Depression, antidepressants, and peripheral blood components

Department of Psychiatry, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
Neuro endocrinology letters (Impact Factor: 0.8). 03/2008; 29(1):17-28.
Source: PubMed


The biological attributes of affective disorders and factors which are able to predict a response to treatment with antidepressants have not been identified sufficiently. A number of biochemical variables in peripheral blood constituents have been tested for this purpose, as a consequence of the lack of availability of human brain tissue. At first, the biological attributes of mental disorders were sought at the level of concentrations of neurotransmitters and their metabolites or precursors. Later on, attention shifted to receptor systems. Since the 1990s, intracellular processes influenced by an illness or its treatment with psychopharmaceuticals have been at the forefront of interest. Interest in biological predictors of treatment with antidepressants has reappeared in recent years, thanks to new laboratory techniques which make it possible to monitor cellular processes associated with the transmission of nerve signals in the brain. These processes can also be studied in plasma and blood elements, especially lymphocytes and platelets. The selection of the qualities to which attention is paid can be derived from today's most widely discussed biochemical hypotheses of affective disorders, especially the monoamine hypothesis and the molecular and cellular theory of depression. Mitochondrial enzymes can also play an important role in the pathophysiology of depression and the effects of antidepressants. In this paper, we sum up the cellular, neurochemical, neuroendocrine, genetic, and neuroimmunological qualities which can be measured in peripheral blood and which appear to be indicators of affective disorders, or parameters which make it possible to predict therapeutic responses to antidepressant administration.

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    • "Blood-based biomarkers have been investigated extensively for both depressive disorder (Fišar and Raboch, 2008) and AD (Doecke et al., 2012). Plasma, platelets and peripheral blood mononuclear cells are the key components of peripheral blood in studies of pathophysiology of neuropsychiatric diseases, such as mood disorders and AD (Maes et al., 2009). "
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    ABSTRACT: Glycogen synthase kinase-3β (GSK3β), cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) play critical roles in neuronal survival, synaptic plasticity and memory and participate in the pathophysiology of both depressive disorder and Alzheimer's disease (AD). This study was designed to determine the association of GSK3β activity, CREB activity and BDNF concentration in peripheral blood of patients with AD with or without depressive symptoms and in depressive patients without AD. GSK3β activity in platelets, CREB activity in lymphocytes and BDNF concentration in plasma, platelet-rich plasma or platelets were measured in 85AD patients (36 of whom displayed co-morbid depressive symptoms), 65 non-AD patients with depressive disorder and 96 healthy controls. AD patients were clinically assessed for stage of dementia, cognitive impairment and severity of depressive symptoms. Depressive patients were clinically assessed for severity of depression. We observed increased CREB and GSK3β activity in AD with depressive symptoms or in AD at mild stage of dementia. Decreased BDNF concentration was found in platelet-rich plasma of AD patients at moderate to severe stages of dementia or in AD without depressive symptoms. An association was revealed of the severity of cognitive impairment with the increase of GSK3β in the platelets of AD patients with mild dementia. In depressive patients, a lower concentration of phosphorylated GSK3β was associated with a higher severity of depression. Association was confirmed between severity of depression, CREB activation, and BDNF concentration in drug-naïve depressive patients. Our data demonstrated that AD is accompanied by increased CREB activity in lymphocytes and a decreased concentration of BDNF in platelet-rich plasma. The decreased BDNF concentration appears to correlate with moderate to severe stages of dementia in AD. Observation of decreased phosphorylation of GSK3β in platelets of both AD patients with depressive symptoms and depressive patients after treatment confirms the role of increased GSK3β activity in the pathophysiology of both AD and depressive disorder. Associations were confirmed between AD and platelet GSK3β activity, lymphocyte CREB activity and plasma BDNF. CREB activity and platelet BDNF concentration seems to be related to depressive disorder.
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    • "It is supposed that MAO-B inhibition may slow the course of various neurodegenerative disorders; so, selective inhibitors of MAO-B may be efficacious in treating of Parkinson's disease (Horstink et al. 2006) and possibly Alzheimer's disease (Riederer et al. 2004). MAO-B is the sole type in human platelets and the amino acid sequences of MAO-B in both platelets and brain are identical (Chen et al. 1993); so, platelet MAO can be adopted as a useful surrogate model for the study of aspects of central neuronal function related to monoaminergic neurotransmission (Fišar & Raboch 2008). "
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    No preview · Article · May 2008 · Neuro endocrinology letters
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