mGluR5 receptor availability is associated with lower levels of negative symptoms and better cognition in male patients with chronic schizophrenia

Hum Brain Mapp. 2020 Jul;41(10):2762-2781. doi: 10.1002/hbm.24976. Epub 2020 Mar 9.

Abstract

Consistent findings postulate disturbed glutamatergic function (more specifically a hypofunction of the ionotropic NMDA receptors) as an important pathophysiologic mechanism in schizophrenia. However, the role of the metabotropic glutamatergic receptors type 5 (mGluR5) in this disease remains unclear. In this study, we investigated their significance (using [11 C]ABP688) for psychopathology and cognition in male patients with chronic schizophrenia and healthy controls. In the patient group, lower mGluR5 binding potential (BPND ) values in the left temporal cortex and caudate were associated with higher general symptom levels (negative and depressive symptoms), lower levels of global functioning and worse cognitive performance. At the same time, in both groups, mGluR5 BPND were significantly lower in smokers (F[27,1] = 15.500; p = .001), but without significant differences between the groups. Our findings provide support for the concept that the impaired function of mGluR5 underlies the symptoms of schizophrenia. They further supply a new perspective on the complex relationship between tobacco addiction and schizophrenia by identifying glutamatergic neurotransmission-in particularly mGluR5-as a possible connection to a shared vulnerability.

Keywords: chronic schizophrenia; cognition; mGluR5 receptor; negative symptoms; positron emission tomography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Caudate Nucleus* / diagnostic imaging
  • Caudate Nucleus* / metabolism
  • Caudate Nucleus* / physiopathology
  • Chronic Disease
  • Cognitive Dysfunction* / etiology
  • Cognitive Dysfunction* / metabolism
  • Cognitive Dysfunction* / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Oximes / pharmacokinetics
  • Positron-Emission Tomography
  • Pyridines / pharmacokinetics
  • Receptor, Metabotropic Glutamate 5 / metabolism*
  • Schizophrenia* / complications
  • Schizophrenia* / metabolism
  • Schizophrenia* / physiopathology
  • Smoking / metabolism
  • Temporal Lobe* / diagnostic imaging
  • Temporal Lobe* / metabolism
  • Temporal Lobe* / physiopathology

Substances

  • GRM5 protein, human
  • Oximes
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • fluoroethyl-desmethyl-ABP688