Changes in corticostriatal connectivity and striatal tissue iron associated with efficacy of clozapine for treatment‑resistant schizophrenia.
Rationale: Though numerous studies demonstrate the superiority of clozapine (CLZ) for treatment of persistent psychotic symptoms that are characteristic of treatment-refractory schizophrenia (TRS), what remains unknown are the neural and molecular mechanisms underlying CLZ's efficacy. Recent work im...
| Publicado en: | Psychopharmacology Vol. 239; no. 8; pp. 2503 - 2515 |
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| Autores principales: | , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Aug2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=158036251&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 158036251 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: Aug2022 vid: 239 iid: 8 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 158036251 10.1007/s00213-022-06138-0 158036251 ppf: 2503 ppct: 12 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Changes in corticostriatal connectivity and striatal tissue iron associated with efficacy of clozapine for treatment‑resistant schizophrenia. aug: au: Blazer, Annie Chengappa, K. N. Roy Foran, William Parr, Ashley C. Kahn, Charles E. Luna, Beatriz Sarpal, Deepak K. affil: Department of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, 15213, Pittsburgh, PA, USA sug: ab: Rationale: Though numerous studies demonstrate the superiority of clozapine (CLZ) for treatment of persistent psychotic symptoms that are characteristic of treatment-refractory schizophrenia (TRS), what remains unknown are the neural and molecular mechanisms underlying CLZ's efficacy. Recent work implicates increased corticostriatal functional connectivity as a marker of response to non-CLZ, dopamine (DA) D2-receptor blocking antipsychotic drugs. However, it is undetermined whether this connectivity finding also relates to CLZ's unique efficacy, or if response to CLZ is associated with changes in striatal DA functioning. Objective: In a cohort of 22 individuals with TRS, we examined response to CLZ in relation to the following: (1) change in corticostriatal functional connectivity; and (2) change in a magnetic resonance-based measure of striatal tissue iron (R2'), which demonstrates utility as a proxy measure for elements of DA functioning. Methods: Participants underwent scanning while starting CLZ and after 12 weeks of CLZ treatment. We used both cortical and striatal regions of interest to examine changes in corticostriatal interactions and striatal R2' in relation to CLZ response (% reduction of psychotic symptoms). Results: We first found that response to CLZ was associated with an increase in corticostriatal connectivity between the dorsal caudate and regions of the frontoparietal network (P < 0.05, corrected). Secondly, we observed no significant changes in striatal R2' across CLZ treatment. Conclusion: Overall, these results indicate that changes in corticostriatal networks without gross shifts in striatal DA functioning underlies CLZ response. Our results provide novel mechanistic insight into response to CLZ treatment. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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