Early Phase Of Psychosis Research Articles

City Avoidance in the Early Phase of Psychosis: A Neglected Domain of Assessment and a Potential Target for Recovery Strategies.

Background: A considerable amount of research has explored the link between living in an urban environment during childhood and the increased risk to develop psychosis. However, the urban milieu is more than a risk factor as it is also a place for socialization and enrichment. The aims of the current study were to explore, in a large sample of early psychosis (EP) patients, their pattern of use of the city, their perception when exposed to various critical stressors, and their sensitivity to diverse forms of stimuli. Methods: We sent a questionnaire (based on previous work conducted in a group of patients, including video-recorded walk-along in the city and a literature review) to 305 EP patients and to 220 medical students. Results: Response rate in patients was low (38%). City avoidance and negative perceptions towards the urban environment increased in patients after onset of psychosis. Patients’ tendency to avoid city center correlates with both problematic social interactions and stimuli perceived as unpleasant. Patients seemed less likely to enjoy urban spaces considered as relaxing, suggesting a lower capacity to benefit from positive aspects of this environment. Conclusions: The development of psychosis influences the way EP patients perceive the city and their capacity to feel at ease in the urban environment, leading to a high rate of city avoidance. Considering the possible influence of city avoidance on social relations and the recovery process, the development of strategies to help patients in this regard may have a significant effect on their recovery process.

Relationship of auditory electrophysiological responses to magnetic resonance spectroscopy metabolites in Early Phase Psychosis

Both auditory evoked responses and metabolites measured by magnetic resonance spectroscopy (MRS) are altered in schizophrenia and other psychotic disorders, but the relationship between electrophysiological and metabolic changes are not well characterized. We examined the relation of MRS metabolites to cognitive and electrophysiological measures in individuals during the early phase of psychosis (EPP) and in healthy control subjects. The mismatch negativity (MMN) of the auditory event-related potential to duration deviant tones and the auditory steady response (ASSR) to 40 Hz stimulation were assessed. MRS was used to quantify glutamate+glutamine (Glx), N-Acetylasparate (NAA), creatine (Cre), myo-inositol (Ins) and choline (Cho) at a voxel placed medially in the frontal cortex. MMN amplitude and ASSR power did not differ between groups. The MRS metabolites Glx, Cre and Cho were elevated in the psychosis group. Partial least squares analysis in the patient group indicated that elevated levels of MRS metabolites were associated with reduced MMN amplitude and increased 40 Hz ASSR power. There were no correlations between the neurobiological measures and clinical measures. These data suggest that elevated neurometabolites early in psychosis are accompanied by altered auditory neurotransmission, possibly indicative of a neuroinflammatory or excitotoxic disturbance which disrupts a wide range of metabolic processes in the cortex.

Structural similarity networks predict clinical outcome in early-phase psychosis.

Despite recent advances, there is still a major need for prediction of treatment success in schizophrenia, a condition long considered a disorder of dysconnectivity in the brain. Graph theory provides a means to characterize the connectivity in both healthy and abnormal brains. We calculated structural similarity networks in each participant and hypothesized that the "hubness", i.e., the number of edges connecting a node to the rest of the network, would be associated with clinical outcome. This prospective controlled study took place at an academic research center and included 82 early-phase psychosis patients (23 females; mean age [SD] = 21.6 [5.5] years) and 58 healthy controls. Medications were administered in a double-blind randomized manner, and patients were scanned at baseline prior to treatment with second-generation antipsychotics. Symptoms were assessed with the Brief Psychiatric Rating Scale at baseline and over the course of 12 weeks. Nodal degree of structural similarity networks was computed for each subject and entered as a predictor of individual treatment response into a partial least squares (PLS) regression. The model fit was significant in a permutation test with 1000 permutations (P = 0.006), and the first two PLS regression components explained 29% (95% CI: 27; 30) of the variance in treatment response after cross-validation. Nodes loading strongly on the first PLS component were primarily located in the orbito- and prefrontal cortex, whereas nodes loading strongly on the second PLS component were primarily located in the superior temporal, precentral, and middle cingulate cortex. These data suggest a link between brain network morphology and clinical outcome in early-phase psychosis.

Are family warmth and positive remarks related to outcomes in psychosis? A systematic review.

Affective attitudes and behaviours manifested within the family environment have been characterised as expressed emotion (EE). High EE environments have been robustly shown to put psychosis patients at a greater risk of relapse compared with low EE exposure. Positive EE dimensions (warmth; positive remarks) have received far less attention than negative EE dimensions such that EE has become synonymous with a negative family atmosphere; the predictive value of positive EE dimensions is largely ignored. A systematic review examining the relationship between positive family EE and outcomes in psychosis is needed. A systematic search was conducted. Studies reporting bias and study quality were assessed. A total of 2368 studies were identified. Of these, 27 met eligibility criteria reporting outcomes including relapse, symptomatology, social functioning and life satisfaction. Relapse was the most commonly measured outcome. Stronger evidence emerged for the association between EE warmth and outcomes compared with EE positive remarks, with effects mostly evident in the early phase of psychosis. Evidence for protective effects of warmth on relapse was found up to 9 months follow-up. No effects were evident between positive remarks and relapse. Studies assessing symptom outcomes showed inconsistent findings. Evidence for an association with social functioning was evident, primarily in at risk mental states. Warmth and positive remarks predicted life satisfaction. The positive aspects of EE require further investigation with longitudinal research designs. Clinical interventions should focus not only on reducing negative aspects of EE but also foster warmth within families in the context of psychosis.

Negative Interpretation Biases Precede the Onset of Psychosis

This study investigated whether a negative interpretation bias was present in people at high risk for psychosis. People with an At Risk Mental State (ARMS; n = 21), patients with First Episode Psychosis (FEP; n = 20), and healthy controls (n = 20) performed three tasks, each of which was designed to measure interpretation bias. Both ARMS and FEP participants showed an attenuated positive bias compared to controls. These findings extend previous results investigating interpretation bias in psychosis by showing that interpretative biases are present before the onset of psychosis, and could therefore contribute to its development. Biased interpretation mechanisms could be a new target for clinical intervention in the early phase of psychosis.

Trois profils cliniques à risque de comportements violents dans une cohorte de patients présentant un premier épisode de psychose

ObjectiveThis study aims to determine whether it is possible to identify clinical profiles at risk of violent behaviors (VB) in the early phase of psychotic disorders, on the basis of the main dynamic psychopathological risk factors and describe characteristics of the groups with highest levels of violent behaviors. MethodA total of 265 patients, aged 18 to 35, treated at the Treatment and early Intervention in Psychosis Program (TIPP–Lausanne), a specialized early psychosis program, were included in this study. We conducted a latent-class analysis and a discriminative analysis on the basis of the main dynamic VB risk factors: substance use disorder, impulsivity, positive symptoms, insight, aggression, hostility, anger, emotional instability and adherence to treatment. These factors were evaluated by specialized scales and on the basis of the Positive and Negative Syndrome Scale (PANSS). VB were restricted to physical aggression against people, defined as “serious violence”. They were assessed on the basis of a questionnaire listing violent offenses (Swiss Criminal Code) and VB such as assault and battery, information through the forensic psychiatric services and on the basis of the Staff Observation Aggression Scale (SOAS-R scale) during inpatient treatment phase. ResultsFour heterogeneous subgroups were identified with respect to the studied clinical characteristics, including two groups with high rates of VB. The first group, comprising 46% of patients with VB, is distinguished by the prevalence of a range of dimensions related to hostility, impulsivity and emotional instability, associated with high levels of substance abuse and positive symptoms. These clinical dimensions are very significant at the statistical level, since they explain 70% of the construction of subgroups (discriminant analysis). The second group with 37% of patients with VB, is characterized by a lack of insight, lack of adherence to treatment and substance use. These two clinical profiles could increase the impairment of cognitive, functional and relational abilities and contribute to the development of VB in this early phase of psychosis. The third subgroup, with a violent behaviors rate of 28.6%, is distinguished by its high proportion of diagnoses of substance abuse (100%) and women (54%). A last subgroup of patients, the largest quantitatively, has a low proportion of VB (15%) and the lowest levels on the studied factors, suggesting that the majority of patients with this profile commit few VB. ConclusionOur results show that it is possible to identify groups at risk of violent behaviors during the early phase of psychosis on the basis of clinical characteristics that may evolve and therefore be the focus of preventive care. These results highlight the need to target substance use, impulsivity and lack of insight at follow-up in order to prevent VB.

Validity of a two-item screen for early psychosis

Well-validated screening tools have been developed to identify people at high risk for psychosis, but these are rarely used outside of specialty clinics or research settings. The development of extremely brief and simple screening tools could increase dissemination, especially in settings with low buy-in such as those with low base rates of psychosis and/or time constraints. We sought to identify such a brief measure by modeling participant responses to three psychosis screening questionnaires (Prime Screen; Prodromal Questionnaire-Brief; Youth Psychosis At Risk Questionnaire) in a sample of 139 help-seeking individuals and 335 college students (age range: 12–25). Two screening questions with especially strong information characteristics were identified: "Do you see things that others can't or don't see?" and "Have you ever felt that someone was playing with your mind?" (Alternative two-item screens with similarly strong properties were also identified and validated using uncertainty quantified through Bayesian modeling.) The resulting measure was validated against clinician ratings of psychosis. The screen performed with a sensitivity of 53% and specificity 98% for clinically significant hallucinations or delusions, and sensitivity of 32% and specificity 99% for identifying people in an early phase of psychosis (clinical high risk or first episode psychosis).

Microstructural Findings in White Matter Associated with Cannabis and Alcohol Use in Early-Phase Psychosis: A Diffusion Tensor Imaging and Relaxometry Study

Accumulating evidence suggests that brain white matter (WM) abnormalities may be central to the pathophysiology of psychotic disorders. In addition, there is evidence that cannabis use and alcohol use each is associated with WM abnormalities. However, there are very limited data on the effects of these substances on WM microstructure in patients with psychosis, especially for those at the early phase of illness. This project aimed to examine the impact of cannabis use and alcohol use on WM tissue in early-phase psychosis (EPP). WM was investigated in 21 patients with EPP using diffusion tensor imaging (DTI) and transverse relaxation time of tissue water (T2), with the primary outcomes being mean fractional anisotropy (FA) and T2. DTI analyses were performed at the full-brain level using tract-based spatial statistics with both DTI and T2 analysis done within a WM volume of interest (VOI) implicated in psychosis (containing the left superior longitudinal fasciculus). Our findings revealed that younger age of onset of regular alcohol use (more than one drink per week) was associated with lower FA values in the left thalamic radiation and left parahippocampal and left amygdalar WM. More frequent lifetime cannabis use was correlated with increased mean full-brain FA. There was no significant relationship found between FA and alcohol or cannabis use within the VOI. Relaxometry analysis revealed trend-level evidence of shortened T2 with later onset of regular alcohol use and with more frequent cannabis use. This study provides novel data demonstrating cortical and subcortical WM findings related to alcohol use in EPP and is the first to combine DTI and relaxometry, relating to this patient population.

Confused Connections? Targeting White Matter to Address Treatment Resistant Schizophrenia.

Despite development of comprehensive approaches to treat schizophrenia and other psychotic disorders and improve outcomes, there remains a proportion (approximately one-third) of patients who are treatment resistant and will not have remission of psychotic symptoms despite adequate trials of pharmacotherapy. This level of treatment response is stable across all stages of the spectrum of psychotic disorders, including early phase psychosis and chronic schizophrenia. Our current pharmacotherapies are beneficial in decreasing positive symptomology in most cases, however, with little to no impact on negative or cognitive symptoms. Not all individuals with treatment resistant psychosis unfortunately, even benefit from the potential pharmacological reductions in positive symptoms. The existing pharmacotherapy for psychosis is targeted at neurotransmitter receptors. The current first and second generation antipsychotic medications all act on dopamine type 2 receptors with the second generation drugs also interacting significantly with serotonin type 1 and 2 receptors, and with varying pharmacodynamic profiles overall. This focus on developing dopaminergic/serotonergic antipsychotics, while beneficial, has not reduced the proportion of patients experiencing treatment resistance to date. Another pharmacological approach is imperative to address treatment resistance both for response overall and for negative symptoms in particular. There is research suggesting that changes in white matter integrity occur in schizophrenia and these may be more associated with cognition and even negative symptomology. Here we review the evidence that white matter abnormalities in the brain may be contributing to the symptomology of psychotic disorders. Additionally, we propose that white matter may be a viable pharmacological target for pharmacoresistant schizophrenia and discuss current treatments in development for schizophrenia that target white matter.

A NEET distinction: youths not in employment, education or training follow different pathways to illness and care in psychosis

PurposeThe early phases of psychosis, including the prodrome, often feature educational/occupational difficulties and various symptoms and signs, that can render or keep youths “Not in Employment, Education or Training” (NEET). Conversely, NEET status itself may increase risk for illness progression and impaired functioning, and impede access to appropriate services for psychosis. As these issues have not been investigated, we aimed to examine differences in the illness and care pathways and characteristics of youths with psychosis who are NEET and non-NEET.MethodsYouths entering a catchment-based Canadian early intervention service for psychosis (N = 416) were assessed as being NEET or non-NEET and compared on symptomatology, premorbid adjustment, prodrome and duration of untreated psychosis (DUP).ResultsThirty-nine percent of the sample was NEET. Compared to non-NEET youths, NEET youths had 34% higher negative symptoms scores, longer prodromes (median of 52 weeks vs. 24 weeks), and were more often continuously ill after their first psychiatric change until the onset of psychosis (62% vs. 45%). Both groups had similar premorbid adjustment scores until late adolescence when scores were significantly worse for NEET youths. Accounting for other predictors, NEET youths had 23% longer DUPs on average, despite having made more help-seeking attempts.ConclusionsDespite being more narrowly defined, NEET status was thrice as prevalent in our sample as in the Canadian population. The NEET group followed a distinct trajectory of persistent symptoms and functional decline before presenting with a psychotic disorder. The systemic delays that NEET youths encountered indicate a need for better-targeted early identification efforts.

Cannabis, a Significant Risk Factor for Violent Behavior in the Early Phase Psychosis. Two Patterns of Interaction of Factors Increase the Risk of Violent Behavior: Cannabis Use Disorder and Impulsivity; Cannabis Use Disorder, Lack of Insight and Treatment Adherence.

Background: Previous literature suggests that prevalence of cannabis use in the early phase of psychosis is high, and that early psychosis patients are at high-risk for violent behavior. However, the link between cannabis use and violent behavior in early psychosis patients is unclear. We carried out a study on a sample of early psychosis patients, in order to explore the impact of cannabis use on the risk of violent behavior (VB), while taking into account (1) potential confounding factors and, (2) interactions with other dynamic risk factors of VB.Method: In a sample of 265 early psychosis patients, treated at the Treatment and Early Intervention in Psychosis Program (TIPP) in Lausanne, we used logistic regression models to explore the link between various dynamic risk factors of VB [positive symptoms, substance use disorder (drugs including cannabis, alcohol and others drugs), insight, impulsivity, affective instability, and treatment adherence], and VB occurring during treatment. In order to understand hierarchical effects attributable to the combinations of risk factors on VB we conducted a Classification and Regression Tree (CART).Results: Our results show that cannabis use disorder is a risk factor for VB. The associations among risk factors suggest the presence of two patient profiles with an increased rate of VB: the first is composed of patients with cannabis use disorder and impulsivity, and the second of patients combining cannabis use disorder, absence of insight and non-adherence to treatment. The results also show the moderating role of insight and adherence to treatment on the rate of VB in patients with cannabis use disorder.Conclusion: This study suggests that cannabis use disorder is a significant risk factor for VB amongst early psychosis patients, particularly when combined with either impulsivity, lack of insight and non-adherence to treatment. These results suggest that preventive strategies could be developed on the basis of such patient profiles.

Cognitive effects of bilateral high frequency repetitive transcranial magnetic stimulation in early phase psychosis: a pilot study.

Cognitive dysfunction is a core facet of schizophrenia that is present early in the course of the illness and contributes to diminished functioning and outcomes. Repetitive transcranial magnetic stimulation (rTMS) is a relatively new neuropsychiatric intervention. Initially used in treatment resistant depression, investigators are now studying rTMS for other psychiatric diseases such as schizophrenia. In this study we examined the effect of high frequency rTMS on cognitive function in a group of individuals with early phase psychosis. Twenty subjects were randomized (1:1) in double-blind fashion to rTMS or sham condition. Over two weeks subjects underwent ten sessions of high frequency, bilateral, sequential rTMS targeting the dorsolateral prefrontal cortex (DLPFC). Prior to beginning and following completion of study treatment, subjects completed a cognitive assessment and magnetic resonance imaging. Subjects receiving rTMS, compared to sham treatment, displayed improvement on a standardized cognitive battery both immediately following the course of study treatment and at follow-up two weeks later. Imaging results revealed that left frontal cortical thickness at baseline was correlated with treatment response. The study treatment was found to be safe and well tolerated. These results suggest that rTMS may hold promise for the treatment of cognitive dysfunction in the early phase of psychosis, and that MRI may provide biomarkers predicting response to the treatment.

Frontal cortical thickness correlates positively with impulsivity in early psychosis male patients.

Impulsive behaviours, which are frequent in young people suffering from psychosis have been linked to risky and violent behaviours and participate to the burden of psychotic illness. Given that morphological brain correlates of impulsivity in schizophrenia have been poorly investigated especially in young adults, the aim of this study was to investigate the relationship between impulsivity and cortical thickness in early psychosis (EP) patients. A total of 17 male subjects in the early phase of psychosis were recruited. Impulsivity was assessed with the Lecrubier Impulsivity Rating Scale. Mean cortical thickness was extracted from magnetic resonance imaging brain scans, using surface-based methods. Mean cortical thickness in the frontal lobe correlated positively with mean impulsivity in EP male patients. Our results suggest that psychotic subjects exhibiting higher impulsivity have larger frontal cortical thickness, which may pave the way towards the identification of patients with a higher risk to display impulsive behaviours.

Comparison of Early Intervention Services vs Treatment as Usual for Early-Phase Psychosis

The value of early intervention in psychosis and allocation of public resources has long been debated because outcomes in people with schizophrenia spectrum disorders have remained suboptimal. To compare early intervention services (EIS) with treatment as usual (TAU) for early-phase psychosis. Systematic literature search of PubMed, PsycINFO, EMBASE, and ClinicalTrials.gov without language restrictions through June 6, 2017. Randomized trials comparing EIS vs TAU in first-episode psychosis or early-phase schizophrenia spectrum disorders. This systematic review was conducted according to PRISMA guidelines. Three independent investigators extracted data for a random-effects meta-analysis and prespecified subgroup and meta-regression analyses. The coprimary outcomes were all-cause treatment discontinuation and at least 1 psychiatric hospitalization during the treatment period. Across 10 randomized clinical trials (mean [SD] trial duration, 16.2 [7.4] months; range, 9-24 months) among 2176 patients (mean [SD] age, 27.5 [4.6] years; 1355 [62.3%] male), EIS was associated with better outcomes than TAU at the end of treatment for all 13 meta-analyzable outcomes. These outcomes included the following: all-cause treatment discontinuation (risk ratio [RR], 0.70; 95% CI, 0.61-0.80; P < .001), at least 1 psychiatric hospitalization (RR, 0.74; 95% CI, 0.61-0.90; P = .003), involvement in school or work (RR, 1.13; 95% CI, 1.03-1.24; P = .01), total symptom severity (standardized mean difference [SMD], -0.32; 95% CI, -0.47 to -0.17; P < .001), positive symptom severity (SMD, -0.22; 95% CI, -0.32 to -0.11; P < .001), and negative symptom severity (SMD, -0.28; 95% CI, -0.42 to -0.14; P < .001). Superiority of EIS regarding all outcomes was evident at 6, 9 to 12, and 18 to 24 months of treatment (except for general symptom severity and depressive symptom severity at 18-24 months). In early-phase psychosis, EIS are superior to TAU across all meta-analyzable outcomes. These results support the need for funding and use of EIS in patients with early-phase psychosis.

F231. Microstructural Changes in White Matter Associated With Alcohol Use in Early Phase Psychosis: A Diffusion Tensor Imaging (DTI) and Relaxometry Study

Accumulating evidence suggests that brain white matter (WM) abnormalities may be central to the pathophysiology of psychotic disorders. Additionally, cannabis use and alcohol use are each associated with WM abnormalities, however there is limited data on these substances effects on WM microstructure in psychosis, especially early phase psychosis (EPP). This study examined the impact of cannabis use and alcohol use in WM in EPP (N=21) using diffusion tensor imaging (DTI) and transverse relaxation time of tissue water (T2), with the primary outcomes being mean fractional anisotropy (FA) and T2.

197. Omega-3 Polyunsaturated Fatty Acids May Protect Against White Matter Abnormalities Found in Early Phase Psychosis

197. Omega-3 Polyunsaturated Fatty Acids May Protect Against White Matter Abnormalities Found in Early Phase Psychosis

T96. A RETROSPECTIVE DATABASE STUDY OF THE RELATIONSHIP BETWEEN ALCOHOL AND CANNABIS USE AND CLINICAL MEASURES IN EARLY PHASE PSYCHOSIS

BackgroundAlcohol is the most commonly abused substance in Canada (18%), with cannabis use being the second most commonly abused substance (7%). People diagnosed with psychotic disorders have similar or increased risk of alcohol and cannabis use disorders compared to the general population. While there is ample data investigating the negative impact cannabis has on the development and course of psychosis, there is very limited data examining the potential role that alcohol might play. This study, therefore, investigates the pattern of alcohol and cannabis use and the clinical impact it might have in those at the early phase of psychotic illness.MethodsThis is a cross-sectional, retrospective, database study of 264 patients at time of admission to the NSEPP (Nova Scotia Early Psychosis Program), in Nova Scotia, Canada. Outcome measures included the following domains: demographics/pattern of use, symptomatology, cognition and function. Four groups of patients with early phase psychosis (EPP) were analyzed according to risk level of current substance use: 1) low risk substance use (LR, n = 44), 2) moderate-high alcohol use only (AU, n = 33), 3) moderate-high cannabis use only (CU, n = 55), and 4) moderate-high combined alcohol and cannabis use (AU+CU, n = 132).ResultsBetween group comparisons revealed statistically significant differences in: age (with the AU group being oldest), gender (with LR and AU groups with higher % females compared to CU and CU+AU groups), Positive psychotic symptoms (with AU group having the least positive symptoms), anxiety (with AU group having most anxiety symptoms), and functioning (with AU group having higher social/occupational functioning scores).DiscussionOur findings reveal significant between group differences in a group of 264 patients at time of entry into the NSEPP. The age differences may suggest that those who develop psychosis at an older age could be more predisposed to use alcohol primarily. Alternatively, it is possible that alcohol somehow delays the onset of psychosis. The gender differences suggest that females with EPP use cannabis less commonly, and seem to choose alcohol use only if they are substance users. There are less intense positive psychotic symptoms (as measured by the positive and negative syndrome scale, PANSS) and more intense trait anxiety symptoms (measured by the state trait anxiety inventory, STAI) in the AU group which may either indicate that anxiety is worsened and positive symptoms are somehow suppressed with alcohol use, or else might reflect a subgroup in the EPP population (with less positive symptoms and more anxiety symptoms) that self-select for alcohol use. Finally, the AU group have the highest social/occupational functioning (measured with the social and occupational functioning assessment scale, SOFAS), which may indicate that alcohol facilitates social interaction/functioning; however based on existing literature, this finding more likely represents the fact that the more social someone is, the more likely they are to be exposed to alcohol in their peer group, and are therefore more likely to drink alcohol.

T52. N-ACETYL-CYSTEINE ADD-ON TREATMENT LEADS TO AN IMPROVEMENT OF FORNIX WHITE MATTER INTEGRITY IN EARLY PSYCHOSIS

BackgroundBeneficial effects of N-acetyl-cysteine (NAC) on negative symptoms in chronic schizophrenia have been reported in two studies. A recent study in early psychosis from our group, did not report significant improvement in negative symptoms (potentially linked to the modest baseline levels) but showed improvement in cognition (i.e. processing speed) and an increase in the brain antioxidant glutathione (GSH) levels, indicating good target engagement.1 Indeed, research in animal models highlights the critical role of redox regulation by brain GSH for white matter maturation and maintenance. Given the strong evidence of white matter (WM) alterations in schizophrenia as well as the current lack of etiological treatments, redox dysregulation is an interesting target. The current study aims at investigating the impact of NAC, a precursor of GSH, the main antioxidant in the brain, on WM integrity in patients in the early psychosis phase. We focused on the fornix bundle that has been shown to be impaired in an animal model of oxidative stress2 (i.e. impaired GSH synthesis) as well as in early psychosis patients.3MethodsWM diffusion properties were estimated using generalized fractional anisotropy (gFA) computed from diffusion spectrum imaging (DSI) brain scans acquired in patients who received either NAC (n=10; mean age=25.3 ± 5.7; males/females 9/1) or placebo (n=10; mean age=24.8 ± 7.9; males/females 5/5) as add-on treatment over 6-months. GSH levels were measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (MRS).ResultsA non-parametric longitudinal voxel-based analysis limited to the fornix revealed a time x treatment interaction which reached significance in the body of the fornix (corrected p<.04) with NAC patients showing an increase in gFA over 6-month of treatment. Importantly, improvement of gFA (i.e. increase) in the fornix of early psychosis patients (NAC and placebo) correlated with increase in cerebral GSH levels (r=.67; p<.005).DiscussionThis study is the first to assess the effect of NAC on WM integrity as assessed by diffusion weighted-imaging in the early phase of psychosis. WM alterations appear early in the illness and become widespread in a more chronic phase of the disease.4 To the best of our knowledge there is currently no approved medication for schizophrenia that show significant effect on WM integrity. In this study, effects of NAC on WM integrity in the fornix were significant despite the limited sample size. This is a small-scale proof of concept study, which was very demanding for early psychosis patients and needs replication in a larger study. Its potential properties to counteract WM deficits may be even more important in individuals at clinical high risk for psychosis. As NAC add-on treatment is safe with no side effects, this study paves the way for preventive approach at the early stages of psychosis.

O11.5. EFFECTIVENESS OF COORDINATED SPECIALTY CARE FOR EARLY PSYCHOSIS

BackgroundThe value of early intervention in psychosis and allocation of public resources has long been debated since outcomes in people with schizophrenia-spectrum disorders have remained suboptimal. Several research programs for early psychosis yielded promising results for team-based, multi-element coordinated specialty care (CSC).MethodsSystematic literature search of PubMed/PsycInfo/Embase/clinicaltrials.gov without language restrictions until 06/06/2017. Random effects meta-analysis of randomized trials comparing CSC versus Treatment as Usual (TAU) in in first episode psychosis or early-phase schizophrenia-spectrum disorders (schizophrenia, psychotic disorder not otherwise specified, schizoaffective disorder, schizophreniform disorder, delusional disorder), calculating standardized mean differences (SMDs) and risk ratios (RRs) for continuous and categorical outcomes as well as prespecified subgroup and meta-regression analyses.Co-primary outcomes were all-cause treatment discontinuation and ≥1 psychiatric hospitalization during the treatment period. Key secondary outcomes were total symptom improvement, functioning, and work or school involvement.ResultsAcross 10 trials (n=2,176; age=27.5 ± 4.6 years; male=62.3%; trial duration=16.2 ± 7.4 (range=9–24) months), CSC outperformed TAU at the end of treatment regarding all meta-analyzable outcomes. This included all-cause discontinuation (studies=10, n=2,173, RR=0.70, 95% confidence interval (CI)=0.61–0.80, p<0.001; number-needed-to-treat (NNT)=12.4), ≥1 hospitalization (studies=10, n=2,105, RR=0.74, 95%CI=0.61–0.90, p=0.003; NNT=10.1), total symptom severity (studies=8, n=1,179, SMD=-0.32, 95%CI=-0.47, -0.17, p<0.001), positive symptoms (studies=10, n=1,532, SMD=-0.22, 95%CI=-0.32, -0.13, p<0.001), negative symptoms (studies=10, n=1,432, SMD=-0.28, 95%CI=-0.42, -0.14, p<0.001), general symptoms (studies=8, n=1,118, SMD=-0.30, 95%CI=-0.47, -0.13, p=0.001), depressive symptoms (studies=5, n=874, SMD=-0.19, 95%CI=-0.35, -0.03, p=0.017), functioning (studies=7, n=1,005, SMD=0.21, 95%CI=0.09–0.34, p=0.001), involvement in school/work (studies=6, n=1,743, RR=1.13, 95%CI=1.03–1.24, p=0.012; NNT=17.8), and quality of life (studies=4, n=505, SMD=0.23, 95%CI=0.004–0.456, p=0.046). Superiority of CSC regarding all outcomes was also evident at 6, 9–12, and 18–24 months of treatment (except general symptoms and depression at 18–24 months).DiscussionIn early psychosis, CSC is superior to TAU across all meta-analyzable, highly relevant outcomes with small-to-medium effect sizes. These results support the need for funding and utilization of CSC in patients with early-phase psychosis.

Alterations of complex mismatch negativity (cMMN) elicited by a two-tone pattern paradigm in early-phase psychosis

The mismatch negativity (MMN) is a component of the event-related potential (ERP) elicited by a change in auditory stimulation (e.g., the occurrence of a deviant sound that violates the rules or regularities of the preceding stimulus sequence) regardless of whether one is attending to the change or not. As such, the MMN provides a useful index of pre-attentive cognition. While decreases in MMN amplitude are robustly observed in chronic schizophrenia, these deficits are less consistently present at the early phase of the illness. The current study utilizes a two-tone pattern paradigm that requires more complex computations than typical oddball stimulus presentations, which may be more appropriate for elucidating MMN deficits in an early phase psychosis (EP) sample. The stimuli were a standard sequence consisting of two alternating tones with different tonal frequencies (eg. ABABAB…), with MMN-eliciting pattern violations created by repetitions of either the A or the B tone. EEG recordings of 15 EP participants and 12 healthy controls (HCs) were collected. While no between-group differences were observed, MMN amplitudes in the EP group were correlated with positive and negative psychosis symptom scores. Follow-up analysis stratifying EP participants according to illness duration showed a reduced MMN amplitude in EP participants with a longer (2+ years) duration of illness, but not in EP participants who were within the first year of illness. These findings suggest a two-tone pattern paradigm may be useful in characterizing MMN-indexed cortical impairment later in the early phase of the illness, but not at first episode.