SYMPOSIA
SYMPOSIA
SYMPOSIA
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Bulletin of Clinical Psychopharmacology, Vol: 21, Supplement: 2, 2011 - www.psikofarmakoloji.org<br />
Abstracts of the Invited Speakers<br />
search continues for other targets that may give clues for the development of future antidepressant drugs that are effective in a greater<br />
number of depressed patients, are faster acting and have an improved side effect profile over those currently available. Some of those<br />
targets will be discussed in this overview.<br />
The amino acids γ-aminobutyric acid (GABA) and glutamate are major inhibitory and excitatory neurotransmitters, respectively in the<br />
brain, and a delicate balance between them must be maintained for normal brain function. Research on GABA at the animal model and<br />
clinical levels implies a GABAergic deficit in depression, and animal studies and the rapid antidepressant action of intravenous ketamine<br />
in human subjects suggest hyperglutamatergia in depression, although the results of some neuroimaging studies to date do not seem<br />
to support these ideas. In recent years, there has been a great deal of interest in the possible roles of neuroactive steroids (rapid acting<br />
neurosteroids which can act as positive or negative modulators of a number of neurotransmitter receptors, most notably GABA-A and<br />
NMDA glutamate receptors) in the etiology and pharmacotherapy of depression. Allopregnanolone has received particular attention<br />
in this regard. Several researchers have proposed that the hypothalamic-pituitary-adrenal (HPA) axis plays a central role in the etiology<br />
of depression and there has been considerable interest in corticotropin-releasing hormone (CRH) receptor antagonists as potential<br />
antidepressants. The peptide substance P acts on neurokinin 1 (NK1) receptors, and there is ongoing interest in NK1 receptor antagonists<br />
as potential antidepressants. The role of the immune system in depression has been the focus of considerable research and it has been<br />
proposed that excessive proinflammatory cytokines (which are released by activated microglia) may result in depressive symptoms; it<br />
is of interest that such cytokines can activate CRH release and reduce levels of 5-HT in the brain. Although there are some contradictory<br />
results, several studies suggest that antidepressants increase expression of cyclic AMP-regulated element-binding protein (CREB) and<br />
brain-derived neurotrophic factor (BDNF). Dysfunction of melatonin secretion in depression has been suggested and this may account,<br />
at least in part, for sleep disorders experienced by many depressed subjects. Agomelatine, a melatonin receptor agonist and 5-HT2C<br />
receptor antagonist, is now marketed as an antidepressant. The potential interactions of several of the targets mentioned above will be<br />
discussed.<br />
Acknowledgements: The authors are grateful to the Canadian Institutes of Health Research (CIHR), the Canada Research Chairs program<br />
and the University of Alberta for Funding.<br />
Key words: Antidepressants, biogenic amines, GABA, glutamate, HPA axis, CRH, substance P, neuroactive steroids, glia<br />
Bulletin of Clinical Psychopharmacology 2011;21(Suppl. 2):S50-1<br />
<strong>SYMPOSIA</strong><br />
[PS-01]<br />
Symposium Title: Epigenetics or genetics: Gene-environment interactions over the life - span<br />
Alzheimer’s disease: Genes and/or life style<br />
Engin Eker<br />
Istanbul University, Cerrahpaşa School of Medicine, Department of Psychiatry<br />
E-mail: enginekertr@yahoo.com<br />
A number of genetic risk factors have been identified, but only a small proportion of Alzheimer’s disease (AD) cases can be explained by<br />
specific gene mutations. Several genetic risk factors have been linked to AD. Mutations in APP, PS1, and PS2 genes have consistently been<br />
associated with early-onset familial Alzheimer’s disease (FAD). A majority of AD cases manifest as sporadic late onset form (LOAD) typically<br />
with onset above the age of 65 years. Most people who develop Alzheimer’s are diagnosed after age 80. More recently a large number<br />
of genes have been implicated as a risk to LOAD, but only a few of these associations have been replicated such as the gene encoding<br />
for the APOE4 allele or loci in the clusterin (CLU), phosphatidylinositol binding clathrin assembly protein (PICALM), and complement<br />
receptor1 (CR1).<br />
Most diseases of aging are influenced by gene-environment interactions. AD has both genetic and environmental risk factors. The genetic<br />
susceptibility influenced by genes like ApoE4 are factors to be aware of, but perhaps more important are the environmental risk factors.<br />
Environmental risk factors can act as triggers in the expression of gene potential. Numerous studies indicate that ApoE4 carriers may be<br />
more vulnerable to environmental factors.<br />
Recent studies have shown that dietary factors, such as exposure to a Mediterranean diet, fish and high omega-3 diets, cigarette<br />
smoking, head trauma, infections, systemic inflammation, and metal exposure can significantly alter an individual’s risk of developing<br />
AD. On the other hand psychosocial factors such as education, social network, leisure activities and physical activity, chronic stress, and<br />
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