SYMPOSIA

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