Dopamine antagonists and dynamic symptom networks in schizophrenia

The symptoms of psychotic disorders do not exist in isolation, but interact with one another as part of a dynamic network. For example, hallucinations may worsen mood, which may exacerbate hallucinations, creating self-reinforcing cycles. These symptom interactions have been shown to lead to the onset and maintenance of disorders. Effective treatments should therefore not only reduce overall symptom severity, but also disrupt these pathological interactions. Although antipsychotics are known to reduce symptom burden, their effects on the dynamic architecture of symptom networks remain unclear.

This study aims to characterise how 6 weeks of antipsychotic treatment alters the structure of temporal symptom networks in schizophrenia.

Data were pooled from 8 randomised controlled trials evaluating the efficacy of paliperidone over 6 weeks, in 2508 participants with schizophrenia spectrum disorders. Twenty symptoms assessed across four time points were modelled using a panel graphical vector autoregression approach. Temporal networks were estimated for treatment and placebo groups. Network-level and symptom-level connectivity were compared using resampling-based permutation tests.

Antipsychotic treatment was associated with significantly lower global symptom network connectivity than placebo treatment (18.92 v. 26.52; S = 7.60; p < 0.001). Specific inter-symptom connections were attenuated, most notably a reduced influence of 'lack of spontaneity' on other symptoms (0.97 v. 1.74; p < 0.001).

Antipsychotic treatment not only decreases symptom severity, but also disrupts dynamic interdependencies among symptoms. These findings suggest that effective treatment weakens maladaptive symptom coupling, offering new insights into the mechanisms of clinical improvement and potential targets for intervention.