Stratification and prediction of remission in first-episode psychosis patients: the OPTiMiSE cohort study

Abstract

Early response to first-line antipsychotic treatments is strongly associated with positive long-term symptomatic and functional outcome in psychosis. Unfortunately, attempts to identify reliable predictors of treatment response in first-episode psychosis (FEP) patients have not yet been successful. One reason for this could be that FEP patients are highly heterogeneous in terms of symptom expression and underlying disease biological mechanisms, thereby impeding the identification of one-size-fits-all predictors of treatment response. We have used a clustering approach to stratify 325 FEP patients into four clinical subtypes, termed C1A, C1B, C2A and C2B, based on their symptoms assessed using the Positive and Negative Syndrome Scale (PANSS) scale. Compared to C1B, C2A and C2B patients, those from the C1A subtype exhibited the most severe symptoms and were the most at risk of being non-remitters when treated with the second-generation antipsychotic drug amisulpride. Before treatment, C1A patients exhibited higher serum levels of several pro-inflammatory cytokines and inflammation-associated biomarkers therefore validating our stratification approach on external biological measures. Most importantly, in the C1A subtype, but not others, lower serum levels of interleukin (IL)-15, higher serum levels of C-X-C motif chemokine 12 (CXCL12), previous exposure to cytomegalovirus (CMV), use of recreational drugs and being younger were all associated with higher odds of being non-remitters 4 weeks after treatment. The predictive value of this model was good (mean area under the curve (AUC) = 0.73 ± 0.10), and its specificity and sensitivity were 45 ± 0.09% and 83 ± 0.03%, respectively. Further validation and replication of these results in clinical trials would pave the way for the development of a blood-based assisted clinical decision support system in psychosis.

Identification of inflammatory subgroups of schizophrenia and bipolar disorder patients with HERV-W ENV antigenemia by unsupervised cluster analysis

“…using composite scores analyses [44], regularized regression [45], k-means clustering [26,46,47], or through a combination of unsupervised exploratory factor analysis and hierarchical clustering [48]. Consistent with our findings, the majority of these previous studies demonstrated that inflammatory profiles in patients with psychotic disorders can be sub-grouped into two main clusters, namely "high inflammatory" and a "low inflammatory" subgroups.…”

Dopamine and Glutamate in Antipsychotic-Responsive Compared With Antipsychotic-Nonresponsive Psychosis: A Multicenter Positron Emission Tomography and Magnetic Resonance Spectroscopy Study (STRATA)

“…They may also have increased predictive power in combination with other factors that may associate with antipsychotic response, such as clinical and demographic measures, 11–13 brain network connectivity, 74 genetic factors, 75 , 76 and blood measures. 77 We plan to address these issues in future studies.…”

Changes in peripheral blood compounds following psychopharmacological treatment in drug-naïve first-episode patients with either schizophrenia or major depressive disorder: a meta-analysis

“…High inflammation before the start of treatment in both depression and schizophrenia seems to be associated with worse treatment response. A multinational, multi-center, randomized, double-blind study of first-episode psychosis patients showed that those with the most severe symptoms before treatment presented with higher pro-inflammatory compounds and were the most at risk of non-remission compared to psychosis patients with less severe symptoms (Martinuzzi et al, 2019 ). Additionally, in a longitudinal study of first-episode psychosis patients an association was found between increased high-sensitivity CRP, triglycerides and BMI at baseline, and higher PANSS scores and reduced treatment response at 1-year follow-up (Nettis et al, 2019 ).…”