202 research outputs found
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
A new clinical evidence-based gene-environment interaction model of depression.
In our current understanding of mood disorders, the role of
genes is diverse including the mediation of the effects of
provoking and protective factors. Different or partially
overlapping gene sets play a major role in the development of
personality traits including also affective temperaments, in the
mediation of the effects of environmental factors, and in the
interaction of these elements in the development of depression.
Certain genes are associated with personality traits and
temperaments including e.g., neuroticism, impulsivity, openness,
rumination and extroversion. Environmental factors consist of
external (early and provoking life events, seasonal changes,
social support etc.) and internal factors (hormones, biological
rhythm generators, comorbid disorders etc). Some of these
environmental factors, such as early life events and some
prenatal events directly influence the development of
personality traits and temperaments. In the NEWMOOD cohort
polymorphisms of the genes of the serotonin transporter, 5-HT1A,
5-HT1B and 5-HT2A and endocannabinoid CB1 receptors, tryptophan
hydroxylase, CREB1, BDNF and GIRK provide evidence for the
involvement of these genes in the development of depression.
Based on their role in this process they could be assigned to
different gene sets. The role of certain genes, such as promoter
polymorphisms of the serotonin transporter (5-HTTLPR) and CB1
receptor has been shown in more than one of the above factors.
Furthermore, gene-gene interactions of these promoters
associated with anxiety suggest the application of these
polymorphisms in personalized medicine. In this review we
introduce a new model including environmental factors, genes,
trait and temperament markers based on human genetic studies
Dehydroepiandrosterone sulfate (DHEAS) is neuroprotective when administered either before or after injury in a focal cortical cold lesion model
Dehydroepiandrosterone and its sulfate (DHEAS) are sex hormone precursors that exert marked neurotrophic and/or neuroprotective activity in the central nervous system. The
present study evaluated the effects of DHEAS and 17�-estradiol (E2) in a focal cortical cold lesion model, in which DHEAS (50 mg/kg, sc) and E2 (35 mg/kg, sc) were administered either as pretreatment (two subsequent injections 1 d and 1 h before lesion induction) or posttreatment (immediately after lesion induction). The focal cortical cold lesion was induced in the primary motor cortex by means of a cooled copper cylinder placed directly onto the cortical surface. One hour later, the animals were killed, the brains cut into 0.4-mm-thick slices, and the sections stained with 1% triphenyltetrazolium chloride.
The volume of the hemispheric lesion was calculated for
each animal. The results demonstrated that the lesion area
was significantly attenuated in both the DHEAS- and E2- preand posttreated groups and that in the presence of letrozole, a nonsteroidal aromatase inhibitor, no neuroprotection was observed, suggesting that the beneficial effect of DHEAS on the cold injury might depend on the conversion of DHEAS to E2 within the brain. It is concluded that even a single posttraumatic administration of DHEAS may be of substantial therapeutic benefit in the treatment of focal brain injury with vasogenic edema
Genetically reduced FAAH activity may be a risk for the development of anxiety and depression in persons with repetitive childhood trauma
Fatty acid amide hydrolase (FAAH) inhibitors are addressed for promising anxiolytics, but human studies on genetically reduced FAAH activity, stress and affective phenotypes are scarce. We investigated the effect of a functional polymorphism of FAAH (FAAH C385A or rs324420; low FAAH activity and high anandamide concentration are associated with the A allele) together with childhood adversity on the anxious and depressive phenotypes in 858 subjects from the general population. Phenotypes were measured by the Zung Self-Rating Depression Scale (ZSDS), the depression and anxiety subscales of the Brief Symptom Inventory (BSI-DEP, BSI-ANX) and the State-Trait Anxiety scales (STAI-S, STAI-T). Childhood Adversity Questionnaire (CHA) was used to assess early life traumas. Frequency of the A allele was greater among subjects with high ZSDS scores compared to the CC genotype. Furthermore, FAAH C385A and the CHA have shown a robust gene-environment interaction, namely, significantly higher anxiety and depression scores were exhibited by individuals carrying the A allele if they had high CHA scores compared to CC carriers. These data provided preliminary evidence that genetically reduced FAAH activity and repetitive stress in the childhood are associated with increased vulnerability for anxiety and depression in later life. Our results together with earlier experimental data suggest that permanently elevated anandamide level together with early life stress may cause a lifelong damage on stress response probably via the downregulation of CB1R during the neurodevelopment in the brain. It may also point to pharmacogenomic consequences, namely ineffectiveness or adverse effects of FAAH inhibitors in this subpopulation
Nem pszichiátriai gyógyszerek szorongást és depressziót kiváltó mellékhatásai
Annak ellenére, hogy számos szomatikus betegség kezelésére alkalmazott – például daganatellenes, antimikrobás,
immunmoduláns, neurológiai, illetve hormonháztartásra ható – gyógyszer hathat negatív irányban a hangulatra,
ezt egészen a rimonabant 2008-ban emiatt történt visszavonásáig nem kezelték jelentőségének megfelelően. A szerzők
a teljes gyógyszerpalettát áttekintve tárgyalják a szorongást és a depressziót, mint gyógyszer-mellékhatásokat.
A gyógyszerválasztásnál minden esetben fi gyelembe kell venni, ha a betegeknél magas a depresszió kialakulásának
a kockázata, például, ha már korábban előfordult vagy jelenleg is fennáll a depressziós epizód vagy betegség, ha a
családi anamnézisben előfordul depresszió, illetve ha a betegnél olyan neurotikus személyiségvonások állnak fenn,
amelyek következtében sérülékenyebb a depressziót kiváltó hatásokkal szemben. A veszélyt jelentő gyógyszerek felírása
előtt emellett célszerű fi gyelembe venni az alkalmazni kívánt szer hatékonyságát, a rendelkezésre álló alternatív
gyógyszeres és nem gyógyszeres terápiás lehetőségeket, és minden esetben biztosítani kell a beteg monitorozását a
kezelés során az esetleges depressziós vagy szorongásos tünetek mihamarabbi észlelése érdekében
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
Structural and parametric uncertainties in full Bayesian and graphical lasso based approaches: beyond edge weights in psychological networks
Uncertainty over model structures poses a challenge
for many approaches exploring effect strength parameters at
system-level. Monte Carlo methods for full Bayesian model
averaging over model structures require considerable computational
resources, whereas bootstrapped graphical lasso and its
approximations offer scalable alternatives with lower complexity.
Although the computational efficiency of graphical lasso based
approaches has prompted growing number of applications, the
restrictive assumptions of this approach are frequently ignored,
such as its lack of coping with interactions. We demonstrate
using an artificial and a real-world example that full Bayesian
averaging using Bayesian networks provides detailed estimates
through posterior distributions for structural and parametric
uncertainties and it is a feasible alternative, which is routinely
applicable in mid-sized biomedical problems with hundreds of
variables. We compare Bayesian estimates with corresponding
frequentist quantities from bootstrapped graphical lasso using
pairwise Markov Random Fields, discussing also their interpretational
differences. We present results using synthetic data from
an artificial model and using the UK Biobank data set to explore
a psychopathological network centered around depression (this
research has been conducted using the UK Biobank Resource
under Application Number 1602)
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
A farmakológiai funkcionális mágneses rezonancia vizsgálat (phMRI) felhasználásának lehetőségei a hangulatzavarok kutatásában | Application of pharmaco functional magnetic resonance imaging (phMRI) in the research of affective disorders
Napjaink leggyakoribb pszichiátriai betegségei, a depresszió és a szorongásos zavarok, feltehetőleg
a központi idegrendszer monoamin neurotranszmissziójának elégtelenségével
kapcsolatosak. Ugyanakkor ezeknek a patofiziológiai folyamatoknak a vizsgálata az élő emberi
agyban komoly kihívást jelent. A funkcionális mágneses rezonancia képalkotás (fMRI)
olyan noninvazív módszer, ami lehetőséget nyújt az agyi aktivitás vizsgálatára. Legtöbb
esetben az aktivitást előidéző stimulus kognitív pszichológiai feladat, azonban lehetőség
nyílik arra, hogy farmakológiai funkcionális mágneses rezonancia (phMRI) vizsgálat során
egy specifikus farmakon indukálta aktivitásváltozást vizsgáljunk. Jelen munkánk célja az ezzel
a módszerrel végzett eredmények összefoglalása, melyet a PubMed adatai alapján készítettünk
el. A challenge phMRI vizsgálatok során egy szelektív farmakon, például a szelektív
szerotonin visszavétel gátló (SSRI) citalopram és escitalopram alkalmazásával a szerotonerg
neurotranszmisszió és a gyógyszerhatásban résztvevő agyi területek aktivitásváltozása vizsgálható.
Modulation phMRI segítségével megfigyelhetjük, milyen akut hatással van az adott
farmakon alkalmazása az olyan kognitív pszichés funkciókra, mint az érzelemfeldolgozás,
és hogyan változnak meg ezek a funkciók hosszabb távú gyógyszeralkalmazást követően.
A phMRI különböző módszerei ezért komoly segítséget nyújthatnak abban, hogy az emberi
agy szerotonerg transzmissziójának szerepét és az ezzel összefüggő pszichés betegségek
patomechanizmusát jobban megérthessük |
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
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