SYMPOSIA

Abstracts of the Invited Speakers
The glutamatergic system and its importance in the neurobiology of depression
Feyza Arıcıoğlu
Department of Pharmacology, Marmara University, Istanbul, Turkey
E-mail: feyza.aricioglu@gmail.com
Recent advances in research on depression have confirmed that it is common, recurrent and disabling mental disorder affecting millions
of individuals worldwide. Current medications for the treatment of depression have limited efficacy and delayed onset of therapeutic
action. Existing antidepressants used to treat these disorders are insufficient for many. Patients continue to have low remission rates,
delayed onset of action, residual subsyndromal symptoms, and relapses. New therapeutic agents able to exert faster and more sustained
antidepressant effects are urgently needed to treat these disorders. Multiple lines of evidence suggest that inflammation and glutamate
dysfunction contribute to the pathophysiology of depression. Excess levels of inflammatory mediators occur in a subgroup of depressed
patients. Patients with depression have been found to exhibit increased blood inflammatory biomarkers, including inflammatory cytokines,
which have been shown to be involved in depression. Activation of inflammatory pathways is believed to contribute to a confluence of
decreased neurotrophic support and altered glutamate release/reuptake, as well as oxidative stress, leading to excitotoxicity and loss of
glial elements, consistent with findings that characterize depressive disorders. Neurotrophic factors such as brain-derived neurotrophic
factor (BDNF) are involved in the pathogenesis of mood disorders and in the action of at least some drugs. It has been shown that serum
BDNF levels are decreased in patients with depressive disorder and antidepressant treatment induces BDNF expression. In this context,
the glutamatergic system has been implicated in the pathophysiology of depression in unique clinical and neurobiological ways. The data
from depressed patients, suggest that inhibiting proinflammatory cytokines or their signaling pathways may improve depressed mood
and increase treatment response to conventional antidepressant medication. The past decade of efforts to find improved treatment for
depression has been dominated by genome-driven programs of rational drug discovery directed toward highly selective ligands for
nonmonoaminergic agents. To date, the monoaminergic systems (serotonin, norepinephrine, and dopamine) have received the most
attention in the neurobiology of depression, and all classes of antidepressants target these monoaminergic systems. Accumulating
evidence suggests that the glutamatergic system plays an important role in the neurobiology and treatment of depression. Many
reports have highlighted alterations in glutamate signaling as well as changes in the expression of AMPA or NMDA receptor subunits
in depression. In parallel, there is growing interest in the non-competitive NMDA receptor antagonist, ketamine, which produces a
rapid and sustained antidepressant response in patients with treatment-resistant depression. Importantly, such effects of ketamine are
seen at subpsychomimetic doses of the drug. Moreover, ketamine produces a profound reduction in suicidality. Based on findings with
ketamine, there is interest in developing subtype-selective NMDA antagonists, particularly those that act through allosteric mechanisms.
A final glutamatergic strategy for treating depression may be through modulating metabotropic (G protein-coupled) glutamate (mGlu)
receptors. During the last 10 years, several selective mGlu receptor competitive antagonists and potentiators have been discovered.
Selective mGlu receptor antagonists are among the most promising agents under development for the treatment of depression. Overall,
this system holds considerable promise for developing the next generation of therapeutics for the treatment of depression.
Key words: Glutamate, depression, cytokines, neurotrophic factors, NMDA, mGLU receptors
Bulletin of Clinical Psychopharmacology 2011;21(Suppl. 2):S70
[PS-11]
Symposium Title: Psychotropic drug treatments during pregnancy and lactation
Pharmacotherapy of panic disorder during pregnancy and lactation
Faruk Uğuz
Selcuk University, Meram Faculty of Medicine, Department of Psychiatry
E-mail: farukuguz@gmail.com;farukuguz@hotmail.com
Panic disorder is one of important psychiatric problems during pregnancy and lactation. The prevalence rate of this disorder has been
reported to be 0.4%-4.0% in the perinatal period. In addition, the perinatal period may affect the onset or course of panic disorder.
Although pharmacotherapy of panic disorder is well known, data on treatment of this disorder during pregnancy and lactation are very
limited. It is difficult to decide about pharmacotherapy of panic disorder during the perinatal period, particularly during pregnancy,
S70 Bulletin of Clinical Psychopharmacology, Vol: 21, Supplement: 2, 2011 - www.psikofarmakoloji.org