disorder.

The development of a new frontier for research and early intervention in psychotic disorders is highly dependent on the construction of synergistic clinical infrastructures. This has catalyzed great progress in the recognition, enhanced treatment, and study of first episode psychosis, and the task is even more challenging when the boundaries are extended to include the earliest clinical phase of illness, the prodromal or prepsychotic phase. This article describes the conceptual and practical building blocks for the construction of service models for intervention in the postonset clinical phase prior to the attainment of current diagnostic thresholds. This is best regarded as indicated prevention, a form of very early secondary prevention, which involves a blend of immediate clinical care combined with research-oriented preventive intervention. The experience of the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne across several stages of growth is described and contrasted with that of several emerging centers in Europe and North America. The progress to date, the lessons learned, and the unresolved challenges and opportunities are detailed. It is concluded that service models can be developed that are acceptable and helpful to young people and their families, and that create a unique environment for the study of the transition to frank psychotic disorder. The ultimate clinical utility and general safety of this approach and the range of effective treatments remain unclear, and will be determined by more extensive research. Such research must be conducted in a logical and rigorous manner with the best designs possible, sensitive to input from consumers and caregivers and to ethical considerations.

Academies and Institutes↗