Catecholamines hypothesis

Schildkraut, JJ (1965) The catecholamine hypothesis of affective disorders a review of supporting evidence. Am. J. Psychiat. 122 509-522. 

Schildkraut, Joseph J., The Catecholamine Hypothesis of Affective Disorders A Review of Supporting Evidence , American Journal of Psychiatry 122 (1965) 509-22... 

The catecholamine hypothesis of depression proposed that major... 

The catecholamine hypothesis brought several pharmacological findings together in an illuminating relationship but contradicted a number of clinical observations, in particular the delayed onset of action of antidepressant drugs. This also applies to the serotonin hypothesis, which was formulated at about the same time. 

This a a2-noradrenergic presynaptic receptor agonist is approved by the FDA as an antihypertensive. The rationale for using clonidine for mania is based on the original catecholamine hypothesis (21, 22), which postulates a hyperfunctionality of the noradrenergic system predisposing to mania. Because the hypothesis... 

Manji HK, Lenox RH. Protein kinase C signaling in the brain molecular transduction of mood stabilization in the treatment of manic-depressive illness. Biol Psychiatry 1999 46 1328-1351. Schiidkraut JJ. The catecholamine hypothesis of affective disorders (a review of supporting evidence). Am J Psychiatry 1965 122 509-522. 

Lambert G, Johansson M, Agren H, Friberg P (2000) Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness evidence in support of the catecholamine hypothesis of mood disorders. Arch Gen Psychiatry 57 787-793. 

Before discussing the cyclics and MAOIs in more detail, we need to present the postulated biochemical hypotheses for depression. It is believed that depression results from a deficiency in biogenic amines, specifically catecholamines and serotonin, which act as central nervous system neurotransmitters (see Chapter 3). According to the catecholamine hypothesis, depression results from a deficiency in catecholamines (particularly norepinephrine) at varied neuron receptor sites in the brain. The cyclics are believed to block the reuptake of norepinephrine from the synaptic cleft. Thus, the result is a greater concentration of norepinephrine in the synaptic cleft, alleviating the hypothesized neurotransmitter deficiency. This cyclic-mediated process is thought to occur in the amygdala and reticular formation areas of the brain. 

The catecholamine hypothesis of mood disorders suggests that increased DA and norepinephrine (NE) activity contribute to hyperactivity and psychosis associated with the severe stages of mania, and reduced activity causes depression. A y-aminobutyric acid (GABA) deficiency theory has been proposed for mania since it inhibits NE and DA activity. Glutamate and aspartate, excitatory amino... 

The cause of ADHD is unknown. It is possible that there is loss of inhibitory control in the limbic system because of a disorder in the right frontal cerebral cortex. Dopamine D4 receptors are implicated in ADHD and there is a catecholamine hypothesis of a deficit of... 

The other end of the psychiatric spectrum (Fig. 12-19) is depression. A catecholamine hypothesis that evolved here during the mid-1960s essentially stated that most of depression is associated with a relative or absolute catecholamine deficiency, especially NE at functionally important adrenergic receptor sites in the brain (Schildkraut, 1965). It is presumed that the opposite situation, which is excess catecholamines, may produce mania. Even though overly simplistic, the hypothesis served as a useful initiation into the developing complexity that followed. The NE deficiency, of course, can arise in any of several ways (1) decreased synthesis, (2) impairment of receptor binding, (3) storage impairment, (4) increased intracellular release, (5) increased oxidative metabolism rate, and (6) decreased receptor sensitivity. It is possible that different depression subtypes relate to dif-... 

The catecholamine hypothesis was then modified to include 5-HT in the etiology of depression (9,10). It should be noted, however, that not all Inhibitors of monoamine reuptake are antidepressants, because cocaine, a potent inhibitor of NE and dopamine reuptake, is not an antidepressant but, rather, an addictive stimulant. Subsequent studies with inhibitors of monoamine biosynthesis appear to confirm Kielholz s opinion and Schiidkraut s modified theory that clinical depression is the result of a deficiency in both 5-HT and NE and that the antidepressive mechanism of action most likely affects levels of both. 

Goodwin, F. K. and Sack, R. L. (1973) Affective disorders the catecholamine hypothesis revised In E. Usdin and S. H. Syuder, (Eds.), Frontiers in Catecholamine Research. Pergamon Press, Oxford, pp. 1157-1164. 

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