Connectivity, pharmacology, and computation: Toward a mechanistic understanding of neural system dysfunction in schizophrenia

Alan Anticevic, Michael W. Cole, Grega Repovs, Aleksandar Savic, Naomi R. Driesen, Genevieve Yang, Youngsun T. Cho, John D. Murray, David C. Glahn, Xiao-Jing Wang, John H. Krystal

Research output: Contribution to journalArticle

Abstract

Neuropsychiatric diseases such as schizophrenia and bipolar illness alter the structure and function of distributed neural networks. Functional neuroimaging tools have evolved sufficiently to reliably detect system-level disturbances in neural networks. This review focuses on recent findings in schizophrenia and bipolar illness using resting-state neuroimaging, an advantageous approach for biomarker development given its ease of data collection and lack of task-based confounds. These benefits notwithstanding, neuroimaging does not yet allow the evaluation of individual neurons within local circuits, where pharmacological treatments ultimately exert their effects. This limitation constitutes an important obstacle in translating findings from animal research to humans and from healthy humans to patient populations. Integrating new neuroscientific tools may help to bridge some of these gaps. We specifically discuss two complementary approaches. The first is pharmacological manipulations in healthy volunteers, which transiently mimic some cardinal features of psychiatric conditions. We specifically focus on recent neuroimaging studies using the NMDA receptor antagonist, ketamine, to probe glutamate synaptic dysfunction associated with schizophrenia. Second, we discuss the combination of human pharmacological imaging with biophysically informed computational models developed to guide the interpretation of functional imaging studies and to inform the development of pathophysiologic hypotheses. To illustrate this approach, we review clinical investigations in addition to recent findings of how computational modeling has guided inferences drawn from our studies involving ketamine administration to healthy subjects. Thus, this review asserts that linking experimental studies in humans with computational models will advance to effort to bridge cellular, systems, and clinical neuroscience approaches to psychiatric disorders.

Original languageEnglish (US)
Article numberArticle 169
JournalFrontiers in Psychiatry
Volume4
Issue numberDEC
DOIs
StatePublished - 2013

Fingerprint

Schizophrenia
Neuroimaging
Pharmacology
Ketamine
Psychiatry
Healthy Volunteers
Functional Neuroimaging
Neurosciences
N-Methyl-D-Aspartate Receptors
Glutamic Acid
Biomarkers
Neurons
Population
Therapeutics

Keywords

  • Computational modeling
  • Functional connectivity
  • Glutamate
  • NMDA receptors
  • Pharmacology
  • Schizophrenia
  • Thalamus

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Anticevic, A., Cole, M. W., Repovs, G., Savic, A., Driesen, N. R., Yang, G., ... Krystal, J. H. (2013). Connectivity, pharmacology, and computation: Toward a mechanistic understanding of neural system dysfunction in schizophrenia. Frontiers in Psychiatry, 4(DEC), [Article 169]. https://doi.org/10.3389/fpsyt.2013.00169

Connectivity, pharmacology, and computation : Toward a mechanistic understanding of neural system dysfunction in schizophrenia. / Anticevic, Alan; Cole, Michael W.; Repovs, Grega; Savic, Aleksandar; Driesen, Naomi R.; Yang, Genevieve; Cho, Youngsun T.; Murray, John D.; Glahn, David C.; Wang, Xiao-Jing; Krystal, John H.

In: Frontiers in Psychiatry, Vol. 4, No. DEC, Article 169, 2013.

Research output: Contribution to journalArticle

Anticevic, A, Cole, MW, Repovs, G, Savic, A, Driesen, NR, Yang, G, Cho, YT, Murray, JD, Glahn, DC, Wang, X-J & Krystal, JH 2013, 'Connectivity, pharmacology, and computation: Toward a mechanistic understanding of neural system dysfunction in schizophrenia', Frontiers in Psychiatry, vol. 4, no. DEC, Article 169. https://doi.org/10.3389/fpsyt.2013.00169
Anticevic, Alan ; Cole, Michael W. ; Repovs, Grega ; Savic, Aleksandar ; Driesen, Naomi R. ; Yang, Genevieve ; Cho, Youngsun T. ; Murray, John D. ; Glahn, David C. ; Wang, Xiao-Jing ; Krystal, John H. / Connectivity, pharmacology, and computation : Toward a mechanistic understanding of neural system dysfunction in schizophrenia. In: Frontiers in Psychiatry. 2013 ; Vol. 4, No. DEC.
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