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Objective: Social interactions and experiences are increasingly occurring online, including for young adults with psychosis. Healthy social interactions and experiences are widely recognized as a critical component of social recovery, yet research thus far has focused predominantly on offline interactions with limited understanding of these interactions online. We developed the Social Media and Internet sociaL Engagement (SMILE) questionnaire to assess the type, frequency, and nature of online social interactions and experiences among young adults with early psychosis to better assess online social activity and ultimately support personalized interventions. Methods: Participants (N = 49) completed the SMILE questionnaire which asked about online platforms used, frequency of use, and if positive and negative experiences were more likely to happen online or offline. Participants completed additional self-report measures of victimization, positive psychotic symptoms, social functioning, and demographics. Exploratory factor analysis and correlations between identified factors and clinical measures of interest were completed. Results: Exploratory factor analysis revealed three factors: positive engagement, victimization, and internalizing experiences. Most participants (6%-37%) experienced positive engagement offline. Victimization occurred equally online and offline (8%-27% and 4%-24%, respectively). Most participants (37%-51%) endorsed internalizing experiences as occurring equally offline and online, but approximately a third of participants reported internalizing experiences more frequently offline (20%-35%). Victimization was moderately (r = 0.34) correlated with overall online social experiences, suggesting more online time may increase the likelihood of victimization. Age was inversely related to the frequency of overall online social experiences. Conclusion: Young adults with early psychosis experience positive and negative social experiences online and offline. New scales and measures to comprehensively assess the nature and function of online social interactions and experiences are needed.

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BACKGROUND: Schizophrenia is a disorder associated with neurocognitive deficits that adversely affect daily functioning and impose an economic burden. Cognitive rehabilitation interventions, particularly during the early phases of illness, have been shown to improve cognition, functionality, and quality of life. The Feuerstein Instrumental Enrichment (FIE) program, based on the Mediated Learning Experience and the Structural Cognitive Modifiability theory, has been applied in various disorders, but its applicability in schizophrenia has not yet been clarified. OBJECTIVE: This study aims to investigate the effects of the FIE program on the functionality of patients with first-episode schizophrenia. METHODS: In total, 17 patients will be recruited for an open-label intervention consisting of twice-weekly sessions for 10 weeks. The primary outcome measure will be changes in the Goal Achievement Scale score. Maze task performance from the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery will serve as a secondary outcome measure. At the same time, changes in Positive and Negative Syndrome Scale scores and other MATRICS domains will be analyzed as exploratory outcomes. Assessments will be administered before and after the intervention, with a follow-up period of 6 months. RESULTS: This trial was preregistered in The Brazilian Registry of Clinical Trials (RBR-4gzhy4s). By February 2024, 11 participants were enrolled in the training. Recruitment is expected to be completed by May 2024. Data analysis will be conducted between May and September 2024. The results are expected to be published in January 2025. CONCLUSIONS: This study may establish a protocol for the FIE program that uses mediation techniques for individuals in the early stages of schizophrenia. The results will add to the knowledge about strategies to promote cognitive skills and functional impairment in daily life. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57031.

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PURPOSE: The influence of rurality on the duration of untreated psychosis (DUP) in first-episode psychosis (FEP) is poorly understood. We investigated factors associated with FEP in rural/urban settings and whether there are rural/urban differences in DUP and the mode (speed) of onset of psychosis. METHODS: We used the Cambridgeshire and Peterborough NHS Foundation Trust Research Database (CPFTRD) to identify all persons presenting to an early intervention for psychosis service with FEP between 2013 and 2015. We performed descriptive statistics and multivariable linear and multinomial regression to assess the relationships between the study outcomes and the independent variables. RESULTS: One hundred and fifty-five FEP patients were identified, with a mean age of 23.4 (SD, 5.3) years. The median DUP was 129.0 (IQR: 27.5-524.0) days. In rural areas, FEP patients were more likely to be employed and live with family than those in urban areas. A longer DUP was observed among patients with an insidious onset of psychosis compared with an acute onset (619.5 (IQR: 333.5-945.0)) vs. (17.0 (IQR: 8.0-30.5)) days respectively, p < 0.0001. We found evidence that the mode of onset of psychosis differed by employment status and living circumstances. There was insufficient evidence of rural/urban differences in DUP and mode of onset of psychosis. CONCLUSIONS: Our results suggest that the mode of onset of psychosis is an important indicator of treatment delay and could provide vital information for service planning and delivery. Sociodemographic variations in FEP exist in rural populations, and our findings are similar to those observed in urban settings.

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Substance-induced psychosis (SIP) is characterized by both substance use and a psychotic state, and it is assumed that the first causes the latter. In ICD-10 the diagnosis is categorized as and grouped together with substance use disorders, and to a large extent also treated as such in the health care system. Though criticism of the diagnostic construct of SIP dates back several decades, numerous large and high-quality studies have been published during the past 5-10 years that substantiate and amplify this critique. The way we understand SIP and even how we name it is of major importance for treatment and it has judicial consequences. It has been demonstrated that substance use alone is not sufficient to cause psychosis, and that other risk factors besides substance use are at play. These are risk factors that are also known to be associated with schizophrenia spectrum disorders. Furthermore, register-based studies from several different countries find that a large proportion, around one in four, of those who are initially diagnosed with an SIP over time are subsequently diagnosed with a schizophrenia spectrum disorder. This scoping review discusses the construct validity of SIP considering recent evidence. We challenge the immanent causal assumption in SIP, and advocate that the condition shares many features with the schizophrenia spectrum disorders. In conclusion, we argue that SIP just as well could be considered a first-episode psychotic disorder in patients with substance use.

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BACKGROUND: People experiencing psychosis are at greater risk of physical health conditions and premature mortality. It is likely that Indigenous Maori youth, who experience additional systemic inequities caused by settler-colonisation, face even greater physical health and mortality risks following a diagnosis of first-episode psychosis. OBJECTIVE: Compare Maori and non-Maori for risk of hospitalisation and mortality for up to 15 years following first-episode psychosis diagnosis. METHODS: A cohort (N = 14,122) of young people (16-24 years) with first-episode psychosis diagnosis between 2001 and 2019 were identified. Using crude Kaplan-Meier and adjusted Cox proportional hazards models, Maori (n = 5211) and non-Maori (n = 8911) were compared on hospitalisation and mortality outcomes for up to 15 years. RESULTS: In the 15 years following first-episode psychosis diagnosis, Maori had higher adjusted risk of all-cause mortality (hazard ratio = 1.21, 95% confidence interval = [1.01, 1.45]), hospitalisation with diabetes (hazard ratio = 1.44, 95% confidence interval = [1.15, 1.79]), injury/poisoning (hazard ratio = 1.11, 95% confidence interval = [1.05, 1.16]), general physical health conditions (hazard ratio = 1.07, 95% confidence interval = [1.02, 1.13]) and also appeared to be at greater risk of cardiovascular hospitalisations (hazard ratio = 1.34, 95% confidence interval = [0.97, 1.86]). Kaplan-Meier plots show hospitalisation and mortality inequities emerging approximately 4-7 years following first-episode psychosis diagnosis. CONCLUSIONS: Maori are at greater risk for hospitalisation and premature mortality outcomes following first-episode psychosis. Early screening and intervention, facilitated by culturally safe health service delivery, is needed to target these inequities early.

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Introduction: Research data show the impact of the endocannabinoid system on psychosis through its neurotransmission homeostatic functions. However, the effect of the endocannabinoid system genetic variability on the relationship between cannabis use and psychosis has been unexplored, even less in first-episode patients. Here, through a case-only design, we investigated the effect of cannabis use and the genetic variability of endocannabinoid receptors on clinical and cognitive outcomes in first-episode psychosis (FEP) patients. Methods: The sample comprised 50 FEP patients of European ancestry (mean age (sd) = 26.14 (6.55) years, 76% males), classified as cannabis users (58%) or cannabis non-users. Two Single Nucleotide Polymorphisms (SNP) were genotyped at the cannabinoid receptor type 1 gene (CNR1 rs1049353) and cannabinoid receptor type 2 gene (CNR2 rs2501431). Clinical (PANSS, GAF) and neuropsychological (WAIS, WMS, BADS) assessments were conducted. By means of linear regression models, we tested the main effect of cannabis use and its interaction with the polymorphic variants on the clinical and cognitive outcomes. Results: First, as regards cannabis effects, our data showed a trend towards more severe positive symptoms (PANSS, p = 0.05) and better performance in manipulative abilities (matrix test-WAIS, p = 0.041) among cannabis users compared to non-users. Second, concerning the genotypic effects, the T allele carriers of the CNR1 rs1049353 presented higher PANSS disorganization scores than CC homozygotes (p = 0.014). Third, we detected that the observed association between cannabis and manipulative abilities is modified by the CNR2 polymorphism (p = 0.022): cannabis users carrying the G allele displayed better manipulative abilities than AA genotype carriers, while the cannabis non-users presented the opposite genotype-performance pattern. Such gene-environment interaction significantly improved the overall fit of the cannabis-only model (Δ-R2 = 8.4%, p = 0.019). Discussion: Despite the preliminary nature of the sample, our findings point towards the role of genetic variants at CNR1 and CNR2 genes in the severity of the disorganized symptoms of first-episode psychosis and modulating cognitive performance conditional to cannabis use. This highlights the need for further characterization of the combined role of endocannabinoid system genetic variability and cannabis use in the understanding of the pathophysiology of psychosis.

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AIM: To analyze the clinical, neurocognitive, and functional impact of prolactin levels according to sex in patients with a First Episode Psychosis (FEP). METHODS: We measured prolactin levels in 221 non-affective FEP patients treated with antipsychotics (AP) and 224 healthy controls, at baseline and 2-year follow-up. We examined whether the relationships between clinical and functional variables were mediated by prolactin, controlling for antipsychotic use, according to sex. RESULTS: Prolactin levels were higher in patients when compared to controls at both time points. Baseline factors associated with prolactin were chlorpromazine equivalents, attention, and executive functioning. In the FEP group, prolactin levels were associated with functioning and diminished expression in males, and with working memory in females. Prolactin levels (p=0.0134) played a role as a mediator between negative symptomatology (p=0.086) and functional outcome (p=0.008) only in FEP male patients at baseline. CONCLUSIONS: Prolactin plays a role in the functionality and clinical symptomatology of FEP patients. Our results suggest that pharmacological counselling in patients with hyperprolactinemia at baseline and negative symptomatology might improve their functional and clinical outcomes.

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BACKGROUND: In Australia, the first nationwide COVID-19 lockdown occurred in March 2020 bringing challenges for early intervention psychosis (EIP) services. Limited evidence exists on the impacts of the pandemic on treatment outcomes among EIP clients. METHODS: This prospective cohort study analysed routine data from 15 headspace Early Psychosis centres in Australia. Participants were 12 to 25 years, meeting criteria for First Episode Psychosis (FEP) or Ultra High Risk of psychosis (UHR) comparing those who commenced treatment 'pre-COVID-19' (between 16th August 2018 and 15th August 2019), and 'during-COVID-19' (between 1st March 2020 and 15th September 2020). Clinical symptoms at treatment commencement were assessed using the Brief Psychiatric Rating Scale (BPRS) and the Kessler Psychological Distress Scale (K10). with outcomes after 6 months compared between cohorts using linear mixed-effects regression, controlling for confounders. RESULTS: Of 1246 young people analysed (653 FEP, 596 UHR), significant improvements were observed with treatment in both groups (5 to 13-point reduction in BPRS score per 6-months treatment). Treatment effectiveness reduced during-COVID-19 for psychosis symptoms, with the FEP BPRS treatment effect lower by 4.3 points (95%CI: 0.5, 8.1). UHR clients had lower BPRS negative symptoms during-COVID-19 (p = 0.020). Service contacts increased during-COVID-19, with increased telehealth services (p < 0.001). CONCLUSIONS: Early intervention remained effective for FEP and UHR, despite the pandemic and transition of EIP services to virtual service delivery. Reduced treatment efficacy in FEP psychosis symptoms may indicate potential limitations of telehealth. Further research to examine longer term clinical and functional outcomes due to the pandemic is required.

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Background: Research has established a relationship between psychosis and physical harm in the early course of psychosis. However, little is known about the relationship between specific psychosis symptoms, such as hearing voices, and physical harm. Objective: This study aimed to determine the prevalence and typology of physical harm related to hearing voices, as well as what aspects of the voice-hearing experience retrospectively predicted incidents of harm within an Early Intervention in Psychosis Service (EIPS). Methods: We conducted a quality improvement project in a single EIPS. We reviewed case notes of patients and extracted information on the cognitive-phenomenological features of the voices patients heard, as well as any incidents of physical harm that were causally linked to these voices. Results: It was found that 32.2% of EI patients had an actual incident of physical harm in their case notes that was causally linked to hearing voices. The most common type of physical harm was neglect. In terms of cognitive phenomenological binary correlations that retrospectively predicted physical harm in the case notes, patients were 20 and 7 times more likely to have harmed themselves if they heard self-harm commands (i.e., directions to harm themselves physically) and perceived the voice as omnipotent, respectively. Patients were 6 times more likely to have harmed someone else if they heard violent commands. Conclusion: Verbal auditory hallucinations commonly influence physical harm in the early course of psychosis. Hearing commands and/or believing the voice to be omnipotent are strong retrospective-correlative predictors that may aid in the assessment and therapeutic intervention.

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Background: Evidence suggests inflammation plays a role in the pathophysiology of psychosis even in early illness, indicating a potential avenue for anti-inflammatory interventions that simultaneously address high rates of metabolic disease in this population. The aim of this study is to design a novel anti-inflammatory diet intervention (DI) that is feasible to implement in a first-episode psychosis (FEP) population. Methods: Eligible FEP Participants are aged 15-30. The DI is currently being refined through a multi-phase process that includes the recruitment of focus groups that provide insight into feasibility of measures and nutritional education, as well as the implementation of the DI. The phases in the study are the Development Phase, Formative Phase, and the Feasibility Phase. Results: The Development phase has resulted in the creation of a flexible DI for FEP based on existing research on nutritional health and informed by providers. This study has just completed the Formative phase, recruiting eligible participants to join focus groups that gleaned information about dietary habits, preferences, and food environments to further refine the DI. Conclusion: Findings from earlier phases have advised the current Feasibility Phase in which this novel DI is being administered to a small cohort of FEP participants (N = 12) to determine acceptability of the DI from a lived experience perspective. Naturalistic changes in inflammatory biomarkers, metabolic health, and symptoms will also be measured.

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Background and Hypothesis: Schizophrenia is associated with white matter disruption and topological reorganization of cortical connectivity but the trajectory of these changes, from the first psychotic episode to established illness, is poorly understood. Current studies in first-episode psychosis (FEP) patients using diffusion magnetic resonance imaging (dMRI) suggest such disruption may be detectable at the onset of psychosis, but specific results vary widely, and few reports have contextualized their findings with direct comparison to young adults with established illness. Study Design: Diffusion and T1-weighted 7T MR scans were obtained from N = 112 individuals (58 with untreated FEP, 17 with established schizophrenia, 37 healthy controls) recruited from London, Ontario. Voxel- and network-based analyses were used to detect changes in diffusion microstructural parameters. Graph theory metrics were used to probe changes in the cortical network hierarchy and to assess the vulnerability of hub regions to disruption. The analysis was replicated with N = 111 (57 patients, 54 controls) from the Human Connectome Project-Early Psychosis (HCP-EP) dataset. Study Results: Widespread microstructural changes were found in people with established illness, but changes in FEP patients were minimal. Unlike the established illness group, no appreciable topological changes in the cortical network were observed in FEP patients. These results were replicated in the early psychosis patients of the HCP-EP datasets, which were indistinguishable from controls in most metrics. Conclusions: The white matter structural changes observed in established schizophrenia are not a prominent feature in the early stages of this illness.

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Background Psychotic disorders are commonly diagnosed in the mid-20s but symptoms often emerge earlier during late teenage years to mid-20s. Notably, studies have shown that psychotic symptoms can also affect younger individuals, with a higher prevalence among preteens than teens. Head imaging via computed tomography (CT) or magnetic resonance imaging (MRI) can be performed to rule out non-psychiatric causes of psychotic symptoms in this population but may pose additional risks and financial burdens. Practice patterns vary regarding when to utilize head imaging in pediatric patients with first-episode psychosis (FEP). The purpose of this study is to better understand the use of head imaging in pediatric FEP and associated patient characteristics. Methods A retrospective cohort study was performed. Eligible patients were <18 years of age with an encounter documented between 2013 and 2023 where a diagnosis code for psychosis was first applied. Medical records were manually reviewed if head imaging was performed during the index encounter or within one month. Descriptive statistics were used to report the study population demographics. Independent t-testing was used to compare characteristics between patients who did and did not receive head imaging. Results A total of 113 patients met the inclusion criteria for the study, of which 12 (10.6%) received head imaging within the specified timeframe. All received CT criteria head scans, and a significantly higher proportion were African American or Black when compared to those who did not receive head imaging (10/12 (83.3%) vs. 53/101 (52.5%) p=0.023). None of the imaging tests performed yielded significant neurological findings that suggested an underlying pathology for psychosis. Conclusions Head imaging was rarely utilized for the initial assessment of pediatric FEP in this study. When it was used, CT head scans were the modality of choice but did not yield any remarkable findings to suggest a non-psychiatric cause of psychotic symptoms. This adds to the body of evidence supporting a conservative approach when considering head imaging in pediatric FEP.

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Little is known about the individual course of suicidal ideations and attempts (i.e., suicidality) after treatment initiation. We examined the trajectories of suicidality and associated risk factors over a 2-year early intervention program for first-episode psychosis in 450 patients (age range 18-35 years at admission) consecutively admitted from 2003 to 2017. Suicidality was assessed via systematic file review, while sociodemographic and clinical variables were assessed at admission. Latent class growth modelling identified three trajectories: low (69.6 %), initially high (22.9 %), and persistently high (7.6 %) suicidality. Patients who were younger, lived alone and were diagnosed with affective psychosis were significantly more likely to follow the initially high trajectory. Patients who attempted suicide up to 3 months before admission, lived alone and presented lower levels of the PANSS excited factor were significantly more likely to follow the persistently high trajectory. Attempting suicide up to 3 months before admission distinguished persistently high and initially high suicidality trajectories. Suicide risk during early intervention program for first-episode psychosis is heterogenous, with acute and enduring suicidal risk, suggesting the need to adapt suicide prevention strategies to these different risk profiles.

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PURPOSE: Diagnostic stability for people with First Episode Psychosis (FEP) is essential for treatment, but it remains poorly investigated, especially in adolescents and within a prospective design. The aims of this research were: (a) to examine diagnostic change in Italian adolescents with FEP treated within an "Early Intervention in Psychosis" program during a 2-year follow-up period and (b) to investigate any sociodemographic and clinical predictors at baseline. METHODS: At baseline, 66 adolescents with FEP was recruited. Their primary diagnosis was formulated both at baseline and at the end of follow-up. At presentation, FEP adolescents completed the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA). As for diagnostic stability, the Kappa statistic was calculated. The associations of diagnostic change with baseline clinical and sociodemographic features were analyzed using a logistic model with the diagnostic shift as dependent variable. A propensity score was finally calculated based on logistic analysis results. RESULTS: 38 (57.6%) FEP adolescents changed their opening diagnosis. The highest prospective diagnostic stability was for initial diagnosis of schizophrenia (95.4%) and affective spectrum psychoses (75%). Diagnostic instability was high for opening diagnosis of psychosis not otherwise specified, brief psychosis and schizophreniform disorder (100%). The best predictors of diagnostic change were fewer years of education, shorter duration of untreated psychosis and higher baseline levels of psychiatric symptoms. CONCLUSION: Diagnostic stability is crucial for treatment and clinical decision making. Addressing instability in FEP diagnoses is an important challenge for future diagnostic development in early psychosis, especially in adolescence.

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BACKGROUND: Early identification of treatment non-response in first-episode psychosis (FEP) is essential to outcome. Despite indications that exposure to childhood trauma (CT) can have adverse effects on illness severity, its impact on treatment non-response and the interplay with other pre-treatment characteristics is sparsely investigated. We use a lack of clinical recovery as an early indicator of treatment resistance to investigate the relationship between CT and treatment resistance status at one-year follow-up and the potential mediation of this effect by other pre-treatment characteristics. METHODS: This prospective one-year follow-up study involved 141 participants recruited in their first year of treatment for a schizophrenia-spectrum disorder. We investigated clinical status, childhood trauma (CT), premorbid adjustment (PA), and duration of untreated psychosis (DUP) at baseline and clinical status at one-year follow-up. Ordinal regression analyses were conducted to investigate how PA and DUP affected the relationship between CT and one-year outcome in FEP. RESULTS: 45 % of the FEP sample reported moderate to severe CT, with significantly higher levels of CT in the early treatment resistant group compared to participants with full or partial early recovery. Ordinal regression analysis showed that CT was a significant predictor of being in a more severe outcome group (OR = 4.59). There was a partial mediation effect of PA and a full mediation effect of DUP on the effect of CT on outcome group membership. DISCUSSION: Our findings indicate that reducing treatment delays may mitigate the adverse effects of CT on clinical outcomes and support the inclusion of broad trauma assessment in FEP services.

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PURPOSE: Despite the high rates of psychotic disorders amongst people in prison, current prison mental health screening approaches have not included assessment of the full psychosis spectrum to capture those at-risk of an emerging psychosis as well as those with established illness nor assessed the concurrent validity of psychosis symptom screening. METHODS: Using a clinical staging approach to establish the prevalence of Ultra High Risk (UHR), first episode of psychosis (FEP) and established psychosis (EP) groups, 291 adults entering custody in two prison reception centres in NSW completed a two-stage (screening and validation) interview process. The Comprehensive Assessment of At-Risk Mental States (CAARMS) was used to determine the clinical stages of psychosis and concurrent validity of symptom screening in identifying individuals on the psychosis spectrum was formally assessed. RESULTS: Amongst men and women entering prison, almost one quarter (24.1%) met UHR criteria, 5.1% met the FEP threshold and 10.6% had an established psychosis. Those on the psychosis spectrum reported greater disadvantage across sociodemographic and justice factors. The presence of perceptual disturbance and paranoid beliefs emerged as the two best screening items for identifying those with an underlying psychosis spectrum illness. CONCLUSION: The prevalence of psychosis spectrum illness, including the UHR state, amongst those entering prison is high. Current prison mental health approaches should include screening for the presence of perceptual disturbances and paranoid beliefs to improve the detection of psychosis spectrum illness.

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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.

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INTRODUCTION: Suicidal ideation is common among individuals with first episode psychosis (FEP), with prevalence estimates up to 56.5 %. Despite its high prevalence, relatively little is known about how sociodemographic, clinical and/or developmental characteristics contribute to the experience of suicidal ideation in individuals with FEP. METHODS: In this cross-sectional study (FEP n = 551 and controls n = 857), univariate logistic regression analyses were performed to study the associations of sociodemographic, clinical, and developmental factors with suicidal ideation in individuals with FEP as well as controls. Suicidal ideation was assessed using the Community Assessment of Psychic Experiences (CAPE). In addition, multivariate logistic regression analyses were conducted based on a stepwise approach. RESULTS: In FEP, only depressive symptoms remained significantly associated with suicidal ideation when all correlates were integrated into one model. In the multivariate model in controls, depressive symptoms, positive symptoms, and traumatic childhood experiences were significantly associated with suicidal ideation. CONCLUSIONS: This study showed that depressive symptoms are an important factor relating to suicidal ideation in individuals with FEP, over and above other clinical, sociodemographic, and developmental factors. This underscores the relevance of screening for suicidal ideation in individuals with FEP, and highlights the need for a better understanding of the diagnostic uncertainty and course of mood symptoms in early psychosis. LIMITATIONS: Cross-sectional study design, self-reported questionnaires.

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Tobacco smoking is highly prevalent among patients with psychosis and associated with worse clinical outcomes. Neurometabolites, such as glutamate and choline, are both implicated in psychosis and tobacco smoking. However, the specific associations between smoking and neurometabolites have yet to be investigated in patients with psychosis. The current study examines associations of chronic smoking and neurometabolite levels in the anterior cingulate cortex (ACC) in first-episode psychosis (FEP) patients and controls. Proton magnetic resonance spectroscopy (1H MRS) data of 59 FEP patients and 35 controls were analysed. Associations between smoking status (i.e., smoker yes/no) or cigarettes per day and Glx (glutamate + glutamine, as proxy for glutamate) and total choline (tCh) levels were assessed at baseline in both groups separately. For patients, six months follow-up data were acquired for multi-cross-sectional analysis using linear mixed models. No significant differences in ACC Glx levels were found between smoking (n = 28) and non-smoking (n = 31) FEP patients. Smoking patients showed lower tCh levels compared to non-smoking patients at baseline, although not surving multiple comparisons correction, and in multi-cross-sectional analysis (pFDR = 0.08 and pFDR = 0.044, respectively). Negative associations were observed between cigarettes smoked per day, and ACC Glx (pFDR = 0.02) and tCh levels (pFDR = 0.02) in controls. Differences between patients and controls regarding Glx might be explained by pre-existing disease-related glutamate deficits or alterations at nicotine acetylcholine receptor level, resulting in differences in tobacco-related associations with neurometabolites. Additionally, observed alterations in tCh levels, suggesting reduced cellular proliferation processes, might result from exposure to the neurotoxic effects of smoking.

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