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Georg S Kranz,
Andreas Hahn,
Pia Baldinger,
Daniela Haeusler,
Cecile Philippe,
Ulrike Kaufmann,
Wolfgang Wadsak,
Markus Savli,
Anna Hoeflich,
Christoph Kraus,
Thomas Vanicek,
Markus Mitterhauser,
Siegfried Kasper,
Rupert Lanzenberger
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ABSTRACT: The serotonergic system modulates brain functions that are considered to underlie affective states, emotion and cognition. Several lines of evidence point towards a strong lateralization of these mental processes, which indicates similar asymmetries in associated neurotransmitter systems. Here, our aim was to investigate a potential asymmetry of the serotonin transporter distribution using positron emission tomography and the radioligand [(11)C]DASB in vivo. As brain asymmetries may differ between sexes, we further aimed to compare serotonin transporter asymmetry between females, males and male-to-female (MtF) transsexuals whose brains are considered to be partly feminized. Voxel-wise analysis of serotonin transporter binding in all groups showed both strong left and rightward asymmetries in several cortical and subcortical structures including temporal and frontal cortices, anterior cingulate, hippocampus, caudate and thalamus. Further, male controls showed a rightward asymmetry in the midcingulate cortex, which was absent in females and MtF transsexuals. The present data support the notion of a lateralized serotonergic system, which is in line with previous findings of asymmetric serotonin-1A receptor distributions, extracellular serotonin concentrations, serotonin turnover and uptake. The absence of serotonin transporter asymmetry in the midcingulate in MtF transsexuals may be attributed to an absence of brain masculinization in this region.
Brain Structure and Function 12/2012; · 5.63 Impact Factor
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Christoph Kraus,
Andreas Hahn,
Markus Savli, Georg S Kranz,
Pia Baldinger,
Anna Höflich,
Christoph Spindelegger,
Johanna Ungersboeck,
Daniela Haeusler,
Markus Mitterhauser,
Christian Windischberger,
Wolfgang Wadsak,
Siegfried Kasper,
Rupert Lanzenberger
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ABSTRACT: Animal models revealed that the serotonin-1A (5-HT(1A)) receptor modulates gray matter structure. However, there is a lack of evidence showing the relationship between 5-HT(1A) receptor concentration and gray matter in the human brain in vivo. Here, to demonstrate an association between the 5-HT(1A) receptor binding potential, an index for receptor concentration, and the local gray matter volume (GMV), an index for gray matter structure, we measured 35 healthy subjects with both positron emission tomography (PET) and structural magnetic resonance imaging (MRI). We found that regional heteroreceptor binding was positively associated with GMV in distinctive brain regions such as the hippocampi and the temporal cortices in both hemispheres (R(2) values ranged from 0.308 to 0.503, p<0.05 cluster-level FDR-corrected). Furthermore, autoreceptor binding in the midbrain raphe region was positively associated with GMV in forebrain projection sites (R(2)=0.656, p=0.001). We also observed a broad range between 5-HT(1A) receptor binding and GMV. Given the congruence of altered 5-HT(1A) receptor concentrations and GMV reduction in depression or Alzheimer's disease as reported by numerous studies, these results might provide new insights towards understanding the mechanisms behind GMV alterations observed in these brain disorders.
NeuroImage 07/2012; 63(3):1091-8. · 5.89 Impact Factor
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Proceedings of the National Academy of Sciences 06/2012; 109(29):E2000. · 9.68 Impact Factor
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Andreas Hahn,
Wolfgang Wadsak,
Christian Windischberger,
Pia Baldinger,
Anna S Höflich,
Jan Losak,
Lukas Nics,
Cécile Philippe, Georg S Kranz,
Christoph Kraus,
Markus Mitterhauser,
Georgios Karanikas,
Siegfried Kasper,
Rupert Lanzenberger
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ABSTRACT: Reflecting one's mental self is a fundamental process for evaluating the personal relevance of life events and for moral decision making and future envisioning. Although the corresponding network has been receiving growing attention, the driving neurochemical mechanisms of the default mode network (DMN) remain unknown. Here we combined positron emission tomography and functional magnetic resonance imaging to investigate modulations of the DMN via serotonin-1A receptors (5-HT(1A)), separated for 5-HT autoinhibition (dorsal raphe nucleus) and local inhibition (heteroreceptors in projection areas). Using two independent approaches, regional 5-HT(1A) binding consistently predicted DMN activity in the retrosplenial cortex for resting-state functional magnetic resonance imaging and the Tower of London task. On the other hand, both local and autoinhibitory 5-HT(1A) binding inversely modulated the posterior cingulate cortex, the strongest hub in the resting human brain. In the frontal part of the DMN, a negative association was found between the dorsal medial prefrontal cortex and local 5-HT(1A) inhibition. Our results indicate a modulation of key areas involved in self-referential processing by serotonergic neurotransmission, whereas variations in 5-HT(1A) binding explained a considerable amount of the individual variability in the DMN. Moreover, the brain regions associated with distinct introspective functions seem to be specifically regulated by the different 5-HT(1A) binding sites. Together with previously reported modulations of dopamine and GABA, this regional specialization suggests complex interactions of several neurotransmitters driving the default mode network.
Proceedings of the National Academy of Sciences 02/2012; 109(7):2619-24. · 9.68 Impact Factor
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ABSTRACT: Functional magnetic resonance imaging (fMRI) has become the primary non-invasive method for investigating the human brain function. With an increasing number of ultra-high field MR systems worldwide possibilities of higher spatial and temporal resolution in combination with increased sensitivity and specificity are expected to advance detailed imaging of distinct cortical brain areas and subcortical structures. One target region of particular importance to applications in psychiatry and psychology is the amygdala. However, ultra-high field magnetic resonance imaging of these ventral brain regions is a challenging endeavor that requires particular methodological considerations. Ventral brain areas are particularly prone to signal losses arising from strong magnetic field inhomogeneities along susceptibility borders. In addition, physiological artifacts from respiration and cardiac action cause considerable fluctuations in the MR signal. Here we show that, despite these challenges, fMRI data from the amygdala may be obtained with high temporal and spatial resolution combined with increased signal-to-noise ratio. Maps of neural activation during a facial emotion discrimination paradigm at 7T are presented and clearly show the gain in percental signal change compared to 3T results, demonstrating the potential benefits of ultra-high field functional MR imaging also in ventral brain areas.
European journal of radiology 12/2011; · 2.65 Impact Factor
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ABSTRACT: Progesterone (P) is thought to influence mood and affective states. Alterations of the inhibitory serotonin-1A (5-HT(1A)) receptor distribution are associated with depression and anxiety. This study evaluates the influence of plasma P levels on the 5-HT(1A) receptor binding in healthy male subjects.
Molecular neuroimaging of the 5-HT(1A) receptor distribution using positron emission tomography and hormone assays for total plasma P and cortisol were done in a sample of 18 healthy men.
Plasma P levels explained up to 65% of the variability in 5-HT(1A) receptor binding in limbic regions including the amygdala, orbitofrontal cortex and retrosplenial cortex. When controlling for cortisol in the model, there was an expected decline in explained variances of 5-HT(1A) binding attributed to P.
The results of this study provide further support for the effect of P on 5-HT(1A) receptor expression and raise the possibility that P mediates the vulnerability to mood disorders by affecting the serotonergic system.
Neuroendocrinology 05/2011; 94(1):84-8. · 2.38 Impact Factor
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Rupert Lanzenberger,
Wolfgang Wadsak,
Christoph Spindelegger,
Markus Mitterhauser,
Elena Akimova,
Leonhard-Key Mien,
Martin Fink,
Ulrike Moser,
Markus Savli, Georg S Kranz,
Andreas Hahn,
Kurt Kletter,
Siegfried Kasper
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ABSTRACT: Dysregulation of the hypothalamic-pituitary-adrenocortical axis with deficient glucocorticoid feedback and alterations in the serotonergic system have been identified as biological correlates of mood disorders. Close examination of the interaction between these systems may offer insights into the pathophysiology of anxiety disorders and depression to understand how stress and these disorders are related. In this study, we investigated the relationship between plasma levels of cortisol and the dominant inhibitory serotonergic receptor, serotonin-1A (5-HT1A). Using positron emission tomography (PET) and the radioligand [carbonyl-11C]WAY-100635, we quantified the 5-HT1A receptor binding. Data from 12 male patients with social phobia and 18 matched control subjects were analysed. Seven brain regions were investigated: the anterior and posterior cingulate cortices, hippocampus, amygdala, medial orbitofrontal and retrosplenial cortices, and dorsal raphe nucleus. Partial correlation analysis, controlled for age and radiochemical variables, was performed to demonstrate the association between cortisol plasma levels and 5-HT1A receptor binding. Cortisol plasma levels were significantly lower in patients with social phobia compared to healthy controls. Moreover, we found strong negative correlations between cortisol plasma levels and 5-HT1A binding in the amygdala (r=-0.93, p=0.0004), hippocampus (r=-0.80, p=0.009), and retrosplenial cortex (r=-0.48, p=0.04) in patients with social phobia. Within the former two regions, these associations were significantly higher in patients than in healthy controls. This PET study confirms a negative association between plasma cortisol levels and the 5-HT1A receptor distribution consistent with studies in rodents and non-human primates. Dysregulation of the cortisol level might increase the vulnerability for mood disorders by altering limbic 5-HT1A receptors.
The International Journal of Neuropsychopharmacology 10/2010; 13(9):1129-43. · 4.58 Impact Factor
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ABSTRACT: The possible interference of combined laser hair removal and Botulinum toxin A (BoNT/A) injections in the treatment of axillary hyperhidrosis has not previously been explored. In order to examine this potential interference, we assessed the effect of BoNT/A on axillary hyperhidrosis with and without concomitant diode laser axillary hair removal.
In a prospective, double blind, randomized cross over trial, nine patients suffering from primary axillary hyperhidrosis were laser-treated on one randomly assigned axilla. One week later, both axillas were injected intradermally with BoNT/A (100 MU per axilla). During the same session, the previously untreated axilla was lasered. Axillary sweat rates (in g/5 minutes.) were determined by gravimetry and compared at rest, during mental exercise, and during physical exercise. Additionally, subjective outcome measures were assessed by a visual analogue scale, Dermatology Life Quality Index, and Global Clinical Impression score.
No differences were found regarding the effect of BoNT/A on previously laser-treated and laser co-treated sides over time course for any of the outcome parameters. Sweat production was reduced 3 weeks after BoNT/A treatment by 93.5% at rest, 96.5% during mental exercise, and 67% during physical exercise.
Concomitant laser hair removal does not interfere with BoNT/A treatment on axillary hyperhidrosis.
Lasers in Surgery and Medicine 03/2010; 42(3):211-4. · 2.75 Impact Factor
