Deficits In First-episode Psychosis Research Articles

Computational Synaptic Modeling of Pitch and Duration Mismatch Negativity in First-Episode Psychosis Reveals Selective Dysfunction of the N-Methyl-D-Aspartate Receptor.

Mismatch negativity (MMN) to pitch (pMMN) and to duration (dMMN) deviant stimuli is significantly more attenuated in long-term psychotic illness compared to first-episode psychosis (FEP). It was recently shown that source-modeling of magnetically recorded MMN increases the detection of left auditory cortex MMN deficits in FEP, and that computational circuit modeling of electrically recorded MMN also reveals left-hemisphere auditory cortex abnormalities. Computational modeling using dynamic causal modeling (DCM) can also be used to infer synaptic activity from EEG-based scalp recordings. We measured pMMN and dMMN with EEG from 26 FEP and 26 matched healthy controls (HCs) and used a DCM conductance-based neural mass model including α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, N-methyl-D-Aspartate (NMDA), and Gamma-aminobutyric acid receptors to identify any changes in effective connectivity and receptor rate constants in FEP. We modeled MMN sources in bilateral A1, superior temporal gyrus, and inferior frontal gyrus (IFG). No model parameters distinguished groups for pMMN. For dMMN, reduced NMDA receptor activity in right IFG in FEP was detected. This finding is in line with literature of prefrontal NMDA receptor hypofunction in chronic schizophrenia and suggests impaired NMDA-induced synaptic plasticity may be present at psychosis onset where scalp dMMN is only moderately reduced. To the best of our knowledge, this is the first report of impaired NMDA receptor activity in FEP found through computational modeling of dMMN and shows the potential of DCM to non-invasively reveal synaptic-level abnormalities that underly subtle functional auditory processing deficits in early psychosis.

Functional and structural connectivity correlates of semantic verbal fluency deficits in first-episode psychosis

IntroductionSemantic verbal fluency (SVF) impairments are debilitating and present early in the course of psychotic illness. Deficits within frontal, parietal, and temporal brain regions contribute to this deficit, as long-range communication across this functionally integrated network is critical to SVF. This study sought to isolate disruptions in functional and structural connectivity contributing to SVF deficits during first-episode psychosis in the schizophrenia spectrum (FESz). MethodsThirty-three FESz and 34 matched healthy controls (HC) completed the Animal Naming Task to assess SVF. Magnetoencephalography was recorded during an analogous covert SVF task, and phase-locking value (PLV) used to measure functional connectivity between inferior frontal and temporoparietal structures bilaterally. Diffusion imaging was collected to measure fractional anisotropy (FA) of the arcuate fasciculus, the major tract connecting frontal and temporoparietal language areas. ResultsSVF scores were lower among FESz compared to HC. While PLV and FA did not differ between groups overall, FESz exhibited an absence of the left-lateralized nature of both measures observed in HC. Among FESz, larger right-hemisphere PLV was associated with worse SVF performance (ρ = −0.51) and longer DUP (ρ = −0.50). DiscussionIn addition to worse SVF, FESz exhibited diminished leftward asymmetry of structural and functional connectivity in fronto-temporoparietal SVF network. The relationship between theta-band hyperconnectivity and poorer performance suggests a disorganized executive network and may reflect dysfunction of frontal cognitive control centers. These findings illustrate an aberrant pattern across the distributed SVF network at disease onset and merit further investigation into development of asymmetrical hemispheric connectivity and its failure among high-risk populations.

54 The Influence of Sex on Cognitive Control Performance and Frontoparietal Network Integrity in First-Episode Psychosis

Objective:Cognitive deficits in first-episode psychosis (FEP) are well documented, particularly aspects of cognitive control, which is one of the primary hypothesized functions of the frontoparietal network (FPN). The clinical features of psychotic disorders are known to differ between men and women, but little work has systematically studied neurobiological differences between the sexes, particularly in FEP. The current study aimed to examine sexual dimorphisms in structural integrity of the frontoparietal network (FPN) and its role in cognitive control in FEP.Participants and Methods:A total of 111 FEP patients (68 male, 43 female) and 55 healthy control participants (35 male, 20 female) from the Human Connectome Project for Early Psychosis underwent T1-weighted magnetic resonance imaging and neuropsychological testing were included in the study. Regions of interest (ROIs) included: left and right superior frontal gyrus, left and right middle frontal gyrus, left inferior frontal gyrus, left and right inferior parietal gyrus, right caudate and left thalamus. Using high-dimensional brain mapping procedures, surface shape of the caudate and thalamus was characterized using Large Deformation Diffeomorphic Metric Mapping, and cortical thickness of frontal and parietal regions was estimated using the FreeSurfer toolkit. Cognitive control was assessed using the Fluid Cognition Composite score from the NIH Toolbox Cognition Battery. Multivariate ANOVA models tested group differences, separated by sex, in cortical thickness ROIs, in addition to a whole-brain vertex-wise analysis. Vertex-wise statistical surface t-maps evaluated differences in subcortical surface shape, and Pearson correlations tested relationships between brain regions and Fluid Cognition performance.Results:Results of deep brain region comparisons between schizophrenia males (SCZM) and schizophrenia females (SCZF) groups revealed significant outward deformation at the tail of the right caudate and significant inward deformation along the dorsal aspects of the right caudate. Additionally, significant inward deformation in multiple nuclei of the left thalamus were revealed. Significant negative relationships between Fluid Cognition and the left superior/middle frontal gyrus (r = -0.24, p = 0.05) in the male FEP group were observed. Additionally, significant positive relationships between Fluid Cognition and left inferior frontal gyrus (r = 0.35, p = 0.02) and left inferior parietal gyrus (r = 0.35, p = 0.02) in the female FEP group were found.Conclusions:Overall, findings revealed significant brain differences of the FPN in deep-brain structures only, including abnormal caudal and thalamic shape, in male FEP compared to female FEP, providing evidence of the importance to examine sex differences in deep-brain regions at the first episode. Differential brain relationships with cognitive control also highlight sex-specific presentations that may aid in clinical management and further characterization of the illness in early stages.

A tablet-based quantitative assessment of manual dexterity for detection of early psychosis.

We performed a pilot study on whether tablet-based measures of manual dexterity can provide behavioral markers for detection of first-episode psychosis (FEP), and whether cortical excitability/inhibition was altered in FEP. Behavioral and neurophysiological testing was undertaken in persons diagnosed with FEP (N = 20), schizophrenia (SCZ, N = 20), autism spectrum disorder (ASD, N = 20), and in healthy control subjects (N = 20). Five tablet tasks assessed different motor and cognitive functions: Finger Recognition for effector (finger) selection and mental rotation, Rhythm Tapping for temporal control, Sequence Tapping for control/memorization of motor sequences, Multi Finger Tapping for finger individuation, and Line Tracking for visuomotor control. Discrimination of FEP (from other groups) based on tablet-based measures was compared to discrimination through clinical neurological soft signs (NSS). Cortical excitability/inhibition, and cerebellar brain inhibition were assessed with transcranial magnetic stimulation. Compared to controls, FEP patients showed slower reaction times and higher errors in Finger Recognition, and more variability in Rhythm Tapping. Variability in Rhythm Tapping showed highest specificity for the identification of FEP patients compared to all other groups (FEP vs. ASD/SCZ/Controls; 75% sensitivity, 90% specificity, AUC = 0.83) compared to clinical NSS (95% sensitivity, 22% specificity, AUC = 0.49). Random Forest analysis confirmed FEP discrimination vs. other groups based on dexterity variables (100% sensitivity, 85% specificity, balanced accuracy = 92%). The FEP group had reduced short-latency intra-cortical inhibition (but similar excitability) compared to controls, SCZ, and ASD. Cerebellar inhibition showed a non-significant tendency to be weaker in FEP. FEP patients show a distinctive pattern of dexterity impairments and weaker cortical inhibition. Easy-to-use tablet-based measures of manual dexterity capture neurological deficits in FEP and are promising markers for detection of FEP in clinical practice.

The influence of modifiable cardiovascular risk factors on cognition, functioning, and inflammatory markers in first-episode psychosis: Results from a 2-year follow-up study

To explore the influence of cardiovascular risk factors (CVRFs) on cognitive symptoms, functional impairment, and systemic inflammatory markers in first-episode psychosis (FEP) patients at baseline and 2-year follow-up. Method: In a sample of 70 FEP patients and 85 age- and sex-matched healthy controls, we assessed nine modifiable CVRFs. All participants were classified into two subgroups according to their CVRF profile: lower (0–1 CVRFs) or higher (≥2 CVRFs). The following outcomes were measured at baseline and 2-year follow-up: cognition; functional outcomes; and white blood cell (WBC) subtype. Adjusted general linear models were conducted to study the effect of diagnosis and CVRF profile on cognition, functioning, WBC, and longitudinal changes in these variables. At baseline, FEP patients with a higher CVRF profile showed a significantly slower performance on the TMT-A test for psychomotor speed and higher lymphocyte levels than patients with a lower CVRF profile. No longitudinal changes were observed in primary outcomes at 2-year follow-up. Among FEP patients with a higher CVRF profile, slower psychomotor speed performance did not correlate with increased lymphocyte levels. Our findings suggest that the cognitive effects of CVRFs manifest early in the course of psychosis, thus highlighting the importance of targeting both CVRFs and cognitive deficits in FEP.

Severe childhood trauma and emotion recognition in males and females with first-episode psychosis.

Childhood trauma increases social functioning deficits in first-episode psychosis (FEP) and is negatively associated with higher-order social cognitive processes such as emotion recognition (ER). We investigated the relationship between childhood trauma severity and ER capacity, and explored sex as a potential factor given sex differences in childhood trauma exposure. Eighty-three FEP participants (52 males, 31 females) and 69 nonclinical controls (49 males, 20 females) completed the CogState Research Battery. FEP participants completed the Childhood Trauma Questionnaire. A sex×group (FEP, controls) ANOVA examined ER differences and was followed by two-way ANCOVAs investigating sex and childhood trauma severity (none, low, moderate, and severe) on ER and global cognition in FEP. FEP participants had significantly lower ER scores than controls (p=.035). No significant sex×group interaction emerged for ER F(3, 147)=.496, p=.438 [95% CI=-1.20-0.57], partial η2 =.003. When controlling for age at psychosis onset, a significant interaction emerged in FEP between sex and childhood trauma severity F(3, 71)=3.173, p=.029, partial η2 =.118. Males (n=9) with severe trauma showed ER deficits compared to females (n=8) (p=.011 [95% CI=-2.90 to -0.39]). No significant interaction was observed for global cognition F(3, 69)=2.410, p=.074, partial η2 =.095. These preliminary findings provide support for longitudinal investigations examining whether trauma severity differentially impacts ER in males and females with FEP.

Facial Emotion Recognition in Psychosis and Associations With Polygenic Risk for Schizophrenia: Findings From the Multi-Center EU-GEI Case–Control Study

Background and HypothesisFacial Emotion Recognition is a key domain of social cognition associated with psychotic disorders as a candidate intermediate phenotype. In this study, we set out to investigate global and specific facial emotion recognition deficits in first-episode psychosis, and whether polygenic liability to psychotic disorders is associated with facial emotion recognition.Study Design828 First Episode Psychosis (FEP) patients and 1308 population-based controls completed assessments of the Degraded Facial Affect Recognition Task (DFAR) and a subsample of 524 FEP and 899 controls provided blood or saliva samples from which we extracted DNA, performed genotyping and computed polygenic risk scores for schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MD).Study ResultsA worse ability to globally recognize facial emotion expressions was found in patients compared with controls [B= −1.5 (0.6), 95% CI −2.7 to −0.3], with evidence for stronger effects on negative emotions (fear [B = −3.3 (1.1), 95% CI −5.3 to −1.2] and anger [B = −2.3 (1.1), 95% CI −4.6 to −0.1]) than on happiness [B = 0.3 (0.7), 95% CI −1 to 1.7]. Pooling all participants, and controlling for confounds including case/control status, facial anger recognition was associated significantly with Schizophrenia Polygenic Risk Score (SZ PRS) [B = −3.5 (1.7), 95% CI −6.9 to −0.2].ConclusionsPsychosis is associated with impaired recognition of fear and anger, and higher SZ PRS is associated with worse facial anger recognition. Our findings provide evidence that facial emotion recognition of anger might play a role as an intermediate phenotype for psychosis.

Is blood-brain-barrier disruption associated with cognitive deficits in first-episode psychosis? Findings from a retrospective chart analysis

Is blood-brain-barrier disruption associated with cognitive deficits in first-episode psychosis? Findings from a retrospective chart analysis

Mnemonic Discrimination Deficits in First-Episode Psychosis and a Ketamine Model Suggest Dentate Gyrus Pathology Linked to NMDA Receptor Hypofunction

BackgroundConverging evidence from neuroimaging and postmortem studies suggests that hippocampal subfields are differentially affected in schizophrenia. Recent studies report dentate gyrus dysfunction in chronic schizophrenia, but the underlying mechanisms remain to be elucidated. Here, we sought to examine if this deficit is already present in first-episode psychosis and if NMDA receptor hypofunction, a putative central pathophysiological mechanism in schizophrenia, experimentally induced by ketamine, would result in a similar abnormality. MethodsWe applied a mnemonic discrimination task selectively taxing pattern separation in two experiments: 1) a group of 23 patients with first-episode psychosis and 23 matched healthy volunteers and 2) a group of 19 healthy volunteers before and during a ketamine challenge (0.27 mg/kg over 10 min, then 0.25 mg/kg/hour for 50 min, 0.01 mL/s). We calculated response bias–corrected pattern separation and recognition scores. We also examined the relationships between task performance and symptom severity as well as ketamine levels. ResultsWe reported a deficit in pattern separation performance in patients with first-episode psychosis compared with healthy volunteers (p = .04) and in volunteers during the ketamine challenge compared with baseline (p = .003). Pattern recognition was lower in patients with first-episode psychosis than in control subjects (p < .01). Exploratory analyses revealed no correlation between task performance and Repeatable Battery for the Assessment of Neuropsychological Status total scores or positive symptoms in patients with first-episode psychosis or with ketamine serum levels. ConclusionsWe observed a mnemonic discrimination deficit in both datasets. Our findings suggest a tentative mechanistic link between dentate gyrus dysfunction in first-episode psychosis and NMDA receptor hypofunction.

4327 Structural Neural Correlates of Social Functioning in First Episode Psychosis and Malleability in Response to Targeted Cognitive Training

OBJECTIVES/GOALS: Development of interventions that improve social functioning (SF) in first episode psychosis (FEP) is hindered by a poor understanding of the neural mechanisms underlying SF deficits. This research aims to identify neural correlates of social functioning in FEP, and to evaluate whether this substrate is malleable in response to cognitive training. METHODS/STUDY POPULATION: This is a secondary data-analysis of participants in an ongoing randomized clinical trial investigating whether 12 weeks of targeted cognitive training is neuroprotective in FEP, versus treatment as usual. Baseline and post-training assessments include a brain MRI, three measures of SF, and a neurocognitive battery. Healthy controls complete MRI only. Differences in cortical thickness (CTh) and gray matter volume (GMV) in regions of interest between FEP and controls will be determined with ANCOVA. Multiple linear regression will be used to determine the relationship between neural substrate and SF in FEP. Linear mixed models will be used to examine the relationship between change in CTh and GMV and change in SF. Data collection is ongoing for this study. RESULTS/ANTICIPATED RESULTS: In preliminary data including 12 FEP and 9 healthy controls, FEP demonstrated cortical loss in the right superior frontal cortex and the right isthmus-posterior cingulate. Greater cortical thickness in the posterior cingulate cortex was associated with better social functioning across multiple measures when controlling for global cognition. Gray matter volume in the parahippocampal gyrus was also associated with better social functioning. Preliminary results evaluating whether targeted cognitive training is neuroprotective in these regions of interest in a manner that is associated with improved social functioning will also be presented. DISCUSSION/SIGNIFICANCE OF IMPACT: Preliminary results link the posterior cingulate and parahippocampal gyrus to SF in FEP. Further research will investigate the contribution of changes in these brain regions to improved SF. The identification of biological treatment targets for SF may lead to development and optimization of novel interventions to alleviate SF deficits in FEP.

S70. PROFILES OF SOCIAL COGNITION AND METACOGNITION IN FIRST-EPISODE PSYCHOSIS: A LATENT PROFILE ANALYSIS

BackgroundSocial cognition and metacognition have emerged as cornerstones of research and treatment of schizophrenia. Both constructs are known to influence the onset of psychosis, to predict functional outcome and to be associated with symptoms. However, whether the deficits in first-episode psychosis are homogeneous or group in patterns remains to be studied. This study aimed to analyze patterns of social cognitive and metacognitive variables in a sample of subjects with first-episode psychosis.MethodsWe recruited 192 subjects with first-episode psychosis from ten public mental-health services in Spain. We collected: demographic information, measures of functioning, performance in social cognition (the Faces Test, IPSAQ and the Hinting Task), a battery of metacognitive tasks (BCIS, and the Beads Task) and a neuropsychological assessment. We performed a Latent Profile Analysis (LPA) with the metacognitive and social-cognitive variables. The variable importance was assessed via a classification tree (CART) and the mean differences among the resulting groups for clinical, neuropsychological and functioning variables were calculated with ANOVA and Kruskal-Wallis tests.ResultsOur sample was comprised of 192 (62 women) with first-episode psychosis. The mean age of the sample was 27.93(1.39). The mean PANSS total score of the sample was 58.48 (17.79). The average GAF score was 58.93 (12.25). We included 174 cases with complete social-cognitive and metacognitive data in the cluster analysis. We identified three type-VEE clusters (i.e. ellipsoidal clusters with equal shape and orientation) according to BIC (BIC=-3600.651). The 85-15 condition of the Beads Task and the Hinting Task emerged as the most important variables in determining the clustering structure. The first cluster (60.9%) was characterized by average scores in most of the metacognitive and social cognitive variables, but the presence of the jumping to conclusions bias. The second cluster (5.7%) was characterized by low self-reflectiveness, presence of personalizing bias and an excessive number of trials in the beads task. The third cluster (33.5%) was characterized by average scores in all metacognitive tasks but low scores in the social cognitive tasks.DiscussionWe found three clusters in a large sample of subjects with first-episode psychosis. Our results indicate that the three groups differ in the proneness to present deficits in specific domains. Furthermore, in our sample, patients may not exhibit a homogeneous deficit in all social-cognitive and metacognitive variables. Instead, the impairment may be particularly prominent in either social-cognitive or metacognitive variables. Subjects in different clusters may present differences in their clinical characteristics, what could be relevant in the treatment. Therefore, with further research, a thorough assessment of social cognition and metacognition may help personalize the treatment according to the person’s subtype of the deficit.

Localization of Early-Stage Visual Processing Deficits in First-Episode Psychosis

Impairments in sensory-perceptual visual processing are observed in long-term psychosis. However, their presence and contribution to symptoms remain less well established early in disease course. We used magnetoencephalography (MEG) to examine sensory responses within primary visual cortex (V1) in individuals at their first psychotic episode in the schizophrenia spectrum (FESz).

Disruption of gamma-delta relationship related to working memory deficits in first-episode psychosis.

Working memory (WM) deficits constitute a core symptom of schizophrenia. Inadequacy of WM maintenance in schizophrenia has been reported to reflect abnormalities in the excitation/inhibition (E/I) balance between pyramidal neurons and parvalbumin basket cells, which may explain alterations of the dynamics of gamma and delta oscillations. To address this issue, we assessed event-related gamma (35-45Hz) and delta (0.5-4Hz) oscillatory responses in a visual n-back WM task in patients with first-episode psychosis (FEP) and healthy controls (HC). Periodicity analyses of oscillations were computed to explore the relationship between the psychiatric status and the WM load-related processes reflected by each frequency range. The correspondence between nested delta-gamma oscillations was estimated to assess the strength of the frontal E/I balance. In HC, gamma oscillations were synchronized by the stimulus in a 50-150ms time range for all tasks, and periodicity of the delta cycle was comparable between the tasks. In addition, synchronization of gamma oscillations in HC occurred at the maximal descending phase of the delta cycle half-period, supporting the coexistence of delta-nested gamma oscillations. Compared with controls, FEP patients showed a lack of gamma synchronization independently of the nature of the task, and the period of delta oscillation increased significantly with the difficulty of the WM task. We thus demonstrated in FEP an inability to encode multiple items in short-term memory associated with abnormalities in the relationship between oscillations related to the difficulty of the WM task. These results argue in favor of a dysfunction of the E/I balance in psychosis.

Exploring the use of the Hinting Task in first-episode psychosis

ABSTRACTIntroduction: The aim of the study was to elucidate the association between performance-related neurocognitive abilities and Theory of Mind (ToM) as measured by the Hinting Task (HT) performance and investigate the psychometric properties of the HT for use in First-Episode Psychosis (FEP).Methods: Cross-sectional data of 132 participants with FEP, aged 15–25 years, enrolled in a randomised controlled trial of vocational intervention, were analysed. A comprehensive cognitive battery including social cognitive and neurocognitive measures, a social and occupational functioning measure and psychopathological measures, were used. Psychometric properties were measured through bivariate correlations and associations with neurocognitive domains were assessed through hierarchical regression.Results: Low convergent validity of the HT with other ToM measures, moderate discriminant validity with an emotion recognition task, low predictive validity with social and occupational functioning, and high internal consistency were revealed. HT performance was significantly associated with verbal reasoning and verbal memory.Conclusion: Results provide preliminary evidence of low convergent validity and moderate discriminant validity of the HT in FEP, and the influence of verbal reasoning and verbal memory on HT performance, indicating that caution is warranted when employing the HT as a screening tool in isolation for detection of ToM deficits in FEP.

S204. NUTRITIONAL DEFICIENCIES AND CLINICAL CORRELATES IN FIRST-EPISODE PSYCHOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

BackgroundDiet is increasingly recognised as a modifiable factor influencing the onset and outcomes of psychiatric disorders. Previous meta-analyses of blood nutrient levels in schizophrenia have already shown significant reductions in various individual vitamins/minerals. However, studies to date have largely focused on individual nutrients, and only considered nutrient status in patients with long-term schizophrenia. Meta-analytic evaluation of the evidence for nutrient deficits in first-episode psychosis (FEP) is completely absent. Therefore, we conducted a systematic review of all published studies comparing blood levels of vitamins and/or mineral in FEP to healthy control samples; and applied meta-analytic techniques to determine the prevalence and extent of deficiencies across the full spectrum of nutrients examined in this population to date.MethodsWe searched electronic databases from inception to July 2017 for all studies examining blood levels (i.e. serum, plasma or whole blood) of nutrient levels in people with FEP compared to healthy controls. Our systematic search identified 28 eligible studies, examining blood levels of 16 different nutrients (six vitamins, ten dietary minerals) across 2,612 individuals: 1,221 patients with FEP and 1,391 control subjects. Random effects meta-analyses compared nutrient levels in FEP to healthy controls. Clinical correlates of nutritional status in patient samples were systematically reviewed.ResultsRandom effects meta-analyses found that people with FEP had large, significant reductions in blood levels of vitamin B9 (i.e. folate) compared to healthy controls(N=6, n=827, g=-0.624, 95% C.I.=-1.176 to -0.072, p=0.027). Significant reductions were also found for vitamin D (N=7, n=906, g=-1.055, 95% C.I.=-1.99 to -0.119, p=0.027) and, among fewer studies, vitamin C (N=2, n=96, g=-2.207, 95% C.I.=-3.71 to -0.71, p=0.004). No differences were found for other vitamins or minerals. Systematic synthesis of clinical correlates showed that reductions in both folate and vitamin D held significant relationships with greater psychiatric symptoms in FEP.DiscussionThis is the first meta-analysis to examine the prevalence, extent and clinical correlates of nutritional deficiencies in FEP to date. The deficits in vitamin D and folate which have previously been observed in long-term schizophrenia appear to exist from illness onset, even prior to antipsychotic treatment, and are associated with more severe symptoms. The extent and importance of these deficiencies suggests that routine screening for vitamin D and folate deficiencies should be considered in early intervention services. Furthermore, since our previous meta-analyses have shown that high-dose b-vitamin supplementation can reduce symptoms in long-term schizophrenia, this should now be investigated in FEP. The potential physical and psychological benefits of vitamin D supplementation in early psychosis should also be explored. However, further research is needed to establish casual and mechanistic relationships between vitamin deficiencies, poor diet and the onset and outcomes of psychotic disorders.

Impairment of perceptual metacognitive accuracy and reduced prefrontal grey matter volume in first-episode psychosis

ABSTRACTIntroduction: Metacognition, or “thinking about thinking”, is a higher-order thought process that allows for the evaluation of perceptual processes for accuracy. Metacognitive accuracy is associated with the grey matter volume (GMV) in the prefrontal cortex (PFC), an area also impacted in schizophrenia. The present study set out to investigate whether deficits in metacognitive accuracy are present in the early stages of psychosis.Methods: Metacognitive accuracy in first-episode psychosis (FEP) was assessed on a perceptual decision-making task and their performance compared to matched healthy control participants (N = 18). A novel signal detection theory approach was used to model metacognitive sensitivity independently from objective perceptual performance. A voxel-based morphometry investigation was also conducted on GMV.Results: We found that the FEP group demonstrated significantly worse metacognitive accuracy compared to controls (p = .039). Importantly, GMV deficits were also observed in the superior frontal gyrus. The findings suggest a specific deficit in this processing domain to exist at first episode; however, no relationship was found between GMV and metacognitive accuracy.Conclusions: Our findings support the notion that an inability to accurately scrutinise perception may underpin functional deficits observed in later schizophrenia; however, the exact neural basis of metacognitive deficits in FEP remains elusive.

Nutritional Deficiencies and Clinical Correlates in First-Episode Psychosis: A Systematic Review and Meta-analysis.

ObjectiveDiet is increasingly recognized as a potentially modifiable factor influencing the onset and outcomes of psychiatric disorders. Whereas, previous research has shown long-term schizophrenia is associated with various nutritional deficiencies, this meta-analysis aimed to determine the prevalence and extent of nutritional deficits in first-episode psychosis (FEP).MethodA search of electronic databases conducted in July 2017 identified 28 eligible studies, examining blood levels of 6 vitamins and 10 minerals across 2612 individuals: 1221 individuals with FEP and 1391 control subjects. Meta-analyses compared nutrient levels in FEP to nonpsychiatric controls. Clinical correlates of nutritional status in patient samples were systematically reviewed.ResultsSignificantly lower blood levels of folate (N = 6, n = 827, g = −0.624, 95% confidence interval [CI] = −1.176 to −0.072, P = .027) and vitamin D (N = 7, n = 906, g = −1.055, 95% CI = −1.99 to −0.119, P = .027) were found in FEP compared to healthy controls. Synthesis of clinical correlates found both folate and vitamin D held significant inverse relationships with psychiatric symptoms in FEP. There was also limited evidence for serum level reductions of vitamin C (N = 2, n = 96, g = −2.207, 95% CI = −3.71 to −0.71, P = .004). No differences were found for other vitamins or minerals.ConclusionsDeficits in vitamin D and folate previously observed in long-term schizophrenia appear to exist from illness onset, and are associated with worse symptomology. Further research must examine the direction and nature of these relationships (ie, mediator, moderator, or marker) with clinical status in FEP. Future trials assessing efficacy of nutrient supplementation in FEP samples should consider targeting and stratifying for baseline deficiency.

RETRACTED: Mnemonic Discrimination Deficits in First-Episode Psychosis and a Ketamine Model Suggests Dentate Gyrus Pathology Linked to N-Methyl-D-Aspartate Receptor Hypofunction

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). Retraction notice to: “Mnemonic Discrimination Deficits in First-Episode Psychosis and a Ketamine Model Suggests Dentate Gyrus Pathology Linked to N-Methyl-D-Aspartate Receptor Hypofunction” by Nina Vanessa Kraguljac, Matthew Carle, Michael A. Frölich, Steve Tran, Michael A. Yassa, David Matthew White, Abhishek Reddy, and Adrienne Carol Lahti (Biol Psychiatry Cogn Neurosci Neuroimaging 2018; 3:231-238); https://doi.org/10.1016/j.bpsc.2017.02.005. This article has been retracted at the request of Cameron S. Carter, M.D., Editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, with agreement from all authors. The authors discovered an error in the calculation of the response bias–corrected pattern recognition score in this article, which has significantly changed the results for experiment 1. Specifically, the authors discovered that the response bias corrected pattern recognition score was erroneously computed as P(‘old’|target) minus P(‘old’|lure) rather than P(‘old’|target) minus P(‘old’|foil). After re-running statistical analyses with the correct values, the authors found a significant difference in the response bias–corrected pattern recognition score in healthy volunteers (HV) compared with first-episode psychosis (FEP) patients (HV: 84.13 ± 10.96; FEP: 63.70 ± 21.83; t = 4.01; p < .01) in experiment 1. This finding is not consistent with the original report, where the authors reported no group differences in bias-corrected pattern recognition scores (originally reported values: t = 0.93, p = .36). The authors again found no significant correlations between pattern completion scores and BPRS total, positive, or negative symptom scores or RBANS scores, consistent with the original report. In experiment 2, bias-corrected pattern recognition scores did not differ between the saline and ketamine conditions (saline: 78.29 ± 28.04; ketamine: 73.59 ± 18.94; t = 0.81; p = 0.43), which is consistent with the original report (originally reported values: t = −0.69, p = .50). Contrary to the original report, task performance during the saline and ketamine infusions was no longer correlated at trend level for pattern recognition. Repeat analyses showed no correlations between pattern recognition scores during the ketamine challenge and BPRS total, positive, and negative symptom scores, or ketamine plasma levels at either time point, consistent with the original report. The authors have verified that bias-corrected pattern separation scores were calculated correctly for both experiments in the initial report. This error affects the abstract, the results, Figure 1, and discussion of the manuscript. The authors voluntarily informed the Journal of this honest error upon its discovery. Because of the extent and nature of the changes to the paper, the editors and authors concluded that, to ensure maximum clarity and transparency, the only course of action was to retract this version of the paper. The authors are revising the paper, which the Journal will re-review and consider further for publication.

Sensory Gating Deficits in First-Episode Psychosis: Evidence From Neurophysiology, Psychophysiology, and Neuropsychology.

Sensory gating deficits are commonly found in patients with schizophrenia. However, there is still scarce research on this issue. Thirty-eight patients with first-episode psychosis (FEP) were compared to thirty-eight controls. A condition-test paradigm of event-related potentials (ERP), prepulse inhibition (PPI), and some specific tasks of the MATRICS Consensus Cognitive Battery (MCCB) were used (i.e., TMT, BACS-SC, and Fluency for processing speed and CPT-IP for attention and vigilance). The ERP components measured were P50, N1, and P2. The PPI intervals examined were 30, 60, and 120 msec. Regarding the MCCB, processing speed and attention/vigilance cognitive domains were selected. FEP patients showed significant deficits in N1 and P2 components, at 30 and 60 PPI levels and in all the MCCB subtests selected. We obtained significant relationships in N1 with PPI-60, and with one MCCB subtest for processing speed. In addition, this same subtest showed significant association with P2. Therefore, sensory gating functioning is widely impaired since the very early stages of schizophrenia.

Cognitive impairments in patients with first episode psychosis: The relationship between neurophysiological and neuropsychological assessments

Cognitive deficits in schizophrenia have been widely reported. Neurophysiological and neuropsychological assessments have been conducted to study these impairments. Event-related potentials (ERPs) are relevant markers of cognitive deficits in schizophrenia, and reductions in specific ERP components have been found. The MATRICS Consensus Cognitive Battery (MCCB) was developed to obtain a consensus battery for the assessment of cognitive deficits in schizophrenia. Here, we aimed to study modulations of several ERP components in first episode psychosis (FEP). We also examined neuropsychological deficits using the MCCB, and correlations between ERP and MCCB impairments. Thirty-eight FEP patients were compared to thirty-eight healthy controls. The following ERP components were examined: P1, N1, MMN, P2, early-P3 and late-P3. We used an auditory three-stimulus oddball paradigm, with standard (60%), target (20%) and distractor (20%) stimuli. FEP patients showed significantly lower amplitudes of P2, early-P3 and late-P3 components. FEP patients also showed significant deficits in all the MCCB cognitive domains. Finally, correlational analyses found strong associations between amplitudes of P2, early-P3 and late-P3 components and MCCB tests for attention and speed of processing. These findings indicate that deficits in late auditory ERP components are present in FEP, whereas early components are preserved. These reductions in late ERP components were related to attentional deficits in FEP as assessed by MCCB. These findings indicate that MCCB is a valid battery for studying cognitive impairments in the initial stages of schizophrenia, and highlight the utility of converging neurophysiological and neuropsychological measures to examine attentional impairments in schizophrenia.