Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor

被引：251

作者：

Preller, Katrin H. ^{[1
,2
]}

Burt, Joshua B. ^{[2
,3
]}

Ji, Jie Lisa ^{[2
]}

Schleifer, Charles H. ^{[2
]}

Adkinson, Brendan D. ^{[2
]}

Stampfli, Philipp ^{[4
]}

Seifritz, Erich ^{[4
]}

Repovs, Grega ^{[5
]}

Krystal, John H. ^{[2
]}

Murray, John D. ^{[2
,3
,6
]}

Vollenweider, Franz X. ^{[1
]}

Anticevic, Alan ^{[2
]}

机构：

[1] Univ Hosp Psychiat Zurich, Dept Psychiat Psychotherapy & Psychosomat, Neuropsychopharmacol & Brain Imaging, Zurich, Switzerland

[2] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA

[3] Yale Univ, Dept Phys, New Haven, CT USA

[4] Univ Hosp Psychiat Zurich, Dept Psychiat Psychotherapy & Psychosomat, Zurich, Switzerland

[5] Univ Ljubljana, Dept Psychol, Mind & Brain Lab, Ljubljana, Slovenia

[6] Yale Univ, Sch Med, Dept Neurosci, New Haven, CT USA

来源：

ELIFE | 2018年 / 7卷

基金：

美国国家卫生研究院;

关键词：

INTRINSIC FUNCTIONAL CONNECTIVITY; HUMAN CEREBRAL-CORTEX; DOUBLE-BLIND; SCHIZOPHRENIA; DYSCONNECTIVITY; PSILOCYBIN; ORGANIZATION; PSYCHOSIS; DISORDER; AMYGDALA;

D O I：

10.7554/eLife.35082

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background:Lysergic acid diethylamide (LSD) has agonist activity at various serotonin (5-HT) and dopamine receptors. Despite the therapeutic and scientific interest in LSD, specific receptor contributions to its neurobiological effects remain unknown. Methods: We therefore conducted a double-blind, randomized, counterbalanced, cross-over study (ClinicalTrials.gov, NCT02451072) during which 24 healthy human participants received either (i) placebo+placebo, (ii) placebo+LSD (100 mu g po), or (iii) Ketanserin, a selective 5-HT2A receptor antagonist,+LSD. We quantified resting-state functional connectivity via a data-driven global brain connectivity method and compared it to cortical gene expression maps. Findings: LSD reduced associative, but concurrently increased sensory-somatomotor brain-wide and thalamic connectivity. Ketanserin fully blocked the subjective and neural LSD effects. Whole-brain spatial patterns of LSD effects matched 5-HT2A receptor cortical gene expression in humans. Conclusion: Together, these results strongly implicate the 5-HT2A receptor in LSD's neuropharmacology. This study therefore pinpoints the critical role of 5-HT2A in LSD's mechanism, which informs its neurobiology and guides rational development of psychedelic-based therapeutics. Funding: Swiss National Science Foundation (SNSF, P2ZHP1_161626, KHP), the Swiss Neuromatrix Foundation (2015 - 0103, FXV), the Usona Institute (2015 - 2056, FXV), the NIH (R01MH112746, JDM; DP5OD012109, AA; R01MH108590, AA), the NIAA (P50AA012870-16, AA & JHK), the NARSAD Independent Investigator Grant (AA), the Yale CTSA grant (UL1TR000142 Pilot Award, AA), and the Slovenian Research Agency (ARRS J7-6829 & ARRS J7-8275, GR).

引用

页数：31

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