While treatment non-adherence is a well-established relapse risk factor, broader contributors require investigation. Studying chronic, high-risk schizophrenia cohorts in real-world lower middle-income country (LMIC) settingsremains methodologically challenging.

To explore multidimensional factors moderating treatment trajectories in individuals with chronic schizophrenia at high risk of relapse, comparing relapsers and non-relapsers in a real-world LMIC setting.

In this 12-month prospective naturalistic study, 56 clinically stable adults with chronic schizophrenia (≥2 relapses within 3 years), receiving long-acting injectable and/or oral antipsychotics were followed up monthly. Relapse was defined as worsening psychotic symptoms requiring re-hospitalisation. Linear mixed-effects models examined trajectories of Positive and Negative Syndrome Scale (PANSS) total and factor domains (positive, negative and disorganised) and tested group*time*moderator interactions for neurological soft signs (NSS), quality of life (QOL), aberrant salience, anxiety, resilience, self-esteem, social adversity and childhood trauma.

Twenty-three participants (41%) relapsed; overall attrition was 59%, with 21% of discontinuations relapsing. Most relapses (87%) involved non-adherence and substance misuse. No group*time interaction effects were found for PANSS domains. Poorer overall QOL (F(4, 31 = 4.0), p = 0.009) was associated with worse negative symptom trajectory in the relapse group, while more pronounced NSS was associated with worse positive symptom trajectory in the non-relapse group (F(2, 23 = 8.4), p = 0.002).

Conducting longitudinal research in chronic, high-risk schizophrenia populations in LMICs is challenging. Although exploratory and hypothesis-generating, QOL and NSS may represent clinically meaningful moderators of treatment course and potential targets for intervention and future research.

Epigenetics hypothesizes a crucial link between postnatal risk factors, individual response to stress, DNA methylation and psychiatric symptomatology changes during life.

We analyzed methylation within two gene exons: NR3C1 and SLC6A4, which are involved in responses to environmental stressors. We investigated the relationship between methylation, postnatal risk factors and psychopathology assessed by Child Behavior Checklist (CBCL) in our help-seeking sample evaluated in infancy (W1), preadolescence (W2) and adult life (W3).

Postnatal risk factors data were collected at W1 in 205 clinical subjects (156 M, 49 F; age=9,13±1,95). The CBCL scores were collected at W1 and W2 (W2 age=14,52±2,12). Data regarding methylation were collected at W2. At W3 we are also collecting clinical scores. A Spearman correlation coefficient was calculated between methylation percentage and clinical data at W2. The externalizing and internalizing trajectories were evaluated through repeated measure ANOVA with postnatal risk factors (presence/absence) as between-groups factor.

Significant associations were found between methylation and internalizing and total clinical scores (Table 1). The rm-ANOVA results showed a significant interaction between the CBCL internalizing score and presence/absence of postnatal risk, with higher internalizing problems in subjects that were exposed to postnatal risk factors. This effect was significant at W2 but not at W1 (Figure 1).

Psychopathological symptoms trajectories could depend on epigenetics and early environmental risk factors. Further analyses will address a Linear Discriminant Analysis to proceed to a machine learning oriented approach.

No significant relationships.

Our 15-years follow-up ReMIND project aims to re-assess an epidemiological and a clinical sample of adults (Wave 3), who were assessed in preadolescence (Wave 1) and adolescence (Wave 2), to evaluate symptoms trajectories and their relationship with genetic/epigenetic data, environmental risk factors and neuroimaging measures.

Here, we depict preliminary results regarding the epidemiological sample.

We assessed internalizing and externalizing symptoms in 40 italian subjects (25 F) from general population at three waves (W1 mean age: 12±0,82; W2 mean age: 17±0,88, W3 mean age: 28±1), through the Child Behavior Checklist (W1 and W2) or the Adult Self Report (W3), and perinatal risk factors through a socio-anamnestic questionnaire, by a new online platform (MedicalBit). We analyzed symptoms trajectories and their relation with perinatal risk factors through a repeated measures multivariate analysis of variance (rm-MANOVA).

rm-MANOVA results show that high number of perinatal risks was significantly associated with higher internalizing symptomatology in preadolescence but not in adolescence and adult life. The mean difference was 8 T-points. The same trend is evident in adolescence but not in adult age (Graph 1). Perinatal risk factors did not have a significant effect on externalizing symptoms at any time point, despite a non-significant trend is evident (Graph 2).

Our preliminary results suggest a trend of increased internalizing symptoms from childhood to adulthood and a significant role of perinatal risk factors in pre-adolescence. Further investigations are necessary to better understand symptoms trajectories and the role of biological and environmental factors.

No significant relationships.