A farmakologiai funkcionalis magneses rezo-nancia vizsgalat (phMRI) felhasznalasanak lehetosegei a hangulatzavarok kutatasaban.

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

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

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

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

Háttér és célkitûzés – Általános és betegségspecifikus életminőség-kérdőívet használó vizsgálatok eredményei alapján mind migrénben, mind fájdalomcsillapító-túlfogyasztáshoz társuló fejfájásban (FTTF) szenvedő betegek esetében alacsonyabb életminôség-értékeket mértek a kontrollrésztvevőkhöz hasonlítva. Vizsgálatunk célja egyrészt a migrénben és FTTF-ben szenvedő betegek életminőségének, valamint a fejfájás-karakterisztika (fejfájós évek száma, auratünetek, triptánhasználat, fejfájássúlyosság és fejfájás-gyakoriság) életminőségre gyakorolt hatásának vizsgálata volt. Módszerek – Keresztmetszeti vizsgálatunkban 334 beteg vett részt (248 beteg fejfájás-ambulanciánkról, valamint 86 beteg hirdetés útján). A résztvevők életminőségének értékeléséhez az Átfogó Fejfájással Kapcsolatos Életminőség kérdőívet (CHQQ) használtuk. Adataink normáleloszlást mutattak, így χ2-próba mellett parametrikus teszte ket alkalmaztunk (például független mintás t-próba), a szignifikanciaszintet p < 0,05-ban határoztuk meg. A nem, életkor, beválogatási kritériumok, fejfájástípus, valamint fejfájás-karakterisztika (auratünetek megléte, fejfájós évek száma, fejfájás súlyossága, fejfájás gyakorisága, triptánhasználat) életminőségre gyakorolt hatásának vizsgálatához lineáris regressziós modelleket használtunk mind a három CHQQ-alskála és az összpontszám tekintetében is. Az utóbbi esetében az I. típusú hiba elkerülésének érdekében a szignifikanciaszintet p<=0,0125 (0,05/4) értékben határoztuk meg. Eredmények – A fejfájástípust önmagában vizsgálva az FTTF-ben szenvedő betegek a szociális alskála kivételével szignifikánsan alacsonyabb CHQQ-értékeket értek el, mint a migrénes betegek. A többi változó bevonásával elvégzett regressziós elemzések alapján a triptánhasználat mutatott fordított összefüggést az összes CHQQ-alskálaértékkel (p < 0,0125). A vizsgált fejfájás-karakterisztikák közül a fejfájás súlyossága mutatott szignifikáns kapcsolatot az alacsonyabb fizikaialskála-értékekkel (p = 0,001), valamint az alacsonyabb CHQQ-összpontszámmal (p = 0,002). Következtetés – Eredményeink azt mutatják, hogy a fejfájás-karakterisztika (és nem a fejfájás típusa önmagában) összefüggést mutat a fejfájós betegek alacsonyabb életminôségével. Az életminőség-változást előidézô faktorok meghatározása fontos a különböző betegpopulációk adekvát kezelésének, valamint az egészségügyi szolgáltatások igénybevételével és az egészségügyi költségekkel kapcsolatos népegészségügyi intézkedéseknek a megtervezése érdekében

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 high-light 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

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 GxE interactions, on the other hand, are connected to the regulation of stress and the HPA axis and thus could serve as drug targets for a 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 in the therapy, the optimization of current medications can be approached by pharmacogenomics, where metabolizing enzyme polymorphisms remain prominent determinants of therapeutic success

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