Clinical High-risk Group Research Articles

The impact of affective and negative symptoms on the development of psychosis in a six-year follow-up of a community-based population.

The Clinical High Risk (CHR) concept has a limited transition risk to psychotic disorders (PD). This study investigates the association between affective and negative symptoms, currently not included in the CHR concept, and the risk of transition to PD in a community-based population of 2185 participants in Turkey. Participants were assessed twice over six years using a multistage sampling technique. Two separate linear regression analyses were conducted on data from both assessments, investigating the relationship between affective and negative symptoms, subclinical and clinical psychotic experiences (PE) and progression to PD. The overall transition rate to PD was 1.3%. The analysis showed no increased risk of developing PD for the 'subclinical PE only' group at follow-up, compared to the 'no PE' group. However, being classified as having 'clinical PE only' (OR: 6.23; p = 0.010) and 'clinical PE + affective/negative symptoms' (OR: 8.48; p = 0.001) at baseline was associated with an increased risk of developing PD at follow-up. The presence of 'affective/negative symptoms' at baseline was associated with an increased risk of incident subclinical PE (RR: 1.98; p = 0.001), incident clinical PE (RR: 3.14; p = 0.001), and incident PD (RR: 4.21; p = 0.030) at follow-up. The results confirm the significance of the baseline severity of positive symptoms in predicting the transition to PD and suggest that both positive and affective/negative symptoms impact the transition risk to PD and incident psychotic symptoms. This highlights the potential utility of defining CHR groups based on a combination of positive, affective, and negative symptoms.

Long-term outcomes and risk profile of cT3N0 breast cancer treated with neoadjuvant chemotherapy and curative surgery.

We evaluated the treatment outcomes and failure patterns in cT3N0 breast cancer patients classified for rigorous pretreatment evaluation and treated with neoadjuvant chemotherapy (NAC) and curative surgery. We reviewed the records of 87 cT3N0 breast cancer patients who received NAC and curative surgery between 2000 and 2015. The clinical high-risk group was defined as having two or more risk factors: age < 40, histologic grade 3, lymphovascular invasion, hormone receptor negativity, and Ki-67 labeling index >20%. Of the patients, 84 (96.6%) and 79 (90.8%) were initially evaluated using magnetic resonance imaging and positron emission tomography/computed tomography. Most patients received anthracycline based NAC regimen (n = 69, 79.3%) and modified radical mastectomy (n = 61, 70.1%). During a 91.5-month median follow-up, ten patients experienced distant metastasis (DM) only, two had isolated local recurrence, one had local recurrence and DM, and another had local recurrence, regional recurrence, and DM. The 5-year rates of locoregional recurrence, DM, any recurrence (AR), and overall survival (OS) were 1.2%, 11.6%, 11.6%, and 90.8%, respectively. The risk group was an independent prognostic factor of recurrence, and the high-risk group had worse rates of DM (19.2% vs. 0%, P = 0.009), AR (19.2% vs. 0%, P = 0.016) and OS (82.8% vs. 100%, P = 0.001). Patients with cT3N0 breast cancer classified for rigorous pretreatment evaluation and treated with NAC and radical surgery had favourable oncological outcomes. A clinical risk group based on clinical and immunohistochemical risk factors was an excellent predictor of survival and recurrence.

Neural dysfunction underlying working memory processing at different stages of the illness course in schizophrenia: a comparative meta-analysis.

Schizophrenia, as a chronic and persistent disorder, exhibits working memory deficits across various stages of the disorder, yet the neural mechanisms underlying these deficits remain elusive with inconsistent neuroimaging findings. We aimed to compare the brain functional changes of working memory in patients at different stages: clinical high risk, first-episode psychosis, and long-term schizophrenia, using meta-analyses of functional magnetic resonance imaging studies. Following a systematic literature search, 56 whole-brain task-based functional magnetic resonance imaging studies (15 for clinical high risk, 16 for first-episode psychosis, and 25 for long-term schizophrenia) were included. The separate and pooled neurofunctional mechanisms among clinical high risk, first-episode psychosis, and long-term schizophrenia were generated by Seed-based d Mapping toolbox. The clinical high risk and first-episode psychosis groups exhibited overlapping hypoactivation in the right inferior parietal lobule, right middle frontal gyrus, and left superior parietal lobule, indicating key lesion sites in the early phase of schizophrenia. Individuals with first-episode psychosis showed lower activation in left inferior parietal lobule than those with long-term schizophrenia, reflecting a possible recovery process or more neural inefficiency. We concluded that SCZ represent as a continuum in the early stage of illness progression, while the neural bases are inversely changed with the development of illness course to long-term course.

Excessive interstitial free-water in cortical gray matter preceding accelerated volume changes in individuals at clinical high risk for psychosis.

Recent studies show that accelerated cortical gray matter (GM) volume reduction seen in anatomical MRI can help distinguish between individuals at clinical high risk (CHR) for psychosis who will develop psychosis and those who will not. This reduction is suggested to represent atypical developmental or degenerative changes accompanying an accumulation of microstructural changes, such as decreased spine density and dendritic arborization. Detecting the microstructural sources of these changes before they accumulate into volume loss is crucial. Our study aimed to detect these microstructural GM alterations using diffusion MRI (dMRI). We tested for baseline and longitudinal group differences in anatomical and dMRI data from 160 individuals at CHR and 96 healthy controls (HC) acquired in a single imaging site. Of the CHR individuals, 33 developed psychosis (CHR-P), while 127 did not (CHR-NP). Among all participants, longitudinal data was available for 45 HCs, 17 CHR-P, and 66 CHR-NP. Eight cortical lobes were examined for GM volume and GM microstructure. A novel dMRI measure, interstitial free water (iFW), was used to quantify GM microstructure by eliminating cerebrospinal fluid contribution. Additionally, we assessed whether these measures differentiated the CHR-P from the CHR-NP. In addition, for completeness, we also investigated changes in cortical thickness and in white matter (WM) microstructure. At baseline the CHR group had significantly higher iFW than HC in the prefrontal, temporal, parietal, and occipital lobes, while volume was reduced only in the temporal lobe. Neither iFW nor volume differentiated between the CHR-P and CHR-NP groups at baseline. However, in many brain areas, the CHR-P group demonstrated significantly accelerated changes (iFW increase and volume reduction) with time than the CHR-NP group. Cortical thickness provided similar results as volume, and there were no significant changes in WM microstructure. Our results demonstrate that microstructural GM changes in individuals at CHR have a wider extent than volumetric changes or microstructural WM changes, and they predate the acceleration of brain changes that occur around psychosis onset. Microstructural GM changes, as reflected by the increased iFW, are thus an early pathology at the prodromal stage of psychosis that may be useful for a better mechanistic understanding of psychosis development.

Abnormal Scanning Patterns Based on Eye Movement Entropy in Early Psychosis

BackgroundRestricted scan path mode is hypothesized to explain abnormal scanning patterns in patients with schizophrenia. Here, we calculated entropy scores (drawing on gaze data to measure the statistical randomness of eye movements) to quantify how strategical and random participants were when processing image stimuli. MethodsEighty-six patients with first-episode schizophrenia (FES), 124 individuals at clinical high risk (CHR) for psychosis, and 115 healthy control participants (HCs) completed an eye-tracking examination while freely viewing 35 static images (each presented for 10 seconds) and cognitive assessments. We compared group differences in the overall entropy score, as well as entropy scores under various conditions. We also investigated the correlations between entropy scores and symptoms and cognitive function. ResultsIncreased overall entropy scores were noted in the FES and CHR groups compared with the HC group, and these differences were already apparent within 0 to 2.5 seconds. In addition, the CHR group exhibited higher entropy than the HC group when viewing low-meaning images. Moreover, the entropy within 0 to 2.5 seconds showed significant correlations with negative symptoms in the FES group, attention/vigilance scores in the CHR group, and speed of processing and attention/vigilance scores across all 3 groups. ConclusionsThe results indicate that individuals with FES and those at CHR scanned pictures more randomly and less strategically than HCs. These patterns also correlated with clinical symptoms and neurocognition. The current study highlights the potential of the eye movement entropy measure as a neurophysiological marker for early psychosis.

Emotional tone in clinical high risk for psychosis: novel insights from a natural language analysis approach.

Individuals at clinical high risk (CHR) for psychosis experience subtle emotional disturbances that are traditionally difficult to assess, but natural language processing (NLP) methods may provide novel insight into these symptoms. We predicted that CHR individuals would express more negative emotionality and less emotional language when compared to controls. We also examined associations with symptomatology. Participants included 49 CHR individuals and 42 healthy controls who completed a semi-structured narrative interview. Interview transcripts were analyzed using Linguistic Inquiry and Word Count (LIWC) to assess the emotional tone of the language (tone -the ratio of negative to positive language) and count positive/negative words used. Participants also completed clinical symptom assessments to determine CHR status and characterize symptoms (i.e., positive and negative symptom domains). The CHR group had more negative emotional tone compared to healthy controls (t=2.676, p=.009), which related to more severe positive symptoms (r2=.323, p=.013). The percentages of positive and negative words did not differ between groups (p's>.05). Language analyses provided accessible, ecologically valid insight into affective dysfunction and psychosis risk symptoms. Natural language processing analyses unmasked differences in language for CHR that captured language tendencies that were more nuanced than the words that are chosen.

Unlocking insights from actigraphy: examining feature selection and activation detection approaches for enhanced data interpretation

IntroductionAlterations in motor activity are an extremely important characteristic and one of the leading symptoms of major functional psychiatric disorders. These pattern disturbances can be observed in schizophrenia. Actigraphy is a non-invasive method that can be used to monitor these changes, and recent studies emphasize its significance in the early identification of disorders like schizophrenia.ObjectivesThis study uniquely focuses on distinguishing latent liabilities for schizotypy from manifested schizophrenia using specific actigraphy features.Methods Actigraphy data were collected using specialized devices from the University of Szeged and Haukeland University Hospital datasets (Berle et al., 2010). At Haukeland University Hospital patients with chronic schizophrenia (N=23) (so-called: manifested group) were collected, separately, at the University of Szeged, healthy university students were recruited and screened for latent tendencies towards shizotypic pathological development. In the latter study, two main groups were formed based on their scores: a positive schizotypy factor group (so-called: latent group) (N=22) and a control group (N=25), with actigraphy data. Utilizing the pyActigraphy library (Hammad et al., 2021) and wavelet analysis, features such as activity mean, interdaily stability and sleep movement characteristics were derived. Feature selection employed machine learning algorithms, notably Logistic Regression, Random Forest, ANN, and AHFS aided by Shapley values and Click Forming Feature Selection for insight into the most influential features.ResultsThe three models exhibited similar performance with a 60% accuracy threshold. In the latent group, sleep-related movements have a substantial impact, while in the manifested group, in addition to sleep characteristics, features like RA, IV, ADAT, M10, the mean activity level (all of which decreased), and the ratio of zero values also play a significant role. In the latent group, features related to the length of small amplitude movements were dominant, particularly the increased values, along with a decrease in the density of large movements.Conclusions Our study indicates that in the latent phase of schizophrenia, actigraphy features related to sleep are most significant, but as the disease progresses, both sleep and daytime activity patterns are crucial. Sleep disturbances may signal early susceptibility, with nighttime movements offering clearer insights. These variations might be influenced by medication effects in the manifested group, reflecting the broader challenges in schizophrenia research where the drug-free study of patients remains elusive. Further studies should explore these features in the Clinical High Risk and prodromal groups to refine our understanding of the development of the disorder.Disclosure of InterestNone Declared

Alteration in left frontoparietal connectivity correlates with impaired cognitive reappraisal in early psychosis

BackgroundImpaired cognitive reappraisal is a notable symptom of early psychosis, but its neurobiological basis remains underexplored. We aimed to identify the underlying neurobiological mechanism of this impairment by using resting-state functional connectivity (FC) analyses focused on brain regions related to cognitive reappraisal. MethodsResting-state functional magnetic resonance images were collected from 36 first-episode psychosis (FEP) patients, 32 clinical high-risk (CHR) individuals, and 48 healthy controls (HCs). Whole-brain FC maps using seed regions associated with cognitive reappraisal were generated and compared across the FEP, CHR and HC groups. We assessed the correlation between resting-state FC, reappraisal success ratio, positive symptom severity and social functioning controlling for covariates. ResultsFEP patients showed higher FC between the left superior parietal lobe and left inferior frontal gyrus than HCs. Higher FC between the left superior parietal lobe and left inferior frontal gyrus negatively correlated with the reappraisal success ratio in the FEP group after controlling for covariates. Lower FC correlated with lower positive symptom severity and improved global functioning in the FEP group. ConclusionsAlteration in left frontoparietal connectivity reflects impaired cognitive reappraisal in early psychosis, and such alteration correlates with increased positive symptoms and decreased global functioning. These findings offer a potential path for interventions targeting newly emerging symptoms in the early stages of psychosis.

Models of mild cognitive deficits in risk assessment in early psychosis.

Mild cognitive deficits (MCD) emerge before the first episode of psychosis (FEP) and persist in the clinical high-risk (CHR) stage. This study aims to refine risk prediction by developing MCD models optimized for specific early psychosis stages and target populations. A comprehensive neuropsychological battery assessed 1059 individuals with FEP, 794 CHR, and 774 matched healthy controls (HCs). CHR subjects, followed up for 2 years, were categorized into converters (CHR-C) and non-converters (CHR-NC). The MATRICS Consensus Cognitive Battery standardized neurocognitive tests were employed. Both the CHR and FEP groups exhibited significantly poorer performance compared to the HC group across all neurocognitive tests (all p < 0.001). The CHR-C group demonstrated poorer performance compared to the CHR-NC group on three sub-tests: visuospatial memory (p < 0.001), mazes (p = 0.005), and symbol coding (p = 0.023) tests. Upon adjusting for sex and age, the performance of the MCD model was excellent in differentiating FEP from HC, as evidenced by an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.895 (p < 0.001). However, when applied in the CHR group for predicting CHR-C (AUC = 0.581, p = 0.008), the performance was not satisfactory. To optimize the efficiency of psychotic risk assessment, three distinct MCD models were developed to distinguish FEP from HC, predict CHR-C from CHR-NC, and identify CHR from HC, achieving accuracies of 89.3%, 65.6%, and 80.2%, respectively. The MCD exhibits variations in domains, patterns, and weights across different stages of early psychosis and diverse target populations. Emphasizing precise risk assessment, our findings highlight the importance of tailored MCD models for different stages and risk levels.

Abnormal theta and alpha oscillations in children and adolescents with first-episode psychosis and clinical high-risk psychosis.

Cognitive control deficits are one of the main symptoms of psychosis. The basic neural oscillation patterns associated with cognitive control are already present in early adolescence. However, as previous studies have focused on adults with psychosis, it is unclear whether neurobiological impairments in cognitive control are present in children and adolescents with first-episode psychosis (FEP) or clinical high-risk (CHR) state for psychosis. To explore the deficits of electroencephalogram related to cognitive control tasks in children and adolescents with FEP and CHR. Electroencephalogram was recorded in untreated 48 patients with FEP, 24 patients with CHR and 42 healthy controls aged 10-17 years, while performing the visual oddball task. The N2 amplitude, theta and alpha oscillations were then analysed and compared between groups. There was no significant group difference in N2 amplitude (P = 0.099). All groups showed increased theta and alpha oscillations relative to baseline before the stimulus in the frontal, central, left fronto-central and right fronto-central areas. These changes differed significantly between groups, with the FEP group showing significantly smaller theta (P < 0.001) and alpha (P < 0.01) oscillation than healthy controls. Theta and alpha oscillations in the CHR group did not differ significantly from the FEP group and healthy controls. These results suggest that neural damage has already occurred in the early stage of psychosis, and that abnormal rhythmic activity of neurons may constitute the pathophysiological mechanism of cognitive dysfunction related to early-onset psychosis.

Glutamate levels and symptom burden in high-risk and first-episode schizophrenia: a dual-voxel study of the anterior cingulate cortex.

Reduced glutamatergic excitability of the anterior cingulate cortex (ACC) has been long suspected in schizophrenia; recent observations support low glutamatergic tone as the primary pathophysiology contributing to subtle early features of this illness, with a secondary disinhibition (higher glutamate tone) resulting in more prominent clinical symptoms later in its course. We sought to investigate whether people with genetic high risk (GHR) for schizophrenia have lower glutamate levels in the ACC than those at later stages of clinical high risk (CHR) and those with first-episode schizophrenia (FES), among whom symptoms are already prominent. We recruited people with CHR, GHR, or FES, as well as healthy controls. Using proton magnetic resonance spectroscopy, we determined glutamate levels in the perigenual ACC (pACC) and dorsal ACC (dACC) using a 3 T scanner. We recruited 302 people across multiple stages of psychosis, including 63 with CHR, 76 with GHR, and 96 with FES, as well as 67 healthy controls. Those with GHR had lower glutamate levels in the dACC than those with CHR, while those with CHR had higher glutamate levels in the pACC than those with FES. Higher disorganization, but not any other symptom domain, was associated with lower levels of glutamate in the GHR group (dACC and pACC) and in the CHR group (pACC). The cross-sectional design precluded inferences regarding individual clinical trajectory and resolution at 3 T was insufficient to separate spectra of glutamine from glutamate. Reduced glutamatergic tone among people genetically predisposed to schizophrenia supports diminished excitability as an early feature of schizophrenia, contributing to the subtle symptom of disorganization across high-risk states. Higher glutamate levels become apparent when psychotic symptoms become prominent, possibly as a disinhibitory effect and, at the full-blown stage of psychosis, the relationship between glutamate concentrations and symptoms ceases to be simply linear.

A mixed-methods study to evaluate the feasibility and preliminary efficacy of delivering the optimal health program (OHP) for youth at clinical high risk (CHR) for psychosis: A study protocol.

Individuals with clinical high risk (CHR) for psychosis experience significant distress, impaired general functioning and a high lifetime risk of self-harm and attempted suicide. The CHR period is an important phase in an individual's mental health where appropriate interventions may reduce the risk of progression to several negative outcomes, including the development of schizophrenia. Given that up to 80% of individuals with CHR have another diagnosable mental illness and almost half experience poor psychosocial functioning, developing interventions that address psychosocial functioning in young people with CHR is of great importance. This mixed-methods study aims to employ qualitative and quantitative methods to adapt an evidence-based comprehensive psychosocial and mental health self-efficacy program, the Optimal Health Program (OHP), and evaluate the feasibility, acceptability and preliminary clinical efficacy in young people with CHR. We aim to recruit 30 CHR participants (age 16-29 years) in a single-arm 12-week exploratory clinical trial. Feasibility metrics will include recruitment, retention, and data completion rates. Acceptability will be informed by the Client Satisfaction Questionnaire. Clinical assessments (psychosis spectrum symptoms, depression, and anxiety), functional measures, and cognitive outcomes will be completed at study entry and repeated post-intervention at 12-weeks. We will run pre-post test data analysis to examine changes following engagement in the OHP intervention. Qualitative interviews will be conducted post-intervention to further evaluate the acceptability of the intervention and the trial design, and will be analyzed using thematic analysis. OHP may enhance the long-term mental health, well-being and functioning of CHR youth. However, the intervention must first be adapted to a CHR population; then, the feasibility and preliminary efficacy of delivering an intervention tailored around the varied needs of the CHR group must be established before a larger-scale appropriately powered study is pursued. Trial registration: The trial is registered with ClinicalTrials.gov NCT05757128.

Implementation of cognitive reappraisal in subthreshold psychosis

Cognitive reappraisal is an emotion regulation strategy based in cognitive behavioral therapy and can be associated with positive outcomes for individuals with and at risk for psychosis. However, the literature is mixed regarding whether this population uses cognitive reappraisal effectively. The current study examinedcognitive reappraisal effectiveness in individuals at clinical high risk for psychosis and healthy control participants (N = 66; 34 clinical high risk, 32 healthy controls). The experimental task instructed participants to engage in reappraisal in real-time to regulate distress. We hypothesized that control participants would be more effective at using cognitive reappraisal compared to psychosis-risk participants, resulting in greater distress reduction post-reappraisal. Results demonstrated the opposite: the psychosis-risk group reported a greater change in distress level than the healthy control group after reappraisal was employed (Cohen’s d = 0.52). Exploratory analyses revealed that the clinical high risk group reported higher pre-task distress, but reported post-reappraisal distress levels equivalent to the healthy control group. These results contribute to emerging evidence that suggests individuals on the psychosis spectrum can implement reappraisal effectively. Therefore, complex training to improve cognitive reappraisal may not be needed. Instead, future research should examine the potential clinical utility of using simple reminders and/or guided prompts to promote cognitive reappraisal in individuals on the psychosis spectrum.

Proteomic profiling in the progression of psychosis: Analysis of clinical high-risk, first episode psychosis, and healthy controls

Background and hypothesisRecent 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 designThe 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 resultsA 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. ConclusionsOur 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.

Speech characteristics yield important clues about motor function: Speech variability in individuals at clinical high-risk for psychosis

Background and hypothesis: Motor abnormalities are predictive of psychosis onset in individuals at clinical high risk (CHR) for psychosis and are tied to its progression. We hypothesize that these motor abnormalities also disrupt their speech production (a highly complex motor behavior) and predict CHR individuals will produce more variable speech than healthy controls, and that this variability will relate to symptom severity, motor measures, and psychosis-risk calculator risk scores. Study design: We measure variability in speech production (variability in consonants, vowels, speech rate, and pausing/timing) in N = 58 CHR participants and N = 67 healthy controls. Three different tasks are used to elicit speech: diadochokinetic speech (rapidly-repeated syllables e.g., papapa…, pataka…), read speech, and spontaneously-generated speech. Study results: Individuals in the CHR group produced more variable consonants and exhibited greater speech rate variability than healthy controls in two of the three speech tasks (diadochokinetic and read speech). While there were no significant correlations between speech measures and remotely-obtained motor measures, symptom severity, or conversion risk scores, these comparisons may be under-powered (in part due to challenges of remote data collection during the COVID-19 pandemic). Conclusion: This study provides a thorough and theory-driven first look at how speech production is affected in this at-risk population and speaks to the promise and challenges facing this approach moving forward.

Magnetic resonance texture analysis reveals stagewise nonlinear alterations of the frontal gray matter in patients with early psychosis.

Although gray matter (GM) abnormalities are present from the early stages of psychosis, subtle/miniscule changes may not be detected by conventional volumetry. Texture analysis (TA), which permits quantification of the complex interrelationship between contrasts at the individual voxel level, may capture subtle GM changes with more sensitivity than does volume or cortical thickness (CTh). We performed three-dimensional TA in nine GM regions of interest (ROIs) using T1 magnetic resonance images from 101 patients with first-episode psychosis (FEP), 85 patients at clinical high risk (CHR) for psychosis, and 147 controls. Via principal component analysis, three features of gray-level cooccurrence matrix - informational measure of correlation 1 (IMC1), autocorrelation (AC), and inverse difference (ID) - were selected to analyze cortical texture in the ROIs that showed a significant change in volume or CTh in the study groups. Significant reductions in GM volume and CTh of various frontotemporal regions were found in the FEP compared with the controls. Increased frontal AC was found in the FEP group compared to the controls after adjusting for volume and CTh changes. While volume and CTh were preserved in the CHR group, a stagewise nonlinear increase in frontal IMC1 was found, which exceeded both the controls and FEP group. Increased frontal IMC1 was also associated with a lesser severity of attenuated positive symptoms in the CHR group, while neither volume nor CTh was. The results of the current study suggest that frontal IMC1 may reflect subtle, dynamic GM changes and the symptomatology of the CHR stage with greater sensitivity, even in the absence of gross GM abnormalities. Some structural mechanisms that may contribute to texture changes (e.g., macrostructural cortical lamina, neuropil/myelination, cortical reorganization) and their possible implications are explored and discussed. Texture may be a useful tool to investigate subtle and dynamic GM abnormalities, especially during the CHR period.

Temporal Interactions Between Social Motivation and Behavior In Daily Life Among Individuals at Clinical High-Risk for Psychosis.

Poor social functioning is common among individuals at clinical high-risk (CHR) for psychosis and is associated with greater likelihood of conversion. Unfortunately, processes contributing to social impairment are unclear, making social functioning difficult to improve via treatment. The current study examined whether abnormalities in social functioning result from aberrant temporal interactions between social motivation and behavior. Participants included 105 individuals at CHR and 62 healthy controls (CN) who completed 6 days of ecological momentary assessment. Multilevel models examined time-lagged interactions between social behavior and motivation. CHR and CN did not differ in social motivation; however, CHR were less likely to interact with family and coworkers and more likely to engage in interactions via phone and text/social media. Autocorrelations indicated that social behavior and motivation were generally consistent across time in CHR and CN groups. Time-lagged analyses indicated that both groups had an increase in social motivation across time when they were alone and a decrease in social motivation across time when they were with others. However, the relative decrease when with others and increase when alone were less robust in CHR than CN, particularly for in-person interactions. Social motivation at time t did not differentially impact social partner or modality at time t+1 in the groups. Findings suggest that social behavior and motivation have different temporal interactions in CHR and CN. Psychosocial interventions may benefit from targeting the frequency of social behavior with specific partners and modalities to change social motivation.

Differential Expression of Anomalous Self-Experiences in Spontaneous Speech in Clinical High-Risk and Early-Course Psychosis Quantified by Natural Language Processing

BackgroundBasic self-disturbance, or anomalous self-experiences (ASEs), is a core feature of the schizophrenia spectrum. We propose a novel method of natural language processing to quantify ASEs in spoken language by direct comparison to an inventory of self-disturbance, the Inventory of Psychotic-Like Anomalous Self-Experiences (IPASE). We hypothesized that there would be increased similarity in open-ended speech to the IPASE items in individuals with early-course psychosis (PSY) compared with healthy individuals, with clinical high-risk (CHR) individuals intermediate in similarity. MethodsOpen-ended interviews were obtained from 170 healthy control participants, 167 CHR participants, and 89 PSY participants. We calculated the semantic similarity between IPASE items and “I” sentences from transcribed speech samples using S-BERT (Sentence Bidirectional Encoder Representation from Text). Kolmogorov-Smirnov tests were used to compare distributions across groups. A nonnegative matrix factorization of cosine similarity was performed to rank IPASE items. ResultsSpoken language of CHR individuals had the greatest semantic similarity to IPASE items when compared to both healthy control (s = 0.44, p < 10−14) and PSY (s = 0.36, p < 10−6) individuals, while IPASE scores were higher among PSY than CHR group participants. In addition, the nonnegative matrix factorization approach produced a data-driven domain that differentiated the CHR group from the others. ConclusionsWe found that open-ended interviews elicited language with increased semantic similarity to the IPASE by participants in the CHR group compared with patients with psychosis. This demonstrates the utility of these methods for differentiating patients from healthy control participants. This complementary approach has the capacity to scale to large studies investigating phenomenological features of schizophrenia and potentially other clinical populations.

Attentional biases in facial emotion processing in individuals at clinical high risk for psychosis.

Individuals at clinical high risk (CHR) for psychosis exhibit altered facial emotion processing (FEP) and poor social functioning. It is unclear whether FEP deficits result from attentional biases, and further, how these abnormalities are linked to symptomatology (e.g., negative symptoms) and highly comorbid disorders that are also tied to abnormal FEP (e.g., depression). In the present study, we employed an eye-tracking paradigm to assess attentional biases and clinical interviews to examine differences between CHR (N = 34) individuals and healthy controls (HC; N = 46), as well as how such biases relate to symptoms and functioning in CHR individuals. Although no CHR-HC differences emerged in attentional biases, within the CHR group, symptoms and functioning were related to biases. Depressive symptoms were related to some free-view attention switching biases (e.g., to and from fearful faces, r = .50). Negative symptoms were related to more slowly disengaging from happy faces (r = .44), spending less time looking at neutral faces (r = - .42), and more time looking at no face (Avolition, r = .44). In addition, global social functioning was related to processes that overlapped with both depression and negative symptoms, including time looking at no face (r = - .68) and free-view attention switching with fearful faces (r = - .40). These findings are consistent with previous research, indicating that negative symptoms play a prominent role in the CHR syndrome, with distinct mechanisms relative to depression. Furthermore, the results suggest that attentional bias indices from eye-tracking paradigms may be predictive of social functioning.

Serum complement proteins rather than inflammatory factors is effective in predicting psychosis in individuals at clinical high risk

Immunological/inflammatory factors are implicated in the development of psychosis. Complement is a key driver of inflammation; however, it remains unknown which factor is better at predicting the onset of psychosis. This study aimed to compare the alteration and predictive performance of inflammation and complement in individuals at clinical high risk (CHR). We enrolled 49 individuals at CHR and 26 healthy controls (HCs). Twenty-five patients at CHR had converted to psychosis (converter) by the 3-year follow-up. Inflammatory cytokines, including interleukin (IL)-1β, 6, 8, 10, tumor necrosis factor-alpha (TNF-alpha), macrophage colony-stimulating factor levels, and complement proteins (C1q, C2, C3, C3b, C4, C4b, C5, C5a, factor B, D, I, H) were measured by enzyme-linked immunosorbent assay at baseline. Except for TNF- alpha, none of the inflammatory cytokines reached a significant level in either the comparison of CHR individuals and HC or between CHR-converters and non-converters. The C5, C3, D, I, and H levels were significantly lower (C5, p = 0.006; C3, p = 0.009; D, p = 0.026; I, p = 0.016; H, p = 0.019) in the CHR group than in the HC group. Compared to non-converters, converters had significantly lower levels of C5 (p = 0.012) and C5a (p = 0.007). None of the inflammatory factors, but many complement factors, showed significant correlations with changes in general function and symptoms. None of the inflammatory markers, except for C5a and C5, were significant in the discrimination of conversion outcomes in CHR individuals. Our results suggest that altered complement levels in the CHR population are more associated with conversion to psychosis than inflammatory factors. Therefore, an activated complement system may precede the first-episode of psychosis and contribute to neurological pathogenesis at the CHR stage.