Beta Adrenergic Receptor Function in Depression and the Effect of Antidepressant Drugs

Abstract

I t h a s been suggested t h a t alterations of monoamine receptor sensitivity in t h e c e n t r a l nervous system may b e associated with some f o r m s of a f f e c t i v e illness. I t h a s been observed by several investigators t h a t chronic t r e a t m e n t with antidepressant drugs causes down regulation of NE receptor coupled adenylate cyclase and b e t a adrenergic receptor binding in r a t brain. This observation h a s led to t h e suggestion t h a t t h e therapeutic e f f e c t s of antidepressant drugs may b e related to t h e changes in t h e responsivity of b e t a adrenergic receptors. In order to examine if depressive illness may be associated with a l t e r e d b e t a adrenergic function, we studied adenylate cyclase and i t s responsiveness to norepinephrine and isoproterenol in t h e leukocytes obtained from patients with psychiatric illness and normal controls as a n index of beta adrenergic receptor function. We also studied t h e e f f e c t s of antidepressant drugs, in vitro, on isoproterenol sensitive leukocyte adenylate cyclase. W e observed t h a t norepinephrine and isoproterenol sensitive leukocyte adenylate cyclase in depressed patients a r e significantly decreased as compared to normal controls. Our results appear to have been replicated by another group of investigators. W e also observed t h a t c e r t a i n antidepressnt drugs potentiate isoproterenol stimulated accumulation of cyclic AMP in human leukocytes. This potentiation w a s most pronounced in t h e case of iprindole. These results thus indicated a decreased beta adrenergic receptor function in patients with depressive illness.Whether or not such decreased receptor function is associated with depressive illness o r is a manifestation of s o m e other changes unrelated to t h e illness is not clear. Our results also indicate t h a t some antidepressant drugs may enhance adrenergic transmission by potentiating t h e e f f e c t s of neurotransmitters on b e t a adrenergic receptors.An abnormality of amine function in a f f e c t i v e illness may result due to changes in a m i n e biosynthesis, metabolism, uptake o r due to a n imbalance in neurotransmitter systems. I t is also possible t h a t amine dysfunction in a f f e c t i v e illness may b e associated with altered sensitivity of t h e c e n t r a l neurotransmitter receptors. Alterations in t h e neurotransmitter input from t h e presynaptic neuron may cause compensatory changes in t h e postsynaptic neurotransmitter receptor sensitivity o r response. In r e c e n t years, i t has been suggested t h a t in addition to t h e studies of monoamine metabolites and t h e e n z y m e s associated with t h e biosynthesis o r metabolism of t h e monoamines such as monoamineoxidase (MAO) or catechol-o-methyltransferase (COMT), t h e role of monoamine receptor sensitivity in a f f e c t i v e illness needs to b e examined as h a s been emphasized by Aschcroft et al. (1972).T h e observation by several groups of investigators t h a t chronic t r e a t m e n t with alm...

Potential depression and antidepressant-response biomarkers in human lymphoblast cell lines from treatment-responsive and treatment-resistant subjects: roles of SSRIs and omega-3 polyunsaturated fatty acids

“…4a). A previous study also reported that cAMP levels in leucocytes from healthy control and depressive subjects were not different [62], which is consistent with our findings (fig. 4a).…”

Neural Plasticity and Proliferation in the Generation of Antidepressant Effects: Hippocampal Implication

“…In peripheral cells and postmortem brains of patient with mayor depression, there is a reduction of the adenylyl cyclase (AC) activity in response to forskolin [87], β 2 -adrenergic agonists [88–93], and α 2-adrenoceptor agonists [94]. Chronic treatment with antidepressant drugs produces the increase in cAMP levels in rat hippocampus, cortex, and striatum, as well as in postmortem human frontal cortex samples from depressed patients (Figure 3(a); personal observation).…”

A novel peripheral biomarker for depression and antidepressant response

“…Earlier studies that employed more cumbersome cAMP assays suggested that attenuated PGE1 in platelets ( 32 ) and impaired β–adrenergic signaling in white blood cells ( 31 ) could be associated with both depression and clinical improvement. It is noteworthy, however, that, in lymphoblasts from depressed subjects we observed increased cAMP signaling which was reversed by antidepressant treatment ( 45 ).…”

“…Studies in white blood cells ( 31 ) and platelets ( 32 – 33 ) suggested the possibility that Gsα stimulated adenylyl cyclase showed results consistent with attenuated cAMP generation in MDD. These findings suggest that a modern adenylyl cyclase assay taken from blood cells might reflect a diagnosis of MDD and antidepressant response and may be adaptable to high throughput screening.…”