Cognitive impairment is a core feature of psychosis, which adversely affects global functioning and quality of life and has been consistently reported from the early stages of illness. Patients with first-episode psychosis (FEP) exhibit deficits in processing speed, short-term memory, attention, working memory, and executive functioning, which respond poorly to psychotropic drugs. Among non-pharmacological approaches, physical activity has shown promise in improving cognitive functioning in schizophrenia spectrum disorders. However, current evidence lacks specific data on individuals with FEP. In this review, we aim to explore the potential role of physical activity-based interventions in ameliorating the cognitive functions of people with FEP.

The literature search was conducted on PubMed, PsycINFO, and Web of Science in March 2024, identifying 127 de-duplicated records. One additional article was identified by screening the reference lists of the included studies. A total of six studies fulfilled the inclusion criteria and were reviewed. They all analyzed the effect of structured physical activity interventions on the cognitive functioning of patients with FEP.

Preliminary findings suggest that physical activity interventions enhance memory, attention, and executive functions of patients with FEP but not social cognition and motor function.

Study differences in sample characteristics, design, and intervention protocols prevent firm conclusions about the cognitive-boosting effects of the interventions in FEP. Further studies using more rigorous methodologies are needed to understand the durability of these effects and the underlying mechanisms.

To assess the impact of the COVID-19 pandemic on first-episode psychosis (FEP) presentations across two Early Intervention in Psychosis (EIP) services in Ireland, by comparing pre-pandemic and post-pandemic cohorts.

A cross-sectional observational design with retrospective medical record review was employed. The study population comprised 187 FEP patients (77 in pre-pandemic and 110 in post-pandemic cohort). Outcomes measured included duration of untreated psychosis (DUP), FEP presentation numbers, referral sources, global assessment of functioning scores, inpatient admissions, substance misuse and service delivery methods. Statistical analyses utilised chi-square tests to assess categorical variables, Mann–Whitney U tests to compare non-normally distributed continuous variables and Kruskal–Wallis tests to examine interactions between categorical and continuous variables.

A significant increase in FEP presentations was observed in the post-pandemic cohort (p = 0.003), with an increase in all urban areas and a decrease in the study’s only rural area. The difference in DUP between cohorts was not significant. However, significant interaction between gender, cohort and DUP was shown (p = 0.008), with women in the post-pandemic cohort experiencing longer DUP (p = 0.01). A significant rise in telephone (p = 0.05) and video consultations (p = 0.001) offered was observed, in the post-pandemic cohort. A similar number of in-person appointments were attended across both cohorts.

This study highlights the impact of the pandemic on FEP presentations, particularly rurally and regarding increased DUP among women. These findings underscore the need for flexible EIP services to respond to public health crises. Despite increased presentations, services adapted, maintaining service continuity through telehealth and modified in-person contact.

The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.

Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.

In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10−10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.

Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.

Executive control over low-level information processing is impaired proximal to psychosis onset with evidence of recovery over the first year of illness. However, previous studies demonstrating diminished perceptual modulation via attention are complicated by simultaneously impaired perceptual responses. The present study examined the early auditory gamma-band response (EAGBR), a marker of early cortical processing that appears preserved in first-episode psychosis (FEP), and its modulation by attention in a longitudinal FEP sample.

Magnetoencephalography was recorded from 25 FEP and 32 healthy controls (HC) during active and passive listening conditions in an auditory oddball task at baseline and follow-up (4–12 months) sessions. EAGBR inter-trial phase coherence (ITPC) and evoked power were measured from responses to standard tones. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS).

There was no group difference in EAGBR power or ITPC. While EAGBR ITPC increased with attention in HC, this modulation was impaired among FEP. Diminished EAGBR modulation in FEP persisted at longitudinal follow-up. However, among FEP, recovery of EAGBR modulation was associated with reduced PANSS negative scores.

FEP exhibit impaired executive control over the flow of information at the earliest stages of sensory processing within auditory cortex. In contrast to previous work, this deficit was observed despite an intact measure of sensory processing, mitigating potential confounds. Recovery of sensory gain modulation over time was associated with reductions in negative symptoms, highlighting a source of potential resiliency against some of the most debilitating and treatment refractory symptoms in early psychosis.

Cognitive impairment constitutes a prevailing issue in the schizophrenia spectrum, severely impacting patients' functional outcomes. A global cognitive score, sensitive to the stages of the spectrum, would benefit the exploration of potential factors involved in the cognitive decline.

First, we performed principal component analysis on cognitive scores from 768 individuals across the schizophrenia spectrum, including first-degree relatives of patients, individuals at ultra-high risk, who had a first-episode psychosis, and chronic schizophrenia patients, alongside 124 healthy controls. The analysis provided 10 g-factors as global cognitive scores, validated through correlations with intelligence quotient and assessed for their sensitivity to the stages on the spectrum using analyses of variance. Second, using the g-factors, we explored potential mechanisms underlying cognitive impairment in the schizophrenia spectrum using correlations with sociodemographic, clinical, and developmental data, and linear regressions with genotypic data, pooled through meta-analyses.

The g-factors were highly correlated with intelligence quotient and with each other, confirming their validity. They presented significant differences between subgroups along the schizophrenia spectrum. They were positively correlated with educational attainment and the polygenic risk score (PRS) for cognitive performance, and negatively correlated with general psychopathology of schizophrenia, neurodevelopmental load, and the PRS for schizophrenia.

The g-factors appeared as valid estimators of global cognition, enabling discerning cognitive states within the schizophrenia spectrum. Educational attainment and genetics related to cognitive performance may have a positive influence on cognitive functioning, while general psychopathology of schizophrenia, neurodevelopmental load, and genetic liability to schizophrenia may have an adverse impact.

Short-term exposure to antipsychotics has proven to be beneficial. However, naturalistic studies are lacking regarding the long-term use of antipsychotics. This study aimed to investigate changes in use of antipsychotics over 20 years after a first-episode schizophrenia.

This study is part of the Danish OPUS trial (1998–2000), including 496 participants with first-episode schizophrenia. Participants were reassessed four times over 20 years. The main outcomes were days on medication, redeemed prescriptions of clozapine, psychiatric hospitalizations, and employment.

At the 20-year follow-up, an attrition of 71% was detected. In total, 143 out of 496 participated, with 36% (n = 51) in remission-of-psychotic-symptoms-off-medication. The lowest number of days on medication (mean [s.d.], 339 [538] days) was observed in this group over 20 years. Register data on redeemed antipsychotics were available for all trial participants (n = 416). Individuals in treatment with antipsychotics (n = 120) at the 20-year follow-up had spent significantly more days in treatment (5405 [1857] v. 1434 [1819] mean days, p = 0.00) and more had ever redeemed a prescription of clozapine (25% v. 7.8%, p = 0.00) than individuals who had discontinued antipsychotics (n = 296). Further, discontinuers had significantly higher employment at the 20-year follow-up (28.4% v. 12.5%, p = 0.00).

In a cohort of individuals with first-episode schizophrenia, 36% were in remission-of-psychotic-symptoms-off-medication. However, high attrition was detected, potentially affecting study results by inflating results from individuals with favorable outcomes. From register data, free from attrition, approximately 30% were in treatment with antipsychotics, and 70% had discontinued antipsychotics. Individuals in treatment had the least favorable outcomes, implying greater illness severity.

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.

Evidence suggests a possible relationship between exposure to childhood adversity (CA) and functional impairment in psychosis. However, the impact of CA on long-term outcomes of psychotic disorders remains poorly understood.

Two hundred and forty-three patients were assessed at their first episode of psychosis for CA and re-assessed after a mean of 21 years of follow-up for several outcome domains, including symptoms, functioning, quality of life, cognitive performance, neurological dysfunction, and comorbidity. The unique predictive ability of CA exposure for outcomes was examined using linear regression analysis controlling for relevant confounders, including socioeconomic status, family risk of schizophrenia, and obstetric complications.

There were 54% of the patients with a documented history of CA at mild or higher levels. CA experiences were more prevalent and severe in schizophrenia than in other psychotic disorders (p < 0.001). Large to very large effect sizes were observed for CA predicting most role functioning variables and negative symptoms (ΔR2 between 0.105 and 0.181). Moderate effect sizes were observed for positive symptoms, personal functioning, impaired social cognition, impaired immediate verbal learning, poor global cognition, internalized stigma, poor personal recovery, and drug abuse severity (ΔR2 between 0.040 and 0.066). A dose–response relationship was observed between levels of CA and severity of outcome domains.

Our results suggest a strong and widespread link between early adversity exposure and outcomes of psychotic disorders. Awareness of the serious long-term consequences of CA should encourage better identification of those at risk and the development of effective interventions.

First-episode psychotic disorders comprise a heterogeneous phenotype with a complex etiology involving numerous common small-effect genetic variations and a wide range of environmental exposures. We examined whether a family of schizophrenia spectrum disorder (FH-Sz) interacts with an environmental risk score (ERS-Sz) regarding the outcome of patients with non-affective first episode psychosis (NAFEP).

We included 288 patients with NAFEP who were evaluated after discharge from an intensive 2-year program. We evaluated three outcome measures: symptomatic remission, psychosocial functioning, and personal recovery. We analyzed the main and joint associations of a FH-Sz and the ERS-Sz on the outcomes by using the relative excess risk due to interaction (RERI) approach.

A FH-Sz showed a significant association with poor symptomatic remission and psychosocial functioning outcomes, although there was no significant interaction between a FH-Sz and the ERS-Sz on these outcomes. The ERS-Sz did not show a significant association with poor symptomatic remission and psychosocial functioning outcomes, even though the magnitude of the interaction between ERS-Sz and FH-Sz with the later outcome was moderate (RERI = 6.89, 95% confidence interval −16.03 to 29.81). There was no association between a FH-Sz and the ERS-Sz and personal recovery.

Our results provide further empirical support regarding the contribution of FH-Sz to poor symptomatic remission and poor psychosocial functioning outcomes in patients with NAFEP.

The intelligence quotient (IQ) of patients with first-episode psychosis (FEP) and their unaffected relatives may be related to the genetic burden of schizophrenia (SCZ). The polygenic score approach can be useful for testing this question.

To assess the contribution of the polygenic risk scores for SCZ (PGS-SCZ) and polygenic scores for IQ (PGS-IQ) to the individual IQ and its difference from the mean IQ of the family (named family-IQ) through a family-based design in an FEP sample.

The PAFIP-FAMILIES sample (Spain) consists of 122 FEP patients, 131 parents, 94 siblings, and 176 controls. They all completed the WAIS Vocabulary subtest for IQ estimation and provided a DNA sample. We calculated PGS-SCZ and PGS-IQ using the continuous shrinkage method. To account for relatedness in our sample, we performed linear mixed models. We controlled for covariates potentially related to IQ, including age, years of education, sex, and ancestry principal components.

FEP patients significantly deviated from their family-IQ. FEP patients had higher PGS-SCZ than other groups, whereas the relatives had intermediate scores between patients and controls. PGS-IQ did not differ between groups. PGS-SCZ significantly predicted the deviation from family-IQ, whereas PGS-IQ significantly predicted individual IQ.

PGS-SCZ discriminated between different levels of genetic risk for the disorder and was specifically related to patients’ lower IQ in relation to family-IQ. The genetic background of the disorder may affect neurocognition through complex pathological processes interacting with environmental factors that prevent the individual from reaching their familial cognitive potential.

Cognitive deficits are a core feature of schizophrenia and are closely associated with poor functional outcomes. It remains unclear if cognitive deficits progress over time or remain stable. Determining patients at increased risk of progressive worsening might help targeted neurocognitive remediation approaches.

This 20-year follow-up study examined neurocognitive outcomes of 156 participants from the OPUS I trial. Neurocognition was assessed using the brief assessment of cognition in schizophrenia at the 10- and 20-year follow-up, allowing us to examine changes in neurocognition over ten years.

We found that 30.5% of patients had a declining course of neurocognition, 49.2% had a stable course of neurocognition and 20.3% experienced improvements in neurocognition. Good cognitive functioning at the 20-year follow-up was significantly associated with higher levels of social functioning (B 6.86, CI 4.71–9.02, p < 0.001) while increasing experiential negative symptoms were significantly correlated to cognitive worsening (PC-0.231, p = 0.029). Younger age at inclusion (B: 0.23 per 10-years, CI 0.00–0.045, p = 0.047) and low level of education (below ten years) (mean difference: −0.346, CI −0.616 to −0.076, p = 0.012) predicted declining neurocognition.

Our findings support the notion of different schizophrenia subtypes with varying trajectories. Neurocognitive impairment at the 20-year follow-up was associated with other poor outcomes, highlighting the importance of treatments aimed at improving neurocognition in patients with schizophrenia spectrum disorders.

The optimal duration of antipsychotic treatment following remission of first-episode psychosis (FEP) is uncertain, considering potential adverse effects and individual variability in relapse rates. This study aimed to investigate the effect of antipsychotic discontinuation compared to continuation on recovery in remitted FEP patients.

CENTRAL, MEDLINE (Ovid), Embase, and PsycINFO databases were searched on November 2, 2023, with no language restrictions. RCTs evaluating antipsychotic discontinuation in remitted FEP patients were selected. The primary outcome was personal recovery, and secondary outcomes included functional recovery, global functioning, hospital admission, symptom severity, quality of life, side effects, and employment. Risk of bias was assessed using the Cochrane risk-of-bias tool 2, and the certainty of evidence was evaluated with GRADE. Meta-analysis used a random-effect model with an inverse-variance approach.

Among 2185 screened studies, 8 RCTs (560 participants) were included. No RCTs reported personal recovery as an outcome. Two studies measured functional recovery, and discontinuation group patients were more likely to achieve functional recovery (RR 2.19; 95% CIs: 1.13, 4.22; I2 = 0%; n = 128), although evidence certainty was very low. No significant differences were found in hospital admission, symptom severity, quality of life, global functioning, or employment between the discontinuation and continuation groups.

Personal recovery was not reported in any antipsychotic discontinuation trial in remitted FEP. The observed positive effect of discontinuation on functional recovery came from an early terminated trial and an RCT followed by an uncontrolled period. These findings should be interpreted cautiously due to very low certainty of evidence.

The ‘at-risk mental state’ (ARMS) for psychosis has been critiqued for its limited prognostic ability and identification of a limited proportion of those who will develop a first episode of psychosis (FEP). Broadening the search for high-risk groups is key to improving population-level ascertainment of psychosis risk.

To explore risk enrichment in diagnostic, demographic and socio-functional domains among individuals referred to an early intervention in psychosis (EIP) service not meeting ARMS or FEP criteria.

A retrospective file review of 16 years of referrals to a tertiary EIP service in Ireland was undertaken. Diagnostic outcomes from standardised assessments (Structured Clinical Interview for DSM), demographic (age, gender, family history, nationality) and socio-occupational (relationship status, living status, working status) variables were compiled for those not meeting criteria. These were compared with individuals diagnosed with an FEP in the same period.

From 2005 to 2021 inclusive, of 2025 index assessments, 27.6% (n = 558) did not meet either FEP or ARMS criteria, which is notably higher than the 5.4% (n = 110) meeting ARMS criteria. This group had high psychiatric morbidity, with 65.4% meeting criteria for at least one DSM Axis I disorder. Depressive, anxiety and substance use disorders predominated. Their functional markers were poor, and comparable to the FEP cohort.

This group is enriched for psychosis risk factors. They are a larger group than those meeting ARMS criteria, a finding that may reflect EIP service configuration. They may be an important focus for further study in the search for at-risk populations beyond the current ARMS model.

Early intervention programmes (EIPs) in psychosis have gained attention as specialised interventions to improve health-related and societal impacts for people with psychotic disorders. Previous studies have presented evidence in favour of EIPs over the first year of intervention, despite none considering the critical period before psychosis onset (5 years).

To compare the associated costs of the First Episode Psychosis Intervention Program (CRUPEP) and treatment as usual (TAU) in a real-world cohort in a non-specialised psychiatric community setting.

Direct and indirect mental health-related costs were calculated over 1 year and up to 7 years. Healthcare and societal costs were calculated from economic data related to the consumption of all healthcare resources, including emergency department attendances, hospital admissions, psychotropic medication prescriptions and societal costs.

From a healthcare perspective, the intervention (CRUPEP) group initially showed a marginally higher cost per patient than the TAU group (€7621 TAU group v. €11 904 CRUPEP group) over the first year of follow-up. However, this difference was reversed between the groups on considering the entire follow-up, with the TAU group showing considerably higher associated costs per patient (€77 026 TAU v. €25 247 CRUPEP).

The EIP (CRUPEP) showed clinical benefits and minimised the direct and indirect health-related costs of the management of psychosis. Although the CRUPEP intervention initially reported increased costs over 1 year, TAU surpassed the global costs over the entire follow-up.

Although diagnostic instability in first-episode psychosis (FEP) is of major concern, little is known about its determinants. This very long-term follow-up study aimed to examine the diagnostic stability of FEP diagnoses, the baseline predictors of diagnostic change and the timing of diagnostic change.

This was a longitudinal and naturalistic study of 243 subjects with FEP who were assessed at baseline and reassessed after a mean follow-up of 21 years. The diagnostic stability of DSM-5 psychotic disorders was examined using prospective and retrospective consistencies, logistic regression was used to establish the predictors of diagnostic change, and survival analysis was used to compare time to diagnostic change across diagnostic categories.

The overall diagnostic stability was 47.7%. Schizophrenia and bipolar disorder were the most stable diagnoses, with other categories having low stability. Predictors of diagnostic change to schizophrenia included a family history of schizophrenia, obstetric complications, developmental delay, poor premorbid functioning in several domains, long duration of untreated continuous psychosis, spontaneous dyskinesia, lack of psychosocial stressors, longer duration of index admission, and poor early treatment response. Most of these variables also predicted diagnostic change to bipolar disorder but in the opposite direction and with lesser effect sizes. There were no significant differences between specific diagnoses regarding time to diagnostic change. At 10-year follow-up, around 80% of the diagnoses had changed.

FEP diagnoses other than schizophrenia or bipolar disorder should be considered as provisional. Considering baseline predictors of diagnostic change may help to enhance diagnostic accuracy and guide therapeutic interventions.