Combining neuroimaging and brain stimulation to test alternative causal pathways for nicotine addiction in schizophrenia.

Autor: Du X; Louis A. Faillace Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: Xiaoming.Du@uth.tmc.edu., Choa FS; Department of Electrical Engineering and Computer Science, University of Maryland Baltimore County, Baltimore, MD, USA., Chiappelli J; Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA., Bruce H; Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA., Kvarta M; Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA., Summerfelt A; Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA., Ma Y; Louis A. Faillace Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA., Regenold WT; Noninvasive Neuromodulation Unit, Experimental Therapeutics and Pathophysiology Branch, Division of Intramural Research Program, National Institute of Mental Health, National Institutes of Health, NIH Clinical Center, Bethesda, MD, USA., Walton K; Clinical Research Grants Branch, Division of Therapeutics and Medical Consequences, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA., Wittenberg GF; Human Engineering Research Laboratories, VA RR&D Center of Excellence, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA; Rehabilitation Neural Engineering Laboratories, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA., Hare S; Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA., Gao S; Louis A. Faillace Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA., van der Vaart A; Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA., Zhao Z; Department of Mathematics, University of Maryland, College Park, USA., Chen S; Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA., Kochunov P; Louis A. Faillace Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA., Hong LE; Louis A. Faillace Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Jazyk: angličtina
Zdroj: Brain stimulation [Brain Stimul] 2024 Mar-Apr; Vol. 17 (2), pp. 324-332. Date of Electronic Publication: 2024 Mar 05.
DOI: 10.1016/j.brs.2024.02.020
Abstrakt: The smoking rate is high in patients with schizophrenia. Brain stimulation targeting conventional brain circuits associated with nicotine addiction has also yielded mixed results. We aimed to identify alternative circuitries associated with nicotine addiction in both the general population and schizophrenia, and then test whether modulation of such circuitries may alter nicotine addiction behaviors in schizophrenia. In Study I of 40 schizophrenia smokers and 51 non-psychiatric smokers, cross-sectional neuroimaging analysis identified resting state functional connectivity (rsFC) between the dorsomedial prefrontal cortex (dmPFC) and multiple extended amygdala regions to be most robustly associated with nicotine addiction severity in healthy controls and schizophrenia patients (p = 0.006 to 0.07). In Study II with another 30 patient smokers, a proof-of-concept, patient- and rater-blind, randomized, sham-controlled rTMS design was used to test whether targeting the newly identified dmPFC location may causally enhance the rsFC and reduce nicotine addiction in schizophrenia. Although significant interactions were not observed, exploratory analyses showed that this dmPFC-extended amygdala rsFC was enhanced by 4-week active 10Hz rTMS (p = 0.05) compared to baseline; the severity of nicotine addiction showed trends of reduction after 3 and 4 weeks (p ≤ 0.05) of active rTMS compared to sham; Increased rsFC by active rTMS predicted reduction of cigarettes/day (R = -0.56, p = 0.025 uncorrected) and morning smoking severity (R = -0.59, p = 0.016 uncorrected). These results suggest that the dmPFC-extended amygdala circuit may be linked to nicotine addiction in schizophrenia and healthy individuals, and future efforts targeting its underlying pathophysiological mechanisms may yield more effective treatment for nicotine addiction.
Competing Interests: Declaration of Competing interest LEH has received or plans to receive research funding or consulting fee on research projects from Mitsubishi, Your Energy Systems LLC, Neuralstem, Taisho, Heptares, Pfizer, Sound Pharma, IGC Pharma, Regeneron, and Takeda. All other authors declare no conflict of interest. The content is solely the responsibility of the authors. The views expressed are the authors’ own and do not necessarily represent the views of the National Institutes of Health, the Department of Health, or the US government. The ClinicalTrials.gov Identifier for this study is NCT03281629.
(Published by Elsevier Inc.)
Databáze: MEDLINE
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