Psychosis Study Research Articles

The role of the behavioural inhibition and activation system in the association between attachment style and positive or negative symptoms in patients with psychosis and unaffected siblings.

The association between attachment style and psychotic symptomatology is well established. However, little is known about the mechanisms underlying this relationship. In the present study, we aimed to investigate whether the sensitivity of the behavioural inhibition and activation system mediates the association between attachment style and positive or negative symptoms, in patients with psychotic disorders and unaffected siblings. In a subsample of the Genetic Risk and Outcome of Psychosis (GROUP) study (87 patients and 94 siblings), attachment style was assessed using the Psychotic Attachment Measure, behavioural inhibition or activation with the Behavioral Inhibition System (BIS) and Behavioral Activation System (BAS) Scale and positive and negative symptomatology with the Community Assessment of Psychic Experiences. Linear regression models and mediation models were used, while correcting for age and gender and adjusting for multiple testing. We found that anxious and avoidant attachment were associated with negative symptoms across both groups. Additionally, in siblings, anxious and avoidant attachment were associated with positive symptoms. In the patient group, BIS sensitivity mediated the association between anxious attachment and negative symptoms. In the sibling group, BIS sensitivity mediated the association between avoidant attachment and both positive and negative symptoms, and between anxious attachment and positive symptoms. Findings indicate that BIS sensitivity, but not BAS sensitivity, is a possible mediating mechanism contributing to the association between insecure attachment and psychotic symptoms. Longitudinal studies are required to confirm the associations between attachment style, BIS and BAS sensitivity, and psychotic symptoms, and explore causality.

Validation of the Amharic version of Cognitive Assessment Interview (CAI-A) in people with schizophrenia in Ethiopia

Assessing cognition with interview-based measures could be a low-resource alternative to traditional cognitive tests. We previously adapted the Cognitive Assessment Interview (CAI) into Amharic (CAI-A) for use with people with schizophrenia (PWS) in Ethiopia. This study examined the convergent and structural validity of the CAI-A in a group of 350 PWS sub-sampled from the Neuropsychiatric Genetics of African Populations – Psychosis (NeuroGAP-Psychosis) study, who fulfilled the inclusion criteria. Data were analyzed using confirmatory factor analysis (CFA), Spearman's correlation coefficient (ρ), multiple regression, and Item Response Theory (IRT). A one-factor solution best fits the items in the tool (factor loadings between 0.58 and 0.79), suggesting structural validity. The total score of the CAI-A moderately correlated with functioning (ρ = 0.44, p < 0.001) and symptom dimensions (ρ between 0.38 and 0.46, p < 0.001), suggesting convergent validity. Multiple regression showed that age (β = −0.06, 95 % CI (−0.12, 0.00), p = 0.044), the duration of illness (β = 0.08, 95 % CI (0.01, 0.14), p = 0.033), and medication side effects (β = 0.35, 95 % CI (0.21, 0.50), p < 0.001) were positively and significantly associated with the CAI-A total score. The IRT analysis suggested that the tool best functions among participants with moderate to severe impairment (difficulty coefficient between 0.05 and 2.73). We found that the CAI-A is a valid tool for use in Ethiopia. The moderate correlation with symptom and functional measures suggested that self-reported cognitive symptoms parallel other symptom dimensions and functional disability. The CAI-A can be used in clinical practice and research activities in PWS in Ethiopia when subjective assessment of cognition is desired.

Effects of positive mGlu5 modulation on D2 signaling and nicotine-conditioned place preference: Mechanisms of epigenetic inheritance in a transgenerational model of drug abuse vulnerability in psychosis.

The metabotropic glutamate type 5 (mGlu5) receptor has emerged as a potential target for the treatment of psychosis that is suggested to have greater efficacy than antipsychotic medications that are currently utilized. This study sought to elucidate mechanisms of therapeutic action associated with the modulation of the mGlu5 receptor in a disordered system marked by dopamine dysfunction. We further explored epigenetic mechanisms contributing to heritable transmission of a psychosis-like phenotype in a novel heritable model of drug abuse vulnerability in psychosis. F1 generation male and female Sprague-Dawley rats that were the offspring of two neonatal quinpirole-treated (QQ) or two saline-treated (SS) animals were tested on nicotine-conditioned place preference (CPP). Regulators of G protein signaling 9 (RGS9) and β-arrestin 2 (βA2), which mediate dopamine (DA) D2 signaling, were measured in the nucleus accumbens shell, prelimbic and infralimbic cortices. Reduced Representation Bisulfite Sequencing (RRBS) was used to analyze the cytosine methylation in these brain regions. Pretreatment with the mGlu5-positive allosteric modulator 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) 20 min prior to conditioning trials blocked enhanced nicotine CPP and mitigated aberrant G protein-dependent and -independent signaling in QQ animals. RRBS analysis revealed region-specific changes in several pathways, including nicotine addiction, dopamine synapses, and neural connectivity. These results reveal an important region-specific mechanism of action for CDPPB in a system marked by enhanced DAD2 receptor signaling. Results additionally reveal DNA methylation as an epigenetic mechanism of heritability, further validating the current model as a useful tool for the study of psychosis and comorbid nicotine use.

Psychotic symptoms associated increased CpG methylation of metabotropic glutamate receptor 8 gene in Chinese Han males with schizophrenia and methamphetamine induced psychotic disorder: a longitudinal study

Methamphetamine use can produce psychotic symptoms almost indistinguishable from schizophrenia (SCZ). Variation in DNA methylation may be closely implicated in the etiology and longitudinal development of psychiatric disorders. However, the relationship between psychotic symptoms, functional disability, and DNA methylation is still unclear. This study consists of three periods: discovery, validation, and follow-up. In the discovery stage, we employed genome-wide DNA methylation profiling (Illumina 450K) in peripheral blood mononuclear cells to test whether DNA methylation associates with psychotic symptoms and function state in representative SCZ and methamphetamine-induced psychotic disorder (MIP) patients. Then, we found seven differentially methylated regions/genes (DMRs, in UBA6, APOL3, KIF17, MLLT3, GRM8, CSNK1E, SETDB1) overlapping with genetic variants reported in previous studies of psychosis. In the validation stage, we compared the above-mentioned seven genes by MethLight qPCR method in Chinese Han males (N = 109 SCZ patients, N = 99 methamphetamine use disorder with MIP patients, N = 150 methamphetamine use disorder without MIP patients, N = 282 normal controls, age range: 18–50 years). GRM8 showed robustly altered methylation, which has passed rigorous filtration in subsequent validation, suggesting a remarkable contribution to SCZ and MIP. In addition, hypermethylation of GRM8 showed a significant association with the total scores of the Positive Negative Syndrome Scale and WHO disability assessment schedule II in both baseline and follow-up periods. Our findings suggest that increased CpG methylation in the promoter of GRM8 is a potential candidate epigenetic biomarker of psychotic symptoms in transdiagnostic samples of SCZ and MIP.

Unmet Financial Needs of People with Psychotic Disorders-A Cross-Sectional Study in People with Psychotic Disorders, Parents, Siblings, and Controls.

Background. Psychotic disorders have a strong negative impact on people's lives, including their financial situation. This study aimed to examine differences in unmet financial needs between people with psychotic disorders, parents, siblings, and controls. Secondly, we aimed to examine whether family clustering contributes to unmet financial needs. Lastly, we aimed to examine to what extent demographic, economic, psychiatric, functional, and cognitive characteristics and substance use predict unmet financial needs in people with psychosis. Methods. Data from the first assessment of people with psychosis (n = 956), siblings (n = 889), parents (n = 858), and controls (n = 496) included in the Genetic Risk and Outcome of Psychosis study were used. Group differences were assessed with Kruskal-Wallis tests (aim 1), while a mixed-effects logistic regression analysis and explorative and confirmative ordinal logistic regression analyses were conducted for aims 2 and 3, respectively. Results. Twenty-four percent of people with psychotic disorders reported unmet financial needs. These levels of unmet financial needs were significantly higher than levels for siblings, parents, and controls. We found a negligible influence of (direct) familial clustering on unmet financial needs. Lastly, cannabis and tobacco use significantly and consistently predicted higher levels of unmet financial needs of people with psychosis. Conclusions. Relatively high levels of unmet financial needs occurred in a heterogeneous group of people with psychosis, especially when people used cannabis or tobacco. Unmet financial needs can have detrimental consequences for mental health, stigmatization, leisure time activities, and social engagement. Thus, it is pivotal to recognize unmet financial needs, especially combined with substance use, as a crucial stressor for people with psychosis.

An Exploratory Study of Cognitive Distortions and Psychosis among Meth-Amphetamine Users

This research aims at studying the cognitive distortions and psychosis among the meth-amphetamine users. This study was exploratory in nature and qualitative research design was used. The sample size of this study was N = 19 meth-amphetamine users who were residing in different rehabilitation centers of Islamabad/Rawalpindi and convenient sampling technique was used. Semi-structured interviews were conducted and then the thematic analysis was used to analyze the data. The results of the analysis indicates that there is a strong association between cognitive distortions and psychotic symptoms. The results also highlighted that the most common type of cognitive distortions includes all or nothing thinking, mental filtering, and catastrophizing. This study has shown that hallucinations and paranoid delusions can cause significant harm to their day-to-day functioning as well as to their quality of life. The research highlight the critical role that social and emotional support plays in mitigating the impact of cognitive distortions on mental illness. The results of this study highlights the need of comprehensive intervention techniques which will target both the cognitive and psychosocial levels in the treatment of addiction to prevent the relapse rate.

Psychosis metabolic risk calculator (PsyMetRiC) in early psychosis: External validation study in Finland.

Accurate detection of cardiometabolic risk in early psychosis is crucial to reducing somatic morbidity and mortality in people with psychotic disorders. We conducted an external validation of the psychosis metabolic risk calculator (PsyMetRiC), a cardiometabolic risk prediction tool developed in the UK and tailored for young people with psychosis. We compared the predictive accuracy and clinical usefulness of PsyMetRiC and a general population-based risk prediction tool for type 2 diabetes, the Finnish Diabetes Risk Score (FINDRISC). We included first-episode psychosis and ultra-high-risk for psychosis patients without metabolic syndrome aged 18-35 years from the Helsinki Early Psychosis and Turku Early Psychosis Study cohorts. We tested two versions of PsyMetRiC: the full model including age, sex, ethnicity, body-mass index, smoking status, prescription of metabolically-active antipsychotic medication, high-density lipoprotein, and triglyceride concentrations, and the partial-model excluding biochemical predictors, and the simplified FINDRISC including BMI, sex, systolic blood pressure, and fasting glucose. Discrimination, calibration, and decision curve analyses were used to assess the predictive performance and clinical usefulness of both PsyMetRiC and FINDRISC. We performed a site-specific re-calibration of PsyMetRiC (PsyMetRiC-Fi). The study sample consisted of 278 individuals (all White European ethnicity, 58.6% male, mean age 24.8 years, 37.8% smoking, mean BMI 23.5). Discrimination was marginally better in the PsyMetRiC full model (C = 0.72, 95% CI, 0.59-0.82) compared with partial model (C = 0.70, 95% CI 0.59-0.80) or FINDRISC (C = 0.63, 95% CI 0.54-0.71). Calibration plots displayed evidence of minor miscalibration for PsyMetRiC, which corrected following recalibration. Miscalibration was more pronounced for FINDRISC. Decision curve analysis showed that PsyMetRiC offers likely clinical usefulness in improving cardiometabolic risk management in early psychosis compared with giving everyone or no one an intervention. PsyMetRiC has utility in predicting cardiometabolic risk in Finnish patients with early psychosis. It has better discriminatory accuracy and offers more accurate risk prediction compared to other available strategies.

Long-term clinical recovery and treatment resistance in first-episode psychosis: a 10-year follow-up study

Illness trajectories in people with first-episode psychosis (FEP) vary significantly over time. Identifying early-course parameters predicting outcomes is essential, but long-term data still needs to be provided. We conducted a 10-year follow-up study of a comprehensive first-episode psychosis (FEP) cohort investigating the prevalence of clinical recovery (CR) and treatment resistance (TR) after ten years, as well as clinical, demographic, and pre-illness predictors of long-term outcomes. 102 participants with FEP DSM-IV Schizophrenia spectrum disorders were recruited within their first year of treatment. The Treatment Response and Resistance in Psychosis Working Group (TRRIP) and the Remission in Schizophrenia Working Group (RSWG) criteria were used to define TR and CR, respectively. At 10-year follow-up, 29 (29%) of the participants were classified as in CR, while 32 (31%) were classified as TR. We also identified a larger middle group (n = 41, 40%) consisting of participants in partial recovery. 7% of all participants had tried Clozapine at the 10-year follow-up. Logistic regression analyses identified insidious onset (OR = 4.16) and baseline disorganized symptoms (OR = 2.96) as significantly associated with an increased risk of developing TR. Good premorbid academic adjustment (OR = 1.60) and acute onset (OR = 3.40) were associated with an increased chance of CR. We identified three long-term outcome groups by using recent consensus definitions. We also identified the potential importance of assessing baseline disorganized symptoms and monitoring patients with insidious onset more closely. Further, the findings suggest that clinicians should pay close attention to early-course parameters and provide adequate treatment to improve long-term outcomes of FEP.

Racial and Ethnic Disparities in the Diagnosis and Early Treatment of First-Episode Psychosis.

Despite recognition that early intervention for first-episode psychosis (FEP) improves outcomes, Black youth with FEP continue to experience critical disparities in care. A historical lack of scientific focus on racial and ethnic factors in the study of psychosis and scant investigations among publicly insured (ie, Medicaid-enrolled) youth hinder our ability to understand and address factors that contribute to disparities in early FEP care. Strategies for improving FEP services for Black youth are reliant on more precise identification of who faces disparities and when during the early course of illness disparities are experienced. A retrospective longitudinal analysis of Ohio Medicaid claims data was performed for 987982 youth aged 15-24 years between 2010 and 2020 to examine: (1) the likelihood of FEP diagnosis, (2) the type of psychotic disorder diagnosis received, and (3) receipt of treatment following psychosis onset. Non-Hispanic Black (NHB) youth, relative to non-Hispanic White (NHW) peers, were more likely to be diagnosed with a psychotic disorder and were further more likely to receive a diagnosis of schizophrenia relative to an affective psychotic disorder. In the first year following FEP diagnosis, NHB youth were also less likely to receive psychotherapy than NHW youth; this disparity was no longer present when examined at 2 years following FEP. In this study, Black youth experienced disparities in both the diagnosis and early treatment of FEP. Additional efforts are needed to understand and address these observed disparities and to promote equitable access to FEP care during the critical early illness phases.

Neurocognitive and social cognitive correlates of social exclusion in psychotic disorders: a 20-year follow-up cohort study.

Little is known about the relationship between social exclusion and cognitive impairment in psychosis. We conducted a long-term cohort study of first-episode psychosis to examine the association between comprehensive measures of cognitive impairment and social exclusion assessed at follow-up. A total of 173 subjects with first-episode psychosis were assessed after a 20-year follow-up for 7 cognitive domains and 12 social exclusion indicators. Associations between sets of variables were modeled using multivariate regression, where social exclusion indicators were the dependent variables, cognitive domains were the independent variables, and age, gender, and duration of follow-up were covariates. The total scores on the measures of cognition and social exclusion were strongly associated (β = - .469, ∆R2 = 0.215). Participants with high social exclusion were 4.24 times more likely to have cognitive impairment than those with low social exclusion. Verbal learning was the cognitive function most related to social exclusion domains, and legal capacity was the exclusion domain that showed the strongest relationships with individual cognitive tests. Neurocognition uniquely contributed to housing, work activity, income, and educational attainment, whereas social cognition uniquely contributed to neighborhood deprivation, family and social contacts, and discrimination/stigma. Neurocognition explained more unique variance (11.5%) in social exclusion than social cognition (5.5%). The domains of cognitive impairment were strongly and differentially related to those of social exclusion. Given that such an association pattern is likely bidirectional, a combined approach, both social and cognitive, is of paramount relevance in addressing the social exclusion experienced by individuals with psychotic disorders.

Robust Brain Correlates of Cognitive Performance in Psychosis and Its Prodrome

BackgroundNeurocognitive impairment is a well-known phenomenon in schizophrenia that begins prior to psychosis onset. Connectome-wide association studies have inconsistently linked cognitive performance to resting-state functional magnetic resonance imaging. We hypothesized that a carefully selected cognitive instrument and refined population would allow identification of reliable brain-behavior associations with connectome-wide association studies. To test this hypothesis, we first identified brain-cognition correlations via a connectome-wide association study in early psychosis. We then asked, in an independent dataset, if these brain-cognition relationships would generalize to individuals who develop psychosis in the future. MethodsThe Seidman Auditory Continuous Performance Task (ACPT) effectively differentiates healthy participants from those with psychosis. Our connectome-wide association study used the HCP-EP (Human Connectome Project for Early Psychosis) (n = 183) to identify links between connectivity and ACPT performance. We then analyzed data from the NAPLS2 (North American Prodrome Longitudinal Study 2) (n = 345), a multisite prospective study of individuals at risk for psychosis. We tested the connectome-wide association study–identified cognition-connectivity relationship in both individuals at risk for psychosis and control participants. ResultsOur connectome-wide association study in early-course psychosis identified robust associations between better ACPT performance and higher prefrontal-somatomotor connectivity (p < .005). Prefrontal-somatomotor connectivity was also related to ACPT performance in at-risk individuals who would develop psychosis (n = 17). This finding was not observed in nonconverters (n = 196) or control participants (n = 132). ConclusionsThis connectome-wide association study identified reproducible links between connectivity and cognition in separate samples of individuals with psychosis and at-risk individuals who would later develop psychosis. A carefully selected task and population improves the ability of connectome-wide association studies to identify reliable brain-phenotype relationships.

The TIPS family psychoeducational group work approach in first episode psychosis and related disorders: 25 years of experiences.

The aim of this paper is to present 25 years of clinical experience with family psychoeducation (FPE) work at Stavanger University Hospital in Norway, highlighting the lessons learned in overcoming implementation barriers in publicly funded specialized mental health care. This retrospective analysis reviews the integration and sustainability of FPE work within the hospital's standard treatment protocols for psychosis, tracing its origins from the Early Treatment and Intervention in Psychosis (TIPS) study (1997-2000) to its current application. The paper examines key strategies for successful implementation, including staff training and resource allocation, as emphasized by international research. Stavanger University Hospital has successfully implemented and maintained both multi- and single-family FPE approaches over the past 25 years. Initially part of the TIPS study, FPE has been integrated into routine clinical practice for treating psychosis and has recently been extended to families of patients with other severe mental disorders. The sustained success at Stavanger University Hospital is attributed to consistent staff training and the prioritization of sufficient resource allocation. The successful and sustainable integration of FPE at Stavanger University Hospital is relatively unique. International guidelines recommend FPE for psychosis, but its implementation remains inconsistent globally, despite over 50 years of supporting evidence. The hospital's experience underscores the critical role of continuous training and dedicated resources in embedding FPE into regular clinical practice. These findings suggest that addressing these areas can significantly enhance the uptake of FPE in other clinical settings. The 25-year experience at Stavanger University Hospital demonstrates that with appropriate training and resources, FPE can be successfully integrated and sustained within standard mental health care practices. This case study provides valuable insights for other institutions aiming to implement FPE and improve treatment outcomes for patients with severe mental disorders.

Multimodal prediction of the need of clozapine in treatment resistant schizophrenia; a pilot study in first-episode psychosis

As many as one third of the patients diagnosed with schizophrenia do not respond to first-line antipsychotic medication. This group may benefit from the atypical antipsychotic medication clozapine, but initiation of treatment is often delayed, which may worsen prognosis. Predicting which patients do not respond to traditional antipsychotic medication at the onset of symptoms would provide fast-tracked treatment for this group of patients. We collected data from patient records of 38 first-episode psychosis patients, of whom seven did not respond to traditional antipsychotic medications. We used clinical data including medical records, voxel-based morphometry MRI data and inter-subject correlation fMRI data, obtained during movie viewing, to predict future treatment resistance. Using a neural network model, we correctly predicted future treatment resistance in six of the seven treatment resistance patients and 25 of 31 patients who did not require clozapine treatment. Prediction improved significantly when using imaging data in tandem with clinical data. The accuracy of the neural network model was significantly higher than the accuracy of a support vector machine algorithm. These results support the notion that treatment resistant schizophrenia could represent a separate entity of psychotic disorders, characterized by morphological and functional changes in the brain which could represent biomarkers detectable at early onset of symptoms.

A 10-Year Longitudinal Study of Brain Cortical Thickness in People with First-Episode Psychosis Using Normative Models.

Clinical forecasting models have potential to optimize treatment and improve outcomes in psychosis, but predicting long-term outcomes is challenging and long-term follow-up data are scarce. In this 10-year longitudinal study, we aimed to characterize the temporal evolution of cortical correlates of psychosis and their associations with symptoms. Structural magnetic resonance imaging (MRI) from people with first-episode psychosis and controls (n = 79 and 218) were obtained at enrollment, after 12 months (n = 67 and 197), and 10 years (n = 23 and 77), within the Thematically Organized Psychosis (TOP) study. Normative models for cortical thickness estimated on public MRI datasets (n = 42 983) were applied to TOP data to obtain deviation scores for each region and timepoint. Positive and Negative Syndrome Scale (PANSS) scores were acquired at each timepoint along with registry data. Linear mixed effects models assessed effects of diagnosis, time, and their interactions on cortical deviations plus associations with symptoms. LMEs revealed conditional main effects of diagnosis and time × diagnosis interactions in a distributed cortical network, where negative deviations in patients attenuate over time. In patients, symptoms also attenuate over time. LMEs revealed effects of anterior cingulate on PANSS total, and insular and orbitofrontal regions on PANSS negative scores. This long-term longitudinal study revealed a distributed pattern of cortical differences which attenuated over time together with a reduction in symptoms. These findings are not in line with a simple neurodegenerative account of schizophrenia, and deviations from normative models offer a promising avenue to develop biomarkers to track clinical trajectories over time.

Genomic insights into the shared and distinct genetic architecture of cognitive function and schizophrenia

Cognitive impairment is a major determinant of functional outcomes in schizophrenia, however, understanding of the biological mechanisms underpinning cognitive dysfunction in the disorder remains incomplete. Here, we apply Genomic Structural Equation Modelling to identify latent cognitive factors capturing genetic liabilities to 12 cognitive traits measured in the UK Biobank. We identified three broad factors that underly the genetic correlations between the cognitive tests. We explore the overlap between latent cognitive factors, schizophrenia, and schizophrenia symptom dimensions using a complementary set of statistical approaches, applied to data from the latest schizophrenia genome-wide association study (Ncase = 53,386, Ncontrol = 77,258) and the Thematically Organised Psychosis study (Ncase = 306, Ncontrol = 1060). Global genetic correlations showed a significant moderate negative genetic correlation between each cognitive factor and schizophrenia. Local genetic correlations implicated unique genomic regions underlying the overlap between schizophrenia and each cognitive factor. We found substantial polygenic overlap between each cognitive factor and schizophrenia and biological annotation of the shared loci implicated gene-sets related to neurodevelopment and neuronal function. Lastly, we show that the common genetic determinants of the latent cognitive factors are not predictive of schizophrenia symptoms in the Norwegian Thematically Organized Psychosis cohort. Overall, these findings inform our understanding of cognitive function in schizophrenia by demonstrating important differences in the shared genetic architecture of schizophrenia and cognitive abilities.

Effects of N-Methyl-d-Aspartate Receptor Antagonists on Gamma-Band Activity During Auditory Stimulation Compared With Electro/Magneto-encephalographic Data in Schizophrenia and Early-Stage Psychosis: A Systematic Review and Perspective.

N-Methyl-d-aspartate receptor (NMDA-R) hypofunctioning has been hypothesized to be involved in circuit dysfunctions in schizophrenia (ScZ). Yet, it remains to be determined whether the physiological changes observed following NMDA-R antagonist administration are consistent with auditory gamma-band activity in ScZ which is dependent on NMDA-R activity. This systematic review investigated the effects of NMDA-R antagonists on auditory gamma-band activity in preclinical (n = 15) and human (n = 3) studies and compared these data to electro/magneto-encephalographic measurements in ScZ patients (n = 37) and 9 studies in early-stage psychosis. The following gamma-band parameters were examined: (1) evoked spectral power, (2) intertrial phase coherence (ITPC), (3) induced spectral power, and (4) baseline power. Animal and human pharmacological data reported a reduction, especially for evoked gamma-band power and ITPC, as well as an increase and biphasic effects of gamma-band activity following NMDA-R antagonist administration. In addition, NMDA-R antagonists increased baseline gamma-band activity in preclinical studies. Reductions in ITPC and evoked gamma-band power were broadly compatible with findings observed in ScZ and early-stage psychosis patients where the majority of studies observed decreased gamma-band spectral power and ITPC. In regard to baseline gamma-band power, there were inconsistent findings. Finally, a publication bias was observed in studies investigating auditory gamma-band activity in ScZ patients. Our systematic review indicates that NMDA-R antagonists may partially recreate reductions in gamma-band spectral power and ITPC during auditory stimulation in ScZ. These findings are discussed in the context of current theories involving alteration in E/I balance and the role of NMDA hypofunction in the pathophysiology of ScZ.

Long-Term Course of Remission and Recovery in Psychotic Disorders.

Understanding prognosis is critical to anticipating public health needs and providing care to individuals with psychotic disorders. However, the long-term course of remission and recovery remains unclear. In this study, the most common trajectories of illness course are described for a cohort of individuals followed for 25 years since first admission for psychosis. Participants are from the Suffolk County Mental Health Project, an epidemiological study of first-admission psychosis. Data for the present study was collected from six follow-ups, with 311 individuals assessed at the 25-year follow-up. Common patterns of remission and recovery were assessed in the baseline cohort of 591 individuals and the subsample from the 25-year follow up. In the baseline cohort and the 25-year subsample, the most common trajectory for individuals with schizophrenia spectrum disorders was no remission and no recovery. Among individuals with other psychotic disorders, in both the baseline and 25-year cohorts, the modal pattern was one of intermittent remission and recovery. Individuals with other psychotic disorders were more likely to experience stable remission (15.1%) and stable recovery (21.1%), outcomes that were rare among individuals with schizophrenia spectrum disorders (0% and 0.6%, respectively). The modal longitudinal pattern for individuals with other psychoses is one of multiple transitions into and out of symptomatic and functional recovery. Engagement in a long-term health care plan may help individuals detect and respond to these changes. Sustained remission and recovery are rare among people with schizophrenia spectrum disorders. Efforts should be directed toward developing more effective treatments for this population.

Response to psychotic experiences: Impact of personality traits on perceived levels of distress

BackgroundThis study examined the influence of personality traits on (subclinical) positive symptom distress in patients with a psychotic disorder, their unaffected siblings and healthy controls. MethodsData were obtained from the Genetic Risk and Outcome of Psychosis study (GROUP), a Dutch longitudinal multicenter cohort study. Data from 140 patients, 216 unaffected siblings and 102 healthy controls was available for baseline levels of Five Factor Model personality traits and frequency and distress due to psychotic experiences three years later, assessed with the Community Assessment of Psychic Experience questionnaire. Main effects of all five personality traits on symptom distress were investigated as well as moderating effects of Neuroticism, Extraversion and Openness on positive symptom frequency and positive symptom distress. Age, gender, symptom frequency and IQ were controlled for. ResultsIn both patients and siblings, the observed main effects of Neuroticism and Openness on (subclinical) positive symptom distress three years later either lost significance or had a very small effect size when controlling for covariates, mainly due to the correction for the effect of positive symptoms on personality traits at baseline. In both groups, levels of Openness at baseline moderated the association between positive symptom frequency and positive symptom distress three years later, in the direction that higher levels of Openness were associated with weaker associations between positive symptom frequency and - distress, even when covariates were controlled for. DiscussionThe level of Openness to Experiences influences the perceived distress from (subclinical) positive symptoms in both patients and siblings.

On Inference for Modularity Statistics in Structured Networks

This article revisits the classical concept of network modularity and its spectral relaxations used throughout graph data analysis. We formulate and study several modularity statistic variants for which we establish asymptotic distributional results in the large-network limit for networks exhibiting nodal community structure. Our work facilitates testing for network differences and can be used in conjunction with existing theoretical guarantees for stochastic blockmodel random graphs. Our results are enabled by recent advances in the study of low-rank truncations of large network adjacency matrices. We provide confirmatory simulation studies and real data analysis pertaining to the network neuroscience study of psychosis, specifically schizophrenia. Collectively, this article contributes to the limited existing literature to date on statistical inference for modularity-based network analysis. Supplemental materials for this article are available online.

Response rates to sequential trials of antipsychotic medications according to algorithms or treatment guidelines in psychotic disorders. A systematic review and meta-analysis

BackgroundThere is a relative lack of research evaluating the outcomes when treatment guidelines or algorithms for psychotic disorders are followed. This systematic review and meta-analysis determined the response rates to antipsychotic medications at different stages of these algorithms and whether these response rates differ in first episode cohorts. MethodsData sources: A systematic search strategy was conducted across four databases PubMed, EMBASE, PsycINFO (Ovid) and CINAHL. Studies that had sequential trials of different antipsychotic medications were included. A meta-analysis of proportions was performed using random effects models and sub-group analysis in first episode psychosis studies. ResultsOf the 4078 unique articles screened, fourteen articles, from nine unique studies, were eligible and included 2522 participants. The proportion who experienced a response to any antipsychotic in the first stage of an algorithm was 0.53 (95 % C.I.:0.38,0.68) and this decreased to 0.26 (95 % C.I.:0.15,0.39) in the second stage. When clozapine was used in the third stage, the proportion that achieved a response was 0.43 (95 % C.I. 0.19, 0.69) compared to 0.26 (95 % C.I.:0.05,0.54) if a different antipsychotic was used. Four studies included 907 participants with a first episode of psychosis and the proportions that achieved a response were: 1st stage: 0.63 (95 % C.I.: 0.45, 0.79); 2nd stage: 0.34 (95 % C.I.:0.16,0.55); clozapine 3rd stage: 0.45 (95 % C.I.:0.0,0.97), different antipsychotic 3rd stage: 0.15 (95 % C.I.,0.01,0.37). DiscussionThese findings support the recommendation to have a trial of clozapine after two other antipsychotic medications have been found to be ineffective.