The cortical serotonin2 receptors studied with positron-emission tomography and [18F]-setoperone during depressive illness and antidepressant treatment with clomipramine

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.

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 86%

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

Sheline

Mintun

Deanna

et al. 2004

“…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.

“…In vivo studies in people with major depression have found both reduced (Biver et al, 1997;Attar-Levy et al, 1999;Yatham et al, 2000;Messa et al, 2003) and normal (Meyer et al, 2001) 5-HT 2A receptor binding values. In addition, decreased volume (Hirayasu et al, 1999) and reduced cerebral blood flow and metabolism (Drevets et al, 1997(Drevets et al, , 2002Buchsbaum et al, 1997) have been found in the left subgenual cingulate in depressed subjects relative to controls.…”

Section: Only Rec An Have Reduced [mentioning

confidence: 99%

Altered 5-HT2A Receptor Binding after Recovery from Bulimia-Type Anorexia Nervosa: Relationships to Harm Avoidance and Drive for Thinness

Bailer

Price

Meltzer

et al. 2004

154

107

Several lines of evidence suggest that a disturbance of serotonin neuronal pathways may contribute to the pathogenesis of anorexia nervosa (AN) and bulimia nervosa (BN). This study applied positron emission tomography (PET) to investigate the brain serotonin 2A (5-HT 2A ) receptor, which could contribute to disturbances of appetite and behavior in AN and BN. To avoid the confounding effects of malnutrition, we studied 10 women recovered from bulimia-type AN (REC AN-BN, 41 year normal weight, regular menstrual cycles, no binging, or purging) compared with 16 healthy control women (CW) using PET imaging and a specific 5-HT 2A 18 F]altanserin binding potential and drive for thinness in several cortical regions. In conclusion, this study extends research suggesting that altered 5-HT neuronal system activity persists after recovery from bulimia-type AN, particularly in subgenual cingulate regions. Altered 5-HT neurotransmission after recovery also supports the possibility that this may be a trait-related disturbance that contributes to the pathophysiology of eating disorders. It is possible that subgenual cingulate findings are not specific for AN-BN, but may be related to the high incidence of lifetime major depressive disorder diagnosis in these subjects.