How do glial-neuronal interactions fit into current neurotransmitter hypotheses of schizophrenia?
Evidence is accumulating that the exclusive dopamine hypothesis of schizophrenia has to be abandoned. Instead, a more integrative approach combines different neurotransmitter systems, in which glutamatergic, GABAergic and dopaminergic pathways interact. This paradigm shift coincides with the recognition that, while typical and modern atypical antipsychotic drugs have efficiently controlled the dramatic psychotic symptoms of schizophrenia, their impact on negative and cognitive symptoms is negligible. Indeed, cognitive decline is now believed to represent the core of schizophrenic morbidity and in this context, impairment of glutamate and more specifically NMDA function is of major importance. Given that astrocytes are important in controlling glutamate homeostasis, it is necessary to assign a significant role to glial-neuronal interactions in the pathophysiology of schizophrenia. Indeed, recent data from several animal and human studies corroborate this notion. This review outlines current neurotransmitter hypotheses and evidence for glial impairment in schizophrenia. Furthermore, findings from recent studies of (13)C nuclear magnetic resonance spectroscopy in experimental models of schizophrenia and NMDA hypofunction are presented and their implications for future research on glial-neuronal interactions discussed.
Kondziella
Daniel
D
Department of Neuroscience, Norwegian University of Science and Technology (NTNU), N-7489 Trondheim, Norway.
Brenner
Eiliv
E
Eyjolfsson
Elvar M
EM
Sonnewald
Ursula
U
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D012559:Schizophrenia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D004298:Dopamine