Serotonin 5-HT 2 receptor imaging in major depression: focal changes in orbito-insular cortex

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.

Section: Introductionmentioning

confidence: 70%

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

Lang

Hellweg

Gallinat

2005

“…Some studies have found decreased 5-HT 2A receptor binding in depressed patients more diffusely (Larisch et al, 2001;Yatham et al, 2000;Moresco et al, 2000). Biver et al (1997b) found decreased 5-HT 2A receptor binding in a single region of the frontal cortex. Methods of analysis and selectivity of radiotracers used varied widely across these reports and may be a source of the variability of the results.…”

Section: Discussionmentioning

confidence: 99%

“…[ 18 F]altanserin has high affinity (K i ¼ 0.13 nM) and selectivity for imaging 5-HT 2A receptors (Lemaire et al, 1991), and has in vivo binding in rat brain comparable to in vitro mapping of 5-HT 2A receptors (Biver et al, 1997a). It also has good in vivo test-retest reliability in humans (Smith et al, 1998) with an established literature in human brain mapping using PET (Biver et al, 1997b;Smith et al, 1998;Meltzer et al, 1999;Larisch et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…Using spiperone, Moresco et al (2000) found significant differences in 15 antidepressant-free depressed subjects in frontal, temporal, and occipital cortex but not in the anterior cingulate. Biver et al (1997b) found significant reduction in orbito-frontal and insular 5-HT 2A receptors in eight depressed antidepressant-free subjects using [ 18 F]altanserin, a ligand with virtually no affinity for dopamine. Also using altanserin, Larisch et al (2001) found significant reductions in frontal, temporal, parietal, and occipital cortex in 12 subjects who were on antidepressants.…”

Section: Introductionmentioning

confidence: 99%

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Decreased Hippocampal 5-HT2A Receptor Binding in Older Depressed Patients Using [18F]Altanserin Positron Emission Tomography

Sheline

Mintun

Deanna

et al. 2004

Serotonin receptor changes have been associated with the pathophysiology and treatment of major depression. Only one other study has investigated serotonin receptor changes in older depressed patients. We used positron emission tomography (PET) and [ 18 F]altanserin, a ligand with high affinity for the 5-HT 2A receptor, to examine the relationship between 5-HT 2A receptor density and depression. Depressed subjects (n ¼ 16), age450 years, were recruited as part of a larger study. Older depressed subjects consisted of early-onset recurrent depression (EORD, n ¼ 11) and late-onset depression (LOD, n ¼ 5). An age-matched control group (n ¼ 9) was also recruited. All subjects were right-handed, nonsmokers and antidepressant-free. Regions of interest were determined on a summed MPRAGE scan transformed into Talairach space and coregistered with the PET images. Depressed subjects had less hippocampal 5-HT 2A receptor binding than controls (p ¼ 0.05). No significant differences in receptor binding were found between EORD and LOD subjects. Depressed subjects not previously treated for depression (n ¼ 6) had less hippocampal 5-HT 2A receptor binding (p ¼ 0.04) than previously treated subjects (n ¼ 10). It may be that prior medication treatment provides a compensatory upregulation of the 5-HT 2A receptor.

“…However, the involvement of 5-HT 2A receptor binding in major depression has been explored in several cross-sectional postmortem (Stockmeier, 2003) and imaging studies (Attar-Levy et al, 1999;Biver et al, 1997;Yatham et al, 2000;Messa et al, 2003) of which two studies took into account measures of negativistic thinking. A recent study by Bhagwagar et al (2006), in un-medicated, euthymic patients recovered from depression, support that a higher frontolimbic 5-HT 2A receptor level may be a trait factor of the susceptibility to develop depression and correlate positively with measures of negativistic thinking.…”

Section: Discussionmentioning

confidence: 99%

Familial Risk for Mood Disorder and the Personality Risk Factor, Neuroticism, Interact in Their Association with Frontolimbic Serotonin 2A Receptor Binding

Frøkjær¹,

Vinberg

Erritzoe³

et al. 2009

Life stress is a robust risk factor for later development of mood disorders, particularly for individuals at familial risk. Likewise, scoring high on the personality trait neuroticism is associated with an increased risk for mood disorders. Neuroticism partly reflects stress vulnerability and is positively correlated to frontolimbic serotonin 2A (5-HT 2A ) receptor binding. Here, we investigate whether neuroticism interacts with familial risk in relation to frontolimbic 5-HT 2A receptor binding. Twenty-one healthy twins with a co-twin history of mood disorder and 16 healthy twins without a co-twin history of mood disorder were included. They answered self-report personality questionnaires and underwent [ 18 F]altanserin positron emission tomography. We found a significant interaction between neuroticism and familial risk in predicting the frontolimbic 5-HT 2A receptor binding (p ¼ 0.026) in an analysis adjusting for age and body mass index. Within the high-risk group only, neuroticism and frontolimbic 5-HT 2A receptor binding was positively associated (p ¼ 0.0037). In conclusion, our data indicate that familial risk and neuroticism interact in their relation to frontolimbic 5-HT 2A receptor binding. These findings point at a plausible neurobiological link between genetic and personality risk factors and vulnerability to developing mood disorders. It contributes to our understanding of why some people at high risk develop mood disorders while others do not. We speculate that an increased stress reactivity in individuals at high familial risk for mood disorders might enhance the effect of neuroticism in shaping the impact of potential environmental stress and thereby influence serotonergic neurotransmission.