Correlates of substance use in a large naturalistic cohort of young people with early and emerging psychosis.

BACKGROUND: Substance use remains a barrier to recovery for young people accessing early intervention services for psychosis. While correlates of use have been explored in populations experiencing a first episode of psychosis (FEP), sample sizes have been small and less research assesses cohorts at ultrahigh risk of psychosis (UHR). METHODS: This study uses data from a naturalistic cohort including UHR and FEP participants (N = 1252) to elucidate clinical correlates of use in the past 3 months of any illicit substance, amphetamine-type stimulants (ATS), cannabis, and tobacco. Moreover, network analysis based on use of these substances and additionally alcohol, cocaine, hallucinogens, sedatives, inhalants, and opioids was completed. RESULTS: Young people with FEP used substances at significantly higher rates than those at UHR. High concurrence of use was seen between substances. In the FEP group, participants who had used any illicit substance, ATS, and/or tobacco had increased positive symptoms and decreased negative symptoms. Young people with FEP who used cannabis had increased positive symptoms. In the UHR group, participants who had used any illicit substance, ATS, and/or cannabis in the past 3 months showed decreased negative symptoms compared to those who had not. CONCLUSION: A distinct clinical picture of more florid positive symptoms and alleviated negative symptoms seen in those who use substances in the FEP group appears muted in the UHR cohort. Treating young people at UHR in early intervention services represents the earliest opportunity to address substance use early to improve outcomes.

Social inclusion, intersectionality, and profiles of vulnerable groups of young people seeking mental health support.

BACKGROUND: headspace centres provide enhanced primary mental healthcare for young people. A priority is to provide services for all young people irrespective of a range of social disadvantages or social exclusion. The aims of this study were to: (i) delineate extent of social inclusion across domains of housing, studying/employment, functioning, alcohol, and other drug use; and (ii) map profiles of young people deemed vulnerable to experiencing additional barriers to accessing services based on their social inclusion domains (e.g., those living in unstable housing, not in employment/education, and/or experiencing intersecting or multiple forms of disadvantage or difficulties), including detailing their clinical characteristics. METHODS: Young people were recruited from five headspace centres. Data relevant to social inclusion were examined. Multivariate logistic regression models were used to determine overlap between vulnerable groups, functional, social, clinical, and behavioural factors. RESULTS: 1107 young people participated, aged 12-25 years (M = 18.1 years, SD = 3.3), most living in stable housing (96.5%) and engaged in studying/employment (84.8%). Specific vulnerabilities were evident in young people with NEET status (15.2%); in unstable accommodation (3.5%); of culturally diverse backgrounds (CALD) (12.2%); living in regional areas (36.1%); and identifying as lesbian, gay, bisexual, transgender, intersex, queer/questioning, and asexual plus (LGBTIQA+; 28.2%). Higher levels of distress, substance use, functional impairment, and lower social support were reported by those who were NEET and/or in unstable housing. LGBTIQA+ status was associated with high distress, depressive symptoms, and suicidal ideation. CONCLUSIONS: Most participants reported good social support, stable housing, and engagement in work or education. Those deemed vulnerable were likely to experience social exclusion across multiple domains and reported more mental health problems. The co-occurrence of mental ill-health and social exclusion highlights the importance of integrated mental healthcare.

Clinical and functional characteristics of a subsample of young people presenting for primary mental healthcare at headspace services across Australia.

PURPOSE: Headspace services provide treatment options to young people seeking mental healthcare. To obtain a better understanding of needs and characteristics of this population, and effectively evaluate services, we require novel youth-specific outcome measures. As part of our broad research program to establish such measures, a sample of young people were recruited and assessed. The study describes (i) methodology used to obtain clinical, functioning, and substance use characteristics of young people presenting to headspace services; and (ii) an overview of these characteristics. METHODS: Young people presenting to headspace centres were recruited. Multidimensional information was obtained relating to clinical and functional outcomes, demographic information, and lifestyle factors. RESULTS: 1107 young help-seeking individuals were recruited. Participants were most likely young adults aged M = 18.1 years, SD = 3.3, with diagnoses of depression and/or anxiety (76.6%, n = 801), engaged in work and study (84.9%, n = 890), and living with parent(s) (68.9%, n = 736). Impairments in functioning were moderate as indicated by the Social and Occupational Functioning Assessment Scale (M = 65.2, SD = 9.5), substance use was common (alcohol 62.7%, n = 665; illicit substances 30.5%, n = 324), and current suicidal ideation was reported by a third (33.6%, n = 358). CONCLUSIONS: A broad dataset was obtained providing an insight into key clinical, functional and quality of life characteristics of these individuals. We observed that young people present with complex problems, comorbid diagnoses, moderate levels of symptomatology, impairments in functioning, substance use, and suicidal ideation. This work provides the foundation for our broader research program aiming to develop novel, relevant and youth-specific, change and outcome measures.

Migrant status and identification as ultra-high risk for psychosis and transitioning to a psychotic disorder.

BACKGROUND: Certain migrant groups are more likely to develop a psychotic disorder compared to the native-born populations, and a younger age at migration is associated with greater risk. However, it is not known at which stage migration has an effect on the development of psychotic disorders. We examined whether migrants were more likely to be identified as ultra-high risk for psychosis (UHR) compared to native-born young people and whether migrant status was associated with the risk of transition to a full-threshold psychotic disorder. METHODS: The cohort included all young people aged 15-24 who were identified as UHR at a specialist clinic over a five-year period (2012-16). Australian census data were used to obtain the at-risk population. Poisson regression was used to calculate rate ratios and Cox regression analysis determined hazard ratios. RESULTS: 467 young people were identified as UHR, of which 13.5% (n = 63) were born overseas. First-generation migrants were 2.6-fold less likely to be identified as UHR compared to Australian-born young people (IRR = 0.39, 95% CI [0.30, 0.51], P < 0.001). There was no difference between migrant and native-born young people in their risk of transitioning to a psychotic disorder (HR = 0.90, 95% CI [0.39, 2.08], P = 0.81). CONCLUSIONS: UHR first-generation migrants may be under-accessing mental health services.

The neurophenomenology of early psychosis: An integrative empirical study.

BACKGROUND: The integration of various domains or levels of analysis (clinical, neurobiological, genetic, etc.) has been a challenge in schizophrenia research. A promising approach is to use the core phenomenological features of the disorder as an organising principle for other levels of analysis. Minimal self-disturbance (fragility in implicit first-person perspective, presence and agency) is emerging as a strong candidate to play this role. This approach was adopted in a previously described theoretical neurophenomenological model that proposed that source monitoring deficits and aberrant salience may be neurocognitive/neurobiological processes that correlate with minimal self-disturbance on the phenomenological level, together playing an aetiological role in the onset of schizophrenia spectrum disorders. The current paper presents full cross-sectional data from the first empirical test of this model. METHODS: Fifty ultra-high risk for psychosis patients, 39 first episode psychosis patients and 34 healthy controls were assessed with a variety of clinical measures, including the Examination of Anomalous Self-Experience (EASE), and neurocognitive and neurophysiological (EEG) measures of source monitoring deficits and aberrant salience. RESULTS: Linear regression indicated that source monitoring (composite score across neurocognitive and neurophysiological measures), with study group as an interaction term, explained 39.8% of the variance in EASE scores (R2 = 0.41, F(3,85) = 14.78, p < 0.001), whereas aberrant salience (composite score) explained only 6% of the variance in EASE scores (R2 = 0.06, F(3,85) = 1.44, p = 0.93). Aberrant salience measures were more strongly related to general psychopathology measures, particularly to positive psychotic symptoms, than to EASE scores. DISCUSSION: A neurophenomenological model of minimal self-disturbance in schizophrenia spectrum disorders may need to be expanded from source monitoring deficits to encompass other relevant constructs such as temporal processing, intermodal/multisensory integration, and hierarchical predictive processing. The cross-sectional data reported here will be expanded with longitudinal analysis in subsequent reports. These data and other related recent research show an emerging picture of neuro-features of core phenomenological aspects of schizophrenia spectrum disorders beyond surface-level psychotic symptoms.

Awareness of headspace youth mental health service centres across Australian communities between 2008 and 2015.

Background: Two common barriers to help-seeking are lack of awareness of appropriate services, and low mental health literacy. The headspace awareness campaigns are designed to address these factors.Aims: To examine whether distance from a headspace centre affects community awareness of headspace, and whether general awareness of headspace changed between 2008 and 2015.Method: Responses from 4707 participants aged 12-25 years, collected in 2008 and 2015, were analysed. The effect of headspace centre location on awareness of services was assessed by comparing awareness between those living in headspace areas (within 20 km of a centre) and those who were not. Change in awareness between 2008 and 2015 was assessed.Results: Awareness of headspace and its services was significantly greater among those living in headspace areas than among those living further away. Within headspace areas, awareness increased by 27% between 2008 and 2015. Prompted and unprompted awareness were significantly greater in 2015 than in 2008.Conclusions: Awareness of headspace has increased over time; however, innovative awareness campaigns are needed for those residing in non-headspace areas. Continued funding to increase headspace's national coverage, improving mental health literacy and service access for youth and their families, particularly those living in non-headspace areas, is needed.

Duration of untreated psychosis and neurocognitive functioning in first-episode psychosis: a systematic review and meta-analysis.

BACKGROUND: Previous reviews suggest there is minimal evidence for an association between duration of untreated psychosis (DUP) and neurocognition. This is based on tallied findings of studies with small samples and neurocognition viewed as a single construct. We aimed to conduct a systematic review and meta-analysis examining the association between DUP and individual neurocognitive domains and tests in first-episode psychosis (FEP). METHOD: MOOSE and PRISMA guidelines were followed. Forty-three studies involving 4647 FEP patients were included. For studies providing correlations between DUP and neurocognition, 12 separate meta-analyses were performed based on neurocognitive domains/indices. The influence of demographic/clinical variables was tested using weighted linear meta-regression analyses. RESULTS: The relationship between DUP and most neurocognitive domains/indices was not significant. Longer DUP was associated with a larger cognitive deterioration index, i.e. current minus premorbid intellectual functioning (N = 4; mean ES -0.213, 95% confidence interval (CI) (-0.344 to -0.074), p = 0.003). Findings were homogeneous, with no evidence of publication bias or significant influence from moderators. For studies providing mean and standard deviations for neurocognitive measures and DUP, 20 meta-regressions were performed on individual neurocognitive tests. One significant finding emerged showing that longer DUP was associated with fewer Wisconsin Card Sorting Test-perseverative errors (mean ES -0.031, 95% CI (-0.048 to -0.013), p < 0.001). Exploratory meta-regressions in studies with mean DUP <360 days showed longer DUP was significantly associated with poorer performance on Trail Making Test A and B and higher Full-Scale IQ. CONCLUSION: There may not be a generalised association between DUP and neurocognition, however, specific cognitive functions may be associated with longer DUP or delayed help-seeking.

Deterioration of visuospatial associative memory following a first psychotic episode: a long-term follow-up study.

BACKGROUND: Cognitive deficits are a core feature of schizophrenia, and impairments in most domains are thought to be stable over the course of the illness. However, cross-sectional evidence indicates that some areas of cognition, such as visuospatial associative memory, may be preserved in the early stages of psychosis, but become impaired in later established illness stages. This longitudinal study investigated change in visuospatial and verbal associative memory following psychosis onset. METHODS: In total 95 first-episode psychosis (FEP) patients and 63 healthy controls (HC) were assessed on neuropsychological tests at baseline, with 38 FEP and 22 HCs returning for follow-up assessment at 5-11 years. Visuospatial associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery Visuospatial Paired-Associate Learning task, and verbal associative memory was assessed using Verbal Paired Associates subtest of the Wechsler Memory Scale - Revised. RESULTS: Visuospatial and verbal associative memory at baseline did not differ significantly between FEP patients and HCs. However, over follow-up, visuospatial associative memory deteriorated significantly for the FEP group, relative to healthy individuals. Conversely, verbal associative memory improved to a similar degree observed in HCs. In the FEP cohort, visuospatial (but not verbal) associative memory ability at baseline was associated with functional outcome at follow-up. CONCLUSIONS: Areas of cognition that develop prior to psychosis onset, such as visuospatial and verbal associative memory, may be preserved early in the illness. Later deterioration in visuospatial memory ability may relate to progressive structural and functional brain abnormalities that occurs following psychosis onset.

Lithium suppression of tau induces brain iron accumulation and neurodegeneration.

Lithium is a first-line therapy for bipolar affective disorder. However, various adverse effects, including a Parkinson-like hand tremor, often limit its use. The understanding of the neurobiological basis of these side effects is still very limited. Nigral iron elevation is also a feature of Parkinsonian degeneration that may be related to soluble tau reduction. We found that magnetic resonance imaging T2 relaxation time changes in subjects commenced on lithium therapy were consistent with iron elevation. In mice, lithium treatment lowers brain tau levels and increases nigral and cortical iron elevation that is closely associated with neurodegeneration, cognitive loss and parkinsonian features. In neuronal cultures lithium attenuates iron efflux by lowering tau protein that traffics amyloid precursor protein to facilitate iron efflux. Thus, tau- and amyloid protein precursor-knockout mice were protected against lithium-induced iron elevation and neurotoxicity. These findings challenge the appropriateness of lithium as a potential treatment for disorders where brain iron is elevated (for example, Alzheimer's disease), and may explain lithium-associated motor symptoms in susceptible patients.

Cannabis-induced attenuated psychotic symptoms: implications for prognosis in young people at ultra-high risk for psychosis.

BACKGROUND: Cannabis use shows a robust dose-dependent relationship with psychosis risk among the general population. Despite this, it has been difficult to link cannabis use with risk for transitioning to a psychotic disorder among individuals at ultra-high risk (UHR) for psychosis. The present study examined UHR transition risk as a function of cannabis use characteristics which vary substantially between individuals including age of first use, cannabis abuse severity and a history of cannabis-induced attenuated psychotic symptoms (APS). METHOD: Participants were 190 UHR individuals (76 males) recruited at entry to treatment between 2000 and 2006. They completed a comprehensive baseline assessment including a survey of cannabis use characteristics during the period of heaviest use. Outcome was transition to a psychotic disorder, with mean time to follow-up of 5.0 years (range 2.4-8.7 years). RESULTS: A history of cannabis abuse was reported in 58% of the sample. Of these, 26% reported a history of cannabis-induced APS. These individuals were 4.90 (95% confidence interval 1.93-12.44) times more likely to transition to a psychotic disorder (p = 0.001). Greater severity of cannabis abuse also predicted transition to psychosis (p = 0.036). However, this effect was mediated by higher abuse severity among individuals with a history of cannabis-induced APS. CONCLUSIONS: Findings suggest that cannabis use poses risk in a subpopulation of UHR individuals who manifest cannabis-induced APS. Whether this reflects underlying genetic vulnerability requires further study. Nevertheless, findings reveal an important early marker of risk with potentially significant prognostic utility for UHR individuals.

White matter connectivity disruptions in early and chronic schizophrenia.

BACKGROUND: White matter disruptions in schizophrenia have been widely reported, but it remains unclear whether these abnormalities differ between illness stages. We mapped the connectome in patients with recently diagnosed and chronic schizophrenia and investigated the extent and overlap of white matter connectivity disruptions between these illness stages. METHODS: Diffusion-weighted magnetic resonance images were acquired in recent-onset (n = 19) and chronic patients (n = 45) with schizophrenia, as well as age-matched controls (n = 87). Whole-brain fiber tracking was performed to quantify the strength of white matter connections. Connections were tested for significant streamline count reductions in recent-onset and chronic groups, relative to separate age-matched controls. Permutation tests were used to assess whether disrupted connections significantly overlapped between chronic and recent-onset patients. Linear regression was performed to test whether connectivity was strongest in controls, weakest in chronic patients, and midway between these extremities in recent-onset patients (controls > recent-onset > chronic). RESULTS: Compared with controls, chronic patients displayed a widespread network of connectivity disruptions (p < 0.01). In contrast, connectivity reductions were circumscribed to the anterior fibers of the corpus callosum in recent-onset patients (p < 0.01). A significant proportion of disrupted connections in recent-onset patients (86%) coincided with disrupted connections in chronic patients (p < 0.01). Linear regression revealed that chronic patients displayed reduced connectivity relative to controls, while recent-onset patients showed an intermediate reduction compared with chronic patients (p < 0.01). CONCLUSIONS: Connectome pathology in recent-onset patients with schizophrenia is confined to select tracts within a more extensive network of white matter connectivity disruptions found in chronic illness. These findings may suggest a trajectory of progressive deterioration of connectivity in schizophrenia.

A systematic review and meta-analysis of prospective transition from major depression to bipolar disorder.

OBJECTIVE: Some people with major depressive disorder (MDD) may be at a pre-onset stage for bipolar disorder (BD), where early identification or prevention efforts may be feasible. We aimed to identify rates and characteristics predictive of transition to BD in prospective follow-up studies of people with MDD. METHODS: Using a systematic search strategy, we identified studies with a diagnostic ascertainment of MDD and BD of an adequate standard, and where the minimum length of follow-up was 6 months. We examined the incidence and point prevalence of BD and the pooled odds ratios (OR) for baseline predictors. RESULTS: From 5554 unique publications, 56 were included. Nearly a quarter of adults (22.5%) and adolescents with MDD followed up for a mean length of 12-18 years developed BD, with the greatest risk of transition being in the first 5 years. The meta-analysis identified that transition from MDD to BD was predicted by family history of BD (OR = 2.89, 95% CI: 2.01-4.14, N = 7), earlier age of onset of depression (g = -0.33, SE = 0.05, N = 6) and presence of psychotic symptoms (OR = 4.76, 95% CI: 1.79-12.66, N = 5). CONCLUSIONS: Participants with the identified risk factors merit closer observation and may benefit from prevention efforts, especially if outcomes broader than BD are considered.

Predictors of functional status at service entry and discharge among young people with first episode psychosis.

OBJECTIVE: Most patients with first episode psychosis (FEP) are neither studying nor employed (have a poor functional status) when first accessing care. Knowledge of the characteristics of patients with poor functioning and the features influencing functional status over time may pave the way to better treatment. METHOD: A medical file audit was used to collect data on premorbid, entry, treatment and 18-month outcome characteristics on 661 FEP patients who consecutively attended the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia, between 1998 and 2000. Functional status was ascertained using the modified vocational status index and was rated at baseline (poor or good) and according to its evolution over the treatment period (stable good, stable poor, deteriorating or improved functional status). RESULTS: 52.0% of patients had a poor functional status at service entry. They were more likely to be male with a non-affective psychosis. They also had lower levels of premorbid global functioning and education, and were more likely to have self-reported histories of learning disability, forensic issues, traumatic experiences and substance use. At service entry, they had more severe symptoms and poorer global functioning. 37% of these patients maintained a poor functional status at discharge, and 18% of those with a good functional status at service entry experienced a decline. CONCLUSIONS: Although psychosocial interventions might assist a young person with FEP with working towards functional goals, for some, the impact of factors such as ongoing substance use and forensic issues on functional status needs to be addressed.

Early psychosis research at Orygen, The National Centre of Excellence in Youth Mental Health.

BACKGROUND: Specialised early intervention (SEI) programs have offered individuals with psychotic disorders and their families new hope for improving illness trajectories and outcomes. The Early Psychosis Prevention and Intervention Centre (EPPIC) was one of the first SEI programs developed in the world, providing services for young people experiencing their first episode of psychosis. METHODS: We conducted a narrative synthesis of controlled and uncontrolled studies that have been conducted at EPPIC. DISCUSSION: The history of the EPPIC model is first described. This is followed by a discussion of clinical research emerging from EPPIC, including psychopharmacological, psychotherapeutic trials and outcome studies. Neurobiological studies are also described. Issues pertaining to the conduct of clinical research and future research directions are then described. Finally, the impact of the EPPIC model on the Australian environment is discussed.

Childhood maltreatment and transition to psychotic disorder independently predict long-term functioning in young people at ultra-high risk for psychosis.

BACKGROUND: Individuals identified as at ultra-high risk (UHR) for psychosis are at risk of poor functional outcome regardless of development of psychotic disorder. Studies examining longitudinal predictors of poor functioning have tended to be small and report only medium-term follow-up data. We sought to examine clinical predictors of functional outcome in a long-term longitudinal study. METHOD: Participants were 268 (152 females, 116 males) individuals identified as UHR 2-14 years previously. A range of clinical and sociodemographic variables were assessed at baseline. Functioning at follow-up was assessed using the Social and Occupational Functioning Assessment Scale (SOFAS). RESULTS: Baseline negative symptoms, impaired emotional functioning, disorders of thought content, low functioning, past substance use disorder and history of childhood maltreatment predicted poor functioning at follow-up in univariate analyses. Only childhood maltreatment remained significant in the multivariate analysis (p < 0.001). Transition to psychosis was also significantly associated with poor functioning at long-term follow-up [mean SOFAS score 59.12 (s.d. = 18.54) in the transitioned group compared to 70.89 (s.d. = 14.00) in the non-transitioned group, p < 0.001]. Childhood maltreatment was a significant predictor of poor functioning in both the transitioned and non-transitioned groups. CONCLUSIONS: Childhood maltreatment and transition to psychotic disorder independently predicted poor long-term functioning. This suggests that it is important to assess history of childhood maltreatment in clinical management of UHR individuals. The finding that transition to psychosis predicts poor long-term functioning strengthens the evidence that the UHR criteria detect a subgroup at risk for schizophrenia.

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

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

Omega-3 fatty acid supplementation changes intracellular phospholipase A2 activity and membrane fatty acid profiles in individuals at ultra-high risk for psychosis.

The identification of an ultra-high risk (UHR) profile for psychosis and a greater understanding of its prodrome have led to increasing interest in early intervention to delay or prevent the onset of psychotic illness. In a randomized placebo-controlled trial, we have identified long-chain ω-3 (ω-3) polyunsaturated fatty acid (PUFA) supplementation as potentially useful, as it reduced the rate of transition to psychosis by 22.6% 1 year after baseline in a cohort of 81 young people at UHR of transition to psychosis. However, the mechanisms whereby the ω-3 PUFAs might be neuroprotective are incompletely understood. Here, we report on the effects of ω-3 PUFA supplementation on intracellular phospholipase A2 (inPLA(2)) activity, the main enzymes regulating phospholipid metabolism, as well as on peripheral membrane lipid profiles in the individuals who participated in this randomized placebo-controlled trial. Patients were studied cross-sectionally (n=80) and longitudinally (n=65) before and after a 12-week intervention with 1.2 g per day ω-3 PUFAs or placebo, followed by a 40-week observation period to establish the rates of transition to psychosis. We investigated inPLA(2) and erythrocyte membrane FAs in the treatment groups (ω-3 PUFAs vs placebo) and the outcome groups (psychotic vs non-psychotic). The levels of membrane ω-3 and ω-6 PUFAs and inPLA(2) were significantly related. Some of the significant associations (that is, long-chain ω-6 PUFAs, arachidonic acid) with inPLA(2) activity were in opposite directions in individuals who did (a positive correlation) and who did not (a negative correlation) transition to psychosis. Supplementation with ω-3 PUFA resulted in a significant decrease in inPLA(2) activity. We conclude that ω-3 PUFA supplementation may act by normalizing inPLA(2) activity and δ-6-desaturase-mediated metabolism of ω-3 and ω-6 PUFAs, suggesting their role in neuroprogression of psychosis.

Lessons learned from the psychosis high-risk state: towards a general staging model of prodromal intervention.

BACKGROUND: The past two decades have seen exponential clinical and research interest in help-seeking individuals presenting with potentially prodromal symptoms for psychosis. However, the epidemiological validity of this paradigm has been neglected, limiting future advancements in the field. METHOD: We undertook a critical review of core epidemiological issues underlying the clinical high-risk (HR) state for psychosis and which model of prodromal intervention is best suited for mental health. RESULTS: The HR state for psychosis model needs refining, to bring together population-based findings of high levels of psychotic experiences (PEs) and clinical expression of risk. Traditionally, outcome has been attributed to 'HR criteria' alone rather than taking into account sampling strategies. Furthermore, the exclusive focus on variably defined 'transition' obscures true variation in the slow and non-linear progression across stages of psychopathology. Finally, the outcome from HR states is variable, indicating that the underlying paradigm of 'schizophrenia light progressing to schizophrenia' is inadequate. CONCLUSIONS: In the general population, mixed and non-specific expression of psychosis, depression, anxiety and subthreshold mania is common and mostly transitory. When combined with distress, it may be considered as the first, diagnostically neutral stage of potentially more severe psychopathology, which only later may acquire a degree of diagnostic specificity and possible relative resistance to treatment. Therefore, rather than creating silos of per-disorder ultra-HR syndromes, an early intervention focus on the broad syndrome of early mental distress, requiring phase-specific interventions, may be more profitable.

Reduced parahippocampal cortical thickness in subjects at ultra-high risk for psychosis.

BACKGROUND: Grey matter volume and cortical thickness represent two complementary aspects of brain structure. Several studies have described reductions in grey matter volume in people at ultra-high risk (UHR) of psychosis; however, little is known about cortical thickness in this group. The aim of the present study was to investigate cortical thickness alterations in UHR subjects and compare individuals who subsequently did and did not develop psychosis. METHOD: We examined magnetic resonance imaging data collected at four different scanning sites. The UHR subjects were followed up for at least 2 years. Subsequent to scanning, 50 UHR subjects developed psychosis and 117 did not. Cortical thickness was examined in regions previously identified as sites of neuroanatomical alterations in UHR subjects, using voxel-based cortical thickness. RESULTS: At baseline UHR subjects, compared with controls, showed reduced cortical thickness in the right parahippocampal gyrus (p < 0.05, familywise error corrected). There were no significant differences in cortical thickness between the UHR subjects who later developed psychosis and those who did not. CONCLUSIONS: These data suggest that UHR symptomatology is characterized by alterations in the thickness of the medial temporal cortex. We did not find evidence that the later progression to psychosis was linked to additional alterations in cortical thickness, although we cannot exclude the possibility that the study lacked sufficient power to detect such differences.

Psychosis prevalence and physical, metabolic and cognitive co-morbidity: data from the second Australian national survey of psychosis.

BACKGROUND: There are insufficient data from nationwide surveys on the prevalence of specific psychotic disorders and associated co-morbidities. METHOD: The 2010 Australian national psychosis survey used a two-phase design to draw a representative sample of adults aged 18-64 years with psychotic disorders in contact with public treatment services from an estimated resident population of 1 464 923 adults. This paper is based on data from 1642 participants with an International Classification of Diseases (ICD)-10 psychotic disorder. Its aim is to present estimates of treated prevalence and lifetime morbid risk of psychosis, and to describe the cognitive, physical health and substance use profiles of participants. RESULTS: The 1-month treated prevalence of psychotic disorders was 3.10 cases per 1000 population aged 18-64 years, not accounting for people solely accessing primary care services; lifetime morbid risk was 3.45 per 1000. Mean premorbid intelligence quotient was approximately 0.5 s.d.s below the population mean; current cognitive ability (measured with a digit symbol coding task) was 1.6 s.d.s below the population mean. For both cognitive tests, higher scores were significantly associated with better independent functioning. The prevalence of the metabolic syndrome was high, affecting 60.8% of participants, and pervasive across diagnostic groups. Of the participants, two-thirds (65.9%) were current smokers, 47.4% were obese and 32.4% were sedentary. Of the participants, half (49.8%) had a lifetime history of alcohol abuse/dependence and 50.8% lifetime cannabis abuse/dependence. CONCLUSIONS: Our findings highlight the need for comprehensive, integrative models of recovery to maximize the potential for good health and quality of life for people with psychotic illness.