Motivation Symptoms Sit at the Hub of Treatment-Resistant Schizophrenia

Researchers mapping the symptom networks of people with treatment-resistant schizophrenia have found that motivation-and-pleasure difficulties occupy a central position in the architecture of the illness, showing the strongest and most direct association with social functioning. The study, published in the journal Schizophrenia, analysed clinical data from 402 people with schizophrenia, of whom 230 met criteria for treatment resistance and 172 did not, and compared the web of connections among negative symptoms, other clinical symptoms and day-to-day functioning in the two groups.

Participants completed the Clinical Assessment Interview for Negative Symptoms (CAINS), a detailed measure of negative symptom experiences, alongside the Positive and Negative Syndrome Scale (PANSS) and the Social and Occupational Functioning Assessment Scale (SOFAS). The researchers constructed a regularized partial correlation network and a flow-diagram to examine the role of negative symptoms and their direct and indirect associations with social functioning in treatment-resistant schizophrenia, and to compare network structure and global strength between the treatment-resistant and non-treatment-resistant groups.

The motivation-and-pleasure (MAP) factor and the expressivity (EXP) factor of negative symptoms were both examined, because earlier work in broader schizophrenia populations had suggested that MAP affects social functioning more than EXP. The new analysis tested whether this differential pattern extended to patients whose illness is resistant to treatment.

The regularized partial correlation network linking clinical symptoms, illness duration and social functioning in the treatment-resistant group proved highly stable. Within it, four nodes stood out as central: the MAP factor, the EXP factor, a PANSS-derived disorganized symptom factor and the SOFAS score itself, indicating that motivational problems, expressive deficits and disorganization are tightly woven into the fabric of treatment-resistant illness.

The flow-diagram analysis then traced how symptom effects reach social functioning. The MAP factor showed the strongest and most direct association with functioning in treatment-resistant patients. The PANSS disorganized factor followed as the next most influential pathway. The EXP factor, by contrast, contributed to the variance of social functioning largely indirectly, channelling its effects through the MAP factor rather than acting on functioning on its own.

Comparisons between the two patient groups added a further layer of findings. The symptom-domain network in treatment-resistant patients showed stronger connectivity overall than the network in non-treatment-resistant patients, suggesting that in treatment resistance, symptoms are more densely interlinked. Similarly, when the researchers compared item-level CAINS networks, negative symptoms in treatment-resistant patients displayed more cross-item connections than in their non-treatment-resistant counterparts.

According to the authors, these results concur with previous network analysis findings in patients with schizophrenia and extend the evidence on the role of negative symptoms specifically to the treatment-resistant population. On the basis of these findings, the authors state that interventions targeting negative symptoms in treatment-resistant patients are warranted.

The study was an observational analysis of clinical assessment data, so it identifies associations among symptoms and functioning rather than testing whether changing one symptom changes another. Even so, by pinpointing the motivation-and-pleasure factor as the most direct correlate of social functioning in treatment-resistant schizophrenia, the network approach offers a data-driven map of where this difficult-to-treat condition’s symptom architecture is most tightly connected.

Subject of Research: Network analysis of negative symptoms and social functioning in treatment-resistant schizophrenia

Article Title: Characterizing negative symptoms in patients with treatment-resistant schizophrenia: a network analysis

Article References: Wong, T. T. Y., Choi, L.-Y., Ng, E. S. H., Lam, E. H. Y., Chan, J. W. S., Yip, K. K. Y., Chiu, M. W. Y., Lam, J. P. H., Siu, B. W. M., Tang, D. Y. Y., Liu, A. C. Y., Chan, R. C. K., & Lui, S. S. Y. (2026). Characterizing negative symptoms in patients with treatment-resistant schizophrenia: a network analysis. Schizophrenia. https://doi.org/10.1038/s41537-026-00820-4

Image Credits: AI Generated

DOI: 10.1038/s41537-026-00820-4

Keywords: treatment-resistant schizophrenia, negative symptoms, network analysis, motivation and pleasure, social functioning, CAINS, PANSS, SOFAS, expressivity, psychiatry, Characterizing, negative