Transition to adulthood: the critical period for pre-emptive, disease-modifying care for schizophrenia and related disorders.

There is an urgent need and a global opportunity to rethink not only the dominant research paradigms in etiological research but also to invest in less constrained strategies which cut across the existing diagnostic silos to seek out common risk factors, late as well as early neurodevelopmental processes, pathophysiologies, and novel treatment strategies. The high-quality research presented in this special issue of Schizophrenia Bulletin makes a compelling case for such a rethink. While there is still a genuine disconnect between our understanding of the complex and dramatic brain changes that occur during the transition to adulthood and the concurrent surge in incidence of mental ill-health, there is no doubt that a much more serious focus on the perionset stage of clinical disorders in young people with their rapidly evolving brains, social environments, and life trajectories could be extremely productive.

Cannabis use disorder and age at onset of psychosis--a study in first-episode patients.

Introduction: Age at onset of psychosis (AAO) may be younger in patients with cannabis use disorders (CUD) compared to those without CUD (NCUD). Previous studies included CUD co-morbid with other substance use disorders (SUD), and many did not control for confounders.

Methods: Controlling for relevant confounders, differences in AAO between patients with and without CUD excluding those with any other SUD were analyzed in a large representative file audit of 625 first-episode psychosis (FEP) patients (age 14 to 29years) admitted to the Early Psychosis Prevention and Intervention Centre in Melbourne, Australia.

Relational memory in first episode psychosis: implications for progressive hippocampal dysfunction after illness onset.

Objective: Verbal episodic memory deficits are prominent in schizophrenia and have also been found in first episode psychosis (FEP) and individuals at clinical risk of the disorder. The central role of the hippocampus in verbal memory processing and the consistent findings of hippocampal volume reductions in chronic patients have prompted the suggestion that impaired verbal memory performance may be a biomarker of schizophrenia. However, it is currently unclear as to when, during the early phase of psychosis, verbal memory performance becomes significantly impaired.

Emotion recognition in individuals at clinical high-risk for schizophrenia.

Problems in the perception of emotional material, in particular deficits in the recognition of negative stimuli, have been demonstrated in schizophrenia including in first-episode samples. However, it is largely unknown if emotion recognition impairment is present in people with subthreshold psychotic symptoms. Here, we examined the capacity to recognize facially expressed emotion and affective prosody in 79 individuals at ultra high-risk for psychosis, 30 clinically stable individuals with first-episode schizophrenia assessed as outpatients during the early recovery phase of illness, and 30 unaffected healthy control subjects.

The effectiveness of simple psychological and exercise interventions for high prevalence mental health problems in young people: a factorial randomised controlled trial.

Background: The prevalence of mental illness in young people is the highest of any age group, with the onset of depression, anxiety and substance use peaking between 18 and 24 years. Effective treatments that target sub-threshold or mild to moderate levels of disorder in young people are required to reduce the risk of persistence and recurrence. The aims of this study are to evaluate whether treatments that are less intensive than cognitive-behaviour therapy, such as problem solving therapy and exercise treatments, are acceptable and effective in managing depression and anxiety symptoms in young people and to identify possible attributes in those who are likely to respond to these treatments.

Does stage of illness impact treatment response in bipolar disorder? Empirical treatment data and their implication for the staging model and early intervention.

Objective: The staging model suggests that early stages of bipolar disorder respond better to treatments and have a more favourable prognosis. This study aims to provide empirical support for the model, and the allied construct of early intervention.

Methods: Pooled data from mania, depression, and maintenance studies of olanzapine were analyzed.

Very low-dose risperidone in first-episode psychosis: a safe and effective way to initiate treatment.

Patients experiencing a first psychotic episode have high rates of extrapyramidal symptoms (EPSs) when treated with the doses of neuroleptics used in multiepisode or chronic schizophrenia. There is some evidence that lower doses may be equally, if not more, effective but less toxic in this population. Here, we report the results of a biphasic open label trial designed to assess the efficacy, safety, and tolerability of low-dose (2-4 mg/day) risperidone treatment in a group of 96 first-episode nonaffective psychosis patients.

Phospholipase A₂ activity in first episode schizophrenia: associations with symptom severity and outcome at week 12.

Objectives: Intracellular phospholipases A₂ (inPLA₂) are activated during monoaminergic neurotranismision and act as key enzymes in cell membrane repair and remodelling, neuroplasticity, neurodevelopment, apoptosis, synaptic pruning, neurodegenerative processes and neuroinflammation. Several independent studies found increased inPLA₂ activity in drug-naïve first episode and chronic schizophrenia. This study investigates if inPLA₂ activity is associated with symptoms severity and treatment response in first episode schizophrenia (FES).

Randomized controlled trial of interventions for young people at ultra high risk for psychosis: 6-month analysis.

Objective: Cognitive therapy and/or low-dose antipsychotic administered during the prodromal phase of schizophrenia may prevent or delay the onset of full-blown illness. However, it is unclear which of these treatments are most effective, how long treatment should be given, and whether effects will be sustained over a prolonged period.

Method: In order to examine these issues, we conducted a randomized controlled trial of cognitive therapy + risperidone; cognitive therapy + placebo; and supportive therapy + placebo in young people at ultra high risk for developing a psychotic disorder (that is, putatively prodromal).

Promoting physical health in youth mental health services: ensuring routine monitoring of weight and metabolic indices in a first episode psychosis clinic.

Objective: Clinicians are increasingly being asked to implement guideline recommendations into their practice, but are given little practical guidance on this complex task. In this paper we outline a promising theory-driven approach we took to implementing guideline recommendations about routine monitoring of weight gain and metabolic disturbance in our first-episode psychosis clinic. While there is significant psychological and physical morbidity associated with weight gain and metabolic disturbance, routine monitoring was not being undertaken according to guideline recommendations.

Prevalence, predictors, and consequences of long-term refusal of antipsychotic treatment in first-episode psychosis.

Objective: Studies investigating medication adherence in psychosis are limited by the need of a certain degree of medication adherence and the inclusion of mostly multiple-episode patients. By contrast, noninformed consent, epidemiological studies in first-episode psychosis (FEP) allow the assessment of an important subgroup of patients who persistently refuse antipsychotic medication and thereby never receive an adequate antipsychotic trial. The present study aims to assess the prevalence and predictors of such a "medication refusal" subgroup and its association with illness outcome.

Clinical staging: a heuristic and practical strategy for new research and better health and social outcomes for psychotic and related mood disorders.

Most mental illnesses emerge during adolescence and early adulthood, with considerable associated distress and functional decline appearing during this critical developmental phase. Our current diagnostic system lacks therapeutic validity, particularly for the early stages of mental disorders when symptoms are still emerging and intensifying and have not yet stabilized sufficiently to fit the existing syndromal criteria. While this is, in part, due to the difficulty of distinguishing transient developmental or normative changes from the early symptoms of persistent and disabling mental illness, these factors have contributed to a growing movement for the reform of our current diagnostic system to more adequately inform the choice of therapeutic strategy, particularly in the early stages of a mental illness.

From neuroprogression to neuroprotection: implications for clinical care.

Bipolar disorder follows a staged trajectory in which persistence of illness is associated with a number of clinical features such as progressive shortening of the inter-episode interval and decreased probability of treatment response. This neuroprogressive clinical process is reflected by both progressive neuroanatomical changes and evidence of cognitive decline. The biochemical foundation of this process appears to incorporate changes in inflammatory cytokines, cortisone, neurotrophins and oxidative stress.

The impact of cannabis use on cognitive functioning in patients with schizophrenia: a meta-analysis of existing findings and new data in a first-episode sample.

Cannabis use is highly prevalent among people with schizophrenia, and coupled with impaired cognition, is thought to heighten the risk of illness onset. However, while heavy cannabis use has been associated with cognitive deficits in long-term users, studies among patients with schizophrenia have been contradictory. This article consists of 2 studies.

A preliminary evaluation of the validity of at-risk criteria for bipolar disorders in help-seeking adolescents and young adults.

Introduction: We have developed ultra-high risk criteria for bipolar affective disorder (bipolar at-risk - BAR) which include general criteria such as being in the peak age range of the onset of the disorder and a combination of specific criteria including sub-threshold mania, depressive symptoms, cyclothymic features and genetic risk. In the current study, the predictive validity of these criteria were tested in help-seeking adolescents and young adults.

Method: This medical file-audit study was conducted at ORYGEN Youth Health (OYH), a public mental health program for young people aged between 15 and 24years and living in metropolitan Melbourne, Australia.

Cortisol and dehydroepiandrosterone-sulphate levels correlate with symptom severity in first-episode psychosis.

Background: Dehydroepiandrosterone (DHEA) and its sulphate form (DHEA) are neuroactive steroids with antiglucocorticoid properties. An imbalance in the ratio of cortisol to DHEA(S) has been implicated in the pathophysiology of stress-related psychiatric disorders. This study prospectively investigated circulating cortisol, DHEAS and their ratio in first-episode psychosis (FEP) patients compared to healthy controls, and their relationship to perceived stress, psychotic, negative and mood symptoms.

Corpus callosum morphology and relationship to orbitofrontal and lateral ventricular volume in teenagers with first-presentation borderline personality disorder.

Unlabelled: Previous studies have demonstrated alterations to fronto-limbic circuitry and callosal structure in borderline personality disorder (BPD). We predicted that a first-presentation BPD cohort who demonstrated orbitofrontal cortex (OFC) reductions would show regional reductions in the anterior corpus callosum.

Method: Twenty teenage first-presentation BPD patients and twenty matched healthy controls underwent Magnetic resonance imaging (MRI) was performed in 20 teenaged first-presentation BPD patients and 20 matched healthy controls.

The EPPIC follow-up study of first-episode psychosis: longer-term clinical and functional outcome 7 years after index admission.

Objective: To describe the longer-term clinical and functional outcome of a large, epidemiologic representative cohort of individuals experiencing a first episode of psychosis.

Method: A naturalistic, prospective follow-up of an epidemiologic sample of 723 consecutive first-episode psychosis patients, followed between January 1998 and April 2005, at a median of 7.4 years after initial presentation to the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne, Australia.

Pretreatment and outcome correlates of past sexual and physical trauma in 118 bipolar I disorder patients with a first episode of psychotic mania.

Objectives: To assess the prevalence and correlates of childhood and adolescent sexual and/or physical abuse (SPA) in bipolar I disorder (BDI) patients treated for a first episode of psychotic mania.

Methods: The Early Psychosis Prevention and Intervention Centre admitted 786 first-episode psychosis patients between 1998 and 2000. Data were collected from patients' files using a standardized questionnaire.

The staging model in schizophrenia, and its clinical implications.

Introduction: Illnesses which develop in a complex way are best described in stages, and those stages will describe not only a particular point in the course of the disease but also the appropriate treatment for that stage. This approach has, over the years, proved to be very appropriate for planning the treatment of various cancers. It is suggested that in the same way, it can be very important in planning the treatment of a complex illness such as schizophrenia.