Early Psychosis Patients Research Articles

Statistical implication analysis: a novel approach to understand the reciprocal relationships between outcomes in early psychosis.

Patients can respond differently to intervention in the early phase of psychosis. Diverse symptomatic and functional outcomes can be distinguished and achieving one outcome may mean achieving another, but not necessarily the other way round, which is difficult to disentangle with cross-sectional data. The present study's goal was to evaluate implicative relationships between diverse functional outcomes to better understand their reciprocal dependencies in a cross-sectional design, by using statistical implication analysis (SIA). Early psychosis patients of an early intervention program were evaluated for different outcomes (symptomatic response, functional recovery, and working/living independently) after 36 months of treatment. To determine which positive outcomes implied other positive outcomes, SIA was conducted by using the Iota statistical implication index, a newly developed approach allowing to measure asymmetrical bidirectional relationships between outcomes. Two hundred and nineteen recent onset patients with early psychosis were assessed. Results at the end of the three-years in TIPP showed that working independently statistically implied achieving all other outcomes. Symptomatic and functional recovery reciprocally implied one another. Living independently weakly implied symptomatic and functional recovery and did not imply independent working. The concept of implication is an interesting way of evaluating dependencies between outcomes as it allows us to overcome the tendency to presume symmetrical relationships between them. We argue that a better understanding of reciprocal dependencies within psychopathology can provide an impetus to tailormade treatments and SIA is a useful tool to address this issue in cross-sectional designs.

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

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

Associations between antipsychotics-induced weight gain and brain networks of impulsivity

Given the unpredictable rapid onset and ubiquitous consequences of weight gain induced by antipsychotics, there is a pressing need to get insights into the underlying processes at the brain system level that will allow stratification of “at risk” patients. The pathophysiological hypothesis at hand is focused on brain networks governing impulsivity that are modulated by neuro-inflammatory processes. To this aim, we investigated brain anatomy and functional connectivity in patients with early psychosis (median age: 23 years, IQR = 21–27) using anthropometric data and magnetic resonance imaging acquired one month to one year after initiation of AP medication. Our analyses included 19 patients with high and rapid weight gain (i.e., ≥5% from baseline weight after one month) and 23 patients with low weight gain (i.e., <5% from baseline weight after one month). We replicated our analyses in young (26 years, IQR = 22–33, N = 102) and middle-aged (56 years, IQR = 51–62, N = 875) healthy individuals from the general population. In early psychosis patients, higher weight gain was associated with poor impulse control score (β = 1.35; P = 0.03). Here, the observed brain differences comprised nodes of impulsivity networks - reduced frontal lobe grey matter volume (Pcorrected = 0.007) and higher striatal volume (Pcorrected = 0.048) paralleled by disruption of fronto-striatal functional connectivity (R = −0.32; P = 0.04). Weight gain was associated with the inflammatory biomarker plasminogen activator inhibitor-1 (β = 4.9, P = 0.002). There was no significant association between increased BMI or weight gain and brain anatomy characteristics in both cohorts of young and middle-aged healthy individuals. Our findings support the notion of weight gain in treated psychotic patients associated with poor impulse control, impulsivity-related brain networks and chronic inflammation.

A Narrative Review Exploring Attention Deficit/Hyperactivity Disorder in Patients with Early Psychosis.

While both Attention deficit hyperactivity disorder (ADHD) and schizophrenia are considered to have neurodevelopmental origins with associated impairments in executive functioning, there is a paucity of clinical guidelines pertaining specifically to this comorbidity. We sought to summarize the existing literature on ADHD in early psychosis patients, focusing on issues that would be most relevant to clinical practice. For this narrative review, we completed a search on PubMed and PsycINFO with 22 papers meeting criteria for review. Overall, it appears that a diagnosis of ADHD in childhood increases the risk of the subsequent development of a primary psychotic disorder. This risk may be modified by higher rates of substance use and could be related to shared premorbid risk factors for both conditions, such as obstetrical complications. Stimulant use has been associated with the onset of psychotic symptoms in some individuals, but it is unclear whether certain subgroups are more susceptible. Despite the fact that these two conditions co-occur relatively frequently, there is currently a lack of objective diagnostic tests for ADHD specific to populations with primary psychotic disorders, and a paucity of evidence on whether stimulants are effective for ADHD symptoms in this sub-group. Future research is warranted to investigate whether stimulant treatment confers any additional risks for symptom exacerbation in individuals with primary psychotic disorders taking antipsychotic maintenance treatment.

Effect of long-acting antipsychotic treatment on psychiatric hospitalization rate in early psychosis patients: a naturalistic study.

The effectiveness of long-acting injectable (LAI) antipsychotics in preventing relapses of first-episode psychosis is currently debated. The study aimed to investigate the number of psychiatric hospitalizations comparing the LAI cohort versus the oral cohort during different phases of the illness, pre-LAI treatment, during LAI treatment, and after LAI treatment. A naturalistic study was conducted on two independent cohorts of early psychosis patients receiving treatment from a specific early intervention service. The first cohort comprised 228 patients who received LAIs, while the second cohort comprised 667 patients who had never received LAIs. This study was designed as a longitudinal observational study conducted within a naturalistic clinical setting in two cohorts of early psychosis patients. Repeated series ANCOVA (ANCOVA-r) was used to study the number of hospitalizations in the different study periods (T1 = from the date of the first psychiatric record to the beginning of the mirror period; T2 = the mirror period; T3 = from the LAI implementation to the LAI discontinuation; and T4 = from the LAI discontinuation to the end). In all cases, discontinuation of LAI involved the return to oral treatment. In all, 35 patients had not T4 as they were still on LAI treatment at the time of database closing (September 2020), and their data were not included in the analysis of the effect of the LAI discontinuation. The patients in the LAI cohort were younger, more frequently males, presented more schizophrenia diagnoses, and had a higher number of hospitalizations (2.50 ± 2.61 versus 1.19 ± 1.69; p < 0.001) than the oral cohort. The number of hospitalizations at the end of the follow-up was higher in the LAI cohort [0.20 (standard deviation (SD)) = 0.79] versus 0.45 [SD = 0.45 (SD = 1.13); F(23.90), p < 0.001]. However, after the introduction of LAIs, the differences in hospitalization rates between the two cohorts became less pronounced. Once LAI treatment was ceased, the hospitalization rate increased again. In our study, early psychosis patients receiving LAIs experienced a greater decrease in hospitalizations after introducing the LAI treatment than those treated solely with oral medication. These findings support using LAIs as a viable strategy for preventing rehospitalization and improving the overall course of treatment for individuals with early psychosis.

Increased whole-brain functional heterogeneity in psychosis during rest and task

Past work has shown that people with schizophrenia exhibit more cross-subject heterogeneity in their functional connectivity patterns. However, it remains unclear whether specific brain networks are implicated, whether common confounds could explain the results, or whether task activations might also be more heterogeneous. Unambiguously establishing the existence and extent of functional heterogeneity constitutes a first step toward understanding why it emerges and what it means clinically. Methods. We first leveraged data from the HCP Early Psychosis project. Functional connectivity (FC) was extracted from 718 parcels via principal components regression. Networks were defined via a brain network partition (Ji et al., 2019). We also examined an independent data set with controls, later-stage schizophrenia patients, and ADHD patients during rest and during a working memory task. We quantified heterogeneity by averaging the Pearson correlation distance of each subject’s FC or task activity pattern to that of every other subject of the same cohort. Results. Affective and non-affective early psychosis patients exhibited more cross-subject whole-brain heterogeneity than healthy controls (ps < 0.001, Hedges’ g > 0.74). Increased heterogeneity could be found in up to seven networks. In-scanner motion, medication, nicotine, and comorbidities could not explain the results. Later-stage schizophrenia patients exhibited heterogeneous connectivity patterns and task activations compared to ADHD and control subjects. Interestingly, individual connection weights, parcel-wise task activations, and network averages thereof were not more variable in patients, suggesting that heterogeneity becomes most obvious over large-scale patterns. Conclusion. Whole-brain cross-subject functional heterogeneity characterizes psychosis during rest and task. Developmental and pathophysiological consequences are discussed.

Cortical Network Disruption Is Minimal in Early Stages of Psychosis.

Schizophrenia is associated with white matter disruption and topological reorganization of cortical connectivity but the trajectory of these changes, from the first psychotic episode to established illness, is poorly understood. Current studies in first-episode psychosis (FEP) patients using diffusion magnetic resonance imaging (dMRI) suggest such disruption may be detectable at the onset of psychosis, but specific results vary widely, and few reports have contextualized their findings with direct comparison to young adults with established illness. Diffusion and T1-weighted 7T MR scans were obtained from N = 112 individuals (58 with untreated FEP, 17 with established schizophrenia, 37 healthy controls) recruited from London, Ontario. Voxel- and network-based analyses were used to detect changes in diffusion microstructural parameters. Graph theory metrics were used to probe changes in the cortical network hierarchy and to assess the vulnerability of hub regions to disruption. The analysis was replicated with N = 111 (57 patients, 54 controls) from the Human Connectome Project-Early Psychosis (HCP-EP) dataset. Widespread microstructural changes were found in people with established illness, but changes in FEP patients were minimal. Unlike the established illness group, no appreciable topological changes in the cortical network were observed in FEP patients. These results were replicated in the early psychosis patients of the HCP-EP datasets, which were indistinguishable from controls in most metrics. The white matter structural changes observed in established schizophrenia are not a prominent feature in the early stages of this illness.

The effect of using group-averaged or individualized brain parcellations when investigating connectome dysfunction in psychosis.

Functional magnetic resonance imaging (fMRI) is widely used to investigate functional coupling (FC) disturbances in a range of clinical disorders. Most analyses performed to date have used group-based parcellations for defining regions of interest (ROIs), in which a single parcellation is applied to each brain. This approach neglects individual differences in brain functional organization and may inaccurately delineate the true borders of functional regions. These inaccuracies could inflate or underestimate group differences in case-control analyses. We investigated how individual differences in brain organization influence group comparisons of FC using psychosis as a case study, drawing on fMRI data in 121 early psychosis patients and 57 controls. We defined FC networks using either a group-based parcellation or an individually tailored variant of the same parcellation. Individualized parcellations yielded more functionally homogeneous ROIs than did group-based parcellations. At the level of individual connections, case-control FC differences were widespread, but the group-based parcellation identified approximately 7.7% more connections as dysfunctional than the individualized parcellation. When considering differences at the level of functional networks, the results from both parcellations converged. Our results suggest that a substantial fraction of dysconnectivity previously observed in psychosis may be driven by the parcellation method, rather than by a pathophysiological process related to psychosis.

Central insulin dysregulation in antipsychotic-naïve first-episode psychosis: In silico exploration of gene expression signatures

Antipsychotic drug (AP)-naïve first-episode psychosis (FEP) patients display premorbid cognitive dysfunctions and dysglycemia. Brain insulin resistance may link metabolic and cognitive disorders in humans. This suggests that central insulin dysregulation represents a component of the pathophysiology of psychosis spectrum disorders (PSDs). Nonetheless, the links between central insulin dysregulation, dysglycemia, and cognitive deficits in PSDs are poorly understood. We investigated whether AP-naïve FEP patients share overlapping brain gene expression signatures with central insulin perturbation (CIP) in rodent models. We systematically compiled and meta-analyzed peripheral transcriptomic datasets of AP-naïve FEP patients along with hypothalamic and hippocampal datasets of CIP rodent models to identify common transcriptomic signatures. The common signatures were used for pathway analysis and to identify potential drug treatments with discordant (reverse) signatures. AP-naïve FEP and CIP (hypothalamus and hippocampus) shared 111 and 346 common signatures respectively, which were associated with pathways related to inflammation, endoplasmic reticulum stress, and neuroplasticity. Twenty-two potential drug treatments were identified, including antidiabetic agents. The pathobiology of PSDs may include central insulin dysregulation, which contribute to dysglycemia and cognitive dysfunction independently of AP treatment. The identified treatments may be tested in early psychosis patients to determine if dysglycemia and cognitive deficits can be mitigated.

A better understanding of the impact of childhood trauma on depression in early psychosis: A differential item functioning approach.

Childhood trauma (CT) has been shown to impact depressive symptoms measured broadly in early psychosis patients. Beyond the broad intensity of such impact, less is known about which depressive features are more impacted. Patients of a specialized early intervention programme were evaluated after the first two and six months of treatment with the Montgomery-Asberg Depression Rating Scale (MADRS). We used the first assessment available. We estimated an Item-response model to reveal potential differential item functioning (DIF) in order to highlight depressive features that could be impacted differently than others by experiences of abuse (sexual physical and emotional) and neglect (physical and emotional). Two hundred and sixty-two recent onset patients with psychosis were assessed. Results at the beginning of the Treatment and Early Intervention in Psychosis Program (TIPP) showed that abuse but not neglect was associated with more severe depression levels, measured at a global MADRS score. Concerning specific depressive symptoms, concentration difficulties were left largely unaffected by abuse in contrast with other aspects of depression. The cognitive item of the depressive dimension assessed by the MADRS was not impacted by experiences of abuse, while the remaining subdomains involving anxiety, suicidality, somatic symptoms, and anhedonia were. Trials focusing on improving the impact of depression in traumatised individuals should account for the possible diluting effect of concentration when measuring the depression broadly. DIF is a promising method to better understand the impact many variables may have on various psychological dimensions at the item level.

Rates and correlates of medication non-adherence behaviors and attitudes in adult patients with early psychosis.

Literature on antipsychotic medication adherence in early psychosis primarily assessed adherence behaviors and focused on young patients. There is a paucity of research investigating negative medication attitude and its determinants in the early illness course, particularly in older-aged sample. We aimed to examine prevalence and correlates of medication non-adherence behaviors and negative medication attitudes separately in adult patients with early psychosis. One hundred ninety-nine Chinese early psychosis patients aged 26-55years who had received three-year treatment for first psychotic episode in Hong Kong were examined. Assessments encompassing socio-demographics, premorbid adjustment, clinical and treatment profiles, self-stigma and therapeutic alliance were conducted. Patients were evaluated with Medication Compliance Questionnaire, which is a modified Chinese-translated version of Medication Adherence Rating Scale and includes items measuring adherence behaviors and attitudes towards medications. Rates of medication non-adherence and negative attitude towards medications were 38.7% and 50.8%, respectively. Multivariate regression analysis showed that more severe positive symptoms, greater self-stigma and negative medication attitude were independently associated with medication non-adherence. Negative attitude towards medications was significantly associated with younger age, higher educational attainment, diagnosis of other psychotic disorders, poorer insight, greater self-stigma and less satisfaction with communication with healthcare staff, which represented an index reflecting suboptimal therapeutic alliance. Antipsychotic non-adherence and negative medication attitudes are frequently observed in adult early psychosis patients. Our findings indicate that poor insight, elevated self-stigma and suboptimal therapeutic alliance may constitute potential treatment targets for promoting medication adherence and rectifying negative medication attitudes in the early illness stage.

Rate and correlates of self-stigma in adult patients with early psychosis.

Self-stigma impedes recovery process and is associated with poorer clinical and functional outcomes in people with psychotic disorders. However, there is limited research specifically examining self-stigma in the early stage of illness, and mixed findings were observed regarding factors associated with increased self-stigma. We aimed to investigate the rate and correlates of self-stigma in a cohort of adult patients with early psychosis using a comprehensive array of clinical, treatment and other illness-related variables. A total of 101 Chinese adult early psychosis patients aged 26-55 years who had received three-year psychiatric treatment for first psychotic episode in Hong Kong and completed self-stigma assessment were included for the current investigation. A broad range of assessments encompassing socio-demographics, premorbid adjustment, onset and illness profiles, symptom severity, psychosocial functioning, treatment characteristics and medication side-effects were conducted. Twenty-eight (27.7%) patients had moderate-to-high levels of self-stigma. Univariate linear regression analyses showed that age at study entry, sex, educational level, age at psychosis onset, duration of untreated psychosis (DUP), insight level, global psychosocial functioning, and the use of second-generation antipsychotic were related to self-stigma levels. Final multivariable regression model revealed that female sex, younger age at entry, longer DUP and better insight were independently associated with higher levels of self-stigma. More than one-fourth of early psychosis patients experienced significant self-stigma, highlighting an unmet need for early detection and intervention of self-stigma in the initial years of illness. Further investigation is warranted to clarify trajectories and predictors of self-stigma in the early illness course.

Cariprazine for negative symptoms in early psychosis: a pilot study with a 6-month follow-up.

Cariprazine, a novel antipsychotic drug that is a partial agonist with preferential binding to the D3 receptor, has demonstrated efficacy in clinical trials across all symptom domains, including negative symptoms, which can occur early in the course of psychotic illness. However, evidence, to date regarding its effects in early psychosis patients with primary negative symptoms has been limited. To evaluate the efficacy of cariprazine for negative symptoms in early psychosis patients. Demographic and clinical information of the study population were collected from the electronic records and PANSS scale administered at baseline, 3 and 6 months. Tolerability and discontinuation reasons, where applicable, were also recorded. Ten patients with early psychosis (four men and six women, mean age - 25.5 years) with prominent or predominant negative symptoms were treated with cariprazine (range 1.5 - 3 mg). Three patients discontinued cariprazine within the first 3 months due to patient choice, lack of response and non-compliance, respectively. In the remaining patients, there was a significant reduction in the mean negative PANSS score from baseline to 6 months (from 26.3 to 10.6), mean total PANSS score (from 81.4 to 43.3) and in the mean positive PANSS score (from 14.4 to 9.9) which correspond to a 53.1, 41.5, and 28.5% mean score reduction. This pilot study suggests that cariprazine is a safe and effective treatment in early psychosis, particularly for the alleviation of negative symptoms which remains an area of unmet treatment need.

The time is now to start evaluating biomarkers in the clinic.

The time is now to start evaluating biomarkers in the clinic.

Investigation of momentary negative symptoms in patients with early psychosis in daily life: An experience sampling study

Negative symptoms are a key therapeutic target in promoting functional recovery in early psychosis intervention, but momentary negative symptom manifestations remain understudied in the early stage of illness. We employed an experience-sampling methodology (ESM) to evaluate momentary affective experiences, hedonic capacity for an event recalled, current activities and social interactions, and associated appraisals for 6 consecutive days in 33 clinically-stable early psychosis patients (within 3 years of treatment for first-episode psychosis) and 35 demographically-matched healthy controls. Adjusted multilevel linear-mixed models revealed higher intensity and variability of negative affect in patients than controls, but no group difference in affect instability as well as positive affect intensity and variability. Patients demonstrated no significantly greater anhedonia for event, activity or social interactions relative to controls. Higher preference for company (when alone) and to be alone (when in company) was observed in patients than controls. No significant group difference in pleasantness to be alone or proportion of time being alone. Our results indicate no evidence for blunting of affective experiences, anhedonia (social and non-social) and asociality in early psychosis. Future research complementing ESM with multiple digital phenotyping measures will facilitate more refined negative symptom assessment in the daily life of patients with early psychosis.

Prospective memory in early and established psychosis: An Indian perspective.

Individuals affected by psychosis often have deficits in several neurocognitive functions. Prospective memory (PM), the ability to remember to do things, is crucial for activities of daily living, social and occupational functioning, but very few studies have attempted to examine this domain of functioning in people with psychosis, particularly in India. A total of 71 patients with psychosis, (both early and established psychosis), and 140 age, gender and education-matched healthy controls were assessed using the Positive and Negative Symptom Scale, Hospital Anxiety and Depression scale, and Addenbrooke's Cognitive Examination. PM was assessed using the Cambridge Prospective Memory Test and the Prospective and Retrospective Memory Questionnaire (PRMQ). Group differences were evaluated using Mann-Whitney U-tests. Significantly greater cognitive deficits, higher anxiety and depression were evident in the psychosis group compared with controls. The psychosis group performed significantly poorer on both time- and event-based tests in CAMPROMPT than controls. These differences remained when controlling for age, education, general cognitive functioning and mood. The subjective measure of PM (PRMQ) did not differentiate the two groups. The PM performance of early and established psychosis patients was similar. Comparisons with cross-cultural data (PRMQ UK norms and CAMPROMPT and PRMQ Chinese data) revealed important differences in PM performance. Individuals with psychosis have significant deficits in both time- and event-based PM. CAMPROMPT emerged as a more sensitive PM measure compared with PRMQ. Results from cross-cultural comparisons underscore the need for cultural contextualization of assessments.

58. The Potential Use of Visual Contrast Sensitivity as a Biomarker in Early Psychosis Patients

58. The Potential Use of Visual Contrast Sensitivity as a Biomarker in Early Psychosis Patients

Characterization of early psychosis patients carrying a genetic vulnerability to redox dysregulation: a computational analysis of mechanism-based gene expression profile in fibroblasts

In view of its heterogeneity, schizophrenia needs new diagnostic tools based on mechanistic biomarkers that would allow early detection. Complex interaction between genetic and environmental risk factors may lead to NMDAR hypofunction, inflammation and redox dysregulation, all converging on oxidative stress. Using computational analysis, the expression of 76 genes linked to these systems, known to be abnormally regulated in schizophrenia, was studied in skin-fibroblasts from early psychosis patients and age-matched controls (N = 30), under additional pro-oxidant challenge to mimic environmental stress. To evaluate the contribution of a genetic risk related to redox dysregulation, we investigated the GAG trinucleotide polymorphism in the key glutathione (GSH) synthesizing enzyme, glutamate-cysteine-ligase-catalytic-subunit (gclc) gene, known to be associated with the disease. Patients and controls showed different gene expression profiles that were modulated by GAG-gclc genotypes in combination with oxidative challenge. In GAG-gclc low-risk genotype patients, a global gene expression dysregulation was observed, especially in the antioxidant system, potentially induced by other risks. Both controls and patients with GAG-gclc high-risk genotype (gclcGAG-HR) showed similar gene expression profiles. However, under oxidative challenge, a boosting of other antioxidant defense, including the master regulator Nrf2 and TRX systems was observed only in gclcGAG-HR controls, suggesting a protective compensation against the genetic GSH dysregulation. Moreover, RAGE (redox/inflammation interaction) and AGMAT (arginine pathway) were increased in the gclcGAG-HR patients, suggesting some additional risk factors interacting with this genotype. Finally, the use of a machine-learning approach allowed discriminating patients and controls with an accuracy up to 100%, paving the way towards early detection of schizophrenia.

Memory deficits in children and adolescents with psychotic disorders: A systematic review and meta-analysis

IntroductionCognitive symptoms in psychosis represent a major unmet clinical need (Acuna-Vargas et al. Cog in Psych 2019; 21(3), 223–224). Deficit in memory has been largely described in first episode early onset psychosis (Mayoral et al. Eur Psych 2008; 23(5), 375-383) and has been associated to a worse functionality (Øie et al. Neuropsychology 2011; 25(1), 25–35). However, results from existing studies are quite mixed on memory deficits of early psychosis patients, particularly in terms of memory contents and storage resources.ObjectivesThe aims of this study were 1) to examine the nature and extent of cognitive impairment in early-onset psychosis and 2) to analyze which type of memory (verbal and visual) is more affected in the disorder.MethodsThe present systematic review and meta-analysis was conducted according to the PRISMA criteria (Moher et al. Systematic Reviews 2015; 4(1), 1 - 9). A systematic search of CINAHL, PsycInfo, PubMed, Redalyc, SCOPUS and Web of Science (published from 2000 to 2020) identified case-control studies of early onset psychotic disorder (under 18 years old). Those studies focused on both verbal and visual memory performance.ResultsTwenty articles were included in the review. A deficit in memory in child and adolescent psychotic disorders was obtained displaying a large effect size in memory tasks (g = -0.83). Also, a medium effect size was found in visual memory tasks (g = - 0.61) and a large effect size was found in verbal memory tasks (g = -1.00).ConclusionsIt was observed a strong memory deficit on early psychotic disorders already present at the onset of the illness. This deficit was stronger when verbal memory tasks were used compared to the effect found with visual memory tasks. Based on previous literature (García-Nieto et al. Jou Cli Child &amp; Ado Psych 2011; 40(2), 266-280; Lepage et al. Eur Psych 2008; 23(5):368- 74; Hui et al. Psych Med 2016; 46(11):2435-44), these results contribute to describe and characterize the cognitive symptoms in the first-episode psychosis in a youth population.Disclosure of InterestNone Declared

Cross-sectional and longitudinal assessment of the association between DDR1 variants and processing speed in patients with early psychosis and healthy controls

Recent evidence indicates that DDR1 participates in myelination and that variants of DDR1 are associated with decreased cognitive processing speed (PS) in schizophrenia (SZ). Here, we explored whether DDR1 variants were associated with PS in subjects diagnosed with an early psychosis (EP), a condition often preceding SZ. Data from two Spanish independent samples (from Reus and Santander) including patients with EP (n = 75 and n = 312, respectively) and healthy controls (HCs; n = 57 and n = 160) were analyzed. The Trail Making Test part A was used to evaluate PS. Participants underwent genotyping to identify DDR1 variants rs1264323 and rs2267641. Cross-sectional data were analyzed with general linear models and longitudinal data were analyzed using mixed models. We examined the combined rs1264323AA-rs2267641AC/CC genotypes (an SZ-risk combination) on PS. The SZ-risk combined genotypes were associated with increased PS in EP patients but not in HCs in the cross-sectional analysis. In the longitudinal analysis, the SZ-risk combined genotypes were significantly associated with increased PS in both HCs and EP patients throughout the 10-year follow-up but no genotype × time interaction was observed. These results provide further evidence that DDR1 is involved in cognition and should be replicated with other samples.