From bias to signal: the prognostic meaning of baseline pharmacotherapy in clinical high-risk for psychosis - Nature
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Observational evidence is increasingly central to prognostic precision in early intervention in mental health, particularly in Clinical High-Risk for Psychosis (CHR-P) populations where trajectories are heterogeneous and clinical decisions unfold sequentially. In this context, baseline pharmacological exposure should not be treated merely as a nuisance variable or dismissed because it may reflect confounding by indication, confounding by severity, or protopathic bias. These mechanisms limit causal interpretation, but they may also explain why treatment exposure carries prognostic information. Antipsychotic, antidepressant, benzodiazepine, or combined exposure at CHR-P inception may encode prior clinical deterioration, symptom burden, comorbidity, treatment-seeking pathways, clinician concern, partial treatment response, or pharmacologically attenuated expression of emerging psychosis.
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