Bioenergetics and synaptic plasticity as potential targets for individualizing treatment for depression

J. Blair Price, Carrie Bronars, Sophie Erhardt, Kathyrn R. Cullen, Lilly Schwieler, Michael Berk, Ken Walder, Sean L. McGee, Mark A. Frye, Susannah J. Tye

Research output: Contribution to journalReview articlepeer-review

28 Scopus citations


Disruptions of bioenergetic signaling and neurogenesis are hallmarks of depression physiology and are often the product of dysregulation of the inflammatory, stress-response, and metabolic systems. These systems are extensively interrelated at the physiological level, yet the bulk of the literature to date addresses pathophysiological mechanisms in isolation. A more integrated understanding of the etiology, progression, and treatment response profiles of depression is possible through wider consideration of relevant preclinical and clinical studies that examine the result of disruptions in these systems. Here, we review recent data demonstrating the critical effects of bioenergetic disruption on neuroplasticity and the development and progression of depressive illness. We further highlight the interactive and dynamic nature of the inflammatory and stress response systems and how disruption of these systems influences bioenergetic signaling pathways critical to treatment outcomes. In so doing, we underscore the pressing need to reconsider the implications of treatment resistance and present a framework for developing novel, personalized treatment approaches for depression.

Original languageEnglish (US)
Pages (from-to)212-220
Number of pages9
JournalNeuroscience and Biobehavioral Reviews
StatePublished - Jul 2018

Bibliographical note

Funding Information:
JBP is supported by a Deakin University Postgraduate Award. MB is supported by a NHMRC Senior Principal Research Fellowship (GNT1059660) and has received Grant/Research Support from the NIH , Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Meat and Livestock Board, Organon, Novartis, Mayne Pharma, Servier, Woolworths, Avant and the Harry Windsor Foundation, and has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth, and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Eli Lilly, Grunbiotics, Glaxo SmithKline, Janssen Cilag, LivaNova, Lundbeck, Merck, Mylan, Otsuka, Pfizer, and Servier. KW and SLM have received grant support from NHMRC. MAF has received grant support from AssureRx, Myriad, NIAAA, NIMH, and Pfizer, and has served as a consultant for Janssen, Mitsubishi Tanabe Pharma Corporation, Myriad, Neuralstem Inc., Otsuka American Pharmaceutical, Sunovion, and Teva Pharmaceuticals. SJT has received Grant/Research Support from the State of Minnesota, TEVA pharmaceuticals, International Bipolar Foundation, Brain & Research Foundation, and Mayo Clinic Center for Individualized Medicine. SE has received grant support from AstraZeneca and Jansen Pharmaceuticals as principal investigator, has served as a one-off speaker for Roche pharmaceuticals, Eli Lilly, Bristol Myers Squibb and participated in workshops organized by Otsuka Pharmaceuticals. The other authors report no biomedical financial interests of potential conflicts of interest.

Publisher Copyright:
© 2018 Elsevier Ltd


  • Bioenergetics
  • Bipolar disorder (BD)
  • Brain-derived neurotrophic factor (BDNF)
  • Hypothalamic-pituitary-adrenal axis (HPA axis)
  • Inflammation
  • Kynurenine
  • Major depressive disorder (MDD)
  • Mammalian target of rapamycin (mTOR)
  • Metabolism
  • Proinflammatory cytokine
  • Stress


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