Showing papers in "Schizophrenia Bulletin in 2011"

The Brief Negative Symptom Scale: Psychometric Properties

Abstract: The participants in the NIMH-MATRICS Consensus Development Conference on Negative Symptoms recommended that an instrument be developed that measured blunted affect, alogia, asociality, anhedonia, and avolition. The Brief Negative Symptom Scale (BNSS) is a 13-item instrument designed for clinical trials and other studies that measures these 5 domains. The interrater, test-retest, and internal consistency of the instrument were strong, with respective intraclass correlation coefficients of 0.93 for the BNSS total score and values of 0.89-0.95 for individual subscales. Comparisons with positive symptoms and other negative symptom instruments supported the discriminant and concurrent validity of the instrument.

Psychoeducation for Schizophrenia

Abstract: Background Schizophrenia can be a severe and chronic illness characterised by lack of insight and poor compliance with treatment. Psychoeducational approaches have been developed to increase patients' knowledge of, and insight into, their illness and its treatment. It is supposed that this increased knowledge and insight will enable people with schizophrenia to cope in a more effective way with their illness, thereby improving prognosis. Objectives To assess the effects of psychoeducational interventions compared to the standard levels of knowledge provision. Search strategy Electronic searches of CINAHL (1982-1999), The Cochrane Library CENTRAL (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (May 2001), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLit (1974-1999), and Sociofile (1974-1999) were undertaken. These were supplemented by cross-reference searching and personal contact with authors of all included studies. Selection criteria All relevant randomised controlled trials focusing on psychoeducation for schizophrenia and/or related serious mental illnesses involving individuals or groups. Quasi-randomised trials were excluded. Data collection and analysis Data were extracted independently from included papers by at least two reviewers. Authors of trials were contacted for additional and missing data. Relative risks (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data were calculated. A random effects model was used for heterogeneous dichotomous data. Where possible the numbers needed to treat (NNT) were also calculated. Weighted or standardised means were calculated for continuous data. Main results Ten studies are included in this review. All studies of group education included family members. Compliance with medication was significantly improved in a single study using brief group intervention (at one year) but other studies produced equivocal or skewed data. Any kind of psychoeducational intervention significantly decreased relapse or readmission rates at nine to 18 months follow-up compared with standard care (RR 0.8 CI 0.7-0.9 NNT 9 CI 6-22). Several of the secondary outcomes (knowledge gain, mental state, global level of functioning, expressed emotion in family members) were measured using scales that are difficult to interpret. Generally, however, findings were consistent with the possibility that psychoeducation has a positive effect on a persons' well being. No impact was found on insight, medication related attitudes or on overall satisfaction with services of patients or relatives but these findings rested on very few studies. Health economic outcome was only measured in one study and data were skewed. It was not possible to analyse whether different duration or formats of psychoeducation influenced effectiveness. Authors' conclusions Evidence from trials suggests that psychoeducational approaches are useful as a part of the treatment programme for people with schizophrenia and related illness. The fact that the interventions are brief and inexpensive should make them attractive to managers and policy makers. More well-designed, conducted and reported randomised studies investigating the efficacy of psychoeducation are needed.

How Prevalent Are Anxiety Disorders in Schizophrenia? A Meta-Analysis and Critical Review on a Significant Association

Abstract: Objective: The presence of anxiety disorders (AD) in schizophrenia (SZ) is attracting increasing interest. However, published studies have yielded very broad variations in prevalence rates across studies. The current meta-analysis sought to (1) investigate the prevalence of co-occurring AD in SZ by reporting pooled prevalence rates and (2) identify potential sources of variations in reported rates that could guide our efforts to identify and treat these co-occurring disorders in patients with SZ. Methods: We performed a systematic search of studies reporting prevalence of AD in SZ and related psychotic disorders. Mean prevalence rates and 95% confidence intervals (CIs) were first computed for each disorder. We then examined the impact of potential moderators related to patient sampling or to AD assessment methods on these rates. Results: Fifty-two eligible studies were identified. Pooled prevalence rates and CIs were 12.1% (7.0%–17.1%) for obsessive-compulsive disorders, 14.9% (8.1%–21.8%) for social phobia, 10.9% (2.9%–18.8%) for generalized AD, 9.8% (4.3%–15.4%) for panic disorders, and 12.4% (4.0%–20.8%) for post-traumatic stress disorders. For all disorders, we found significant heterogeneity in rates across studies. This heterogeneity could at least partially be explained by the effect of moderator variables related to patient characteristics or assessment methods. Conclusions: AD are highly prevalent in SZ, but important variations in rates are observed between studies. This meta-analysis highlights several factors that affect risk for, or detection of AD in SZ, and could, thus, have an important impact on treatment and outcome of SZ patients.

Social Cognition as a Mediator Variable Between Neurocognition and Functional Outcome in Schizophrenia: Empirical Review and New Results by Structural Equation Modeling

Abstract: Cognitive impairments are currently regarded as important determinants of functional domains and are promising treatment goals in schizophrenia. Nevertheless, the exact nature of the interdependent relationship between neurocognition and social cognition as well as the relative contribution of each of these factors to adequate functioning remains unclear. The purpose of this article is to systematically review the findings and methodology of studies that have investigated social cognition as a mediator variable between neurocognitive performance and functional outcome in schizophrenia. Moreover, we carried out a study to evaluate this mediation hypothesis by the means of structural equation modeling in a large sample of 148 schizophrenia patients. The review comprised 15 studies. All but one study provided evidence for the mediating role of social cognition both in cross-sectional and in longitudinal designs. Other variables like motivation and social competence additionally mediated the relationship between social cognition and functional outcome. The mean effect size of the indirect effect was 0.20. However, social cognitive domains were differentially effective mediators. On average, 25% of the variance in functional outcome could be explained in the mediation model. The results of our own statistical analysis are in line with these conclusions: Social cognition mediated a significant indirect relationship between neurocognition and functional outcome. These results suggest that research should focus on differential mediation pathways. Future studies should also consider the interaction with other prognostic factors, additional mediators, and moderators in order to increase the predictive power and to target those factors relevant for optimizing therapy effects.

Evidence That Onset of Clinical Psychosis Is an Outcome of Progressively More Persistent Subclinical Psychotic Experiences: An 8-Year Cohort Study

Abstract: This study examined the hypothesis that developmental expression of psychometric risk in the form of subclinical psychotic experiences in the general population is usually transitory but in some instances may become abnormally persistent and progress to a clinical psychotic state A prospective cohort study was conducted in a general population sample of 845 adolescents, aged 14–17 years, in Munich, Germany (Early Developmental Stages of Psychopathology Study) Expression of psychosis was assessed 4 times (T0–T3) over a period of 84 years Transition from subclinical psychosis at T0–T2 to clinical psychosis in terms of impairment at T3 was examined as a function of the level of prior persistence of subclinical psychosis (present never, once, twice, or thrice) The more the subclinical psychosis persisted over the period T0–T2, the greater the risk of transition to clinical psychosis at T3 in a dose-response fashion (subclinical psychosis expression once over T0–T2: odds ratio [OR] 5 15 [95% confidence interval {CI} 5 06–37], posttest probability [PP] 5 5%; twice: OR 5 50 [95% CI 5 16–159], PP 5 16%; at all 3 measurements: OR 5 99 [95% CI 5 25–398], PP 5 27%) Of all clinical psychosis at T3, more than a third (383%) was preceded by subclinical psychotic experiences at least once and a fifth (196%) at least twice Consequently, a significant proportion of psychotic disorder may be conceptualized as the rare poor outcome of a common developmental phenotype characterized by persistence of psychometrically detectable subclinical psychotic experiences This may be summarized descriptively as a psychosis proneness-persistence-impairment model of psychotic disorder

Reliability and Comparability of Psychosis Patients’ Retrospective Reports of Childhood Abuse

Abstract: An increasing number of studies are demonstrating an association between childhood abuse and psychosis. However, the majority of these rely on retrospective self-reports in adulthood that may be unduly influenced by current psychopathology. We therefore set out to explore the reliability and comparability of first-presentation psychosis patients’ reports of childhood abuse. Psychosis case subjects were drawn from the Aetiology and Ethnicity of Schizophrenia and Other Psychoses (AESOP) epidemiological study and completed the Childhood Experience of Care and Abuse Questionnaire to elicit abusive experiences that occurred prior to 16 years of age. High levels of concurrent validity were demonstrated with the Parental Bonding Instrument (antipathy: rs = 0.350–0.737, P < .001; neglect: rs = 0.688–0.715, P < .001), and good convergent validity was shown with clinical case notes (sexual abuse: κ = 0.526, P < .001; physical abuse: κ = 0.394, P < .001). Psychosis patients’ reports were also reasonably stable over a 7-year period (sexual abuse: κ = 0.590, P < .01; physical abuse: κ = 0.634, P < .001; antipathy: κ = 0.492, P < .01; neglect: κ = 0.432, P < .05). Additionally, their reports of childhood abuse were not associated with current severity of psychotic symptoms (sexual abuse: U = 1768.5, P = .998; physical abuse: U = 2167.5, P = .815; antipathy: U = 2216.5, P = .988; neglect: U = 1906.0, P = .835) or depressed mood (sexual abuse: χ2 = 0.634, P = .277; physical abuse: χ2 = 0.159, P = .419; antipathy: χ2 = 0.868, P = .229; neglect: χ2 = 0.639, P = .274). These findings provide justification for the use in future studies of retrospective reports of childhood abuse obtained from individuals with psychotic disorders.

Altered Functional and Anatomical Connectivity in Schizophrenia

Abstract: Background: Schizophrenia is characterized by a lack of integration between thought, emotion, and behavior. A disruption in the connectivity between brain processes may underlie this schism. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were used to evaluate functional and anatomical brain connectivity in schizophrenia. Methods: In all, 29 chronic schizophrenia patients (11 females, age: mean = 41.3, SD = 9.28) and 29 controls (11 females, age: mean = 41.1, SD = 10.6) were recruited. Schizophrenia patients were assessed for severity of negative and positive symptoms and general cognitive abilities of attention/concentration and memory. Participants underwent a resting-fMRI scan and a DTI scan. For fMRI data, a hybrid independent components analysis was used to extract the group default mode network (DMN) and accompanying time-courses. Voxel-wise whole-brain multiple regressions with corresponding DMN time-courses was conducted for each subject. A t-test was conducted on resulting DMN correlation maps to look between-group differences. For DTI data, voxel-wise statistical analysis of the fractional anisotropy data was carried out to look for between-group differences. Voxel-wise correlations were conducted to investigate the relationship between brain connectivity and behavioral measures. Results: Results revealed altered functional and anatomical connectivity in medial frontal and anterior cingulate gyri of schizophrenia patients. In addition, frontal connectivity in schizophrenia patients was positively associated with symptoms as well as with general cognitive ability measures. Discussion: The present study shows convergent fMRI and DTI findings that are consistent with the disconnection hypothesis in schizophrenia, particularly in medial frontal regions, while adding some insight of the relationship between brain disconnectivity and behavior.

Neurocognitive Dysfunction in Bipolar and Schizophrenia Spectrum Disorders Depends on History of Psychosis Rather Than Diagnostic Group

Abstract: Objectives: Neurocognitive dysfunction is milder in bipolar disorders than in schizophrenia spectrum disorders, supporting a dimensional approach to severe mental disorders. The aim of this study was to investigate the role of lifetime history of psychosis for neurocognitive functioning across these disorders. We asked whether neurocognitive dysfunctioninbipolarandschizophreniaspectrumdisordersdepends more on history of psychosis than diagnostic category or subtype. Methods: A sample of individuals with schizophrenia (n 5 102), schizoaffective disorder (n 5 27), and bipolar disorder (I or II) with history of psychosis (n 5 75) and without history of psychosis (n 5 61) and healthy controls (n 5 280), from a large ongoing study on severe mental disorder, were included. Neurocognitive function was measured with a comprehensive neuropsychological test battery. Results: Compared with controls, all 3 groups with a history of psychosis performed poorer across neurocognitive measures, while the bipolar group without a history of psychosis was only impaired on a measure of processing speed. The groups with a history of psychosis did not differ from each other but performed poorer than the group without a history of psychosis on a number of neurocognitive measures. These neurocognitive group differences were of a magnitude expected to have clinical significance. In the bipolar sample,historyofpsychosisexplainedmoreoftheneurocognitivevariancethanbipolardiagnosticsubtype.Conclusions: Our findings suggest that neurocognitive dysfunction in bipolar and schizophrenia spectrum disorders is determined more by history of psychosis than by Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnostic category or subtype, supporting a more dimensional approach in future diagnostic systems.

Are Screening Instruments Valid for Psychotic-Like Experiences? A Validation Study of Screening Questions for Psychotic-Like Experiences Using In-Depth Clinical Interview

Abstract: Individuals who report psychotic-like experiences are at increased risk of future clinical psychotic disorder. They constitute a unique “high-risk” group for studying the developmental trajectory to schizophrenia and related illnesses. Previous research has used screening instruments to identify this high-risk group, but the validity of these instruments has not yet been established. We administered a screening questionnaire with 7 items designed to assess psychotic-like experiences to 334 adolescents aged 11–13 years. Detailed clinical interviews were subsequently carried out with a sample of these adolescents. We calculated sensitivity and specificity and positive predictive value (PPV) and negative predictive value (NPV) for each screening question for the specific symptom it enquired about and also in relation to any psychotic-like experience. The predictive power varied substantially between items, with the question on auditory hallucinations (“Have you ever heard voices or sounds that no one else can hear?”) providing the best predictive power. For interview-verified auditory hallucinations specifically, this question had a PPV of 71.4% and an NPV of 90.4%. When assessed for its predictive power for any psychotic-like experience (including, but not limited to, auditory hallucinations), it provided a PPV of 100% and an NPV of 88.4%. Two further questions—relating to visual hallucinations and paranoid thoughts—also demonstrated good predictive power for psychotic-like experiences. Our results suggest that it may be possible to screen the general adolescent population for psychotic-like experiences with a high degree of accuracy using a short self-report questionnaire.

Brain Anatomical Abnormalities in High-Risk Individuals, First-Episode, and Chronic Schizophrenia: An Activation Likelihood Estimation Meta-analysis of Illness Progression

Abstract: Objective: The present study reviewed voxel-based morphometry (VBM) studies on high-risk individuals with schizophrenia, patients experiencing their first-episode schizophrenia (FES), and those with chronic schizophrenia. We predicted that gray matter abnormalities would show progressive changes, with most extensive abnormalities in the chronic group relative to FES and least in the high-risk group. Method: Forty-one VBM studies were reviewed. Eight high-risk studies, 14 FES studies, and 19 chronic studies were analyzed using anatomical likelihood estimation meta-analysis. Results: Less gray matter in the high-risk group relative to controls was observed in anterior cingulate regions, left amygdala, and right insula. Lower gray matter volumes in FES compared with controls were also found in the anterior cingulate and right insula but not the amygdala. Lower gray matter volumes in the chronic group were most extensive, incorporating similar regions to those found in FES and high-risk groups but extending to superior temporal gyri, thalamus, posterior cingulate, and parahippocampal gryus. Subtraction analysis revealed less frontotemporal, striatal, and cerebellar gray matter in FES than the high-risk group; the high-risk group had less gray matter in left subcallosal gyrus, left amygdala, and left inferior frontal gyrus compared with FES. Subtraction analysis confirmed lower gray matter volumes through ventral-dorsal anterior cingulate, right insula, left amygdala and thalamus in chronic schizophrenia relative to FES. Conclusions: Frontotemporal brain structural abnormalities are evident in nonpsychotic individuals at high risk of developing schizophrenia. The present meta-analysis indicates that these gray matter abnormalities become more extensive through first-episode and chronic illness. Thus, schizophrenia appears to be a progressive cortico-striato-thalamic loop disorder.

Neurocognitive Predictors of Work Outcome in Recent-Onset Schizophrenia

Abstract: While the role of neurocognitive impairment in predicting functional outcome in chronic schizophrenia is now widely accepted, the results that have examined this relationship in the early phase of psychosis are surprisingly rather mixed. The predictive role of cognitive impairment early in the illness is of particular interest because interventions during this initial period may help to prevent the development of chronic disability. In a University of California, Los Angeles (UCLA) longitudinal study, we assessed schizophrenia patients with a recent first episode of psychosis using a neurocognitive battery at an initial clinically stabilized outpatient point and then followed them during continuous treatment over the next 9 months. Three orthogonal cognitive factors were derived through principal components analysis: working memory, attention and early perceptual processing, and verbal memory and processing speed. All patients were provided a combination of maintenance antipsychotic medication, case management, group skills training, and family education in a UCLA research clinic. A modified version of the Social Adjustment Scale was used to assess work outcome. Multiple regression analyses indicate that the combination of the 3 neurocognitive factors predicts 52% of the variance in return to work or school by 9 months after outpatient clinical stabilization. These data strongly support the critical role of neurocognitive factors in recovery of work functioning after an onset of schizophrenia. Cognitive remediation and other interventions targeting these early cognitive deficits are of major importance to attempts to prevent chronic disability.

Age of Onset of Schizophrenia: Perspectives From Structural Neuroimaging Studies

Abstract: Many of the major neuropsychiatric illnesses, including schizophrenia, have a typical age of onset in late adolescence. Late adolescence may reflect a critical period in brain development making it particularly vulnerable for the onset of psychopathology. Neuroimaging studies that focus on this age range may provide unique insights into the onset and course of psychosis. In this review, we examine the evidence from 2 unique longitudinal cohorts that span the ages from early childhood through young adulthood; a study of childhood-onset schizophrenia where patients and siblings are followed from ages 6 through to their early twenties, and an ultra-high risk study where subjects (mean age of 19 years) are studied before and after the onset of psychosis. From the available evidence, we make an argument that subtle, regionally specific, and genetically influenced alterations during developmental age windows influence the course of psychosis and the resultant brain phenotype. The importance of examining trajectories of development and the need for future combined approaches, using multimodal imaging together with molecular studies is discussed.

Perceptual Organization Impairment in Schizophrenia and Associated Brain Mechanisms: Review of Research from 2005 to 2010

Abstract: Perceptual organization (PO) refers to the processes by which visual information is structured into coherent patterns such as groups, contours, perceptual wholes, and object representations. Impairments in PO have been demonstrated in schizophrenia since the 1960s and have been linked to several illness-related factors including poor premorbid functioning, poor prognosis, and disorganized symptoms. This literature was last reviewed in 2005. Since then, electrophysiological (electroencephalographic, event-related potential, and magnetoencephalographic) and fMRI studies in both patient and nonpatient samples have clarified brain mechanisms involved in the impairment, and additional behavioral studies in patients and nonpatients have clarified the computational mechanisms. In addition, data now exist on the functional consequences of PO impairments, in terms of secondary difficulties in face processing, selective attention, working memory, and social cognition. Preliminary data on drug effects on PO and on changes in response to treatment suggest that anomalies in PO may furnish a biomarker for the integrity of its associated biological mechanisms. All of this recent evidence allows for a clearer picture of the nature of the impairment and how it relates to broader aspects of brain and behavioral functioning in schizophrenia.

Psychotic-Like Experiences in Major Depression and Anxiety Disorders: A Population-Based Survey in Young Adults

Abstract: Objective: Population-based surveys have confirmed that psychotic-like experiences are prevalent in the community. However, it is unclear if these experiences are associated with common mental disorders. The aim of this study was to examine the prevalence of psychotic-like experiences in those with affective and anxiety disorders. Methods: Subjects were drawn from the Mater-University of Queensland Study of Pregnancy. Delusion-like experiences were assessed with the Peters Delusional Inventory (PDI). The Composite International Diagnostic Interview (CIDI) was used to identify individuals with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) lifetime diagnoses of major depression, anxiety disorder, substance use/dependence, and psychotic disorders. The influence of affective and anxiety disorders on PDI and CIDI psychosis-related items' scores were assessed with logistic regression, with adjustments for age, sex, and the presence of the other comorbid psychiatric diagnoses. Results: Having either a lifetime diagnosis of major depressive disorder or an anxiety disorder was associated with significantly higher PDI total scores (highest vs lowest quartile adjusted odds ratios [ORs] and 95% confidence intervals [CIs] = 4.43, 3.09-6.36; 3.08, 2.26-4.20, respectively). The odds of endorsing any CIDI hallucination or delusion item was increased in those with a major depressive or anxiety disorder. The presence of current anxiety disorder symptoms was significantly associated with PDI score (OR = 5.81, 95% CI = 3.68-9.16). Conclusion: While psychotic-like experiences are usually associated with psychotic disorders, individuals with depression and anxiety are also more likely to report these symptoms compared with well individuals. Psychotic-like experiences are associated with a range of common mental disorders.

A Disappearing Heritage: The Clinical Core of Schizophrenia

Abstract: This article traces the fundamental descriptive features of schizophrenia described in the European continental literature form Kraepelin and Bleuler, culminating with the creation of the International Classification of Diseases (ICD)-8 (1974).Therewasaconsensusamongtheresearchersthatthe specificityandtypicalityofschizophreniawasanchoredtoits ‘‘fundamental’’clinicalcore(withtraitstatus)andnottopositive psychotic features, which were considered as ‘‘state’’, ‘‘accessory’’ phenomena.Theclinicalcoreofschizophrenia was,inadilutedform,constitutiveofthespectrumconditions (‘‘schizoidia’’and‘‘latentschizophrenia’’).Thefundamental features are manifest across all domains of consciousness: subjectiveexperience,expression,cognition,affectivity,behavior, and willing. Yet, the specificity of the core was only graspable at a more comprehensive Gestalt-level, variously designated(eg,discordance,autism,‘‘Spaltung’’),andnoton the level of single features. In other words, the phenomenological specificity was seen as being expressive of a fundamental structural or formal change of the patient’s mentality (consciousness, subjectivity). This overall change transpires through the single symptoms and signs, lending them a characteristic phenomenological pattern. This concept of schizophrenia bears little resemblance to the current operational definitions. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and ICD-10 seemtodiagnoseasubsetofpatientswithchronicparanoidhallucinatory variant of schizophrenia.

Toward the Next Generation of Negative Symptom Assessments: The Collaboration to Advance Negative Symptom Assessment in Schizophrenia

Abstract: Negative symptoms in schizophrenia are related to poor functionaloutcome,persistent overtime, asourceof burden for caregivers, and only minimally responsive to currently available medications. A major challenge to developing efficacious interventions concerns the valid and reliable assessment of negative symptoms. In a recent consensus statement on negative symptoms, a central recommendation was the need to develop new assessment approaches that address the limitations of existing instruments. In the current report, we summarize the background and rationale for the Collaboration to Advance Negative Symptom Assessment in Schizophrenia (CANSAS). The CANSAS project is an National Institute of Mental Health-funded multisite study that is constructing a next-generation negative symptom scale, the Clinical Assessment Interview for Negative Symptoms (CAINS). The CAINS is being developed within a data-driven iterative process that seeks to ensure the measure’s reliability, validity, and utility for both basic psychopathology and treatment development research.

Preventing the Second Episode: A Systematic Review and Meta-analysis of Psychosocial and Pharmacological Trials in First-Episode psychosis

Abstract: Objective: The majority of first-episode psychosis (FEP) patients reach clinical remission; however, rates of relapse are high. This study sought to undertake a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effectiveness of pharmacological and non-pharmacological interventions to prevent relapse in FEP patients. Methods: Systematic review and meta-analysis of RCTs. Results: Of 66 studies retrieved, 18 were eligible for inclusion. Nine studies investigated psychosocial interventions and 9 pharmacological treatments. The analysis of 3 RCTs of psychosocial interventions comparing specialist FEP programs vs treatment as usual involving 679 patients demonstrated the former to be more effective in preventing relapse (odds ratio [OR] = 1.80, 95% confidence interval [CI] = 1.31–2.48; P < .001; number needed to treat [NNT] = 10). While the analysis of 3 different cognitive-behavioral studies not specifically intended at preventing relapse showed no further benefits compared with specialist FEP programs (OR = 1.95, 95% CI = 0.76–5.00; P = .17), the combination of specific individual and family intervention targeted at relapse prevention may further improve upon these outcomes (OR = 4.88, 95% CI = 0.97–24.60; P = .06). Only 3 small studies compared first-generation antipsychotics (FGAs) with placebo with no significant differences regarding relapse prevention although all individual estimates favored FGAs (OR = 2.82, 95% CI = 0.54–14.75; P = .22). Exploratory analysis involving 1055 FEP patients revealed that relapse rates were significantly lower with second-generation antipsychotics (SGAs) compared with FGAs (OR = 1.47, 95% CI = 1.07–2.01; P < .02; NNT = 10). Conclusions: Specialist FEP programs are effective in preventing relapse. Cognitive-based individual and family interventions may need to specifically target relapse to obtain relapse prevention benefits that extend beyond those provided by specialist FEP programs. Overall, the available data suggest that FGAs and SGAs have the potential to reduce relapse rates. Future trials should examine the effectiveness of placebo vs antipsychotics in combination with intensive psychosocial interventions in preventing relapse in the early course of psychosis. Further studies should identify those patients who may not need antipsychotic medication to be able to recover from psychosis.

The Thalamic Reticular Nucleus and Schizophrenia

Abstract: Background: The thalamic reticular nucleus (TRN) is a shell-shaped gamma amino butyric acid (GABA)ergic nucleus, which is uniquely placed between the thalamus and the cortex, because it receives excitatory afferents from both cortical and thalamic neurons and sends inhibitory projections to all nuclei of the dorsal thalamus. Method: A review of the evidence suggesting that the TRN is implicated in the neurobiology of schizophrenia. Results: TRN-thalamus circuits are implicated in bottom-up as well as top-down processing. TRN projections to nonspecific nuclei of the dorsal thalamus mediate top-down processes, including attentional modulation, which are initiated by cortical afferents to the TRN. TRN-thalamus circuits are also involved in bottom-up activities, including sensory gating and the transfer to the cortex of sleep spindles. Intriguingly, deficits in attention and sensory gating have been consistently found in schizophrenics, including first-break and chronic patients. Furthermore, high-density electroencephalographic studies have revealed a marked reduction in sleep spindles in schizophrenics. Conclusion: On the basis of our current knowledge on the molecular and anatomo-functional properties of the TRN, we suggest that this thalamic GABAergic nucleus may be involved in the neurobiology of schizophrenia.

Impaired Kynurenine Pathway Metabolism in The Prefrontal Cortex of Individuals With Schizophrenia

Abstract: The levels of kynurenic acid (KYNA), an astrocyte-derived metabolite of the branched kynurenine pathway (KP) of tryptophan degradation and antagonist of α7 nicotinic acetylcholine and N-methyl-D-aspartate receptors, are elevated in the prefrontal cortex (PFC) of individuals with schizophrenia (SZ). Because endogenous KYNA modulates extracellular glutamate and acetylcholine levels in the PFC, these increases may be pathophysiologically significant. Using brain tissue from SZ patients and matched controls, we now measured the activity of several KP enzymes (kynurenine 3-monooxygenase [KMO], kynureninase, 3-hydroxyanthranilic acid dioxygenase [3-HAO], quinolinic acid phosphoribosyltransferase [QPRT], and kynurenine aminotransferase II [KAT II]) in the PFC, ie, Brodmann areas (BA) 9 and 10. Compared with controls, the activities of KMO (in BA 9 and 10) and 3-HAO (in BA 9) were significantly reduced in SZ, though there were no significant differences between patients and controls in kynureninase, QPRT, and KAT II. In the same samples, we also confirmed the increase in the tissue levels of KYNA in SZ. As examined in rats treated chronically with the antipsychotic drug risperidone, the observed biochemical changes were not secondary to medication. A persistent reduction in KMO activity may have a particular bearing on pathology because it may signify a shift of KP metabolism toward enhanced KYNA synthesis. The present results further support the hypothesis that the normalization of cortical KP metabolism may constitute an effective new treatment strategy in SZ.

Stigma Resistance in Patients With Schizophrenia

Abstract: Background: An individual’s capacity to counteract the stigma of mental illness, stigma resistance (SR), is considered as playing a crucial role in fighting stigma. However, little is known about SR and its correlates in patients with schizophrenia or schizoaffective disorder. Aim: Exploring SR in patients with schizophrenia or schizoaffective disorder. Method: One hundred fifty-seven participants completed the ‘‘Internalized Stigma of Mental Illness’’ (ISMI) Scale including its subscale on SR. Measures of perceived devaluation and discrimination, depression, selfesteem, empowerment, quality of life, and demographic and clinical variables were obtained. Results: Two-thirds of all patients showed high SR. SR correlated positively with self-esteem, empowerment, and quality of life and negatively with stigma measures and depression. A social network with a sufficient number of friends, being single or married, in contrast to being separated, as well as receiving outpatient treatment, was associated with higher SR. Conclusions: SR is a new and promising concept. The development of stigma-resisting beliefs might help individuals in their hope of finding a fulfilling life and in their recovery from mental illness.

Thinking About the Future Cognitive Remediation Therapy—What Works and Could We Do Better?

Abstract: This article reviews progress in the development of effective cognitive remediation therapy (CRT) and its translational process. There is now enough evidence that cognitive difficulties experienced by people with schizophrenia can change and that the agenda for the next generation of studies is to increase these effects systematically through cognitive remediation. We examine the necessary steps and challenges of moving CRT to treatment dissemination. Theories which have been designed to explain the effects of cognitive remediation, are important but we conclude that they are not essential for dissemination which could progress in an empirical fashion. One apparent barrier is that cognitive remediation therapies look different on the surface. However, they still tend to use many of the same training procedures. The only important marker for outcome identified in the current studies seems to be the training emphasis. Some therapies concentrate on massed practice of cognitive functions, whereas others also use direct training of strategies. These may produce differing effects as noted in the most recent meta-analyses. We recommend attention to several critical issues in the next generation of empirical studies. These include developing more complex models of the therapy effects that take into account participant characteristics, specific and broad cognitive outcomes, the study design, as well as the specific and nonspecific effects of treatment, which have rarely been investigated in this empirical programme.

Who Benefits From Supported Employment: A Meta-analytic Study

Abstract: Aims: This meta-analysis sought to identify which subgroups of clients with severe mental illness (SMI) benefited from evidence-based supported employment. Methods: We used meta-analysis to pool the samples from 4 randomized controlled trials comparing the Individual Placement and Support (IPS) model of supported employment to well-regarded vocational approaches using stepwise models and brokered services. Meta-analysis was used to determine the magnitude of effects for IPS/control group differences within specific client subgroups (defined by 2 work history, 7 sociodemographic, and 8 clinical variables) on 3 competitive employment outcomes (obtaining a job, total weeks worked, and job tenure). Results: The findings strongly favored IPS, with large effect sizes across all outcomes: 0.96 for job acquisition, 0.79 for total weeks worked, and 0.74 for job tenure. Overall, 90 (77%) of the 117 effect sizes calculated for the 39 subgroups exceeded 0.70, and all 117 favored IPS. Conclusions: IPS produces better competitive employment outcomes for persons with SMI than alternative vocational programs regardless of background demographic, clinical, and employment characteristics.

Looking at the Schizophrenia Spectrum Through the Prism of Self-disorders: An Empirical Study

Abstract: Nonpsychotic anomalies of subjective experience were emphasized in both classic literature and phenomenological psychiatry as essential clinical features of schizophrenia. However, only in recent years, their topicality with respect to the construct validity of the concept of the schizophrenia spectrum has been explicitly acknowledged, mainly as a consequence of the increasing focus on early detection and prevention of psychosis. The current study tested the hypothesis of a specific aggregation of self-disorders (SDs, various anomalies of self-awareness) in schizophrenia-spectrum conditions, comparing different diagnostic groups; 305 subjects, previously assessed in the Copenhagen Schizophrenia Linkage Study, were grouped into 4 experimental samples, according to their Diagnostic and Statistical Manual of Mental Disorders (Third Edition Revised) main diagnosis: schizophrenia, (n 5 29), schizotypal personality disorder (n 5 61), other mental illness not belonging to the schizophrenia spectrum (n 5 112), and no mental illness (n 5 103). The effect of diagnostic grouping on the level of SDs was explored via general linear model and logistic regression. The diagnosis of schizophrenia and schizotypy predicted higher levels of SDs, and SDs scores were significantly different between spectrum and nonspectrum samples; the likelihood of experiencing SDs increased as well with the diagnostic severity. The findings support the assumption that SDs are a discriminant psychopathological feature of the schizophrenia spectrum and suggest their incorporation to strengthen its construct validity, with potential benefit for both early detection and pathogenetic research.

High vs Low Frequency Neural Oscillations in Schizophrenia

Abstract: There is growing recognition that neural oscillations are important in a wide range of perceptual and cognitive functions. One of the key issues in electrophysiological studies of schizophrenia is whether high or low frequency oscillations, or both, are related to schizophrenia because many brain functions are modulated with frequency specificities. Many recent electrophysiological studies of schizophrenia have focused on high frequency oscillations at gamma band and in general support gamma band dysfunction in schizophrenia. We discuss the concept that gamma oscillation abnormalities in schizophrenia often occur in the background of oscillation abnormalities of lower frequencies. The review discusses the basic neurobiology for the emergence of oscillations of all frequency bands in association with networks of inhibitory interneurons and the convergence and divergence of such mechanisms in generating high vs low frequency oscillations. We then review the literature of oscillatory frequency abnormalities identified in each frequency band in schizophrenia. By describing some of the key functional roles exerted by gamma, low frequencies, and their cross-frequency coupling, we conceptualize that even isolated alterations in gamma or low frequency oscillations may impact the interactions of high and low frequency bands that are involved in key cognitive functions. The review concludes that studying the full spectrum and the interaction of gamma and low frequency oscillations may be critical for deciphering the complex electrophysiological abnormalities observed in schizophrenia patients.

Maternal Infection and Schizophrenia: Implications for Prevention

Abstract: Accumulating evidence suggests that maternal infection is a risk factor for schizophrenia. Prospective epidemiological studies indicate that maternal influenza, toxoplasmosis, and genital/reproductive infection are associated with this disorder in offspring. Preclinical models of maternal immune activation have supported the neurobiological plausibility of these microbes in schizophrenia. Previous studies suggest that treatment or prophylactic efforts targeting these and other infections could have significant effects on reducing the incidence of schizophrenia, given that they are common in the population and the effect sizes derived from epidemiological studies of these and other microbial pathogens and schizophrenia, to date, are not small. Fortunately, the occurrence of many of these infections can be reduced with relatively practical and inexpensive interventions that are scalable to large populations given adequate resources. Hence, in the present article, we focus on the potential for prevention of schizophrenia by control of infection, using these 3 categories of infection as examples. Lessons learned from previous successful public health efforts targeting these infections, including the relative advantages and disadvantages of these measures, are reviewed.

Meta-analysis of Paternal Age and Schizophrenia Risk in Male Versus Female Offspring

Abstract: Introduction: Advanced paternal age (APA) is a reported risk factor for schizophrenia in the offspring. We performed a meta-analysis of this association, considering the effect of gender and study design. Methods: We identified articles by searching Pub Med, PsychInfo, ISI, and EMBASE, and the reference lists of identified studies. Previously unpublished data from the Northern Finland 1966 Birth Cohort (NFBC 1966) study were also included. Results: There were 6 cohort studies and 6 case–control studies that met the inclusion criteria. In both study designs, there was a significant increase in risk of schizophrenia in the offspring of older fathers (‡30) compared to a reference paternal age of 25–29, with no gender differences. The relative risk (RR) in the oldest fathers (‡50) was 1.66 [95% confidence interval (95% CI): 1.46–1.89, P < 0.01]. A significant increase in risk was also found for younger fathers (<25) in males (RR 5 1.08, 95% CI: 1.02–1.14, P 5 0.01) but not females (RR 5 1.04, 95% CI: 0.97– 1.14,P 5 0.28). The population attributable risk percentage (PAR%) was 10% for paternal age ‡30 and 5% for paternal age <25. Discussion: Both APA (‡30) and younger paternal age (<25) increase the risk of schizophrenia; younger paternal age may be associated with an increased risk in males but not females. This risk factor increases the risk of schizophrenia as much as any single candidate gene of risk. The mechanism of these associations is not known and may differ for older and younger fathers.

The Structure of The Extended Psychosis Phenotype in Early Adolescence—A Cross-sample Replication

Abstract: The extended psychosis phenotype, or the expression of nonclinical positive psychotic experiences, is already prevalent in adolescence and has a dose-response risk relationship with later psychotic disorder. In 2 large adolescent general population samples (n = 5422 and n = 2230), prevalence and structure of the extended psychosis phenotype was investigated. Positive psychotic experiences, broadly defined, were reported by the majority of adolescents. Exploratory analysis with Structural Equation Modelling (Exploratory Factor Analysis followed by Confirmatory Factor Analysis [CFA]) in sample 1 suggested that psychotic experiences were best represented by 5 underlying dimensions; CFA in sample 2 provided a replication of this model. Dimensions were labeled Hallucinations, Delusions, Paranoia, Grandiosity, and Paranormal beliefs. Prevalences differed strongly, Hallucinations having the lowest and Paranoia having the highest rates. Girls reported more experiences on all dimensions, except Grandiosity, and from age 12 to 16 years rates increased. Hallucinations, Delusions, and Paranoia, but not Grandiosity and Paranormal beliefs, were associated with distress and general measures of psychopathology. Thus, only some of the dimensions of the extended psychosis phenotype in young people may represent a continuum with more severe psychopathology and predict later psychiatric disorder.

Effectiveness of Integrated Psychological Therapy (IPT) for Schizophrenia Patients: A Research Update

Abstract: Standardized recovery criteria go beyond symptom remission and put special emphasis on personal and social functioning in residence, work, and leisure. Against this background, evidence-based integrated approaches combining cognitive remediation with social skills therapy show promise for improving functional recovery of schizophrenia patients. Over the past 30 years, research groups in 12 countries have evaluated integrated psychological therapy (IPT) in 36 independent studies. IPT is a group therapy program for schizophrenia patients. It combines neurocognitive and social cognitive interventions with social skills and problem-solving approaches. The aim of the present study was to update and integrate the growing amount of research data on the effectiveness of IPT. We quantitatively reviewed the results of these 36 studies, including 1601 schizophrenia patients, by means of a meta-analytic procedure. Patients undergoing IPT showed significantly greater improvement in all outcome variables (neurocognition, social cognition, psychosocial functioning, and negative symptoms) than those in the control groups (placebo-attention conditions and standard care). IPT patients maintained their mean positive effects during an average follow-up period of 8.1 months. They showed better effects on distal outcome measures when all 5 subprograms were integrated. This analysis summarizes the broad empirical evidence indicating that IPT is an effective rehabilitation approach for schizophrenia patients and is robust across a wide range of sample characteristics as well as treatment conditions. Moreover, the cognitive and social subprograms of IPT may work in a synergistic manner, thereby enhancing the transfer of therapy effects over time and improving functional recovery.

The Development of Neural Synchrony and Large-Scale Cortical Networks During Adolescence: Relevance for the Pathophysiology of Schizophrenia and Neurodevelopmental Hypothesis

Abstract: Recent data from developmental cognitive neuroscience highlight the profound changes in the organization and function of cortical networks during the transition from adolescence to adulthood While previous studies have focused on the development of gray and white matter, recent evidence suggests that brain maturation during adolescence extends to fundamental changes in the properties of cortical circuits that in turn promote the precise temporal coding of neural activity In the current article, we will highlight modifications in the amplitude and synchrony of neural oscillations during adolescence that may be crucial for the emergence of cognitive deficits and psychotic symptoms in schizophrenia Specifically, we will suggest that schizophrenia is associated with impaired parameters of synchronous oscillations that undergo changes during late brain maturation, suggesting an important role of adolescent brain development for the understanding, treatment, and prevention of the disorder

Oxytocin, Dopamine, and the Amygdala: A Neurofunctional Model of Social Cognitive Deficits in Schizophrenia

Abstract: Until recently, the social cognitive impairment in schizophrenia has been underappreciated and remains essentially untreated. Deficits in emotional processing, social perception and knowledge, theory of mind, and attributional bias may contribute to functional social cognitive impairments in schizophrenia. The amygdala has been implicated as a key component of social cognitive circuitry in both animal and human studies. In addition, structural and functional studies of schizophrenia reproducibly demonstrate abnormalities in the amygdala and dopaminergic signaling. Finally, the neurohormone oxytocin plays an important role in multiple social behaviors in several mammals, including humans. We propose a model of social cognitive dysfunction in schizophrenia and discuss its therapeutic implications. The model comprises abnormalities in oxytocinergic and dopaminergic signaling in the amygdala that result in impaired emotional salience processing with consequent social cognitive deficits.