Beyond monoamines: glutamatergic
function in mood disorders

by
Kugaya A, Sanacora G.
Department of Psychiatry,
Yale University School of Medicine,
New Haven, CT, USA.
CNS Spectr. 2005 Oct;10(10):808-19.


ABSTRACT

The monoamine theory has implicated abnormalities in serotonin and norepinephrine in the pathophysiology of major depression and bipolar illness and contributed greatly to our understanding of mood disorders and their treatment. Nevertheless, some limitations of this model still exist that require researchers and clinicians to seek further explanation and develop novel interventions that reach beyond the confines of the monoaminergic systems. Recent studies have provided strong evidence that glutamate and other amino acid neurotransmitters are involved in the pathophysiology and treatment of mood disorders. Studies employing in vivo magnetic resonance spectroscopy have revealed altered cortical glutamate levels in depressed subjects. Consistent with a model of excessive glutamate-induced excitation in mood disorders, several antiglutamatergic agents, such as riluzole and lamotrigine, have demonstrated potential antidepressant efficacy. Glial cell abnormalities commonly associated with mood disorders may at least partly account for the impairment in glutamate action since glial cells play a primary role in synaptic glutamate removal. A hypothetical model of altered glutamatergic function in mood disorders is proposed in conjunction with potential antidepressant mechanisms of antiglutamatergic agents. Further studies elucidating the role of the glutamatergic system in the pathophysiology of mood and anxiety disorders and studies exploring the efficacy and mechanism of action of antiglutamatergic agents in these disorders, are likely to provide new targets for the development of novel antidepressant agents.
NMDA
Riluzole
Serotonin
Dopamine
Memantine
Monoamines
21st Century
Noradrenaline
Neurotrophins
NMDA antagonists
New antidepressants
Glutamate and GABA
Glutamate and depression
Depression and antidepressants
Glutamate-modulating drugs for mood disorders


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