Monoamine metabolites in cerebrospinal fluid and serotonin uptake inhibition during treatment with chlorimipramine

Åsberg, Marie; Ringberger, Vivi‐Ann; Sjöqvist, Folke; Thorén, Peter; Träskman, Lil; Tuck, J. R.

doi:10.1002/cpt1977212201

Cited by 90 publications

(22 citation statements)

References 8 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2) indicates that there is such an effect on the serotonin system. We have previously obtained data indicating that the serotonin uptake inhibitors, chlorimipramine and zimelidme, give secondary effect on the dopaminergic system (Asberg et al (1977), Bertilsson et al (1981)). The present results indicate that the primary dopaminergic stimulation elicited by bromocriptine gives a secondary effect on the serotonin system.…”

Section: Discussionmentioning

confidence: 95%

Bromocriptine treatment of depressive disorders

Nordin

Siwers

Bertilsson

1981

Acta Psychiatr Scand

View full text Add to dashboard Cite

Fifteen depressed patients were treated with increasing doses of bromocriptine in an open study. Twelve were treated for 5 weeks (final dose 20-60 mg daily) and nine of these recovered almost completely. As expected from a dopamine agonist, bromocriptine decreased the level of homovanillic acid (HVA) in cerebrospinal fluid (CSF) by 15% (P less than 0.05) and 23% (P less than 0.01) after 2 and 5 weeks of treatment, respectively. After 2 but not after 5 weeks of treatment there was also a small but significant decrease (13%; P less than 0.001) of the noradrenaline metabolite HMPG in CSF. Although there was no mean effect on 5-HIAA in CSF, there was a significant relationship between the HVA and 5-HIAA levels (as % of pretreatment level) both after 2 and 5 weeks of treatment (r = 0.96 and r = 0.62, respectively). This may indicate that the drug has an effect on the serotonin system secondary to the dopamine receptor stimulation. The amelioration of depression was not related to HVA, but did correlate to HMPG in CSF (r = 0.65; P less than 0.05) both metabolites measured before treatment. These results indicate that bromocriptine may have antidepressant effects possibly mediated through the noradrenergic system rather than the dopaminergic system.

show abstract

Section: Discussionmentioning

confidence: 95%

Bromocriptine treatment of depressive disorders

Nordin

Siwers

Bertilsson

1981

Acta Psychiatr Scand

View full text Add to dashboard Cite

show abstract

“…Although the original catecholamine hypothesis of major depression stated that a deficient NE delivery to its receptors in the CNS was one of the main causes of depression, 77 studies of NE or its metabolites in CSF, plasma, or urine, or of components of the noradrenergic system in post-mortem brain samples, reported indices suggestive of decreased, [79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96] normal, [97][98][99][100][101][102][103][104][105] or increased [106][107][108][109][110] delivery of NE to its intended receptors in the CNS or periphery. It should be noted that almost all of the prior studies of CSF NE or its metabolites in depressed patients were based on single time points.…”

Section: The Locus Ceruleus Norepinephrine Systemmentioning

confidence: 99%

Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states

2002

View full text Add to dashboard Cite

Stress precipitates depression and alters its natural history. Major depression and the stress response share similar phenomena, mediators and circuitries. Thus, many of the features of major depression potentially reflect dysregulations of the stress response. The stress response itself consists of alterations in levels of anxiety, a loss of cognitive and affective flexibility, activation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system, and inhibition of vegetative processes that are likely to impede survival during a life-threatening situation (eg sleep, sexual activity, and endocrine programs for growth and reproduction). Because depression is a heterogeneous illness, we studied two diagnostic subtypes, melancholic and atypical depression. In melancholia, the stress response seems hyperactive, and patients are anxious, dread the future, lose responsiveness to the environment, have insomnia, lose their appetite, and a diurnal variation with depression at its worst in the morning. They also have an activated CRH system and may have diminished activities of the growth hormone and reproductive axes. Patients with atypical depression present with a syndrome that seems the antithesis of melancholia. They are lethargic, fatigued, hyperphagic, hypersomnic, reactive to the environment, and show diurnal variation of depression that is at its best in the morning. In contrast to melancholia, we have advanced several lines of evidence of a down-regulated hypothalamic-pituitary adrenal axis and CRH deficiency in atypical depression, and our data show us that these are of central origin. Given the diversity of effects exerted by CRH and cortisol, the differences in melancholic and atypical depression suggest that studies of depression should examine each subtype separately. In the present paper, we shall first review the mediators and circuitries of the stress system to lay the groundwork for placing in context physiologic and structural alterations in depression that may occur as part of stress system dysfunction. Molecular Psychiatry (2002) 7, 254-275. DOI: 10.1038/sj/mp/4001032 Keywords: atypical depression; corticotropin releasing hormone (CRH); melancholic depression; norepinephrine (NE); stress Stress precipitates major depression and influences its incidence, severity and course. 1,2 The stress response and major depression share many features because of similar brain circuitries and mediators (reviewed in 3-5 ). Each is associated with a diminution of cognitive and affective flexibility, alterations in arousal, and perturbations in neuroendocrine and autonomic function (reviewed in 5 ). Because major depression is a heterogeneous disorder, we focus here on two subtypes, melancholic and atypical depression. Our data and those of others indicate that the principal arousal producing mediators of the stress response, such as the corticotropin releasing hormone (CRH) system, are hyperactive in melancholic depression. 6 Not surprisingly, melan- cholia is associated with anxiety, dread of the ...

show abstract

“…The reduction of 5-HIAA and HMPG in CSF during CI treatment is in line with reported data. 5 • \0 It is probably due to a feedbackmediated reduction of biosynthesis of serotonin and norepinephrine caused by reuptake inhibition of the two neurotransmitters. A reduction of serotonin synthesis may be due to either decreased activity of tryptophan hydroxylase (the rate-limiting enzyme) or to decreased availability of tryptophan (the precursor amino acid).…”

Section: Level Of Significancementioning

confidence: 99%