A cross-sectional study on the quality of life in migraine and medication overuse headache in a Hungarian sample: understanding the effect of headache characteristics.

Background and purpose: Previous studies using generic and disease specific instruments showed that both migraine and medication overuse headache are associated with lower health-related quality of life (HRQoL). The aim of our study was to assess HRQoL differences in migraineurs and in patients with MOH and to examine how headache characteristics such as years with headache, aura symptoms, triptan use, headache pain severity and headache frequency are related to HRQoL. Methods: In this cross-sectional study 334 participants were examined (248 were recruited from a tertiary headache centre and 86 via advertisements). The Comp-rehensive Headache-related Quality of life Questionnaire (CHQQ) was used to measure the participants' HRQoL. Data showed normal distribution, therefore beside Chi-squared test parametric tests (e.g. independent samples t-test) were used with a two-tailed p<0.05 threshold. Linear regression models were used to determine the independent effects of sex, age, recruitment method, headache type (migraine vs. MOH) and headache characteristics (presence of aura symptoms, years with headache, headache pain severity, headache frequency and triptan use) separately for each domain and for the total score of CHQQ. Significance threshold was adopted to p0.0125 (0.05/4) to correct for multiple testing and avoid Type I error. Results: Independent samples t-tests showed that patients with MOH had significantly lower scores on all CHQQ domains than migraineurs, except on the social subscale. Results of a series of regression analyses showed that triptan use was inversely related to all the domains of HRQoL after correction for multiple testing (p<0.0125). In addition, headache pain severity was associated with lower physical (p=0.001) and total scores (p=0.002) on CHQQ subscales. Conclusion: Based on the results, different headache characteristics (but not the headache type, namely migraine or MOH) were associated with lower levels of HRQoL in patients with headache. Determining which factors play significant role in the deterioration of HRQoL is important to adequately manage different patient populations and to guide public health policies regarding health service utilization and health-care costs.

Citalopram Neuroendocrine Challenge Shows Altered Tryptophan and Kynurenine Metabolism in Migraine.

Altered tryptophan (TRP) metabolism may have an important role in migraine susceptibility through its main metabolites, serotonin and kynurenine (KYN). Both affect pain processing and stress response by interfering with neural and brain hypersensitivity and by interacting with chemokines and cytokines that control vascular and inflammatory processes. The involvement of these pathways in migraine has been widely studied, but acute citalopram neuroendocrine challenge on TRP metabolism and cytokine profile has not been investigated yet. In our study, females with episodic migraine without aura and healthy controls were studied before and after acute citalopram or placebo in a double-blind setting. At baseline, increased TRP/large neutral amino acid (LNAA) ratio and decreased RANTES chemokine concentration were detected in migraine patients compared to controls. The challenge induced a significant increase in TRP, KYN, and TRP/LNAA in healthy controls, but not in migraine patients. Furthermore, migraine attack frequency negatively correlated with KYN/TRP ratio and positively correlated with the neuroendocrine-challenge-induced KYN concentration increase. Our results support a decreased breakdown of TRP via KYN pathway and a failure to modulate TRP-KYN pathway during citalopram-induced acute stress together with an increased vascular sensitivity in migraine. These mechanisms may provide useful drug targets for future drug development.

Circadian Variation of Migraine Attack Onset Affects fMRI Brain Response to Fearful Faces.

Background: Previous studies suggested a circadian variation of migraine attack onset, although, with contradictory results - possibly because of the existence of migraine subgroups with different circadian attack onset peaks. Migraine is primarily a brain disorder, and if the diversity in daily distribution of migraine attack onset reflects an important aspect of migraine, it may also associate with interictal brain activity. Our goal was to assess brain activity differences in episodic migraine subgroups who were classified according to their typical circadian peak of attack onset. Methods: Two fMRI studies were conducted with migraine without aura patients (n = 31 in Study 1, n = 48 in Study 2). Among them, three subgroups emerged with typical Morning, Evening, and Varying start of attack onset. Whole brain activity was compared between the groups in an implicit emotional processing fMRI task, comparing fearful, sad, and happy facial stimuli to neutral ones. Results: In both studies, significantly increased neural activation was detected to fearful (but not sad or happy) faces. In Study 1, the Evening start group showed increased activation compared to the Morning start group in regions involved in emotional, self-referential (left posterior cingulate gyrus, right precuneus), pain (including left middle cingulate, left postcentral, left supramarginal gyri, right Rolandic operculum) and sensory (including bilateral superior temporal gyrus, right Heschl's gyrus) processing. While in Study 2, the Morning start group showed increased activation compared to the Varying start group at a nominally significant level in regions with pain (right precentral gyrus, right supplementary motor area) and sensory processing (bilateral paracentral lobule) functions. Conclusion: Our fMRI studies suggest that different circadian attack onset peaks are associated with interictal brain activity differences indicating heterogeneity within migraine patients and alterations in sensitivity to threatening fearful stimuli. Circadian variation of migraine attack onset may be an important characteristic to address in future studies and migraine prophylaxis.

Inter-individual differences in pain anticipation and pain perception in migraine: Neural correlates of migraine frequency and cortisol-to-dehydroepiandrosterone sulfate (DHEA-S) ratio.

Previous studies targeting inter-individual differences in pain processing in migraine mainly focused on the perception of pain. Our main aim was to disentangle pain anticipation and perception using a classical fear conditioning task, and investigate how migraine frequency and pre-scan cortisol-to-dehydroepiandrosterone sulfate (DHEA-S) ratio as an index of neurobiological stress response would relate to neural activation in these two phases. Functional Magnetic Resonance Imaging (fMRI) data of 23 participants (18 females; mean age: 27.61± 5.36) with episodic migraine without aura were analysed. We found that migraine frequency was significantly associated with pain anticipation in brain regions comprising the midcingulate and caudate, whereas pre-scan cortisol-to DHEA-S ratio was related to pain perception in the pre-supplementary motor area (pre-SMA). Both results suggest exaggerated preparatory responses to pain or more general to stressors, which may contribute to the allostatic load caused by stressors and migraine attacks on the brain.

Development, validation and application of LC-MS/MS method for quantification of amino acids, kynurenine and serotonin in human plasma.

Altered serotonergic neurotransmission is a key factor in several neurologic and psychiatric disorders such as migraine. Human and animal studies suggest that chronically low interictal serotonin levels of plasma and brain may facilitate increased activity of the trigeminovascular pathway, and may contribute to development of repeated migraine attacks. However, brain serotonin synthesis is affected by the concentration of tryptophan, its metabolites and a number of amino acids. In this work a simple and robust LC-MS/MS method for the quantitative determination of valine, leucine, isoleucine, phenylalanine, tyrosine, tryptophan, serotonin and kynurenine in human plasma has been developed and validated. Sample preparation was achieved by protein precipitation, using trifluoroacetic acid. Chromatographic separation was carried out on a Supelco Ascentis® Express C18 column (3.0 mm i.d. × 150 mm, 2.7 µm) equipped with an Agilent Zorbax Eclipse XDB C8 guard-column under isocratic conditions at a flow rate of 0.4 mL/min, over a 6.5 min run time. Mobile phase was 0.2% trifluoroacetic acid - acetonitrile (85:15, v/v). The eight analytes and two internal standards were ionized by positive electrospray ionization and detected in multiple reaction monitoring mode. A "fit-for-purpose" validation approach was adopted using surrogate matrix for the preparation of calibration samples. The calibration curves of all analytes showed excellent linearities with a correlation coefficient (r2) of 0.998 or better. Spiked surrogate matrix samples and pooled human plasma were used as quality control samples. Intra-day and inter-day precisions were less than 11.8% and 14.3%, and accuracies were within the ranges of 87.4-114.3% and 87.7-113.3%, respectively. Stability of the components in standard solutions, surrogate matrix, pooled plasma and processed samples were found to be acceptable under all relevant conditions. No significant carryover effect was observed. The surrogate matrix behaved parallel to human plasma when assessed by standard addition method and diluting the authentic matrix with surrogate matrix. The method was successfully applied for analysis of 800 human plasma samples to support a clinical study.

Spatiotemporal brain activation pattern following acute citalopram challenge is dose dependent and associated with neuroticism: A human phMRI study.

BACKGROUND: The initial effects of selective serotonin reuptake inhibitors (SSRIs) in the human living brain are poorly understood. We carried out a 3T resting state fMRI study with pharmacological challenge to determine the brain activation changes over time following different dosages of citalopram. METHODS: During the study, 7.5 mg i.v. citalopram was administered to 32 healthy subjects. In addition, 11.25 mg citalopram was administered to a subset of 9 subjects to investigate the dose-response. Associations with neuroticism (assessed by the NEO PI-R) of the emerging brain activation to citalopram was also investigated. RESULTS: Citalopram challenge evoked significant activation in brain regions that are part of the default mode network, the visual network and the sensorimotor network, extending to the thalamus, and midbrain. Most effects appeared to be dose-dependent and this was statistically significant in the middle cingulate gyrus. Individual citalopram-induced brain responses were positively correlated with neuroticism scores and its subscales in specific brain areas; anxiety subscale scores in thalamus and midbrain and self-consciousness scores in middle cingulate gyrus. There were no sex differences. LIMITATIONS: We investigated only healthy subjects and we used a relatively low sample size in the 11.25 mg citalopram analysis. DISCUSSION: Our results suggest that SSRIs acutely induce an increased arousal-like state of distributed cortical and subcortical systems that is mediated by enhanced serotonin neurotransmission according to levels of neuroticism and underpins trait sensitivity to environmental stimuli and stressors. Studies in depression are needed to determine how therapeutic effects eventually emerge. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.

Increased activation of the pregenual anterior cingulate cortex to citalopram challenge in migraine: an fMRI study.

BACKGROUND: The anterior cingulate cortex (ACC) is a key structure of the pain processing network. Several structural and functional alterations of this brain area have been found in migraine. In addition, altered serotonergic neurotransmission has been repeatedly implicated in the pathophysiology of migraine, although the exact mechanism is not known. Thus, our aim was to investigate the relationship between acute increase of brain serotonin (5-HT) level and the activation changes of the ACC using pharmacological challenge MRI (phMRI) in migraine patients and healthy controls. METHODS: Twenty-seven pain-free healthy controls and six migraine without aura patients participated in the study. All participant attended to two phMRI sessions during which intravenous citalopram, a selective serotonin reuptake inhibitor (SSRI), or placebo (normal saline) was administered. We used region of interest analysis of ACC to compere the citalopram evoked activation changes of this area between patients and healthy participants. RESULTS: Significant difference in ACC activation was found between control and patient groups in the right pregenual ACC (pgACC) during and after citalopram infusion compared to placebo. The extracted time-series showed that pgACC activation increased in migraine patients compared to controls, especially in the first 8-10 min of citalopram infusion. CONCLUSIONS: Our results demonstrate that a small increase in 5-HT levels can lead to increased phMRI signal in the pregenual part of the ACC that is involved in processing emotional aspects of pain. This increased sensitivity of the pgACC to increased 5-HT in migraine may contribute to recurring headache attacks and increased stress-sensitivity in migraine.

Association between migraine frequency and neural response to emotional faces: An fMRI study.

Previous studies have demonstrated that migraine is associated with enhanced perception and altered cerebral processing of sensory stimuli. More recently, it has been suggested that this sensory hypersensitivity might reflect a more general enhanced response to aversive emotional stimuli. Using functional magnetic resonance imaging and emotional face stimuli (fearful, happy and sad faces), we compared whole-brain activation between 41 migraine patients without aura in interictal period and 49 healthy controls. Migraine patients showed increased neural activation to fearful faces compared to neutral faces in the right middle frontal gyrus and frontal pole relative to healthy controls. We also found that higher attack frequency in migraine patients was related to increased activation mainly in the right primary somatosensory cortex (corresponding to the face area) to fearful expressions and in the right dorsal striatal regions to happy faces. In both analyses, activation differences remained significant after controlling for anxiety and depressive symptoms. These findings indicate that enhanced response to emotional stimuli might explain the migraine trigger effect of psychosocial stressors that gradually leads to increased somatosensory response to emotional clues and thus contributes to the progression or chronification of migraine.

A systematic review of structural and functional MRI studies on pain catastrophizing.

Objectives: Pain catastrophizing is reliably associated with pain reports during experimental pain in healthy, pain-free subjects and in people with chronic pain. It also correlates with self-reports of clinical pain intensity/severity in a variety of disorders characterized by chronic pain in adults, adolescents and children. However, processes, through which it exerts its effects are yet unclear. In this paper, our primary aim was to synthesize neuroimaging research to open a window to possible mechanisms underlying pain catastrophizing in both chronic pain patients and healthy controls. We also aimed to compare whether the neural correlates of pain catastrophizing are similar in these two groups. Methods: PubMed and the Web of Science were searched for magnetic resonance imaging (MRI) studies that explored neural correlates of pain catastrophizing. Results: Twenty articles met the inclusion criteria. The results of our review show a connection between pain catastrophizing and brain areas tightly connected to pain perception (including the somatosensory cortices, anterior insula, anterior cingulate cortex and thalamus) and/or modulation (eg, the dorsolateral prefrontal cortex). Our results also highlight that these processes - in relation to pain catastrophizing - are more pronounced in chronic pain patients, suggesting that structural and functional brain alterations (and perhaps mechanisms) related to pain catastrophizing may depend on prior and/or relatively stable/constant pain experience. However, we also found methodological issues and differences that could lead to divergent results. Discussion: Based on our results, pain catastrophizing might be related to salience detection, pain processing, and top-down attentional processes. More research is recommended to explore neural changes to specific types of catastrophizing thoughts (eg, experimentally induced and/or state). Furthermore, we provide ideas regarding pain catastrophizing studies in the future for a more standardized approach.

Altered neural activity to monetary reward/loss processing in episodic migraine.

The dysfunctions of the mesolimbic cortical reward circuit have been proposed to contribute to migraine pain. Although supporting empirical evidence was mainly found in connection with primary rewards or in chronic migraine where the pain experience is (almost) constant. Our goal however was to investigate the neural correlates of secondary reward/loss anticipation and consumption using the monetary incentive delay task in 29 episodic migraine patients and 41 headache-free controls. Migraine patients showed decreased activation in one cluster covering the right inferior frontal gyrus during reward consumption compared to controls. We also found significant negative correlation between the time of the last migraine attack before the scan and activation of the parahippocampal gyrus and the right hippocampus yielded to loss anticipation. During reward/loss consumption, a relative increase in the activity of the visual areas was observed the more time passed between the last attack and the scan session. Our results suggest intact reward/loss anticipation but altered reward consumption in migraine, indicating a decreased reactivity to monetary rewards. The findings also raise the possibility that neural responses to loss anticipation and reward/loss consumption could be altered by the proximity of the last migraine attack not just during pre-ictal periods, but interictally as well.

Anticipation and violated expectation of pain are influenced by trait rumination: An fMRI study.

Rumination - as a stable tendency to focus repetitively on feelings related to distress - represents a transdiagnostic risk factor. Theories suggest altered emotional information processing as the key mechanism of rumination. However, studies on the anticipation processes in relation to rumination are scarce, even though expectation in this process is demonstrated to influence the processing of emotional stimuli. In addition, no published study has investigated violated expectation in relation to rumination yet. In the present study we examined the neural correlates of pain anticipation and perception using a fear conditioning paradigm with pain as the unconditioned stimulus in healthy subjects (N = 30). Rumination was assessed with the 10-item Ruminative Response Scale (RRS). Widespread brain activation - extending to temporal, parietal, and occipital lobes along with activation in the cingulate cortex, insula, and putamen - showed a positive correlation with rumination, supporting our hypothesis that trait rumination influences anticipatory processes. Interestingly, with violated expectation (when an unexpected, non-painful stimulus follows a pain cue compared to when an expected, painful stimulus follows the same pain cue) a negative association between rumination and activation was found in the posterior cingulate cortex, which is responsible for change detection in the environment and subsequent behavioral modification. Our results suggest that rumination is associated with increased neural response to pain perception and pain anticipation, and may deteriorate the identification of an unexpected omission of aversive stimuli. Therefore, targeting rumination in cognitive behavioral therapy of chronic pain could have a beneficial effect.

Genetic variants in major depressive disorder: From pathophysiology to therapy.

In spite of promising preclinical results there is a decreasing number of new registered medications in major depression. The main reason behind this fact is the lack of confirmation in clinical studies for the assumed, and in animals confirmed, therapeutic results. This suggests low predictive value of animal studies for central nervous system disorders. One solution for identifying new possible targets is the application of genetics and genomics, which may pinpoint new targets based on the effect of genetic variants in humans. The present review summarizes such research focusing on depression and its therapy. The inconsistency between most genetic studies in depression suggests, first of all, a significant role of environmental stress. Furthermore, effect of individual genes and polymorphisms is weak, therefore gene x gene interactions or complete biochemical pathways should be analyzed. Even genes encoding target proteins of currently used antidepressants remain non-significant in genome-wide case control investigations suggesting no main effect in depression, but rather an interaction with stress. The few significant genes in GWASs are related to neurogenesis, neuronal synapse, cell contact and DNA transcription and as being nonspecific for depression are difficult to harvest pharmacologically. Most candidate genes in replicable gene x environment interactions, on the other hand, are connected to the regulation of stress and the HPA axis and thus could serve as drug targets for depression subgroups characterized by stress-sensitivity and anxiety while other risk polymorphisms such as those related to prominent cognitive symptoms in depression may help to identify additional subgroups and their distinct treatment. Until these new targets find their way into therapy, the optimization of current medications can be approached by pharmacogenomics, where metabolizing enzyme polymorphisms remain prominent determinants of therapeutic success.

Decreased Openness to Experience Is Associated with Migraine-Type Headaches in Subjects with Lifetime Depression.

INTRODUCTION: Migraine and depression frequently occur as comorbid conditions, and it has been hypothesized that migraine with and without depression may have a different genetic background. A distinct personality trait constellation has been described in migraineurs. Less attention, however, was paid to personality differences in migraineurs with and without depression which may also shed light on differences in the neurobiological, background. The aim of our study was to investigate big five personality traits, headaches, and lifetime depression (DEP) in a large European general population sample. METHODS: Relationship between DEP, Big Five Inventory personality traits, and headaches identified by the ID-Migraine Questionnaire were investigated in 3,026 individuals from Budapest and Manchester with multivariate and logistic regression analyses. RESULTS: Both DEP and migraine(ID) showed differences in personality traits. Neuroticism was an independent risk factor for both conditions while a significant interaction effect appeared between the two in the case of openness. Namely, subjects with migraine(ID) and without DEP scored higher on openness compared to those who had depression. CONCLUSION: While we confirmed previous results that high neuroticism is a risk factor for both depression and migraine, openness to experience was significantly lower in the co-occurrence of migraine and depression. Our results suggest that increased openness, possibly manifested in optimal or advantageous cognitive processing of pain experience in migraine may decrease the risk of co-occurrence of depression and migraine and thus may provide valuable insight for newer prevention and intervention approaches in the treatment of these conditions.

Trait Rumination Influences Neural Correlates of the Anticipation but Not the Consumption Phase of Reward Processing.

Cumulative evidence suggests that trait rumination can be defined as an abstract information processing mode, which leads people to constantly anticipate the likely impact of present events on future events and experiences. A previous study with remitted depressed patients suggested that enhanced rumination tendencies distort brain mechanisms of anticipatory processes associated with reward and loss cues. In the present study, we explored the impact of trait rumination on neural activity during reward and loss anticipation among never-depressed people. We analyzed the data of 37 healthy controls, who performed the monetary incentive delay (MID) task which was designed for the simultaneous measurement of the anticipation (motivational) and consumption (hedonic) phase of reward processing, during functional magnetic resonance imaging (fMRI). Our results show that rumination-after controlling for age, gender, and current mood-significantly influenced neural responses to reward (win) cues compared to loss cues. Blood-oxygenation-level-dependent (BOLD) activity in the left inferior frontal gyrus (IFG) triangularis, left anterior insula, and left rolandic operculum was positively related to Ruminative Response Scale (RRS) scores. We did not detect any significant rumination-related activations associated with win-neutral or loss-neutral cues and with reward or loss consumption. Our results highlight the influence of trait rumination on reward anticipation in a non-depressed sample. They also suggest that for never-depressed ruminators rewarding cues are more salient than loss cues. BOLD response during reward consumption did not relate to rumination, suggesting that rumination mainly relates to processing of the motivational (wanting) aspect of reward rather than the hedonic (liking) aspect, at least in the absence of pathological mood.

Spontaneous migraine attack causes alterations in default mode network connectivity: a resting-state fMRI case report.

BACKGROUND: Although migraine is one of the most investigated neurologic disorders, we do not have a perfect neuroimaging biomarker for its pathophysiology. One option to improve our knowledge is to study resting-state functional connectivity in and out of headache pain. However, our understanding of the functional connectivity changes during spontaneous migraine attack is partial and incomplete. CASE PRESENTATION: Using resting-state functional magnetic resonance imaging we assessed a 24-year old woman affected by migraine without aura at two different times: during a spontaneous migraine attack and in interictal phase. Seed-to-voxel whole brain analysis was carried out using the posterior cingulate cortex as a seed, representing the default mode network (DMN). Our results showed decreased intrinsic connectivity within core regions of the DMN with an exception of a subsystem including the dorsal medial and superior frontal gyri, and the mid-temporal gyrus which is responsible for pain interpretation and control. In addition, increased connectivity between the DMN and pain and specific migraine-related areas, such as the pons and hypothalamus, developed during the spontaneous migraine attack. CONCLUSION: Our preliminary results provide further support for the hypothesis that alterations of the DMN functional connectivity during migraine headache may lead to maladaptive top-down modulation of migraine pain-related areas which might be a specific biomarker for migraine.

Rumination in migraine: Mediating effects of brooding and reflection between migraine and psychological distress.

OBJECTIVE: The relationship between migraine and psychological distress has been consistently reported in cross-sectional and longitudinal studies. We hypothesised that a stable tendency to perseverative thoughts such as rumination would mediate the relationship between migraine and psychological distress. Design and Main Outcomes Measures: Self-report questionnaires measuring depressive rumination, current psychological distress and migraine symptoms in two independent European population cohorts, recruited from Budapest (N = 1139) and Manchester (N = 2004), were used. Structural regression analysis within structural equation modelling was applied to test the mediational role of brooding and reflection, the components of rumination, between migraine and psychological distress. Sex, age and lifetime depression were controlled for in the analysis. RESULTS: Migraine predicted higher brooding and reflection scores, and brooding proved to be a mediator between migraine and psychological distress in both samples, while reflection mediated the relationship significantly only in the Budapest sample. CONCLUSIONS: Elevated psychological distress in migraine is partially attributed to ruminative response style. Further studies are needed to expand our findings to clinical samples and to examine how rumination links to the adjustment to migraine.

[Functional magnetic resonance imaging studies in pain research]. / Funkcionális mágneses rezonanciás képalkotó vizsgálatok a fájdalomkutatásban.

Functional imaging studies opened a new way to understand the neural activity underlying pain perception and the pathomechanism of chronic pain syndromes. In the last twenty years several results of functional magnetic resonance imaging (fMRI) studies have been published about examining the different aspects of complex pain experience. The aim of these studies is to understand the functioning of the pain control system, the so-called pain matrix, activated by acute nociceptive stimulus. Another important field of pain research is the investigation of neuronal processes underlying chronic pain, since the pathomechanism of this is still unclear. Our review aims to provide insight into the methods of pain research using fMRI and the achievements of the last few years.

Antidepressant treatment response is modulated by genetic and environmental factors and their interactions.

Although there is a wide variety of antidepressants with different mechanisms of action available, the efficacy of treatment is not satisfactory. Genetic factors are presumed to play a role in differences in medication response; however, available evidence is controversial. Even genome-wide association studies failed to identify genes or regions which would consequently influence treatment response. We conducted a literature review in order to uncover possible mechanisms concealing the direct effects of genetic variants, focusing mainly on reports from large-scale studies including STAR*D or GENDEP. We observed that inclusion of environmental factors, gene-environment and gene-gene interactions in the model improves the probability of identifying genetic modulator effects of antidepressant response. It could be difficult to determine which allele of a polymorphism is the risk factor for poor treatment outcome because depending on the acting environmental factors different alleles could be advantageous to improve treatment response. Moreover, genetic variants tend to show better association with certain intermediate phenotypes linked to depression because these are more objective and detectable than traditional treatment outcomes. Thus, detailed modeling of environmental factors and their interactions with different genetic pathways could significantly improve our understanding of antidepressant efficacy. In addition, the complexity of depression itself demands a more comprehensive analysis of symptom trajectories if we are to extract useful information which could be used in the personalization of antidepressant treatment.

[Application of pharmacologic functional magnetic resonance imaging (phMRI) in the research of affective disorders]. / A farmakológiai funkcionális mágneses rezonancia vizsgálat (phMRI) felhasználásának lehetoségei a hangulatzavarok kutatásában.

Many common psychiatric disorders such as depression and anxiety disorders are associated with dysfunction in the monoamine neurotransmission in the central nervous system. However, the investigation of these pathophysiological processes in the human living brain is difficult. In case of functional magnetic resonance imaging (fMRI), a non-invasive method for the examination of brain activity, the activity-inducing stimulus is generally a cognitive psychological test, while during pharmacological magnetic resonance imaging (phMRI) the activation is triggered by a specific pharmacon. In the present work we review the available scientific literature related to this method using literature search in PubMed. Through application of a selective pharmacon like the selective serotonine reuptake inhibitors (SSRIs) citalopram or escitalopram in a challenge phMRI study, the serotonergic neurotransmitter system can be examined specifically, the functioning brain areas involved in its effect become observable.. With modulation phMRI we can monitor the long-term effect of an antidepressant or we can examine the immediate effect of a single dose of the medication on congitive psychological functions like emotional processing. Thus, the application of phMRI methods may help deepen our understanding of serotonergic function in the living human brain as well as of diseases related to serotonergic neurotransmitter system dysfunction.