Altered glutamatergic response and functional connectivity in treatment resistant schizophrenia: the effect of riluzole and therapeutic implications.

Psychopharmacology
Toby PillingerOliver D Howes

Abstract

Anterior cingulate cortex (ACC) glutamatergic abnormalities are reported in treatment-resistant schizophrenia (TRS) and implicated in functional dysconnectivity and psychopathology. Preclinical evidence indicates riluzole reduces synaptic glutamate. However, it is unknown whether riluzole can modulate glutamate metabolite levels and associated functional connectivity in TRS. To examine the relationship between glutamatergic function and cortical connectivity and determine if riluzole can modulate glutamate metabolite levels and cortical functional connectivity in TRS. Nineteen TRS patients and 18 healthy volunteers (HV) underwent magnetic resonance imaging consisting of MR spectroscopy measuring ACC glutamate plus glutamine (Glx), fMRI measuring resting ACC-functional connectivity, and arterial spin labelling measuring regional cerebral blood flow (rCBF), and clinical measures. They then received 50 mg riluzole twice daily for 2 days when imaging was repeated. Baseline (pre-riluzole) Glx levels were correlated directly with negative symptom severity (r = 0.49; p = 0.03) and inversely with verbal learning in TRS (r = - 0.63; p = 0.002), but not HV (r = - 0.24; p = 0.41). Connectivity between the ACC and anterior prefrontal corte...Continue Reading

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Citations

Jan 11, 2020·World Psychiatry : Official Journal of the World Psychiatric Association (WPA)·Robert A McCutcheonOliver D Howes
Sep 6, 2019·Psychopharmacology·Alice Egerton
Dec 4, 2019·Neuroscience and Biobehavioral Reviews·Benjamín RodríguezMirian A F Hayashi
Nov 13, 2020·Frontiers in Pharmacology·Dennis KätzelDavid M Bannerman
May 29, 2021·Translational Psychiatry·Robert A McCutcheonOliver D Howes
Jul 15, 2021·Molecular Psychiatry·Oliver D HowesToby Pillinger

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Methods Mentioned

BETA
imaging techniques

Software Mentioned

CONN
Automatic Software for ASL Processing ( ASAP ) toolbox
SPM
LCModel
SPSS
SPM12

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