Changes in the structure of spontaneous speech predict the disruption of hierarchical brain organization in first-episode psychosis.

Psychosis implicates changes across a broad range of cognitive functions. These functions are cortically organized in the form of a hierarchy ranging from primary sensorimotor (unimodal) to higher-order association cortices, which involve functions such as language (transmodal). Language has long been documented as undergoing structural changes in psychosis. We hypothesized that these changes as revealed in spontaneous speech patterns may act as readouts of alterations in the configuration of this unimodal-to-transmodal axis of cortical organization in psychosis. Results from 29 patients with first-episodic psychosis (FEP) and 29 controls scanned with 7 T resting-state fMRI confirmed a compression of the cortical hierarchy in FEP, which affected metrics of the hierarchical distance between the sensorimotor and default mode networks, and of the hierarchical organization within the semantic network. These organizational changes were predicted by graphs representing semantic and syntactic associations between meaningful units in speech produced during picture descriptions. These findings unite psychosis, language, and the cortical hierarchy in a single conceptual scheme, which helps to situate language within the neurocognition of psychosis and opens the clinical prospect for mental dysfunction to become computationally measurable in spontaneous speech.

Exploring the associations between momentary cortisol levels and psychotic-like experiences in young adults: Results from a temporal network analysis of daily-life data.

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the development of psychosis and subthreshold psychotic symptoms commonly referred to as psychotic-like experiences (PLEs). The exact mechanisms linking the HPA axis responses with the emergence of PLEs remain unknown. The present study aimed to explore real-life associations between stress, negative affect, salivary cortisol levels (a proxy of the HPA axis activity) as well as PLEs together with their underlying cognitive biases (i.e., threat anticipation and aberrant salience). The study was based on the experience sampling method scheduled over 7 consecutive days in the sample of 77 drug-naïve, young adults (18-35 years). The saliva samples were collected with each prompt to measure cortisol levels. A temporal network analysis was used to explore the directed associations of tested variables. Altogether, 3234 data entries were analyzed. Data analysis revealed that salivary cortisol levels did not directly predict next-moment fluctuations of PLEs. However, higher salivary cortisol levels were associated with higher next-moment levels of PLEs through the effects on threat anticipation and negative affect. In turn, PLEs appeared to predict cortisol levels through the effects on negative affect and event-related stress. Negative affect and threat anticipation were the most central nodes in the network. There might be bidirectional associations between the HPA axis responses and PLEs. Threat anticipation and negative affect might be the most important mediators of these associations. Interventions targeting these mediators might hold promise for disrupting the connection between the HPA axis dysregulation and PLEs.

Cognitive subgroups of affective and non-affective psychosis show differences in medication and cortico-subcortical brain networks.

Cognitive deficits are prevalent in individuals with psychosis and are associated with neurobiological changes, potentially serving as an endophenotype for psychosis. Using the HCP-Early-Psychosis-dataset (n = 226), we aimed to investigate cognitive subtypes (deficit/intermediate/spared) through data-driven clustering in affective (AP) and non-affective psychosis patients (NAP) and controls (HC). We explored differences between three clusters in symptoms, cognition, medication, and grey matter volume. Applying principal component analysis, we selected features for clustering. Features that explained most variance were scores for intelligence, verbal recognition and comprehension, auditory attention, working memory, reasoning and executive functioning. Fuzzy K-Means clustering on those features revealed that the subgroups significantly varied in cognitive impairment, clinical symptoms, and, importantly, also in medication and grey matter volume in fronto-parietal and subcortical networks. The spared cluster (86%HC, 37%AP, 17%NAP) exhibited unimpaired cognition, lowest symptoms/medication, and grey matter comparable to controls. The deficit cluster (4%HC, 10%AP, 47%NAP) had impairments across all domains, highest symptoms scores/medication dosage, and pronounced grey matter alterations. The intermediate deficit cluster (11%HC, 54%AP, 36%NAP) showed fewer deficits than the second cluster, but similar symptoms/medication/grey matter to the spared cluster. Controlling for medication, cognitive scores correlated with grey matter changes and negative symptoms across all patients. Our findings generally emphasize the interplay between cognition, brain structure, symptoms, and medication in AP and NAP, and specifically suggest a possible mediating role of cognition, highlighting the potential of screening cognitive changes to aid tailoring treatments and interventions.

Telomere biology and its maintenance in schizophrenia spectrum disorders: Exploring links to cognition.

OBJECTIVE: Contemporary research suggests reduced telomere length in schizophrenia spectrum disorders (SZ) compared to age-adjusted non-affected individuals. However, the role of telomere maintenance and telomere repair in SZ is poorly understood as well as the involvement of telomere biology in cognitive abnormalities in SZ. METHODS: The study consisted of 758 participants (SZ [n = 357] and healthy controls, HC [n = 401]) collected as part of the Norwegian TOP study. Participants were assessed with standardized neuropsychological tests measuring five cognitive domains. Leucocyte telomere length (TL) was measured via blood and determined by quantitative real-time Polymerase Chain Reaction (qPCR) providing a telomere to single copy ratio (T/S ratio), used to estimate the mean telomere length. Telomerase activity was assessed by the expression levels of the Telomerase Reverse Transcriptase (TERT) and Telomerase RNA Component (TERC) genes. To assess telomere maintenance and telomere repair we calculated the telomerase expression to TL ratio (TERT/TL and TERC/TL respectively). RESULTS: Patients had reduced TERT (F = 5.03, p = 0.03), but not TERC expression (F = 1.04, p = 0.31), and higher TERT/TL (F = 6.68, p = 0.01) and TERC/TL (F = 6.71, p = 0.01), adjusted for age, sex, and ethnicity. No statistically significant association was observed between any of the telomere biology markers and the cognitive domains (p > 0.05). CONCLUSION: Our study shows changes in TERT expression and telomere maintenance and telomere repair in SZ compared HC. However, the role of telomere biology in the mechanism underlying cognitive impairment in psychosis seems limited.

Relations between changes in safety behavior, paranoid ideations, cognitive biases, and clinical characteristics of patients with a psychotic disorder over time.

BACKGROUND: Safety behaviors, both positive (maladaptive coping behavior) and negative (avoidance behavior), are used by people with paranoid delusions to avoid perceived threats. Safety behaviors contribute to the persistence of paranoid delusions by preventing disconfirmation of threat beliefs and may influence other psychiatric symptoms. This study investigated how changes in safety behaviors are related to changes in paranoid ideation, social anxiety, depression, cognitive biases and self-esteem over time. METHODS: This study included 116 patients diagnosed with a psychotic disorder (DSM-IV) and at least moderate levels of paranoid ideations (GTPS >40).The data were collected as part of a multi-center randomized controlled trial where patients were randomized to VR-CBT (n = 58) or treatment as usual (TAU; n = 58). Assessments were completed at baseline (T0), after three months (T3) and after six months (T6). For all variables, change scores between T0 and T3 and T3 and T6 were calculated and Pearson correlations between change scores were computed. RESULTS: A decrease in total safety behavior was related to diminished paranoid ideation, social anxiety, and depression. No significant temporal associations were found between changes in safety behavior and changes in cognitive biases and self-esteem. Similar but less robust results were found for respectively negative safety behavior and positive safety behavior. CONCLUSION: Dropping safety behavior can be specifically targeted in behavioral interventions. Whereas there appears to be a relation with reduction in anxiety, paranoia, and depressive symptoms, changes in safety behavior do not seem to align with changes in cognitive thinking processes.

Impaired 40-Hz and intact hierarchical organization mode of auditory steady-state responses among individuals with clinical high-risk for psychosis.

BACKGROUND: Impaired gamma band oscillation, specifically 40-Hz auditory steady state response (ASSR) has been robustly found in schizophrenia, while there is relatively little evidence characterizing the ASSR before full-blown psychosis. OBJECTIVE: To characterize gamma-band ASSR in populations at clinical high-risk for psychosis (CHR). METHODS: One hundred and seven CHR subjects and sixty-five healthy control (HC) subjects were included and completed clinical assessments, the ASSR paradigm of electroencephalography (EEG) and cognitive assessments. Both indices of event-related spectrum perturbation (ERSP) and intertrial coherence (ITC) in response to 20-Hz, 30-Hz and 40-Hz click sounds were respectively qualified and compared between these two groups, as well as the relationship to clinical psychopathology and cognitive function was assessed. RESULTS: At 40-Hz click sounds, ERSP in HC group (1.042 ± 0.047) was statistical significantly increased than that in CHR group (0.873 ± 0.036) (p = 0.005)；at 30-Hz, ERSP in HC group (0.536 ± 0.024) was increased than that in CHR group (0.483 ± 0.019), but the difference was trend statistical significance (p = 0.083)；at 20-Hz, ERSP in HC group (0.452 ± 0.017) was not different significantly from CHR group (0.418 ± 0.013) (p = 0.104). ERSP of the HC group was the highest at 40-Hz click sounds, followed by 30-Hz, and the lowest at 20-Hz. The difference between any two of the three ERSP showed statistical significance (30-Hz vs. 40-Hz: p < 0.001; 20-Hz vs. 40-Hz: p < 0.001；20-Hz vs. 30-Hz: p = 0.003). Similarly, ERSP of the CHR group was the highest at 40-Hz click sounds, followed by 30-Hz, and the lowest at 20-Hz. The difference between any two of these three ERSP showed statistical significance (30-Hz vs. 40-Hz: p < 0.001; 20-Hz vs. 40-Hz: p < 0.001；20-Hz vs. 30-Hz: p = 0.002). A statistically significant small positive correlation of 40-Hz ERSP with signal processing speed score was observed in the HC group (ρ = 0.27, p = 0.029). A statistically significant small negative correlation of 40-Hz ERSP with visual learning score was observed in the CHR group (ρ = -0.22, p = 0.023). CONCLUSION: Impaired 40-Hz but undamaged hierarchical organization mode of auditory steady state presented in the CHR populations. Abnormal 40 Hz ASSR for CHR might be associated with cognitive functions, such as information processing speed and visual memory.

Diverging functional connectivity timescales: Capturing distinct aspects of cognitive performance in early psychosis.

BACKGROUND: Psychosis spectrum disorders (PSDs) are marked by cognitive impairments, the neurobiological correlates of which remain poorly understood. Here, we investigate the entropy of time-varying functional connectivity (TVFC) patterns from resting-state functional magnetic resonance imaging (rs-fMRI) as potential biomarker for cognitive performance in PSDs. By combining our results with multimodal reference data, we hope to generate new insights into the mechanisms underlying cognitive dysfunction in PSDs. We hypothesized that low-entropy TVFC patterns (LEN) would be more behaviorally informative than high-entropy TVFC patterns (HEN), especially for tasks that require extensive integration across diverse cognitive subdomains. METHODS: rs-fMRI and behavioral data from 97 patients in the early phases of psychosis and 53 controls were analyzed. Positron emission tomography (PET) and magnetoencephalography (MEG) data were taken from a public repository (Hansen et al., 2022). Multivariate analyses were conducted to examine relationships between TVFC patterns at multiple spatial scales and cognitive performance in patients. RESULTS: Compared to HEN, LEN explained significantly more cognitive variance on average in PSD patients, driven by superior encoding of information on psychometrically more integrated tasks. HEN better captured information in specific subdomains of executive functioning. Nodal HEN-LEN transitions were spatially aligned with neurobiological gradients reflecting monoaminergic transporter densities and MEG beta-power. Exploratory analyses revealed a close statistical relationship between LEN and positive symptom severity in patients. CONCLUSION: Our entropy-based analysis of TVFC patterns dissociates distinct aspects of cognition in PSDs. By linking topographies of neurotransmission and oscillatory dynamics with cognitive performance, it enhances our understanding of the mechanisms underlying cognitive deficits in PSDs.

Association between cognitive functioning, suicidal ideation and suicide attempts in major depressive disorder, bipolar disorder, schizophrenia and related disorders: A systematic review and meta-analysis.

INTRODUCTION: Treatable mental disorders, such as psychotic, major depressive disorder (MDD), and bipolar disorder (BD), contribute to a substantial portion of suicide risk, often accompanied by neurocognitive deficits. We report the association between cognitive function and suicidal ideation/suicide attempts (SI/SA) in individuals with schizoaffective disorder, BD, and MDD. METHODS: A systematic search was conducted on PubMed, Ovid and Scopus databases for primary studies published from inception to April 2024. Eligible articles that reported on the effect size of association between cognition and SI/SA were pooled using a random effects model. RESULTS: A total of 41 studies were included for analysis. There was a negative association between executive functioning and SI/SA in schizoaffective disorder (SA: Corr = -0·78, 95 % CI [-1·00, 0·98]; SI: Corr = -0·06, 95 % CI [-0·85, 0·82]) and MDD (SA: Corr = -0·227, 95 % CI [-0·419, -0·017]; SI: Corr = -0·14, 95 % CI [-0·33, 0·06]). Results were mixed for BD, with a significant positive association between SA and global executive functioning (Corr = 0·08, 95 % CI [0·01, 0·15]) and negative association with emotion inhibition. Mixed results were observed for processing speed, attention, and learning and memory, transdiagnostically. LIMITATIONS: There is heterogeneity across sample compositions and cognitive measures. We did not have detailed information on individuals with respect to demographics and comorbidities. CONCLUSIONS: We observed a transdiagnostic association between measures of cognitive functions and aspects of suicidality. The interplay of cognitive disturbances, particularly in reward-based functioning, may underlie suicidality in individuals with mental disorders. Disturbances in impulse control, planning, and working memory may contribute to self-injurious behavior and suicide.

Ontogenesis of self-disorders in the schizophrenia spectrum: A phenomenological neuro-developmental model.

The concept of basic Self-disorders (SD) captures the experiential aspects associated with vulnerability to schizophrenia spectrum disorders (SSD). SD emerge prior to, and constitute the underlying structure for, the emergence of major diagnostic symptoms, including positive psychotic ones. SD are also detectable in populations with familial risk for SSD. This paper proposes a two-stage phenomenological-developmental model, exploring the early deficit in multisensory integration and their impact on the ontogeny of the Minimal Self in the first years of life. It also examines subsequent emergence of schizotaxic vulnerability, which later manifests as typical anomalies of subjectivity, such as basic symptoms and self-disorders.

Difference in Laterality of the Dorsal Striatum in Schizoaffective Disorder.

BACKGROUND: Recent research has demonstrated that the dorsal striatum is directly associated with the integration of cognitive, sensory-motor, and motivational/emotional data. Disruptions in the corticostriatal circuit have been implicated in the pathophysiology of psychosis. The dorsal striatum was reported to show lateralized pathology in psychotic disorders. In this study, we aimed to analyze the laterality of the dorsal striatum with texture analysis of T2-weighted magnetic resonance imaging (MRI) images from schizoaffective disorder (SAD) patients. METHODS: Twenty SAD patients, met the inclusion criteria and had available cranial MRI data were assigned as the patient group. Twenty healthy individuals were determined as the control group. Texture analysis values were obtained from striatum region of interests (ROI) generated from T2-weighted MRI images. Data are presented as mean and standard deviation. The suitability of the data for normal distribution was analyzed with the Kolmogorov-Smirnov test. Analysis of variance (ANOVA) test (Post Hoc TUKEY) was employed to compare the group data based on test findings. RESULTS: There was no significant difference between the groups in terms of gender and age. There were differences in the values of texture analysis parameters of both caudate and putamen nuclei in comparison to controls. We identified differences in the left dorsal striatum nuclei in SAD. The differences in the putamen were more and more pronounced than in the caudate. CONCLUSIONS: Texture analyses suggest that the left dorsal striatum nuclei may be different in SAD patients. Further studies are needed to determine the pathophysiology of SAD and how it may affect disease treatment.

Facial emotion perception in individuals with clinical high risk for psychosis compared with healthy controls, first-episode psychosis, and in predicting psychosis transition: A systematic review and meta-analysis.

Facial emotion perception deficits, a possible indicator of illness progression and transdiagnostic phenotype, were examined in high-risk psychosis (CHR) patients through a systematic review and meta-analysis of 35 studies (2567 CHR individuals, 1103 non-transitioned [CHR-NT], 212 transitioned [CHR-T], 512 first-episode psychosis [FEP], and 1936 healthy controls [HC]). CHR showed overall (g = -0.369 [95 % CI, -0.485 to -0.253]) and specific impairments in detecting anger, disgust, fear, happiness, neutrality, and sadness compared to HC, except for surprise. FEP revealed a general deficit than CHR (g = -0.378 [95 % CI, -0.509 to -0.247]), and CHR-T displayed more pronounced baseline impairments than CHR-NT (g = -0.217 [95 % CI, -0.365 to -0.068]). FEP only exhibited a poorer ability to perceive fear, but not other individual emotions, compared to CHR. Similar performances in perceiving individual emotions were observed regardless of transition status (CHR-NT and CHR-T). However, literature comparing the perception of individual emotions among FEP, CHR-T, and CHR is limited. This study primarily characterized the general and overall impairments of facial emotion perception in CHR which could predict transition risk, emphasizing the need for future research on multimodal parameters of emotion perception and associations with other psychiatric outcomes.

Development of an eye-tracking system based on a deep learning model to assess executive function in patients with mental illnesses.

Patients with mental illnesses, particularly psychosis and obsessive‒compulsive disorder (OCD), frequently exhibit deficits in executive function and visuospatial memory. Traditional assessments, such as the Rey‒Osterrieth Complex Figure Test (RCFT), performed in clinical settings require time and effort. This study aimed to develop a deep learning model using the RCFT and based on eye tracking to detect impaired executive function during visuospatial memory encoding in patients with mental illnesses. In 96 patients with first-episode psychosis, 49 with clinical high risk for psychosis, 104 with OCD, and 159 healthy controls, eye movements were recorded during a 3-min RCFT figure memorization task, and organization and immediate recall scores were obtained. These scores, along with the fixation points indicating eye-focused locations in the figure, were used to train a Long Short-Term Memory + Attention model for detecting impaired executive function and visuospatial memory. The model distinguished between normal and impaired executive function, with an F1 score of 83.5%, and identified visuospatial memory deficits, with an F1 score of 80.7%, regardless of psychiatric diagnosis. These findings suggest that this eye tracking-based deep learning model can directly and rapidly identify impaired executive function during visuospatial memory encoding, with potential applications in various psychiatric and neurological disorders.

Perplexity of utterances in untreated first-episode psychosis: an ultra-high field MRI dynamic causal modelling study of the semantic network.

BACKGROUND: Psychosis involves a distortion of thought content, which is partly reflected in anomalous ways in which words are semantically connected into utterances in speech. We sought to explore how these linguistic anomalies are realized through putative circuit-level abnormalities in the brain's semantic network. METHODS: Using a computational large-language model, Bidirectional Encoder Representations from Transformers (BERT), we quantified the contextual expectedness of a given word sequence (perplexity) across 180 samples obtained from descriptions of 3 pictures by patients with first-episode schizophrenia (FES) and controls matched for age, parental social status, and sex, scanned with 7 T ultra-high field functional magnetic resonance imaging (fMRI). Subsequently, perplexity was used to parametrize a spectral dynamic causal model (DCM) of the effective connectivity within (intrinsic) and between (extrinsic) 4 key regions of the semantic network at rest, namely the anterior temporal lobe, the inferior frontal gyrus (IFG), the posterior middle temporal gyrus (MTG), and the angular gyrus. RESULTS: We included 60 participants, including 30 patients with FES and 30 controls. We observed higher perplexity in the FES group, indicating that speech was less predictable by the preceding context among patients. Results of Bayesian model comparisons showed that a DCM including the group by perplexity interaction best explained the underlying patterns of neural activity. We observed an increase of self-inhibitory effective connectivity within the IFG, as well as reduced self-inhibitory tone within the pMTG, in the FES group. An increase in self-inhibitory tone in the IFG correlated strongly and positively with inter-regional excitation between the IFG and posterior MTG, while self-inhibition of the posterior MTG was negatively correlated with this interregional excitation. LIMITATION: Our design did not address connectivity in the semantic network during tasks that selectively activated the semantic network, which could corroborate findings from this resting-state fMRI study. Furthermore, we do not present a replication study, which would ideally use speech in a different language. CONCLUSION: As an explanation for peculiar speech in psychosis, these results index a shift in the excitatory-inhibitory balance regulating information flow across the semantic network, confined to 2 regions that were previously linked specifically to the executive control of meaning. Based on our approach of combining a large language model with causal connectivity estimates, we propose loss in semantic control as a potential neurocognitive mechanism contributing to disorganization in psychosis.

Novel N100 area reliably captures aberrant sensory processing and is associated with neurocognition in early psychosis.

BACKGROUND: Despite findings from translational and genetic studies in the event-related potential (ERP) literature, the validity and reliability of P50 suppression as a schizophrenia spectrum endophenotype has been questioned. Here, we aimed to examine sensory registration and gating measures derived from P50 and N100 amplitude, as well as N100 area-a novel approach proposed herein-in early psychosis versus health. METHODS: Individuals at clinical high risk for psychosis (CHR; n = 77), first-episode psychosis (FE; n = 52), and healthy controls (HC; n = 65) were assessed in a paired-click auditory ERP paradigm. Eight CHR converted to psychosis (CHRC) and 39 did not (CHR-NC) by 24 months, while 30 CHR were lost to follow-. Group differences, test-retest reliability, and associations with neurocognitive function were assessed in nine ERP measures. RESULTS: Significant differences were observed in N100 S1 amplitude, S1 area, and area difference between HC and FE, as well as in N100 S1 area between HC and CHR, among the total population. Furthermore, significant differences were found in N100 S1 area between HC and CHR-NC (Cliff's delta, Δ = 0.32), as well as in N100 area difference between HC and CHR-C (Δ = 0.55). Both N100 S1 area and area difference demonstrated moderate to acceptable reliability (intraclass correlation coefficients: 0.61-0.78). Processing speed negatively correlated with both N100 S1 area and area difference, while executive function negatively correlated with N100 S1 area alone in CHR and FE. CONCLUSION: Among the ERP measures studied, N100 area measures may serve as a reliable biomarker of aberrant sensory processing and neurocognition in early psychosis.

Neurocognition in adolescents and young adults at clinical high risk for psychosis: Predictive stability for social and role functioning.

The prodromal phase of schizophrenia provides an optimal opportunity to mitigate the profound functional disability that is often associated with fully expressed psychosis. Considerable evidence supports the importance of neurocognition in the development of interpersonal (social) and academic (role) skills. Further findings from adolescents and young adults at clinical high risk for developing psychosis (CHRP) suggest that treatment for functioning might be most effective when targeting early and specific neurocognitive deficits. The current study addresses this critical intervention issue by examining the potential of neurocognitive deficits at intake for predicting social and role functioning over time in CHR-P youth. The study included 345 CHR-P participants from the second phase of the North American Prodrome Longitudinal Study (NAPLS2) with baseline neurocognition and 2-year follow-up data on social and role functioning. Slower baseline processing speed consistently predicted poor social functioning over time, while attention deficits predicted poor role functioning at baseline and follow-up. In addition, the impact of processing speed and attention impairments on social and role functioning, respectively, persisted even when adjusting the regression models for attenuated positive, negative, and disorganized symptoms, and transition status. The current study demonstrates for, arguably the first time, that processing speed and attention are strongly predictive of social and role functioning over time, respectively, above and beyond the impact of symptoms and those CHR-P individuals that develop psychosis over the course of the study. These findings imply that early neurocognition is a critical treatment target linked to the developmental trajectory of social and role functioning.

Altered brain and physiological stress responses in early psychosis.

Stress is proposed to be a crucial factor in the onset and presentation of psychosis. The early stage of psychosis provides a window into how stress interacts with the emergence of psychosis. Yet, how people with early psychosis respond to stress remains unclear. The current study examined how stress responses (brain, physiological, self-report) differ in early psychosis. Forty participants (20 early psychosis [EP], 20 healthy controls [HC]) completed a stress task in the scanner that involved viewing stressful and neutral-relaxing images. Physiological responses (cortisol, heart rate) and self-report of stress were also assessed. Region of Interest analyses were conducted with brain regions previously shown to be activated during the stress task (amygdala, hippocampus, striatum, hypothalamus, prefrontal cortex [dorsolateral, ventrolateral, medial orbital]). Linear mixed models were used to test for effects of group (EP, HC) and emotion (stress, neutral-relaxing). HC had higher hippocampus activation to stress versus neutral-relaxing conditions while EP did not show a difference (group x emotion interaction, p = 0.04). There were also significant main effects of group with EP having higher amygdala activation (p = 0.01), ventrolateral prefrontal cortex activation (vlPFC, p = 0.03), self-report of stress (p = 0.01), and heart rate (p < 0.001). Our study found preliminary evidence that people with early psychosis showed heightened response to stressful and non-threatening situations, across multiple levels of stress responses. Our findings suggest a novel perspective on stress alterations in early psychosis and highlight the importance of considering both stressful and non-stressful situations.

The impact of subclinical psychotic symptoms on delay and effort discounting: Insights from behavioral, computational, and electrophysiological methods.

BACKGROUND: The ability to value rewards is crucial for adaptive behavior and is influenced by the time and effort required to obtain them. Impairments in these computations have been observed in patients with schizophrenia and may be present in individuals with subclinical psychotic symptoms (PS). METHODS: In this study, we employed delay and effort-discounting tasks with food rewards in thirty-nine participants divided into high and low levels of PS. We investigated the underlying mechanisms of effort-discounting through computational modelling of dopamine prefrontal and subcortical circuits and the electrophysiological biomarker of both delay and effort-discounting alterations through resting-state frontal alpha asymmetry (FAA). RESULTS: Results revealed greater delay discounting in the High PS group compared to the Low PS group but no differences in the effort discounting task. However, in this task, the same levels of estimated dopamine release were associated with a lower willingness to exert effort for high-calorie food rewards in High PS participants compared to Low PS participants. Although there were no significant differences in FAA between the High PS and Low PS groups, FAA was significantly associated with the severity of participants' negative symptoms. CONCLUSIONS: Our study suggests that the dysfunction in temporal and effort cost computations, seen in patients with schizophrenia, may be present in individuals with subclinical PS. These findings provide valuable insight into the early vulnerability markers (behavioral, computational, and electrophysiological) for psychosis, which may aid in the development of preventive interventions. These findings are preliminary and warrant further investigation.

Aggressive behaviors in first-episode psychosis: Distinction between the premorbid phase and the onset of psychosis.

BACKGROUND: There is a well-established, although complex, association between aggression and psychosis, particularly in the early stages of illness. Some persons display aggressive behaviors even prior to psychosis onset. However, factors associated with aggressive behaviors prior to and at first-episode psychosis (FEP) onset remain underdocumented. AIMS: The objective is two-fold: 1) to describe the prevalence of verbal and physical aggression occurring during the premorbid phase and at FEP onset; 2) distinguish the factors associated with aggressive behaviors during these two periods. METHOD: Data on aggressive behaviors and factors potentially associated therewith were collected through research interviews and chart reviews among 567 persons with FEP admitted to two early intervention services in Montreal, Canada. Logistic regression analyses were conducted to identify factors associated with aggressive behaviors in both periods. RESULTS: In the premorbid phase, 46.1 % (n = 257/558) of patients presented aggression (verbal: 35.9 %; towards objects: 24.2 %; against others: 27.9 %). At FEP, 18.1 % (n = 101/558) presented aggressive behaviors (verbal: 12.9 %; towards objects: 6.1 %; against others: 8.8 %). In the premorbid phase, lower education, prior justice involvement, cluster B personality traits/disorder and poorer functioning were associated with aggressive behaviors, while, at FEP, only prior homelessness was associated with aggression. CONCLUSIONS: Aggressive behaviors are frequent in patients with FEP, prior onset and at FEP. Premorbid aggressive behaviors seem to be associated with premorbid difficulties. Early detection of youth with psychosis and those at high risk of psychosis, particularly homeless youth, is necessary to provide access to early specialized interventions and possibly prevent aggressive behaviors and their consequences.