Reduced auditory segmentation potentials in first-episode schizophrenia

Background Proponents of early intervention have argued that outcome might be improved if more therapeutic effort were focused on the early stages of schizophrenia. Early intervention in schizophrenia has two elements that are distinct from standard care: early detection and phase-specific treatment. Both elements may be offered in addition to standard care, or may be provided by a specialised early intervention team. Early intervention is now well established as a therapeutic approach in America, Europe and Australasia, but it is unclear how far early detection, phase-specific treatments, and the use of early intervention teams are underpinned by evidence of effectiveness. Objectives This review aims to evaluate the effects of: i. early detection and treatment of people with prodromal symptoms; ii. the use of early intervention teams for people in their first episode of psychosis; and iii. phase-specific treatments for people in their first episode of psychosis. Search strategy We searched CINAHL (1982-2002), The Cochrane Controlled Trials Register (November 2001), The Cochrane Schizophrenia Group Register (July 2003), EMBASE (1980-2002), MEDLINE (1966-2002), PsycINFO (1967-2002), reference lists and contacted the European First Episode Network (2003). Selection criteria Randomised controlled trials designed to prevent progression to psychosis in people showing prodromal symptoms, or improve outcome for people with first episode psychosis. Eligible interventions, alone and in combination, included early detection, phase-specific treatments, and care from specialised early intervention teams. Non-randomised trials would only have been included if they had been studies of the effects of early detection strategies in reducing the duration of untreated psychosis (since this issue cannot be addressed by simple randomisation). Data collection and analysis Data were extracted independently by two reviewers and cross-checked. Relative risks (RR) and 95% confidence intervals (CI) were calculated for dichotomous data. Weighted mean differences (WMD) were calculated for continuous data. Main results In theory, seventeen different comparisons are possible, but the review only identified three studies that met inclusion criteria. One small trial (n=59) was concerned with a phase-specific intervention (low dose risperidone and cognitive behavioural therapy) for people with prodromal symptoms. This group were significantly less likely to develop psychosis at 6 month follow up than people who only received care from a specialised team which did not involve phase-specific treatment (n=59, 1 RCT, RR 0.27 CI 0.08 to 0.89, NNT 4 CI 2 to 20). This effect was not significant at 12 month follow up (n=59, 1 RCT, RR 0.54 CI 0.23 to 1.30). Another trial found that people in their first episode receiving a phase-specific intervention (family therapy) plus out patient care did have reduced admission rates care compared with those who received only outpatient care (n=83, 1 RCT, RR 0.28 CI 0.13 to 0.62, NNT 3 CI 2 to 6). The applicability of this finding was, however, questionable.Finally, one last study (n=76), comparing phase-specific intervention (family therapy) plus specialised team with specialised team for people in their first episode of schizophrenia found no difference between intervention and control groups at 12 months for the outcome of relapse but confidence intervals were wide (n=76, RR 1.06 CI 0.31 to 3.65). Reviewers' conclusions We identified insufficient trials to draw any definitive conclusions, although five ongoing trials should report shortly. The substantial international interest in early intervention offers an opportunity to make major positive changes in psychiatric practice, but this opportunity may be missed without a concerted international programme of research to address key unanswered questions.

Hippocampal Volumes in First-Episode Psychosis

Background. The significance of cognitive dysfunction in schizophrenia is the subject of modern psychiatric and cognitive research. In particular, some authors propose to consider cognitive impairments as “core” symptoms of schizophrenia. The cognitive status affects the functional outcome and the level of social readaptation. The investigation of changes in the cognitive status of patients with schizophrenia at various stages of the disease, as well as the prognostic and differential role of cognitive diagnostics of patients, remains an urgent task. Objective. The aim is to structure information on the current state of cognitive impairment at various stages of schizophrenia. Methods. The research presents a literature review of studies on cognitive functions and their impairments at various stages of schizophrenia (premorbid, prodrome with high risk for psychosis, the first episode of schizophrenia). Publications were selected from the Russian Science Citation Index (RSCI), Web of Science, and PubMed databases according to the PRISMA-ScR guidelines, using the following keywords: cognitive dysfunction in schizophrenia, cognitive impairment in schizophrenia, the first episode, attenuated psychotic symptoms, ultra-high risk for psychosis. The review included articles on empirical research, metaanalytic studies, and systematic reviews. Results. The obtained research data indicate that cognitive dysfunction manifests itself in the premorbid period, long before the manifestation of the disease. Patients with an extremely high risk of psychosis demonstrate a significant severity of cognitive deficit associated with the severity of erased psychotic symptoms. Cognitive deficit is not a consequence of past psychotic episodes and does not depend on the duration of an untreated psychosis. Conclusions. The level of cognitive functioning in patients at the pre-psychotic states of schizophrenia development has an important prognostic significance along with the criteria of extremely high risk and familial risk. Cognitive deficit is a separate,“core” group of symptoms for schizophrenia, not secondary to productive symptoms.

Lack of insight is frequent in schizophrenia and usually influences negatively both patient's treatment and prognosis. This study aimed to investigate the relationship between insight, symptomatology and cognitive dysfunctions in schizophrenia using the PANSS five-factor model (modified from Gaag et al. in Schizophr Res 85:280-287, 2006). Forty patients diagnosed with chronic schizophrenia (DSM-IV) were evaluated with the scale to assess unawareness of mental disorder (SUMD), the PANSS and a neuropsychological battery. Spearman correlation and linear regression analyses were performed to investigate the relationship between clinical, neurocognitive and insight measures. The SUMD current and past awareness of symptoms score showed a correlation with WCST indices (correct answers and non-persevering errors). The negative and disorganization factor of the PANSS showed a positive correlation with current and past awareness of symptoms. However, when submitted to a linear regression model only the disorganization factor emerged as significant contributor for insight. Considering that the core items of the "disorganization factor" of the PANSS are related to cognition (e.g., poor attention, difficult in abstract thinking), insight is associated cognitive symptoms although no direct relationship between insight and neuropsychological tests was observed.

Aberrant social cognition is a core feature of schizophrenia, persisting from clinical high-risk and genetic high-risk states to the first episode of psychosis. This study aimed to identify shared and distinct social cognition-related functional alterations across clinical high-risk, genetic high-risk, and first episode of psychosis groups, shedding light on varying risk levels for first episode of psychosis development. Meta-analyses were performed on 38 whole-brain task-based functional magnetic resonance imaging studies (12 clinical high risk, 15 genetic high risk, 11 first episode of psychosis) using Seed-based d Mapping. Function abnormalities were assessed within each patient group, with quantitative comparisons made against controls. Clinical high-risk and genetic high-risk individuals showed neither shared nor distinct abnormal brain activation during social cognition tasks. A shared cluster of increased activation in the right anterior cingulate cortex was observed between genetic high-risk and first episode of psychosis groups. However, no conjunction or disjunction results were found between clinical high-risk and first episode of psychosis groups. Meta-regression analyses revealed accelerated age-related greater activation decline in the left insula in individuals with clinical high risk. In conclusion, the absence of shared social cognition-related brain activation between clinical high risk and genetic high risk may signify differences in neural correlates underlying social cognition deficits between these groups and they follow distinct neural pathways toward first episode of psychosis. The shared abnormal anterior cingulate cortex activation in genetic high risk and first episode of psychosis may represent an endophenotype of schizophrenia.

BackgroundApproximately 30% of patients with schizophrenia do not improve with antipsychotic drug (APD) treatment and 60% show sub-optimal response. Converging lines of evidence point to hippocampal dysfunction in schizophrenia. It is thought that hippocampal dysfunction spreads across hippocampal subfields and to cortical regions by way of long-range efferent projections. Our prior studies have shown altered hippocampal regional cerebral blood flow in unmedicated patients and normalization after APD treatment. Meta-analyses show reduced hippocampal volume in first episode psychosis (FEP) patients. We evaluated resting state hippocampal functional connectivity (hFC) as well as hippocampal and hippocampal subfield volumes as predictors of treatment response (TR) in two cohorts of patients with a psychosis spectrum disorder. All patients were subsequently treated with an APD for 6 weeks.MethodsCohort 1 consisted of 55 medication-naïve first episode psychosis (FEP) subjects (36 male; mean age 24.18 years). Cohort 2 consisted of 42 unmedicated patients with schizophrenia (SZ) (31 male; mean age 27.9 years).FEP were scanned on a Siemens MAGNETOM Prisma MRI scanner using a 20 channel head coil. Anatomical scans were acquired via T1-weighted and T2-weighted images. Two 6-minute resting state scans were acquired in opposing phase encoding directions (A > P and P > A).SZ were scanned on a Siemens MAGNETOM Allegra MRI scanner with a circularly polarized transmit/receive head coil. Anatomical scans were acquired via a T1-weighted sequence. Resting state scans were acquired with a single 5-minute gradient recalled echo-planar imaging sequence.For both datasets, resting state data were preprocessed in the CONN toolbox (version 18a). We used the left hippocampus as a seed region to create whole brain seed-to-voxel correlation maps for each subject. Regression analyses were then performed to assess the relationship between resting state connectivity and TR (% change in BPRS positive score from (A) baseline to (B) after 6 weeks of APD: (((B-A)/A)*-100). Analyses were corrected using voxel (p < 0.05, uncorrected) and cluster level correction (p < 0.05, FDR corrected). Age, sex, and framewise displacement were used as covariates of no interest.T1 and T2 weighted images were preprocessed using FreeSurfer 6.0. Freesurfer’s hippocampus subfield segmentation module was used to calculate left and right subfield volumes. SPSS 25 was used to regress hippocampal subfield volumes on TR. Age and estimated total intracranial volume (eTIV) were included as covariates of no interest.ResultsIn both cohorts greater hFC to the cuneus and precuneus was predictive of better TR, as was greater hFC to the fusiform gyrus, medial prefrontal cortex (PFC) and anterior cingulate cortex in cohort 2. Reduced hFC connectivity to the angular gyrus in supramarginal gyrus and temporal pole in cohort 1 as well as the orbitofrontal cortex and dorsolateral PFC in cohort 2 were also predictive of better TR. Results from the stepwise regression showed that neither right nor left whole hippocampal volume, or subfield volumes, significantly predict TR for either cohort.DiscussionIn two patient cohorts, we observed a similar pattern where increased hFC to the cuneus and precuneus was predictive of better response to APD. Furthermore, the lack of a significant predictive value of hippocampal volumes in predicting TR was replicated in each cohort. The replicability of these findings, particularly in a cohort of medication-naïve FEP provides potential biological patterns useful in determining initial response to APD medication in patients with a psychosis spectrum disorder.

Over the last decades the study of schizophrenia-spectrum disorders has been focused on early and comprehensive intervention during the first episode of psychosis (FEP), but studies in rural settings are only rare. In Greece mental healthcare in rural areas is mostly delivered by the locally-based Mobile Mental Health Units (MMHUs). The aim of the present study was to address treatment of FEP patients by the MMHUs in rural areas in Greece, focusing on patients with a first episode of schizophrenia. This is a multicenter, retrospective observational study with the participation of nine MMHUs across several areas in rural mainland and some islands of Greece. Patients of the age range of 15 to 55 years with a diagnosis of non-affective psychosis were included in the study. The study sample consisted of 216 patients, while analysis was performed for patients with a diagnosis of schizophrenia (n = 153, 70.8% of the sample). Most patients were males (n = 93, 60.8%), with a mean age at first presentation 34.9 years (Md = 34.5, SD = 11.94). The mean duration of untreated psychosis (DUP) was 7.85 months (Md = 3, IQR = 10.00) and was shorter in younger (15-25 years) patients. More than 60% of patients had been successfully engaged to treatment with the MMHUs, with a mean follow-up duration of 5.17 years (Md = 5.00, IQR = 5.00). Younger patients (26-35 years) tend to disengage from treatment, while those aged 36 to 45 years were more likely to continue follow-up. A reduction of 47.22% in hospital admissions among patients with schizophrenia was observed over follow-up of patients by the MMHUS. The most noteworthy findings of the study are the low percentage of patients seeking help from the MMHUs, compared to the expected cases and the high attendance rate of those that are examined in this context. Further research on psychosis/schizophrenia in the rural context is warranted.

Predicting relapse after a first episode of non-affective psychosis: A three-year follow-up study

Altered default network resting state functional connectivity in patients with a first episode of psychosis

Services for individuals with a first episode of psychosis or at ultra-high risk of psychosis have become a treatment model of choice in mental health care. The longitudinal changes in clinical and functional outcomes as a result of real-world treatment remain under-reported. We analysed data from first episode of psychosis and ultra-high risk services delivered across Australian primary youth mental health care services known as headspace between 19 June 2017 and 30 September 2019. Outcome measures were completed and entered into a minimum dataset every 90 days a participant was receiving treatment and included psychiatric symptomatology (Brief Psychiatric Rating Scale and psychological distress, K10) and psychosocial functioning (Social and Occupational Functioning Assessment Scale and My Life Tracker). Linear mixed-effects models were used to evaluate changes in outcome over time. Outcome data from a total of 1252 young people were evaluated (643 first episode of psychosis, 609 ultra-high risk). Of those who entered ultra-high risk services, 11.8% transitioned to first episode of psychosis services. Overall, substantial improvement in clinical (Brief Psychiatric Rating Scale, K10) and functional (Social and Occupational Functioning Assessment Scale, My Life Tracker) outcomes were seen across groups and outcomes. Ultra-high risk patients showed a greater reduction in distress symptoms, while first episode of psychosis patients experienced a greater reduction in positive psychosis symptoms. Although clinical outcomes showed a plateau effect after approximately 3 months of care, improvement in functional outcomes (Social and Occupational Functioning Assessment Scale, My Life Tracker) continued later in treatment. These findings support the use of real-time, real-world and low-cost administrative data to rigorously evaluate symptomatic and functional outcomes in early psychosis treatment settings. Findings that functional outcomes improve past the remittance of clinical outcomes also support the functional recovery focus of early psychosis services and remaining high levels of distress suggest the need for ultra-high risk services to extend beyond 6 months of care.

Selective Left Hemisphere Auditory Cortex Mismatch Negativity Source Deficit in First Episode Psychosis

BodyPrevention of the First Episode of Psychosis: What Have we Reached by 2021? The first episode of psychosis is usually preceded by a prodromal period or stage of psychosis, where early signs of symptoms indicating onset of first episode psychosis (FEP) occur. In the last twenty years, enormous progress was made in the tretment of FEP and subsequently schizophrenia, as the focus of treatment of FEP shifted to this prodromal period with the aim of preventing the first episode of psychosis in people at risk.Treatment for the prodromal stage of psychosis is provided within specialized early intervention services, which are somtimes part of the services for the treatment of FEP. Early intervention services, which have been gradually developed in many countries worldwide, usually incorporate multimodal treatment approaches (pharmacotherapy, psychotherapy and psychosocial interventions). However, there are still many differences in the treatment of prodromes across early intervention services, even within one country, leaving open the questions on what kind or combinations of treatments really work in the prevention of FEP. The methods of studies in the scientific psychiatric literature do not allow easy translation of scientific data to clinical practice. In the presentation, an up-to-date overview of the available treatments offered witin early intervention services for prevention of FEP is given.DisclosureNo significant relationships.

Clinical and demographic predictors of continuing remission or relapse following discontinuation of antipsychotic medication after a first episode of psychosis. A systematic review

Acta Psychiatrica ScandinavicaVolume 128, Issue 6 p. 492-492 Letter to the Editor Response to ‘A systematic review and meta-regression analysis of aggression during first episode of psychosis’ E. Kline, E. Kline Department of Psychology, University of Maryland, Baltimore, MD, USASearch for more papers by this authorJ. M. Gold, J. M. Gold Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USASearch for more papers by this authorJ. Schiffman, J. Schiffman [email protected] Department of Psychology, University of Maryland, Baltimore, MD, USASearch for more papers by this author E. Kline, E. Kline Department of Psychology, University of Maryland, Baltimore, MD, USASearch for more papers by this authorJ. M. Gold, J. M. Gold Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USASearch for more papers by this authorJ. Schiffman, J. Schiffman [email protected] Department of Psychology, University of Maryland, Baltimore, MD, USASearch for more papers by this author First published: 17 August 2013 https://doi.org/10.1111/acps.12181Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume128, Issue6December 2013Pages 492-492 RelatedInformation

Prevalence of item level negative symptoms in first episode psychosis diagnoses