Association between the COMT gene and rumination in a Hungarian sample.

Introduction: Rumination is a multidimensional trait which is a proven risk factor in the vulnerability to depression. The aim to identify the main risk genes for depression in addition to the gene-environment interactions pointed to the importance of intermediate phenotypes, like rumination, to improve our understanding of the biological mechanisms of depression. Catechol-O-Methyltransferase (COMT) gene is extensively investigated in depression with contradictory results but its association with rumination, as an intermediate phenotype in depression, has not been investigated yet. Methods: In our study, four tagging SNPs in the COMT gene (rs933271, rs740603, rs4680, rs4646316) were genotyped in a nonclinical Hungarian sample (n=939). We investigated the association between the COMT gene and rumination scores measured by the Ruminative Response Scale using haplotype trend regression. Results: We found a significant association between COMT haplotypes and rumination scores (p=0.013) but no significant association was apparent between the functional Val158Met polymorphism (rs4680) and rumination in any genetic model. Discussion: Variations in the COMT gene exert complex effects on susceptibility to depression involving intermediate phenotypes, such as rumination and also impulsivity, as we previously demonstrated. Both rumination and impulsivity represent maladaptive cognitive styles that can lead to depressive state by influencing the response to negative life events and life stressors. In conclusion, our findings provide evidence that in addition to other genes, COMT also has a significant role in the development of depression, and demonstrate that analysing the complex phenotype associations of genes by haplotype tagging is a powerful method

Cultural differences in the development and characteristics of depression.

Depression is a highly prevalent mental illness with increasing burden for the patients, their families and society as well. In spite of its increasing importance, we still do not have complete understanding either of the phenomenology or the etiopathological background of depression, and cross-country, cross-ethnic and cross-cultural differences in the prevalence and symptomatic manifestation of depression further obscure this picture. Culturally-related features of depressive illness are gaining more importance in clinical practice with the increasing migration trends worldwide. In spite of the differences replicated in multiple studies, no exhaustive explanations are offered so far. In the present paper we describe the most consistently replicated findings concerning the most important cross-national differences in the rates and characteristics of depression with a short comment on possible background factors

Mood parameters and severe physical symptoms of the female reproductive cycle

OBJECTIVE: The cyclic variation of physical and psychological phenomena has been accepted as a natural consequence of the cyclicity of the human female reproductive function. The exact nature of these changes, however, has not been fully understood. The aim of our study was to investigate the fluctuation of psychological and physical symptoms throughout the female reproductive cycle in healthy, non-PMDD women. METHOD: 63 psychiatrically healthy, non-PMDD women with normal regular menstrual cycles and not using hormonal contraceptive methods participated in the study. Participants completed the PRISM calendar every night for three consecutive cycles and on three predefined days of the first cycle they completed several other psychometric measures (SCL-51, STAI, ZSDS, EAT and Mind and Body Cathexis Scale). Based on an at least 66% increase in physical symptoms from the late follicular to the late luteal phase on the PRISM, subjects were assigned to LPPS (luteal phase physical symptoms) and nonLPPS (no luteal phase physical symptoms) groups. Average of psychometric scores obtained at the three predefined days were compared between the two groups. RESULTS: There was a significant difference between the two groups only in case of the interpersonal sensitivity subscale of the SCL-51. CONCLUSION: Our results indicate that the appearance of severe physical symptoms in the late luteal phase of the female reproductive cycle is not accompanied by a worsening of psychological symptoms. The appearance of enhanced psychological symptomatology attributed to the luteal phase of the female reproductive cycle thus seems to be independent of the appearance of severe physical symptoms

Vaszkuláris ultrahangvezérelt vena femoralis punkciók szív-elektrofiziológiai beavatkozások során = Vascular ultrasound guided femoral vein puncture in cardiac electrophysiology procedures

Az invazív szív-elektrofiziológia vizsgálatok és katéterablációk leggyakoribb szövődményei a vaszkuláris behatolással kapcsolatosak. Szemben a hagyományos anatómiai alapokon nyugvó, palpáció-irányított technikával, az ultrahangvezérléssel végzett punkciók potenciális előnyöket biztosíthatnak, amelyekkel a vaszkuláris szövődmények aránya csökkenthető. Összefoglaló közleményünk célja az elektrofiziológiai beavatkozások során ultrahangvezérléssel végzett vena femoralis punkciókkal kapcsolatos tudományos adatok áttekintése, saját eredményeink ismertetése, továbbá a saját laboratóriumukban alkalmazott metódus bemutatása

Distinct effects of folate pathway genes MTHFR and MTHFD1L on ruminative response style: a potential risk mechanism for depression

Alterations in the folate pathway have been related to both major depression and cognitive inflexibility; however, they have not been investigated in the genetic background of ruminative response style, which is a form of perseverative cognition and a risk factor for depression. In the present study, we explored the association of rumination (measured by the Ruminative Responses Scale) with polymorphisms of two distinct folate pathway genes, MTHFR rs1801133 (C677T) and MTHFD1L rs11754661, in a combined European white sample from Budapest, Hungary (n=895) and Manchester, United Kingdom (n=1309). Post hoc analysis investigated whether the association could be replicated in each of the two samples, and the relationship between folate pathway genes, rumination, lifetime depression and Brief Symptom Inventory depression score. Despite its functional effect on folate metabolism, the MTHFR rs1801133 showed no effect on rumination. However, the A allele of MTHFD1L rs11754661 was significantly associated with greater rumination, and this effect was replicated in both the Budapest and Manchester samples. In addition, rumination completely mediated the effects of MTHFD1L rs11754661 on depression phenotypes. These findings suggest that the MTHFD1L gene, and thus the C1-THF synthase enzyme of the folate pathway localized in mitochondria, has an important effect on the pathophysiology of depression through rumination, and maybe via this cognitive intermediate phenotype on other mental and physical disorders. Further research should unravel whether the reversible metabolic effect of MTHFD1L is responsible for increased rumination or other long-term effects on brain development

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

Effects of IL1B single nucleotide polymorphisms on depressive and anxiety symptoms are determined by severity and type of life stress

Interleukin-1b is one of the main mediators in the cross-talk between the immune system and the central nervous system. Higher interleukin-1b levels are found in mood spectrum disorders, and the stressinduced expression rate of the interleukin-1b gene (IL1B) is altered by polymorphisms in the region. Therefore we examined the effects of rs16944 and rs1143643 single nucleotide polymorphisms (SNPs) within the IL1B gene on depressive and anxiety symptoms, as measured by the Brief Symptom Inventory, in a Hungarian population sample of 1053 persons. Distal and proximal environmental stress factors were also included in our analysis, namely childhood adversity and recent negative life-events. We found that rs16944 minor (A) allele specifically interacted with childhood adversity increasing depressive and anxiety symptoms, while rs1143643’s minor (A) allele showed protective effect against depressive symptoms after recent life stress. The genetic main effects of the two SNPs were not significant in the main analysis, but the interaction effects remained significant after correction for multiple testing. In addition, the effect of rs16944 A allele was reversed in a subsample with low-exposure to life stress, suggesting a protective effect against depressive symptoms, in the post hoc analysis. In summary, both of the two IL1B SNPs showed specific environmental stressor-dependent effects on mood disorder symptoms. We also demonstrated that the presence of exposure to childhood adversity changed the direction of the rs16944 effect on depression phenotype. Therefore our results suggest that it is advisable to include environmental factors in genetic association studies when examining the effect of the IL1B gene