Measurement of Brain Regional α-[11C]Methyl-L-Tryptophan Trapping as a Measure of Serotonin Synthesis in Medication-FreePatients With Major Depression

Rosa‐Neto, Pedro; Dikšić, Mirko; Okazawa, Hidehiko; Leyton, Marco; Ghadirian, Nayyer; Mzengeza, B. Shadreck; Nakai, Asami; Debonnel, Guy; Blier, Pierre; Benkelfat, Chawki

doi:10.1001/archpsyc.61.6.556

Cited by 114 publications

(60 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, behavioral antidepressant-like properties of BDNF in animal models have been reported (Shirayama et al, 2002;Siuciak et al, 1997). This scenario is compatible with recent investigations supporting the serotonin deficit hypothesis in depression: A study employing a-methyl-tryptophan positron emission tomography found evidence for a reduced serotonin synthesis in limbic and paralimbic structures in patients with depression compared to controls (Rosa-Neto et al, 2004).…”

Section: Discussionsupporting

confidence: 85%

Association of BDNF Serum Concentrations with Central Serotonergic Activity: Evidence from Auditory Signal Processing

Lang

Hellweg

Gallinat

2005

Neuropsychopharmacol

View full text Add to dashboard Cite

Disturbances of serotonergic neurotransmission in the brain have been implicated in the pathogenesis and maintenance of several psychiatric disorders. According to recent preclinical and clinical studies, the loudness dependence of auditory evoked potentials (LD) is related to the central serotonergic neurotransmission in humans. As the serotonergic phenotype has been reported to be associated with brain-derived neurotrophic factor (BDNF), we studied whether BDNF serum concentrations are related to LD in 109 healthy human volunteers (62 male, 47 female, age: 42.5713.1 years). Pearson correlation showed a significant negative correlation between the BDNF serum concentrations and the LD measured at Fz (r ¼ À0.259, p ¼ 0.007) and a trend for the Cz electrode (r ¼ À0.185, p ¼ 0.055). Although this association needs to be replicated, the results are in line with the assumption that low serum BDNF levels reflect low central serotonergic neurotransmission as indicated by a strong LD.

show abstract

Section: Discussionsupporting

confidence: 85%

Association of BDNF Serum Concentrations with Central Serotonergic Activity: Evidence from Auditory Signal Processing

Lang

Hellweg

Gallinat

2005

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…The effects of the acute treatment on 5-HT synthesis in the FRL rats presented here accord with the effects of the sub-chronic (7 day) treatment with the 5-HT 1B/1D agonist, CGS 12066B, which decreased 5-HT synthesis in the median raphe and terminal areas, but produced no effect on 5-HT synthesis in the DR [51]. Regarding the relative clinical importance of the 5-HT synthesis in the raphe nuclei vs. the terminal regions, in the currently depressed patients, 5-HT synthesis was significantly decreased in some of the 5-HT terminal regions (cingulate and temporal cortices), relative to age and gender-matched healthy controls, as measured by positron emission tomography [43]. However, the degree of the 5-HT synthesis decrease was not correlated with the severity of the depression symptoms, as measured by the clinically used rating scales.…”

Section: Discussionmentioning

confidence: 88%

The opposite effect of a 5-HT1B receptor agonist on 5-HT synthesis, as well as its resistant counterpart, in an animal model of depression

Skelin

Kovačević

Sato

et al. 2012

Brain Research Bulletin

Self Cite

View full text Add to dashboard Cite

Flinders Sensitive Line (FSL) rat is as an animal model of depression with altered parameters of the serotonergic (5-HT) system function (5-HT synthesis rates, tissue concentrations, release, receptor density and affinity), as well as an altered sensitivity of these parameters to different 5-HT based antidepressants. The effects of acute and chronic treatments with the 5-HT 1B agonist, CP-94253 on 5-HT synthesis, in the FSL rats and the Flinders Resistant Line (FRL) controls were measured using α-[ 14 C]methyl-L-tryptophan (α-MTrp) autoradiography. CP-94253 (5 mg/kg), or an adequate volume of saline, was injected i.p. as a single dose in the acute experiment or delivered via the subcutaneously implanted osmotic minipump (5 mg/kg/day for 14 days) in the chronic experiment. The acute treatment with CP-94253 significantly decreased the 5-HT synthesis in both the FRL and FSL rats, with a more widespread effect in the FRL rats. Chronic treatment with CP-94253 significantly decreased 5-HT synthesis in the FRL rats, while 5-HT synthesis in the FSL rats was significantly increased throughout the brain. In both the acute and chronic experiment, the FRL rats had higher brain 5-HT synthesis rates, relative to the FSL rats.The shift in the direction of the treatment effect from acute to chronic, using the 5-HT 1B agonist, CP-94253, on 5-HT synthesis in the FSL model of depression, with an opposite effect on the control FRL rats, suggests the differential adaptation of the 5-HT system in the FSL and FRL rats to chronic stimulation of 5-HT 1B receptors.

show abstract

“…For example, the finding that the rate of serotonin synthesis may be low in depressed patients can be explained in multiple ways. 7 A reduction in serotonin synthesis may result in depression, depression may result in a reduction in serotonin synthesis, or a third factor may be responsible for both lowering serotonin synthesis rates and triggering depression.…”

Section: A Revised Monoamine Hypothesismentioning

confidence: 99%

Neurobiological mechanisms in major depressive disorder

Rot¹,

Mathew²,

Charney³

2009

Canadian Medical Association Journal

378

200

View full text Add to dashboard Cite

N early 1 in 5 people will experience a major depressive episode at some point in their lives.1 In this review, we discuss data describing how genes, psychosocial adversity in childhood, and ongoing or recent psychosocial stress may impact multiple neurobiological systems relevant to major depressive disorder. Major depressive disorder may be caused by the cumulative effects of these 3 factors on the brain.

show abstract

Measurement of Brain Regional α-[11C]Methyl-L-Tryptophan Trapping as a Measure of Serotonin Synthesis in Medication-FreePatients With Major Depression

Abstract: Reduction of normalized K*, an index of serotonin synthesis, in parts of the limbic and paralimbic cortices may contribute to the biochemical alterations associated with MD.

Cited by 114 publications

References 66 publications

Association of BDNF Serum Concentrations with Central Serotonergic Activity: Evidence from Auditory Signal Processing

Association of BDNF Serum Concentrations with Central Serotonergic Activity: Evidence from Auditory Signal Processing

The opposite effect of a 5-HT1B receptor agonist on 5-HT synthesis, as well as its resistant counterpart, in an animal model of depression

Neurobiological mechanisms in major depressive disorder

Contact Info

Product

Resources

About