Brain entropy and neurotrophic molecular markers accompanying clinical improvement after ketamine: Preliminary evidence in adolescents with treatment-resistant depression.

Autor:	Roy AV; Department of Psychiatry and Behavioral Sciences, Medical School, University of Minnesota, Minneapolis, USA., Thai M; Department of Psychology, College of Liberal Arts, University of Minnesota, Minneapolis, USA., Klimes-Dougan B; Department of Psychology, College of Liberal Arts, University of Minnesota, Minneapolis, USA., Westlund Schreiner M; Department of Psychiatry, University of Utah, Salt Lake City, USA., Mueller BA; Department of Psychiatry and Behavioral Sciences, Medical School, University of Minnesota, Minneapolis, USA., Albott CS; Department of Psychiatry and Behavioral Sciences, Medical School, University of Minnesota, Minneapolis, USA., Lim KO; Department of Psychiatry and Behavioral Sciences, Medical School, University of Minnesota, Minneapolis, USA., Fiecas M; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, USA., Tye SJ; Queensland Brain Institute, The University of Queensland, Brisbane, Australia., Cullen KR; Department of Psychiatry and Behavioral Sciences, Medical School, University of Minnesota, Minneapolis, USA.
Jazyk:	angličtina
Zdroj:	Journal of psychopharmacology (Oxford, England) [J Psychopharmacol] 2021 Feb; Vol. 35 (2), pp. 168-177. Date of Electronic Publication: 2020 Jul 09.
DOI:	10.1177/0269881120928203
Abstrakt:	Background: Current theory suggests that treatment-resistant depression (TRD) involves impaired neuroplasticity resulting in cognitive and neural rigidity, and that clinical improvement may require increasing brain flexibility and adaptability. Aims: In this hypothesis-generating study, we sought to identify preliminary evidence of brain flexibility correlates of clinical change within the context of an open-label ketamine trial in adolescents with TRD, focusing on two promising candidate markers of neural flexibility: (a) entropy of resting-state functional magnetic resonance imaging (fMRI) signals; and (b) insulin-stimulated phosphorylation of mammalian target of rapamycin (mTOR) and glycogen synthase-3-beta (GSK3β) in peripheral blood mononuclear cells. Methods: We collected resting-state functional magnetic resonance imaging data and blood samples from 13 adolescents with TRD before and after a series of six ketamine infusions over 2 weeks. Usable pre/post ketamine data were available from 11 adolescents for imaging and from 10 adolescents for molecular signaling. We examined correlations between treatment response and changes in the central and peripheral flexibility markers. Results: Depression reduction correlated with increased nucleus accumbens entropy. Follow-up analyses suggested that physiological changes were associated with treatment response. In contrast to treatment non-responders ( n =6), responders ( n =5) showed greater increase in nucleus accumbens entropy after ketamine, together with greater post-treatment insulin/mTOR/GSK3β signaling. Conclusions: These data provide preliminary evidence that changes in neural flexibility may underlie symptom relief in adolescents with TRD following ketamine. Future research with adequately powered samples is needed to confirm resting-state entropy and insulin-stimulated mTOR and GSK3β as brain flexibility markers and candidate targets for future clinical trials. Clinical Trial Name: Ketamine in adolescents with treatment-resistant depression URL: https://clinicaltrials.gov/ct2/show/NCT02078817 Registration number: NCT02078817.
Databáze:	MEDLINE
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