Frontolimbic Serotonin 2A Receptor Binding in Healthy Subjects Is Associated with Personality Risk Factors for Affective Disorder

Frøkjær, Vibe G.; Mortensen, Erik Lykke; Nielsen, Finn Årup; Haugbøl, Steven; Pinborg, Lars H.; Adams, Karen; Svarer, Claus; Hasselbalch, Steen G.; Holm, Sven; Paulson, Olaf B.; Knudsen, Gitte M.

doi:10.1016/j.biopsych.2007.07.009

Cited by 221 publications

(154 citation statements)

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“…15 In the occupancy plotting of [ 11 C]Cimbi-36 we found V ND values around 12 mL/cm 3 . With corresponding neocortical V T values of 30 mL/cm 3 we thus found an approximate signal-to-noise ratio of 1.5 for quantifying 5-HT 2A receptor binding in cortical areas of the human brain with [ 11 C]Cimbi-36.…”

Section: Resultsmentioning

confidence: 83%

Serotonin 2A Receptor Agonist Binding in the Human Brain with [¹¹C]Cimbi-36

Ettrup

Cunha-Bang

McMahon

et al. 2014

J Cereb Blood Flow Metab

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111

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[ 11 C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT 2A ) receptor agonist radioligand for positron emission tomography (PET) brain imaging. Such an agonist PET radioligand may provide a novel, and more functional, measure of the serotonergic system and agonist binding is more likely than antagonist binding to reflect 5-HT levels in vivo. Here, we show data from a first-in-human clinical trial with INTRODUCTIONThe neurotransmitter serotonin (5-HT) is a modulator of a vast variety of normal physiologic effects and is also involved in the pathophysiology of central nervous system disorders such as depression and schizophrenia. The serotonin 2A (5-HT 2A ) receptor is the main excitatory 5-HT receptor in the human central nervous system, it is responsible for the hallucinogenic effects of recreational agonist drugs such as lysergic acid diethylamide and psilocybin, and 5-HT 2A receptor antagonism is a characteristic of atypical antipsychotics. 1 Furthermore, changes in 5-HT 2A receptor levels have been linked to the pathophysiology of human diseases such as depression. 2,3 Positron emission tomography (PET) has unsurpassed sensitivity and selectivity to detect and quantify specific proteins and processes in the human brain. Positron emission tomography imaging with radioligands is a widely used tool to quantify differences in receptor binding, for example, between patient and control groups, to quantify receptor occupancy of pharmacological interventions or to measure neurotransmitter release in vivo. 4,5 In clinical studies, 5-HT 2A receptor antagonists have for decades been in use as PET radioligands, most notably [ 18 F]altanserin and [ 11 C]MDL100907. 6 However, agonist PET radioligands may functionally possess several advantages over antagonists. Importantly, agonist radioligands in the dopamine system have an increased sensitivity to endogenously released neurotransmitter. Here, several studies using pharmacologically increased dopamine

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Section: Resultsmentioning

confidence: 83%

Serotonin 2A Receptor Agonist Binding in the Human Brain with [¹¹C]Cimbi-36

Ettrup

Cunha-Bang

McMahon

et al. 2014

J Cereb Blood Flow Metab

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111

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“…The background for a heritable stress vulnerability is most likely to be genetically complex in nature (Levinson, 2006), even though Caspi et al, 2003 have shown a link between stress vulnerability and the low expressing variant of a polymorphism in the promoter region of the serotonin transporter gene, a finding that has been replicated in 15 independent studies so far (Uher and McGuffin, 2008). In a study by our group, we have, again, linked stress vulnerability and serotonergic neurotransmission by showing a coupling between the personality trait neuroticism and frontolimbic serotonin 2A (5-HT 2A ) receptor binding in a large sample of healthy volunteers (Frokjaer et al, 2008). Repeatedly, studies have shown that environmental experience moderates genes' effect on mental health.…”

Section: Introductionmentioning

confidence: 65%

“…Twelve of the participants from the low-risk group were also included in a study linking neuroticism and frontolimbic 5-HT 2A in 83 healthy volunteers (Frokjaer et al, 2008).…”

Section: Methodsmentioning

confidence: 99%

“…Serotonergic neurotransmission is an important component of the pathophysiology of mood disorders and, moreover, neuroticism is linked to serotonergic neurotransmission independent on familial risk for mood disorders or psychopathology (Frokjaer et al, 2008). Moreover, serotonergic neurotransmission is critical in the mechanisms of action of antidepressants.…”

Section: Introductionmentioning

confidence: 99%

“…Although initial findings of in vivo receptor imaging studies were contradictory, two recent studies have confirmed that frontal cortex 5-HT 2A receptor binding is increased, both in recovered, un-medicated patients with a history of major depression (Bhagwagar et al, 2006), and in un-medicated patients with severe depression (Meyer et al, 2003). Interestingly, negativistic thinking and 5-HT 2A receptor binding is correlated both in depressed patients (Bhagwagar et al, 2006;Meyer et al, 2003) and in healthy individuals (Frokjaer et al, 2008) in terms of dysfunctional attitudes and neuroticism scores, respectively. So far, no studies have investigated whether this coupling is a trait or state feature of depression.…”

Section: Introductionmentioning

confidence: 99%

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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

Neuropsychopharmacol

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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.

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How Can Stress Alter Emotional Balance Through Its Interaction with the Serotonergic System?

Mongeau¹,

Hamon²,

Lanfumey³

2011

The Handbook of Stress

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Frontolimbic Serotonin 2A Receptor Binding in Healthy Subjects Is Associated with Personality Risk Factors for Affective Disorder

Cited by 221 publications

References 48 publications

Serotonin 2A Receptor Agonist Binding in the Human Brain with [¹¹C]Cimbi-36

Serotonin 2A Receptor Agonist Binding in the Human Brain with [¹¹C]Cimbi-36

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

How Can Stress Alter Emotional Balance Through Its Interaction with the Serotonergic System?

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Frontolimbic Serotonin 2A Receptor Binding in Healthy Subjects Is Associated with Personality Risk Factors for Affective Disorder

Cited by 221 publications

References 48 publications

Serotonin 2A Receptor Agonist Binding in the Human Brain with [11C]Cimbi-36

Serotonin 2A Receptor Agonist Binding in the Human Brain with [11C]Cimbi-36

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

How Can Stress Alter Emotional Balance Through Its Interaction with the Serotonergic System?

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Product

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Serotonin 2A Receptor Agonist Binding in the Human Brain with [¹¹C]Cimbi-36

Serotonin 2A Receptor Agonist Binding in the Human Brain with [¹¹C]Cimbi-36