Serotonergic dysregulation in bipolar disorders: a literature review of serotonergic challenge studies

Sobczak, Sjacko; Honig, Adriaan; Duinen, MA Van; Riedel, Wim J.

doi:10.1034/j.1399-5618.2002.01217.x

Cited by 64 publications

(33 citation statements)

References 92 publications

(138 reference statements)

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“…There were no interfering effects of mood and physical side effects. There was a positive association of cortisol response following Trp and memory performance; a higher cortisol response was associated with lower Trpinduced impairments on recognition (see also Sobczak et al, 2002b). A possible memory-enhancing effect of acute elevations of cortisol has been described before (Buchanan and Lovallo, 2001;Adler and Jajcevic, 2001).…”

Section: Discussionmentioning

confidence: 84%

Pronounced Cognitive Deficits Following an Intravenous L-Tryptophan Challenge in First-Degree Relatives of Bipolar Patients Compared to Healthy Controls

Sobczak

Honig

Schmitt

et al. 2002

Neuropsychopharmacol

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Cognitive impairment has repeatedly been described in bipolar disorders (BD). Serotonin (5-hydroxytryptophan; 5-HT) is possibly involved in these cognitive processes, more particularly in executive functions, learning, memory, and attention. The aim of this study was to investigate serotonergic vulnerability and its relation to cognitive functioning in healthy first-degree relatives of BD patients. We investigated the effects of an intravenous (i.v.) tryptophan (Trp) challenge and placebo on cognitive performance in 30 healthy firstdegree relatives of bipolar patients (FH) and 15 matched controls in a double-blind crossover design. A distinction was made between relatives of type I BD patients (FH I) and type II BD patients (FH II). Performances on planning, memory, attention, and psychomotor tasks were assessed 3 h after Trp infusion. After Trp, planning and attention were impaired in FH subjects but not in controls. Independent of Trp, FH subjects showed cognitive deficits on memory, focused and divided attention, and psychomotor performance. FH I subjects showed more pronounced cognitive impairments then FH II and controls. In all groups, Trp impaired memory and psychomotor performance significantly. In conclusions, cognitive deficits in FH following Trp may reflect a central 5-HT vulnerability in frontal brain areas. Independent of Trp, cognitive deficits in FH provide evidence for a trait marker for BD.

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Section: Discussionmentioning

confidence: 84%

Pronounced Cognitive Deficits Following an Intravenous L-Tryptophan Challenge in First-Degree Relatives of Bipolar Patients Compared to Healthy Controls

Sobczak

Honig

Schmitt

et al. 2002

Neuropsychopharmacol

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“…3,46 The 'monoamine hypothesis' was mainly based on the action mechanisms of antidepressants and antimanic agents, and this has gradually been confirmed by clinical and postmortem brain studies. [47][48][49] In the brain of Tg mice, we found altered level and/or turnover of monoamines, 5-HT, DA, and NA (Table 2). Chronic treatment with a tricyclic antidepressant-induced manic switch-like behavior in some Tg mice and worsened the distorted day-night rhythm ( Figure 4).…”

Section: Face Validitymentioning

confidence: 98%

Mice with neuron-specific accumulation of mitochondrial DNA mutations show mood disorder-like phenotypes

et al. 2006

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There is no established genetic model of bipolar disorder or major depression, which hampers research of these mood disorders. Although mood disorders are multifactorial diseases, they are sometimes manifested by one of pleiotropic effects of a single major gene defect. We focused on chronic progressive external ophthalmoplegia (CPEO), patients with which sometimes have comorbid mood disorders. Chronic progressive external ophthalmoplegia is a mitochondrial disease, which is accompanied by accumulation of mitochondrial DNA (mtDNA) deletions caused by mutations in nuclear-encoded genes such as POLG (mtDNA polymerase). We generated transgenic mice, in which mutant POLG was expressed in a neuron-specific manner. The mice showed forebrain-specific defects of mtDNA and had altered monoaminergic functions in the brain. The mutant mice exhibited characteristic behavioral phenotypes, a distorted day-night rhythm and a robust periodic activity pattern associated with estrous cycle. These abnormal behaviors resembling mood disorder were worsened by tricyclic antidepressant treatment and improved by lithium, a mood stabilizer. We also observed antidepressant-induced mania-like behavior and long-lasting irregularity of activity in some mutant animals. Our data suggest that accumulation of mtDNA defects in brain caused mood disorder-like mental symptoms with similar treatment responses to bipolar disorder. These findings are compatible with mitochondrial dysfunction hypothesis of bipolar disorder.

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“…There has been some evidence in the literature to suggest that cortisol release is mediated by activation of serotonin 5-HT 1A receptors located at the hypothalamus, whereas PRL release is the net effect of stimulation of serotonin 5-HT 2A/2C receptors and inhibition of dopamine D 2 receptors [7] . In this regard it is expected that CMI enhances central serotonin and exhibits an excitatory functioning on the release of PRL and cortisol.…”

Section: Discussionmentioning

confidence: 99%

Prolactin and Cortisol Responses to Acute Intravenous Clomipramine Challenge in Patients with Mania, Depression and Healthy Controls: Evidence for Reduced Serotonergic Responsivity

Lykouras

Markianos²,

Hatzimanolis

2010

Neuropsychobiology

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Serotonergic dysregulation has been shown to be involved in the pathophysiology of unipolar and bipolar depression. Neuroendocrine challenge tests have been extensively used to investigate serotonin functioning in the brain. Although the role of serotonin has received a great deal of attention using neuroendocrine challenge paradigms, little effort has been made to explore the role of serotonin in mania. We assessed serotonergic neuroendocrine responsivity in patients with depression (n = 22), mania (n = 11) and 15 healthy controls by measuring the prolactin (PRL) and cortisol responses to i.v. clomipramine (CMI) and searched for possible differences among the groups. Blunted PRL responses to CMI in manic and depressed patients compared to healthy controls were found. The response to CMI disclosed similar results for the 2 patient groups. No significant differences were found among the 3 subject groups in the cortisol response to CMI. The blunted PRL responses to CMI in patients with mania and depression suggest that serotonergic functioning in mania and depression is similarly impaired, at least at the level of hypothalamus-hypophysis.

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Serotonergic dysregulation in bipolar disorders: a literature review of serotonergic challenge studies

Cited by 64 publications

References 92 publications

Pronounced Cognitive Deficits Following an Intravenous L-Tryptophan Challenge in First-Degree Relatives of Bipolar Patients Compared to Healthy Controls

Pronounced Cognitive Deficits Following an Intravenous L-Tryptophan Challenge in First-Degree Relatives of Bipolar Patients Compared to Healthy Controls

Mice with neuron-specific accumulation of mitochondrial DNA mutations show mood disorder-like phenotypes

Prolactin and Cortisol Responses to Acute Intravenous Clomipramine Challenge in Patients with Mania, Depression and Healthy Controls: Evidence for Reduced Serotonergic Responsivity

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