GAPi: A description of the initiative for early psychosis intervention in Latin America and the short- to medium-term outcomes in early psychosis patients.

INTRODUCTION: Schizophrenia is a debilitating disorder that affects a significant proportion of the population and leads to impaired functionality and long-term challenges. The first episode of psychosis (FEP) is a critical intervention stage for improving long-term outcomes. The GAPi program was established in São Paulo, Brazil to provide early intervention services and evaluate biomarkers in individuals with FEP. This article delineates the objectives of the GAPi program, detailing its innovative research protocol, examining the clinical outcomes achieved, and discussing the operational challenges encountered during its initial decade of operation. METHODS: The study comprised a prospective cohort of antipsychotic-naïve individuals with first-episode psychosis aged between 16 and 35 years. Participants were recruited from a public psychiatric facility in São Paulo. Emphasizing the initiative's commitment to early intervention, clinical assessments were systematically conducted at baseline and at two months, one year, two years, and five years of treatment to capture both short- and medium-term outcomes. Various assessment tools were utilized, including structured interviews, symptom scales, the Addiction Severity Index, and functional assessments. RESULTS: A total of 232 patients were enrolled in the cohort. Among them, 65.95 % completed the 2-month follow-up. Most patients presented with schizophrenia spectrum disorders, followed by bipolar disorder and major depressive disorder with psychotic features. Treatment response rates and remission rates were evaluated at different time points, with promising outcomes observed. The program also assessed socio-demographic factors, substance use, family history, and genetic and biomarker profiles, providing valuable data for research. DISCUSSION: The GAPi program has emerged as the largest ongoing cohort of antipsychotic-naïve first-episode psychosis in Latin America, contributing to the understanding of early psychosis in low- and middle-income countries. Despite operational challenges, the program has demonstrated efficacy in reducing the duration of untreated psychosis and in improving clinical outcomes. A multidisciplinary approach, including pharmacological treatment, psychosocial interventions, and family involvement, has been instrumental in enhancing treatment adherence and long-term prognosis. CONCLUSION: The GAPi program represents a valuable model for early intervention in first-episode psychosis and provides insights into the pathophysiology, treatment, and long-term outcomes of individuals with schizophrenia and related disorders. Continued research and resource allocation are essential for addressing operational challenges and expanding early intervention services in low- and middle-income countries.

Montreal Cognitive Assessment (MoCA) as a screening tool for cognitive impairment in early stages of psychosis.

Background: Cognitive alterations have been reported in early stages of psychosis including people with First Episode Psychosis (FEP), Clinical High-Risk Mental State (CHR), and Psychotic-Like Experience (PLE). This study aimed to compare the cognitive function in early stages of psychosis using the Montreal Cognitive Assessment (MoCA), a low-cost and brief assessment tool of cognitive functions. Methods: A total of 154 individuals, including 35 with FEP, 38 CHR, 44 PLE, and 37 healthy controls (HC), were evaluated with the MoCA in Santiago, Chile. We calculated the mean total score of the MoCA and the standard deviation of the mean. Groups were assessed for a trend to lower scores in a pre-determined sequence (HC > PLE > CHR > FEP) using the Jonckheere-Terpstra test (TJT). Results: The mean total MoCA scores were 24.8 ± 3.3 in FEP, 26.4 ± 2.4 in CHR, 26.4 ± 2.3 in PLE, and 27.2 ± 1.8 in HC. The analyses revealed a significant trend (p < 0.05) toward lower MoCA individual domain scores and MoCA total scores in the following order: HC > PLE > CHR > FEP. The mean total scores of all groups were above the cut-off for cognitive impairment (22 points). Conclusions: The MoCA describes lower scores in cognition across early stages of psychosis and may be a useful low-cost assessment instrument in early intervention centers of poorly resourced settings.

Racial differences in pathways to care preceding first episode mania or psychosis: a historical cohort prodromal study.

Background: There is evidence suggesting racial disparities in diagnosis and treatment in bipolar disorder (BD) and schizophrenia (SZ). The purpose of this study is to compare psychiatric diagnoses and psychotropic use preceding a first episode of mania (FEM) or psychosis (FEP) in racially diverse patients. Methods: Using a comprehensive medical records linkage system (Rochester Epidemiology Project, REP), we retrospectively identified individuals diagnosed with BD or SZ and a documented first episode of mania or psychosis. Illness trajectory before FEP/FEM were characterized as the time from first visit for a mental health complaint to incident case. Pathways to care and clinical events preceding FEP/FEM were compared based on subsequent incident case diagnosis (BD or SZ) and self-reported race (White vs. non-White). Results: A total of 205 (FEM = 74; FEP = 131) incident cases were identified in the REP. Duration of psychiatric antecedents was significantly shorter in non-White patients, compared to White patients (2.2 ± 4.3 vs. 7.4 ± 6.6 years; p < 0.001) with an older age at time of first visit for a mental health complaint (15.7 ± 6.3 vs. 11.1 ± 6.0 years; p = 0.005). There were no significant differences by race in FEM pathway to care or age of first seeking mental health. Overall non-White patients had lower rates of psychotropic use. Conclusion: These data are unable to ascertain reasons for shorter duration of psychiatric antecedents and later age of seeking care, and more broadly first age of initial symptom presentation. If symptoms are confirmed to be earlier than first time seeking care in both groups, it would be important to identify barriers that racial minorities face to access timely psychiatric care and optimize early intervention strategies.

Longitudinal Investigation of Auditory Dynamic Range Deficits in Early Psychosis and its Relationship to Negative Symptoms.

BACKGROUND AND HYPOTHESIS: Despite accounting for significant disease morbidity in schizophrenia, the neuropathological basis of negative symptoms remains poorly understood and options for treatment limited. Our recent study identified robust associations between diminished auditory cortex (AC) dynamic range and social functioning impairments and negative symptoms in first episode psychosis (FESz). The current investigation examined the progression of these relationships 4-8 months from baseline testing. STUDY DESIGN: Twenty-six FESz and 38 healthy controls (HC) were tested at baseline and follow-up. Magnetoencephalography (MEG) was recorded during binaural presentation of tones (75, 80, and 85 dB). Assessments included the MATRICS cognitive consensus battery (MCCB) and Global Functioning: Role and Social scales (GFR/GFS) and the Positive and Negative Syndrome Scale. STUDY RESULTS: Overall, FESz exhibited a blunted response to increasing tone intensity relative to HC. While this deficit did not change over time at the group level, recovery of right hemisphere AC dynamic range (85-75 dB response) among FESz individuals was associated with reductions in negative symptoms (ρ = -0.50). Diminished dynamic range was also associated with impaired GFS (ρ = 0.65), GFR (ρ = 0.51), and MCCB (ρ = 0.49) at baseline and increased negative symptoms at baseline (ρ = -0.53) and follow-up (ρ = -0.51). CONCLUSION: Despite persistent dynamic range impairment in FESz as a group, individual recovery of this AC response property was associated with significant reduction in negative symptoms. Identification of a functional neural deficit that tracts progression of negative symptoms during a critical period for disease modification is essential to the management of these devastating and historically treatment refractory symptoms.

Corrigendum: Initial adaptation of the OnTrack coordinated specialty care model in Chile: An application of the Dynamic Adaptation Process.

[This corrects the article DOI: 10.3389/frhs.2022.958743.].

Lifetime cannabis use and childhood trauma associated with CNR1 genetic variants increase the risk of psychosis: findings from the STREAM study.

OBJECTIVES: Gene-environment interactions increase the risk of psychosis. The objective of this study was to investigate gene-gene and gene-environment interactions in psychosis, including single nucleotide variants (SNVs) of dopamine-2 receptor (D2R), N-methyl-d-aspartate receptor (NMDAR), and cannabinoid receptor type 1 (CB1R), lifetime cannabis use, and childhood trauma. METHODS: Twenty-three SNVs of genes encoding D2R (DRD2: rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R (CNR1: rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898) were genotyped in 143 first-episode psychosis patients (FEPp) and 286 community-based controls by Illumina HumanCoreExome-24 BeadChip. Gene-gene and gene-environment associations were assessed using nonparametric Multifactor Dimensionality Reduction software. RESULTS: Single-locus analyses among the 23 SNVs for psychosis and gene-gene interactions were not significant (p > 0.05 for all comparisons); however, both environmental risk factors showed an association with psychosis (p < 0.001). Moreover, gene-environment interactions were significant for an SNV in CNR1 and cannabis use. The best-performing model was the combination of CNR1 rs12720071 and lifetime cannabis use (p < 0.001), suggesting an increased risk of psychosis. CONCLUSION: Our study supports the hypothesis of gene-environment interactions for psychosis involving T-allele carriers of CNR1 SNVs, childhood trauma, and cannabis use.

Lifetime cannabis use and childhood trauma increase risk of psychosis in carriers of CNR1 genetic variants: findings from the STREAM study

Objectives: Gene-environment interactions increase the risk of psychosis. The objective of this study was to investigate gene-gene and gene-environment interactions in psychosis, including single nucleotide variants (SNVs) of dopamine-2 receptor (D2R), N-methyl-d-aspartate receptor (NMDAR), and cannabinoid receptor type 1 (CB1R), lifetime cannabis use, and childhood trauma. Methods: Twenty-three SNVs of genes encoding D2R (DRD2: rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R (CNR1: rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898) were genotyped in 143 first-episode psychosis patients (FEPp) and 286 community-based controls by Illumina HumanCoreExome-24 BeadChip. Gene-gene and gene-environment associations were assessed using nonparametric Multifactor Dimensionality Reduction software. Results: Single-locus analyses among the 23 SNVs for psychosis and gene-gene interactions were not significant (p > 0.05 for all comparisons); however, both environmental risk factors showed an association with psychosis (p < 0.001). Moreover, gene-environment interactions were significant for an SNV in CNR1 and cannabis use. The best-performing model was the combination of CNR1 rs12720071 and lifetime cannabis use (p < 0.001), suggesting an increased risk of psychosis. Conclusion: Our study supports the hypothesis of gene-environment interactions for psychosis involving T-allele carriers of CNR1 SNVs, childhood trauma, and cannabis use.

Mutually exclusive disorder-dependent hearing discomfort in first-episode psychosis and panic disorder: two experiments using the same auditory stimulus set and two similar musical sequences.

We investigated the level of hearing tolerance in patients with first-episode psychosis (FEP) and panic disorder (PD) as compared to two different groups of healthy controls (HC, HC2), one for each experiment, because we used two distinct psychophysical paradigms. We evaluated auditory discomfort of 28 volunteers (14 with FEP and 14 HC) in the first study and of 42 volunteers (21 with PD and 21 HC2) in the second study. We presented 20 sounds: 16 pure-tone frequency sweeps (specially designed for use with FEP) and 11 s or 13 s musical sequences from the very beginning of the music "Play the Game" (PLAY) from Queen and its reverses. The first procedure used a Likert-like 0-10 scale ranging from "nothing bad" to "too bad" where volunteers made vertical marks along a horizontal line according to their discomfort. The second procedure involved subjective magnitude estimation online due to the SARS-COV-19 pandemic. Sounds were placed online and played by PD and HC2 volunteers themselves after having listened to the standard (the first 8 s from RADIO, "Radio Ga Ga" by Queen). Then, PD and HC2 volunteers were asked to assign values equal to, or multiples of 10 that felt like, or proportional to, their hearing "discomfort" in comparison with Sound 00 (RADIO). Our findings showed that FEP volunteers assign more discomfort to the 16 specially designed frequency sweep stimuli that appear not to affect HC, HC2, and PD. On the other hand, musical sequences from PLAY caused strong discomfort to PD in the reverse mode, but did not seem to affect HC, HC2, and FEP. Further experiments using the exact same paradigm with FEP and PD are needed to explore these findings.

OnTrack Chile for people with early psychosis: a study protocol for a Hybrid Type 1 trial.

BACKGROUND: Substantial data from high-income countries support early interventions in the form of evidence-based Coordinated Specialty Care (CSC) for people experiencing First Episode Psychosis (FEP) to ameliorate symptoms and minimize disability. Chile is unique among Latin American countries in providing universal access to FEP services through a national FEP policy that mandates the identification of FEP individuals in primary care and guarantees delivery of community-based FEP treatments within a public health care system. Nonetheless, previous research has documented that FEP services currently provided at mental health clinics do not provide evidence-based approaches. This proposal aims to address this shortfall by first adapting OnTrackNY (OTNY), a CSC program currently being implemented across the USA, into OnTrackChile (OTCH), and then examine its effectiveness and implementation in Chile. METHODS: The Dynamic Adaptation Process will be used first to inform the adaptation and implementation of OTCH to the Chilean context. Then, a Hybrid Type 1 trial design will test its effectiveness and cost and evaluate its implementation using a cluster-randomized controlled trial (RCT) (N = 300 from 21 outpatient clinics). The OTCH program will be offered in half of these outpatient clinics to individuals ages 15-35. Usual care services will continue to be offered at the other clinics. Given the current COVID-19 pandemic, most research and intervention procedures will be conducted remotely. The study will engage participants over the course of 2 years, with assessments administered at enrollment, 12 months, and 24 months. Primary outcomes include implementation (fidelity, acceptability, and uptake) and service outcomes (person-centeredness, adherence, and retention). Secondary outcomes comprise participant-level outcomes such as symptoms, functioning, and recovery orientation. Over the course of the study, interviews and focus groups with stakeholders will be conducted to better understand the implementation of OTCH. DISCUSSION: Findings from this study will help determine the feasibility, effectiveness, and cost for delivering CSC services in Chile. Lessons learned about facilitators and barriers related to the implementation of the model could help inform the approach needed for these services to be further expanded throughout Latin America. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT04247711 . Registered 30 January 2020. TRIAL STATUS: The OTCH trial is currently recruiting participants. Recruitment started on March 1, 2021, and is expected to be completed by December 1, 2022. This is the first version of this protocol (5/12/2021).

Initial adaptation of the OnTrack coordinated specialty care model in Chile: An application of the Dynamic Adaptation Process.

Background: In 2005, Chile became the first country in Latin America to guarantee universal free access for the diagnosis and treatment of schizophrenia. A cluster randomized control trial utilizing the Dynamic Adaptation Process framework is underway to adapt and test the OnTrack coordinated specialty care model to provide recovery-oriented, person-centered care by a multidisciplinary team for individuals with first episode psychosis (FEP) in Chile. Methods: A qualitative formative research study was conducted to inform the initial adaptation of the OnTrack Chile (OTCH) program. We conducted key informant interviews (n = 17) with various stakeholders (policymakers; directors/managers of community mental health centers; mental health professionals) and focus group discussions (n = 6) with individuals with FEP and caregivers (n = 35 focus group participants total). Data was analyzed using thematic analysis, organized by participants' perspectives on the benefits, barriers, and recommendations for the key principles, multidisciplinary team, psychosocial components, and the training and supervision model of OnTrack. Results: Participants expressed enthusiasm and support for OnTrack's recovery-oriented and person-centered principles of care. While many participants lauded the emphasis on shared decision-making and family involvement, some reported reticence, citing that it is culturally normative for patients and families to adopt a passive role in treatment. Peer specialists, and the family psychoeducation and support and supported education and employment components were perceived as aspects that could encourage the promotion of personhood and autonomy development. However, implementation challenges, including the prevailing biomedical approach, professional hierarchy, and the lack of infrastructure, human, and financial resources necessitate some modifications to these aspects. Some mental health professionals further conveyed reservations regarding the perceived hierarchical structure of the supervision model. Conclusion: OnTrack represents a shift from a biomedical model to a valued, aspirational, person-centered and culturally responsive model that focuses on recovery, shared decision-making and psychosocial care. With the appropriate governmental and agency-level provision of resources and modifications to some of the program components, particularly regarding the shared decision-making framework, peer specialist, family engagement, and the training supervision model, OTCH could be a transformative program for a more comprehensive, evidence-based care for individuals with FEP in Chile.

Early intervention in psychosis in emerging countries: Findings from a first-episode psychosis programme in the Ribeirão Preto catchment area, southeastern Brazil.

AIM: People presenting with first-episode psychosis (FEP) can benefit from early intervention programmes. However, such programmes are scarce in low- and middle-income countries (LMICs). In Brazil, there are a few programmes, but they are unequally distributed across the country. We aimed to describe the implementation and performance of the Ribeirão Preto Early Intervention in Psychosis Programme (Ribeirão Preto-EIP), an outpatient service for patients presenting with FEP residing in the Ribeirão Preto catchment area in Southeastern Brazil. METHODS: A detailed description of the service, staff and theoretical framework was compiled. Furthermore, a retrospective cohort study of patients attending the programme throughout 4 years (2015-2018) was conducted. Data were obtained by analysing the medical records of all patients, and sociodemographic and diagnostic stability information for this period was recorded. RESULTS: The Ribeirão Preto-EIP had 358 new referrals during the study period. Among them, 237 patients were assessed for an average (median) duration of 14 months. Most patients were male (64.1%) and single (84.8%). The median age was 23.5 years (range, 9-86 years). Schizophrenia was the main diagnosis (43.4%), followed by substance-induced (25.7%) and affective (18.6%) psychosis. Referrals occurred from emergency, inpatient, community-based mental health and primary care services. CONCLUSIONS: Programmes such as the Ribeirão Preto-EIP demonstrate that early intervention in psychosis is feasible in LMICs despite significant challenges for their access and integration in the health system. Strategic scale-up policies could be undertaken to offer better short- and long-term outcomes for individuals presenting with FEP and their families.

BDNF as a Biomarker of Cognition in Schizophrenia/Psychosis: An Updated Review.

Brain Derived Neurotrophic Factor (BDNF) has been linked to cognitive symptoms of schizophrenia, which has been documented in previous reviews by several authors. However, a trend has recently emerged in this field moving from studying schizophrenia as a disease to studying psychosis as a group. This review article focuses on recent BDNF studies in relation to cognition in human subjects during different stages of the psychotic process, including subjects at high risk of developing psychosis, patients at their first episode of psychosis, and patients with chronic schizophrenia. We aim to provide an update of BDNF as a biomarker of cognitive function on human subjects with schizophrenia or earlier stages of psychosis, covering new trends, controversies, current research gaps, and suggest potential future developments in the field. We found that most of current research regarding BDNF and cognitive symptoms in psychosis is done around schizophrenia as a disease. Therefore, it is necessary to expand the study of the relationship between BDNF and cognitive symptoms to psychotic illnesses of different stages and origins.

Evaluation of relationships between presence of adhesio interthalamica and cannabis use in first-episode psychosis: a magnetic resonance imaging investigation

ABSTRACT Recent studies suggested that cannabis use influences on the emergence of psychosis by disrupting neurodevelopmental processes that occur during adolescence and early adulthood and which are reflected on brain anatomical changes detectable with MRI. However, no MRI studies have investigated whether intrauterine neurodevelopmental abnormalities also interact with later cannabis use to influence on psychosis risk. We investigated differences between first-episode psychosis (FEP) patients with history of cannabis use (FEPC+, n=28), FEP subjects without cannabis use (FEPC-, n=78) and healthy controls (n=80) in regard to the frequency of absent or short Adhesio Interthalamica (AI), a well-established marker of intrauterine neurodevelopment. The FEPC+ subgroup had a significantly lower prevalence of absent AI than FEPC- subjects, as well as a lack of a significantly shorter AI length compared to controls (as found in FEPC- subjects). These preliminary results show that psychosis subjects with cannabis use present a low rather than high frequency of absent AI, suggesting that fixed intrauterine neurodevelopmental abnormalities may not be associated with cannabis use later in life to influence on the emergence of psychosis. This is consistent with a view that multiple different etiological processes may lead to similar clinical presentations in patients with FEP.

Plasma prevalence of anti-N-methyl-d-aspartate receptor IgG antibodies in early stages of psychosis / Prevalência plasmática de anticorpos IgG antirreceptor N-metil-d-aspartato nos estágios iniciais de psicose

Abstract We investigated the feasibility of including plasma anti-NMDAR antibody screening in the assessment of first-episode psychosis patients in an early intervention programme in the Southern hemisphere. Anti-NMDAR IgG antibodies were assessed by ELISA in 166 patients (64.0% men), 166 matched population-based controls and 76 patients' siblings (30.3% men). Fisher's exact test and ANOVA were performed. Positive anti-NMDAR antibody patients were more often observed in bipolar disorder (10.0%) than schizophrenia (2.4%) or psychotic depression (3.1%), although no significant differences were observed. Our results are not conclusive regarding the inclusion of plasma anti-NMDAR IgG antibodies in differential diagnostic protocols for psychosis.

Resumo Nós investigamos a viabilidade de incluir a pesquisa de anticorpos anti-NMDAR na avaliação de pacientes em primeiro episódio psicótico em um programa de intervenção precoce no Hemisfério Sul. Anticorpos IgG anti-NMDAR foram avaliados por ELISA em 166 pacientes (64,0% homens), 166 controles de base populacional pareados e 76 irmãos (30,3% homens). Foram realizados teste exato de Fisher e ANOVA. Os anticorpos anti-NMDAR positivos foram mais observados no transtorno afetivo bipolar (10,0%) do que na esquizofrenia (2,4%) ou depressão psicótica (3,1%), embora não tenham sido observadas diferenças significativas. Nossos resultados não são conclusivos quanto à inclusão de anticorpos IgG anti-NMDAR no plasma em protocolos de diagnósticos diferenciais para psicose.

White Matter Microstructural Abnormalities in the Broca's-Wernicke's-Putamen "Hoffman Hallucination Circuit" and Auditory Transcallosal Fibers in First-Episode Psychosis With Auditory Hallucinations.

BACKGROUND: Functional connectivity abnormalities between Broca's and Wernicke's areas and the putamen revealed by functional magnetic resonance imaging (fMRI) are related to auditory hallucinations (AH). In long-term schizophrenia, reduced white matter structural integrity revealed by diffusion imaging in left arcuate fasciculus (connecting Broca's and Wernicke's areas) is likely related to AH. The structural integrity of connections with putamen and their relation to AH are unknown. Little is known about this relationship in first-episode psychosis (FEP), although auditory transcallosal connections were reported to play a role. White matter in the Broca's-Wernicke's-putamen language-related circuit and auditory transcallosal fibers was examined to investigate associations with AH in FEP. METHODS: White matter connectivity was measured in 40 FEP and 32 matched HC using generalized fractional anisotropy (gFA) derived from diffusion spectrum imaging (DSI). RESULTS: FEP and HC did not differ in gFA in any fiber bundle. In FEP, AH severity was significantly inversely related to gFA in auditory transcallosal fibers and left arcuate fasciculus. Although the right hemisphere arcuate fasciculus-AH association did not attain significance, the left and right arcuate fasciculus associations were not significantly different. CONCLUSIONS: Despite overall normal gFA in FEP, AH severity was significantly related to gFA in transcallosal auditory fibers and the left hemisphere connection between Broca's and Wernicke's areas. Other bilateral tracts' gFA were weakly associated with AH. At the first psychotic episode, AH are more robustly associated with left hemisphere arcuate fasciculus and interhemispheric auditory fibers microstructural deficits, likely reflecting mistiming of information flow between language-related cortical centers.

A study in first-episode psychosis patients: does angiotensin I-converting enzyme (ACE) activity associated with genotype predict symptoms severity reductions after treatment with the atypical antipsychotic risperidone?

BACKGROUND: Our previous studies showed increased angiotensin I-converting enzyme (ACE) activity in chronic schizophrenia (SCZ) patients compared to healthy control (HC) volunteers, and the relevance of combining ACE genotype and activity for predicting SCZ was suggested. METHODS: ACE activity was measured in plasma of ACE insertion/deletion (I/D) genotyped HC volunteers (N = 53) and antipsychotic-naïve first-episode psychosis (FEP) patients (N = 45), assessed at baseline (FEB-B) and also after 2-months (FEP-2M) of treatment with the atypical antipsychotic risperidone. RESULTS: ACE activity measurements showed significant differences among HC, FEP-B and FEP-2M groups (F = 5.356, df = 2, p = 0.005), as well as between HC and FEP-2M (post-hoc Tukey's multiple comparisons test, p = 0.004). No correlation was observed for ACE activity increases and symptom severity reductions in FEP as assessed by total PANSS (r = -0.131, p = 0.434). FEP subgrouped by ACE I/D genotype showed significant ACE activity increases, mainly in the DD genotype subgroup. No correlation between ACE activity and age was observed in FEP or HC groups separately (r = 0.210, p = 0.392), but ACE activity levels differences observed between these groups were influenced by age. CONCLUSIONS: The importance of measuring the ACE activity in blood plasma, associated to ACE I/D genotyping to support the follow-up of FEP patients did not show correlation with general symptoms amelioration in the present study. However, new insights into the influence of age and I/D genotype for ACE activity changes in FEP individuals upon treatment was demonstrated.

Similarities and Differences in Associations Between Duration of Untreated Psychosis (DUP) and Demographic, Premorbid, and Symptom Severity Measures in Two Samples of First-Episode Psychosis Patients from Mexico and the United States.

Early-psychosis researchers have documented that duration of untreated psychosis (DUP) is an important predictor of outcomes in first-episode psychosis. Very few cross-national studies have been conducted, and none have been carried out involving patients from both Mexico and the U.S. We collaborated to answer three questions: (1) Are DUP estimates similar in two very different settings and samples? (2) Are demographic variables, premorbid adjustment, and symptom severity similarly related to DUP in the two different settings? (3) Does the same set of variables account for a similar proportion of variance in DUP in the two settings? Data on sociodemographic characteristics, premorbid adjustment, symptom severity, and DUP were available for 145 Mexican and 247 U.S. first-episode psychosis patients. DUP was compared, and bivariate analyses and multiple linear regressions were carried out in each sample. DUP estimates were similar (medians of 35 weeks in Mexico and 38 weeks in the U.S.). In the Mexican sample, DUP was associated with gender, employment status, premorbid social adjustment, and positive symptom severity (explaining 18% of variance). In the U.S. sample, DUP was associated with age, employment status, premorbid social adjustment, and positive symptom severity (but in the opposite direction of that observed in the Mexican sample), accounting for 25% of variance. Additional cross-national collaborations examining key facets of early-course psychotic disorders, including DUP, will clarify the extent of generalizability of findings, strengthen partnerships for more internationally relevant studies, and support the global movement to help young people struggling with first-episode psychosis and their families.

Immuno-inflammatory changes across phases of early psychosis: The impact of antipsychotic medication and stage of illness.

INTRODUCTION: Research examining the role of inflammation in psychosis has produced inconsistent results. Variables that influence inflammation, including antipsychotic medication, are inconsistently controlled across studies and variation of inflammatory analytes across stages of psychosis may also influence findings. The purpose of this study was to assess for evidence of immuno-inflammatory dysregulation across the stages of early psychosis. We examined a immuno-inflammatory analytes in subjects at clinical high risk (CHR) for developing a psychotic disorder, antipsychotic-naïve (-n) and antipsychotic treated (-a) subjects in their first episode of psychosis (FEP), and healthy control (HC) subjects. METHODS: A total of 11 subjects at CHR, 50 subjects within their FEP (40 FEP-n, 10 FEP-a), and 10 HC subjects were recruited from early psychosis programs in San Diego and Mexico City. Plasma was collected for biomarker assay. RESULTS: Immuno-inflammatory analytes significantly differed between groups: Interferon-gamma (IFN-γ), Interleukin-10 (IL-10), Eotaxin-1, Interferon Gamma-Induced Protein-10 (IP-10), Monocyte Chemotactic Protein-1 (MCP-1), Macrophage-Derived Chemokine (MDC), Macrophage Inflammatory Protein-1 beta (MIP-1ß), Thymus and Activation Regulated Chemokine (TARC), and Brain Derived Neurotropic Factor (BDNF). Post-hoc analyses revealed an overall pattern of higher levels of IL-10, MCP-1, MIP-1ß, TARC, and BDNF in CHR as compared to FEP-a, FEP-n, and HC subjects. CONCLUSIONS: Results reveal a profile of immuno-inflammatory dysregulation in early stages of psychosis prior to psychotic conversion and treatment with antipsychotic medication. The CHR phase of early psychosis may represent a period of increased immuno-inflammatory activation, but due to limited sample size, these results deserve replication in a well characterized early psychosis population.

The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI): Incidence and First-Episode Case-Control Programme.

PURPOSE: The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study contains an unparalleled wealth of comprehensive data that allows for testing hypotheses about (1) variations in incidence within and between countries, including by urbanicity and minority ethnic groups; and (2) the role of multiple environmental and genetic risk factors, and their interactions, in the development of psychotic disorders. METHODS: Between 2010 and 2015, we identified 2774 incident cases of psychotic disorders during 12.9 million person-years at risk, across 17 sites in 6 countries (UK, The Netherlands, France, Spain, Italy, and Brazil). Of the 2774 incident cases, 1130 cases were assessed in detail and form the case sample for case-control analyses. Across all sites, 1497 controls were recruited and assessed. We collected data on an extensive range of exposures and outcomes, including demographic, clinical (e.g. premorbid adjustment), social (e.g. childhood and adult adversity, cannabis use, migration, discrimination), cognitive (e.g. IQ, facial affect processing, attributional biases), and biological (DNA via blood sample/cheek swab). We describe the methodology of the study and some descriptive results, including representativeness of the cohort. CONCLUSIONS: This resource constitutes the largest and most extensive incidence and case-control study of psychosis ever conducted.

Impact of duration of untreated psychosis in short-term response to treatment and outcome in antipsychotic naïve first-episode psychosis.

AIM: Duration of untreated psychosis (DUP) is one of the few potentially modifiable outcome predictors in psychosis. Previous studies have associated a longer DUP with a poor prognosis, but few of them were performed in countries with low and middle level of income. This study aimed to investigate the DUP in a Brazilian sample of antipsychotic-naïve first-episode psychosis (AN-FEP) patients and its association with clinical characteristics and treatment outcomes in a short-term follow-up. METHODS: One hundred forty-five AN-FEP patients between 16 and 40 years were enrolled and were reassessed 10 weeks after risperidone treatment. We investigated the association between DUP and symptom severity, functionality and response to treatment, using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity Scale (CGI) and the Global Assessment of Functionality (GAF) scale. DUP was defined as the period between the onset of the first psychotic symptoms and the first effective antipsychotic treatment. For the analysis, we performed multivariate linear regressions. RESULTS: The DUP's median was 61 days. At baseline, we did not find any significant association between DUP and clinical characteristics. After treatment, the longer DUP predicted worse positive and negative symptom dimensions, worse total PANSS, GAF and CGI scores and poorer response to treatment. CONCLUSION: Our results showed that DUP is associated with worse outcomes after short treatment, but it does not modify the baseline clinical profile of the AN-FEP patients. Such results reinforce the need to develop early intervention strategies, reducing DUP.