Furthermore, the monoaminergic systems are extensively distribute

Furthermore, the monoaminergic systems are extensively distributed throughout the network of limbic, striatal, and prefrontal cortical (PFC) neuronal circuits implicated in the behavioral and visceral manifestations of mood disorders.12 Over the past 40 years, clinical studies have aimed to uncover specific flaws

in these neurotransmitter systems in mood disorders by using various biochemical and neuroendocrine approaches. In fact, assessment of cerebrospinal fluid (CSF) chemistry, neuroendocrine responses to pharmacological challenge, and neuroreceptor and transporter binding have demonstrated a number of abnormalities of the serotonergic, noradrenergic, Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical and other neurotransmitter and neuropeptide systems in mood disorders. Although such studies have been useful in the past, they have proved to be of limited value in clarifying the particular pathophysiology of depressive disorders. In order to clarify the biological those underpinnings of these disorders, there should be an appreciation of the episodic and often intense Inhibitors,research,lifescience,medical mood disturbance, which can become progressive over the time. Furthermore, the phenotypic expression of the disease involves

not only episodic and often profound mood disturbances, but also a constellation of cognitive, motor, autonomic, endocrine, and sleep/wake abnormalities. Additionally, while Inhibitors,research,lifescience,medical most antidepressants exert their initial effects by increasing

the levels of serotonin and/or norepinephrine in the synapse, clinical antidepressant effects exclusively selleck screening library result after chronic administration (days to weeks). This suggests that a cascade of downstream effects is ultimately responsible for the clinical antidepressant effects of these medications. These observations have led to the recognition that, although monoaminergic neurotransmitter system Inhibitors,research,lifescience,medical dysfunction undoubtedly plays an important role in mediating some facets of the pathophysiology of depressive disorders, additional fundamental alterations in cellular plasticity cascades are most likely involved.13-15 The functional impairments Anacetrapib during mood episodes have long been recognized; however, there is increasing evidence of significant interepisode impairment as well. The devastation of these disorders is further complicated by the fact that the medications currently used for their treatment are associated with variable rates of efficacy and not intolerable side effects. An appreciation for both the need for more efficacious treatment for mood disorders and the absence of significant advances in the development of truly innovative therapeutics has led to the investigation of intracellular signaling cascades and their role in the pathophysiology and treatment of mood disorders.

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