Consistency of Delusion Themes Across First and Subsequent Episodes of Psychosis.

Importance: Despite growing interest in the phenomenology of delusions in psychosis, at present little is known about their content and evolution over time, including whether delusion themes are consistent across episodes. Objective: To examine the course of delusions and thematic delusion content across relapse episodes in patients presenting to an early intervention service for psychosis. Design, Setting, and Participants: This longitudinal, observational study used clinical data systematically collected from January 2003 to March 2018 from a cohort of consenting patients with affective or nonaffective first-episode psychosis, followed up naturalistically for up to 2 years in an early intervention service for psychosis in Montréal, Quebec, Canada. Data included the thematic content and severity of delusions (scores ≥3 using the Scale for the Assessment of Positive Symptoms) and associated psychotic and nonpsychotic symptoms, both across an initial episode and, in the event of remission, a potential relapse. Data were analyzed from September 2021 to February 2023. Exposure: An early intervention service for psychosis, organized around intensive case management and a multidisciplinary team approach, which observed each patient for up to 2 years of care. Main Outcomes and Measures: The primary outcome was positive symptom relapse and remission, including the presence and content of delusions, which was coded per the Scale for the Assessment of Positive Symptoms and accepted definitions. The main statistical measures included repeated paired-sample t tests and binary logistic regression analyses. Results: Of 636 consenting patients, mean (SD) age was 23.8 (4.75) years; 191 patients were female, 444 were male, and 1 patient was nonbinary. Remission rates were high, and relapse rates were relatively low: 591 individuals had baseline delusions, of which 558 (94.4%) achieved remission. Of these 558 patients, only 182 (32.6%) had a subsequent relapse to a second or later episode of psychosis. Of the 182 patients who did relapse, however, a large proportion (115 [63.2%]) reported threshold-level delusions. Of these 115, 104 patients (90.4%) had thematic delusion content consistent with that reported during the index (first) episode. Those who relapsed with delusions had fewer delusion themes present during subsequent episodes of psychosis compared with the index episode and lower levels of other psychotic and nonpsychotic symptoms. Conclusions and Relevance: Specialized early intervention services for psychosis can achieve high rates of sustained remission. However, in this study, the minority of individuals with delusions who later relapsed experienced similar delusion themes during subsequent episodes. These findings raise important considerations for the conceptualization of delusions and have clinical implications for trajectories of illness and care.

The role of motivation in clinical presentation, treatment engagement and response in schizophrenia-spectrum disorders: A systematic review.

Schizophrenia, a debilitating psychiatric disorder, has a long-term impact on social and occupational functioning. While negative symptoms, notably amotivation, are recognized as poor prognostic factors, the positive force of patient motivation (autonomous motivation) remains underexplored. This systematic review, guided by Self-Determination Theory (SDT), investigated the impact of motivation on clinical presentation, and treatment engagement and response in schizophrenia-spectrum disorders. Fifty-five independent studies (N = 6897), using 23 different motivation scales, met inclusion criteria. Results were categorized into cross-sectional and longitudinal correlates of autonomous motivation, and the effects of motivational interventions. Cross-sectionally, autonomous motivation was positively associated with social/occupational functioning, and negatively associated with negative and positive symptom severity. In longitudinal studies, baseline autonomous motivation predicted engagement in and response to social/occupational treatments, with mixed results in cognitive interventions. In the 16 randomized controlled trials (RCTs), the most common motivational interventions were individualized goal setting and goal attainment support, followed by increasing sense of competence by challenging defeatist beliefs, and enhancing relatedness by increasing contact time. Motivational interventions consistently increased autonomous motivation, treatment engagement and response. More studies are needed, particularly studies that monitor motivation during treatment: proximal assessments could facilitate the identification of treatment elements that impact motivation and engagement and inform treatment modifications to enhance the patient experience and improve treatment efficacy.

An intersectional perspective on the sociodemographic and clinical factors influencing the status of not in Education, Employment, or training (NEET) in patients with first-episode psychosis (FEP).

PURPOSE: High rates of Not in Education, Employment or Training (NEET) are seen in people with first episode of psychosis (FEP). Sociodemographic and clinical factors were reported to be associated with NEET status in FEP patients. This study follows Intersectionality to examine the independent and additive effects, and most importantly the intersections of sociodemographic and clinical variables concerning NEET status in FEP patients. It was hypothesized that NEET status in FEP patients would be described by the intersection between at least two predictor variables. METHODS: Secondary analyses with chi-square tests, multiple logistic regression and Chi-squared Automatic Interaction Detection (CHAID) analyses were performed on 440 participants with FEP. RESULTS: Chi-square tests indicated that patient socioeconomic status and negative symptom severity were significantly and independently associated with their NEET status. Multiple logistic regression suggested additive effects of age (odds ratio = 1.61), patient socioeconomic status (odds ratio = 1.55) and negative symptom severity (odds ratio = 1.75) in predicting patients' NEET status. CHAID detected an intersection between patients' negative symptom severity and socioeconomic status in shaping their NEET status. CONCLUSION: This study explored how the NEET status of patients with FEP was explained not only by the separate effects of negative symptom severity and socioeconomic status but also by the unique intersections of their clinical and social identities. Findings indicated that functional outcomes of patients appear co-constructed by the intersections of multiple identities. Crucial clinical implications of complementing care for negative symptom severity with vocational resources to improve functional outcomes of patients are discussed.

Strategies for Achieving Better Cognitive Health in Individuals with Schizophrenia Spectrum: A Focus on the Canadian Landscape: Stratégies pour atteindre une meilleure santé cognitive chez les personnes souffrant du spectre de la schizophrénie : un regard sur le paysage canadien.

BACKGROUND: Schizophrenia spectrum disorders (SSDs) are a group of psychiatric disorders characterized by positive and negative symptoms as well as cognitive impairment that can significantly affect daily functioning. METHOD: We reviewed evidence-based strategies for improving cognitive function in patients with SSDs, focusing on the Canadian landscape. RESULTS: Although antipsychotic medications can address the positive symptoms of SSDs, cognitive symptoms often persist, causing functional impairment and reduced quality of life. Moreover, cognitive function in patients with SSDs is infrequently assessed in clinical practice, and evidence-based recommendations for addressing cognitive impairment in people living with schizophrenia are limited. While cognitive remediation (CR) can improve several domains of cognitive function, most individuals with SSDs are currently not offered such an intervention. While the development of implementation strategies for CR is underway, available and emerging pharmacological treatments may help overcome the limited capacity for psychosocial approaches. Furthermore, combining pharmacological with non-pharmacological interventions may improve outcomes compared to pharmacotherapy or CR alone. CONCLUSION: This review highlights the challenges and discusses the potential solutions related to the assessment and management of cognitive impairment to help mental health-care practitioners better manage cognitive impairment and improve daily functioning in individuals with SSDs.

Improving Thinking Skills in People With Schizophrenia: A Focus on CanadaPlain Language SummarySchizophrenia spectrum disorders (SSDs) are mental health conditions that can cause a mix of symptoms making everyday life difficult for people. For example, some people might experience positive symptoms like seeing and hearing things that are not there, having false believes, or feeling suspicious. Others might experience negative symptoms like isolating from social interactions, having trouble showing emotion, or finding it hard to connect with others. Finally, they might also have trouble with thinking skills, like paying attention, planning and organizing, remembering things, or understanding social cues. While some medicines can help with some of the symptoms, they often do not help with improving thinking skills. In addition, these thinking problems are not checked often enough in patients with SSDs. In fact, there are not many proven ways to help with these issues. One method that can help with thinking skills is called cognitive remediation (CR), but it is not offered to most people with SSDs. There are ongoing efforts to make CR more available. It is also possible that CR may be combined with new medicines to make it work better than using just one treatment. This article looks at ways to improve thinking skills in people with SSDs, with a focus on what is happening in Canada. We present the challenges and possible solutions for checking and managing thinking problems, to help health-care workers better care for people with SSDs.

Overlap between individual differences in cognition and symptoms of schizophrenia.

BACKGROUND: Neurocognitive impairment is a core feature of schizophrenia spectrum disorders (SSDs), and the relationship between cognition and symptoms in SSDs has been widely researched. Negative symptoms are related to a wide range of cognitive impairments; however, the aspects of negative symptoms that underpin this relationship have yet to be specified. STUDY DESIGN: We used iterative Constrained Principal Component Analysis (iCPCA) to explore the relationship between 18 cognitive measures (including processing speed, attention, working, spatial and verbal memory and executive functions) and 46 symptoms in schizophrenia at the individual item level while minimizing the risk of Type I errors. ICPCA was conducted on a sample of SSD patients in the early stages of psychiatric treatment (n = 121) to determine the components of cognition overlapping with symptoms measured by the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS). RESULTS: We found that a verbal memory component was associated with items from SANS and SAPS related to impoverished and disorganized emotional communication, language, and thought. In contrast, a working memory component was associated with SANS items related to motor system impoverishment. CONCLUSIONS: The iCPCA allowed us to explore the associations between individual items, optimized to understand the overlap between symptoms and cognition. The specific symptoms linked to verbal and working memory impairments imply distinct brain networks, which further investigation may lead to our deeper understanding of the illness and the development of treatment methods.

Sociodemographic and clinical correlates of hallucinations in patients entering an early intervention program for first episode psychosis.

Hallucinations are a core feature of psychosis, and their severity during the acute phase of illness is associated with a range of poor outcomes. Various clinical and sociodemographic factors may predict hallucinations and other positive psychotic symptoms in first episode psychosis (FEP). Despite this, the precise factors associated with hallucinations at first presentation to an early intervention service have not been extensively researched. Through detailed interviews and chart reviews, we investigated sociodemographic and clinical predictors in 636 minimally-medicated patients who entered PEPP-Montréal, an early intervention service for FEP, between 2003 and 2018. Hallucinations were measured using the Scale for the Assessment of Positive Symptoms (SAPS), while negative symptoms were assessed using the Scale for the Assessment of Negative symptoms (SANS). Depressive symptoms were evaluated through the Calgary Depression Scale for Schizophrenia (CDSS), and anxiety symptoms via the Hamilton Rating Scale for Anxiety (HAS). A majority (n = 381, 59.9 %) of the sample presented with clinically significant hallucinations (SAPS global hallucinations score ≥ 3) at program entry. These patients had an earlier age at onset, fewer years of education, and a higher severity of delusions, depression and negative symptoms than those without clinical-level hallucinations. These results suggest that individuals with clinically significant hallucinations at admission tend to be younger and have a greater overall symptom burden. This makes it especially important to monitor hallucinations alongside delusions, depression and negative symptoms in order to identify who might benefit from targeted interventions. The implications of these findings for early intervention and person-centered care are discussed.

Longitudinal inference of multiscale markers in psychosis: from hippocampal centrality to functional outcome.

Multiscale neuroscience conceptualizes mental illness as arising from aberrant interactions across and within multiple biopsychosocial scales. We leverage this framework to propose a multiscale disease progression model of psychosis, in which hippocampal-cortical dysconnectivity precedes impairments in episodic memory and social cognition, which lead to more severe negative symptoms and lower functional outcome. As psychosis represents a heterogeneous collection of biological and behavioral alterations that evolve over time, we further predict this disease progression for a subtype of the patient sample, with other patients showing normal-range performance on all variables. We sampled data from two cross-sectional datasets of first- and multi-episode psychosis, resulting in a sample of 163 patients and 119 non-clinical controls. To address our proposed disease progression model and evaluate potential heterogeneity, we applied a machine-learning algorithm, SuStaIn, to the patient data. SuStaIn uniquely integrates clustering and disease progression modeling and identified three patient subtypes. Subtype 0 showed normal-range performance on all variables. In comparison, Subtype 1 showed lower episodic memory, social cognition, functional outcome, and higher negative symptoms, while Subtype 2 showed lower hippocampal-cortical connectivity and episodic memory. Subtype 1 deteriorated from episodic memory to social cognition, negative symptoms, functional outcome to bilateral hippocampal-cortical dysconnectivity, while Subtype 2 deteriorated from bilateral hippocampal-cortical dysconnectivity to episodic memory and social cognition, functional outcome to negative symptoms. This first application of SuStaIn in a multiscale psychiatric model provides distinct disease trajectories of hippocampal-cortical connectivity, which might underlie the heterogeneous behavioral manifestations of psychosis.

Navigating Social Cognitive Impairments in Schizophrenia Spectrum Disorders: Protocol for a Pilot Pre-Post Quasi-Experimental Study for Remote Avatar-Assisted Cognitive Remediation Therapy.

BACKGROUND: Social cognitive impairments are prevalent in schizophrenia spectrum disorder (SSD) and have detrimental effects on functioning. Cognitive remediation (CR) has shown its efficacy in improving social cognitive impairments, although the transfer of these skills to daily life and the personalization of these interventions remain challenging. RC2S (Remédiation Cognitive de la Cognition Sociale dans la Schizophrénie; Cognitive remediation of social cognition in Schizophrenia) is a French CR that combines the learning of strategies and practice using paper-and-pencil exercises and digital relational simulations. This French program was designed as an in-person intervention. OBJECTIVE: This project aims to culturally adapt the RC2S program, in French-Canadian and North American English and to assess the feasibility, acceptability, safety, and implementation of a remote version in people with SSD. An exploratory objective is to assess the preliminary effect of remote RC2S on goal attainment, social cognition, and psychosocial outcomes. METHODS: We will use a pre-post quasi-experimental design. First, the translation and cultural adaptation in North American English and French-Canadian of RC2S is presented. Then, 20 participants aged ≥18 years with a diagnosis of SSD, presenting with a subjective or an objective impairment in social cognition, will be included to receive RC2S. In addition, 5 therapists will be included as research participants to assess their perspective on RC2S. Participants with SSD will undergo a baseline remote assessment of their social cognition, clinical symptoms, and functioning. They will then start remote RC2S for 24 biweekly individual 1-hour sessions with a therapist. Following the case formulation and goal setting, participants will complete personalized paper-and-pencil exercises to develop strategies and integrative digital relational simulations, during which they will help an avatar navigate through a variety of social contexts and relationships. The last 2 sessions are dedicated to the transfer to daily life. All participants will complete in-session questionnaires assessing therapeutic alliance, motivation, acceptability, feasibility, and implementation. Following RC2S, the participants with SSD will repeat the same assessment as the baseline. Descriptive statistics will be used to summarize the data about acceptability, feasibility, safety, and implementation. To assess the preliminary effect of RC2S, an intention-to-treat approach will be used with linear mixed models for repeated measures with fixed effects of time. RESULTS: So far, 45% (9/20) of participants with SSD (mean age 37.9, SD 9.3 years) have completed the project. They received a mean of 20.5 out of 24 (SD 3.5) sessions of RC2S. A total of 5 therapists also completed the project. CONCLUSIONS: Improving social cognitive impairments is an important target in SSD to promote functional recovery. Using digital technologies to address these impairments and deliver the intervention is a promising approach to increase the ecological validity of CR and access to the intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT05017532; https://classic.clinicaltrials.gov/ct2/show/NCT05017532. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54251.

Using virtual reality to improve verbal episodic memory in schizophrenia: A proof-of-concept trial.

Background: Schizophrenia is associated with impairments in verbal episodic memory. Strategy for Semantic Association Memory (SESAME) training represents a promising cognitive remediation program to improve verbal episodic memory. Virtual reality (VR) may be a novel tool to increase the ecological validity and transfer of learned skills of traditional cognitive remediation programs. The present proof-of-concept study aimed to assess the feasibility, acceptability, and preliminary efficacy of a VR-based cognitive remediation module inspired by SESAME principles to improve the use of verbal episodic memory strategies in schizophrenia. Methods: Thirty individuals with schizophrenia/schizoaffective disorder completed this study. Participants were randomized to either a VR-based verbal episodic memory training condition inspired by SESAME principles (intervention group) or an active control condition (control group). In the training condition, a coach taught semantic encoding strategies (active rehearsal and semantic clustering) to help participants remember restaurant orders in VR. In the active control condition, participants completed visuospatial puzzles in VR. Attrition rate, participant experience ratings, and cybersickness questionnaires were used to assess feasibility and acceptability. Trial 1 of the Hopkins Verbal Learning Test - Revised was administered pre- and post-intervention to assess preliminary efficacy. Results: Feasibility was demonstrated by a low attrition rate (5.88 %), and acceptability was demonstrated by limited cybersickness and high levels of enjoyment. Although the increase in the number of semantic clusters used following the module did not reach conventional levels of statistical significance in the intervention group, it demonstrated a notable trend with a medium effect size (t = 1.48, p = 0.15, d = 0.54), in contrast to the control group where it remained stable (t = 0.36, p = 0.72, d = 0.13). These findings were similar for the semantic clustering ratio in the intervention (t = 1.61, p = 0.12, d = 0.59) and control (t = 0.36, p = 0.72, d = 0.13) groups. There was no significant change in the number of recalled words in either group following VR immersion. Discussion: This VR intervention was feasible, acceptable, and may be useful for improving the use of semantic encoding strategies. These findings support the use of more ecological approaches for the treatment of cognitive impairments in schizophrenia, such as VR-based cognitive remediation.

Speech markers to predict and prevent recurrent episodes of psychosis: A narrative overview and emerging opportunities.

Preventing relapse in schizophrenia improves long-term health outcomes. Repeated episodes of psychotic symptoms shape the trajectory of this illness and can be a detriment to functional recovery. Despite early intervention programs, high relapse rates persist, calling for alternative approaches in relapse prevention. Predicting imminent relapse at an individual level is critical for effective intervention. While clinical profiles are often used to foresee relapse, they lack the specificity and sensitivity needed for timely prediction. Here, we review the use of speech through Natural Language Processing (NLP) to predict a recurrent psychotic episode. Recent advancements in NLP of speech have shown the ability to detect linguistic markers related to thought disorder and other language disruptions within 2-4 weeks preceding a relapse. This approach has shown to be able to capture individual speech patterns, showing promise in its use as a prediction tool. We outline current developments in remote monitoring for psychotic relapses, discuss the challenges and limitations and present the speech-NLP based approach as an alternative to detect relapses with sufficient accuracy, construct validity and lead time to generate clinical actions towards prevention.

Perception of social inclusion/exclusion and response inhibition in adolescents with past suicide attempt: a multidomain task-based fMRI study.

The occurrence of suicidal behaviors increases during adolescence. Hypersensitivity to negative social signals and deficits in cognitive control are putative mechanisms of suicidal behaviors, which necessitate confirmation in youths. Multidomain functional neuroimaging could enhance the identification of patients at suicidal risk beyond standard clinical measures. Three groups of adolescents (N = 96; 78% females, age = 11.6-18.1) were included: patients with depressive disorders and previous suicide attempts (SA, n = 29); patient controls with depressive disorders but without any suicide attempt history (PC, n = 35); and healthy controls (HC, n = 32). We scanned participants with 3T-MRI during social inclusion/exclusion (Cyberball Game) and response inhibition (Go-NoGo) tasks. Neural activation was indexed by the blood-oxygenation-level dependent (BOLD) of the hemodynamic response during three conditions in the Cyberball Game ("Control condition", "Social Inclusion", and "Social Exclusion"), and two conditions in Go-NoGo task ("Go" and "NoGo" blocks). ANCOVA-style analysis identified group effects across three whole-brain contrasts: 1) NoGo vs. Go, 2) Social inclusion vs. control condition, 3) Social exclusion vs. control condition. We found that SA had lower activation in the left insula during social inclusion vs. control condition compared to PC and HC. Moreover, SA compared to PC had higher activity in the right middle prefrontal gyrus during social exclusion vs. control condition, and in bilateral precentral gyri during NoGo vs. Go conditions. Task-related behavioral and self-report measures (Self-reported emotional reactivity in the Cyberball Game, response times and number of errors in the Go-NoGo Task) did not discriminate groups. In conclusion, adolescent suicidal behaviors are likely associated with neural alterations related to the processing of social perception and response inhibition. Further research, involving prospective designs and diverse cohorts of patients, is necessary to explore the potential of neuroimaging as a tool in understanding the emergence and progression of suicidal behaviors.

Effects of metacognitive training (MCT) on social cognition for schizophrenia spectrum and related psychotic disorders: a systematic review and meta-analysis.

BACKGROUND: Individuals with schizophrenia spectrum and related psychotic disorders (SSD) experience significant impairments in social cognition that impede functioning. Social cognition is a multidimensional construct consisting of four domains: 1. theory of mind, 2. emotion processing, 3. attributional style and 4. social perception. Metacognitive training (MCT) is an intervention designed to target cognitive biases in psychosis containing two modules addressing social cognition. METHODS: A systematic review and meta-analysis was conducted to investigate the effects of MCT on social cognition and two of its domains: theory of mind and emotion processing. Ten electronic databases were scoured from 2007 to 1 February 2022 for MCT studies reporting social cognition outcomes for people with SSD (1050 identified, 282 assessed). Effect sizes were calculated using Cohen's d in R. RESULTS: Nine studies were included in the meta-analysis (nMCT = 212, ncontrol = 194). MCT had a small but positive effect on global social cognition (d = 0.28 [95% CI 0.07-0.49]) and theory of mind (d = 0.27 [95% CI 0.01-0.52]). MCT showed no evidence of an effect on emotion processing (d = 0.03 [95% CI -0.26 to 0.32]). CONCLUSION: MCT has a small but significant effect on social cognition for people with SSD. Our results add to other recent meta-analyses showing significant effects of MCT on clinically relevant outcomes such as positive symptoms, cognitive biases and cognitive insight. We recommend that future studies on MCT report outcomes on all four domains of social cognition. TRIAL REGISTRATION: PROSPERO (in the process of registration) available at https://www.crd.york.ac.uk/prospero/#recordDetails.

Transdiagnostic cognitive biases in psychiatric disorders: A systematic review and network meta-analysis.

Psychiatric disorders are characterized by cognitive deficits, which have been proposed as a transdiagnostic feature of psychopathology ("C" factor). Similarly, cognitive biases (e.g., in attention, memory, and interpretation) represent common tendencies in information processing that are often associated with psychiatric symptoms. However, the question remains whether cognitive biases are also transdiagnostic or are specific to certain psychiatric disorders/symptoms. The current systematic review sought to address whether the proposed "C" factor of transdiagnostic cognitive dysfunction in psychopathology can be extended to cognitive biases. Overall, 31 studies comprising 4401 participants (2536 patients, 1865 non-clinical controls) met inclusion criteria, assessing 19 cognitive biases across 20 diagnostic categories, with most studies focusing on interpretation (k = 22) and attention (k = 11) biases and only 2 assessing memory biases. Traditional meta-analyses found a moderate effect size (g = 0.32) for more severe cognitive biases in all patients relative to non-clinical controls, as well as small but significant associations between interpretation biases and transdiagnostic symptom categories (general psychopathology: r = 0.20, emotion dysfunction: r = 0.17, psychotic symptoms: r = 0.25). Network meta-analyses revealed significant patient versus non-clinical control differences on attention and interpretation biases across diagnoses, as well as significant differences between diagnoses, with highest severity in panic disorder for attention biases and obsessive-compulsive disorder for interpretation biases. The current findings extend the big "C" interpretation of transdiagnostic cognitive dysfunction in psychiatric disorders to cognitive biases and transdiagnostic symptom dimensions. Results also suggest that while the presence of cognitive biases is transdiagnostic, bias severity differs across diagnoses, as in traditional neurocognitive deficits.

Exploring the Relationship Between Suicidality and Persistent Negative Symptoms Following a First Episode of Psychosis.

BACKGROUND AND HYPOTHESIS: Suicide is a leading cause of death in first-episode psychosis (FEP), with an elevated risk during the first year following illness onset. The association between negative symptoms and suicidality remains contentious. Some studies suggest that negative symptoms may be associated with lower suicidality, while others fail to find an association between the two. No previous studies have specifically investigated suicidality in Persistent Negative Symptoms (PNS) and its associated subgroups. STUDY DESIGN: In a large cohort of FEP patients (n = 515) from an early intervention service, we investigated suicidality in those with PNS, secondary PNS (ie, sPNS; PNS with clinical-level positive, depressive, or extrapyramidal symptoms), and non-PNS (all other patients) over 24 months. Patients were categorized into PNS groups based on symptoms from month 6 to month 12, and suicidality was evaluated using the Brief Psychiatric Rating Scale (BPRS). STUDY RESULTS: Covarying for age and sex, we found that sPNS had higher suicidality relative to PNS and non-PNS throughout the 24-month period, but PNS and non-PNS did not differ. These differences were maintained after adjusting for depressive symptoms. CONCLUSION: We observed that PNS did not significantly differ from non-PNS. However, we identified sPNS as a group with elevated suicidality above and beyond depression, suggesting that sPNS would benefit from targeted intervention and that PNS categorization identifies a subgroup for whom negative symptoms are not associated with lower suicidality.

Combinations and Temporal Associations Among Precursor Symptoms Before a First Episode of Psychosis.

BACKGROUND AND HYPOTHESIS: Symptoms that precede a first episode of psychosis (FEP) can ideally be targeted by early intervention services with the aim of preventing or delaying psychosis onset. However, these precursor symptoms emerge in combinations and sequences that do not rest fully within traditional diagnostic categories. To advance our understanding of illness trajectories preceding FEP, we aimed to investigate combinations and temporal associations among precursor symptoms. STUDY DESIGN: Participants were from PEPP-Montréal, a catchment-based early intervention program for FEP. Through semistructured interviews, collateral from relatives, and a review of health and social records, we retrospectively measured the presence or absence of 29 precursor symptoms, including 9 subthreshold psychotic and 20 nonpsychotic symptoms. Sequences of symptoms were derived from the timing of the first precursor symptom relative to the onset of FEP. STUDY RESULTS: The sample included 390 participants (68% men; age range: 14-35 years). Combinations of precursor symptoms most frequently featured depression, anxiety, and substance use. Of 256 possible pairs of initial and subsequent precursor symptoms, many had asymmetrical associations: eg, when the first symptom was suspiciousness, the incidence rate ratio (IRR) of subsequent anxiety was 3.40 (95% confidence interval [CI]: 1.79, 6.46), but when the first symptom was anxiety, the IRR of subsequent suspiciousness was 1.15 (95% CI: 0.77, 1.73). CONCLUSIONS: A detailed examination of precursor symptoms reveals diverse clinical profiles that cut across diagnostic categories and evolve longitudinally prior to FEP. Their identification may contribute to risk assessments and provide insights into the mechanisms of illness progression.

Sex differences in cognition and structural covariance-based morphometric connectivity: evidence from 28,000+ UK Biobank participants.

There is robust evidence for sex differences in domain-specific cognition, where females typically show an advantage for verbal memory, whereas males tend to perform better in spatial memory. Sex differences in brain connectivity are well documented and may provide insight into these differences. In this study, we examined sex differences in cognition and structural covariance, as an index of morphometric connectivity, of a large healthy sample (n = 28,821) from the UK Biobank. Using T1-weighted magnetic resonance imaging scans and regional cortical thickness values, we applied jackknife bias estimation and graph theory to obtain subject-specific measures of structural covariance, hypothesizing that sex-related differences in brain network global efficiency, or overall covariance, would underlie cognitive differences. As predicted, females demonstrated better verbal memory and males showed a spatial memory advantage. Females also demonstrated faster processing speed, with no observed sex difference in executive functioning. Males showed higher global efficiency, as well as higher regional covariance (nodal strengths) in both hemispheres relative to females. Furthermore, higher global efficiency in males mediated sex differences in verbal memory and processing speed. Findings contribute to an improved understanding of how biological sex and differences in cognition are related to morphometric connectivity as derived from graph-theoretic methods.

The relationship between negative symptoms and MATRICS neurocognitive domains: A meta-analysis and systematic review.

BACKGROUND: Negative symptoms (NS) are a core symptom domain in schizophrenia spectrum disorders and are associated with poorer social and vocational functioning, and with increased likelihood and durations of hospital admission. NS are not well understood, limiting available interventions. However, numerous studies have reported associations between neurocognitive domains and NS severity. Thus, one promising area in understanding NS is in relation to neurocognition. Currently, the specificity of the relationship between NS and neurocognition is unknown, meaning that there is no consensus regarding which neurocognitive domain is most strongly associated with NS. There is a need to systematically examine the relationship between NS and various neurocognitive domains within study samples. METHODS: A systematic search of Ovid PsycINFO, Ovid MEDLINE and Web of Science was performed for articles published since 2004 (year of MATRICS Consensus publication). Inclusion criteria were: 1) individuals with schizophrenia spectrum disorders, first episode psychosis or clinical high risk 2) assessed all six MATRICS neurocognitive domains (processing speed, attention, working memory, verbal learning & memory, visual learning & memory, reasoning & problem solving), 3) reported correlations between all six MATRICS neurocognitive domains and global NS. A three-level random effects hierarchical meta-analysis was performed to assess the relationship between NS (global, expressive, and experiential dimensions) and the six MATRICS neurocognitive domains. RESULTS: 21 studies were included in the review (n = 3619). All MATRICS neurocognitive domains had small significant correlations with global NS (r = -0.16 to -0.20, p < 0.0001). This relationship was significantly moderated by diagnosis and the moderating effect of sex/ gender trended on significance. Analysis of a subset of the studies revealed that MATRICS neurocognitive domains also had small significant correlations with the two NS dimensions, expressive and experiential. Correlations were stronger with the expressive NS dimension. CONCLUSIONS: This review is novel in assessing the relationship between multiple neurocognitive domains and NS within the same sample, by synthesizing close to two decades of research. Our results suggest that there is a non-specific relationship between neurocognition and NS, and that expressive NS may have a stronger relationship with neurocognitive functioning-based on the MATRICS classification of neurocognition and the neurocognitive assessments used in the included studies. This has implications on our understanding of NS and neurocognition, as well as their treatments. As we gain better understanding of the directionality of the NS-cognition relationship, it could suggest that NS, particularly in the expressive domain, could be improved by targeting cognition globally or that neurocognitive treatments could be more effective if NS are addressed first. Further implications of these results are discussed.

C-Reactive protein and cognition: Mediation analyses with brain morphology in the UK Biobank.

Cognitive impairments and abnormal immune activity are both associated with various clinical disorders. The association between C-Reactive protein (CRP), a marker associated with inflammation, and cognitive performance remains unclear. Further, mechanisms potentially linking CRP to cognition are not yet established. Brain structure may well mediate this relationship: immune processes play crucial roles in shaping and maintaining brain structure, with brain structure and function driving cognition. The United Kingdom Biobank (UKBB) is a large cohort study with extensive assessments, including high-sensitivity serum CRP levels, brain imaging, and various cognitive tasks. With data from 39,200 UKBB participants, we aimed first to determine the relationship between CRP and cognitive performance, and second, to assess metrics of brain morphology as potential mediators in this relationship. Participants were aged 40 to 70 at initial assessment and were mostly Caucasian. After accounting for potential covariates (e.g., age, sex, medical diagnoses, use of selective-serotonin reuptake inhibitors), we found CRP levels to have small, negative associations with fluid intelligence (b = -0.03, 95%CI[-0.05,-0.02], t(14381) = -3.62, pcor = .004), and numeric memory (b = -0.03, 95%CI[-0.05,-0.01], t(14366) = -3.31, pcor = .007). We found no evidence of brain morphology mediating these relationships (all |ab| < 0.001, all pcor > .55). Our findings from this large sample suggest that serum-assessed CRP is of marginal importance for cognitive performance in mid-to-late aged Caucasians; the small effect sizes of statistically significant associations provide context to previous inconsistent results. The seeming lack of involvement of brain morphology suggests that other brain metrics (e.g., connectivity, functional activation) may be more pertinent to this relationship. Future work should also consider CRP levels measured in the central nervous system and/or other cytokines that may better predict cognitive performance in this population.

Sociodemographic and clinical risk factors associated with suicidal ideation and attempt during a 2-year early intervention program for first-episode psychosis.

BACKGROUND: Identifying risk factors for suicidal ideation and attempt among first-episode psychosis patients is essential to prevent suicide in this high-risk population. We investigated risk factors at admission for suicidal ideation and attempt during a 2-year early intervention program. METHODS: Our sample included patients aged 18-35 years who were consecutively admitted to an early intervention program (2003-2017). Sociodemographic and clinical variables were obtained from a longitudinal study, while data on suicidal ideation and attempt were collected via systematic file review. Univariable and multivariable logistic regressions assessed the association of these variables with suicide ideation and attempt. RESULTS: Of 446 participants, 35 (7.8 %) attempted suicide during the 2-year follow up, including two resulting in death (0.45 %), and 168 (37.7 %) reported solely suicidal ideation. Multivariable analyses indicated living alone (OR = 4.01, CI = 2.11-7.63), affective psychosis (OR = 1.95, CI = 1.22-3.14) and depressive symptomatology (OR = 1.45, CI = 1.13-1.86) were associated with increased risk for suicidal ideation. Attempting suicide close to admission (OR = 10.29, CI = 3.63-29.22), living alone (OR = 4.17, CI = 1.40-12.35), and depressive (OR = 1.67, CI = 1.06-2.63) and positive symptomatology (OR = 1.60, CI = 1.02-2.50) were associated with increased risk for suicide attempt. Attempting suicide close to admission (OR = 11.65, CI = 4.08-33.30), being part of an ethnic minority (OR = 3.71, CI = 1.59-8.63), and presenting lower anxiety (OR = 0.58, CI = 0.36-0.94) were the only factors specifically associated with suicide attempt compared to ideation. CONCLUSION: Close monitoring of patients who recently attempted suicide, live alone, are part of an ethnic minority, and present with affective and positive symptomatology may help reduce the risk of suicide-related outcomes during early intervention programs.

Amelioration of Cognitive and Olfactory System Deficits in APOE4 Transgenic Mice with DHA Treatment.

Olfactory dysfunction and atrophy of olfactory brain regions are observed early in mild cognitive impairment and Alzheimer disease. Despite substantial evidence showing neuroprotective effects in MCI/AD with treatment of docosahexaenoic acid (DHA), an omega-3 fatty acid, few studies have assessed DHA and its effects on the olfactory system deficits. We therefore performed structural (MRI), functional (olfactory behavior, novel object recognition), and molecular (markers of apoptosis and inflammation) assessments of APOE4 and wild-type mice ± DHA treatment at 3, 6, and 12 months of age. Our results demonstrate that APOE4 mice treated with the control diet show recognition memory deficits, abnormal olfactory habituation, and discrimination abilities and an increase in IBA-1 immunoreactivity in the olfactory bulb. These phenotypes were not present in APOE4 mice treated with a DHA diet. Alterations in some brain regions' weights and/or volumes were observed in the APOPE4 mice and may be due to caspase activation and/or neuroinflammatory events. These results suggest that the consumption of a diet rich in DHA may provide some benefit to E4 carriers but may not alleviate all symptoms.