Major self-mutilation in the first episode of psychosis

Major self-mutilation (MSM) is a rare but catastrophic complication of severe mental illness. Most people who inflict MSM have a psychotic disorder, usually a schizophrenia spectrum psychosis. It is not known when in the course of psychotic illness, MSM is most likely to occur. In this study, the proportion of patients in first episode of psychosis (FEP) was assessed using the results of a systematic review of published case reports. Histories of patients who had removed an eye or a testicle, severed their penis, or amputated a portion of a limb and were diagnosed with a schizophrenia spectrum psychosis were included. A psychotic illness was documented in 143 of 189 cases (75.6%) of MSM, of whom 119 of 143 (83.2%) were diagnosed with a schizophrenia spectrum psychosis. The treatment status of a schizophrenia spectrum psychosis could be ascertained in 101 of the case reports, of which 54 were in the FEP (53.5%, 95% confidence interval = 43.7%-63.2%). Patients who inflict MSM in FEP exhibited similar symptoms to those who inflict MSM later in their illness. Acute psychosis, in particular first-episode schizophrenia, appears to be the major cause of MSM. Although MSM is extremely uncommon, earlier treatment of psychotic illness may reduce the incidence of MSM.     

Incidence and diagnostic diversity in first‐episode psychosis

Reay R, Mitford E, McCabe K, Paxton R, Turkington D. Incidence and diagnostic diversity in first‐episode psychosis. Objective: To investigate the incidence and range of diagnostic groups in patients with first‐episode psychosis (FEP) in a defined geographical area. Method: An observational database was set up on all patients aged 16 years and over presenting with FEP living in a county in Northern England between 1998 and 2005. Results: The incidence of all FEP was 30.95/100 000. The largest diagnostic groups were psychotic depression (19%) and acute and transient psychotic disorder (19%). Fifty‐four per cent of patients were aged 36 years and over. Patients with schizophrenia spectrum disorder only accounted for 55% of cases. Conclusion: This clinical database revealed marked diversity in age and diagnostic groups in FEP with implications for services and guidelines. These common presentations of psychoses are grossly under researched, and no treatment guidelines currently exist for them.     

Non-reduction in hippocampal volume is associated with higher risk of psychosis

Previous research using MRI scans has shown reduced hippocampal volumes in chronic schizophrenia and first-episode psychosis compared to well subjects. There are few MRI volumetric studies of high-risk cohorts and no studies that have compared structural measures between high-risk subjects who later developed a psychotic illness and those who did not. Therefore, the question of whether structural changes to the hippocampi precede the onset of an acute psychotic episode has not been answered.Hippocampal and whole brain volumes of 60 people at ultra high-risk (UHR) of developing a psychotic episode (identified through state and trait criteria) were obtained through MRI scan and compared with subjects with first episode psychosis (FEP: n=32), and no mental illness (n=139). Thirty-three percent (n=20) of the UHR cohort developed a psychotic disorder during the 12-month period following the MRI scan.The UHR group as a whole, like the FEP group, had significantly smaller left and right hippocampal volumes than the normal comparison group. Contrary to our initial hypothesis, the left hippocampal volume of the UHR subjects who developed a psychotic disorder was larger than the UHR-non-psychotic subgroup and the FEP group, but no differences were found between the UHR-psychotic and normal groups. The right hippocampus of the UHR-non-psychotic group was significantly smaller than the Normal group but not different to the FEP group. Furthermore, a larger left hippocampal volume of the UHR cohort at intake was associated with the subsequent development of acute psychosis rather than smaller volumes.These results contradicted the expected outcomes, which had been influenced by the neurodevelopmental model of the development of psychosis and an earlier study comparing hippocampal volumes of first episode, chronic schizophrenia and normal populations. One implication of these results is that a process of dynamic central nervous system change may occur during the onset phase of schizophrenia and related disorders, rather than earlier in life as suggested by the neurodevelopmental model. Alternatively, selection factors associated with the UHR cohort may have created a bias in the results. Replication of these results is required in other high-risk cohorts.     

The First‐Episode Psychosis Outcome Study: premorbid and baseline characteristics of an epidemiological cohort of 661 first‐episode psychosis patients

Aims: Studies conducted in first‐episode psychosis (FEP) samples avoid many biases. However, very few studies are based on epidemiological cohorts treated in specialized FEP services. The aim of this file audit study was to examine premorbid and baseline characteristics of a large epidemiological sample of FEP. Methods: File audit study of all patients admitted to the Early Psychosis Prevention and Intervention Centre between 1998 and 2000 using a specialized questionnaire. Results: There were 661 patient files included in the study. Premorbid evaluation revealed high rates of substance use disorder (74.1%), history of psychiatric disorder (47.5%), past traumatic events (82.7%) suicide attempts (14.3%) and family history of psychiatric illness (55.6%). Baseline characteristics revealed high intensity of illness (mean CGI 5.5), high prevalence of lack of insight (62%) and high rate of comorbidity (70%). Conclusion: High rates of traumatic events or episodes of mental illness before treatment for FEP must be considered when designing treatment approaches because a too narrow focus on positive psychotic symptoms will inevitably lead to incomplete treatment. Additionally, early intervention programmes need sufficient range of resources to address the multiple challenges presented by FEP patients such as high severity of illness, comorbidities and functional impairment. Finally, observation of an important degree of functional impairment despite short duration of untreated psychosis suggests that while early detection of FEP is a necessary step in early intervention, it may not be sufficient to improve functional recovery in psychosis and that efforts aimed at identifying people during the prodromal phase of psychotic disorders should be pursued.     

When things are not as they seem: detecting first‐episode psychosis upon referral to ultra high risk (‘prodromal’) clinics

The current paper examines a neglected function of ‘ultra high risk’ (UHR) clinics: to detect first‐episode psychosis (FEP) mistakenly identified as a prodrome. A clinical audit was conducted of referrals to a UHR service, the Personal Assessment and Crisis Evaluation Clinic, over a 12‐month period (April 2005–March 2006). In this audit, 11.4% of the total number of referrals (n= 149) and 11.9% of those who attended a first appointment were psychotic on referral. These figures indicate that a substantial proportion of individuals thought to be prodromal are in fact suffering FEP. UHR clinics minimize duration of untreated psychosis for FEP patients mistaken as prodromal.     

Clinical and sociodemographic comparison of people at high‐risk for psychosis and with first‐episode psychosis

Zimbrón J, Ruiz de Azúa S, Khandaker GM, Gandamaneni PK, Crane CM, González‐Pinto A, Stochl J, Jones PB, Pérez J. Clinical and sociodemographic comparison of people at high‐risk for psychosis and with first‐episode psychosis. Objective: To compare clinical and sociodemographic characteristics previously associated with psychosis, between individuals at high‐risk for psychosis (HR) and patients experiencing a first episode psychosis (FEP), to achieve a better understanding of factors associated with psychosis. Method: Cross‐sectional comparison of 30 individuals at HR with 30 age‐gender matched FEP, presenting to an early intervention service for psychosis. Participants were followed‐up for 2 years to establish the proportion of HR who made the transition into FEP. Results: Both groups showed similar socio‐clinical characteristics, including immigration status, employment history, marital status, family history of psychotic illness, self‐harm and alcohol and drug use. The HR group had a lower level of education, higher burden of trauma, earlier onset of psychiatric symptoms and a longer delay in accessing specialised services. A younger onset of symptoms was associated with a longer delay in accessing services in both groups. After a 2 year follow‐up, only three (10%) of the HR group made a transition into FEP. Conclusion: The similarities observed between individuals at HR and those with FEP suggest that known variables associated with psychosis may be equally prevalent in people at HR who do not develop a psychotic disorder.     

Sustained attention in young people at high risk of psychosis does not predict transition to psychosis

Early detection of imminent psychosis allows for the possibility of interventions to prevent onset, or to minimise severity and disability. It also has potential to enhance knowledge of the factors important in the etiology of psychotic illnesses. Neurocognitive deficits are well documented in psychotic illnesses and there is evidence to suggest that such deficits are present in individuals long before they develop the illness. Further, it has been proposed that such impairments may indicate an underlying predisposition to develop psychosis and may thus be described as 'vulnerability indicators'. This study aimed to investigate the proposed vulnerability indicator of impaired sustained attention in young people thought to be at ultra high-risk of developing psychosis imminently to see whether it would improve the prediction of psychosis in this group. The Continuous Performance Test - Identical Pairs (CPT-IP) version performance of an ultra high-risk group (UHR, N=70) was compared with that of a healthy comparison group (NC, N=51) and a first-episode psychosis group (FEP, N=32). The UHR group exhibited performance deficits compared to the NC group and performed at a level similar to that of the FEP group. However, within the UHR group, those who developed psychosis within the timeframe of the study did not differ from those who did not develop psychosis on their CPT-IP performance. These results support sustained attention as an indicator of vulnerability to psychosis, but suggest that CPT-IP performance does not help to predict transition to psychosis in an ultra high-risk group.     

Depression in first episode psychosis: The role of subordination and shame

Depression in early psychosis is linked to poor outcome, relapse and risk of suicide, yet remains poorly understood. This article aims to examine the development of depression in acute and post psychotic phases of first episode psychosis (FEP), and its relationship to persecutors, voices, insight, and recovery. Data were gathered on 92 patients with acute FEP on depression course, severity and experience of positive symptoms, insight and appraisals of illness using validated semi-structured interviews and questionnaires. Measures were repeated at 12 months. Malevolent voices, use of safety behaviours and subordination to persecutors were associated with depression and suicidal behaviour in acute FEP. Loss, Shame, low level continuing positive symptoms and longer duration of untreated psychosis were associated with post psychotic depression. Negative appraisals remained stable despite recovery in other symptom domains. Thus, depression and risk in early psychosis may be propagated by the personal significance and content of positive symptoms experienced. When in recovery, low level symptoms, longer period of illness and negative appraisals are significant factors.     

Insight in individuals with an At Risk Mental State

PURPOSE: On average, people with an At Risk Mental State (ARMS) for psychosis are more willing to seek and accept clinical help than patients with psychotic disorders, suggesting that insight in this group is relatively less impaired. We compared the level and quality of insight in the ARMS and in first episode psychosis. MATERIALS AND METHODS: Insight about illness was assessed in subjects with an ARMS and in patients with first episode psychosis (FEP) who were and were not help-seeking, using the Schedule for Assessment of Insight (SAI-E). RESULTS: Insight was impaired in ARMS subjects, but there was considerable variability in the insight displayed between subjects. Compared to FEP subjects, ARMS subjects showed greater insight, particularly with respect to Symptom Relabelling. ARMS subjects were more likely to interpret anomalous experiences as symptoms of illness, and to perceive themselves as needing treatment. CONCLUSIONS: Insight in people at high risk for psychosis is impaired, despite the fact that they are help-seeking. Insight varies between subjects, highlighting the need to comprehensively assess all aspects of insight in those with an ARMS. ARMS subjects are impaired in their ability to appraise anomalous experiences as symptoms of illness, but much less impaired than FEP subjects. This is consistent with cognitive models that propose that the way symptoms are appraised determines whether the individual develops a psychotic illness.     

Self-inflicted eye injuries in first-episode and previously treated psychosis

The purpose of the present paper was to describe the circumstances and phenomenology of patients who remove or pierce their eyes or orbits during psychotic illness. In particular, the aim was to determine if patients in their first-episode psychosis (FEP) carry an increased risk of self-inflicted eye injury when compared to patients with previously treated psychosis (PTP). Data were extracted from all of the case reports published in English since 1960 and from two unpublished Australian cases. More than half of the cases of self-inflicted eye injury that resulted in permanent loss of vision occurred during FEP. Serious self-inflicted eye injuries are rare, but the risk appears to be greatest during FEP. Earlier treatment of emerging psychosis and close attention to patients who attempt to injure their eyes may occasionally prevent blindness.     

A qualitative study exploring personal recovery meaning and the potential influence of clinical recovery status on this meaning 20 years after a first-episode psychosis

Purpose

Long-term data on recovery conceptualisation in psychotic illness are needed to support mental health services to organise themselves according to recovery-oriented frameworks. To our knowledge, no previous research has investigated how first-episode psychosis (FEP) service users (sampled across psychotic illness type) perceive recovery beyond 5 years after diagnosis. We aimed to explore personal recovery meaning with individuals 20 years after their FEP and examine the potential influence of clinical recovery status on how they defined recovery (i.e. personal recovery).

Methods

Twenty participants were purposefully sampled from an epidemiologically representative FEP incidence cohort. At 20-year follow-up, semi-structured interviews were conducted with 10 cohort members who met full ‘functional recovery criteria’ (Clinically Recovered Group) and 10 who did not (Not Clinically Recovered Group). A thematic analysis was performed to develop shared themes and group-specific sub-themes to capture agreement and divergence between groups.

Results

Five shared themes were produced: pursuing balance in conflict, generating meaning in life, experiencing a dynamic personal relationship with time, redressing inequality while managing added challenges/vulnerability, and directing life from resilience to flourishing. The five group-specific sub-themes developed illuminate differences in the meaning ascribed to personal recovery by each group.

Conclusion

Findings emphasise the role of time in how personal recovery is conceptualised by service users and identify ways clinical recovery may influence personal recovery meaning in FEP at mid-later life. Mental health services failing to consider temporal changes in meaning-making and discounting clinical recovery risk ignoring key factors affecting personal recovery.

     

Suicidality prior to presentation in first-episode psychosis

Introduction: Suicide and attempted suicide contribute significantly to the increased mortality and morbidity associated with psychotic illness. The period of highest risk is reportedly in the early years of illness. While the literature concentrates on completed suicide in chronic psychosis, less is understood about attempted suicide in first‐episode psychosis (FEP). Aim: We aimed to examine rates and correlates of suicide attempts in individuals with FEP. Method: Individuals in this study were all those, both in‐ and outpatients, diagnosed with FEP over a 2‐year period, from a defined catchment area. Assessment included Structured Clinical Interview for DSM‐IV, Schedule for Assessment of Positive Symptoms, Schedule for Assessment of Negative Symptoms, Calgary Scale, Beiser Scale and Birchwood Insight Scale. Results: Of 107 patients with FEP, 50 (47%) individuals reported suicidal ideation: 41 (38%) in the month prior to first presentation. Ten individuals (9%) made a suicide attempt. The only factor significantly associated with previous suicide attempt was higher insight scores at first presentation (P = 0.04). Conclusion: Individuals with a history of suicide attempt tend to have higher insight into having a mental illness at first presentation.     

Social Deprivation,Inequality, and the Neighborhood-Level Incidence of Psychotic Syndromes in East London

Although urban birth, upbringing, and living are associated with increased risk of nonaffective psychotic disorders, few studies have used appropriate multilevel techniques accounting for spatial dependency in risk to investigate social, economic, or physical determinants of psychosis incidence. We adopted Bayesian hierarchical modeling to investigate the sociospatial distribution of psychosis risk in East London for DSM-IV nonaffective and affective psychotic disorders, ascertained over a 2-year period in the East London first-episode psychosis study. We included individual and environmental data on 427 subjects experiencing first-episode psychosis to estimate the incidence of disorder across 56 neighborhoods, having standardized for age, sex, ethnicity, and socioeconomic status. A Bayesian model that included spatially structured neighborhood-level random effects identified substantial unexplained variation in nonaffective psychosis risk after controlling for individual-level factors. This variation was independently associated with greater levels of neighborhood income inequality (SD increase in inequality: Bayesian relative risks [RR]: 1.25; 95% CI: 1.04–1.49), absolute deprivation (RR: 1.28; 95% CI: 1.08–1.51) and population density (RR: 1.18; 95% CI: 1.00–1.41). Neighborhood ethnic composition effects were associated with incidence of nonaffective psychosis for people of black Caribbean and black African origin. No variation in the spatial distribution of the affective psychoses was identified, consistent with the possibility of differing etiological origins of affective and nonaffective psychoses. Our data suggest that both absolute and relative measures of neighborhood social composition are associated with the incidence of nonaffective psychosis. We suggest these associations are consistent with a role for social stressors in psychosis risk, particularly when people live in more unequal communities.Key words: psychosis, epidemiology, urban, social environment, inequality, deprivation, Bayesian modeling, schizophrenia     

Group cognitive behavioural therapy as a treatment for negative symptoms in first-episode psychosis

Aim: We aimed to test the idea that there is an early critical time period during a psychotic illness when patients may be more responsive to psychological treatment attention. Methods: We tested this hypothesis by comparing the treatment responsiveness to group cognitive behavioural therapy (CBT) of 25 first‐episode psychosis participants (FEP) and 15 patients with currently stable psychosis (n = 40). Results: Following 12 sessions of outpatient‐based group CBT, there were significant decreases in positive, depressive and anxiety symptoms, and an improvement in quality of life for both groups. However, negative symptoms only improved in the FEP group. Conclusion: Considering the pernicious nature of negative symptoms as well as the difficulties in treating them, this study provides some support for the concept of early intervention with CBT.     

A public early intervention approach to first-episode psychosis: Treated incidence over 7 years in the Emilia-Romagna region

Aim

To estimate the treated incidence of individuals with first-episode psychosis (FEP) who contacted the Emilia-Romagna public mental healthcare system (Italy); to examine the variability of incidence and user characteristics across centres and years.

Methods

We computed the raw treated incidence in 2013–2019, based on FEP users aged 18–35, seen within or outside the regional program for FEP. We modelled FEP incidence across 10 catchment areas and 7 years using Bayesian Poisson and Negative Binomial Generalized Linear Models of varying complexity. We explored associations between user characteristics, study centre and year comparing variables and socioclinical clusters of subjects.

Results

Thousand three hundred and eighteen individuals were treated for FEP (raw incidence: 25.3 / 100.000 inhabitant year, IQR: 15.3). A Negative Binomial location-scale model with area, population density and year as predictors found that incidence and its variability changed across centres (Bologna: 36.55; 95% CrI: 30.39–43.86; Imola: 3.07; 95% CrI: 1.61–4.99) but did not follow linear temporal trends or density. Centers were associated with different user age, gender, migrant status, occupation, living conditions and cluster distribution. Year was associated negatively with HoNOS score (R = −0.09, p < .001), duration of untreated psychosis (R = −0.12, p < .001) and referral type.

Conclusions

The Emilia-Romagna region presents a relatively high but variable incidence of FEP across areas, but not in time. More granular information on social, ethnic and cultural factors may increase the level of explanation and prediction of FEP incidence and characteristics, shedding light on social and healthcare factors influencing FEP.     

Formal thought disorder in first-episode psychosis

Formal thought disorder (FTD) is one of the fundamental symptom clusters of schizophrenia and it was found to be the strongest predictor determining conversion from first-episode acute transient psychotic disorder to schizophrenia. Our goal in the present study was to compare a first-episode psychosis (FEP) sample to a healthy control group in relation to subtypes of FTD. Fifty six patients aged between 15 and 45 years with FEP and forty five control subjects were included in the study. All the patients were under medication for less than six weeks or drug-naive. FTD was assessed using the Thought and Language Index (TLI), which is composed of impoverishment of thought and disorganization of thought subscales. FEP patients showed significantly higher scores on the items of poverty of speech, weakening of goal, perseveration, looseness, peculiar word use, peculiar sentence construction and peculiar logic compared to controls. Poverty of speech, perseveration and peculiar word use were the significant factors differentiating FEP patients from controls when controlling for years of education, family history of psychosis and drug abuse.     

Cognitive functioning in young people with first episode psychosis: relationship to diagnosis and clinical characteristics

OBJECTIVE: To examine the extent and nature of neuropsychological deficits in adolescents and young people with first episode psychosis (FEP), and to determine whether the pattern and extent of neuropsychological deficits varied according to diagnosis. METHOD: A total of 83 FEP subjects aged 13-25 years, and 31 healthy controls completed a comprehensive battery of neuropsychological tests, grouped into 10 cognitive domains. First episode psychosis subjects were stratified into three diagnostic groups (schizophrenia, affective disorders, substance-induced psychosis) and differences in cognitive profiles were examined. The contribution of demographic and clinical characteristics to cognitive performance was also explored. RESULTS: The schizophrenia group demonstrated significantly worse performance on tasks of verbal learning and memory than the affective disorders group. Compared to healthy controls, the schizophrenia group also demonstrated global impairment across the majority of cognitive domains. The substance-induced group's performance lay between that of the schizophrenia and affective disorders groups. Analyses of differential deficits revealed that verbal learning, verbal memory and current intellectual functioning were selectively impaired in the schizophrenia group, whereas the affective disorders group demonstrated a selective deficit in speeded processing. Premorbid intellectual functioning, negative symptomatology and medication levels were the strongest predictors of cognitive performance in FEP subjects. CONCLUSIONS: Verbal memory deficits differentiate individuals with schizophrenia from those with psychotic affective disorders. Although significant cognitive deficits are evident across all diagnostic FEP groups, individuals with schizophrenia appear to have more generalized impairment across a broad array of cognitive functions than other psychotic diagnoses. Lower premorbid intellectual functioning does not appear to contribute to greater cognitive deterioration following onset of psychosis, but severity of illness may be a more important factor than levels of mood disturbance.     

Timing,Distribution, and Relationship Between Nonpsychotic and Subthreshold Psychotic Symptoms Prior to Emergence of a First Episode of Psychosis

Prospective population studies suggest that psychotic syndromes may be an emergent phenomenon—a function of severity and complexity of more common mental health presentations and their nonpsychotic symptoms. Examining the relationship between nonpsychotic and subthreshold psychotic symptoms in individuals who later developed the ultimate outcome of interest, a first episode of psychosis (FEP), could provide valuable data to support or refute this conceptualization of how psychosis develops. We therefore conducted a detailed follow-back study consisting of semistructured interviews with 430 patients and families supplemented by chart reviews in a catchment-based sample of affective and nonaffective FEP. The onset and sequence of 27 pre-onset nonpsychotic (NPS) or subthreshold psychotic (STPS) symptoms was systematically characterized. Differences in proportions were analyzed with z-tests, and correlations were assessed with negative binomial regressions. Both the first psychiatric symptom (86.24% NPS) and the first prodromal symptom (66.51% NPS) were more likely to be NPS than STPS. Patients reporting pre-onset STPS had proportionally more of each NPS than did those without pre-onset STPS. Finally, there was a strong positive correlation between NPS counts (reflecting complexity) and STPS counts (β = 0.34, 95% CI [0.31, 0.38], P < 2 e-16). Prior to a FEP, NPS precede STPS, and greater complexity of NPS is associated with the presence and frequency of STPS. These findings complement recent arguments that the emergence of psychotic illness is better conceptualized as part of a continuum—with implications for understanding pluripotential developmental trajectories and strengthening early intervention paradigms.     

Duration of untreated psychotic illness

BACKGROUND: A lengthy delay often exists between the onset of psychotic symptoms and the start of appropriate treatment. However, the causes of this long delay remain poorly understood, and there is a need to search for the factors involved in such a delay in order to reduce the time of untreated psychosis. This study aimed at examining the influence of premorbid social networks on the duration of untreated psychotic illness. METHOD: One hundred subjects with a first episode of schizophrenia or related psychotic disorders never treated with antipsychotics made up the study sample. Social support was assessed by means of the Sturtees's social support scale that comprises two subscales measuring close and diffuse social support. Duration of untreated illness was assessed according to three definitions: duration of untreated unspecific symptoms, duration of untreated psychotic symptoms, and duration of untreated continuous psychotic symptoms. We also examined the effect of putative confounding factors such as gender, residence (urban-rural), age at illness onset, years of education, and parental socio-economic status. RESULTS : Correlational analysis showed that poor diffuse social support, but not poor close social support, predicted long duration of untreated illness according to the three definitions; this association being mainly due to poor work/academic support. Logistic regression analysis confirmed such an association, but it was limited to duration of continuous psychotic symptoms (unadjusted OR=3.44, 95% CI=1.51-7.83); this association persisted after adjusting for the confounding variables (adjusted OR=3.39, 95% CI=1.39-8.29). We also found that subjects with low socio-economic status were depending on the definition of duration of untreated illness considered, between 2.7 and 4.3 times more likely to present with a long duration of untreated illness. CONCLUSION : Both poor diffuse social support and a low socio-economic status seem to be relevant factors of a prolonged duration of untreated psychosis.     

Neuroimaging and emerging psychotic disorders: the Melbourne ultra-high risk studies

Although the underlying neurobiology of emerging psychotic disorders is not well understood, evidence from structural imaging and other studies support the notion that schizophrenia arises as a consequence of both an 'early neurodevelopmental' disturbance, as well as 'late neurodevelopmental' changes occurring during the initial stages of a psychotic illness, including around the time of transition to illness. In line with this, our longitudinal MRI findings in individuals at ultra-high risk for developing a psychotic illness show that there are excessive neuroanatomical changes in those who convert to psychosis. These aberrant changes are observed most prominently in medial temporal and prefrontal lobe regions. In a further series of longitudinal studies in first-episode psychosis, we have identified changes in prefrontal regions that indicate an accelerated loss of grey matter in patients compared to healthy control subjects. We suggest that the available evidence is consistent with the presence of subtle regionally and temporally specific neurobiological changes through the course of psychosis (Pantelis et al., 2005), including: (1) evidence for early (pre- and peri-natal) neurodevelopmental anomalies, (2) evidence for progressive grey matter loss involving medial temporal and orbital prefrontal regions around the time of transition to illness, and (3) evidence of late (post-pubertal) neurodevelopmental changes soon after the onset of psychosis, involving an acceleration of normal brain maturational processes, associated with significant loss of grey matter in dorsal prefrontal regions. The pathological processes underlying such changes remain unclear and may reflect anomalies in genetic and/or other endogenous mechanisms responsible for brain maturation, the adverse effects of intense or prolonged stress, or other environmental factors. These findings suggest that early markers of impending illness may prove difficult to define, and that brain changes in psychosis may better be conceptualized as anomalous trajectories of brain development. Further, active changes during transition to illness may present the potential to intervene and ameliorate these changes with potential benefit clinically.