105 As it has been demonstrated that even selective reuptake inhibitors affect both systems,106,107 leading to alterations of neuronal firing and postsynaptic receptor responses, a clear assignment to several symptoms or response to treatment seems impossible. Monoaminergic systems are also modulated by other factors,

eg, CRH, vasopressin, neuropeptide Y, cytokines, excitatory Inhibitors,research,lifescience,medical amino acids, or neurotrophic factors.83 Therefore, a plausible model for the pathophysiology of depression and the action of antidepressant treatment needs to take into account the complexity of the regulation of CNS function. Moreover, chronic stress, which is doubtless an important precipitating factor in depression, has many effects, not only on behavior, but also on the endocrine, immune, and neurotransmitter systems,108 and the data implicate a

close link between stress and changes in the HPA axis and the central NE system. Accordingly, depression Inhibitors,research,lifescience,medical may result from dysfunctions in the areas of the brain that are modulated by these systems, such Inhibitors,research,lifescience,medical as the frontal cortex, hippocampus, amygdala, and basal ganglia. It is also well known that these areas are highly sensitive to the effects of stress, possibly accounting for the adverse impact of life events on depression.105 Thus, many different factors could lead to a Inhibitors,research,lifescience,medical selective or generalized dysfunction in these brain areas, accounting for the probable heterogeneity of depression. Brain imaging Despite the increasing number of biochemical and molecular biological studies in depression research, the advances in neuroimaging techniques now offer the possibility of studying Inhibitors,research,lifescience,medical anatomical alterations in living patients. Application of magnetic resonance imaging (MRI) techniques and positron

emission tomography (PET) has disclosed a battery of abnormalities in the brains of patients with major depression. Several studies have suggested that a large proportion of patients with major depression do indeed isothipendyl have signs of brain atrophy. Increased ventricle-brain volumes have been discussed, as have localized atrophy in the frontal lobes, especially in patients with late -life depression.109,110 Functional studies have revealed reduced blood flow in specific brain regions, particularly the frontal lobe and the basal ganglia.111 One of the brain structures that has been extensively studied with regard to the action of stress, depression, and antidepressant actions is the hippocampus – a brain area that is involved in selleck learning and memory.112 Recent imaging studies have shown that the hippocampus undergoes selective volume reduction in stressrelated neuropsychiatrie disorders, such as recurrent depression; it has been suggested that this is related to hypercortisolemia.