Georg S Kranz

Medical University of Vienna, Wien, Vienna, Austria

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Publications (45)251.92 Total impact

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    ABSTRACT: Recent technological progress enables MRI recordings at ultra-high fields of 7 Tesla and above leading to brain images of higher resolution and increased signal-to-noise ratio. Despite these benefits, imaging at 7T exhibits distinct challenges due to B1 field inhomogeneities, causing decreased image quality and problems in data analysis. Although several strategies have been proposed, a systematic investigation of bias-corrected 7T data for voxel-based morphometry (VBM) is still missing and it is an ongoing matter of debate if VBM at 7T can be carried out properly. Here, an optimized VBM study was conducted, evaluating the impact of field strength (3T vs 7T) and pulse sequence (MPRAGE vs MP2RAGE) on gray matter volume (GMV) estimates. More specifically, twenty-two participants were measured under the conditions 3T MPRAGE, 7T MPRAGE and 7T MP2RAGE. Due to the fact that 7T MPRAGE data exhibited strong intensity inhomogeneities, an alternative preprocessing pipeline was proposed and applied for that data. VBM analysis revealed higher GMV estimates for 7T predominantly in superior cortical areas, caudate nucleus, cingulate cortex and the hippocampus. On the other hand, 3T yielded higher estimates especially in inferior cortical areas of the brain, cerebellum, thalamus and putamen compared to 7T. Besides minor exceptions, these results were observed for 7T MPRAGE as well for the 7T MP2RAGE measurements. Results gained in the inferior parts of the brain should be taken with caution, as native GM segmentations displayed misclassifications in these regions for both 7T sequences. This was supported by the test-retest measurements showing highest variability in these inferior regions of the brain for 7T also for the advanced MP2RAGE sequence. Hence, our data support the use of 7T MRI for VBM analysis in cortical areas, but direct comparison between field strengths and sequences requires careful assessment. Similarly, analysis of inferior cortical regions, cerebellum and subcortical regions still remains challenging at 7T even if the advanced MP2RAGE sequence is used. Copyright © 2015 Elsevier Inc. All rights reserved.
    NeuroImage 03/2015; DOI:10.1016/j.neuroimage.2015.03.019 · 6.13 Impact Factor
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    ABSTRACT: Serotonergic neurotransmission is thought to underlie a dynamic interrelation between different key structures of the serotonin system. The serotonin transporter (SERT), which is responsible for the reuptake of serotonin from the synaptic cleft into the neuron, as well as the serotonin-1A (5-HT1A) and -1B (5-HT1B) receptors, inhibitory auto-receptors in the raphe region and projection areas, respectively, are likely to determine serotonin release. Thereby, they are involved in the regulation of extracellular serotonin concentrations and the extent of serotonergic effects in respective projection areas. Complex receptor interactions can be assessed in vivo with positron emission tomography (PET) and single-nucleotide-polymorphisms, which are thought to alter protein expression levels. Due to the complexity of the serotonergic system, gene x gene interactions are likely to regulate transporter and receptor expression and therefore subsequently serotonergic transmission. In this context, we measured 51 healthy subjects (mean age 45.5±12.9, 38 female) with PET using [carbonyl-(11)C]WAY-100635 to determine 5-HT1A receptor binding potential (5-HT1A BPND). Genotyping for rs6296 (HTR1B) and 5-HTTLPR (SERT gene promoter polymorphism) was performed using DNA isolated from whole blood. Voxel-wise whole-brain ANOVA revealed a positive interaction effect of genotype groups (5-HTTLPR: LL, LS+SS and HTR1B: rs6296: CC, GC+GG) on 5-HT1A BPND with peak t-values in the bilateral parahippocampal gyrus. More specifically, highest 5-HT1A BPND was identified for individuals homozygous for both the L-allele of 5-HTTLPR and the C-allele of rs6296. This finding suggests that the interaction between two major serotonergic structures involved in 5-HT release, specifically the SERT and 5-HT1B receptor, results in a modification of the inhibitory serotonergic tone mediated via 5-HT1A receptors. Copyright © 2015 Elsevier Inc. All rights reserved.
    NeuroImage 01/2015; DOI:10.1016/j.neuroimage.2015.01.049 · 6.13 Impact Factor
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    ABSTRACT: On average, brain network economy represents a trade-off between communication efficiency, robustness and connection cost, though, an analogous understanding on an individual level is largely missing. Evaluating resting-state networks of 42 healthy participants with 7 Tesla functional MRI and graph theory revealed that not even half of all possible connections were common across subjects. The strongest similarities among individuals were observed for interhemispheric and/or short-range connections, which may relate to the essential feature of the human brain to develop specialized systems within each hemisphere. Despite this marked variability in individual network architecture, all subjects exhibited equal small-world properties. Furthermore, interdependency between four major network economy metrics was observed across healthy individuals. The characteristic path length was associated with the clustering coefficient (r=0.93), the response to network attacks (peak correlation r=-0.97) and the physical connection cost in 3D space (r=-0.62). On the other hand, clustering was negatively related to attack response (r=-0.75) and connection cost (r=-0.59). Finally, increased connection cost was associated with better response to attacks (r=0.65). This indicates that functional brain networks with high global information transfer also exhibit strong network resilience. However, it seems that these advantages come at the cost of decreased local communication efficiency and increased physical connection cost. Except for wiring length, the results were replicated on a subsample at 3 Tesla (n=20). These findings highlight the finely tuned interrelationships between different parameters of brain network economy. Moreover, the understanding of the individual diversity of functional brain network economy may provide further insights in the vulnerability to mental and neurological disorders.
    11/2014; DOI:10.1089/brain.2014.0306
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    ABSTRACT: Biological causes underpinning the well known gender dimorphisms in human behavior, cognition, and emotion have received increased attention in recent years. The advent of diffusion-weighted magnetic resonance imaging has permitted the investigation of the white matter microstructure in unprecedented detail. Here, we aimed to study the potential influences of biological sex, gender identity, sex hormones, and sexual orientation on white matter microstructure by investigating transsexuals and healthy controls using diffusion tensor imaging (DTI). Twenty-three female-to-male (FtM) and 21 male-to-female (MtF) transsexuals, as well as 23 female (FC) and 22 male (MC) controls underwent DTI at 3 tesla. Fractional anisotropy, axial, radial, and mean diffusivity were calculated using tract-based spatial statistics (TBSS) and fiber tractography. Results showed widespread significant differences in mean diffusivity between groups in almost all white matter tracts. FCs had highest mean diffusivities, followed by FtM transsexuals with lower values, MtF transsexuals with further reduced values, and MCs with lowest values. Investigating axial and radial diffusivities showed that a transition in axial diffusivity accounted for mean diffusivity results. No significant differences in fractional anisotropy maps were found between groups. Plasma testosterone levels were strongly correlated with mean, axial, and radial diffusivities. However, controlling for individual estradiol, testosterone, or progesterone plasma levels or for subjects' sexual orientation did not change group differences. Our data harmonize with the hypothesis that fiber tract development is influenced by the hormonal environment during late prenatal and early postnatal brain development.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 11/2014; 34(46):15466-75. DOI:10.1523/JNEUROSCI.2488-14.2014 · 6.75 Impact Factor
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    ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) research has long focused on the dopaminergic system's contribution to pathogenesis, although the results have been inconclusive. However, a case has been made for the involvement of the noradrenergic system, which modulates cognitive processes, such as arousal, working memory, and response inhibition, all of which are typically affected in ADHD. Furthermore, the norepinephrine transporter (NET) is an important target for frequently prescribed medication in ADHD. Therefore, the NET is suggested to play a critical role in ADHD.
    JAMA Psychiatry 10/2014; 71(12). DOI:10.1001/jamapsychiatry.2014.1226 · 12.01 Impact Factor
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    ABSTRACT: Objectives: Anticipatory processes prepare the organism for upcoming experiences. The aim of this study was to investigate neural responses related to anticipation and processing of painful stimuli occurring with different levels of uncertainty. Experimental design: Twenty-five participants (13 females) took part in an electroencephalography and functional magnetic resonance imaging (fMRI) experiment at separate times. A visual cue announced the occurrence of an electrical painful or nonpainful stimulus, delivered with certainty or uncertainty (50% chance), at some point during the following 15 s. Principal observations: During the first 2 s of the anticipation phase, a strong effect of uncertainty was reflected in a pronounced frontal stimulus-preceding negativity (SPN) and increased fMRI activation in higher visual processing areas. In the last 2 s before stimulus delivery, we observed stimulus-specific preparatory processes indicated by a centroparietal SPN and posterior insula activation that was most pronounced for the certain pain condition. Uncertain anticipation was associated with attentional control processes. During stimulation, the results revealed that unexpected painful stimuli produced the strongest activation in the affective pain processing network and a more pronounced offset-P2. Conclusions: Our results reflect that during early anticipation uncertainty is strongly associated with affective mechanisms and seems to be a more salient event compared to certain anticipation. During the last 2 s before stimulation, attentional control mechanisms are initiated related to the increased salience of uncertainty. Furthermore, stimulus-specific preparatory mechanisms during certain anticipation also shaped the response to stimulation, underlining the adaptive value of stimulus-targeted preparatory activity which is less likely when facing an uncertain event. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 10/2014; 36(2). DOI:10.1002/hbm.22661 · 6.92 Impact Factor
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    ABSTRACT: Background Women are two times more likely to be diagnosed with depression than men. Sex hormones modulating serotonergic transmission are proposed to partly underlie these epidemiological findings. Here, we used the cross-sex steroid hormone treatment of transsexuals seeking sex reassignment as a model to investigate acute and chronic effects of testosterone and estradiol on serotonin transporter (SERT) binding in female-to-male (FtM) and male-to-female (MtF) transsexuals. Methods 33 transsexuals underwent [11C]DASB PET before start of treatment, a subset of which underwent a second scan four weeks, and a third scan four months, after treatment start. SERT BPND was quantified in 12 regions of interest. Treatment effects were analyzed using linear mixed models. Changes of hormone plasma levels were correlated with changes in regional SERT BPND. Results One and four months of androgen treatment in FtM increased SERT binding in amygdala, caudate, putamen and median raphe nucleus. SERT binding increases correlated with treatment induced increases in testosterone levels, suggesting that testosterone increases SERT expression on the cell surface. Conversely, four months of anti-androgen and estrogen treatment in MtF led to decreases in SERT binding in insula, anterior and mid-cingulate cortex. Increases in estradiol levels correlated negatively with decreases in regional SERT binding, indicating a protective effect of estradiol against SERT loss. Conclusions Given the central role of the SERT in the treatment of depression and anxiety disorders, these findings may lead to new treatment modalities and expand our understanding of the mechanism of action of antidepressant treatment properties. ClinicalTrials.gov Identifier: NCT01065220 https://clinicaltrials.gov/
    Biological Psychiatry 09/2014; DOI:10.1016/j.biopsych.2014.09.010 · 9.47 Impact Factor
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    ABSTRACT: The (fractional) amplitudes of low-frequency fluctuations (f)ALFF are popular measures for the magnitude of low-frequency oscillations in resting-state fMRI (R-fMRI) data. Both measures can be directly derived from the spectral power of R-fMRI time courses. Numerous studies suggest that ALFF and fALFF might be used as biomarkers for a variety of diseases including schizophrenia, major depressive disorder, and obsessive-compulsive disorder. However, the temporal stability of (f)ALFF values, which is of great importance for the application of (f)ALFF both as a biomarker and scaling parameter, have not been studied in detail yet. Here, we quantify the temporal stability, robustness and reproducibility of both ALFF and fALFF maps obtained from R-fMRI data by performing statistical analyses over 55-minute resting-state scans which included a period of NaCl infusion. We also examine the differences of using either raw or standardised (f)ALFF maps. Our analyses show that no significant changes of (f)ALFF values over the 55minute period occur for both raw and standardised (f)ALFF maps. In addition, we demonstrate that raw (f)ALFF maps across subject are correlated with head motion as quantified via frame-wise displacement, whereas no such correlation is present in standardised (f)ALFF maps. In conclusion, the results of our study show that both ALFF and fALFF qualify as potential biomarkers due to their high temporal stability.
    NeuroImage 09/2014; DOI:10.1016/j.neuroimage.2014.09.038 · 6.13 Impact Factor
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    ABSTRACT: Although previous investigations of transsexual people have focused on regional brain alterations, evaluations on a network level, especially those structural in nature, are largely missing. Therefore, we investigated the structural connectome of 23 female-to-male (FtM) and 21 male-to-female (MtF) transgender patients before hormone therapy as compared with 25 female and 25 male healthy controls. Graph theoretical analysis of whole-brain probabilistic tractography networks (adjusted for differences in intracranial volume) showed decreased hemispheric connectivity ratios of subcortical/limbic areas for both transgender groups. Subsequent analysis revealed that this finding was driven by increased interhemispheric lobar connectivity weights (LCWs) in MtF transsexuals and decreased intrahemispheric LCWs in FtM patients. This was further reflected on a regional level, where the MtF group showed mostly increased local efficiencies and FtM patients decreased values. Importantly, these parameters separated each patient group from the remaining subjects for the majority of significant findings. This work complements previously established regional alterations with important findings of structural connectivity. Specifically, our data suggest that network parameters may reflect unique characteristics of transgender patients, whereas local physiological aspects have been shown to represent the transition from the biological sex to the actual gender identity.
    Cerebral Cortex 09/2014; DOI:10.1093/cercor/bhu194 · 8.31 Impact Factor
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    ABSTRACT: BackgroundThe brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) may impact on the in-vivo binding of important serotonergic structures such as the serotonin transporter (5-HTT) and the serotonin-1A (5-HT1A) receptor. Previous positron emission tomography (PET) studies on the association between Val66Met and 5-HTT and 5-HT1A binding potential (BPND) have demonstrated equivocal results.MethodsWe conducted an imaging genetics study investigating the effect of Val66Met genotype on 5-HTT or 5-HT1A BPND in 92 subjects. Forty-one subjects (25 healthy subjects and 16 depressive patients) underwent genotyping for Val66Met and PET imaging with the 5-HTT specific radioligand [11C]DASB. Additionally, in 51 healthy subjects Val66Met genotypes and 5-HT1A binding with the radioligand [carbonyl-11C]WAY-100635 were ascertained. Voxel-wise and region of interest-based analyses of variance were used to examine the influence of Val66Met on 5-HTT and 5-HT1A BPND.ResultsNo significant differences of 5-HTT nor 5-HT1A BPND between BDNF Val66Met genotype groups (val/val vs. met-carrier) were detected. There was no interaction between depression and Val66Met genotype status.ConclusionIn line with previous data, our work confirms an absent effect of BDNF Val66Met on two major serotonergic structures. These results could suggest that altered protein expression associated with genetic variants, might be compensated in vivo by several levels of unknown feedback mechanisms. In conclusion, Val66Met genotype status is not associated with changes of in-vivo binding of 5-HTT and 5-HT1A receptors in human subjects.
    PLoS ONE 09/2014; 9(9):e106810. DOI:10.1371/journal.pone.0106810 · 3.53 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • Biological Psychiatry 08/2014; 76(4):272–273. DOI:10.1016/j.biopsych.2014.06.010 · 9.47 Impact Factor
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    ABSTRACT: Preclinical research and clinical experience point to a modulation of 5-HT1A receptor expression by gonadal steroid hormones. We examined the effect of estradiol, progesterone and DHEAS on serotonin neurotransmission in 16 premenopausal and 28 postmenopausal women, differentiating by reproductive status. By means of positron emission tomography and the radiotracer [carbonyl-11C]WAY-100635, the 5-HT1A receptor binding potential (BP) was quantified in 45 brain regions of interest. Median BP was used as a surrogate marker to estimate the whole brain effect of the steroid hormones on receptor binding. We found a strong negative effect of serum progesterone and DHEAS levels on 5-HT1A receptor binding in postmenopausal women both in the Median BP and on a regional level. Furthermore, there was a non-linear, U-shaped relationship between DHEAS levels and 5-HT1A receptor binding in the pooled sample. Presynaptic 5-HT1A receptor BP in the raphe nuclei was significantly explained in a non-linear way by both progesterone and DHEAS in the pooled sample. Our study confirms in humans a preclinically suggested relation of the steroid hormones progesterone and DHEAS to 5-HT1A receptor binding. We show differential effects of the hormones with regard to reproductive hormonal status. Non-linear, U-shaped relationships between hormone serum concentrations and serotonin neurotransmission might explain paradoxical effects of these hormones on mood.
    Psychoneuroendocrinology 08/2014; DOI:10.1016/j.psyneuen.2014.04.008 · 5.59 Impact Factor
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    ABSTRACT: Preclinical research points to a strong modulatory influence of gonadal hormones on the serotonin system. However, human data corroborating this association remains scarce. The aim of this study was to examine the effects of hormone replacement therapy on 5-HT1A receptor binding in postmenopausal women using positron emission tomography (PET) and the radioligand [carbonyl-11C]WAY-100635. In this randomized, double-blind, longitudinal study, 30 postmenopausal women underwent treatment with either a combination of oral 17β-estradiol valerate and micronized progesterone (group 1, n = 10), oral 17β-estradiol valerate (group 2, n = 10), or placebo (group 3, n = 10). Two PET measurements were performed, one the day before treatment start and the second after at least eight weeks of treatment. Plasma levels of estradiol (E2), progesterone (P4), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were collected prior to PET measurements. As expected, hormone replacement therapy led to a significant increase in E2 and P4 plasma levels in group 1 and to a significant increase in E2 levels in group 2. The 5-HT1A receptor binding did not change significantly after estrogen, combined estrogen/progesterone treatment or placebo in any of the investigated brain regions. There were no significant correlations between changes in E2 or P4 values and changes in 5-HT1A receptor binding. Although we were not able to confirm effects of gonadal hormone treatment on 5-HT1A receptor binding, our data do not preclude associations between sex steroid levels and serotonin, the neurotransmitter implicated most strongly in the pathogenesis of affective and anxiety disorders.
    Psychoneuroendocrinology 07/2014; DOI:10.1016/j.psyneuen.2014.03.004 · 5.59 Impact Factor
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    ABSTRACT: The success of serotonin-selective reuptake inhibitors has lent support to the monoamine theory of major depressive disorder (MDD). This issue has been addressed in a number of molecular imaging studies by positron emission tomography or single-photon emission computed tomography of serotonin reuptake sites (5-HTT) in the brain of patients with MDD, with strikingly disparate conclusions. Our meta-analysis of the 18 such studies, totaling 364 MDD patients free from significant comorbidities or medication and 372 control subjects, revealed reductions in midbrain 5-HTT (Hedges' g=-0.49; 95% CI: (-0.84, -0.14)) and amygdala (Hedges' g=-0.50; 95% CI: (-0.78, -0.22)), which no individual study possessed sufficient power to detect. Only small effect sizes were found in other regions with high binding (thalamus: g=-0.24, striatum: g=-0.32, and brainstem g=-0.22), and no difference in the frontal or cingulate cortex. Age emerged as an important moderator of 5-HTT availability in MDD, with more severe reductions in striatal 5-HTT evident with greater age of the study populations (P<0.01). There was a strong relationship between severity of depression and 5-HTT reductions in the amygdala (P=0.01). Thus, molecular imaging findings indeed reveal widespread reductions of ∼10% in 5-HTT availability in MDD, which may predict altered spatial-temporal dynamics of serotonergic neurotransmission.Journal of Cerebral Blood Flow & Metabolism advance online publication, 7 May 2014; doi:10.1038/jcbfm.2014.82.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 05/2014; DOI:10.1038/jcbfm.2014.82 · 5.46 Impact Factor
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    ABSTRACT: The anticipation of favourable or unfavourable events is a key component in our daily life. However, the temporal dynamics of anticipation processes in relation to brain activation are still not fully understood. A modified version of the monetary incentive delay task was administered during separate functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) sessions in the same 25 participants to assess anticipatory processes with a multi-modal neuroimaging set-up. During fMRI, gain and loss anticipation were both associated with heightened activation in ventral striatum and reward-related areas. EEG revealed most pronounced P300 amplitudes for gain anticipation, whereas CNV amplitudes distinguished neutral from gain and loss anticipation. Importantly, P300, but not CNV amplitudes, were correlated to neural activation in the ventral striatum for both gain and loss anticipation. Larger P300 amplitudes indicated higher ventral striatum blood oxygen level dependent (BOLD) response. Early stimulus evaluation processes indexed by EEG seem to be positively related to higher activation levels in the ventral striatum, indexed by fMRI, which are usually associated with reward processing. The current results, however, point towards a more general motivational mechanism processing salient stimuli during anticipation.
    NeuroImage 04/2014; 96. DOI:10.1016/j.neuroimage.2014.03.077 · 6.13 Impact Factor
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    ABSTRACT: Blocking of the serotonin transporter (SERT) represents the initial mechanism of action of selective serotonin reuptake inhibitors (SSRIs) which can be visualized due to the technical proceedings of SERT occupancy studies. When compared to the striatum, higher SERT occupancy in the midbrain and lower values in the thalamus were reported. This indicates that occupancy might be differently distributed throughout the brain, which is supported by preclinical findings indicating a regionally varying SERT activity and antidepressant drug concentration. The present study therefore aimed to investigate regional SERT occupancies with positron emission tomography and the radioligand [(11)C]DASB in 19 depressed patients after acute and prolonged intake of oral doses of either 10mg/day escitalopram or 20mg/day citalopram. Compared to the mean occupancy across cortical and subcortical regions, we detected increased SERT occupancies in regions commonly associated with antidepressant response, such as the subgenual cingulate, amygdala and raphe nuclei. When acute and prolonged drug intake was compared, SERT occupancies increased in subcortical areas that are known to be rich in SERT. Moreover, SERT occupancy in subcortical brain areas after prolonged intake of antidepressants was predicted by plasma drug levels. Similarly, baseline SERT binding potential seems to impact SERT occupancy, as regions rich in SERT showed greater binding reduction as well as higher residual binding. These findings suggest a region-specific distribution of SERT blockage by SSRIs and stress the postulated link between treatment response and SERT occupancy to certain brain regions such as the subgenual cingulate cortex.
    NeuroImage 10/2013; DOI:10.1016/j.neuroimage.2013.10.002 · 6.13 Impact Factor
  • European Neuropsychopharmacology 10/2013; 23:S279. DOI:10.1016/S0924-977X(13)70435-8 · 5.40 Impact Factor
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    ABSTRACT: Suffering from anhedonia, patients with major depressive disorder (MDD) exhibit alterations in several parts of the serotonergic neurotransmitter system, which are in turn involved in reward processing. However, previous investigations of the serotonin transporter (SERT) focused on regional differences with varying results depending on the clinical syndrome. Here, we aimed to describe the serotonergic system of MDD patients on a network level by evaluating SERT associations across brain regions. Twenty medication free patients with major depression and 20 healthy controls underwent positron emission tomography using the radioligand [(11) C]DASB. SERT binding potentials (BPND ) were quantified voxel-wise with the multilinear reference tissue model 2. In addition, SERT BPND was extracted from the dorsal raphe nucleus (DRN) as an indicator of midbrain serotonergic neurotransmission. Whole-brain linear regression analysis was applied to evaluate the association of DRN SERT bindings to those in projection areas, which was followed by ANCOVA to assess differences in interregional relationships between patients and controls. Although both groups showed widespread positive correlations, group differences were restricted to decreased SERT associations between the DRN and the ventral striatum (right and left respectively: t = 5.85, P < 0.05 corrected and t = 5.07, P < 0.1 corrected) when comparing MDD patients (R(2) = 0.11 and 0.24) to healthy subjects (R(2) = 0.72 and 0.66, P < 0.01 and 0.05 corrected). Adjusting for age and sex did not change these findings. This study indicates a disturbed regulation between key regions involved in reward processing via the SERT. Our interregional approach highlights the importance of evaluating pathophysiological alterations on a network level to gain complementary information in addition to regional investigations. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 10/2013; 23. DOI:10.1002/hbm.22442 · 6.92 Impact Factor
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    ABSTRACT: Preclinical studies have demonstrated that serotonin (5-HT) challenge changes neuronal circuitries and microarchitecture. However, evidence in human subjects is missing. Pharmacologic magnetic resonance imaging (phMRI) applying selective 5-HT reuptake inhibitors (SSRIs) and high-resolution structural and functional brain assessment is able to demonstrate the impact of 5-HT challenge on neuronal network morphology and functional activity. To determine how SSRIs induce changes in gray matter and neuronal activity, we conducted a longitudinal study using citalopram and escitalopram. Seventeen healthy subjects completed a structural and functional phMRI study with randomized, cross-over, placebo-controlled, double-blind design. Significant gray matter increases were observed (amongst other regions) in the posterior cingulate cortex (PCC) and the ventral precuneus after SSRI intake of 10days, while decreases were observed within the pre- and postcentral gyri (all P<0.05, family wise error [FWE] corrected). Furthermore, enhanced resting functional connectivity (rFC) within the ventral precuneus and PCC was associated with gray matter increases in the PCC (all FWE Pcorr<0.05). Corroborating these results, whole-brain connectivity density, measuring the brain's functional network hubs, was significantly increased after SSRI-intake in the ventral precuneus and PCC (all FWE Pcorr<0.05). Short-term administration of SSRIs changes gray matter structures, consistent with previous work reporting enhancement of neuroplasticity by serotonergic neurotransmission. Furthermore, increased gray matter in the PCC is associated with increased functional connectivity in one of the brain's metabolically most active regions. Our novel findings provide convergent evidence for dynamic alterations of brain structure and function associated with SSRI pharmacotherapy.
    NeuroImage 08/2013; DOI:10.1016/j.neuroimage.2013.08.036 · 6.13 Impact Factor
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    ABSTRACT: Alterations of the inhibitory serotonin-1A receptor (5-HT1A) constitute a solid finding in neuropsychiatric research, particularly in the field of mood and anxiety disorders. Manifold factors influencing the density of this receptor have been identified, e.g., steroid hormones, sunlight exposure and genetic variants of serotonin-related genes. Given the close interactions between serotonergic and dopaminergic neurotransmission, we investigated whether a common single-nucleotide-polymorphism of the catechol-O-methyltransferase (COMT) gene (VAL158MET or rs4680) coding for a key enzyme of the dopamine network that is associated with the pathogenesis of mood disorders and antidepressant treatment response, directly affects 5-HT1A receptor binding potential. Fifty-two healthy individuals (38 female, mean age ± standard deviation = 40.48 ± 14.87) were measured via positron emission tomography using the radioligand [carbonyl-(11)C]WAY-100635. Genotyping for rs4680 was performed using DNA isolated from whole blood with the MassARRAY platform of the software SEQUENOM(®). Whole brain voxel-wise ANOVA resulted in a main effect of genotype on 5-HT1A binding. Compared to A carriers (AA + AG) of rs4680, homozygote G subjects showed higher 5-HT1A binding potential in the posterior cingulate cortex (F (2,49) = 17.7, p = 0.05, FWE corrected), the orbitofrontal cortex, the anterior cingulate cortex, the insula, the amygdala and the hippocampus (voxel-level: p < 0.01 uncorrected, t > 2.4; cluster-level: p < 0.05 FWE corrected). In light of the frequently reported alterations of 5-HT1A binding in anxiety and mood disorders, this study proposes a potential implication of the COMT genotype, more specifically the VAL158MET polymorphism, via modulation of the serotonergic neurotransmission.
    Brain Structure and Function 08/2013; DOI:10.1007/s00429-013-0621-8 · 7.84 Impact Factor