This study investigates the long-term trajectories of negative symptoms, specifically diminished expression and apathy, in individuals experiencing first-episode psychosis (FEP). The researchers also explore the impact of cannabis use on these trajectories. Negative symptoms are a significant challenge in schizophrenia and other psychoses, often persisting despite treatment and contributing to poor functional outcomes. They are broadly categorized into two dimensions: diminished expression (blunted affect and alogia) and apathy (avolition, asociality, and anhedonia). These dimensions are distinct but interrelated, potentially stemming from primary (inherent to the disorder) or secondary (resulting from external factors) causes. Secondary negative symptoms are often more responsive to treatment than primary negative symptoms, making the identification of modifiable risk factors crucial for improving patient outcomes. Cannabis use is prevalent among individuals with psychosis and is associated with earlier psychosis onset, increased positive symptoms, higher rates of re-hospitalization, and greater disability. The potential link between cannabis use and negative symptoms remains an area requiring further investigation. While some studies using unidimensional measures of negative symptoms have found no differences between users and non-users, recent research employing a two-dimensional approach suggests a significant association between cannabis use and diminished expression in FEP. The long-term course of negative symptoms is not fully understood, with conflicting findings from previous studies. Some research suggests a worsening of symptoms over time, while others indicate improvement, with some individuals experiencing persistent symptoms. Longitudinal studies are critical for understanding the natural history of negative symptoms and identifying factors influencing their trajectories. There is a notable scarcity of long-term longitudinal studies investigating the impact of cannabis use on the two-dimensional construct of negative symptoms. This study aims to address this gap, characterizing the 10-year trajectories of diminished expression and apathy in FEP and investigating the association between cannabis use and these trajectories, while controlling for potential sources of secondary negative symptoms. The study design allows for examining the separate impacts of baseline cannabis exposure and persistent cannabis use during the follow-up period, to better understand the directionality of any identified associations.

The literature review extensively covers the existing research on the relationship between cannabis use and negative symptoms in psychosis, the long-term trajectory of negative symptoms, and the methodologies for assessing negative symptom dimensions. The authors cite numerous studies demonstrating the high prevalence of cannabis use in patients with psychosis, along with its association with earlier onset of psychosis, increased positive symptoms, and poorer outcomes. They note that studies using unidimensional negative symptom measures have yielded inconsistent results, but recent factor analytic studies suggest the importance of distinguishing between diminished expression and apathy as separate dimensions. Regarding the longitudinal course of negative symptoms, the authors highlight the contradictory findings in the literature. While Kraepelin’s early work posited a progressive worsening of negative symptoms, more recent studies suggest that some improvement can occur over time. These studies, however, often lack the specificity of distinguishing between the two negative symptom dimensions and controlling for sources of secondary symptoms. The authors emphasize the need for longer-term longitudinal studies employing a two-dimensional approach to understand the long-term trajectories of negative symptoms and their relationship with cannabis use. They highlight that the existing research focusing on cannabis use in this area is scarce, making this study crucial for filling a critical gap in the literature.

This 10-year prospective longitudinal study utilized data from the Thematically Organized Psychosis (TOP) Study. The study included 351 participants aged 18–65 with a first episode of non-affective psychosis, diagnosed using the Structured Clinical Interview for DSM-IV Axis I Disorders. The participants were assessed at baseline, 1 year, and 10 years post-diagnosis. The sample included various psychotic diagnoses, with the majority diagnosed with schizophrenia. A significant attrition rate was observed, with 155 participants completing the 1-year follow-up and 139 completing the 10-year follow-up. Clinical assessments included demographic data, substance use history (with a focus on cannabis), positive and negative symptoms (assessed using the Positive and Negative Syndrome Scale (PANSS)), depressive symptoms (Calgary Depression Scale for Schizophrenia (CDSS)), antipsychotic side effects (UKU side effect rating scale), and premorbid functioning (Premorbid Adjustment Scale (PAS)). Negative symptoms were operationalized into two factors based on prior validated factor analyses: diminished expression (N1, N3, N6, G7) and apathy (N2, N4, G16). Statistical analyses included independent samples t-tests, Mann-Whitney U tests, chi-square tests, Spearman’s rho correlation analyses, and linear mixed models. Linear mixed models were used to model the trajectories of diminished expression and apathy over time. The models included time, quadratic time, and various covariates (PAS social score, diagnosis of schizophrenia, antipsychotic side effects, depressive symptoms, gender, and positive symptoms) based on theoretical assumptions and previous research. Cannabis use was categorized into several levels (non-use, sporadic use, monthly use, weekly use, and daily use) and analyzed as both a baseline predictor and a time-varying predictor to assess the impact of both initial exposure and persistent use. A piecewise latent trajectory model was also explored to analyze potential change points in the trajectories. The authors employed various statistical techniques to account for the longitudinal nature of the data and potential confounding variables. The linear mixed model was specifically utilized to analyze the change of negative symptoms across time while controlling for potential covariates. This approach accounts for repeated measurements from the same participants and allows for more precise estimation of changes in symptom severity over time. The stepwise inclusion of predictors ensured that only significant factors contributing to the model's explanatory power were included in the final model.

The study revealed a significant decrease in both diminished expression and apathy over the 10-year follow-up period. The most substantial improvement was observed between baseline and the 1-year follow-up, with the rate of improvement in apathy slowing down after the first year. The trajectories differed somewhat between the two dimensions; diminished expression showed a linear decline, while apathy exhibited a curvilinear decline. Crucially, the study demonstrated a significant association between cannabis use and diminished expression. Baseline cannabis use (at least monthly) was associated with a higher symptom load for diminished expression, which appeared to increase slightly in the first year and then decline thereafter. Persistent weekly cannabis use further strengthened this association. In contrast, cannabis use was not significantly associated with apathy scores. Other predictors of negative symptom severity included lower premorbid social functioning (PAS social score), a diagnosis of schizophrenia, the presence of antipsychotic side effects, and more severe positive symptoms (effects varied across the two symptom dimensions). Depressive symptoms and male gender were predictive of apathy but not diminished expression. The models showed that the effects of several predictors, such as premorbid functioning and schizophrenia diagnosis, persisted throughout the 10-year follow-up period.

The findings of this study strongly suggest a link between cannabis use and diminished expression in individuals with FEP. The persistent effect of cannabis use, both at baseline and during the follow-up, on diminished expression points toward a potential causal relationship. The lack of a similar association with apathy suggests that the underlying neurobiological mechanisms of these two dimensions may respond differently to cannabis exposure. The observed decline in both negative symptom dimensions over the 10-year period, particularly the rapid improvement in the first year, supports the notion of a 'critical period' in early psychosis treatment. The study successfully controlled for potential confounding factors such as premorbid functioning, diagnosis, antipsychotic side effects, depressive symptoms, and positive symptoms. This strengthens the conclusion that cannabis use has an independent effect on diminished expression. The domain-specific effects of certain predictors (e.g., gender and depressive symptoms) further highlight the importance of considering the distinct nature of the two negative symptom dimensions in future research and clinical practice. The identification of cannabis use as a potentially modifiable risk factor for diminished expression opens up new avenues for therapeutic interventions. Targeting cannabis use in early psychosis treatment could be a valuable strategy for mitigating negative symptoms, potentially enhancing overall functional outcomes.

This 10-year longitudinal study provides compelling evidence for a strong association between cannabis use and the severity of diminished expression in FEP. The findings suggest a potential causal relationship and highlight the importance of interventions aimed at reducing cannabis use as a part of comprehensive psychosis treatment. Further research should explore the specific neurobiological mechanisms underlying this relationship, and investigate the potential efficacy of cannabis cessation interventions in reducing expressive negative symptoms. The study also reinforces the importance of using dimensional approaches to assess and understand negative symptoms, recognizing their distinct underlying mechanisms and treatment responses. Future studies should utilize more refined measurement tools and investigate potential moderators and mediators of the relationship between cannabis use and negative symptoms.

The study's high attrition rate is a significant limitation, potentially introducing bias into the results. The authors acknowledge that individuals with higher levels of apathy might be less likely to participate in follow-up assessments. While baseline comparisons between completers and non-completers suggest limited bias, this possibility cannot be entirely ruled out. Furthermore, the relatively large gap between the 1-year and 10-year assessments limits the precision of trajectory analysis, and the use of self-reported cannabis use may not fully capture the complexity of cannabis exposure (e.g., cannabinoid content). Finally, the use of the PANSS, although widely used, has limitations compared to newer psychometric tools for assessing negative symptoms.