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

The motivation-and-pleasure (MAP) factor affects social functioning more than the expressivity (EXP) factor in schizophrenia patients, but less is known regarding the differential associations of negative symptom factors on social functioning in treatment-resistant schizophrenia (TRS) patients. Four-hundred-and-two schizophrenia (230 TRS and 172 non-TRS) patients completed the Clinical-Assessment-Interview-for-Negative-Symptoms (CAINS), the Positive-and-Negative-Syndrome-Scale (PANSS), and the Social-and-Occupational-Functioning Assessment-Scale (SOFAS). A regularized-partial-correlation network and a flow-diagram were constructed to examine the role of negative symptoms, and their direct/indirect associations with social functioning in TRS patients.

The network structure and global strength were compared between TRS and non-TRS patients. We further compared the regularized-partial-correlation network of CAINS items in TRS patients with that in non-TRS patients. The results showed that the regularized-partial-correlation network of clinical symptoms, illness-duration and social functioning in TRS patients was highly stable.

The MAP factor, EXP factor, PANSS-disorganized factor, and SOFAS were central in the network. Moreover, the flow-diagram indicated that the MAP factor had the strongest and most direct association with social functioning in TRS patients, followed by the PANSS-disorganized factor. However, the EXP factor largely contributed to the variance of social functioning via the MAP factor.

The symptom-domain network in TRS patients showed stronger connectivity than the network of non-TRS patients. Comparing the two CAINS-item networks, TRS patients’ negative symptoms showed more cross-item connections than non-TRS patients. Our findings concur with previous network analysis results in patients with schizophrenia, and extended the role of negative symptoms to the TRS population.

Interventions targeting negative symptoms in TRS patients are warranted. This study was supported by HKU Enhanced Start-up Fund for New Staff granted to Lui S.S.Y. Chan R.C.K. was supported by the Philip K.

The funding agents have no role in the study design; collection, analysis, and interpretation of the data; writing of the manuscript; nor decision to submit the paper for publication. We thank our funding agents and all the participants of this study. These authors contributed equally: Timmy T.