BACKGROUND: A previous meta-analysis indicated stable progress in cognitive functions in early psychosis, assessed through various tools. To avoid assessment-related heterogeneity, this study aims to examine the longitudinal cognitive function changes in early psychosis utilizing the MATRICS Consensus Cognitive Battery (MCCB).
METHODS: Embase, PubMed, and Scopus were systematically searched from their inception to September 26th 2023. The inclusion criteria were longitudinal studies that presented follow-up MCCB data for individuals experiencing first-episode psychosis (FEP) and those with ultra-high risk for psychosis (UHR).
RESULTS: Twelve studies with 791 participants (566 FEP patients and 225 healthy controls) were subjected to analysis. Suitable UHR studies were absent. Over time, both FEP patients and healthy controls showed significant improvements in MCCB total scores. Furthermore, FEP patients demonstrated improvements across all MCCB domains, while healthy controls only showed augmentations in specific domains such as speed of processing, attention, working memory, and reasoning and problem-solving. Visuospatial learning improvements were significantly greater in FEP patients compared to healthy controls. Subgroup analyses suggested that neither diagnostic type nor follow-up duration influenced the magnitude of cognitive improvement in FEP patients.
CONCLUSIONS: The magnitude of cognitive improvement for MCCB domains was not significantly different between FEP and healthy controls other than visuospatial learning. This underscores visuospatial learning as a potentially sensitive cognitive marker for early pathologic state changes in psychotic disorders.

While duration of the psychosis prodrome (DPP) attracts attention in relation to the developmental trajectory of psychotic illness and service models, fundamental issues endure in the context of dimensional-spectrum models of psychosis. Among 205 epidemiologically representative subjects in the Cavan-Monaghan First Episode Psychosis Study, DPP was systematically quantified and compared, for the first time, across all 12 DSM-IV psychotic diagnoses. DPP was also compared with duration of untreated psychosis (DUP) and each was then analysed in relation to premorbid features across three age ranges: <12, 12-15 and 16-18 years. For each diagnosis, medians for both DPP and DUP were shorter than means, indicating common right-skewed distributions. Rank orders for both DPP and DUP were longest for schizophrenia, intermediate for other schizophrenia-spectrum psychoses, psychotic depression and psychotic disorder not otherwise specified, and shortest for brief psychotic disorder, bipolar disorder and substance-induced psychotic disorder, though with overlapping right-skewed distributions. DPP was longer than DUP for all diagnoses except substance-induced psychotic disorder. Across functional psychotic diagnoses, longer DPP was predicted by higher premorbid intelligence and better premorbid adjustment during age 16-18 years. These findings indicate that, trans-diagnostically, DPP and DUP share right-skewed continuities, in accordance with a dimensional-spectrum model of psychotic illness, and may reflect a unitary process that has been dichotomized at a subjective threshold along its trajectory. Better premorbid functioning during age 16-18 years appears to confer resilience by delaying progression to overt psychotic symptoms and may constitute a particular target period for psychosocial interventions.

The impact of Coronavirus Disease 2019 (COVID-19) on psychiatric care in remitted patients with first-episode psychosis (FEP) remains unknown. This study compared the demographic, clinical, functional, and cognitive profiles of patients recruited before and during the pandemic. The results showed that COVID patients were significantly older, smokers, alcohol users, experienced more stressors, with better functioning than pre-COVID patients. The former also had fewer severe negative and general psychopathological symptoms, more impaired insight, poorer medication compliance, and worse cognitive performance. Our findings highlighted a timely need to improve awareness into the illness and treatment in FEP patients experiencing pandemic related stressors.

Previous studies have revealed that brain-derived neurotrophic factor (BDNF) levels are inversely associated with the severity of depressive symptoms. In addition, serum BDNF levels tend to increase with improvement in depressive symptoms. There is also evidence that BDNF has a possible role in the pathophysiology of schizophrenia. Therefore, the purpose of this study was to determine whether BDNF levels correlated with depressive symptoms in patients with first-episode and drug-naïve (FEDN) schizophrenia. In this study, 90 patients with FEDN schizophrenia and 60 healthy controls were recruited. The Positive and Negative Syndrome Scale (PANSS) and the 17-item Hamilton Depression Scale (HAMD-17) were used to gage psychopathological and depressive symptoms, respectively. All participants had their BDNF levels measured using a sandwich enzyme-linked immunosorbent test. Serum BDNF levels were lower in patients with FEDN schizophrenia compared with healthy controls. Moreover, patients with depressive symptoms exhibited a higher PANSS total score and a higher general psychopathology score than those without depressive symptoms (p < 0.05). For patients with depressive symptoms, serum BDNF levels were higher than in those without depressive symptoms (p < 0.05). An association between BDNF levels and the positive subscore was also observed (p < 0.01). However, there was no significant association between BDNF levels and HAMD scores (p > 0.05). In conclusion, BDNF levels were shown to be higher in the serum of patients with FEDN schizophrenia with depressive symptoms than in those without. Additionally, low levels of serum BDNF may contribute to the positive symptoms of FEDN schizophrenia but not to depressive symptoms.

Facial Emotion Recognition is a key domain of social cognition associated with psychotic disorders as a candidate intermediate phenotype. In this study, we set out to investigate global and specific facial emotion recognition deficits in first-episode psychosis, and whether polygenic liability to psychotic disorders is associated with facial emotion recognition.
828 First Episode Psychosis (FEP) patients and 1308 population-based controls completed assessments of the Degraded Facial Affect Recognition Task (DFAR) and a subsample of 524 FEP and 899 controls provided blood or saliva samples from which we extracted DNA, performed genotyping and computed polygenic risk scores for schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MD).
A worse ability to globally recognize facial emotion expressions was found in patients compared with controls [B= -1.5 (0.6), 95% CI -2.7 to -0.3], with evidence for stronger effects on negative emotions (fear [B = -3.3 (1.1), 95% CI -5.3 to -1.2] and anger [B = -2.3 (1.1), 95% CI -4.6 to -0.1]) than on happiness [B = 0.3 (0.7), 95% CI -1 to 1.7]. Pooling all participants, and controlling for confounds including case/control status, facial anger recognition was associated significantly with Schizophrenia Polygenic Risk Score (SZ PRS) [B = -3.5 (1.7), 95% CI -6.9 to -0.2].
Psychosis is associated with impaired recognition of fear and anger, and higher SZ PRS is associated with worse facial anger recognition. Our findings provide evidence that facial emotion recognition of anger might play a role as an intermediate phenotype for psychosis.

BACKGROUND: Abnormalities of cortical thickness (CTh) in patients with their first episode psychosis (FEP) have been frequently reported, but findings are inconsistent.
OBJECTIVE: To define the most consistent CTh changes in patients with FEP by meta-analysis of published whole-brain studies.
METHODS: The meta-analysis used seed-based d mapping (SDM) software to obtain the most prominent regional CTh changes in FEP, and meta-regression analyses to explore the effects of demographics and clinical characteristics. The meta-analysis results were verified in an independent sample of 142 FEP patients and 142 age- and sex-matched healthy controls (HCs), using both a vertex-wise and a region of interest analysis, with multiple comparisons correction.
RESULTS: The meta-analysis identified lower CTh in the right middle temporal cortex (MTC) extending to superior temporal cortex (STC), insula, and anterior cingulate cortex (ACC) in FEP compared with HCs. No significant correlations were identified between CTh alterations and demographic or clinical variables. These results were replicated in the independent dataset analysis.
CONCLUSIONS: This study identifies a robust pattern of cortical abnormalities in FEP and extends understanding of gray matter abnormalities and pathological mechanisms in FEP.

This study systematically compared duration of untreated illness (DUI) with duration of untreated psychosis (DUP) in prediction of impairment at first-episode psychosis and investigated the extent to which these relationships are influenced by premorbid features. The Cavan-Monaghan First Episode Psychosis Study ascertained cases of first-episode psychosis in rural Ireland via all routes to care with limited variations in socioeconomic milieu. Cases were evaluated for DUI and DUP and assessed clinically for psychopathology, neuropsychology, neurology, insight and quality of life, together with premorbid features. Analyses then determined prediction of clinical assessments by DUI versus DUP. The study population consisted of 163 cases of first episode psychosis, among which 74 had a schizophrenia spectrum disorder. Shorter DUI but not DUP predicted less severe positive and general symptoms, while shorter DUP and particularly DUI predicted less severe negative symptoms; neither shorter DUP nor shorter DUI predicted less severe cognitive impairment or fewer neurological soft signs; shorter DUP and DUI predicted increased quality of life; shorter DUI but not DUP predicted greater insight. Only prediction of quality of life was weakened by consideration of premorbid features. Results were generally similar across the two diagnostic groupings. The present findings systematically delineate associations with DUI versus DUP across domains of impairment in first episode psychosis. They suggest that DUI may reflect a more insidious process than DUP and that reduction in DUI may be associated with more consistent and broader diminutions in impairment than for DUP.

The association between schizophrenia (SZ) and uric acid (UA) levels has been suggested for many years, but without solid evidence. Therefore, we conducted a systematic review and meta-analysis of all case-control studies examining the serum and plasma UA levels in SZ subjects in comparison to those in healthy controls. Relevant studies published before October 29, 2018, were searched in the main electronic databases, and 17 studies were finally included into the meta-analysis after screening with the criteria. Our results revealed that there were no statistically significant differences of the UA levels between SZ subjects and healthy controls. Further subgroup analyses of the antipsychotic status reported the same finding. Subgroup analyses of clinical status showed that UA levels were decreased in subjects with first episode psychosis (FEP). The subgroup analyses of gender and ethnicity demonstrated that UA levels were decreased in male subjects and in Americans with SZ. Overall, these findings strengthen the clinical evidence that FEP is accompanied by increased oxidative stress response. Reduced UA levels may be a potential risk factor for SZ in male and in the Americans. However, whether there is a causal relationship between the reduced UA levels and the development of SZ deserves further investigation.

The \'jumping to conclusions\' (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.
A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.
The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI -0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25-0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = -1.7, 95% CI -2.8 to -0.5, p = 0.006), but did not relate to delusions in patients.
Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.

Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients.
We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses.
In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14-0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = -0.22; 95% CI -0.37 to -0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use.
Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.