Early Psychosis Patients Research Articles

Violent behaviour in early psychosis patients: Can we identify clinical risk profiles?

The objective of this study is to explore, within a sample of early psychosis patients (EPP), if subgroups regarding rate of violent behaviour (VB) against others can be identified on the basis of dynamic risk factors (treatment modifiable characteristics). In a sample of 265 EPP, treated at the Treatment and Early Intervention in Psychosis Program in Lausanne, we conducted a latent-class analysis on the basis of the main dynamic VB risk factors (substance use disorder [SUD], positive symptoms, insight, and impulsivity). VB were restricted to "serious violence" and were assessed through patients self-report, interview with relatives or forensic services and with a standardized instrument. The analysis confirmed the heterogeneity of the sample regarding rate of VB. Patients could be stratified within 4 subgroups, 3 of which were at increased risk of VB. The two groups with the highest rates of VB displayed specific clinical profiles. The first one was characterized by high levels of impulsivity, hostility, positive symptoms and SUD, and the second, by low level of insight and low social functioning. These patterns suggest that significant difficulties in social interaction may contribute to the emergence of aggressive reactions against others. Identification of EPP at increased risk of VB seems possible on the basis of dynamic risk factors. If confirmed prospectively, this could pave the way to the development of preventive strategies and specific interventions.

N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis.

Biomarker-guided treatments are needed in psychiatry, and previous data suggest oxidative stress may be a target in schizophrenia. A previous add-on trial with the antioxidant N-acetylcysteine (NAC) led to negative symptom reductions in chronic patients. We aim to study NAC’s impact on symptoms and neurocognition in early psychosis (EP) and to explore whether glutathione (GSH)/redox markers could represent valid biomarkers to guide treatment. In a double-blind, randomized, placebo-controlled trial in 63 EP patients, we assessed the effect of NAC supplementation (2700 mg/day, 6 months) on PANSS, neurocognition, and redox markers (brain GSH [GSHmPFC], blood cells GSH levels [GSHBC], GSH peroxidase activity [GPxBC]). No changes in negative or positive symptoms or functional outcome were observed with NAC, but significant improvements were found in favor of NAC on neurocognition (processing speed). NAC also led to increases of GSHmPFC by 23% (P = .005) and GSHBC by 19% (P = .05). In patients with high-baseline GPxBC compared to low-baseline GPxBC, subgroup explorations revealed a link between changes of positive symptoms and changes of redox status with NAC. In conclusion, NAC supplementation in a limited sample of EP patients did not improve negative symptoms, which were at modest baseline levels. However, NAC led to some neurocognitive improvements and an increase in brain GSH levels, indicating good target engagement. Blood GPx activity, a redox peripheral index associated with brain GSH levels, could help identify a subgroup of patients who improve their positive symptoms with NAC. Thus, future trials with antioxidants in EP should consider biomarker-guided treatment.

P.3.d.033 - Redox dysregulation in schizophrenia pathophysiology: add-on trial with N-acetyl-cysteine (NAC) in early psychosis patients

P.3.d.033 - Redox dysregulation in schizophrenia pathophysiology: add-on trial with N-acetyl-cysteine (NAC) in early psychosis patients

3.24 Prevalence of Substance Use in Early-Psychosis Patients Treated in a Specialized First-Episode Psychosis Unit in a City Hospital of New York

3.24 Prevalence of Substance Use in Early-Psychosis Patients Treated in a Specialized First-Episode Psychosis Unit in a City Hospital of New York

Prediction of self-stigma in early psychosis: 3-Year follow-up of the randomized-controlled trial on extended early intervention

BackgroundSelf-stigma represents a major barrier to recovery in people with psychotic disorders but is understudied in early illness stage. Longitudinal investigation of prediction for self-stigma is scarce and none is conducted in early psychosis. We aimed to prospectively examine baseline predictors of self-stigma in early psychosis patients in the context of a 3-year follow-up of a randomized-controlled trial (RCT) comparing 1-year extension of early intervention (EI) with step-down psychiatric care for first-episode psychosis (FEP). MethodOne hundred sixty Chinese patients were recruited from a specialized EI program for FEP in Hong Kong after they had completed this 2-year EI service, and underwent a 12-month RCT. Participants were followed up and reassessed 3years after inclusion to the trial. Comprehensive evaluation encompassing clinical, functional, subjective quality of life and treatment-related variables were conducted. Data analysis was based on 136 participants who completed self-stigma assessment at 3-year follow-up. ResultsFifty patients (36.8%) had moderate to high levels of self-stigma at 3-year follow-up. Multivariate regression analysis revealed that female gender, prior psychiatric hospitalization, longer duration of untreated psychosis and greater positive symptom severity at study intake independently predicted self-stigma at the end of 3-year study period. ConclusionOur results of more than one-third of early psychosis patients experienced significant self-stigma underscore the clinical needs for early identification and intervention of self-stigmatization in the initial years of psychotic illness. Further research is warranted to clarify prediction profile and longitudinal course of self-stigma in the early illness phase.

Comorbidity of chronic somatic diseases in patients with psychotic disorders and their influence on 4-year outcomes of integrated care treatment (ACCESS II study)

BackgroundPeople with psychotic disorders fulfilling criteria of a severe and persistent mental illness (SPMI) display a high risk of somatic comorbidity (SC). MethodsACCESS II is a prospective, long-term study examining the effectiveness of Integrated Care for people with psychotic disorders fulfilling SPMI criteria. Chronic comorbid somatic disorders were systematically assessed according to ICD-10-GM criteria. Patients treated for ≥4years in ACCESS were categorized as early psychosis (treatment: ≤2years) or non-early psychosis (treatment: >2years) patients. ResultsOf 187 patients treated in ACCESS for ≥4years (mean age=41.8years, males=44.4%), 145 (77.5%) had SC, (mean=2.1±2.1). Overall, 55 different diseases from 15 different ICD-10-GM disease areas were identified. Prevalence of ≥1 SC (p=0.09) and specific types of SC (p=0.08–1.00) did not differ between early and non-early psychosis patients, but non-early psychosis patients had a higher mean number of SC (2.3±2.2 vs. 1.3±1.3, p=0.002). SC patients had higher rates of comorbid mental disorders (93% vs. 81%, p=0.002), specifically posttraumatic stress disorder (23% vs. 7%, p=0.002), and suicide attempts (43% vs. 19%, p<0.001). At the 4-year endpoint, both patients with and without comorbidity displayed major improvements in psychopathology, severity of illness, functioning, quality of life and satisfaction with care. ConclusionsSC is frequent in patients with severe psychotic disorders, even in the early psychosis phase. The magnitude of the problem underlines the need for regular screening, comprehensive assessment, preventive pharmacotherapy, and targeted SC management.

Treatment in early psychosis with N-acetyl-cysteine for 6 months improves low-level auditory processing: Pilot study

Sensory impairments constitute core dysfunctions in schizophrenia. In the auditory modality, impaired mismatch negativity (MMN) has been observed in chronic schizophrenia and may reflect N-methyl-d-aspartate (NMDA) hypo-function, consistent with models of schizophrenia based on oxidative stress. Moreover, a recent study demonstrated deficits in the N100 component of the auditory evoked potential (AEP) in early psychosis patients. Previous work has shown that add-on administration of the glutathione precursor N-acetyl-cysteine (NAC) improves the MMN and clinical symptoms in chronic schizophrenia. To date, it remains unknown whether NAC also improves general low-level auditory processing and if its efficacy would extend to early-phase psychosis. We addressed these issues with a randomized, double-blind study of a small sample (N=15) of early psychosis (EP) patients and 18 healthy controls from whom AEPs were recorded during an active, auditory oddball task. Patients were recorded twice: once prior to NAC/placebo administration and once after six months of treatment. The N100 component was significantly smaller in patients before NAC administration versus controls. Critically, NAC administration improved this AEP deficit. Source estimations revealed increased activity in the left temporo-parietal lobe in patients after NAC administration. Overall, the data from this pilot study, which call for replication in a larger sample, indicate that NAC improves low-level auditory processing in early psychosis.

Insight and Violent Behavior in a Cohort of Early Psychosis Patients

Objectifs: Une proportion importante de patients présentant un premier épisode psychotique commettent des actes violents hétéro-agressifs. L’objectif de cette étude est d’explorer l’association entre insight et comportement violent (CV) et l’évolution de l’insight durant la période de suivi. Méthode: L’étude est conduite sur une cohorte prospective de 265 patients recrutés au sein du programme de traitement et d’intervention précoce dans les troubles psychotiques et suivis sur une période de 3 ans. L’évaluation de l’insight est basée sur une échelle d’insight en 3 points et l’item de l’insight à la Positive and Negative Syndrome Scale (PANSS). Les CV ont été évalués par les case-managers, par les informations provenant des services forensiques et par l’intermédiaire d’un relevé des CV en cours d’hospitalisation. Des analyses de régression logistique uni-variées et multi-variées, des tests-t et des corrélations ont été réalisés. Résultats: L’effet significatif de l’insight comme facteur associé aux CV trouvé dans les analyses uni-variées disparaît après avoir contrôlé l’effet des symptômes positifs, du diagnostic de dépendance aux substances, de l’impulsivité et de l’adhésion au traitement. Conclusion: Si la prise de conscience des patients à l’égard de leur maladie évolue positivement au cours du traitement, nos résultats suggèrent que le risque de survenue de CV n’est pas influencé par le degré d’insight. Il est par contre significativement lié à l’abus de substances et à l’impulsivité, impliquant de cibler ces deux dimensions dans les stratégies préventives. L’impact de l’insight sur le CV doit être l’objet d’analyses prospectives plus précises.

Cognitive function in early psychosis patients from a lower middle-income country

Objectives: To establish evidence of cognitive changes in early psychosis (EP) patients compared to healthy controls (HC) in Pakistan.Methods: Fifty-one participants with EP were recruited from psychiatric units in Karachi and Rawalpindi, Pakistan and matched with 51 HC. Neurocognitive domains were assessed using standardised neuropsychological tests [the Stroop test, block design, Matrix Reasoning, picture completion, object assembly, oral fluency, memory for design, Coughlan learning task (verbal and visual)].Results: EP patients had higher scores than controls for both Stroop tests (T1: EP = 122 HC = 65, p <.001; T2: EP = 190 HC = 153, p = .007) and memory for design test (EP = 10 HC = 3, p = .005). EP group had lower values for block design (EP = 4, HC = 11, p = .01), category fluency (EP = 18.9, HC = 26.1, p < .001), Coughlan verbal tasks (EP = 36.4 NC = 51.5, p < .001), matrix reasoning (EP = 4 NC = 10, p < .001), picture completion (EP = 4 NC = 6, p = .003) and object assembly (EP = 10.7, HC = 15.5, p = .002). There were limited significant associations between cognitive performance and PANSS scores.Conclusions: Reduced cognitive performance was found across multiple domains in Pakistani EP patients, which suggests that impaired cognitive performance is homogenous in patients with schizophrenia, regardless of ethnicity.

Age at the time of onset of psychosis: A marker of specific needs rather than a determinant of outcome?

BackgroundWhile there is suggestion that early onset of psychosis is a determinant of outcome; knowledge regarding correlates of later onset age is more limited. This study explores the characteristics of patients developing psychosis after age 26, towards the end of the usual age range of early intervention programs, in order to identify potential specific needs of such patients. MethodsTwo hundred and fifty-six early psychosis patients aged 18–35 were followed-up prospectively over 36 months. Patients with onset after 26 (“later onset”, LO) were compared to the rest of the sample. ResultsLO patients (32% of the sample) had shorter DUP, were less likely to be male, had better premorbid functioning and were more likely to have been exposed to trauma. They had greater insight at presentation and less negative symptoms overall. The trajectories for positive and depressive symptoms were similar in both groups. Evolution of functional level was similar in both groups, but while LO patients recovered faster, they were significantly less likely to return to premorbid functional level. ConclusionsLater psychosis onset correlates with better premorbid functioning and higher rate of trauma exposure; the latter should therefore be a treatment focus in such patients. LO patients were less likely to return to premorbid functional level, which suggests that current treatment strategies may not be efficient to help patients maintain employment. The possibility of distinct illness mechanisms according to onset age and the more central role for trauma in patients with onset after age 26 needs to be further explored.

Mild depressive symptoms mediate the impact of childhood trauma on long-term functional outcome in early psychosis patients

IntroductionThe mechanism linking childhood trauma (CT) to the functional deficits observed in early psychosis (EP) patients is as yet unknown.ObjectivesTo examine the potential mediating effect of depressive symptoms in this well-established association.MethodsTwo hundred nine EP subjects aged 18-35 were assessed for functioning and psychopathology after 2, 6, 12, 18, 24, 30, and 36 months of treatment. Patients were classified into early-trauma if they had faced at least one experience of abuse (physical, sexual, or emotional) or neglect (physical or emotional) before age 12, and late-trauma if the exposure had occurred between ages 12 and 16. Psychopathology was assessed with the Positive and Negative Syndrome Scale and the Montgomery-Asberg Depression Rating Scale. Functioning was measured with the Global Assessment of Functioning (GAF) and the Social and Occupational Functioning Assessment Scale (SOFAS). Mediation analyses were performed in order to study whether the relationship between CT and functioning was mediated by depressive symptoms.ResultsWhen compared with nonexposed patients, early but not late trauma patients showed lower levels of GAF and SOFAS scores over all the time points, excepting after the first assessment. After 30 and 36 months, the effect of early trauma on functioning was completely mediated by depressive symptoms. No mediating effect of positive or negative symptoms was highlighted at those time points.ConclusionMild depressive symptoms mediated the impact of early trauma on long-term functional outcome. Intensifying pharmacologic and/or psychotherapeutic treatment, focused on the depressive dimension, may help traumatized EP patients to improve their functioning.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Age at the time of exposure to trauma modulates the psychopathological profile and the level of functioning in early psychosis patients: A prospective study

IntroductionEvidence suggests a relationship between exposure to trauma and higher levels of symptoms and poorer functional outcomes in early psychotic patients (EPP). However, the impact of the age at the time of exposure to trauma in this association is as yet unknown.ObjectivesTo examine the potential differential impact of trauma, according to age at the time of exposure, on the level of functioning and on the psychopathological profile of EPP followed-up prospectively.MethodsTwo hundred and fifty-five EPP aged 18–35 were followed-up prospectively over 36 months. Patients who had faced at least one experience of abuse or neglect were classified according to age at the time of first exposure (early-trauma: before age 12; late-trauma: between age 12 and 16), and then compared with unexposed patients (non-trauma). The level of symptoms was assessed using the Positive and Negative Syndrome Scale. The Young Mania Rating Scale, and the Montgomery-Asberg Depression Rating Scale. The level of functioning was assessed with the global assessment of functioning.ResultsComparisons over the 3 years of treatment with non-trauma patients revealed that:– early-trauma patients showed consistently higher levels of positive (P = 0.006) depressive (P = 0.001), manic (P = 0.006) and negative (P = 0.029) symptoms and showed poorer functional level (P = 0.025);– late-trauma patients only showed more negative symptoms (P = 0.029) as compared to non-trauma patients.ConclusionsThe age at the time of exposure to trauma has a modulating effect on its impact on symptoms and functional outcome in EPP and it should be systematically examined in clinical and experimental settings.Disclosure of interestThe authors have not supplied their declaration of competing interest.

N-acetyl-cysteine in a double-blind randomized placebo-controlled trial: Towards biomarker guided treatment in early psychosis

PurposeRecent evidence points to a critical role of redox dysregulation induced oxidative stress in the pathophysiology of early phases of schizophrenia. An add-on trial with n-acetyl-cysteine (NAC) led to a reduction in negative symptoms in chronic schizophrenia patients. Aim of this study was to explore impact of addition of NAC to standard treatment in early psychosis (EP) patients.MethodsDouble-blind, randomized, placebo-controlled trial of addition of NAC, 2700 mg daily, to antipsychotic treatment over 6 months. Monthly assessment of PANSS, GAF, SOFAS and antipsychotics treatment; quantification of brain glutathione levels (GSHmPFC) by 1H-magnetic-resonance-spectroscopy and of blood cells glutathione (GSHBC) and glutathione peroxidase activity (GPxBC) as marker of oxidation status at the beginning and end of treatment.ResultsOverall, 63 patients were included. Spectroscopy data showed that GSHmPFC increased by +23% in the NAC group, while it tended to decrease by −5% in the placebo group (P = 0.005). No significant difference between NAC and placebo was observed on global changes in negative symptoms, positive symptoms or functional outcome. However, in patients with high-baseline oxidation status (GPxBC&gt;22.3U/gHb), subgroup explorations revealed an improvement of positive symptoms over time compared to patients with low-baseline GPx (P = 0.02).ConclusionsWhile addition of NAC induced an increase of brain GSH, it had no impact on symptomatic and functional outcome in EP patients. However, in patients with high oxidation status, addition of NAC leads to significantly greater improvement in positive symptoms. Future studies on antioxidant interventions in EP should consider biomarker-guided treatment.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Oxidative Stress and Inflammation in Early Onset First Episode Psychosis: A Systematic Review and Meta-Analysis.

Background:People with schizophrenia and other psychosis show increased proinflammatory and prooxidative status. However, the few studies that have specifically assessed oxidative and inflammatory markers in early onset psychosis (onset before age 18) have shown contradictory results.Methods:Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines for systematic reviews and meta-analyses were used to conduct a systematic literature search to detect studies comparing inflammatory and oxidative markers in early onset psychosis patients and healthy controls.Results:Seven studies met criteria for the qualitative analysis. Four studies met criteria for meta-analysis, comprising an overall sample of 261 early onset psychosis patients and 246 healthy controls. Six independent meta-analyses were performed for catalase, glutathione, glutathione peroxidase, superoxide dismutase, total antioxidant status, and cell/DNA oxidative damage. No significant differences were found between early onset psychosis patients and controls in any of the parameters assessed. Heterogeneity among studies was high. Qualitative analysis of individual studies showed an association of inflammatory and oxidative markers with clinical, cognitive, and neurobiological outcomes, especially in longitudinal assessments.Conclusions:Despite the lack of significant differences between early onset psychosis patients and controls in the oxidative markers assessed in the meta-analyses, results based on individual studies suggest that greater inflammation and oxidative stress might lead to poorer outcomes in patients with first episodes of early onset psychosis.

SU19. Effects of N-Acetyl-Cysteine as an Add-on to Standard Treatment on Neurocognition in Early Psychosis

Abstract Background: Schizophrenia is associated with neurocognitive dysfunction already in the early phase of the disease.1 However, cognitive impairments are actually poorly treated by pharmacological interventions, leaving severe problems in functioning.2 Increasing evidence suggest oxidative stress and redox dysregulation play a role in the emergence of psychosis.3 In particular, levels of glutathione (GSH) are lower in chronic schizophrenia.4 In addition, a previous trial with the antioxidant N-acetyl-cysteine (NAC) led to negative symptoms reduction in chronic patients.5 Therefore, we explored if NAC had also an impact on neurocognition in early psychosis (EP) patients. Methods: The study was a 6-month, double-blind, randomized, placebo-controlled trial of NAC supplementation (2700 mg/d) to standard medications. Neurocognition was assessed at baseline and at the end of treatment with the MATRICS Consensus Cognitive Battery (MCCB),6 excluding the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Sixty-one patients (31 NAC, 30 placebo) with a diagnostic of psychotic disorder and less than 12 months of antipsychotic treatment were enrolled. Results: We found significant interaction Time × Treatment in favor of NAC on the MCCB processing speed factor and for 2 of 3 processing speed’s tasks (Trail Making A and Verbal Fluency). The improvement in processing speed within the NAC group was correlated with a decrease in negative symptoms. In addition, it was possible to identify a subgroup of patients who responded to NAC treatment considering their biological variables. Indeed, patients having a low peroxidase (GPx) activity at baseline benefited more than others from NAC supplementation in terms of processing speed’s scores. Moreover, in those individuals only, the improvement in processing speed was related to a decrease of the GSH reductase (GR) activity and to a regulation of the balance GPx – GR. Conclusion: Addition of NAC improved processing speed in EP patients, in particular in those who displayed a low basal level of redox dysregulation. Further, larger studies on antioxidant interventions are needed to replicate these findings. This work was supported by the National Center of Competence in Research (NCCR) “SYNAPSY – The Synaptic Bases of Mental Diseases” financed by the Swiss National Science Foundation, Damm-Etienne Foundation, Alamaya Foundation, the Commonwealth of Massachusetts Center of Excellence in Clinical Neuroscience and Psychopharmacological Research (SCDMH82101008006, LJS), and the Weisman family (LJS).

SA19. N-Acetyl-Cysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis

Background: Biomarker-guided treatments are needed in psychiatry and previous data suggest redox dysregulation / oxidative stress may be a target in schizophrenia (1,2). A previous add-on trial with the antioxidant N-Acetyl-Cysteine (NAC) led to negative symptoms reductions in chronic patients (3). We aim to study NAC impact on symptoms and neurocognition in early psychosis (EP) and to explore whether glutathione (GSH)/redox markers could represent valid biomarkers to guide treatment. Methods: In a double-blind, randomized, placebo-controlled trial in 63 EP patients, we assessed the effect of NAC supplementation (2700 mg/day, 6 months) on PANSS, neurocognition (MATRICS Consensus Cognitive Battery [MCCB]), and redox markers (brain GSH [GSH-mPFC], blood cells GSH [GSH-BC] levels, and GSH peroxidase activity [GPx-BC]). Results: No changes in negative, positive symptoms, or functional outcome were observed with NAC, but significant improvements were found in favor of NAC on the MCCB Processing Speed factor and two of its components: Trail Making and Verbal Fluency. NAC leads to increases in GSH-mPFC by 23% (P = .005) and GSH-BC by 19% (P = .05). In patients with high-baseline GPx-BC (>22.3U/gHb), subgroup explorations revealed an improvement with NAC of positive symptoms when compared to patients with low-baseline GPx (P = .02), with an improvement of positive symptoms in parallel with that of the redox status. Conclusion: In conclusion, NAC supplementation in a limited sample of EP patients did not improve negative symptoms, which were at modest levels at baseline. However, NAC leads to neurocognition improvement as well as to brain GSH levels increases, pointing to good target engagement. Blood GPx activity, a redox peripheral index associated with brain GSH levels, could help to identify a subgroup of patients who improve their positive symptoms with NAC. Future trials with antioxidant in EP should consider biomarker-guided treatment.

Mild Depressive Symptoms Mediate the Impact of Childhood Trauma on Long-Term Functional Outcome in Early Psychosis Patients.

The mechanism linking childhood trauma (CT) to the functional deficits observed in early psychosis (EP) patients is as yet unknown. We aim to examine the potential mediating effect of depressive symptoms in this well-established association. Two hundred nine EP subjects aged 18-35 were assessed for functioning and psychopathology after 2, 6, 12, 18, 24, 30, and 36 months of treatment. Patients were classified into early trauma if they had faced at least one experience of abuse (physical, sexual, or emotional) or neglect (physical or emotional) before age 12, and late trauma if the exposure had occurred between ages 12 and 16. Diagnosis was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). Psychopathology was assessed with the Positive and Negative Syndrome Scale and the Montgomery-Asberg Depression Rating Scale. Functioning was measured with the Global Assessment of Functioning (GAF) and the Social and Occupational Functioning Assessment Scale (SOFAS). Mediation analyses were performed in order to study whether the relationship between CT and functioning was mediated by depressive symptoms. When compared with nonexposed patients, early but not late trauma patients showed lower levels of GAF and SOFAS scores over all the time points, excepting after the first assessment. After 30 and 36 months, the effect of early trauma on functioning was completely mediated by depressive symptoms. No mediating effect of positive or negative symptoms was highlighted at those time points. Mild depressive symptoms mediated the impact of early trauma on long-term functional outcome. Intensifying pharmacologic and/or psychotherapeutic treatment, focused on the depressive dimension, may help traumatized EP patients to improve their functioning.

P.3.b.038 - Age at the time of exposure to trauma modulates the psychopathological profile in early psychosis patients

P.3.b.038 - Age at the time of exposure to trauma modulates the psychopathological profile in early psychosis patients

Hippocampal arterial cerebral blood volume in early psychosis

Recent studies of patients in the early stage of psychosis have revealed increased cerebral blood volume (CBV) in specific subfields of the anterior hippocampus. These studies required injection of a contrast agent to measure steady state CBV. Here we used a novel, non-invasive method, inflow-based-vascular-space-occupancy with dynamic subtraction (iVASO-DS), to measure the arterial component of CBV (aCBV) in a single slice of the hippocampus. Based on evidence from contrast-enhanced CBV studies, we hypothesized increased aCBV in the anterior hippocampus in early psychosis. We used 3T MRI to generate iVASO-derived aCBV maps in 17 medicated patients (average duration of illness = 7.6 months) and 25 matched controls. We did not find hemispheric or regional group differences in hippocampal aCBV. The limited spatial resolution of the iVASO-DS method did not allow us to test for aCBV differences in specific subfields of the hippocampus. Future studies should investigate venous and arterial CBV changes in the hippocampus of early psychosis patients.

Impact of comorbid cannabis use on outcome in first episode psychosis.

Comorbid cannabis abuse is common in patients with early psychosis. Little is known about the effect of stopping cannabis use on positive, negative and depressive symptoms. Few studies have controlled for multiple substance use that may mask the specific role that cannabis plays in symptom outcomes. The aim of this study was to investigate whether course and level of cannabis use negatively impacted early psychosis patient symptom profiles (positive, negative and depressive symptoms) over 24 months. One hundred and ninety-two patients admitted to an early psychosis intervention programme in a naturalistic setting were followed across three time periods: initial presentation, 12 and 24 months. Patients' clinical characteristics (substance use, positive/negative symptoms and depressive symptoms) were assessed at each time period. There were no significant associations found between cannabis abuse and positive and negative symptoms. Continuation and discontinuation of cannabis use were not significant for cannabis or any other substance when compared to positive and negative symptoms. There was a significant interaction between cannabis and alcohol for depressive symptoms, where depressive symptoms were significantly higher in patients who abused cannabis without co-occurring alcohol abuse when compared to non-cannabis using patients. The current study findings indicate a complex interaction between cannabis and alcohol use in a sample of early psychosis patients across 24 months. More research is needed into the association between ceasing cannabis use and long-term outcome for early psychosis patients. Of particular importance is the interaction between level of cannabis and alcohol use as it is related to symptom outcome in early psychosis patients.