title: Serotonergic dysregulation in bipolar disorders: a literature review of serotonergic challenge studies.
abstract: OBJECTIVE
  Serotonin (5-hydroxytryptamine; 5-HT) and endocrine abnormalities have been repeatedly reported in bipolar disorders (BD). Useful methods to investigate 5-HT responsivity, and the interaction with neuroendocrine functioning, are provided by acute 5-HT challenge and depletion paradigms. In this review 5-HT challenges are limited to paradigms that stimulate 5-HT activity in BD.
  
  
  METHODS
  Literature was searched for in electronic libraries: MEDLINE and PSYCHLIT, period 1966-2001. Papers describing effects of an acute 5-HT challenge on neuroendocrine functioning in BD patients were selected.
  
  
  RESULTS
  Review of the literature revealed 15 studies: five papers described the effects of 5-HT challenges in manic BD patients, four papers in euthymic BD and seven in depressed BD patients. The reviewed 5-HT challenge paradigms are acute administration of oral and intravenous (i.v.) dosage of d,l-fenfluramine, tryptophan, 5-hydroxytryptophan, ipsapirone and buspirone. There were no papers which investigated neuroendocrine effects of m-chlorophenylpiperazine, clomipramine and citalopram in BD patients and were therefore not reviewed.
  
  
  CONCLUSIONS
  The literature on 5-HT challenge procedures in BD shows evidence for a blunted prolactin (PRL) in mania and depression as well as a blunted cortisol in euthymic BD patients. This suggests that in both mania and depression similar changes in the 5-HT system are involved. It is speculated that blunting of cortisol responses in euthymic BD patients may be a result of chronically altered 5-HT functioning, whereas changes in PRL release following 5-HT challenges reflect more state-dependent changes in 5-HT activity. The 5-HT responsivity in BD patients has also been associated with pharmacological treatment, suicidal behaviour, weight loss and age. Recommendations for future research are given.
authors.affiliation: Brain and Behavior Institute, Department of Psychiatry, Academic Hospital Maastricht (AZM), University of Maastricht, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Sobczak
authors.forename: A
authors.initials: A
authors.lastname: Honig
authors.forename: M A
authors.initials: MA
authors.lastname: van Duinen
authors.forename: W J
authors.initials: WJ
authors.lastname: Riedel
mesh_terms: D001714:Bipolar Disorder / Q000145:classification / Q000188:drug therapy* / Q000378:metabolism; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D006801:Humans; D009490:Neurosecretory Systems / Q000378:metabolism* / Q000503:physiopathology; D011985:Receptors, Serotonin / Q000145:classification / Q000378:metabolism* / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000145:classification / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D011985:Receptors, Serotonin; D018490:Serotonin Agents; D012701:Serotonin