First-episode Psychosis Patients Research Articles

Associations between age and neurocognition in individuals at clinical high risk and first-episode psychosis

Neurocognitive deficits differ with age during the early stages of psychosis. This study aimed to explore age-related differences (9–35 years old) in the neurocognitive performance of a large clinical population. In total, 1059 individuals with first-episode psychosis (FEP), 794 individuals with a clinical high risk of psychosis (CHR), and 774 well-matched healthy controls (HC) were recruited between 2016 and 2021. Neurocognitive assessments were performed using the Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Battery(MCCB). The MCCB subtest scores differed significantly among the groups across the age span. The mean scores of subtests in CHR individuals were approximately one standard deviation(SD) lower than that of HC, while that of FEP patients was approximately two SDs. The adolescents performed better than the adults in the HC, CHR, and FEP groups. In the HC group, a stronger correlation was found between age and cognitive function, and more neurocognitive domains were affected by age than in the CHR and FEP groups. These results emphasize that neurocognitive deficits in psychosis are present at the pre-onset stage and deteriorate at the first-episode stage across the age span, implicating the development of specific strategies that could monitor the cognitive trajectory in early psychosis.

Altered neutrophil-to-lymphocyte ratio in patients with non-affective first episode psychosis and its relationship with symptom severity and cognitive impairment

Signatures of immune dysregulation as clinical biomarker for psychosis have remained unclear. We aimed to compare the Neutrophil-to-lymphocyte ratio (NLR) of patients with acute non-affective first-episode psychosis (FEP) with healthy controls after accounting for emotional states. We also explored the associations of NLR with symptom severity, onset profile and cognitive functions. The NLR was enumerated from complete blood count taken within a week of assessment. All FEP patients were rated on the Positive and Negative Syndrome Scale (PANSS) and the Clinician Global Impression-Severity (CGI-S) with verbal memory and executive functions assessed with the Cambridge Neuropsychological Test Automated Battery. Prevailing emotional state was measured with Beck Depression Inventory-II and Beck Anxiety Inventory. Out of seventy-nine consecutive FEP patients presenting to the study site, twenty-seven subjects were eligible and recruited. Twenty-seven age-/sex-matched controls were recruited. FEP patients had an NLR of 1.886 over the controls after accounting for scores on emotional states. The NLR of FEP patients was positively associated with CGI-S scores, PANSS positive symptom, disorganization and excitation scores. There was no significant correlation between NLR with the duration of untreated psychosis and cognitive performances. These findings support using NLR as a clinical biomarker in FEP, purporting further prospective study to measure NLR changes in the course of treatment.

The association of childhood trauma with depressive and negative symptoms in recent onset psychosis: a sex-specific analysis.

Childhood trauma may impact the course of schizophrenia spectrum disorders (SSD), specifically in relation to the increased severity of depressive or negative symptoms. The type and impact of trauma may differ between sexes. In a large sample of recent-onset patients, we investigated the associations of depressive and negative symptoms with childhood trauma and whether these are sex-specific. A total of 187 first-episode psychosis patients in remission (Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment study) and 115 recent-onset SSD patients (Simvastatin study) were included in this cross-sectional study (men: n = 218; women: n = 84). Total trauma score and trauma subtypes were assessed using the Childhood Trauma Questionnaire Short Form; depressive and negative symptoms were rated using the Positive And Negative Symptoms Scale. Sex-specific regression analyses were performed. Women reported higher rates of sexual abuse than men (23.5% v. 7.8%). Depressive symptoms were associated with total trauma scores and emotional abuse ratings in men (β: 0.219-0.295; p ≤ 0.001). In women, depressive symptoms were associated with sexual abuse ratings (β: 0.271; p = 0.011). Negative symptoms were associated with total trauma score and emotional neglect ratings in men (β: 0.166-0.232; p ≤ 0.001). Negative symptoms in women were not linked to childhood trauma, potentially due to lack of statistical power. Depressive symptom severity was associated with different types of trauma in men and women with recent-onset SSD. Specifically, in women, depressive symptom severity was associated with childhood sexual abuse, which was reported three times as often as in men. Our results emphasize the importance of sex-specific analyses in SSD research.

Sex differences in cognitive reserve among first episode of psychosis patients.

Cognitive reserve (CR) has recently been considered a key factor in the onset of a first episode of psychosis (FEP). However, the differences in CR in FEP patients according to sex have not yet been investigated. CR was estimated among 443 FEP patients (246 men and 197 women) and 156 healthy controls (96 men and 60 women) by using the proxies premorbid IQ, years of education and employment status. A neuropsychological battery was administrated to measure neurocognitive specific domains. Analyses of variance were used to make comparisons between groups. FEP women had greater CR than FEP men. This circumstance was not observed in healthy controls. Among the group of patients with low CR, FEP women outperformed FEP men in the cognitive domains verbal memory and processing speed. Meanwhile, among the FEP patients with high CR, men showed better performance in attention than women. Differences in CR observed between FEP men and women could be related to a number of specific factors, such as, age at illness onset, education level, and variability in performance in verbal memory, processing speed, and attention domains. These results provide background information about CR in FEP patients that will be useful in the design of sex specific cognitive remediation interventions.

Subjective quality of life among first-episode psychosis patients in Chennai, India and Montreal, Canada.

Differences in subjective quality of life among persons receiving early intervention for psychosis in varying geo-sociocultural contexts have rarely been examined. Our prospective longitudinal study compared the quality of life of persons with first-episode psychosis receiving two years of similar early intervention in Chennai, India and Montreal, Canada. We hypothesized that general life satisfaction would be higher in Chennai compared to Montreal, and that social relations (a specific quality of life component) would also be higher in Chennai and positively contribute to general life satisfaction. Participants completed the general satisfaction and social relations domains of the Wisconsin Quality of Life Index at baseline, months 12 and 24. Baseline weighted mean general satisfaction and social relations scores were in the low to moderate range. Generalized estimating equation analyses showed that general satisfaction scores increased with time [Wald χ2 (1)=125.28, p<0.001] and were higher in Chennai than in Montreal [Wald χ2 (1)=7.50, p=0.006]. Social relations scores showed the highest association with general satisfaction scores (B=0.52), followed by positive symptom remission (B=0.24) and gender (B=0.18) with Chennai males having the highest general satisfaction scores. Social relations weighted mean scores increased with time [Wald χ2 (1)=87.30, p<0.001] and were positively associated with years of education [Wald χ2 (1)=4.76, p=0.029] and early negative symptom remission [Wald χ2 (1)=7.38, p=0.007]. Our results suggest that subjective quality of life may improve following early intervention for psychosis across contexts. Our findings advance knowledge about the role of sociocultural (e.g., gender) and clinical factors in influencing subjective outcomes in psychosis, and point to social support networks and symptom remission as avenues to boost quality of life.

Inflammatory cytokines and white matter microstructure in the acute phase of first-episode psychosis: A longitudinal study.

Schizophrenia-related psychosis is associated with abnormalities in white matter (WM) microstructure and structural brain dysconnectivity. However, the pathological process underlying such changes is unknown. We sought to investigate the potential association between peripheral cytokine levels and WM microstructure during the acute phase of first-episode psychosis (FEP) in a cohort of drug-naïve patients. Twenty-five non-affective FEP patients and 69 healthy controls underwent MRI scanning and blood collection at study entry. After achieving clinical remission, 21 FEP were reassessed; 38 age and biological sex-matched controls also had a second assessment. We measured fractional anisotropy (FA) of selected WM regions-of-interest (ROIs) and plasma levels of four cytokines (IL-6, IL-10, IFN-γ, and TNF-α). At baseline (acute psychosis), the FEP group showed reduced FA relative to controls in half the examined ROIs. Within the FEP group, IL-6 levels were negatively correlated with FA values. Longitudinally, patients showed increments of FA in several ROIs affected at baseline, and such changes were associated with reductions in IL-6 levels. A state-dependent process involving an interplay between a pro-inflammatory cytokine and brain WM might be associated with the clinical manifestation of FEP. This association suggests a deleterious effect of IL-6 on WM tracts during the acute phase of psychosis.

A Proxy Approach to Family Involvement and Neurocognitive Function in First Episode of Non-Affective Psychosis: Sex-Related Differences.

Schizophrenia spectrum disorders (SSD) often show cognitive deficits (CD) impacting daily life. Family support has been shown to be protective against CD, yet the relationship between these in psychotic patients remains complex and not fully understood. This study investigated the association between a subdomain of family support, namely, family involvement (estimated through a proxy measure), cognitive functioning, and sex in first-episode psychosis (FEP) patients. The sample included 308 patients enrolled in the Program for Early Phases of Psychosis (PAFIP), divided into 4 groups based on their estimated family involvement (eFI) level and sex, and compared on various variables. Women presented lower rates of eFI than men (37.1% and 48.8%). Higher eFI was associated with better cognitive functioning, particularly in verbal memory. This association was stronger in women. The findings suggest that eFI may be an important factor in FEP patients' cognitive functioning. This highlights the importance of including families in treatment plans for psychotic patients to prevent CD. Further research is needed to better understand the complex interplay between family support, sex, and cognitive functioning in psychotic patients and develop effective interventions that target these factors.

A tablet-based quantitative assessment of manual dexterity for detection of early psychosis.

We performed a pilot study on whether tablet-based measures of manual dexterity can provide behavioral markers for detection of first-episode psychosis (FEP), and whether cortical excitability/inhibition was altered in FEP. Behavioral and neurophysiological testing was undertaken in persons diagnosed with FEP (N = 20), schizophrenia (SCZ, N = 20), autism spectrum disorder (ASD, N = 20), and in healthy control subjects (N = 20). Five tablet tasks assessed different motor and cognitive functions: Finger Recognition for effector (finger) selection and mental rotation, Rhythm Tapping for temporal control, Sequence Tapping for control/memorization of motor sequences, Multi Finger Tapping for finger individuation, and Line Tracking for visuomotor control. Discrimination of FEP (from other groups) based on tablet-based measures was compared to discrimination through clinical neurological soft signs (NSS). Cortical excitability/inhibition, and cerebellar brain inhibition were assessed with transcranial magnetic stimulation. Compared to controls, FEP patients showed slower reaction times and higher errors in Finger Recognition, and more variability in Rhythm Tapping. Variability in Rhythm Tapping showed highest specificity for the identification of FEP patients compared to all other groups (FEP vs. ASD/SCZ/Controls; 75% sensitivity, 90% specificity, AUC = 0.83) compared to clinical NSS (95% sensitivity, 22% specificity, AUC = 0.49). Random Forest analysis confirmed FEP discrimination vs. other groups based on dexterity variables (100% sensitivity, 85% specificity, balanced accuracy = 92%). The FEP group had reduced short-latency intra-cortical inhibition (but similar excitability) compared to controls, SCZ, and ASD. Cerebellar inhibition showed a non-significant tendency to be weaker in FEP. FEP patients show a distinctive pattern of dexterity impairments and weaker cortical inhibition. Easy-to-use tablet-based measures of manual dexterity capture neurological deficits in FEP and are promising markers for detection of FEP in clinical practice.

Delphi panel to obtain clinical consensus about using long-acting injectable antipsychotics to treat first-episode and early-phase schizophrenia: treatment goals and approaches to functional recovery

BackgroundSchizophrenia is mostly a chronic disorder whose symptoms include psychosis, negative symptoms and cognitive dysfunction. Poor adherence is common and related relapse can impair outcomes. Long-acting injectable antipsychotics (LAIs) may promote treatment adherence and decrease the likelihood of relapse and rehospitalization. Using LAIs in first-episode psychosis (FEP) and early-phase (EP) schizophrenia patients could benefit them, yet LAIs have traditionally been reserved for chronic patients.MethodsA three-step modified Delphi panel process was used to obtain expert consensus on using LAIs with FEP and EP schizophrenia patients. A literature review and input from a steering committee of five experts in psychiatry were used to develop statements about patient population, adverse event management, and functional recovery. Recruited Delphi process psychiatrists rated the extent of their agreement with the statements over three rounds (Round 1: paper survey, 1:1 interview; Rounds 2–3: email survey). Analysis rules determined whether a statement progressed to the next round and the level of agreement deemed consensus. Measures of central tendency (mode, mean) and variability (interquartile range) were reported back to help panelists assess their previous responses in the context of those of the overall group.ResultsThe Delphi panelists were 17 psychiatrists experienced in treating schizophrenia with LAIs, practicing in seven countries (France, Italy, US, Germany, Spain, Denmark, UK). Panelists were presented with 73 statements spanning three categories: patient population; medication dosage, management, and adverse events; and functional recovery domains and assessment. Fifty-five statements achieved ≥ 80% agreement (considered consensus). Statements with low agreement (40-79%) or very low agreement (< 39%) concerned initiating dosage in FEP and EP patients, and managing loss of efficacy and breakthrough episodes, reflecting current evidence gaps. The panel emphasized benefits of LAIs in FEP and EP patients, with consensus that LAIs can decrease the risk of relapse, rehospitalization, and functional dysfunction. The panel supported links between these benefits and multidimensional longer-term functional recovery beyond symptomatic remission.ConclusionsFindings from this Delphi panel support the use of LAIs in FEP and EP schizophrenia patients regardless of disease severity, number of relapses, or social support status. Gaps in clinician knowledge make generating evidence on using LAIs in FEP and EP patients critical.

Urban distance to mental healthcare units and public transport increases duration of untreated psychosis in first-episode patients.

There is a growing interest in environmental and social determinants of mental health. However, how distance to healthcare and public transportation affect illness is neglected in schizophrenia research. Here, we are interested in how the availability of mental healthcare and the ways to reach it may be associated with psychosis. We aim to investigate the association between distances to healthcare units and subway stations and duration of untreated psychosis (DUP) and greater initial severity in an antipsychotic-naïve first episode of psychosis (FEP) sample. Using 212 untreated FEP patients' data, we calculated the distances from their residences to the places of interest. Diagnoses comprehended schizophrenia spectrum disorders, depressive and bipolar affective disorders, and substance-induced disorders. Linear regressions were performed with distances as independent variables, DUP and Positive and Negative Syndrome Scale (PANSS) scores as dependent variables. Longer distance to emergency mental healthcare was related to longer DUP (95% CI: p = .034, B = 0.152) and higher total PANSS (95% CI: p = .007, B = 0.0189); longer distance to community mental healthcare units was related to longer DUP (95% CI: p = .004, B = 0.0204) and higher total PANSS (95% CI: p = .030, B = 0.152). Moreover, a longer distance to the closest subway station predicted longer DUP (95% CI: p = .019, B = 0.170). Our results indicate that poor healthcare access is related to longer DUP and higher initial PANSS scores. Future research should investigate how investments in mental health access and actions to improve public transport access could impact DUP and treatment outcomes in psychosis patients.

Familiality of the Intelligence Quotient in First Episode Psychosis: Is the Degree of Family Resemblance Associated With Different Profiles?

There is uncertainty about the relationship between the family intelligence quotient (IQ) deviation and the risk for schizophrenia spectrum disorders (SSD). This study tested the hypothesis that IQ is familial in first episode psychosis (FEP) patients and that their degree of familial resemblance is associated with different profiles. The participants of the PAFIP-FAMILIAS project (129 FEP patients, 143 parents, and 97 siblings) completed the same neuropsychological battery. IQ-familiality was estimated through the Intraclass Correlation Coefficient (ICC). For each family, the intra-family resemblance score (IRS) was calculated as an index of familial similarity. The FEP patients were subgrouped and compared according to their IRS and IQ. IQ-familiality was low-moderate (ICC = 0.259). A total of 44.9% of the FEP patients had a low IRS, indicating discordancy with their family-IQ. Of these patients, those with low IQ had more schizophrenia diagnosis and a trend towards poorer premorbid adjustment in childhood and early adolescence. Whereas FEP patients with low IQ closely resembling their family-IQ were characterized by having the lowest performance in executive functions. The deviation from the familial cognitive performance may be related to a particular pathological process in SSD. Individuals with low IQ who do not reach their cognitive familial potential show difficulties in adjustment since childhood, probably influenced by environmental factors. Instead, FEP patients with high phenotypic family resemblance might have a more significant genetic burden for the disorder.

Biomarkers as proxies for cognitive reserve: The role of high density lipoprotein cholesterol in first episode of psychosis

IntroductionThe proxies used to compose cognitive reserve (CR) for patients of a first episode of psychosis (FEP) have varied in the literature. The development of FEP is linked to peripheral pathways of the central nervous system, yet despite this knowledge, no research has considered the introduction of biomarkers as proxies for CR. Meanwhile, schizophrenia has been linked to the metabolic system, indicating that alterations in the levels of biological parameters, in particular high-density lipoproteins (HDL), cause worse global functioning and cognitive impairment. For these reasons, the present study aimed to create a quantifiable and objective CR index that adjusts for the multifactorial nature of FEP. Materials and methodsWe included 668 FEP patients and 217 healthy controls. Participants were assessed for sociodemographic information, years of education, employment status, premorbid IQ and biological parameters: waist circumference, hypertension, and levels of HDL, triglycerides, and glucose. ResultsThe findings suggest that the years of education proxy showed correlational and higher relationship with HDL levels for both FEP patients (r=0.23, b=0.185) and controls (r=0.31, b=0.342). We found that the CR index composed of years of education and HDL levels showed a higher explanatory power for the phenomenon than the classical CR index composed of years of education, employment status and premorbid IQ. ConclusionsThis article proposes an objective and quantifiable method to measure CR that is more the multifactorial nature of FEP.

Association between PLA2 gene polymorphisms and treatment response to antipsychotic medications: A study of antipsychotic-naïve first-episode psychosis patients and nonadherent chronic psychosis patients

Here we investigated whether antipsychotic treatment was influenced by three polymorphisms: rs10798059 (BanI) in the phospholipase A2 (PLA2)G4A gene, rs4375 in PLA2G6, and rs1549637 in PLA2G4C. A total of 186 antipsychotic-naïve first-episode psychosis patients or nonadherent chronic psychosis individuals (99 males and 87 females) were genotyped by polymerase chain reaction analysis/restriction fragment length polymorphism. At baseline, and after 8 weeks of treatment with various antipsychotic medications, we assessed patients’ Positive and Negative Syndrome Scale (PANSS) scores, PANSS factors, and metabolic syndrome-related parameters (fasting plasma lipid and glucose levels, and body mass index). We found that PLA2G4A polymorphism influenced changes in PANSS psychopathology, and PLA2G6 polymorphism influenced changes in PANSS psychopathology and metabolic parameters. PLA2G4C polymorphism did not show any impact on PANSS psychopathology or metabolic parameters. The polymorphisms’ effect sizes were estimated as moderate to strong, with contributions ranging from around 6.2–15.7%. Furthermore, the polymorphisms’ effects manifested in a gender-specific manner.

Basal Metabolic Rate Related to Metabolic and Clinical Features in Male Patients With First-Episode Psychosis

We investigated basal metabolic rate (BMR) in male patients with drug-naïve first-episode psychosis (FEP) in order to explore the hypothesis that a reduced BMR plays a role in severity of illness. The study was conducted with a total of 59 drug-naïve FEP patients, 41 of whom were severe and 18 nonsevere. BMR was measured using Body-Gem Analyzer 3.0 Metabolism Measurement Device indirect calorimetry. At the same time, the clinical characteristics and laboratory tests of the participants were measured. The patients were divided into two groups as severe and nonsevere according to the Clinical Global Impression-Severity. At the end of measurement, the BMR was compared between patients with severe and nonsevere illness. BMR of patients with severe illness was found to be statistically significantly lower than BMR of patients with nonsevere illness. Another finding of the study is that in patients with severe FEP we can expect BMR values below the cut-offvalue of 1,830 kcal/day. The study provides evidence that BMR is reduced with severity of illness in drug-naïve FEP patients. [ Psychiatr Ann . 2023;53(6):264–269.]

Effects of Anticholinergic Burden on Verbal Memory Performance in First-Episode Psychosis.

Antipsychotics are widely used to treat first-episode psychosis but may have an anticholinergic burden, that is, a cumulative effect of medications that block the cholinergic system. Studies suggest that a high anticholinergic burden negatively affects memory in psychosis, where cognitive deficits, particularly those in verbal memory, are a core feature of the disease. The present study sought to replicate this in a large cohort of well-characterized first-episode psychosis patients. We expected that patients in the highest anticholinergic burden group would exhibit the poorest verbal memory compared to those with low anticholinergic burden and healthy controls at baseline (3 months following admission). We further hypothesized that over time, at month 12, patients' verbal memory performance would improve but would remain inferior to controls. Patients (n = 311; low anticholinergic burden [n = 241] and high anticholinergic burden [n = 70], defined by a Drug Burden Index cut-off of 1) and healthy controls (n = 128) completed a clinical and neurocognitive battery including parts of the Wechsler Memory Scale at months 3 and 12. Cross-sectionally, using an analysis of variance, patients in the highest anticholinergic burden group had the poorest performance in verbal memory when compared to the other groups at month 3, F(2,430) = 52.33, P < 0.001. Longitudinally, using a Generalized Estimating Equation model, the verbal memory performance of all groups improved over time. However, patients' performance overall remained poorer than the controls. These findings highlight the importance of considering the anticholinergic burden when prescribing medications in the early stages of the disease.

The co-occurrence of manic and depressive dimensions in early psychosis: a latent transition analysis.

Frequently associated with early psychosis, depressive and manic dimensions may play an important role in its course and outcome. While manic and depressive symptoms can alternate and co-occur, most of the studies in early intervention investigated these symptoms independently. The aim of this study was therefore to explore the co-occurrence of manic and depressive dimensions, their evolution and impact on outcomes. We prospectively studied first-episode psychosis patients (N = 313) within an early intervention program over 3 years. Based on latent transition analysis, we identified sub-groups of patients with different mood profiles considering both manic and depressive dimensions, and studied their outcomes. Our results revealed six different mood profiles at program entry and after 1.5 years follow-up (absence of mood disturbance, co-occurrence, mild depressive, severe depressive, manic and hypomanic), and four after 3 years (absence of mood disturbance, co-occurrence, mild depressive and hypomanic). Patients with absence of mood disturbance at discharge had better outcomes. All patients with co-occurring symptoms at program entry remained symptomatic at discharge. Patients with mild depressive symptoms were less likely to return to premorbid functional level at discharge than the other subgroups. Patients displaying a depressive component had poorer quality of physical and psychological health at discharge. Our results confirm the major role played by mood dimensions in early psychosis, and show that profiles with co-occurring manic and depressive dimensions are at risk of poorer outcome. An accurate assessment and treatment of these dimensions in people with early psychosis is crucial.

Exploration of cannabis use and polygenic risk scores on the psychotic symptom progression of a FEP cohort

Cannabis use is highly prevalent in first-episode psychosis (FEP) and plays a critical role in its onset and prognosis, but the genetic underpinnings promoting both conditions are poorly understood. Current treatment strategies for cannabis cessation in FEP are clearly inefficacious. Here, we aimed to characterize the association between cannabis-related polygenic risk scores (PRS) on cannabis use and clinical course after a FEP. A cohort of 249 FEP individuals were evaluated during 12 months. Symptom severity was measured with the Positive and Negative Severity Scale and cannabis use with the EuropASI scale. Individual PRS for lifetime cannabis initiation (PRSCI) and cannabis use disorder (PRSCUD) were constructed. Current cannabis use was associated with increased positive symptoms. Cannabis initiation at younger ages conditioned the 12-month symptom progression. FEP patients with higher cannabis PRSCUD reported increased baseline cannabis use. PRSCI was associated with the course of negative and general symptomatology over follow-up. Cannabis use and symptom progression after a FEP were modulated by cannabis PRS, suggesting that lifetime initiation and use disorders may have partially independent genetic factors. These exploratory results may be the first step to identify those FEP patients more vulnerable to cannabis use and worse outcomes to ultimately develop tailored treatments.

Systemic inflammation and cortical neurochemistry in never-medicated first episode-psychosis individuals

Studies of cellular and cytokine profiles have contributed to the inflammation hypothesis of schizophrenia; however, precise markers of inflammatory dysfunction remain elusive. A number of proton magnetic resonance spectroscopy (1H-MRS) studies in patients with first-episode psychosis (FEP) have shown higher brain levels of metabolites such as glutamate, myo-inositol (mI) and choline-containing compounds (tCho), suggesting neuroinflammation. Here, we present peripheral inflammatory profiles in antipsychotic-naive FEP patients and age-and-sex matched healthy controls, as well as cortical glutamate, mI and tCho levels using 1H-MRS. Inflammatory profiles were analyzed using cytokine production by peripheral blood mononuclear cells, that were either spontaneous or stimulated, in 48 FEP patients and 23 controls. 1H-MRS of the medial prefrontal cortex was obtained in 29 FEP patients and 18 controls. Finally, 16 FEP patients were rescanned after 4 weeks of treatment (open-label) with Risperidone. FEP patients showed a higher proportion of proinflammatory Th1/Th17 subset, and an increased spontaneous production of Interleukin (IL)-6, IL-2 and IL-4 compared with the control group. Results obtained from 1H-MRS showed no significant difference in either glutamate, mI or tCho between FEP and control groups. At baseline, CD8% showed a negative correlation with glutamate in FEP patients; after 4 weeks of risperidone treatment, the FEP group exhibited a decrease in glutamate levels which positively correlated with CD4 + T cells. Nevertheless, these correlations did not survive correction for multiple comparisons. FEP patients show evidence of immune dysregulation, affecting both the innate and adaptive immune response, with a predominantly Th2 signature. These findings, along with the changes produced by antipsychotic treatment, could be associated with both systemic and central inflammatory processes in schizophrenia.

Immunological protein profiling of first-episode psychosis patients identifies CSF and blood biomarkers correlating with disease severity

Background and HypothesisImmune activation is suggested to play an important role in psychosis. In this study, a large number of immune-related proteins were analyzed to obtain a more comprehensive picture of immune aberrations in schizophrenia. Study DesignNinety-two immune markers were analyzed by the Olink Protein Extension Assay (Inflammatory Panel) in plasma and cerebrospinal fluid (CSF) from 77 first-episode psychosis (FEP) patients (of which 43 later received the diagnosis of schizophrenia) and 56 healthy controls, all recruited from the Karolinska Schizophrenia Project (KaSP), Stockholm, Sweden. Study ResultsDifferential analysis showed that 12 of 92 inflammatory proteins were significantly higher in the plasma of FEP patients (n = 77) than in controls, and several proteins were positively correlated with disease severity. Patients from the same cohort diagnosed with schizophrenia (n = 43), showed significantly higher levels of 15 plasma proteins compared to controls whereas those not receiving this diagnosis showed no significant differences. The presently used OLINK inflammatory panel allowed the detection of only 47 CSF proteins of which only CD5 differed between patients and controls. ConclusionsThe levels of several peripheral immune markers, particularly those interfering with WNT/β-catenin signaling, were significantly higher in patients with FEP than in healthy controls and associated with illness severity.

Cannabis use as a potential mediator between childhood adversity and first-episode psychosis: results from the EU-GEI case–control study

AbstractBackgroundChildhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis.MethodsData were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0–11 years), and late (12–17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use.ResultsThe association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord.ConclusionsHarmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.