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Background and Hypothesis: The nature of the robust association between cannabis use and schizophrenia remains undetermined. Plausible hypotheses explaining this relationship include the premise that cannabis use causes schizophrenia, increased liability for schizophrenia increases the risk of cannabis use initiation (eg, self-medication), or the bidirectional causal hypothesis where both factors play a role in the development of the other. Alternatively, factors that confound the relationship between schizophrenia and cannabis use may explain their association. Externalizing behaviors are related to both schizophrenia and cannabis use and may influence their relationship., Study Design: This study aimed to evaluate whether externalizing behaviors influence the genetic relationship between cannabis use and schizophrenia. We conducted a multivariate genome-wide association analysis of 6 externalizing behaviors in order to construct a genetic latent factor of the externalizing spectrum. Genomic structural equation modeling was used to evaluate the influence of externalizing behaviors on the genetic relationship between cannabis use and schizophrenia., Results: We found that externalizing behaviors partially explained the association between cannabis use and schizophrenia by up to 42%., Conclusions: This partial explanation of the association by externalizing behaviors suggests that there may be other unidentified confounding factors, alongside a possible direct association between schizophrenia and cannabis use. Future studies should aim to identify further confounding factors to accurately explain the relationship between cannabis use and schizophrenia., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To identify and describe the available literature quantifying the economic burden associated with the negative symptoms of schizophrenia., Methods: A search of five electronic databases (Medline, PsycINFO, EconLit, CINAHL, EMBASE) and hand searches of bibliographies was conducted to identify all relevant articles written in English and published from date of database inception to January 2021. Search strategies included terms for schizophrenia, negative symptoms, direct and indirect costs and health-care resource utilisation. Quality assessment of included articles was undertaken using a standardised checklist for the evaluation of cost of illness studies. Annual costs were converted to 2022 Australian dollars (A$)., Results: Four hundred and thirty-six abstracts were identified for inclusion. Following screening, six unique studies utilizing data from 6293 participants with an average age of 40 were identified to inform the review. Study quality was high for four studies. All studies concluded there was a positive relationship between negative symptoms and costs or resource utilisation. Four studies providing cost data show an increase in direct costs per annum associated with negative symptoms (range A$ 4046 to 171,564). The wide range in costs was attributable to between study differences in patient characteristics and cohorts, included costs, and country of study., Conclusion: Health care costs and resource utilisation are associated with negative symptoms in people with schizophrenia. Heterogeneity prevented calculation of an overall dollar value per point increase in negative symptoms. Future research is warranted to further quantify the relationship between negative symptoms and costs, including health sector and societal., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Schizophrenia is a persistent psychotic disorder often accompanied by severe disability and premature mortality. New pharmacological treatments are urgently needed. Sodium benzoate, a common food preservative holds potential to be an effective, accessible treatment for schizophrenia, though the optimal dosing and mechanism of action of the compound requires further investigation., Methods: Individuals with persistent treatment-refractory schizophrenia (n=52) will be recruited. Patients will be randomised in a 1:1:1:1 ratio to receive treatment of one of three active doses (1000, 2000 or 4000 mg daily) of sodium benzoate or placebo for 6 weeks duration. The primary outcome measurement is change in the Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcome measurements are PANSS subscales, Global Assessment of Function (GAF), Clinical Global Impression (CGI) and Patient Global Impression (PGI-I). Change in concentrations of peripheral amino acids (D-alanine, L-alanine, D-serine, L-serine, glycine and glutamate), plasma sodium benzoate, plasma catalase, 3-nitrotyrosine, malondialdehyde and high-sensitivity C-reactive protein (hs-CRP) will be determined as tertiary measures., Discussion: This trial seeks to build upon previous research indicating potential efficacy of sodium benzoate for reduction of symptoms in individuals with treatment-refractory schizophrenia. The trial aims to improve the understanding of the mechanism of action of the compound., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621000327886 . Registered on 23 March 2021., (© 2021. The Author(s).)

Objectives: Garcinia mangostana Linn. ("mangosteen") pericarp contains bioactive compounds that may target biological pathways implicated in schizophrenia. We conducted a double-blind randomized placebo-controlled trial evaluating the efficacy of adjunctive mangosteen pericarp, compared to placebo, in the treatment of schizophrenia., Methods: People diagnosed with schizophrenia or schizoaffective disorder ( Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ), recruited across 2 sites (Brisbane and Victoria, Australia), were randomized to receive 24 weeks of adjunctive mangosteen pericarp (1,000 mg/day) or matched placebo. The primary outcome measure was the Positive and Negative Symptom Scale total score. Secondary outcomes included positive and negative symptoms, general psychopathology, clinical global severity and improvement, participant reported overall improvement, depressive symptoms, functioning, quality of life, and safety data at 24 and 28 weeks (4 weeks postdiscontinuation). Data were collected from July 2016 to February 2019., Results: Baseline assessments were conducted on 148 people (mangosteen = 74, placebo = 74); data analyses were conducted on 136 (92%) participants with postbaseline data. The treatment group had significantly higher symptom severity compared to placebo, and both groups significantly improved on all symptom, functioning, and quality of life measures over time. No between-group differences were found for the rate of change between baseline and 24 or 28 weeks., Conclusion: Despite promising preclinical and clinical work, our results do not support mangosteen pericarp extract as an adjunctive treatment for schizophrenia or schizoaffective disorder.

Background: Deficits in social cognition are common in people with schizophrenia and are associated with impaired functioning. Finding effective interventions to address these deficits is a priority. Social Cognition Interaction Training (SCIT) is a psychosocial intervention that has demonstrated acceptability and feasibility in various health care settings. Larger, well-designed randomized controlled trials are needed to examine the effectiveness of this intervention., Design: A randomized controlled trial., Methods: One hundred and twenty adults diagnosed with schizophrenia spectrum disorder were randomized to receive SCIT (n = 61) or Befriending Therapy (BT) (n = 59). Both intervention groups were delivered weekly for 2 hr over 12 weeks. Neurocognitive assessment was completed at baseline. Participants completed assessments of social cognition, social functioning, and meta-cognition at baseline, post-intervention, and 3-month follow-up., Results: There were no clinically significant differences between group outcomes on any measure of social cognition or social functioning. There was a trend for both groups to improve over time but not at a level of statistical significance., Conclusions: SCIT did not show any additional benefits on measures of social cognition compared to Befriending Therapy for people with schizophrenia spectrum disorder. The findings are discussed in terms of potential improvements to the programme., Practitioner Points: Effective interventions for the social cognitive deficits of schizophrenia spectrum disorders are still being refined. Social Cognition Interaction Training is a promising therapy but requires further modifications to improve its effectiveness., (© 2020 The Authors. British Journal of Clinical Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Objective: Muscarinic receptor dysfunction has been suggested to play an important role in the pathophysiology of schizophrenia. Recently, it has also become clear that immune reactivity directed against neurotransmitter receptors may play a pathogenic role in some cases of schizophrenia. The aim of this review is to summarize the case for muscarinic receptor dysfunction in schizophrenia and the evidence supporting the hypothesis that this dysfunction is related to the development of muscarinic receptor-targeting antibodies., Method: The article reviews studies of muscarinic receptors and the presence and potential role(s) of anti-muscarinic acetylcholine receptor antibodies in people with schizophrenia., Results: There is accumulating evidence that altered or deficient muscarinic signalling underlies some of the key clinical features of schizophrenia. Although the number of studies investigating anti-muscarinic acetylcholine receptor antibodies in schizophrenia is relatively small, they consistently demonstrate that such antibodies are present in a proportion of patients. This evidence suggests that these antibodies could have pathogenic effects or exist as a biomarker to an unknown pathophysiological process in schizophrenia., Conclusion: The presence of elevated levels of anti-muscarinic acetylcholine receptor antibodies may identify a subgroup of people with schizophrenia, potentially informing aetiopathogenesis, clinical presentation and treatment. To date, all studies have examined antibodies in participants with chronic schizophrenia, who have likely received antipsychotic medication for many years. As these medications modulate immune functions and regulate receptor densities, it is recommended that future studies screen for the presence of anti-muscarinic antibodies in people experiencing their first episode of psychosis.

People with schizophrenia often experience difficulties with prospective memory (PM), but few empirical studies have directly compared the effectiveness of different types of reminders in remediating these difficulties. In the present study, two distinct types of reminders were compared to a standard (no reminder) condition in outpatients with schizophrenia (n = 30) and controls (n = 30). Using an adapted version of the well-validated laboratory PM measure, Virtual Week, participants were asked to complete three different conditions (counterbalanced), in which they were (i) provided with access to self-initiated reminders, (ii) provided with experimenter-initiated reminders, and (iii) completed a standard (no-reminder) condition. Both groups benefited from the provision of reminders, but self-initiated reminders were the most beneficial, particularly for time-based tasks. These data align with a broader literature that shows PM can be enhanced by the use of reminders. However, it extends this literature in an important way by showing that these benefits are equivalent for people with schizophrenia, and may be greatest where access to reminders is self-initiated. The implications of these data for the development of rehabilitative interventions are discussed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Cross-sectional studies have suggested inhalant use is associated with psychosis. This association was examined in a longitudinal study accounting for other substance use and potential confounders., Methods: We used a prospective sample (N = 6542) from the Northern Finland Birth Cohort 1986. Self-report questionnaires on substance use and psychotic experiences were completed when the cohort members were 15-16 years old. Inhalant use was categorized into four groups (never, once, 2-4 times, 5 times or more). Subsequent psychosis diagnoses (ICD-10) until age 30 years were obtained from national registers. Cox regression analysis was used to examine the association between adolescent inhalant use and risk of psychosis., Results: During the observation period 124 individuals were diagnosed with incident psychosis. Overall, there were 225 (3.4%) subjects with any inhalant use, 18 (8.0%) of whom were diagnosed with psychosis during the follow up. Of non-inhalant users (n = 6317) 106 (1.7%) were diagnosed with psychosis. Compared to non-users, those using inhalants had increased risk of incident psychosis with most frequent inhalant use associated with the greatest risk (unadjusted HR = 9.46; 3.86-23.20). After adjusting for baseline psychotic experiences, other substance use, comorbid mental disorder and parental substance abuse, the increased risk of psychosis persisted (HR = 3.06; 1.05-8.95). Furthermore, a dose-response effect between inhalant use and risk of psychosis was identified (OR = 2.34; 1.83-2.99)., Conclusions: Inhalant use in adolescence was independently associated with incident psychosis. The adverse health outcomes associated with adolescent inhalant use provide compelling reasons for implementation of policies to reduce the use of volatile substances in adolescents., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Introduction: The global burden of disease (GBD) studies have derived detailed and comparable epidemiological and burden of disease estimates for schizophrenia. We report GBD 2016 estimates of schizophrenia prevalence and burden of disease with disaggregation by age, sex, year, and for all countries., Method: We conducted a systematic review to identify studies reporting the prevalence, incidence, remission, and/or excess mortality associated with schizophrenia. Reported estimates which met our inclusion criteria were entered into a Bayesian meta-regression tool used in GBD 2016 to derive prevalence for 20 age groups, 7 super-regions, 21 regions, and 195 countries and territories. Burden of disease estimates were derived for acute and residual states of schizophrenia by multiplying the age-, sex-, year-, and location-specific prevalence by 2 disability weights representative of the disability experienced during these states., Findings: The systematic review found a total of 129 individual data sources. The global age-standardized point prevalence of schizophrenia in 2016 was estimated to be 0.28% (95% uncertainty interval [UI]: 0.24-0.31). No sex differences were observed in prevalence. Age-standardized point prevalence rates did not vary widely across countries or regions. Globally, prevalent cases rose from 13.1 (95% UI: 11.6-14.8) million in 1990 to 20.9 (95% UI: 18.5-23.4) million cases in 2016. Schizophrenia contributes 13.4 (95% UI: 9.9-16.7) million years of life lived with disability to burden of disease globally., Conclusion: Although schizophrenia is a low prevalence disorder, the burden of disease is substantial. Our modeling suggests that significant population growth and aging has led to a large and increasing disease burden attributable to schizophrenia, particularly for middle income countries.

Objective: Social Cognition and Interaction Training (SCIT) has demonstrated effectiveness in improving social cognition and functioning of people with schizophrenia. This pilot study examines the acceptability, feasibility, and effectiveness of SCIT with individuals who have schizophrenia-spectrum disorders and are receiving care through a public mental health service., Method: In a pragmatic randomized waitlist controlled trial, 36 participants (aged 19-55 years) with a schizophrenia spectrum disorder were randomly allocated to SCIT or treatment as usual (TAU). Measures of theory of mind, emotion perception, attributional bias, social skills, quality of life, life skills, depression, anxiety, and stress were administered pre- and post-intervention with follow-up conducted 4 months later. All wait-list controls subsequently received the intervention and a secondary within-group analysis was conducted including these participants., Results: While no significant differences were found between groups on any outcomes, there was strong engagement with the SCIT intervention. Of the 21 participants in the intervention group, the completion rate was 85.71% with a median attendance rate of 17 sessions. Within subject analyses of SCIT participants over time showed significant improvements in quality of life, emotion recognition, social skills, and a trend towards better life skills from pre- to post-intervention. These gains were sustained at the 4-month follow-up time., Conclusions and Implications for Practice: Although this study showed limited benefits in outcomes associated with SCIT compared with TAU, it demonstrated the acceptability of SCIT to participants in a real world public health setting shown by high retention, attendance, and positive feedback. This pilot shows SCIT can be implemented in routine clinical practice and lays the foundation for a larger pragmatic study., Practitioner Points: SCIT can be implemented successfully in a real-world community mental health setting. SCIT had high levels of acceptability to these participants. Limitations The small sample size meant there was insufficient power to detect differences between groups on outcome measures. The study did not include measures of psychiatric symptoms or neuropsychological functioning which may have influenced participants' capacity to benefit from SCIT., (© 2017 The British Psychological Society.)

Background: Despite electroconvulsive therapy being one of the most effective treatments in psychiatry, few studies report trends in the provision of electroconvulsive therapy over time. This study aims to investigate the use of electroconvulsive therapy between 2009 and 2020 in an Australian public tertiary mental health facility, and to describe the electroconvulsive therapy patient population and change in courses of treatment. Methods: Routinely collected data for 677 patients who received 1669 electroconvulsive therapy courses of treatment at an Australian public tertiary mental health facility between 2009 and 2020 were examined. Results: The provision of acute electroconvulsive therapy was stable across the study period; however, the number of maintenance electroconvulsive therapy courses commenced declined over the study. Schizophrenia was the most common indication for index treatment (37.4%). The majority of patients (85.7%) received acute electroconvulsive therapy only. Voluntary provision of electroconvulsive therapy declined over the study period, reducing from 44.9% in 2009 to 16.3% in 2020. Conclusion: Over the study period, there was a significant reduction in the number of maintenance electroconvulsive therapy courses commenced, and a large increase in involuntary treatment. The provision of electroconvulsive therapy was more likely to occur in males with a diagnosis of schizophrenia. Further studies are needed to generate a greater understanding of the factors influencing the provision of electroconvulsive therapy within differing geographical, social and healthcare landscapes. [ABSTRACT FROM AUTHOR]

Objective: The 22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion in humans with over 180 phenotypic expressions. Approximately 30–40% of affected individuals will develop psychosis and 25% meet the criteria for schizophrenia. Despite this, pharmacotherapy for managing psychosis in 22q11.2DS is poorly understood and 22q11.2DS psychosis is frequently labelled as treatment resistant. The objectives of this paper are to evaluate the effectiveness and tolerability of pharmacotherapy for 22q11.2DS psychosis and evaluate the evidence for treatment resistance. Method: A systematic search was performed using CINAHL, The Cochrane Library (Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials and Cochrane Clinical Answers), EMBASE, PsycINFO, PubMed, Scopus and Web of Science Core Collection from inception to December 2022. It yielded 39 case reports, 6 case series and 1 retrospective study which met the inclusion criteria. Results: Based on the current literature, individuals with 22q11.2DS psychosis experience a greater rate of medical co-morbidities such as cardiac arrhythmias, seizures and movement disorders, which complicate pharmacotherapy. Poor tolerability rather than poor clinical response motivates the switching of antipsychotics, which may explain the labelling of treatment resistance in the literature. Conclusion: There are insufficient data to recommend a single antipsychotic for 22q11.2DS psychosis. Nonetheless, with proactive management of co-morbidities, antipsychotic medication in 22q11.2DS psychosis is an effective treatment commonly resulting in improvement in quality of life. [ABSTRACT FROM AUTHOR]

Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) is the most common enzymopathy globally. Early studies suggested an association with severe psychotic illness; however, changes to laboratory testing and diagnostic classification renders the association unclear. This study aims to explore the interaction between G6PD deficiency and psychotic symptoms, in particular to identify specific patterns of presentation or impact on outcomes. Pubmed, Embase, and PsycInfo databases were searched from inception to May 2023. Descriptive statistics and narrative review of were used to synthesise data on demographics, mental and physical health diagnoses, investigations, treatment, and outcomes. No clear link was found in published data (eight case reports, case series of n = 29) with a high rate (63%) of haemolytic crisis at the time of psychiatric presentation suggested delirium as an alternative diagnosis. Four case control studies found no significant difference in the prevalence of G6PD deficiency. However, catatonic presentation was reported in 40% of the case series and a higher prevalence of G6PD deficiency in catatonic schizophrenia was noted in case control studies. Based on the information available there was no clear association between G6PD deficiency and psychotic illness or treatment resistance, although paucity of studies and risk of bias limit strong conclusions. [ABSTRACT FROM AUTHOR]

People with psychotic disorders commonly feature broad decision-making impairments that impact their functional outcomes. Specific associative/reinforcement learning problems have been demonstrated in persistent psychosis. But these phenotypes may differ in early psychosis, suggesting that aspects of cognition decline over time. The present proof-of-concept study examined goal-directed action and reversal learning in controls and those with early psychosis. Equivalent performance was observed between groups during outcome-specific devaluation, and reversal learning at an 80:20 contingency (reward probability for high:low targets). But when the low target reward probability was increased (80:40) those with early psychosis altered their response to loss, whereas controls did not. Computational modelling confirmed that in early psychosis there was a change in punishment learning that increased the chance of staying with the same stimulus after a loss, multiple trials into the future. In early psychosis, the magnitude of this response was greatest in those with higher IQ and lower clinical severity scores. We show preliminary evidence that those with early psychosis present with a phenotype that includes altered responding to loss and hyper-adaptability in response to outcome changes. This may reflect a compensatory response to overcome the milieu of corticostriatal changes associated with psychotic disorders. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Impairments in the expression, experience, and recognition of emotion are common in early psychosis (EP). Computational accounts of psychosis suggest disrupted top-down modulation by the cognitive control system (CCS) on perceptual circuits underlies psychotic experiences, but their role in emotional deficits in EP is unknown. Study Design The affective go/no-go task was used to probe inhibitory control during the presentation of calm or fearful faces in young persons with EP and matched controls. Computational modeling of functional magnetic resonance imaging (fMRI) data were performed using dynamic causal modeling (DCM). The influence of the CCS on perceptual and emotional systems was examined using parametric empirical bayes. Study Results When inhibiting motor response to fearful faces, EP participants showed higher brain activity in the right posterior insula (PI). To explain this, we used DCM to model effective connectivity between the PI, regions from the CCS activated during inhibition (dorsolateral prefrontal cortex [DLPFC] and anterior insula [AI]), and a visual input region, the lateral occipital cortex (LOC). EP participants exerted a stronger top-down inhibition from the DLPFC to the LOC than controls. Within the EP cohort, increased top-down connectivity between the LOC and AI was associated with a higher burden of negative symptoms. Conclusions Young persons with a recent onset of psychosis show a disturbance in the cognitive control of emotionally salient stimuli and the suppression of irrelevant distractors. These changes are associated with negative symptoms, suggesting new targets for the remediation of emotional deficits in young persons with EP. [ABSTRACT FROM AUTHOR]

Background and Hypothesis The sexual and reproductive health (SRH) of young people with psychosis has been largely overlooked. We hypothesised that there are key deficiencies in the existing literature on the SRH of adolescents and young adults with psychotic disorders. Study Design We conducted a systematic scoping review using Pubmed, Web of Science, Embase, PsycINFO, and CINAHL. We included empirical studies and case reports focused on SRH issues in young people (aged 14–24 years) with psychotic disorders. A qualitative synthesis was completed. Joanna Briggs Institute Critical Appraisal Tools were utilized to assess study quality. Study Results Seventeen empirical studies and 52 case reports met inclusion criteria. Most focused on sexual dysfunction which was identified as common among this cohort and associated with both psychotic disorders and antipsychotics. The study population was more likely to engage in sexual risk-taking behavior and was at higher risk of sexually transmissible infections than those without psychosis. SRH topics of clinical relevance in older patients with psychosis such as pregnancy, abortion, sexual violence, coercion, sexual identity, and gender were poorly addressed in this younger group. We found empirical studies generally lacked identification and controlling of confounders whilst case reports provided limited description of mental health and SRH outcomes following clinical intervention. Conclusion Research and clinical practice addressing sexual and reproductive health is needed for young people living with psychosis. To address research gaps future studies should focus on women's health, sexual violence, gender, and sexuality in young people with psychosis. [ABSTRACT FROM AUTHOR]

Objective: To discuss challenges with the diagnosis of autoimmune psychosis (AP) in people with chronic psychotic disorders.Method: We present a case of a 23-year-old man with an exacerbation of treatment-refractory psychosis after receiving intravenous immunoglobulin (IVIG) for suspected AP, diagnosed 4 years after the onset of psychosis. We highlight the diagnostic and management challenges in such cases.Results: The diagnosis of AP in people with long-standing illness relies on the interpretation of non-specific clinical and laboratory findings in individuals with psychosocial problems and challenges of acceptance and adherence to complex medical investigations and treatments. Equivocal results from investigations undertaken without logical clinical reasoning can lead to inappropriate interventions that are costly and can cause iatrogenic harm.Conclusion: Psychiatrists should restrict screening for antineuronal antibodies in people with chronic psychosis to those with higher risk features such as persistent treatment refractory symptoms with concurrent neurological signs and symptoms. Further research informing the clinical circumstances for antineuronal antibody testing is needed. [ABSTRACT FROM AUTHOR]

New treatments are urgently needed for serious mental illnesses including bipolar disorder and schizophrenia. This review proposes that Garcinia mangostana Linn. (mangosteen) pericarp is a possible adjunctive therapeutic agent for these disorders. Research to date demonstrates that neurobiological properties of the mangosteen pericarp are well aligned with the current understanding of the pathophysiology of bipolar disorder and schizophrenia. Mangosteen pericarp has antioxidant, putative neuroprotective, anti-inflammatory, and putative mitochondrial enhancing properties, with animal studies demonstrating favorable pharmacotherapeutic benefits with respect to these disorders. This review summarizes evidence of its properties and supports the case for future studies to assess the utility of mangosteen pericarp as an adjunctive treatment option for mood and psychotic disorders. [ABSTRACT FROM AUTHOR]

There has been emerging evidence of an association between tobacco smoking and schizophrenia spectrum disorders (SSD). Two meta-analyses have reported that people who smoke tobacco have an ~2-fold increased risk of incident schizophrenia or psychosis, even after adjusting for confounding factors. This study aimed to critically appraise the research which has examined the association between tobacco smoking and SSD against the Bradford Hill criteria for causality, to determine the strength of the evidence for a causal relationship. Eight longitudinal studies (seven cohort studies and one case control study) were identified which examined tobacco smoking as an exposure and psychosis as an outcome. All seven cohort studies were assessed as being of high quality using the Newcastle-Ottawa Scale. Six of the eight studies found a statistically significant positive association between tobacco smoking and onset of SSD. These studies reported a consistent association with a moderate to large effect size and a dose response relationship. The studies adjusted for multiple potential confounders including age, sex, socioeconomic status, shared genetic risk, prodromal symptoms, and comorbid cannabis and other substance use. The studies did not adjust for exposure to childhood trauma or prenatal tobacco. There was substantial though inconclusive evidence supporting a causal relationship between tobacco smoking and increased risk of SSD. If a causal relationship does exist, nicotine is most likely responsible for this association. This raises serious public health concerns about the increasing use of e-cigarettes and other products, particularly by adolescents whose nicotine use may increase their risk of SSD. Research is urgently needed to examine the association between e-cigarette use and incident psychosis, particularly in adolescents and young adults. [ABSTRACT FROM AUTHOR]