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Preview: Schizophrenia Bulletin - current issue

Schizophrenia Bulletin Current Issue





Published: Thu, 15 Feb 2018 00:00:00 GMT

Last Build Date: Thu, 15 Feb 2018 03:47:09 GMT

 



Erratum to: Devoe DJ, Peterson A, Addington J. Negative Symptom Interventions in Youth at Risk of Psychosis: A Systematic Review and Network Meta-Analysis

Thu, 15 Feb 2018 00:00:00 GMT

Erratum to: Devoe DJ, Peterson A, Addington J. Negative Symptom Interventions in Youth at Risk of Psychosis: A Systematic Review and Network Meta-Analysis. Schizophr Bull. doi:10.1093/schbul/sbx139



Can We Predict Psychosis Outside the Clinical High-Risk State? A Systematic Review of Non-Psychotic Risk Syndromes for Mental Disorders

Fri, 09 Feb 2018 00:00:00 GMT

Abstract
Recent evidence has suggested that psychosis could develop not only in people at clinical high risk for psychosis (CHR-P) but also in those with clinical risk syndromes for emergent nonpsychotic mental disorders. The proportion of people with these clinical risk syndromes who will develop psychosis rather than to other nonpsychotic mental disorders is undetermined. Electronic databases were searched for studies reporting on clinical risk syndromes for the development of emergent nonpsychotic mental disorders. Incidence of emerging psychotic and nonpsychotic mental disorders defined on the ICD or DSM. Of a total of 9 studies relating to 3006 nonpsychotic at-risk individuals were included. Within prospective studies (n = 4, sample = 1051), the pooled incidence of new psychotic disorders across these clinical risk syndromes was of 12.9 per 1000 person-years (95% CI: 4.3 to 38.6) and that of nonpsychotic disorders (n = 3, sample = 538) was of 43.5 per 1000 person-years (95% CI: 30.9 to 61.3). Psychotic disorders may emerge outside the CHR-P paradigm, from clinical risk syndromes for incident nonpsychotic disorders, albeit at lower rates than in the CHR-P group. The clinical risk syndromes for emerging nonpsychotic disorders may exhibit a pluripotential risk of developing several types of mental disorders compared with CHR-P. If substantiated by future research, the current findings suggest that it may be useful to move beyond the current strategy of identifying individuals meeting CHR-P criteria only.






Clinical High Risk Controversies and Challenge for the Experts

Wed, 20 Dec 2017 00:00:00 GMT

At risk mental states, ultra high risk and attenuated psychosis syndrome are terms associated with the rapidly expanding field of clinical high risk (CHR) research and initiatives in clinical care. Much is debated as indicated in the theme introduction by Fusar-Poli1 (this issue). Lee et al2 (this issue) address risk prediction for psychopathology beyond the focus on psychosis. Woods et al3 (this issue) test the hypothesis that CHR categories involve pathological processes that are pleuripotential resulting in risk for various disorders. Findings do not support this hypothesis and support a more narrow prediction for associated psychotic disorders. Fusar-Poli et al4 (this issue) provide evidence for the clinical usefulness of the DSM-5, Section 3 attenuated psychosis syndrome. In this, editorial controversies in the field and challenges to the experts will be summarized.



Auditory Verbal Hallucinations in Schizophrenia From a Levels of Explanation Perspective

Tue, 24 Oct 2017 00:00:00 GMT

Abstract
In the present article, we present a “Levels of Explanation” (LoE) approach to auditory verbal hallucinations (AVHs) in schizophrenia. Mental phenomena can be understood at different levels of explanation, including cultural, clinical, cognitive, brain imaging, cellular, and molecular levels. Current research on AVHs is characterized by accumulation of data at all levels, but with little or no interaction of findings between levels. A second advantage with a Levels of Explanation approach is that it fosters interdisciplinarity and collaboration across traditional borders, facilitating a real breakthrough in future research. We exemplify a Levels of Explanation approach with data from 3 levels where findings at 1 level provide predictions for another level. More specifically, we show how functional neuroimaging data at the brain level correspond with behavioral data at the cognitive level, and how data at these 2 levels correspond with recent findings of changes in neurotransmitter function at the cellular level. We further discuss implications for new therapeutic interventions, and the article is ended by suggestion how future research could incorporate genetic influences on AVHs at the molecular level of explanation by providing examples for animal work.



N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis

Sat, 07 Oct 2017 00:00:00 GMT

Abstract
Biomarker-guided treatments are needed in psychiatry, and previous data suggest oxidative stress may be a target in schizophrenia. A previous add-on trial with the antioxidant N-acetylcysteine (NAC) led to negative symptom reductions in chronic patients. We aim to study NAC’s impact on symptoms and neurocognition in early psychosis (EP) and to explore whether glutathione (GSH)/redox markers could represent valid biomarkers to guide treatment. In a double-blind, randomized, placebo-controlled trial in 63 EP patients, we assessed the effect of NAC supplementation (2700 mg/day, 6 months) on PANSS, neurocognition, and redox markers (brain GSH [GSHmPFC], blood cells GSH levels [GSHBC], GSH peroxidase activity [GPxBC]). No changes in negative or positive symptoms or functional outcome were observed with NAC, but significant improvements were found in favor of NAC on neurocognition (processing speed). NAC also led to increases of GSHmPFC by 23% (P = .005) and GSHBC by 19% (P = .05). In patients with high-baseline GPxBC compared to low-baseline GPxBC, subgroup explorations revealed a link between changes of positive symptoms and changes of redox status with NAC. In conclusion, NAC supplementation in a limited sample of EP patients did not improve negative symptoms, which were at modest baseline levels. However, NAC led to some neurocognitive improvements and an increase in brain GSH levels, indicating good target engagement. Blood GPx activity, a redox peripheral index associated with brain GSH levels, could help identify a subgroup of patients who improve their positive symptoms with NAC. Thus, future trials with antioxidants in EP should consider biomarker-guided treatment.



Lack of Diagnostic Pluripotentiality in Patients at Clinical High Risk for Psychosis: Specificity of Comorbidity Persistence and Search for Pluripotential Subgroups

Thu, 28 Sep 2017 00:00:00 GMT

Abstract
More than 20 years after the clinical high risk syndrome for psychosis (CHR) was first articulated, it remains controversial whether the CHR syndrome predicts onset of psychosis with diagnostic specificity or predicts pluripotential diagnostic outcomes. Recently, analyses of observational studies, however, have suggested that the CHR syndrome is not pluripotential for emergent diagnostic outcomes. The present report conducted additional analyses in previously reported samples to determine (1) whether comorbid disorders were more likely to persist in CHR patients compared to a comparison group of patients who responded to CHR recruitment efforts but did not meet criteria, termed help-seeking comparison subjects (HSC); and (2) whether clinically defined pluripotential CHR subgroups could be identified. All data were derived from 2 multisite studies in which DSM-IV structured diagnostic interviews were conducted at baseline and at 6-month intervals. Across samples we observed persistence of any nonpsychotic disorder in 80/147 CHR cases (54.4%) and in 48/84 HSC cases (57.1%, n.s.). Findings with persistence of anxiety, depressive, and bipolar disorders considered separately were similar. Efforts to discover pluripotential CHR subgroups were unsuccessful. These findings add additional support to the view that the CHR syndrome is not pluripotential for predicting various diagnostic outcomes but rather is specific for predicting emergent psychosis.



Prospective Relationships Between Motivation and Functioning in Recovery After a First Episode of Schizophrenia

Fri, 18 Aug 2017 00:00:00 GMT

Abstract
Diminished motivation is associated with robust impairment in psychosocial functioning in schizophrenia (SZ). Little is known about the reciprocal relationships between motivation and functioning, particularly following a first episode of psychosis. We tested bidirectional associations between motivation and social and occupational functioning in the year following a first episode of SZ spectrum disorder among patients in the Recovery After an Initial Schizophrenia Episode—Early Treatment Program (RAISE-ETP) study. Four hundred four individuals (aged 15–40) who presented with a first episode of SZ spectrum disorder (eg, SZ, schizoaffective or schizophreniform disorder, psychotic disorder not otherwise specified) completed assessments of work and school functioning, social functioning, and motivation at 6- and 12-month follow-up, controlling for assessments at study entry. Controlling for cognition, and psychotic and depressive symptoms measured at each time point, motivation at 6 months was associated with work and school participation at 12 months, but work and school participation at 6 months was not associated with motivation at 12 months. Conversely, social functioning at 6 months was associated with motivation at 12 months, but motivation at 6 months was not associated with social functioning at 12 months. Findings suggest that motivation is associated with later occupational, but not social, functioning in the first year following an initial episode of psychosis. Social functioning, on the other hand, is associated with later motivation. Future intervention trials focused on improving occupational functioning in this population may benefit from targeting patient motivation directly (eg, through motivational interviewing), or indirectly by improving relationships and support networks.



Blood-Based Protein Changes in Childhood Are Associated With Increased Risk for Later Psychotic Disorder: Evidence From a Nested Case–Control Study of the ALSPAC Longitudinal Birth Cohort

Thu, 27 Jul 2017 00:00:00 GMT

Abstract
The identification of early biological changes associated with the psychotic disorder (PD) is important as it may provide clues to the underlying pathophysiological mechanisms. We undertook the first proteomic profiling of blood plasma samples of children who later develop a PD. Participants were recruited from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) cohort who also participated in psychiatric assessment interviews at age 18. Protein expression levels at age 11 were compared between individuals who developed PD at age 18 (n = 37) with population-based age-matched controls (n = 38). Sixty out of 181 plasma proteins profiled were found to be differentially expressed (P < .05) in children with an outcome of the PD. Thirty-four of these proteins were found to be differentially expressed following correction for multiple comparisons. Pathway analysis implicated the complement and coagulation cascade. A second, targeted proteomic approach was used to verify these findings in age 11 plasma from subjects who reported psychotic experiences at age 18 (n = 40) in comparison to age-matched controls (n = 66). Our findings indicate that the complement and coagulation system is dysregulated in the blood during childhood before the development of the PD.



Latent Profile Analysis and Conversion to Psychosis: Characterizing Subgroups to Enhance Risk Prediction

Fri, 14 Jul 2017 00:00:00 GMT

Abstract
Background: Groups at clinical high risk (CHR) of developing psychosis are heterogeneous, composed of individuals with different clusters of symptoms. It is likely that there exist subgroups, each associated with different symptom constellations and probabilities of conversion. Method: Present study used latent profile analysis (LPA) to ascertain subgroups in a combined sample of CHR (n = 171) and help-seeking controls (HSCs; n = 100; PREDICT study). Indicators in the LPA model included baseline Scale of Prodromal Symptoms (SOPS), Calgary Depression Scale for Schizophrenia (CDSS), and neurocognitive performance as measured by multiple instruments, including category instances (CAT). Subgroups were further characterized using covariates measuring demographic and clinical features. Results: Three classes emerged: class 1 (mild, transition rate 5.6%), lowest SOPS and depression scores, intact neurocognitive performance; class 2 (paranoid-affective, transition rate 14.2%), highest suspiciousness, mild negative symptoms, moderate depression; and class 3 (negative-neurocognitive, transition rate 29.3%), highest negative symptoms, neurocognitive impairment, social cognitive impairment. Classes 2 and 3 evidenced poor social functioning. Conclusions: Results support a subgroup approach to research, assessment, and treatment of help-seeking individuals. Class 3 may be an early risk stage of developing schizophrenia.



Embracing Psychosis: A Cognitive Insight Intervention Improves Personal Narratives and Meaning-Making in Patients With Schizophrenia

Tue, 04 Jul 2017 00:00:00 GMT

Abstract
Schizophrenia is a complex psychiatric disorder with unknown and presumably heterogeneous etiology. While the disorder can have various outcomes, research is predominantly “deficit-oriented” emphasizing the hardship that the disorder inflicts on sufferers as well as their families and society. Beyond symptom reduction, imparting patients with hope and meaning in life is increasingly considered an important treatment target, which may raise self-esteem, and reduce self-stigma and suicidal ideation. The present study compared a psychotherapeutic treatment aimed at improving cognitive insight, individualized metacognitive intervention (MCT+), with an active control in order to elucidate if personal meaning-making and hope can be improved in patients with psychosis across time. A total of 92 patients were randomized to either individualized metacognitive therapy (MCT+) or CogPack (neuropsychological training) and followed up for up to 6 months. The “Subjective Sense in Psychosis Questionnaire” (SUSE) was administered which covers different salutogenetic vs pathogenetic views of the disorder, valence of symptom experiences and the consequences of psychosis. Patients in the MCT+ group showed a significant positive shift in attitudes towards the consequences of their illness over time relative to patients in the active control condition. There was some evidence that MCT+ also enhanced meaning-making. The perceived negative consequences of psychosis were highly correlated with depression and low self-esteem, as well as suicidality. The study shows that a cognitive insight training can improve meaning-making in patients and help them come to terms with their diagnosis.



Systemic Biomarkers of Accelerated Aging in Schizophrenia: A Critical Review and Future Directions

Tue, 04 Jul 2017 00:00:00 GMT

Abstract
Background: Schizophrenia is associated with increased physical morbidity and early mortality, suggesting that the aging process may be accelerated in schizophrenia. However, the biological underpinnings of these alterations in aging in schizophrenia are unclear. Method: We conducted a detailed search of peer-reviewed empirical studies to evaluate evidence for accelerated biological aging in schizophrenia based on systemic, age-related biomarkers. We included studies that investigated differences between persons with schizophrenia and healthy comparison subjects in levels of biomarkers known to be associated with aging and examined the relationship of these biomarkers to age in the 2 groups. Results: Forty-two articles that met our selection criteria were reviewed. Nearly 75% reported abnormal biomarker levels among individuals with schizophrenia, including indices of inflammation, cytotoxicity, oxidative stress, metabolic health, gene expression, and receptor/synaptic function, with medium to large effect sizes reported in many studies. Twenty-nine percent of the studies observed differential age-related decline in schizophrenia. Markers of receptor/synaptic function and gene expression were most frequently differentially related to age in schizophrenia. Schizophrenia patients with greater disease severity and longer illness duration exhibited higher levels of inflammatory and oxidative stress biomarkers and shorter telomere length. Conclusions: Most studies show biomarker abnormalities in schizophrenia, and there is some suggestion for accelerated aging. Although definitive interpretation is limited by cross-sectional design of the published reports, findings in the area of gene expression and synaptic function are promising and pave the way for future longitudinal studies needed to fully test this hypothesis.



Social Disconnection in Schizophrenia and the General Community

Tue, 20 Jun 2017 00:00:00 GMT

Abstract
Social disability is a defining characteristic of schizophrenia and a substantial public health problem. It has several components that are difficult to disentangle. One component, social disconnection, occurs extensively in the general community among nonhelp-seeking individuals. Social disconnection is an objective, long-standing lack of social/family relationships and minimal participation in social activities. It is associated with negative health effects, including early mortality, and is distinct from subjective loneliness. These 2 topics, social disability in schizophrenia and social disconnection in the general community, have generated entirely distinct research literatures that differ in their respective knowledge gaps and emphases. Specifically, the consequences of social disability in schizophrenia are unknown but its determinants (ie, nonsocial cognition, social cognition, and social motivation) have been well-examined. Conversely, the health consequences of social disconnection in the general community are well-established, but the determinants are largely unknown. Social disconnection is a condition that presents substantial public health concerns, exists within and outside of current psychiatric diagnostic boundaries, and may be related to the schizophrenia spectrum. A comparison of these 2 literatures is mutually informative and it generates intriguing research questions that can be critically evaluated.



Delta Vs Gamma Auditory Steady State Synchrony in Schizophrenia

Tue, 20 Jun 2017 00:00:00 GMT

Abstract
Background
Delta band (1–4 Hz) neuronal responses support the precision and stability of auditory processing, and a deficit in delta band synchrony may be relevant to auditory domain symptoms in schizophrenia patients.
Methods
Delta band synchronization elicited by a 2.5 Hz auditory steady state response (ASSR) paradigm, along with those from theta (5 Hz), alpha (10 Hz), beta (20 Hz), gamma (40 Hz), and high gamma (80 Hz) frequency ASSR, were compared in 128 patients with schizophrenia, 108 healthy controls, and 55 first-degree relatives (FDR) of patients.
Results
Delta band synchronization was significantly impaired in patients compared with controls (F = 18.3, P < .001). There was a significant 2.5 Hz by 40 Hz ASSR interaction (P = .023), arising from a greater reduction of 2.5 Hz ASSR than of 40 Hz ASSR, in patients compared with controls. Greater deficit in delta ASSR was associated with auditory perceptual abnormality (P = .007) and reduced verbal working memory (P < .001). Gamma frequency ASSR impairment was also significant but more modest (F = 8.7, P = .004), and this deficit was also present in FDR (P = .022).
Conclusions
The ability to sustain delta band oscillation entrainment in the auditory pathway is significantly reduced in schizophrenia patients and appears to be clinically relevant.



Stress-Dependent Association Between Polygenic Risk for Schizophrenia and Schizotypal Traits in Young Army Recruits

Tue, 13 Jun 2017 00:00:00 GMT

Abstract
Schizotypal personality traits may increase proneness to psychosis and likely index familial vulnerability to schizophrenia (SZ), implying shared genetic determinants with SZ. Here, we sought to investigate the contribution of common genetic risk variation for SZ on self-reported schizotypy in 2 ethnically homogeneous cohorts of healthy young males during compulsory military service, enrolled in the Athens Study of Proneness and Incidence of Schizophrenia (ASPIS, N = 875) and the Learning on Genetics of Schizophrenia Spectrum study (LOGOS, N = 690). A follow-up psychometric assessment was performed in a sub-sample of the ASPIS (N = 121), 18 months later at military service completion. Polygenic risk scores (PRS) for SZ were derived based on genome-wide association meta-analysis results from the Psychiatric Genomics Consortium. In the ASPIS, higher PRSSZ significantly associated with lower levels of positive (ie, perceptual distortions), disorganization and paranoid facets of schizotypy, whereas no association with negative (ie, interpersonal) facets was noted. Importantly, longitudinal data analysis in the ASPIS subsample revealed that PRSSZ was inversely associated with positive schizotypy at military induction (stressed condition) but not at follow-up (nonstressed condition), providing evidence for environmental rather than SZ-implicated genetic influences. Moreover, consistent with prior reports, PRSSZ was positively correlated with trait anxiety in the LOGOS and additionally the recruits with higher PRSSZ and trait anxiety exhibited attenuated paranoid ideation. Together, these findings do not support an etiological link between increased polygenic liability for SZ and schizotypy, suggesting that psychosocial stress or trait anxiety may impact schizotypal phenotypic expressions among healthy young adults not genetically predisposed to SZ.



Abnormal Resting-State Connectivity in a Substantia Nigra-Related Striato-Thalamo-Cortical Network in a Large Sample of First-Episode Drug-Naïve Patients With Schizophrenia

Sat, 10 Jun 2017 00:00:00 GMT

Abstract
Objective
The dopamine hypothesis is one of the most influential theories of the neurobiological background of schizophrenia (SCZ). However, direct evidence for abnormal dopamine-related subcortical-cortical circuitry disconnectivity is still lacking. The aim of this study was therefore to test dopamine-related substantia nigra (SN)-based striato-thalamo-cortical resting-state functional connectivity (FC) in SCZ.
Method
Based on our a priori hypothesis, we analyzed a large sample resting-state functional magnetic resonance imaging (fMRI) dataset from first-episode drug-naïve SCZ patients (n = 112) and healthy controls (n = 82) using the SN as the seed region for an investigation of striato-thalamo-cortical FC. This was done in the standard band of slow frequency oscillations and then in its subfrequency bands (Slow4 and Slow5). Results: The analysis showed in SCZ: (1) reciprocal functional hypo-connectivity between SN and striatum, with differential patterns for Slow5 and Slow4; (2) functional hypo-connectivity between striatum and thalamus, as well as functional hyper-connectivity between thalamus and sensorimotor cortical areas, specifically in Slow4; (3) correlation of thalamo-sensorimotor functional hyper-connectivity with psychopathological symptoms. Conclusions: We demonstrate abnormal dopamine-related SN-based striato-thalamo-cortical FC in slow frequency oscillations in first-episode drug-naive SCZ. This suggests that altered dopaminergic function in the SN leads to abnormal neuronal synchronization (as indexed by FC) within subcortical-cortical circuitry, complementing the dopamine hypothesis in SCZ on the regional level of resting-state activity.



Isolated Mitochondria Transfer Improves Neuronal Differentiation of Schizophrenia-Derived Induced Pluripotent Stem Cells and Rescues Deficits in a Rat Model of the Disorder

Tue, 06 Jun 2017 00:00:00 GMT

Abstract
Dysfunction of mitochondria, key players in various essential cell processes, has been repeatedly reported in schizophrenia (SZ). Recently, several studies have reported functional recovery and cellular viability following mitochondrial transplantation, mostly in ischemia experimental models. Here, we aimed to demonstrate beneficial effects of isolated active normal mitochondria (IAN-MIT) transfer in vitro and in vivo, using SZ-derived induced pluripotent stem cells (iPSCs) differentiating into glutamatergic neuron, as well as a rodent model of SZ. First, we show that IAN-MIT enter various cell types without manipulation. Next, we show that IAN-MIT transfer into SZ-derived lymphoblasts induces long-lasting improvement in various mitochondrial functions including cellular oxygen consumption and mitochondrial membrane potential (Δ ψ m). We also demonstrate improved differentiation of SZ-derived iPSCs into neurons, by increased expression of neuronal and glutamatergic markers β3-tubulin, synapsin1, and Tbr1 and by an activation of the glutamate-glutamine cycle. In the animal model, we show that intra-prefrontal cortex injection of IAN-MIT in adolescent rats exposed prenatally to a viral mimic prevents mitochondrial Δ ψ m and attentional deficit at adulthood. Our results provide evidence for a direct link between mitochondrial function and SZ-related deficits both in vitro and in vivo and suggest a therapeutic potential for IAN-MIT transfer in diseases with bioenergetic and neurodevelopmental abnormalities such as SZ.



The Validity and Sensitivity of PANSS-6 in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Study

Thu, 01 Jun 2017 00:00:00 GMT

Abstract
It was recently demonstrated in acutely exacerbated schizophrenia that a 6-item version (PANSS-6: P1 = delusions, P2 = conceptual disorganization, P3 = hallucinations, N1 = blunted affect, N4 = social withdrawal, N6 = lack of spontaneity/flow of conversation) of the 30-item Positive and Negative Syndrome Scale (PANSS-30) was scalable (all items provide unique information regarding syndrome severity) and able to separate the effect of antipsychotics from placebo. Here, we tested the validity and sensitivity of PANSS-6 in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) outpatient study. We examined (1) the scalability of PANSS-6 and PANSS-30; (2) the correlation between PANSS-6 and PANSS-30 total scores; (3) whether PANSS-6 could identify symptom remission (Andreasen criteria); and (4) the effect of the 5 antipsychotics studied in CATIE Phase-1, using PANSS-6 and PANSS-30 total scores as outcomes. We found that for the 577 subjects with complete PANSS ratings at baseline, month 1, 3, and 6, PANSS-6 was scalable, whereas PANSS-30 was not. In the 1432 subjects in the intention-to-treat (ITT) sample, PANSS-6 and PANSS-30 total scores were highly correlated (Spearman correlation coefficient = 0.86). Based on 5080 ITT ratings, PANSS-6 identified symptom remission with an accuracy of 0.99 (95% confidence interval = 0.99–0.99). In ITT analyses, PANSS-6 and PANSS-30 identified the same statistically significant differences in antipsychotic efficacy, ie, olanzapine was superior to risperidone (P-value PANSS-6 = 0.0003 and PANSS-30 = 0.0003) and ziprasidone (P-value PANSS-6 = 0.0018 and PANSS-30 = 0.0046). In conclusion, PANSS-6 is a brief schizophrenia rating scale that adequately measures severity, remission, and antipsychotic efficacy related to core positive and negative symptoms in clinical trials. Prospective studies of PANSS-6 in clinical practice are required.



Limbic Interference During Social Action Planning in Schizophrenia

Tue, 30 May 2017 00:00:00 GMT

Abstract
Schizophrenia is characterized by social interaction deficits contributing to poor functional outcome. Hand gesture use is particularly impaired, linked to frontal lobe dysfunction and frontal grey matter deficits. The functional neural correlates of impaired gesturing are currently unclear. We therefore investigated aberrant brain activity during impaired gesturing in schizophrenia. We included 22 patients with schizophrenia and 25 healthy control participants matched for age, gender, and education level. We obtained functional magnetic resonance imaging data using an event-related paradigm to assess brain activation during gesture planning and execution. Group differences in whole brain effects were calculated using factorial designs. Gesture ratings were performed by a single rater, blind to diagnoses and clinical presentation. During gesture planning and execution both groups activated brain areas of the praxis network. However, patients had reduced dorsolateral prefrontal cortex (DLPFC) and increased inferior parietal lobe (IPL) activity. Performance accuracy was associated with IPL activity in patients. Furthermore, patients activated temporal poles, amygdala and hippocampus during gesture planning, which was associated with delusion severity. Finally, patients demonstrated increased dorsomedial prefrontal cortex activity during planning of novel gestures. We demonstrate less prefrontal, but more IPL and limbic activity during gesturing in schizophrenia. IPL activity was associated with performance accuracy, whereas limbic activity was linked to delusion severity. These findings may reflect impaired social action planning and a limbic interference with gestures in schizophrenia contributing to poor gesture performance and consequently poor social functioning in schizophrenia.



Cumulative Effects of Neighborhood Social Adversity and Personal Crime Victimization on Adolescent Psychotic Experiences

Mon, 22 May 2017 00:00:00 GMT

Abstract
Background: Little is known about the impact of urbanicity, adverse neighborhood conditions and violent crime victimization on the emergence of adolescent psychotic experiences. Methods: Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins who were interviewed about adolescent psychotic experiences at age 18. Urbanicity, neighborhood characteristics, and personal victimization by violent crime were measured during childhood and adolescence via geocoded census data, surveys of over 5000 immediate neighbors of the E-Risk participants, and interviews with participants themselves. Results: Adolescents raised in urban vs rural neighborhoods were significantly more likely to have psychotic experiences (OR = 1.67, 95% CI = 1.21–2.30, P = .002). This association remained significant after considering potential confounders including family socioeconomic status, family psychiatric history, and adolescent substance problems (OR = 1.43, 95% CI = 1.01–2.03, P = .042), but became nonsignificant after considering adverse social conditions in urban neighborhoods such as low social cohesion and high neighborhood disorder (OR = 1.35, 95% CI = 0.94–1.92, P = .102). The combined association of adverse neighborhood social conditions and personal crime victimization with adolescent psychotic experiences (adjusted OR = 4.86, 95% CI = 3.28–7.20, P < .001) was substantially greater than for either exposure alone, highlighting a potential interaction between neighborhood conditions and crime victimization (interaction contrast ratio = 1.81, 95% CI = −0.03 to 3.65) that was significant at the P = .054 level. Conclusions: Cumulative effects of adverse neighborhood social conditions and personal victimization by violent crime during upbringing partly explain why adolescents in urban settings are more likely to report psychotic experiences. Early intervention efforts for psychosis could be targeted towards victimized youth living in urban and socially adverse neighborhoods.



22q11.2 Deletion Syndrome Is Associated With Impaired Auditory Steady-State Gamma Response

Wed, 17 May 2017 00:00:00 GMT

Abstract
Background
The 22q11.2 deletion syndrome confers a markedly increased risk for schizophrenia. 22q11.2 deletion carriers without manifest psychotic disorder offer the possibility to identify functional abnormalities that precede clinical onset. Since schizophrenia is associated with a reduced cortical gamma response to auditory stimulation at 40 Hz, we hypothesized that the 40 Hz auditory steady-state response (ASSR) may be attenuated in nonpsychotic individuals with a 22q11.2 deletion.
Methods
Eighteen young nonpsychotic 22q11.2 deletion carriers and a control group of 27 noncarriers with comparable age range (12–25 years) and sex ratio underwent 128-channel EEG. We recorded the cortical ASSR to a 40 Hz train of clicks, given either at a regular inter-stimulus interval of 25 ms or at irregular intervals jittered between 11 and 37 ms.
Results
Healthy noncarriers expressed a stable ASSR to regular but not in the irregular 40 Hz click stimulation. Both gamma power and inter-trial phase coherence of the ASSR were markedly reduced in the 22q11.2 deletion group. The ability to phase lock cortical gamma activity to regular auditory 40 Hz stimulation correlated with the individual expression of negative symptoms in deletion carriers (ρ = −0.487, P = .041).
Conclusions
Nonpsychotic 22q11.2 deletion carriers lack efficient phase locking of evoked gamma activity to regular 40 Hz auditory stimulation. This abnormality indicates a dysfunction of fast intracortical oscillatory processing in the gamma-band. Since ASSR was attenuated in nonpsychotic deletion carriers, ASSR deficiency may constitute a premorbid risk marker of schizophrenia.



Altered White Matter Connectivity Within and Between Networks in Antipsychotic-Naive First-Episode Schizophrenia

Wed, 17 May 2017 00:00:00 GMT

Abstract
Analyzing the schizophrenia connectome can identify illness-related alterations in connectivity across the brain. An important question that remains unanswered is whether connectivity alterations are already evident at the onset of illness, before treatment with antipsychotic medication and possible influences of neuroprogressive or secondary alterations related to chronic illness duration. In the present study, diffusion tensor imaging and deterministic fiber tractography were performed with 137 antipsychotic-naive first-episode schizophrenia patients and 113 matched healthy controls. Using graph theoretic analysis, groups were compared in global and regional measurements and modularity of white matter connectivity. Compared with controls, the patients showed significantly decreased total connection strength. Furthermore, patients demonstrated significantly decreased connections within and between brain modules. Several local brain regions within association cortex exhibited reduced nodal centralities and abnormal participant coefficient or intra-module degree, some of which were correlated with illness duration and overall functional disability. In never-treated schizophrenia patients, networks showed a less effective organizational pattern of white matter pathways. White matter disconnectivity occurred not only within but also between multiple modules, shedding light on the deficits of anatomical network organization early in the course of schizophrenia.



Cross-Tissue Exploration of Genetic and Epigenetic Effects on Brain Gray Matter in Schizophrenia

Wed, 17 May 2017 00:00:00 GMT

Abstract
Closely linking genetics and environment factors, epigenetics has been of increasing interest in psychiatric disease studies. In this work, we integrated single nucleotide polymorphisms (SNPs), DNA methylation of blood and saliva, and brain gray matter (GM) measures to explore the role of genetic and epigenetic variation to the brain structure changes in schizophrenia (SZ). By focusing on the reported SZ genetic risk regions, we applied a multi-stage multivariate analysis to a discovery dataset (92 SZ patients and 110 controls, blood) and an independent replication dataset (93 SZ patients and 99 controls, saliva). Two pairs of SNP-methylation components were significantly correlated (r = .48 and .35) in blood DNA, and replicated (r = .46 and .29) in saliva DNA, reflecting cross-tissue SNP cis-effects. In the discovery data, both SNP-related methylation components were also associated with one GM component primarily located in cerebellum, caudate, and thalamus. Additionally, another methylation component in NOSIP gene with significant SZ patient differences (P = .009), was associated with 8 GM components (7 with patient differences) including superior, middle, and inferior frontal gyri, superior, middle, and inferior temporal gyri, cerebellum, insula, cuneus, and lingual gyrus. Of these, 5 methylation-GM associations were replicated (P < .05). In contrast, no pairwise significant associations were observed between SNP and GM components. This study strongly supports that compared to genetic variation, epigenetics show broader and more significant associations with brain structure as well as diagnosis, which can be cross-tissue, and the potential in explaining the mechanism of genetic risks in SZ.



Diagnostic and Prognostic Significance of DSM-5 Attenuated Psychosis Syndrome in Services for Individuals at Ultra High Risk for Psychosis

Wed, 17 May 2017 00:00:00 GMT

Abstract
Background
The diagnostic and prognostic significance of the DSM-5-defined Attenuated Psychosis Syndrome (DSM-5-APS) in individuals undergoing an ultra high risk (UHR) clinical assessment for suspicion of psychosis risk is unknown.
Methods
Prospective cohort study including all consecutive help-seeking individuals undergoing both a DSM-5-APS and a Comprehensive Assessment of At Risk Mental States (CAARMS 12/2006) assessment for psychosis risk at the Outreach and Support in South London (OASIS) UHR service (March 2013–April 2014). The diagnostic significance of DSM-5-APS was assessed with percent overall agreement, prevalence bias adjusted kappa, Bowker’s test, Stuart-Maxwell test, residual analysis; the prognostic significance with Cox regression, Kaplan–Meier failure function, time-dependent area under the curve (AUC) and net benefits analysis. The impact of specific revisions of the DSM-5-APS was further tested.
Result
In 203 help-seeking individuals undergoing UHR assessment, the agreement between the DSM-5-APS and the CAARMS 12/2006 was only moderate (kappa 0.59). Among 142 nonpsychotic cases, those meeting DSM-5-APS criteria had a 5-fold probability (HR = 5.379) of developing psychosis compared to those not meeting DSM-5-APS criteria, with a 21-month cumulative risk of psychosis of 28.17% vs 6.49%, respectively. The DSM-5-APS prognostic accuracy was acceptable (AUC 0.76 at 24 months) and similar to the CAARMS 12/2006. The DSM-5-APS designation may be clinically useful to guide the provision of indicated interventions within a 7%–35% (2-year) range of psychosis risk. The removal of the criterion E or C of the DSM-5-APS may improve its prognostic performance and transdiagnostic value.
Conclusions
The DSM-5-APS designation may be clinically useful in individuals accessing clinical services for psychosis prevention.



The Cascade of Stress: A Network Approach to Explore Differential Dynamics in Populations Varying in Risk for Psychosis

Fri, 17 Mar 2017 00:00:00 GMT

Abstract
Stress plays a central role in the development and persistence of psychosis. Network analysis may help to reveal mechanisms at the level of the micro-dynamic effects between stress, other daily experiences and symptomatology. This is the first study to examine time-lagged networks of the relations between minor daily stress, momentary affect/thoughts, psychotic experiences, and other potentially relevant daily life contexts in individuals varying in risk for psychosis. Intensive longitudinal data were obtained through 6 studies. The combined sample consisted of 654 individuals varying in risk for psychosis: healthy control subjects (n = 244), first-degree relatives of psychotic patients (n = 165), and psychotic patients (n = 245). Using multilevel models combined with permutation testing, group-specific time-lagged network connections between daily experiences were compared between groups. Specifically, the role of stress was examined. Risk for psychosis was related to a higher number of significant network connections. In all populations, stress had a central position in the network and showed direct and significant connections with subsequent psychotic experiences. Furthermore, the higher the risk for psychosis, the more variables “loss of control” and “suspicious” were susceptible to influences by other network nodes. These findings support the idea that minor daily stress may play an important role in inducing a cascade of effects that may lead to psychotic experiences.



Working While Rehabbing

Tue, 07 Jul 2015 00:00:00 GMT

After experiencing my second episode of schizoaffective disorder, I had difficulty finding meaningful and productive activities to pursue. I spent a great deal of time sitting on the couch watching TV and despairing over having schizoaffective disorder and the state of life it had created for me which was a friendless and lonely place where I had nothing going for me, was lethargic, and lame from inactivity. I had a college degree but I wasn’t at the point where I felt I could handle a job with work commensurate to that which I had completed in college. I realized I can’t do this for the rest of my life and something needs to change.



Journaling as Therapy

Mon, 18 May 2015 00:00:00 GMT

Journaling about my issues with metaphysics and psychoanalysis were paramount in my recovery from schizoaffective disorder. I have gone to talk therapy for 1h/week for the past 4 years and after my third year of therapy I began writing in a metacognitive journal where I have psychoanalyzed myself and learned a great deal about my psyche and everything else in my life. During episodes and other points in my life there were many traumatic experiences from the past that affected me in the present that I needed to face and analyze. There have also been normal life experiences that have been new to me which I have written about and have hashed out to gain a better understanding of or make better decisions regarding them. Talk therapy was an important tool for coming to terms with the experiences I was most afraid of facing. I started at a point where I didn’t want to speak even the slightest of sentences and progressed to being able to talk frankly about any of my experiences in my life. I don’t always share experiences with others but being able to face them on my own has been immensely beneficial. I know the only way I can improve is being honest with myself about my experiences because the past is ingrained in my mind and if I lie about it to myself I’ll never truly understand the reasons and ways trauma is currently affecting me. When I haven’t accurately addressed a past issue it has had a way of still affecting me. I know when I’ve found mistakes I’ve made or areas I could have done better I only need to share this information with myself. Once I developed the ability to freely analyze my experiences I started working with the meaning I had surrounding them and the meaning they had within my life. I discovered I have to find the truth that makes me function as well as I can because ultimately my goal has been to function at my optimal levels. In any well functioning mind there’s a balance of eliminating rigidity in thought and developing mental flexibility but also in having some set of parameters from which to work. The best minds are able to accordingly adapt to the particular set of circumstances they are working within or change situations to their advantage.



Exposure Therapy

Thu, 23 Apr 2015 00:00:00 GMT

During both my schizoaffective disorder episodes I had many obsessive behaviors that were detrimental to my health. One of them was obsessively cleaning everything and anything I owned as well as I possibly could repeatedly. I once emptied my room and cleaned every single thing I owned top to bottom including the room. I scrubbed the ceilings, walls, windows, and hired a carpet cleaner to professionally clean the carpet twice. I cleaned my hands so repetitively and thoroughly that they had tons of little cuts on them and looked as though I had run them through buckets of glass shards. I had become a germaphobe because I believed I was a messiah and thought external purity created internal purity and if I was to save the world I needed to be pure.