Network analysis indicates that avolition is the most central domain for the successful treatment of negative symptoms: Evidence from the roluperidone randomized clinical trial

Gregory P. Strauss*, Farnaz Zamani Esfahlani, Hiroki Sayama, Brian Kirkpatrick, Mark G. Opler, Jay B. Saoud, Michael Davidson, Remy Luthringer

*この研究の対応する著者

研究成果: Article査読

19 被引用数 (Scopus)

抄録

A recent conceptual development in schizophrenia is to view its manifestations as interactive networks rather than individual symptoms. Negative symptoms, which are associated with poor functional outcome and reduced rates of recovery, represent a critical need in schizophrenia therapeutics. MIN101 (roluperidone), a compound in development, demonstrated efficacy in the treatment of negative symptoms in schizophrenia. However, it is unclear how the drug achieved its effect from a network perspective. The current study evaluated the efficacy of roluperidone from a network perspective. In this randomized clinical trial, participants with schizophrenia and moderate to severe negative symptoms were randomly assigned to roluperidone 32 mg (n = 78), 64 mg (n = 83), or placebo (N = 83). Macroscopic network properties were evaluated to determine whether roluperidone altered the overall density of the interconnections among symptoms. Microscopic properties were evaluated to examine which individual symptoms were most influential (ie, interconnected) on other symptoms in the network and are responsible for successful treatment effects. Participants receiving roluperidone did not differ from those randomized to placebo on macroscopic properties. However, microscopic properties (degree and closeness centrality) indicated that avolition was highly central in patients receiving placebo and that roluperidone reduced this level of centrality. These findings suggest that decoupling the influence of motivational processes from other negative symptom domains is essential for producing global improvements. The search for pathophysiological mechanisms and targeted treatment development should be focused on avolition, with the expectation of improvement in the entire constellation of negative symptoms if avolition is effectively treated.

本文言語English
ページ(範囲)964-970
ページ数7
ジャーナルSchizophrenia bulletin
46
4
DOI
出版ステータスPublished - 2020 7月 1
外部発表はい

ASJC Scopus subject areas

  • 精神医学および精神衛生

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