Clinical insight in schizophrenia: Time-specific associations with symptoms, cognition and antipsychotic mechanisms.

Background: Impaired clinical insight in schizophrenia is associated with poor treatment adherence and outcomes. Previous research on the influence of symptoms, cognition, and antipsychotic exposure has been inconclusive and restricted to multi-episode samples. We examined time-specific associations between overall psychopathology, cognitive functioning, antipsychotic D₂ receptor mechanisms, antipsychotic exposure and dosage, and insight, whether these associations changed over time, and whether dosage moderated them. Methods: In 144 individuals with schizophrenia, including antipsychotic-naïve and previously treated participants, multiple regressions were conducted at five cross-sectional time points and examined changes in associations over one year. Insight was assessed using PANSS item G12. Symptom severity was represented by the sum of the remaining PANSS items (mPANSS). Antipsychotic exposure was quantified as cumulative Defined Daily Doses and classified as dopamine antagonists (DA) or partial agonists (DPA). Cognitive functioning was expressed as a mean t-score. Results: Greater symptom severity was consistently associated with poorer insight across time points and was the only variable showing a linear increase in strength over time. Higher DPA doses were associated with poorer insight at baseline and 12 months, but improved insight at 12 weeks. Higher cognitive functioning was associated with better insight at baseline and interacted with lower doses at 6 weeks and 12 months. No consistent associations were observed in antipsychotic-naïve participants. Conclusion: Clinical insight was most consistently associated with symptom severity, with an increasingly robust association over time, highlighting the need to assess insight across the symptom spectrum, including when symptoms are mild and independently of antipsychotic dosage.