Neuroanatomical Maps of Psychosis Onset: Voxel-wise Meta-Analysis of Antipsychotic-Naive VBM Studies

Background: Despite impressive advancements in early interventions in psychosis, there is an urgent need of robust neurobiological markers to improve the predictive value of psychosis transition. Available structural imaging literature in the field is undermined by several methodological caveats and a number of confounders such as exposure to antipsychotic treatment. Methods: Fourteen voxel-based morphometry studies of antipsychotic-naive subjects at enhanced clinical risk for psychosis (high risk [HR]) or experiencing a first-episode psychosis (FEP) were included. Formal meta-analysis of effect sizes and “signed differential mapping” voxel-based meta-analysis were combined to control the results for sample sizes, strength of individual findings, and confounding variables. Results: Formal effect size meta-analysis indicated consistent gray matter (GM) reductions both in subjects at enhanced clinical risk for psychosis and in first-episode subjects when compared with control groups. Voxel-based meta-analysis showed GM reductions in the temporal, limbic prefrontal cortex within the HR group and in the temporal insular cortex and cerebellum within the FEP group. Psychosis onset was characterized by GM decreases in temporal, anterior cingulate, cerebellar, and insular regions. GM alterations in the temporal regions directly related to severity of psychotic symptoms. There was no publication bias. Heterogeneity across studies was low. Sensitivity analyses confirmed robustness of the above results. Conclusions: Vulnerability to psychosis is associated with consistent GM decreases in prefrontal and temporolimbic areas. The onset of full disease is accompanied by temporoinsular, anterior cingulate, and cerebellar GM reductions. Neuroanatomical alterations in temporal regions may underlie the clinical onset of psychotic symptoms.     

White Matter Alterations in Early Stages of Schizophrenia: A Systematic Review of Diffusion Tensor Imaging Studies

Several lines of evidence suggest that the normal integration of cerebral communication may be compromised in schizophrenia, with white matter (WM) abnormalities being integral to these functional deficits. Diffusion tensor imaging (DTI) is a neuroimaging technique which has increasingly been used to study WM through quantitative indices of its structural and orientational characteristics. Identifying the WM differences early in the course of schizophrenia may assist in prevention, early diagnosis and identification of treatment targets. In that respect, the aims of the present study were to (a) systematically review WM integrity in the early stages of schizophrenia as inferred by DTI and (b) specifically examine parameters that may affect WM: age, duration of illness and treatment. In summary, DTI studies in early schizophrenia suggest that structural dysconnectivity may be already present in recent‐onset and drug‐naïve patients, as well as in individuals clinically at high risk for developing schizophrenia. Although the pattern of WM differences is not totally consistent frontal, fronto‐temporal and fronto‐limbic connections, with tracts including the superior longitudinal fasciculus, cingulum bundle, uncinate fasciculus and corpus callosum seem to be affected. These differences may depend on the developmental stage of the subjects, the duration of illness and exposure to antipsychotic medication.     

Epidemiological factors associated with treated incidence of first-episode non-affective psychosis in Cantabria: insights from the Clinical Programme on Early Phases of Psychosis

Aim: The aim of the study was to analyse the treated incidence of schizophrenia in Cantabria (Northern Spain) and the sociodemographic risk factors associated with the illness onset. Methods: Data were obtained from patients included in the Cantabria's Clinical Programme on First‐Episode Psychosis (schizophrenia spectrum DSM‐IV diagnosis) from 2001 to 2005, from the Cantabria first‐episode schizophrenia study (carried out between 1988 and 1989) and from the 2001 Spanish census. Results: Annual incidence was 1.38 per 10 000 inhabitants in the risk‐ageperiod. Identified risk factors were male gender (relative risk (RR): 1.61), age 15–25 years (RR: 3.48), unemployment (RR: 2.82), single status (RR: 5.88), low educational level (RR: 4.38), urban environment (RR: 1.62) and cannabis consumption (odds ratio: 12.83). The incidence in females was significantly lower than the one obtained 15 years ago. Conclusions: The reported factors suggest that underlying biological and social factors modulate the risk of psychosis. This balance operates differently in males and females.     

Expressed emotion in first-episode schizophrenia and in ultra high-risk patients: results from the Programma2000 (Milan, Italy)

Expressed emotion (EE) was examined in a large sample of families of patients with either first-episode psychosis (FEP) within the schizophrenia spectrum, or who met the criteria for ultra high-risk (UHR) of psychosis. The aim of our study was to determine the patterns and relationship of EE with the duration of untreated illness (DUI) or of untreated psychosis (DUP), as well as with illness severity. The sample used in our study included 77 FEP and 66 UHR families. The Camberwell Family Interview was used to assess EE.In both samples, about one-third of patients’ families were classified as high EE, with emotional over-involvement (EOI) being the most frequent reason for a family to be classified as high EE. In FEP, higher EE correlated with longer DUI, and higher paternal EOI with longer DUP. DUI, however, was not found to correlate to EE in UHR patients. Severity of illness at the initial assessment did not relate to EE in either FEP or UHR families. Families of FEP and UHR patients were not found to differ in terms of the prevalence of a high EE rating, or of any of its subcomponents.The results of this study only partially support the hypothesis that high EE develops as a reaction to patient status. Patients from families with high EE could possibly benefit from interventions that are targeted at improving their resilience when dealing with problematic family environments.     

奎硫平与阿立哌唑治疗首发精神分裂症对照研究

目的：探讨奎硫平与阿立哌唑治疗首发精神分裂症的临床疗效与安全性。方法：将70例首发精神分裂症患者,随机分为奎硫平组35例,阿立哌唑组35例,疗程8周。采用阳性与阴性症状量表（PANSS）评定疗效,采用治疗中出现的症状量表（TESS）评定不良反应。结果：奎硫平组的治疗总有效率为85．7％,阿立哌唑组的治疗总有效率为82．9％,两组疗效差异无显著性（P〉0．05）。结论：奎硫平与阿立哌唑治疗首发精神分裂症均有良好效果,不良反应均较轻。     

The Swiss Early Psychosis Project SWEPP: a national network

Aim: The study aims to describe the activities of the Swiss Early Psychosis Project (SWEPP) which was founded in 1999 as a national network to further and disseminate knowledge on early psychosis (EP) and to enhance collaboration between healthcare groups. Methods: The present paper is a detailed account of the initiation and the development of the Swiss network. We describe all activities such as the several educational campaigns that were addressed to primary and secondary care groups since the early days. We also provide an overview of the current status of EP services throughout the country. Results: Today, most regions in Switzerland provide specialized EP inpatient and/or outpatient services with a clinical or combined clinical research approach that targets at‐risk and/or first‐episode populations. Some more recently initiated EP services have been launched as collaborative models between several local or regional psychiatric services. Conclusions: The increasing number of EP services and experts in Switzerland may mirror the catalyzing contribution of the Swiss Early Psychosis Project in this important field of health care. The country's small size and the increasing density of specialized services provide excellent bases for larger‐scale networking activities in the future, both in clinical and research areas.     

Symptom Remission and Brain Cortical Networks at First Clinical Presentation of Psychosis: The OPTiMiSE Study

Individuals with psychoses have brain alterations, particularly in frontal and temporal cortices, that may be particularly prominent, already at illness onset, in those more likely to have poorer symptom remission following treatment with the first antipsychotic. The identification of strong neuroanatomical markers of symptom remission could thus facilitate stratification and individualized treatment of patients with schizophrenia. We used magnetic resonance imaging at baseline to examine brain regional and network correlates of subsequent symptomatic remission in 167 medication-naïve or minimally treated patients with first-episode schizophrenia, schizophreniform disorder, or schizoaffective disorder entering a three-phase trial, at seven sites. Patients in remission at the end of each phase were randomized to treatment as usual, with or without an adjunctive psycho-social intervention for medication adherence. The final follow-up visit was at 74 weeks. A total of 108 patients (70%) were in remission at Week 4, 85 (55%) at Week 22, and 97 (63%) at Week 74. We found no baseline regional differences in volumes, cortical thickness, surface area, or local gyrification between patients who did or did not achieved remission at any time point. However, patients not in remission at Week 74, at baseline showed reduced structural connectivity across frontal, anterior cingulate, and insular cortices. A similar pattern was evident in patients not in remission at Week 4 and Week 22, although not significantly. Lack of symptom remission in first-episode psychosis is not associated with regional brain alterations at illness onset. Instead, when the illness becomes a stable entity, its association with the altered organization of cortical gyrification becomes more defined.     

Mortality After the First Diagnosis of Schizophrenia-Spectrum Disorders: A Population-based Retrospective Cohort Study

There is emerging evidence of high mortality rates after the first diagnosis of psychotic disorder. The objective of this study was to estimate the standardized mortality ratio (SMR) in a population-based cohort of individuals with a first diagnosis of schizophrenia-spectrum psychotic disorder (SSD). The cohort included a population-based sample of individuals with a first diagnosis of SSD based on the first diagnosis occurring during hospitalization or in an outpatient setting between 2007 and 2010 in Ontario, Canada. All patients were followed for 5 years after the first diagnosis. The primary outcome was SMR, including all-cause, suicide-related, accidental, and other causes. Between 2007 and 2010, there were 2382 patients in the hospitalization cohort and 11 003 patients in the outpatient cohort. Over the 5-year observation period, 97 (4.1%) of the hospitalization cohort and 292 (2.7%) of the outpatient cohort died, resulting in an SMR of 13.6 and 9.1, respectively. In both cohorts, suicide was the most common cause of death. Approximately 1 in 25 patients with a first diagnosis of SSD during hospitalization, and 1 in 40 patients with a first diagnosis of SSD in an outpatient setting, died within 5 years of first diagnosis in Ontario, Canada. This mortality rate is between 9 and 13 times higher than would be expected in the age-matched general population. Based on these data, timely access to services should be a public health priority to reduce mortality following a first diagnosis of an SSD.