First-episode Psychosis Research Articles

Early Treatment-Resistance in First Episode Psychosis.

Approximately 30% of individuals with schizophrenia experience treatment resistance (TR), with 70% exhibiting it from the onset. Most research fails to distinguish between acquired and innate resistance, with limited data on TR in first episode psychosis (FEP). However, FEP patients with TR experience progressively worse outcomes compared to those with initial response. To further understand these findings, clinical and demographic data of FEP patients with and without TR were compared in this naturalistic study. Information was extracted on FEP patients who were antipsychotic-naive at the time of admission from a retrospective database on F2x diagnosed patients admitted to the LMU psychiatric clinic between 2008 and 2018. Clozapine was used at discharge as a marker of TR in the FEP cohort. A similarly antipsychotic-naïve FEP control group without clozapine at discharge, was generated by matching for gender and age. Thirty clinical and demographic variables were analyzed to identify differences. Two-hundred forty antipsychotic-naive FEPs were included: 33 with clozapine at discharge (TRC group), and 207 in the control group (non-TRC). Significant differences were observed in inpatient stay duration, chlorpromazine-equivalent dosage, number of antipsychotics, and anticholinergic medication at discharge. The findings indicate that longer inpatient stay, an increased number of antipsychotics, and possibly a more extended prodrome may serve as markers for non-clozapine TR in FEP. Further research is necessary to establish the robustness of these variables as early-stage TR markers.

Meta-analyses of epigenetic age acceleration and GrimAge components of schizophrenia or first-episode psychosis.

Schizophrenia is a common chronic psychiatric disorder that causes age-related dysfunction. The life expectancy in patients with schizophrenia is ≥10 years shorter than that in the general population because of the higher risk of other diseases, such as cardiovascular diseases. Aging studies based on DNA methylation status have received considerable attention. Several epigenetic age accelerations and predicted values of aging-related proteins (GrimAge and GrimAge2 components) have been analyzed in multiple diseases. However, no studies have investigated up to GrimAge and GrimAge2 components between patients with schizophrenia and controls. Therefore, we aimed to conduct multiple regression analyses to investigate the association between schizophrenia and epigenetic age accelerations and GrimAge and GrimAge2 components in seven cohorts. Furthermore, we included patients with first-episode psychosis whose illness duration was often shorter than schizophrenia in our analysis. We integrated these results with meta-analyses, noting the acceleration of GrimAge, GrimAge2, and DunedinPACE, and increase in adrenomedullin, beta-2 microglobulin, cystatin C, and plasminogen activation inhibitor-1 levels, in patients with schizophrenia or first-episode psychosis. These results corroborated the finding that patients with schizophrenia had an increased risk of diabetes, cardiovascular disease, and cognitive dysfunction from a biological perspective. Patients with schizophrenia and first-episode psychosis showed differences in the results when compared with controls. Such analyses may lead to the development of novel therapeutic targets to patients with schizophrenia or relevant diseases from the perspective of aging in the future.

The California collaborative network to promote data driven care and improve outcomes in early psychosis (EPI-CAL) project: rationale, background, design and methodology.

A prolonged first episode of psychosis (FEP) without adequate treatment is a predictor of poor clinical, functional, and health outcomes and significant economic burden. Team-based "coordinated specialty care" (CSC) for early psychosis (EP) has established effectiveness in promoting clinical and functional recovery. However, California's CSC program implementation has been unsystematic and could benefit from standardizing its processes and data collection infrastructure. To address this, we established a consortium of EP clinics across the state via a Learning Health Care Network (LHCN) framework to develop the Early Psychosis Intervention Network of California (EPI-CAL). EPI-CAL's LHCN developed a core battery of evidence-based measures for service users and family members and linked them together using a unique data collection and visualization application, Beehive. EPI-CAL's LHCN collects, visualizes, and aggregates data at the individual and clinic level for EP programs across California via Beehive. Beehive was designed to: (1) collect outcomes data from service users receiving care at EP programs and their support persons, (2) provide the data to providers on a secure web-based dashboard to support measurement-based care, and (3) allow data to be used for program or research analysis. We will (1) determine the feasibility of implementing an LHCN across a diverse, decentralized network of early psychosis programs, (2) determine if the implementation of an LHCN increases the delivery of measurement-based care, and (3) determine if the implementation of measurement-based care is associated with significant improvements in key service user outcomes. EPI-CAL's network will contribute data to the Early Psychosis Intervention Network (EPINET) program. The current study aims to establish an LHCN of EP clinics in California that implements harmonized data collection using Beehive and assesses the feasibility of establishing such a network. Our goal is for this harmonized data collection approach to be used to inform decisions and develop learning opportunities for service users, staff, and administrators, and to improve outcomes for service users and their supporters in CSC care. Further, the data will enable programs and research teams to examine what elements of care lead to program success and improved treatment outcomes for service users. www. gov , identifier NCT04007510; registered 07/05/2019.

Impact of minimal self disorders on naturalistic episodic memory in first-episode psychosis and parallels in healthy individuals with schizotypal traits

BackgroundSelf-disorders constitute a core feature of the schizophrenia spectrum, including early stages such as first-episode psychosis (FEP). These disorders impact the minimal Self, or bodily self-consciousness, which refers to the basic, pre-reflective sense of embodied experience. The minimal Self is intrinsically linked to episodic memory, which captures specific past experiences of the Self. However, research on this relationship in the schizophrenia spectrum remains scarce. This pilot study aimed to investigate how the minimal Self modulated episodic memory of naturalistic events in FEP, using immersive virtual reality. A secondary objective was to examine the relationships between sense of Self, embodiment, episodic memory, schizotypal personality traits in healthy participants (CTL), and psychopathology in FEP.MethodsA full-body illusion was induced in 10 FEP and 35 matched CTL, using a first-person avatar, with synchronous or asynchronous visuomotor stimulation (strong or weak embodiment conditions, respectively). Following embodiment induction, participants navigated a virtual city and encountered naturalistic daily life events, which were incidentally encoded. Episodic memory of these events was assessed through a comprehensive recognition task (factual and contextual information, retrieval phenomenology). Sense of Self, schizotypal personality traits, and psychopathology were assessed via self-reported questionnaires or clinical assessments.ResultsSynchronous visuomotor stimulation successfully induced a stronger sense of embodiment in both FEP and CTL. The strong embodiment condition was associated with reduced perceived virtual space occupation by the body in FEP. Under strong embodiment, FEP performed significantly worse than CTL in contextual information recognition, but their ratings for retrieval phenomenology were comparable to CTL. Conversely, under weak embodiment, FEP performed similarly to CTL in contextual information recognition, but they rated retrieval phenomenology significantly lower. For CTL, we observed a slight, though non-significant, enhancement in recognition memory under strong compared to weak embodiment. Additionally, higher schizotypy in CTL correlated with a diminished sense of Self and poorer episodic memory.ConclusionsDisturbances in the minimal Self in FEP are associated with episodic memory impairments. These findings emphasise the importance of targeting minimal Self-disorders in schizophrenia spectrum disorders, since episodic memory impairments may negatively affect patients’ quality of life and psychosocial outcomes. Additionally, they support a fully dimensional model of schizotypy.

Synaptic Density in Early Stages of Psychosis and Clinical High Risk.

Synaptic dysfunction is involved in schizophrenia pathophysiology. However, whether in vivo synaptic density is reduced in early stages of psychosis, including its high-risk states, remains unclear. To investigate whether synaptic density (synaptic vesicle glycoprotein 2A [SV2A] binding potential) is reduced in first-episode psychosis (FEP) and in clinical high risk (CHR) and investigate the effect of cannabis use on synaptic density and examine its relationship with psychotic symptoms and gray matter microstructure across groups. This cross-sectional study was performed in a tertiary care psychiatric hospital from July 2021 to October 2023. Participants were patients with antipsychotic-free or minimally exposed FEP or CHR and healthy controls with a clean urine drug screen (except cannabis). Synaptic density was quantified with dynamic 90-minute [18F]SynVesT-1 positron emission tomography (PET) scans across prioritized brain regions of interest (ROIs) delineated in individual magnetic resonance images (MRIs). Cannabis use was confirmed with urine drug screens. Gray matter microstructure was assessed using diffusion-weighted MRI to estimate neurite density. A total of 49 participants were included, including 16 patients with FEP (mean [SD] age, 26.1 [4.6] years; 9 males and 7 females), 17 patients at CHR (mean [SD] age, 21.2 [3.5] years; 8 males and 9 females), and 16 healthy controls (mean [SD] age, 23.4 [3.6] years; 7 males and 9 females). Synaptic density was significantly different between groups (F2,273 = 4.02, P = .02, Cohen F = 0.17; ROI: F5,273 = 360.18, P < .01, Cohen F = 2.55) with a group × ROI interaction (F10,273 = 2.67, P < .01, Cohen F = 0.32). Synaptic density was lower in cannabis users (F1,272 = 5.31, P = .02, Cohen F = 0.14). Lower synaptic density across groups was associated with more negative symptoms (Positive and Negative Syndrome Scale negative scores: F1,81 = 4.31, P = .04, Cohen F = 0.23; Scale of Psychosis-Risk Symptoms negative scores: F1,90 = 4.12, P = .04, Cohen F = 0.21). SV2A binding potential was significantly associated with neurite density index (F1,138 = 6.76, P = .01, Cohen F = 0.22). This study found that synaptic density reductions were present during the early stages of psychosis and its risk states and associated with negative symptoms. The implications of SV2A for negative symptoms in psychosis and CHR warrant further investigation. Future studies should investigate the impact of cannabis use on synaptic density in CHR longitudinally.

Reasons for disengagement in first-episode psychosis - perspectives from service users and their caregivers.

The efforts of early psychosis intervention programmes can be impeded by difficulties in maintaining the engagement of service users. As disengagement is often an autonomous decision made by service users, the main aim of this study was to gain insight into the reasons for service user disengagement through qualitative interviews with the service users themselves, and caregivers as proxies or secondary informants. Participants recruited for the study were enrolled in the Early Psychosis Intervention Programme in Singapore for at least a year, aged 21 and above, able to communicate in English, and had disengaged for at least three months. The recruitment and interview processes were conducted independently for service user and caregiver participants. Potential participants were invited to a face-to-face semi-structured interview over video call or in-person. Each interview spanned one to two hours, and comprised five phases - icebreaker, exploration of the participant's experience with EPIP before deciding to disengage, discussion of reasons for disengagement, exploration of the post-disengagement experience, and feedback and suggestions for EPIP. Recruitment aimed to conclude after 10-15 participants were interviewed for both service user and caregiver groups, with the expectation that data sufficiency would be reached with no new themes being generated. Ultimately, 12 service user and 12 caregiver participants were recruited. There were six pairs of service user and caregiver dyads, where the caregivers interviewed were caring for service users also enrolled in the study. Valuable qualitative insights were gathered, including the type of disengagement, medication compliance during disengagement, the decision-making process behind disengaging, and circumstances surrounding re-engagement. A total of five categories each with subthemes were identified from the reasons for service user disengagement - individual factors, stigma, progression, treatment factors, and external factors. There is a need to narrow down urgent areas of attention, aligning the study themes with established risk factors so that feasible solutions can be developed and appropriate care models can be adopted, to minimise adverse outcomes related to disengagement. It is important to keep an open mind to understand what personal recovery means to the individual service user, so that treatment goals can be better harmonised.

Evidence of altered monoamine oxidase B, an astroglia marker, in early psychosis and high-risk state.

A novel radiotracer, [11C]SL25.1188, targets monoamine oxidase-B (MAO-B) enzyme, found primarily in astrocytes, which metabolizes monoamines (including dopamine), particularly in subcortical regions. Altered astrocyte function in schizophrenia is supported by convergent evidence from post-mortem, genetic, transcriptomic, peripheral and preclinical findings. We aimed to test whether levels of MAO-B, an index of astrocyte function are low in the living brains of early psychosis and their high-risk states. Thirty-eight participants including antipsychotic-free/minimally exposed clinical participants with first-episode psychosis (FEP), clinical high-risk (CHR) individuals and healthy volunteers (HVs) underwent a 90-min positron emission tomography (PET) scan with [11C]SL25.1188, to measure MAO-B VT, an index of MAO-B concentration. Participants were excluded if tested positive on urine drug screen (except for cannabis). This study of 14 FEP (mean[SD] age, 25.7[5.7] years; 6 F), 7 CHR (mean[SD] age, 20.9[3.7] years; 4 F) and 17 HV (mean[SD] age, 31.2[13.9] years; 9 F) demonstrated significant group differences in regional MAO-B VT (F(2,37.42) = 4.56, p = 0.02, Cohen's f = 0.49), controlling for tobacco (F (1,37.42) = 5.37, p = 0.03) and cannabis use (F(1,37.42) = 5.11, p = 0.03) with significantly lower MAO-B VT in CHR compared to HV (Cohen's d = 0.99). We report a significant cannabis effect on MAO-B VT (F(1,39.19) = 12.57, p = 0.001, Cohen's f = 0.57), with a significant group-by-cannabis interaction (F(2,37.30) = 3.82, p = 0.03, Cohen's f = 0.45), indicating lower MAO-B VT in cannabis-using clinical groups. Lower MAO-B VT levels were more robust in striatal than cortical regions, in both clinical groups (F(12,46.84) = 2.08, p = 0.04, Cohen's f = 0.73) and in cannabis users (F(6,46.84) = 6.42, p < 0.001, Cohen's f = 0.91). Lower MAO-B concentration supports astrocyte dysfunction in cannabis-using CHR and FEP clinical populations. Lower MAO-B is consistent with replicated striatal dopamine elevation in psychosis, as well as astrocyte dysfunction in schizophrenia.

Exploring the longitudinal course of motor dexterity in first-episode psychosis: a 10-year follow-up.

This study aimed to examine longitudinal changes in motor dexterity (MD) performance in first episode of psychosis (FEP), focusing on diagnosis-specific trajectories. Participants were recruited from the project PAFIP in Spain (134 FEP, 84 HC). MD was assessed using the Grooved Pegboard Test at baseline and at 10-year follow-up. Clinical and premorbid data were collected for the patients. FEP participants were classified as having schizophrenia (SCZ) or other psychosis (OP) and compared with a group of healthy controls (HC). MD correlated significantly with age and intelligence in all participants. MD in SCZ patients was additionally correlated with premorbid adjustment and negative symptoms, whereas in the OP group the association was with antipsychotic dose. SCZ patients showed a slight decline in MD at follow-up, whereas the OP and HC groups remained stable. There may be different long-term trajectories of MD across diagnoses in FEP patients. Early developmental factors such as premorbid adaptation and cognitive function, together with age-related changes, may influence a mild decline in MD specifically in schizophrenia.

Plasma essential amino acid levels in first episode psychosis at baseline and after antipsychotic treatment

This study assessed plasma levels of essential amino acids (EAA) in drug-naïve first episode psychosis (FEP) patients at diagnosis and after 10 weeks of antipsychotic treatment. Forty FEP patients were enrolled at baseline, with blood samples collected before and after a 10-week antipsychotic treatment period. Plasma EAA levels were measured using an LC/MS/MS method. Psychotic symptoms were evaluated using standardized inventories before and after treatment. A decrease in BPRS score of more than 40% was used to indicate treatment response. Thirty-five healthy volunteers served as the control group. Baseline plasma levels of Thr, Met, Leu, Lys, His, and Tyr were higher in FEP patients than in healthy controls. After 10 weeks of treatment, Leu, His, and Tyr increased further, primarily in treatment-responsive patients. Conversely, Val level was lower than controls in patients at baseline and remained unchanged after treatment. Increased EAA levels were correlated with lower (less severe) scores in positive symptom scales. Treatment non-responders had persistently low Tyr/large neutral amino acid (LNAA) ratio. Tyr/LNAA ratio increased after treatment, specifically in treatment-responders. Phe/Tyr ratio decreased post-treatment in both responder and non-responder groups. Elevated EAA levels in FEP patients may signify compensatory responses to increased physiological demand for neurotransmitters or energy. Combining specific EAA supplementation with antipsychotic treatment may enhance treatment response in these patients.

Retina in Clinical High-Risk and First-Episode Psychosis.

Abnormalities in the retina are observed in psychotic disorders, especially in schizophrenia. Using spectral-domain optical coherence tomography, we investigated structural retinal changes in relatively metabolic risk-free youth with clinical high-risk (CHR, n = 34) and first-episode psychosis (FEP, n = 30) compared with healthy controls (HCs, n = 28). Total retinal macular thickness/volume of the right eye increased in FEP (effect sizes, Cohen's d = 0.69/0.66) and CHR (d = 0.67/0.76) compared with HCs. Total retinal thickness/volume was not significantly different between FEP and CHR. Macular retinal nerve fiber layer (RNFL) thickness/volume of the left eye decreased in FEP compared with HCs (d = -0.75/-0.66). Peripapillary RNFL thickness was not different between groups. The ganglion cell (GCL), inner plexiform (IPL), and inner nuclear (INL) layers thicknesses/volumes of both eyes increased in FEP compared with HCs (d = 0.70-1.03). GCL volumes of both eyes, IPL thickness/volume of the left eye, and INL thickness/volume of both eyes increased in CHR compared with HCs (d = 0.64-1.01). In the macula, while central sector thickness/volume decreased (d = -0.62 to -0.72), superior outer (peri-foveal) sector thickness/volume of both eyes increased (d = 0.81 to 0.86) in FEP compared with HCs. The current findings suggest that distinct regions and layers of the retina may be differentially impacted during the emergence and early phase of psychosis. Consequently, oculomics could play significant roles, not only as a diagnostic tool but also as a mirror reflecting neurobiological changes at axonal and cellular levels.

Antipsychotic discontinuation in nonaffective first-episode psychosis after clinical remission: Insights from the PEPsNa naturalistic study

The predictors of clinical evolution after nonaffective first-episode psychosis (NAFEP) have yet to be fully elucidated. It is important to weigh the long-term benefits of maintained antipsychotic (AP) treatment against the risks of relapse upon discontinuation. Between January 2017 and December 2022, we recruited 211 NAFEP patients from the Programa de Primeros Episodios Psicóticos de Navarra (PEPsNa) who achieved clinical remission within two years and continued follow-up. Clinicians recommended discontinuation of antipsychotics for 47 participants, resulting in significantly fewer relapses (10.6%, p≤ 0.05) and a longer relapse-free survival time (95% confidence interval= 16.9 to 18.2 months). For every four individuals out of 72 who voluntarily discontinued APs (in contrast to those who were advised to discontinue APs), there was one more relapse (number needed to harm= 4; p≤ 0.01). Moreover, one additional relapse was prevented for every seven individuals who continued APs instead of voluntarily discontinuing APs (number needed to treat= 7; p≤ 0.05). Lower premorbid risk factors and better clinical profiles, such as shorter DUP, shorter time to remission, good real-world performance, better neurocognitive functioning, lack of a schizophrenia spectrum diagnosis, and a lower average dose of APs led clinicians to recommend AP discontinuation after achieving remission from NAFEP. This guided discontinuation of APs did not lead to a higher risk of relapse, but participants who voluntarily withdrew from treatment had a higher risk of relapse.

Comparative Study of Inflammatory Markers in Schizophrenia, FirstEpisode Psychosis, and Bipolar Disorder

Objective: An elevated level of NLR level is defined as an indicator of systemic inflammation, and it is stated that it can be used as an effective tool in navigating psychosis. The aim of the present study is to explore the blood parameters such as neutrophil, lymphocyte, and monocyte and their ratios (NLR, MLR, PLR) in both affective and non-affective psychosis. Materials and Methods: This is a retrospective case-control study conducted on schizophrenia(Sch), first-episode psychosis(FEP), and bipolar disorder(BD). Digital medical records were retrospectively analyzed between 2016 to 2021. The total number of patients recruited for this study is 437. Patients were divided into 3 groups which are schizophrenia (n:199), FEP (n:127), and Bipolar Disorder (n:111). The healthy control (HC) group (n:200) was selected who had never been diagnosed with any psychiatric disorders. Results: In this study, no difference was found between the patient groups in terms of substance use (Chi-square= 5.008; p= 0.082), platelet count was lower in SCH patients and no difference was found between the other groups in terms of platelet count. There was no statistical difference between the study groups in terms of lymphocyte, neutrophil, and monocyte counts and their ratios (NLR, MLR, PLR) (p&amp;gt;0.05 for each). Conclusion: In contrast to the previous findings, we did not show any significant differences in NLR, MLR, and PLR levels in both affective and non-affective psychosis. To better understand the pathophysiology of psychosis, it might be more suitable to conduct a clinical trial with drug-naive FEP patients in a prospective manner.

The effect of polygenic risk score and childhood adversity on transdiagnostic symptom dimensions at first-episode psychosis: evidence for an affective pathway to psychosis

Childhood adversity is associated with various clinical dimensions in psychosis; however, how genetic vulnerability shapes the adversity-associated psychopathological signature is yet to be studied. We studied data of 583 First Episode Psychosis (FEP) cases from the EU-GEI FEP case-control study, including Polygenic risk scores for major depressive disorder (MDD-PRS), bipolar disorder (BD-PRS) and schizophrenia (SZ-PRS); childhood adversity measured with the total score of the Childhood Trauma Questionnaire (CTQ); and positive, negative, depressive and manic psychopathological domains from a factor model of transdiagnostic dimensions. Genes and environment interactions were explored as a departure from a multiplicative effect of PRSs and total CTQ on each dimension. Analyses were adjusted for age, sex, 10 PCA, site of recruitment and for medication. A childhood adversity and PRS multiplicative interaction was observed between A) the CTQ and MDD-PRS on the predominance of positive (β = 0.42, 95% CI = [0.155, 0.682], p = 0.004); and depressive (β = 0.33, 95% CI = [0.071, 0.591], p = 0.013) dimensions; B) between the CTQ and BD-PRS on the positive dimension (β = 0.45, 95% CI = [0.106, 0.798], p = 0.010), and C) with the CTQ and SZ-PRS on the positive dimension (β = −0.34, 95% CI = [−0.660, −0.015], p = 0.040). Bonferroni corrected p-value of significance was set at 0.0125. In conclusion, despite being underpowered, this study suggests that genetic liability for MDD and BD may have a moderating effect on the sensibility of childhood adversity on depressive and positive psychotic dimensions. This supports the hypothesis of an affective pathway to psychosis in those exposed to childhood adversity.

Effectiveness of Omega-3 Fatty Acids Versus Placebo in Subjects at Ultra-High Risk for Psychosis: The PURPOSE Randomized Clinical Trial.

In the past 2 decades, substantial effort has been put into research on therapeutic options for people at ultra-high risk (UHR) for developing a first episode of psychosis (FEP), focusing on omega-3 polyunsaturated fatty acids (PUFAs) in preventing transition to psychosis. Despite an initial positive finding, subsequent studies failed to find a beneficial effect. The current study aimed to further investigate the effect of omega-3 PUFAs in UHR, to determine whether this line of research is worth pursuing. A double-blind, randomized, placebo-controlled study testing the efficacy of 6-month treatment with omega-3 PUFAs in 135 subjects at UHR for FEP, aged 13 to 20 years on the prevention of a transition to psychosis, followed up for 18 months post-treatment. The trial was conducted at 16 general hospitals and psychiatric specialty centers located in 8 European countries and Israel. There was no beneficial effect of treatment with omega-3 PUFAs compared to placebo; the rate of transition over 2 years did not differ between treatment arms nor was there a difference in change in symptom severity after 6-month treatment. Dropout rates and serious adverse events were similar across the groups. This is the third study that fails to replicate the original finding on the protective effect of omega-3 PUFAs in UHR subjects for transition to psychosis. The accumulating evidence therefore suggests that omega-3 PUFAs do not reduce transition rates to psychosis in those at increased risk at 2 years follow-up. This trial is registered with ClinicalTrials.gov (NCT02597439; Study Details | Placebo-controlled Trial in Subjects at Ultra-high Risk for Psychosis With Omega-3 Fatty Acids in Europe | ClinicalTrials.gov).

Cognitive Impairments Related to COMT and Neuregulin 1 Phenotypes as Transdiagnostic Markers in Schizophrenia Spectrum Patients.

Background: Research on the interaction between antipsychotic treatment and cognitive dysfunction in schizophrenia spectrum disorders (SSDs) is extensive, yet the role of genetic polymorphisms in catechol-O-methyltransferase (COMT) and neuregulin 1 (NRG1) remains underexplored. Methods: This study evaluates the impact of COMT (rs4680) and NRG1 (rs3924999 and rs35753505) polymorphisms on cognitive functions in SSD patients. A cross-sectional study was conducted with fifty-four patients, assessed using the Positive and Negative Syndrome Scale (PANSS) and the CNS Vital Signs battery. Results: Significant cognitive function differences were observed across SSD diagnostic categories (p < 0.001). The NRG1 rs35753505 TT genotype was significantly associated with better verbal memory performance compared to the CC genotype (p = 0.03), while no significant differences were observed for other genotypes. The NRG1 rs3924999 AA genotype showed superior reasoning performance compared to AG and GG genotypes (p = 0.01), with AG and GG associated with lower scores (p = 0.01 and p = 0.02, respectively). Additionally, the COMT Val158Met genotype significantly influenced processing speed, with patients at the first episode of psychosis showing higher scores than chronic patients (p = 0.01). Conclusions: These findings suggest that NRG1 and COMT polymorphisms may influence cognitive domains in schizophrenia spectrum disorders, potentially informing personalized treatment and cognitive rehabilitation strategies.

Sex differences in the association of overweight with cognitive performance in individuals with first-episode psychosis

Cognitive deficits and overweight are prominent challenges in the treatment of psychosis, which have a direct impact on patients’ quality of life. We aim to determine whether there is an association of overweight with cognitive performance and whether there are sex differences in this association. We included 170 individuals with first-episode psychosis (FEP) (mean age 23.08 years, 32.9% females) attending an early intervention service who underwent clinical, biometric, and cognitive assessments by the MATRICS Consensus Cognitive Battery. A set of two-way analyses of covariance (ANCOVAs) were conducted for each cognitive test. Sex, overweight, and their interaction were included as factors. Nearly 34% of the participants were overweight without differences between males and females. The excess of weight did not exert any main effect on cognition; however, overweight females performed significantly worse than non-overweight females in processing speed, verbal learning and memory, reasoning and problem-solving, and global cognitive function, whereas in males, there were no differences. Our findings highlight that sex matters in the study of metabolic and cognitive factors in FEP to develop targeted interventions based on sex perspectives.

Taking what you get or Getting what you Need: A Qualitative Study on Experiences with Mental Health and Welfare Services in Long-Term Recovery in First-Episode Psychosis.

How people in long-term recovery (clinical and personal) in first-episode psychosis (schizophrenia and bipolar spectrum disorders) experience the mental health and welfare services they interact with is not frequently studied but has significant implications. We therefore aimed to explore which aspects of these services people with FEP evaluate as important for their long-term recovery. Twenty participants in clinical and/or personal recovery from two Norwegian long-term follow-up studies after FEP (TOP 10-year and TIPS 20-year) were sampled for this interview-based qualitative study. The research-team included service user experience. A deductive analysis based on personal accounts of recovery generated five service aspects. Few specific types of interventions were reported to promote recovery although medications, psychotherapy and employment support were mentioned. Participants valued services based in collaboration and that focused on their resources rather than limitations. The importance of long-term follow-up with a consistent aim was highlighted, as was the inclusion of caregivers and peers. Welfare services contributed to recovery by supporting basic needs and safety, but some experienced social exclusion when not participating in the labor market. This study is unique in exploring the role of services, including welfare, in long-term FEP recovery from service user perspectives. Participants evaluated that services played a more indirect role in long-term recovery by supporting their personal resources, although what they needed from services had frequently not been offered. Their expertise by experience contributes valuable knowledge. Better service coordination and consistent implementation of this knowledge are crucial to support recovery in FEP.

Methylomic signature of current cannabis use in two first-episode psychosis cohorts.

The rising prevalence and legalisation of cannabis worldwide have underscored the need for a comprehensive understanding of its biological impact, particularly on mental health. Epigenetic mechanisms, specifically DNA methylation, have gained increasing recognition as vital factors in the interplay between risk factors and mental health. This study aimed to explore the effects of current cannabis use and high-potency cannabis on DNA methylation in two independent cohorts of individuals experiencing first-episode psychosis (FEP) compared to control subjects. The combined sample consisted of 682 participants (188 current cannabis users and 494 never users). DNA methylation profiles were generated on blood-derived DNA samples using the Illumina DNA methylation array platform. A meta-analysis across cohorts identified one CpG site (cg11669285) in the CAVIN1 gene that showed differential methylation with current cannabis use, surpassing the array-wide significance threshold, and independent of the tobacco-related epigenetic signature. Furthermore, a CpG site localised in the MCU gene (cg11669285) achieved array-wide significance in an analysis of the effect of high-potency (THC = > 10%) current cannabis use. Pathway and regional analyses identified cannabis-related epigenetic variation proximal to genes linked to immune and mitochondrial function, both of which are known to be influenced by cannabinoids. Interestingly, a model including an interaction term between cannabis use and FEP status identified two sites that were significantly associated with current cannabis use with a nominally significant interaction suggesting that FEP status might moderate how cannabis use affects DNA methylation. Overall, these findings contribute to our understanding of the epigenetic impact of current cannabis use and highlight potential molecular pathways affected by cannabis exposure.

Impact of family engagement on client participation in coordinated specialty care for first episodes of psychosis

BackgroundCoordinated specialty care (CSC) programs for first episodes of psychosis are increasingly offered in the United States. A component of CSC programs is active family engagement in treatment, though research on the impact of this engagement is limited. This study examined the characteristics of families engaged compared to families not engaged in treatment, and the impact of family engagement on client participation and medication adherence over the first 6 months of treatment.MethodsUsing data from the Early Psychosis Intervention Network (EPINET) research hub in Minnesota (EPI-MINN), we compared two groups of individuals: clients who had a family member(s) engaged in their treatment vs. clients who did not. Family engagement was defined as any treatment services provided to a family member(s) by CSC clinical staff. The groups were compared on intake demographic variables, duration of untreated psychosis (DUP), hospitalizations, symptom severity, and functioning. A comparison of the total number of treatment visits during the first 6 months of treatment was tested using both nonparametric (Mann Whitney U) and parametric (ANCOVA) tests. Group comparisons on self ratings of “intent to attend visits,” “intent to complete the program,” and medication adherence were tested with ANCOVA and Chi-Square.ResultsFamily-engaged clients were younger, with less years of education, and more often White; clients without family engagement were more often Black. Family engagement was positively associated with increased total number of visits for all interventions with the exceptions of client peer support and case management visits. Family engagement increased clients’ self-reported intent to attend visits, though not intention to complete the program, which was moderately to markedly high in both groups. No differences were noted with medication adherence, with high rates of adherence across the entire study sample.ConclusionsOverall, results of the study support the benefits of family engagement in CSC on client participation, though future research is needed to understand why Black families are less engaged and what treatment adaptations are needed to reduce these racial differences. The results also support the value of CSC programs for medication adherence, a critical factor in symptom reduction and mental health recovery.

Determining unmet need: clinical relevance of suspected neurodivergence in first-episode psychosis.

We explored the prevalence of autism and attention-deficit hyperactivity disorder in first-episode psychosis. Through service evaluation involving 509 individuals, detailed analyses were conducted on neurodevelopmental traits and patterns of service utilisation. Prevalence of neurodivergence in first-episode psychosis was 37.7%. Neurodivergent individuals used urgent mental health services more frequently (Mann-Whitney U = 25925, Z = -2.832, P = 0.005) and had longer hospital stays (Mann-Whitney U = 22816, Z = -4.886, P ≤ 0.001) than non-neurodivergent people. Neurodivergent people spend more than twice as long in mental health hospitals at a time than the non-neurodivergent people (Mann-Whitney U = 22 909.5, Z = -4.826, P ≤ 0.001). Mediation analysis underscored indirect impact of neurodivergence on hospital stay durations through age at onset of psychosis and use of emergency services. Prevalence of neurodevelopmental conditions in first-episode psychosis is underestimated. Neurodivergent individuals show increased utilisation of mental health services and experience psychosis earlier. Early assessment is crucial for optimising psychosis management and improving mental health outcomes.