Mood disorders function

Lin, C. N., Tsai, S. J. Hong, C. J. (2001a). Association analysis of a functional G protein beta3 subunit Gene polymorphism (C825T) in mood disorders. Neuropsychobiology, 44, 118-21. 

Shiah, I.S.Y.L. GABA function in mood disorders an update and critical review. Life. 63 1289, 1998. 

There is evidence for the contribution of serotonin dysfunction to mania, and in the mechanism of action of mood stabilizers [19], however, specific data on the serotonergic system and mania are fewer and variable. Moreover, altered functioning of other neurotransmitters in mania such as norepinephrine, dopamine, acetylcholine, and GABA, and their interaction with serotonin, are also likely to be involved in the pathogenesis of mood disorders. Differences in these neurotransmitter systems possibly underlie differences in the pathogenesis of depressive and manic episodes. 

There is ample support for the hypothesis of noradrenergic system dysfunction in depression however, the inconsistencies in findings rule out any simple model of increased or decreased noradrenergic activity. It is important to determine which noradrenergic system abnormalities relate specifically to the pathogenesis of mood disorders, and which are related to nonspecific effects of stress, homeostatic mechanisms, or comorbid psychopathology. More work is needed on the mood-state-depen-dence of noradrenergic function. 

Mann, J. J. and Arango, V. Abnormalities of brain structure and function in mood disorders. In Neurobiology of Mental Illness. Ed. Bunney, B. S. New York Oxford University Press,... 

Drevets WC, Price JL, Simpson JR, Jr, Todd RD, Reich T, Vannier M, Raichle ME (1997) Sub-genual prefrontal cortex abnormahties in mood disorders. Nature 386 824-827 Due DL, Huettel SA, HaU WG, Rubin DC (2002) Activation in mesolimbic and visuospatial neural circuits ehcited by smoking cues evidence from functional magnetic resonance imaging. Am J Psychiatry 159 954-960... 

To understand whether cognitive function and mood disorders are cooperatively influenced by genetic factors in AD and to know the potential impact that conventional neuroprotection can exert on mood disorders, we studied the effect of the therapeutic CNLA protocol on anxiety in AD and the differential APOE- and ACE-related responses distinguishing the influence of monogenic and bigenic variants on emotional conditions. 

Mood Disorder Due to a General Medical Condition. Commonly called secondary manias, certain medical and neurological illnesses produce symptoms that mimic mania. Often, secondary manias occur when injury or disease interferes with right-sided brain function. As one might anticipate, this is in contrast to the predilection for left-sided brain injury to be associated with depressive symptoms. 

Neuropsychological impairments in mood disorders, particularly those of working memory and executive function, are the most convincing and objective demonstrations of an impairment of consciousness. Since these impairments do not correlate with the severity of the mood disturbance and persist upon recovery they are not simply epiphenomena of the mood disturbance but rather may index trait pathology in susceptible individuals. It has previously been argued that mood disturbance and neuropsychological impairment may result from disturbances in two different neurochemical systems, the serotonin (5-HT) system and the hypothalamic-pituitary-adrenal (HPA) axis, between which there is a close interaction (McAllister-Williams et al., 1998). 

Tryptophan depletion in healthy volunteers impairs the retrieval of learnt material (Park et al., 1994), an effect probably mediated through a selective impairment of episodic memory consolidation (Riedel et al., 1999 Schmitt et al., 2000). However, tryptophan depletion appears to have no effect on working memory (Riedel et al., 1999) and either no effect or an enhancement of tests of executive function (Park et al., 1994 Schmitt et al., 2000). Thus the abnormality in episodic memory in mood disorders could conceivably be related to an impairment in the 5-HT system, but such an impairment is unlikely to account for the abnormalities in working memory and executive function. Clearly then, changes in consciousness occurring in affective disorders are unlikely to be explainable on the basis of an abnormality in a single neurochemical system. 

The nature of the neurochemical impairment underlying depressive illness remains elusive. There is a great deal of evidence supporting roles for the 5-HT system and the HPA axis. However the evidence is less clear that an abnormality in one system alone can explain the full extent of the clinical features of depressive illness. Subtle abnormalities in the interactions between the HPA axis and the serotonergic system may lead to profound alterations in the functioning of both systems, and it may be this that results in the range of symptoms found in mood disorders. 

In summary, these clinical and preclinical findings support the view that mood disorders can be seen as stress system disorders, in which impairment of GR and MR action plays a causal role. The impairments may be genetically determined or acquired through a variety of early stressors, or both. It is possible that antidepressants exert their clinical efficacy through reinstatement of complete corticosteroid receptor function. Of course, other important actions of these drugs also need careful consideration. 

What then, is the current evidence to support a role of norepinephrine in depression, such that manipulation of noradrenergic activity bears particular relevance to the successful treatment of mood disorders Interpretation of studies depends on the continually evolving conceptualizations of the roles of brain noradrenergic systems. A potentially useful way of thinking about the function of the norepinephrine in the brain can be derived from examining the neuroanatomy of the noradrenergic system. A summary of findings [primarily from rodents and primates) is as follows. 

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