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Background and Hypothesis: Recent evidence has highlighted the benefits of early detection and treatment for better clinical outcomes in patients with psychosis. Biological markers of the disease have become a focal point of research. This study aimed to identify protein markers detectable in the early stages of psychosis and indicators of progression by comparing them with those of healthy controls (HC) and first episode psychosis (FEP)., Study Design: The participants comprised 28 patients in the clinical high-risk (CHR) group, 49 patients with FEP, and 61 HCs aged 15-35 years. Blood samples were collected and analyzed using multiple reaction monitoring-mass spectrometry to measure the expression of 158 peptide targets. Data were adjusted for age, sex, and use of psychotropic drugs., Study Results: A total of 18 peptides (17 proteins) differed significantly among the groups. The protein PRDX2 was higher in the FEP group than in the CHR and HC groups and showed increased expression according to disease progression. The levels of six proteins were significantly higher in the FEP group than in the CHR group. Nine proteins differed significantly in the CHR group compared to the other groups. Sixteen proteins were significantly correlated with symptom severity. These proteins are primarily related to the coagulation cascade, inflammatory response, brain structure, and synaptic plasticity., Conclusions: Our findings suggested that peripheral protein markers reflect disease progression in patients with psychosis. Further longitudinal research is needed to confirm these findings and to identify the specific roles of these markers in the pathogenesis of schizophrenia., Competing Interests: Declaration of competing interest All authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (Copyright © 2023. Published by Elsevier Ltd.)

Negative symptoms are prominent in individuals with schizophrenia (SZ) and youth at clinical high-risk for psychosis (CHR). In SZ, negative symptoms are linked to reinforcement learning (RL) dysfunction; however, previous research suggests implicit RL remains intact. It is unknown whether implicit RL is preserved in the CHR phase where negative symptom mechanisms are unclear, knowledge of which may assist in developing early identification and prevention methods. Participants from two studies completed an implicit RL task: Study 1 included 53 SZ individuals and 54 healthy controls (HC); Study 2 included 26 CHR youth and 23 HCs. Bias trajectories reflecting implicit RL were compared between groups and correlations with negative symptoms were examined. Cluster analysis investigated RL profiles across the combined samples. Implicit RL was comparable between HC and their corresponding SZ and CHR groups. However, cluster analysis was able to parse performance heterogeneity across diagnostic boundaries into two distinct RL profiles: a Positive/Early Learning cluster (65% of participants) with positive bias scores increasing from the first to second task block, and a Negative/Late Learning cluster (35% of participants) with negative bias scores increasing from the second to third block. Clusters did not differ in the proportion of CHR vs. SZ cases; however, the Negative/Late Learning cluster had more severe negative symptoms. Although implicit RL is intact in CHR similar to SZ, distinct implicit RL phenotypic profiles with elevated negative symptoms were identified trans-phasically, suggesting distinct reward-processing mechanisms can contribute to negative symptoms independent of phases of illness., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Negative symptoms (i.e., anhedonia, avolition, asociality, blunted affect, alogia) are frequently observed in the schizophrenia-spectrum (SZ) and associated with functional disability. While semi-structured interviews of negative symptoms represent a gold-standard approach, they require specialized training and may be vulnerable to rater biases. Thus, brief self-report questionnaires measuring negative symptoms may be useful. Existing negative symptom questionnaires demonstrate that this approach may be promising in schizophrenia, but no measure has been devised for use across stages of psychotic illness. The present study reports initial psychometric validation of the Negative Symptom Inventory-Self-Report (NSI-SR), the self-report counterpart of the Negative Symptom Inventory-Psychosis Risk clinical interview. The NSI-SR is a novel transphasic negative symptoms measure assessing the domains of anhedonia, avolition, and asociality. The NSI-SR and related measures were administered to two samples: 1) undergraduates (n = 335), 2) community participants, including: SZ (n = 32), clinical-high risk for psychosis (CHR, n = 25), and healthy controls matched to SZ (n = 31) and CHR (n = 30). The psychometrically trimmed 11-item NSI-SR showed good internal consistency and a three-factor solution reflecting avolition, asociality, and anhedonia. The NSI-SR demonstrated convergent validity via moderate to large correlations with clinician-rated negative symptoms and related constructs in both samples. Discriminant validity was supported by lower correlations with positive symptoms in both samples; however, correlations with positive symptoms were still significant. These initial psychometric findings suggest that the NSI-SR is a reliable and valid brief questionnaire capable of measuring negative symptoms across phases of psychotic illness., Competing Interests: Declaration of competing interest G.P.S. is one of the original developers of the Brief Negative Symptom Scale (BNSS) and receives royalties and consultation fees from ProPhase LLC in connection with commercial use of the BNSS and other professional activities., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Brain dysconnectivity has been posited as a biological marker of schizophrenia. Emerging schizophrenia connectome research has focused on rich-club organization, a tendency for brain hubs to be highly-interconnected but disproportionately vulnerable to dysconnectivity. However, less is known about rich-club organization in individuals at clinical high-risk for psychosis (CHR-P) and how it compares with abnormalities early in schizophrenia (ESZ). Combining diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI), we examined rich-club and global network organization in CHR-P (n = 41) and ESZ (n = 70) relative to healthy controls (HC; n = 74) after accounting for normal aging. To characterize rich-club regions, we examined rich-club MRI morphometry (thickness, surface area). We also examined connectome metric associations with symptom severity, antipsychotic dosage, and in CHR-P specifically, transition to a full-blown psychotic disorder. ESZ had fewer connections among rich-club regions (ps < .024) relative to HC and CHR-P, with this reduction specific to the rich-club even after accounting for other connections in ESZ relative to HC (ps < .048). There was also cortical thinning of rich-club regions in ESZ (ps < .013). In contrast, there was no strong evidence of global network organization differences among the three groups. Although connectome abnormalities were not present in CHR-P overall, CHR-P converters to psychosis (n = 9) had fewer connections among rich-club regions (ps < .037) and greater modularity (ps < .037) compared to CHR-P non-converters (n = 19). Lastly, symptom severity and antipsychotic dosage were not significantly associated with connectome metrics (ps < .012). Findings suggest that rich-club and connectome organization abnormalities are present early in schizophrenia and in CHR-P individuals who subsequently transition to psychosis., Competing Interests: Declaration of competing interest DHM received compensation as a consultant for Boehringer-Ingelheim, Cadent Therapeutics, Neurocrine Biosciences, Gilgamesh Pharma, Recognify Life Sciences, and Syndesi Therapeutics. The other authors report no conflict of interest. The other authors report no conflict of interest. JPYH, SLF, JMF, and DHM are United States Government employees. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government., (Published by Elsevier B.V.)

Aim: This study examines associations between premorbid adjustment and comorbid disorders in individuals at ultra-high risk (UHR) for psychosis., Methods: Premorbid social and academic adjustment data were collected from 146 UHR individuals using the Premorbid Adjustment Scale. Comorbid disorders were determined by the Structural Clinical Interview for DSM-IV., Results: Logistic regressions showed lower premorbid social adjustment associated with personality disorders. Lower premorbid academic adjustment associated with affective disorders. More specifically, poor premorbid social adjustment in early and late adolescence associated with personality disorders. Lower premorbid social adjustment in late adolescence and lower premorbid academic adjustment in early adolescence associated with affective disorders., Conclusion: Partly corroborating evidence from schizophrenia samples, our findings suggest that poor premorbid adjustment relate to distinct comorbid disorders in UHR individuals. If replicated, it indicates that premorbid adjustment deficits may be a key area for targeted interventions improving the clinical prognosis of UHR individuals., (© 2023 John Wiley & Sons Australia, Ltd.)

Aim: Language disturbances are a candidate biomarker for the early detection of psychosis. Temporal and prosodic abnormalities have been observed in schizophrenia patients, while there is conflicting evidence whether such deficits are present in participants meeting clinical high-risk for psychosis (CHR-P) criteria., Methods: Clinical interviews from CHR-P participants (n = 50) were examined for temporal and prosodic metrics and compared against a group of healthy controls (n = 17) and participants with affective disorders and substance abuse (n = 23)., Results: There were no deficits in acoustic variables in the CHR-P group, while participants with affective disorders/substance abuse were characterized by slower speech rate, longer pauses and higher unvoiced frames percentage., Conclusion: Our finding suggests that temporal and prosodic aspects of speech are not impaired in early-stage psychosis. Further studies are required to clarify whether such abnormalities are present in sub-groups of CHR-P participants with elevated psychosis-risk., (© 2022 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Background: Pineal volume reductions have been reported in schizophrenia and clinical high-risk states for the development of psychosis, supporting the role of melatonin dysregulation in the pathophysiology of psychosis. However, it remains unclear whether pineal volume is associated with the later onset of psychosis in individuals at clinical high-risk (CHR) of psychosis or if pineal atrophy is specific to schizophrenia among different psychotic disorders., Methods: This magnetic resonance imaging study examined the volume of and cyst prevalence in the pineal gland in 135 individuals at CHR of psychosis [52 (38.5%) subsequently developed psychosis], 162 with first-episode psychosis (FEP), 89 with chronic schizophrenia, and 87 healthy controls. The potential contribution of the pineal morphology to clinical characteristics was also examined in the CHR and FEP groups., Results: Pineal volumes did not differ significantly between the CHR, FEP, and chronic schizophrenia groups, but were significantly smaller than that in healthy controls. However, pineal volumes were not associated with the later onset of psychosis in the CHR group or FEP sub-diagnosis (i.e., schizophrenia, schizophreniform disorder, affective psychosis, and other psychoses). No significant differences were observed in the prevalence of pineal cysts between the groups, and it also did not correlate with clinical characteristics in the CHR and FEP groups., Conclusion: These results suggest that pineal atrophy is a general vulnerability marker of psychosis, while pineal cysts do not appear to contribute to the pathophysiology of psychosis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Schizophrenia is characterised by cognitive impairments that are already present during early stages, including in the clinical high-risk for psychosis (CHR-P) state and first-episode psychosis (FEP). Moreover, data suggest the presence of distinct cognitive subtypes during early-stage psychosis, with evidence for spared vs. impaired cognitive profiles that may be differentially associated with symptomatic and functional outcomes. Using cluster analysis, we sought to determine whether cognitive subgroups were associated with clinical and functional outcomes in CHR-P individuals. Data were available for 146 CHR-P participants of whom 122 completed a 6- and/or 12-month follow-up; 15 FEP participants; 47 participants not fulfilling CHR-P criteria (CHR-Ns); and 53 healthy controls (HCs). We performed hierarchical cluster analysis on principal components derived from neurocognitive and social cognitive measures. Within the CHR-P group, clusters were compared on clinical and functional variables and examined for associations with global functioning, persistent attenuated psychotic symptoms and transition to psychosis. Two discrete cognitive subgroups emerged across all participants: 45.9% of CHR-P individuals were cognitively impaired compared to 93.3% of FEP, 29.8% of CHR-N and 30.2% of HC participants. Cognitively impaired CHR-P participants also had significantly poorer functioning at baseline and follow-up than their cognitively spared counterparts. Specifically, cluster membership predicted functional but not clinical outcome. Our findings support the existence of distinct cognitive subgroups in CHR-P individuals that are associated with functional outcomes, with implications for early intervention and the understanding of underlying developmental processes., (© 2021. Crown.)

Neurocognitive deficits are implicated in individuals that meet criteria for a clinical high-risk (CHR) syndrome. Evidence in patients with schizophrenia suggests that cerebellar dysfunction may underlie neurocognitive deficits. However, little research has examined if similar associations are present in those meeting CHR criteria. This study examined associations between the MATRICS cognitive battery, postural sway (an index of cerebellar functioning), and SIPS-RC psychosis risk scores in a CHR sample (N = 66). Poorer working memory and processing speed were associated with less postural control. Consistent with the cognitive dysmetria theory of schizophrenia, neurocognitive deficits are associated with cerebellar dysfunction in this critical population., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Impairments in self-recognition (i.e. recognition of own thoughts and actions) have been repeatedly shown in individuals with schizophrenia. According to classical clinical characterizations, schizophrenia is included in a continuum encompassing a large range of genetic statuses, psychotic states and symptoms. The current meta-analysis aims to determine whether self-recognition is affected by individuals within the psychosis continuum., Method: Three populations were considered: people with an at-risk mental state for psychosis (ARMS), hallucination-prone individuals and unaffected relatives of patients with schizophrenia. Eleven studies contrasted self-recognition between these three populations ( n = 386) and healthy controls ( n = 315) and four studies used correlational analysis to estimate comparable effects ( n = 629). Eligible studies used experimental paradigms including source-monitoring and self-monitoring., Results: We observed significantly reduced self-recognition accuracy in these populations [ g = -0.44 (-0.71 to -0.17), p = 0.002] compared to controls. No influence of the type of population, experimental paradigm or study design was observed., Conclusion: The present analysis argues for self-recognition deficits in populations with no full-blown psychotic symptoms represented across the continuum of psychosis.

Background: Consistent with pathophysiological models of psychosis, temporal disturbances in schizophrenia spectrum populations may reflect abnormal cortical (e.g. prefrontal cortex) and subcortical (e.g. striatum) cerebellar connectivity. However, few studies have examined associations between cerebellar connectivity and timing dysfunction in psychosis populations, and none have been conducted in youth at clinical high-risk (CHR) for psychosis. Thus, it is currently unknown if impairments in temporal processes are present in CHR youth or how they may be associated with cerebellar connectivity and worsening of symptoms., Methods: A total of 108 (56 CHR/52 controls) youth were administered an auditory temporal bisection task along with a resting state imaging scan to examine cerebellar resting state connectivity. Positive and negative symptoms at baseline and 12 months later were also quantified., Results: Controlling for alcohol and cannabis use, CHR youth exhibited poorer temporal accuracy compared to controls, and temporal accuracy deficits were associated with abnormal connectivity between the bilateral anterior cerebellum and a right caudate/nucleus accumbens striatal cluster. Poor temporal accuracy accounted for 11% of the variance in worsening of negative symptoms over 12 months., Conclusions: Behavioral findings suggest CHR youth perceive durations of auditory tones as shortened compared to objective time, which may indicate a slower internal clock. Poorer temporal accuracy in CHR youth was associated with abnormalities in brain regions involved in an important cerebellar network implicated in prominent pathophysiological models of psychosis. Lastly, temporal accuracy was associated with worsening of negative symptoms across 12 months, suggesting temporal dysfunction may be sensitive to illness progression.

Prior studies indicate that chronic schizophrenia (SZ) is associated with a specific profile of reinforcement learning abnormalities. These impairments are characterized by: 1) reductions in learning rate, and 2) impaired Go learning and intact NoGo learning. Furthermore, each of these deficits are associated with greater severity of negative symptoms, consistent with theoretical perspectives positing that avolition and anhedonia are associated with impaired value representation. However, it is unclear whether these deficits extend to earlier phases of psychotic illness and when individuals are unmedicated. Two studies were conducted to examine reinforcement learning deficits in earlier phases of psychosis and in high risk patients. In study 1, participants included 35 participants with first episode psychosis (FEP) with limited antipsychotic medication exposure and 25 healthy controls (HC). Study 2 included 17 antipsychotic naïve individuals who were at clinical high-risk for psychosis (CHR) (i.e., attenuated psychosis syndrome) and 18 matched healthy controls (HC). In both studies, participants completed the Temporal Utility Integration Task, a measure of probabilistic reinforcement learning that contained Go and NoGo learning blocks. FEP displayed impaired Go and NoGo learning. In contrast, CHR did not display impairments in Go or NoGo learning. Impaired Go learning was not significantly associated with clinical outcomes in the CHR or FEP samples. Findings provide new evidence for areas of spared and impaired reinforcement learning in early phases of psychosis., Competing Interests: Conflicts of Interest G.P.S. is one of the original developers of the Brief Negative Symptom Scale (BNSS) and receives royalties and consultation fees from Medavante-ProPhase LLC in connection with commercial use of the BNSS and other professional activities; these fees are donated to the Brain and Behavior Research Foundation. GPS has received honoraria and travel support from Medavante-ProPhase LLC for training pharmaceutical company raters on the BNSS. In the past 2 years, GPS has consulted for and/or been on the speaker bureau for Minerva Neurosciences, Acadia, and Lundbeck pharmaceutical companies. All other authors have no relevant disclosures to report., (Copyright © 2021. Published by Elsevier B.V.)

The current study examined the presence of abnormalities in cortical grey-matter (GM) in a sample of clinical high-risk (CHR) participants and examined relationships with psychosocial functioning and neurocognition. CHR-participants (n = 114), participants who did not fulfil CHR-criteria (CHR-negative) (n = 39) as well as a group of healthy controls (HC) (n = 49) were recruited. CHR-status was assessed using the Comprehensive Assessment of At-Risk Mental State (CAARMS) and the Schizophrenia Proneness Interview, Adult Version (SPI-A). The Brief Assessment of Cognition in Schizophrenia Battery (BACS) as well as tests for emotion recognition, working memory and attention were administered. In addition, role and social functioning as well as premorbid adjustment were assessed. No significant differences in GM-thickness and intensity were observed in CHR-participants compared to CHR-negative and HC. Circumscribed abnormalities in GM-intensity were found in the visual and frontal cortex of CHR-participants. Moreover, small-to-moderate correlations were observed between GM-intensity and neuropsychological deficits in the CHR-group. The current data suggest that CHR-participants may not show comprehensive abnormalities in GM. We discuss the implications of these findings for the pathophysiological theories of early stage-psychosis as well as methodological issues and the impact of different recruitment strategies., Competing Interests: Declaration of competing interest P.J.U. has received research support from Lilly and Lundbeck. S.M.L. has received lecture fees from Janssen, Otsuka and Sunovion. The remaining authors report no biomedical financial interests or potential conflicts of interest. The following are the supplementary data related to this article. Supplementary data to this article can be found online at https://doi.org/10.1016/j.schres.2019.08.034., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The lifetime risk of dying by suicide in schizophrenia and related psychoses has been estimated to be approximately between 5% and 7%, though some have estimated that the number is closer to 10%. The highest risk for suicide occurs within the first year after presentation, when patients have a 12 times greater risk of dying by suicide than the general population, or a 60% higher risk compared with patients in other phases of psychosis, although the risk continues for many years. Some 31% of all deaths in first and early episode samples are due to suicide. Studies in individuals at clinical high-risk for psychosis (CHR) or with attenuated positive symptoms also demonstrate that suicidality is common and problematic in these individuals. Therefore, suicide in psychosis is a particularly severe problem. In order to develop interventions aimed at reducing the risk of suicide in psychotic individuals, it will be critical to understand the neurobiology of suicide in psychosis. In this paper, I report on the results of a systematic review of the work done to date on the neurobiology of suicide in psychosis and on suicidality in the CHR period. I will also identify gaps in knowledge and discuss future strategies for studying the neurobiology of suicidality in psychosis that may help to disentangle the links between suicide and psychosis and, by doing so, allow us to gain a greater understanding of the relationship between suicide and psychosis, which is critical for developing interventions aimed at reducing the risk of suicide in psychotic individuals.

Background: Despite its increased use in mental health, both health care provision by telehealth and research are in the early stages. Videoconferencing, a telehealth subfield, has been mainly used for the medication management and delivery of psychological treatments for mood, adjustment and anxiety disorders, and to a lesser extent for psychotic disorders., Objectives: The focus of this scoping review is on studies using videoconferencing for intervention for individuals with a diagnosis of schizophrenia-spectrum disorder and those who may be considered to be in the very early stages of psychosis (clinical high risk). The aim of this review is to assess the feasibility, acceptability and clinical benefits of videoconferencing interventions and compare them with face-to-face interventions for this population., Methods: A scoping review of peer-reviewed original research on the use of videoconferencing for intervention purposes in individuals with a schizophrenia-spectrum disorder or at clinical high risk., Results: Out of 13,750 citations, 60 articles were retrieved for detailed evaluation, resulting in 14 eligible studies ( N  = 439 individuals). There was no study reporting on videoconferencing interventions for individuals at clinical high risk. All the studies reported that videoconferencing implementation was feasible, and most of them described high acceptance by individuals with a schizophrenia-spectrum disorder. However, selection bias of studies was high, and overall methodological quality was poor., Conclusion: Videoconferencing interventions seem feasible for participants with schizophrenia-spectrum disorder who showed high acceptance of this intervention modality.

Objectives: Abnormalities in insular functional connectivity have been implicated in many clinical features of schizophrenia. The aim of this study was to determine to what degree such abnormalities occur in individuals with clinical high risk for psychosis (CHR), and whether which is associated with symptom severity., Methods: Resting-state fMRI data were collected from 47 healthy controls, 24 CHR individuals and 19 patients with first-episode schizophrenia. Using the posterior, dorsal and ventral insular subregions as separate seeds, we examined resting-state functional connectivity differences between different groups and the association between concurrent symptom severity and dysconnectivity., Results: Compared with healthy controls, both CHR individuals and schizophrenia patients showed hypoconnectivity between posterior insula (PI) and somatosensory areas, and between dorsal anterior insula (dAI) and putamen. Schizophrenia patients also showed dAI and ventral anterior insula(vAI) hyperconnectivity with visual areas relative to controls and CHR individuals. Correlation analysis revealed that dAI functional connectivity with superior temporal gyrus was positively correlated with positive symptoms of CHR, and vAI connectivity with dorsolateral prefrontal cortex was negatively correlated with the severity of the symptoms of first-episode schizophrenia., Conclusions: Our findings suggest that insular functional dysconnectivity with the sensory cortex may be a system-level neural substrate preceding the onset of psychosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: During vocalization, efference copy/corollary discharge mechanisms suppress the auditory cortical response to self-generated sounds. Previously, we found attenuated vocalization-related auditory cortical suppression in psychosis and a similar trend in the psychosis risk syndrome. Here, we report data from the final sample of early illness schizophrenia patients (ESZ), individuals at clinical high risk for psychosis (CHR), and healthy controls (HC)., Methods: Event-related potentials (ERP) were recorded from ESZ (n = 84), CHR (n = 71), and HC (n = 103) participants during a vocalization paradigm. The N1 ERP component was elicited during production (Talk) and playback (Listen) of vocalization. Age effects on N1 suppression (Talk-Listen), Talk N1, and Listen N1 were compared across groups. N1 measures were adjusted for normal aging before testing for group differences., Results: Both ESZ and CHR groups showed reduced Talk-Listen N1 suppression relative to HC, but did not differ from each other. Listen N1 was reduced in ESZ, but not in CHR, relative to HC. Deficient Talk-Listen N1 suppression was associated with greater unusual thought content in CHR individuals. N1 suppression increased with age in HC (12-36 years), and while CHR individuals showed a similar age-related increase, no such relationship was evident in ESZ., Conclusions: Putative efference copy/corollary discharge-mediated auditory cortical suppression during vocalization is deficient in ESZ and precedes psychosis onset, particularly in CHR individuals with greater unusual thought content. Furthermore, this suppression increases from adolescence through early adulthood, likely reflecting the effects of normal brain maturation. This maturation effect is disrupted in ESZ, presumably due to countervailing illness effects.

Introduction: Identification of participants at clinical high-risk (CHR) for the development of psychosis is an important objective of current preventive efforts in mental health research. However, the utility of using web-based screening approaches to detect CHR participants at the population level has not been investigated., Methods: We tested a web-based screening approach to identify CHR individuals. Potential participants were invited to a website via e-mail invitations, flyers, and invitation letters involving both the general population and mental health services. Two thousand two hundred seventy-nine participants completed the 16-item version of the prodromal questionnaire (PQ-16) and a 9-item questionnaire of perceptual and cognitive aberrations (PCA) for the assessment of basic symptoms (BS) online. 52.3% of participants met a priori cut-off criteria for the PQ and 73.6% for PCA items online. One thousand seven hundred eighty-seven participants were invited for a clinical interview and n = 356 interviews were conducted (response rate: 19.9%) using the Comprehensive Assessment of At-Risk Mental State (CAARMS) and the Schizophrenia Proneness Interview, Adult Version (SPI-A). n = 101 CHR participants and n = 8 first-episode psychosis (FEP) were detected. ROC curve analysis revealed good to moderate sensitivity and specificity for predicting CHR status based on online results for both UHR and BS criteria (sensitivity/specificity: PQ-16 = 82%/46%; PCA = 94%/12%). Selection of a subset of 10 items from both PQ-16 and PCA lead to an improved of specificity of 57% while only marginally affecting sensitivity (81%). CHR participants were characterized by similar levels of functioning and neurocognitive deficits as clinically identified CHR groups., Conclusion: These data provide evidence for the possibility to identify CHR participants through population-based web screening. This could be an important strategy for early intervention and diagnosis of psychotic disorders., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Individuals at clinical high-risk (CHR) for psychosis are characterized by attenuated psychotic symptoms. Only a minority of CHR individuals convert to full-blown psychosis. Therefore, there is a strong interest in identifying neurobiological abnormalities underlying the psychosis risk syndrome. Dynamic functional connectivity (DFC) captures time-varying connectivity over short time scales, and has the potential to reveal complex brain functional organization. Based on resting-state functional magnetic resonance imaging (fMRI) data from 70 healthy controls (HCs), 53 CHR individuals, and 58 early illness schizophrenia (ESZ) patients, we applied a novel group information guided ICA (GIG-ICA) to estimate inherent connectivity states from DFC, and then investigated group differences. We found that ESZ patients showed more aberrant connectivities and greater alterations than CHR individuals. Results also suggested that disease-related connectivity states occurred in CHR and ESZ groups. Regarding the dominant state with the highest contribution to dynamic connectivity, ESZ patients exhibited greater impairments than CHR individuals primarily in the cerebellum, frontal cortex, thalamus and temporal cortex, while CHR and ESZ populations shared common aberrances mainly in the supplementary motor area, parahippocampal gyrus and postcentral cortex. CHR-specific changes were also found in the connections between the superior frontal gyrus and calcarine cortex in the dominant state. Our findings suggest that CHR individuals generally show an intermediate functional connectivity pattern between HCs and SZ patients but also have unique connectivity alterations., (Copyright © 2017 Elsevier Inc. All rights reserved.)

There is a growing consensus that a symptomatology as complex and heterogeneous as schizophrenia is likely to be produced by widespread perturbations of brain structure, as opposed to isolated deficits in specific brain regions. Structural brain-imaging studies have shown that several features of the brain, such as grey matter, white matter integrity and the morphology of the cortex differ in individuals at high risk of the disorder compared to controls, but to a lesser extent than in patients, suggesting that structural abnormalities may form markers of vulnerability to the disorder. Research has had some success in delineating abnormalities specific to those individuals that transition to psychosis, compared to those at high risk that do not, suggesting that a general risk for the disorder can be distinguished from alterations specific to frank psychosis. In this paper, we review cross-sectional and longitudinal studies of individuals at familial or clinical high risk of the disorder. We conclude that the search for reliable markers of schizophrenia is likely to be enhanced by methods which amalgamate structural neuroimaging data into a coherent framework that takes into account the widespread distribution of brain alterations, and relates this to leading hypotheses of schizophrenia., (© The Author(s) 2014.)

• Negative symptoms impact quality of life and functioning. • Complement regulators and coagulation regulators are prognostic factors of negative symptoms. • Their prognostic value is independent of clinical and demographic prognostic factors. • These results may aid early intervention for negative symptoms of psychosis. Negative symptoms impact the quality of life of individuals with psychosis and current treatment options for negative symptoms have limited effectiveness. Previous studies have demonstrated that complement and coagulation pathway protein levels are related to later psychotic experiences, psychotic disorder, and functioning. However, the prognostic relationship between complement and coagulation proteins and negative symptoms is poorly characterised. In the North American Prodrome Longitudinal Studies 2 and 3, negative symptoms in 431 individuals at clinical high-risk for psychosis (mean age: 18.2, SD 3.6; 42.5 % female) were measured at multiple visits over 2 years using the Scale of Psychosis-Risk Symptoms. Plasma proteins were quantified at baseline using mass spectrometry. Four factors were derived to represent levels of proteins involved in the activation or regulation of the complement or coagulation systems. The relationships between standardised protein group factors and serial measurements of negative symptoms over time were modelled using generalised least squares regression. Analyses were adjusted for baseline candidate prognostic factors: negative symptoms, positive symptoms, functioning, depressive symptoms, suicidal ideation, cannabis use, tobacco use, antipsychotic use, antidepressant use, age, and sex. Clinical and demographic prognostic factors of follow-up negative symptoms included negative, positive, and depressive symptoms, functioning, and age. Adjusting for all candidate prognostic factors, the complement regulators group and the coagulation regulators group were identified as prognostic factors of follow-up negative symptoms (β: 0.501, 95 % CI: 0.160, 0.842; β: 0.430, 95 % CI: 0.080, 0.780 respectively. The relationship between complement regulator levels and negative symptoms was also observed in NAPLS2 alone (β: 0.501, 95 % CI: −0.037, 1.039) and NAPLS3 alone, additionally adjusting for BMI (β: 0.442, 95 % CI: 0.127, 0.757). The results indicate that plasma complement and coagulation regulator levels are prognostic factors of negative symptoms, independent of clinical and demographic prognostic factors. These results suggest complement and coagulation regulator levels could have potential utility in informing treatment decisions for negative symptoms in individuals at risk. [ABSTRACT FROM AUTHOR]

Recent studies have indicated that clinical high risk for psychosis (CHR-P) is highly specific for psychotic disorders other than pluripotential to various serious mental illnesses. However, not all CHR-P develop psychotic disorder only, and psychosis can occur in non-psychotic disorders as well. Our prospective cohort study aims to investigate the characteristics and clinical outcomes of a pluripotent high-risk group with the potential to develop a diverse range of psychiatric disorders. The SPRIM study is a prospective naturalistic cohort program that focuses on the early detection of those at risk of developing serious mental illness, including psychosis (CHR-P), bipolar (CHR-B), and depressive disorder (CHR-D), as well as undifferentiated risk participants (UCHR). Our study has a longitudinal design with a baseline assessment and eight follow-up evaluations at 6, 12, 18, 24, 30, 36, 42, and 48 months to determine whether participants have transitioned to psychosis or mood disorders. The SPRIM sample consisted of 90 CHR participants. The total cumulative incidence rate of transition was 53.3% (95% CI 32.5–77.2). CHR-P, CHR-B, CHR-D, and UCHR had cumulative incidence rates of 13.7% (95% CI 3.4–46.4), 52.4% (95% CI 28.1–81.1), 66.7% (95% CI 24.6–98.6) and 54.3% (95% CI 20.5–93.1), respectively. The cumulative incidence of psychosis, bipolar, and depressive disorder among all participants was 3.3% (95% CI 0.8–11.5), 45.7% (95% CI 24.4–73.6), and 11.2% (95% CI 3.1–36.2), respectively. Our study suggests that the concept of pluripotent high-risk for a diverse range of psychiatric disorders is an integrative approach to examining transdiagnostic interactions between illnesses with a high transition rate and minimizing stigma. • Characteristics and clinical outcomes of pluripotent high-risk group; potential for diverse psychiatric disorders. • The total cumulative incidence rate of transition was 53.3% (95% CI 32.5–77.2). • The cummulative incidence of psychosis, bipolar, and depressive disorder among all participants was 3.3%, 45.7%, and 11.2%. [ABSTRACT FROM AUTHOR]

Brain dysconnectivity has been posited as a biological marker of schizophrenia. Emerging schizophrenia connectome research has focused on rich-club organization, a tendency for brain hubs to be highly-interconnected but disproportionately vulnerable to dysconnectivity. However, less is known about rich-club organization in individuals at clinical high-risk for psychosis (CHR-P) and how it compares with abnormalities early in schizophrenia (ESZ). Combining diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI), we examined rich-club and global network organization in CHR-P (n = 41) and ESZ (n = 70) relative to healthy controls (HC; n = 74) after accounting for normal aging. To characterize rich-club regions, we examined rich-club MRI morphometry (thickness, surface area). We also examined connectome metric associations with symptom severity, antipsychotic dosage, and in CHR-P specifically, transition to a full-blown psychotic disorder. ESZ had fewer connections among rich-club regions (ps

There is a clinical high-risk period (CHR) before the onset of schizophrenia. Early detection and early treatment are crucial for the prognosis of the disease. Event-related potential (ERP) is a special brain evoked potential. Different ERP components can reflect the neuroelectrophysiological changes of the brain in different cog- nitive processes. Exploring the ERP components of CHR abnormalities may have an important role in the early rec- ognition of diseases and transformation risk. This review found that P300 and MMN have predictive effects on the risk of mental illness conversion, while other ERP components such as P50, P1. and N400 require more research to verify their reliability as risk markers for mental illness conversion in high-risk populations. [ABSTRACT FROM AUTHOR]

Aim: Rates of attenuated psychotic symptoms (APS) have increased during the COVID‐19 pandemic; however, it is unclear whether this is most evident among individuals from marginalized racial groups. Methods: The current study evaluated APS screening data across a six‐year period in the state of Georgia in the United States, spanning several years prior to and during the COVID‐19 pandemic to evaluate interactions between time and race. Participants included 435 clinical help‐seeking individuals. Results: The rate of individuals scoring above the APS screening cut‐off was higher during the pandemic compared to pre‐pandemic (41% vs 23%). This pandemic‐related increase in APS was significant for Black, but not White or Asian participants. Conclusions: Findings indicate APS are increasing during the COVID‐19 pandemic among clinical help‐seeking populations. Black individuals may be at greater risk for developing a psychotic disorder during the pandemic, suggesting increased need for screening, mental health monitoring, and treatment. [ABSTRACT FROM AUTHOR]

Background: Clinical implementation of risk calculator models in the clinical high-risk for psychosis (CHR-P) population has been hindered by heterogeneous risk distributions across study cohorts which could be attributed to pre-ascertainment illness progression. To examine this, we tested whether the duration of attenuated psychotic symptom (APS) worsening prior to baseline moderated performance of the North American prodrome longitudinal study 2 (NAPLS2) risk calculator. We also examined whether rates of cortical thinning, another marker of illness progression, bolstered clinical prediction models. Methods: Participants from both the NAPLS2 and NAPLS3 samples were classified as either 'long' or 'short' symptom duration based on time since APS increase prior to baseline. The NAPLS2 risk calculator model was applied to each of these groups. In a subset of NAPLS3 participants who completed follow-up magnetic resonance imaging scans, change in cortical thickness was combined with the individual risk score to predict conversion to psychosis. Results: The risk calculator models achieved similar performance across the combined NAPLS2/NAPLS3 sample [area under the curve (AUC) = 0.69], the long duration group (AUC = 0.71), and the short duration group (AUC = 0.71). The shorter duration group was younger and had higher baseline APS than the longer duration group. The addition of cortical thinning improved the prediction of conversion significantly for the short duration group (AUC = 0.84), with a moderate improvement in prediction for the longer duration group (AUC = 0.78). Conclusions: These results suggest that early illness progression differs among CHR-P patients, is detectable with both clinical and neuroimaging measures, and could play an essential role in the prediction of clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Negative symptoms such as blunted facial expressivity are characteristic of schizophrenia. However, it is not well-understood if and what abnormalities are present in individuals at clinical high-risk (CHR) for psychosis. Methods: This experimental study employed facial electromyography (left zygomaticus major and left corrugator supercilia) in a sample of CHR individuals (N = 34) and healthy controls (N = 32) to detect alterations in facial expressions in response to emotionally evocative film clips and to determine links with symptoms. Results: Findings revealed that the CHR group showed facial blunting manifested in reduced zygomatic activity in response to an excitement (but not amusement, fear, or sadness) film clip compared to controls. Reductions in zygomatic activity in the CHR group emerged in response to the emotionally evocative peak period of the excitement film clip. Lower zygomaticus activity during the excitement clip was related to anxiety while lower rates of change in zygomatic activity during the excitement video clip were related to higher psychosis risk conversion scores. Conclusions: Together, these findings inform vulnerability/disease driving mechanisms and biomarker and treatment development. [ABSTRACT FROM AUTHOR]

Familial emotional word usage has long been implicated in symptom progression in schizophrenia. However, few studies have examined caregiver emotional word usage prior to the onset of psychosis, among those with a clinical high-risk (CHR) syndrome. The current study examined emotional word usage in a sample of caregivers of CHR individuals (N = 37) and caregivers of healthy controls (N = 40) and links with clinical symptoms in CHR individuals. Caregivers completed a speech sample task in which they were asked to speak about the participant; speech samples were then transcribed and analyzed for general positive (e.g. good) and negative (e.g., worthless) emotional words as well as words expressing three specific negative emotions (i.e., anxiety, anger, and sadness) using Linguistic Inquiry and Word Count (LIWC). Findings indicated that (1) CHR caregivers used more negative and anxiety words compared to control caregivers; and (2) less positive word usage among CHR caregivers were related to more positive symptomatology among CHR individuals. These findings point toward the utility of automated language analysis in assessing the intersections between caregiver emotional language use and psychopathology. [ABSTRACT FROM AUTHOR]

Background: Beliefs about the usefulness and controllability of emotions are associated with emotion regulation and psychological distress in the general population. Although individuals with schizophrenia-spectrum disorders evidence emotion regulation abnormalities, it is unclear whether emotional beliefs contribute to these difficulties and their associated poor clinical outcomes. Methods: Participants included 72 individuals with schizophrenia-spectrum diagnoses (outpatients with schizophrenia n = 38; youth at clinical high-risk for psychosis, n = 34) and healthy controls (CN: n = 61) who completed the Emotional Beliefs Questionnaire, Emotion Regulation Questionnaire, and measures of clinical symptom severity. Results: Those with schizophrenia-spectrum diagnoses reported believing that emotions were less controllable than CN; however, groups did not differ regarding beliefs about the usefulness of emotion. Greater beliefs of the uncontrollability of emotion were associated with greater use of suppression, less use of reappraisal, and increased negative symptoms. Emotion regulation partially mediated the association between emotional beliefs and negative symptoms. Conclusions: Individuals in the schizophrenia-spectrum display superordinate beliefs that emotions are uncontrollable. These beliefs may influence emotion regulation strategy selection and success, which contributes to negative symptoms. Findings suggest that beliefs of emotional uncontrollability reflect a novel process related to both emotion regulation and negative symptoms that could be targeted in psychosocial treatments. [ABSTRACT FROM AUTHOR]

Aim: Early psychosis is typically operationalized as a categorical construct by dividing people into one of three diagnostic statuses: low‐risk, clinical high‐risk, and first episode psychosis. We empirically assess whether an alternative dimensional approach focused on observed symptom severity may be more desirable for clinical and research purposes. Methods: Participants were 152 help‐seeking youths ages 12–22 years old. Structured interview for psychosis risk syndromes interviews were used to obtain dimensional psychosis symptom severity ratings, and to classify participants by categorical psychosis risk status. Twenty‐five participants were classified as having a diagnosable psychotic disorder, 52 participants as clinical high‐risk, and 75 participants as help‐seeking controls. We assessed the relation between categorical and dimensional measurements of psychosis severity, and then compared categorical versus dimensional psychosis severity in their ability to predict social and role functioning. Results: On average, dimensional psychosis symptom severity increased along with categorical risk status (help‐seeking control < clinical high‐risk < diagnosable psychotic disorder). There was, however, considerable overlap between categories, with people at clinical high‐risk being particularly hard to distinguish from people with diagnosable psychotic disorders on the basis of symptom severity. Dimensional symptom severity was more predictive of functioning than categorical risk status. Conclusions: Categorical risk status and psychosis symptom severity are related but not interchangeable, and dimensional models of psychosis may be more predictive of functional outcomes. Adopting a dimensional rather than categorical approach to the psychosis risk spectrum may facilitate better predictive models and a richer theoretical understanding of early psychosis. [ABSTRACT FROM AUTHOR]

Prediction and prevention of negative clinical and functional outcomes represent the two primary objectives of research conducted within the clinical high-risk for psychosis (CHR-P) paradigm. Several multivariable "risk calculator" models have been developed to predict the likelihood of developing psychosis, although these models have not been translated to clinical use. Overall, less progress has been made in developing effective interventions. In this paper, we review the existing literature on both prediction and prevention in the CHR-P paradigm and, primarily, outline ways in which expanding and combining these paths of inquiry could lead to a greater improvement in individual outcomes for those most at risk. [ABSTRACT FROM AUTHOR]

The debilitating nature of schizophrenia necessitates early detection of individuals at clinical high-risk (CHR) in order to facilitate early intervention. In particular, comparisons between those who develop fully psychotic features (CHR+) and those who do not (CHR-) offer the opportunity to reveal distinct risk factors for psychosis, as well as possible intervention target points. Recent studies have investigated baseline clinical, neurocognitive, neuroanatomic, neurohormonal, and psychophysiological predictors of outcome; premorbid social dysfunction, deficits in neurocognitive performance, neuroanatomic changes, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction have been implicated in psychosis emergence. However, several challenges within CHR research remain: heterogeneity in long-term diagnostic outcome, the variability of research tools and definitions utilized, and limited longitudinal follow-up. Future work in the field should focus on replication via extended longitudinal designs, aim to explore the trajectories and inter-relationships of hypothesized biomarkers, and continue to investigate interventions that seek to prevent psychosis emergence through symptom reduction.

Prediction and prevention of negative clinical and functional outcomes represent the two primary objectives of research conducted within the clinical high-risk for psychosis (CHR-P) paradigm. Several multivariable “risk calculator” models have been developed to predict the likelihood of developing psychosis, although these models have not been translated to clinical use. Overall, less progress has been made in developing effective interventions. In this paper, we review the existing literature on both prediction and prevention in the CHR-P paradigm and, primarily, outline ways in which expanding and combining these paths of inquiry could lead to a greater improvement in individual outcomes for those most at risk.

Individuals diagnosed with psychotic disorders exhibit abnormalities in the perception of expressive behaviors, which are linked to symptoms and visual information processing domains. Specifically, literature suggests these groups have difficulties perceiving gestures that accompany speech. While our understanding of gesture perception in psychotic disorders is growing, gesture perception abnormalities and clues about potential causes and consequences among individuals meeting criteria for a clinical high-risk (CHR) syndrome is limited. Presently, 29 individuals with a CHR syndrome and 32 healthy controls completed an eye-tracking gesture perception paradigm. In this task, participants viewed an actor using abstract and literal gestures while presenting a story and eye gaze data (eg, fixation counts and total fixation time) was collected. Furthermore, relationships between fixation variables and both symptoms (positive, negative, anxiety, and depression) and measures of visual information processing (working memory and attention) were examined. Findings revealed that the CHR group gazed at abstract gestures fewer times than the control group. When individuals in the CHR group did gaze at abstract gestures, on average, they spent significantly less time fixating compared to controls. Furthermore, reduced fixation (ie, count and time) was related to depression and slower response time on an attentional task. While a similar pattern of group differences in the same direction appeared for literal gestures, the effect was not significant. These data highlight the importance of integrating gesture perception abnormalities into vulnerability models of psychosis and inform the development of targeted treatments for social communicative deficits. [ABSTRACT FROM AUTHOR]

Introduction: Electrophysiological (EEG) abnormalities in subjects with schizophrenia have been largely reported. In the last decades, research has shifted to the identification of electrophysiological alterations in the prodromal and early phases of the disorder, focusing on the prediction of clinical and functional outcome. The identification of neuronal aberrations in subjects with a first episode of psychosis (FEP) and in those at ultra high-risk (UHR) or clinical high-risk (CHR) to develop a psychosis is crucial to implement adequate interventions, reduce the rate of transition to psychosis, as well as the risk of irreversible functioning impairment. The aim of the review is to provide an up-to-date synthesis of the electrophysiological findings in the at-risk mental state and early stages of schizophrenia. Methods: A systematic review of English articles using Pubmed, Scopus, and PsychINFO was undertaken in July 2020. Additional studies were identified by hand-search. Electrophysiological studies that included at least one group of FEP or subjects at risk to develop psychosis, compared to healthy controls (HCs), were considered. The heterogeneity of the studies prevented a quantitative synthesis. Results: Out of 319 records screened, 133 studies were included in a final qualitative synthesis. Included studies were mainly carried out using frequency analysis, microstates and event-related potentials. The most common findings included an increase in delta and gamma power, an impairment in sensory gating assessed through P50 and N100 and a reduction of Mismatch Negativity and P300 amplitude in at-risk mental state and early stages of schizophrenia. Progressive changes in some of these electrophysiological measures were associated with transition to psychosis and disease course. Heterogeneous data have been reported for indices evaluating synchrony, connectivity, and evoked-responses in different frequency bands. Conclusions: Multiple EEG-indices were altered during at-risk mental state and early stages of schizophrenia, supporting the hypothesis that cerebral network dysfunctions appear already before the onset of the disorder. Some of these alterations demonstrated association with transition to psychosis or poor functional outcome. However, heterogeneity in subjects' inclusion criteria, clinical measures and electrophysiological methods prevents drawing solid conclusions. Large prospective studies are needed to consolidate findings concerning electrophysiological markers of clinical and functional outcome. [ABSTRACT FROM AUTHOR]

Psychosocial stress and the stress hormone prolactin are assumed to play an important role in the pathogenesis of schizophrenia and related psychoses, and have been frequently observed to be increased in antipsychotic-naïve patients with a clinical high risk for psychosis (CHR-P) or first episode of psychosis (FEP). The aim of this study was to further elucidate the relationships between self-perceived stress, psychopathological symptoms and prolactin levels in these patients. In this cross-sectional study, 45 healthy controls, 31 CHR-P patients and 87 FEP patients were recruited from two different study centers. Prolactin was measured under standardized conditions between 8 and 10 am. All patients were antipsychotic-naïve and not taking any prolactin influencing medication. Self-perceived stress during the last month was measured with the perceived stress scale (PSS-10) immediately before blood taking. Both CHR-P and FEP patients showed significantly higher levels of self-perceived stress and prolactin than controls. Hyperprolactinemia (i.e. prolactin levels above the reference range) was observed in 26% of CHR-P and 45% of FEP patients. Self-perceived stress was significantly positively associated with affective symptoms, but not with other symptoms. There was no significant association between self-perceived stress and prolactin levels. Our results confirm that CHR-P and FEP patients have higher stress levels than healthy controls and frequently have hyperprolactinemia, independent of antipsychotic medication. However, although it is well established that prolactin increases in response to stress, our results do not support the notion that increased prolactin levels in these patients are due to stress. [ABSTRACT FROM AUTHOR]

Deficits in mismatch negativity (MMN) generation are among the best-established biomarkers for cognitive dysfunction in schizophrenia and predict conversion to schizophrenia (Sz) among individuals at symptomatic clinical high risk (CHR). Impairments in MMN index dysfunction at both subcortical and cortical components of the early auditory system. To date, the large majority of studies have been conducted using deviants that differ from preceding standards in either tonal frequency (pitch) or duration. By contrast, MMN to sound location deviation has been studied to only a limited degree in Sz and has not previously been examined in CHR populations. Here, we evaluated location MMN across Sz and CHR using an optimized, multi-deviant pattern that included a location-deviant, as defined using interaural time delay (ITD) stimuli along with pitch, duration, frequency modulation (FM) and intensity deviants in a sample of 42 Sz, 33 CHR and 28 healthy control (HC) subjects. In addition, we obtained resting state functional connectivity (rsfMRI) on CHR subjects. Sz showed impaired MMN performance across all deviant types, along with strong correlation between MMN deficits and impaired neurocognitive function. In this sample of largely non-converting CHR subjects, no deficits were observed in either pitch or duration MMN. By contrast, CHR subjects showed significant impairments in location MMN generation particularly over right hemisphere and significant correlation between impaired location MMN and negative symptoms including deterioration of role function. In addition, significant correlations were observed between location MMN and rsfMRI involving brainstem circuits. In general, location detection using ITD stimuli depends upon precise processing within midbrain regions and provides a rapid and robust reorientation of attention. Present findings reinforce the utility of MMN as a pre-attentive index of auditory cognitive dysfunction in Sz and suggest that location MMN may index brain circuits distinct from those indexed by other deviant types.

Deficits in mismatch negativity (MMN) generation are among the best-established biomarkers for cognitive dysfunction in schizophrenia and predict conversion to schizophrenia (Sz) among individuals at symptomatic clinical high risk (CHR). Impairments in MMN index dysfunction at both subcortical and cortical components of the early auditory system. To date, the large majority of studies have been conducted using deviants that differ from preceding standards in either tonal frequency (pitch) or duration. By contrast, MMN to sound location deviation has been studied to only a limited degree in Sz and has not previously been examined in CHR populations. Here, we evaluated location MMN across Sz and CHR using an optimized, multi-deviant pattern that included a location-deviant, as defined using interaural time delay (ITD) stimuli along with pitch, duration, frequency modulation (FM) and intensity deviants in a sample of 42 Sz, 33 CHR and 28 healthy control (HC) subjects. In addition, we obtained resting state functional connectivity (rsfMRI) on CHR subjects. Sz showed impaired MMN performance across all deviant types, along with strong correlation between MMN deficits and impaired neurocognitive function. In this sample of largely non-converting CHR subjects, no deficits were observed in either pitch or duration MMN. By contrast, CHR subjects showed significant impairments in location MMN generation particularly over right hemisphere and significant correlation between impaired location MMN and negative symptoms including deterioration of role function. In addition, significant correlations were observed between location MMN and rsfMRI involving brainstem circuits. In general, location detection using ITD stimuli depends upon precise processing within midbrain regions and provides a rapid and robust reorientation of attention. Present findings reinforce the utility of MMN as a pre-attentive index of auditory cognitive dysfunction in Sz and suggest that location MMN may index brain circuits distinct from those indexed by other deviant types. [ABSTRACT FROM AUTHOR]

Structural and functional abnormalities of the amygdala in schizophrenia have been well documented. Post-mortem studies suggest that the lateral nucleus is particularly affected in schizophrenia. It is not known whether the amygdala subnuclei are differently affected at the time of the first-episode psychosis or already at high-risk state. 75 first-episode psychosis patients (FEP), 45 clinical high-risk patients (CHR) and 76 population controls participated in this cross-sectional case-control study. Participants underwent T1-weighted 3T MRI scans, from which the amygdala was segmented using a newly developed automated algorithm. Because early adverse events increase risk for psychosis and affect the amygdala, we also tested whether experiences of childhood maltreatment associate with the putative amygdala subnuclei abnormalities. Compared to the population controls, FEP had smaller volumes of the lateral, and basal nuclei. In CHR, only the lateral nucleus was significantly smaller compared to the control subjects. Experience of childhood maltreatment was inversely associated with lateral nucleus volumes in FEP but not in CHR. These results show that the lateral and basal nuclei of the amygdala are already affected in FEP. These volumetric changes may reflect specific cellular abnormalities that have been observed in post-mortem studies in schizophrenia in the same subnuclei. Decreased volume of the lateral nucleus in CHR suggest that a smaller lateral nucleus could serve as a potential biomarker for psychosis risk. Finally, we found that the lateral nucleus volumes in FEP may be sensitive to the effects of childhood maltreatment. [ABSTRACT FROM AUTHOR]

Functional disability is a key component of many psychiatric illnesses, particularly schizophrenia. Impairments in social and role functioning are linked to cognitive deficits, a core feature of psychosis. Retrospective analyses demonstrate that substantial functional decline precedes the onset of psychosis. Recent investigations reveal that individuals at clinical-high-risk (CHR) for psychosis show impairments in social relationships, work/school functioning and daily living skills. CHR youth also demonstrate a pattern of impairment across a range of cognitive domains, including social cognition, which is qualitatively similar to that of individuals with schizophrenia. While many studies have sought to elucidate predictors of clinical deterioration, specifically the development of schizophrenia, in such CHR samples, few have investigated factors relevant to psychosocial outcome. This review integrates recent findings regarding cognitive and social-cognitive predictors of outcome in CHR individuals, and proposes potential directions for future research that will contribute to targeted interventions and improved outcome for at-risk youth.

Background: Current methods to identify people with psychosis risk involve administration of specialized tools such as the Structured Interview for Psychosis-Risk Syndromes (SIPS), but these methods have not been widely adopted. Validation of a more multipurpose assessment tool—such as the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS)—may increase the scope of identification efforts. Methods: We assessed the correspondence between SIPS-determined clinical high risk/early psychosis (CHR/early psychosis) status and K-SADS psychosis screen (child and parent reports and their combination) in a sample of 147 help-seeking individuals aged 12–25. Detailed classification results are reported. Results: Both the child and parent interviews on the K-SADS psychosis screen were strongly predictive of CHR/early psychosis status, although parent reports contributed no significant additional information beyond child reports. Across informants, the presence of either subthreshold hallucinations or subthreshold delusions was highly suggestive of CHR/early psychosis status as determined by SIPS interview (78% (child) and 74% (parent) accuracy). Conclusions: Subthreshold scores on the two-item K-SADS psychosis screen may be good indicators of the presence or absence of early signs of psychosis. The option of using a non-specialized assessment such as the K-SADS as a staged approach to assess for CHR/early psychosis status could increase rates of early psychosis screening and treatment. [ABSTRACT FROM AUTHOR]

Abstract Individuals at clinical high-risk (CHR) for psychosis are characterized by attenuated psychotic symptoms. Only a minority of CHR individuals convert to full-blown psychosis. Therefore, there is a strong interest in identifying neurobiological abnormalities underlying the psychosis risk syndrome. Dynamic functional connectivity (DFC) captures time-varying connectivity over short time scales, and has the potential to reveal complex brain functional organization. Based on resting-state functional magnetic resonance imaging (fMRI) data from 70 healthy controls (HCs), 53 CHR individuals, and 58 early illness schizophrenia (ESZ) patients, we applied a novel group information guided ICA (GIG-ICA) to estimate inherent connectivity states from DFC, and then investigated group differences. We found that ESZ patients showed more aberrant connectivities and greater alterations than CHR individuals. Results also suggested that disease-related connectivity states occurred in CHR and ESZ groups. Regarding the dominant state with the highest contribution to dynamic connectivity, ESZ patients exhibited greater impairments than CHR individuals primarily in the cerebellum, frontal cortex, thalamus and temporal cortex, while CHR and ESZ populations shared common aberrances mainly in the supplementary motor area, parahippocampal gyrus and postcentral cortex. CHR-specific changes were also found in the connections between the superior frontal gyrus and calcarine cortex in the dominant state. Our findings suggest that CHR individuals generally show an intermediate functional connectivity pattern between HCs and SZ patients but also have unique connectivity alterations. [ABSTRACT FROM AUTHOR]

Background: Individuals with psychotic disorders experience disruptions to both the sleep and circadian components of the sleep/wake cycle. Recent evidence has supported a role of sleep disturbances in emerging psychosis. However, less is known about how circadian rhythm disruptions may relate to psychosis symptoms and prognosis for adolescents with clinical high-risk (CHR) syndromes. The present study examines circadian rest/activity rhythms in CHR and healthy control (HC) youth to clarify the relationships among circadian rhythm disturbance, psychosis symptoms, psychosocial functioning, and the longitudinal course of illness.Methods: Thirty-four CHR and 32 HC participants were administered a baseline evaluation, which included clinical interviews, 5days of actigraphy, and a sleep/activity diary. CHR (n=29) participants were re-administered clinical interviews at a 1-year follow-up assessment.Results: Relative to HC, CHR youth exhibited more fragmented circadian rhythms and later onset of nocturnal rest. Circadian disturbances (fragmented rhythms, low daily activity) were associated with increased psychotic symptom severity among CHR participants at baseline. Circadian disruptions (lower daily activity, rhythms that were more fragmented and/or desynchronized with the light/dark cycle) also predicted severity of psychosis symptoms and psychosocial impairment at 1-year follow-up among CHR youth.Conclusions: Circadian rhythm disturbances may represent a potential vulnerability marker for emergence of psychosis, and thus, rest/activity rhythm stabilization has promise to inform early-identification and prevention/intervention strategies for CHR youth. Future studies with longer study designs are necessary to further examine circadian rhythms in the prodromal period and rates of conversion to psychosis among CHR teens. [ABSTRACT FROM AUTHOR]

Background: Hyperprolactinemia is a known side effect of antipsychotics. In recent reports it has also been shown in antipsychotic-naïve at-risk mental state (ARMS) and first-episode psychosis (FEP) patients. Prolactin is not only involved in reproduction and lactation, but is also synthesized in response to stress. As stress is thought to play an important role in the onset and relapse of schizophrenia, the aim of this study was to further elucidate the influence of prolactin in emerging psychosis.Methods: The data analysed in this study were collected within the prospective Früherkennung von Psychosen (FePsy) study. Blood sample collection took place under standardized conditions between 8 and 10am after an overnight fast and 30minutes of rest. All patients were antipsychotic-naïve and did not take any prolactin influencing medication.Results: Our sample consisted of 116 antipsychotic-naïve ARMS and 49 FEP patients. Hyperprolactinemia was shown in 32% of ARMS and 35% of FEP patients. After correction for the normal biological variation between the sexes, we still found higher average prolactin levels in female than in male patients (β=0.42; t=2.47; p=0.01) but no difference in prolactin levels between ARMS and FEP patients (β=-0.05; t=-0.30; p=0.76). The survival analysis revealed no significant predictive value for prolactin levels to predict transition to psychosis.Conclusion: Our findings support a possible role of prolactin in emerging psychosis and it could be speculated that stress, which can induce hyperprolactinemia, has a stronger effect on women than on men in emerging psychosis. [ABSTRACT FROM AUTHOR]