Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 56
Filtrar
1.
Int J Psychiatry Clin Pract ; : 1-9, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32852246

RESUMO

The treatment of depression represents a major challenge for healthcare systems and choosing among the many available drugs without objective guidance criteria is an error-prone process. Recently, pharmacogenetic biomarkers entered in prescribing guidelines, giving clinicians the possibility to use this additional tool to guide prescription and improve therapeutic outcomes. This marked an important step towards precision psychiatry, which aim is to integrate biological and environmental information to personalise treatments. Only genetic variants in cytochrome enzymes are endorsed by prescribing guidelines, but in the future polygenic predictors of treatment outcomes may be translated into the clinic. The integration of genetics with other relevant information (e.g., concomitant diseases and treatments, drug plasma levels) could be managed in a standardised way through ad hoc software. The overcoming of the current obstacles (e.g., staff training, genotyping and informatics facilities) can lead to a broad implementation of precision psychiatry and represent a revolution for psychiatric care. Key points Precision psychiatry aims to integrate biological and environmental information to personalise treatments and complement clinical judgement Pharmacogenetic biomarkers in cytochrome genes were included in prescribing guidelines and represented an important step towards precision psychiatry Therapeutic drug monitoring is an important and cost-effective tool which should be integrated with genetic testing and clinical evaluation in order to optimise pharmacotherapy Other individual factors relevant to pharmacotherapy response (e.g., individual's symptom profile, concomitant diseases) can be integrated with genetic information through artificial intelligence to provide treatment recommendations The creation of pharmacogenetic services within healthcare systems is a challenging and multi-step process, education of health professionals, promotion by institutions and regulatory bodies, economic and ethical barriers are the main issues.

2.
Mol Psychiatry ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31712720

RESUMO

Panic disorder (PD) has a lifetime prevalence of 2-4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0-34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10-4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10-7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD.

3.
Curr Top Behav Neurosci ; 40: 437, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30488349

RESUMO

This chapter was inadvertently published with Fig. 1 which do not belong to this chapter and hence Fig. 1 is deleted from this chapter later.

4.
Curr Top Behav Neurosci ; 40: 219-292, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29796838

RESUMO

Anxiety disorders are the most common mental health problem in the world and also claim the highest health care cost among various neuropsychiatric disorders. Anxiety disorders have a chronic and recurrent course and cause significantly negative impacts on patients' social, personal, and occupational functioning as well as quality of life. Despite their high prevalence rates, anxiety disorders have often been under-diagnosed or misdiagnosed, and consequently under-treated. Even with the correct diagnosis, anxiety disorders are known to be difficult to treat successfully. In order to implement better strategies in diagnosis, prognosis, treatment decision, and early prevention for anxiety disorders, tremendous efforts have been put into studies using genetic and neuroimaging techniques to advance our understandings of the underlying biological mechanisms. In addition to anxiety disorders including panic disorder, generalised anxiety disorder (GAD), specific phobias, social anxiety disorders (SAD), due to overlapping symptom dimensions, obsessive-compulsive disorder (OCD), and post-traumatic stress disorder (PTSD) (which were removed from the anxiety disorder category in DSM-5 to become separate categories) are also included for review of relevant genetic and neuroimaging findings. Although the number of genetic or neuroimaging studies focusing on anxiety disorders is relatively small compare to other psychiatric disorders such as psychotic disorders or mood disorders, various structural abnormalities in the grey or white matter, functional alterations of activity during resting-state or task conditions, molecular changes of neurotransmitter receptors or transporters, and genetic associations have all been reported. With continuing effort, further genetic and neuroimaging research may potentially lead to clinically useful biomarkers for the prevention, diagnosis, and management of these disorders.


Assuntos
Transtornos de Ansiedade , Biomarcadores , Marcadores Genéticos , Transtorno Obsessivo-Compulsivo , Ansiedade , Transtornos de Ansiedade/genética , Humanos , Transtorno Obsessivo-Compulsivo/genética , Qualidade de Vida , Transtornos de Estresse Pós-Traumáticos/genética
5.
Nord J Psychiatry ; 72(5): 354-360, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29688152

RESUMO

BACKGROUND: Selective serotonin re-uptake inhibitors (SSRI) have proven to be effective in treatment of depression. Still, treatment efficacy varies significantly from patient to patient and about 40% of patients do not respond to initial treatment. Personality traits have been considered one source of variability in treatment outcome. AIM: Current study aimed at identifying specific personality traits that could be predictive of treatment response and/or the dynamics of symptom change in depressive patients. METHOD: In a sample of 132 outpatients with major depressive disorder (MDD) treated with an SSRI-group antidepressant escitalopram, the Swedish universities Scales of Personality (SSP) were used in order to find predictive personality traits. For the assessment of the severity of depressive symptoms and the improvement rates, the Hamilton Depression Scale (HAM-D) and Montgomery-Åsberg Depression Rating Scale (MADRS) were used. RESULTS: Escitalopram-treated MDD patients with higher social desirability achieved more rapid decrease in symptom severity. None of the studied traits predicted the end result of the treatment. CONCLUSION: The findings suggest that specific personality traits may predict the trajectory of symptom change rather than the overall improvement rate.


Assuntos
Citalopram/uso terapêutico , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Personalidade/efeitos dos fármacos , Inibidores de Captação de Serotonina/uso terapêutico , Adulto , Antidepressivos/uso terapêutico , Antidepressivos de Segunda Geração/farmacologia , Antidepressivos de Segunda Geração/uso terapêutico , Citalopram/farmacologia , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Personalidade/fisiologia , Escalas de Graduação Psiquiátrica , Inibidores de Captação de Serotonina/farmacologia , Resultado do Tratamento
6.
Focus (Am Psychiatr Publ) ; 16(2): 210-218, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32015708

RESUMO

(Reprinted with permission from Dialogues in Clinical Neuroscience, 2017; 19:147-157).

7.
Dialogues Clin Neurosci ; 19(2): 147-158, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28867939

RESUMO

Generalized anxiety disorder (GAD) is a prevalent and highly disabling mental health condition; however, there is still much to learn with regard to pertinent biomarkers, as well as diagnosis, made more difficult by the marked and common overlap of GAD with affective and anxiety disorders. Recently, intensive research efforts have focused on GAD, applying neuroimaging, genetic, and blood-based approaches toward discovery of pathogenetic and treatment-related biomarkers. In this paper, we review the large amount of available data, and we focus in particular on evidence from neuroimaging, genetic, and neurochemical measurements in GAD in order to better understand potential biomarkers involved in its etiology and treatment. Overall, the majority of these studies have produced results that are solitary findings, sometimes inconsistent and not clearly replicable. For these reasons, they have not yet been translated into clinical practice. Therefore, further research efforts are needed to distinguish GAD from other mental disorders and to provide new biological insights into its pathogenesis and treatment.


Assuntos
Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/sangue , Transtornos de Ansiedade/etiologia , Transtornos de Ansiedade/terapia , Biomarcadores/sangue , Diagnóstico Diferencial , Humanos , Transtornos Mentais/diagnóstico , Neuroimagem , Prevalência
8.
Nord J Psychiatry ; 71(6): 433-440, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28472591

RESUMO

BACKGROUND: There is strong evidence to suggest that personality factors may interact with the development and clinical expression of panic disorder (PD). A greater understanding of these relationships may have important implications for clinical practice and implications for searching reliable predictors of treatment outcome. AIMS: The study aimed to examine the effect of escitalopram treatment on personality traits in PD patients, and to identify whether the treatment outcome could be predicted by any personality trait. METHOD: A study sample consisting of 110 outpatients with PD treated with 10-20 mg/day of escitalopram for 12 weeks. The personality traits were evaluated before and after 12 weeks of medication by using the Swedish universities Scales of Personality (SSP). RESULTS: Although almost all personality traits on the SSP measurement were improved after 12 weeks of medication in comparison with the baseline scores, none of these changes reached a statistically significant level. Only higher impulsivity at baseline SSP predicted non-remission to 12-weeks treatment with escitalopram; however, this association did not withstand the Bonferroni correction in multiple comparisons. LIMITATIONS: All patients were treated in a naturalistic way using an open-label drug, so placebo responses cannot be excluded. The sample size can still be considered not large enough to reveal statistically significant findings. CONCLUSIONS: Maladaptive personality disposition in patients with PD seems to have a trait character and shows little trend toward normalization after 12-weeks treatment with the antidepressant, while the association between impulsivity and treatment response needs further investigation.


Assuntos
Antidepressivos/uso terapêutico , Citalopram/uso terapêutico , Transtorno de Pânico/tratamento farmacológico , Transtorno de Pânico/psicologia , Transtornos da Personalidade/tratamento farmacológico , Transtornos da Personalidade/psicologia , Adulto , Antidepressivos/farmacologia , Citalopram/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/epidemiologia , Personalidade/efeitos dos fármacos , Transtornos da Personalidade/epidemiologia , Inventário de Personalidade , Suécia/epidemiologia , Resultado do Tratamento
9.
World J Biol Psychiatry ; 18(3): 162-214, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27419272

RESUMO

OBJECTIVE: Biomarkers are defined as anatomical, biochemical or physiological traits that are specific to certain disorders or syndromes. The objective of this paper is to summarise the current knowledge of biomarkers for anxiety disorders, obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD). METHODS: Findings in biomarker research were reviewed by a task force of international experts in the field, consisting of members of the World Federation of Societies for Biological Psychiatry Task Force on Biological Markers and of the European College of Neuropsychopharmacology Anxiety Disorders Research Network. RESULTS: The present article (Part II) summarises findings on potential biomarkers in neurochemistry (neurotransmitters such as serotonin, norepinephrine, dopamine or GABA, neuropeptides such as cholecystokinin, neurokinins, atrial natriuretic peptide, or oxytocin, the HPA axis, neurotrophic factors such as NGF and BDNF, immunology and CO2 hypersensitivity), neurophysiology (EEG, heart rate variability) and neurocognition. The accompanying paper (Part I) focuses on neuroimaging and genetics. CONCLUSIONS: Although at present, none of the putative biomarkers is sufficient and specific as a diagnostic tool, an abundance of high quality research has accumulated that should improve our understanding of the neurobiological causes of anxiety disorders, OCD and PTSD.


Assuntos
Transtornos de Ansiedade/diagnóstico , Biomarcadores , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Comitês Consultivos , Psiquiatria Biológica , Consenso , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sociedades Médicas
10.
Schizophr Res ; 182: 31-41, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27746055

RESUMO

Our aim with the present study was to evaluate rank-order and mean-level cognitive functioning stability among first-episode psychosis (FEP) patients, measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB), over a six month period. We also aimed to examine longitudinal measurement invariance and identify factors-such as age, gender, educational level, treatment and psychopathological change scores-potentially linked to cognitive change among patients. In addition, correlations between objectively measured and subjectively evaluated cognitive functioning were estimated. Neuropsychological assessments were administered to 85 patients after the initial stabilisation of their psychosis; 82 of the patients were retested. Subjectively perceived cognitive functioning was measured using a subscale derived from the Estonian version of the Subjective Well-Being Under Neuroleptic Scale (SWN-K-E). On average, executive functioning and processing speed improved significantly, while memory test scores decreased significantly, over time. Very high rank-order stability (r=0.80 to 0.94, p<0.001) was observed with all measured ability scores. Confirmatory factor analysis revealed the loadings of a single (broad ability) factor model were equal across both measurement occasions, but the lack of intercept invariance suggested that mean-level comparisons are more appropriately carried out at a subtest level. On average psychopathology scores and antipsychotics doses declined over time, with the latter also significantly correlating with better executive functioning. Gender was a significant moderator of some domains of cognitive performance, and decline tended to be somewhat more pronounced for women. The results also indicated the lack of any relationship between objective and subjective measurements of cognitive functioning.


Assuntos
Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Transtornos Psicóticos/complicações , Adolescente , Adulto , Análise Fatorial , Feminino , Seguimentos , Humanos , Masculino , Memória de Curto Prazo , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Adulto Jovem
11.
World J Biol Psychiatry ; 17(5): 321-65, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27403679

RESUMO

OBJECTIVES: Biomarkers are defined as anatomical, biochemical or physiological traits that are specific to certain disorders or syndromes. The objective of this paper is to summarise the current knowledge of biomarkers for anxiety disorders, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). METHODS: Findings in biomarker research were reviewed by a task force of international experts in the field, consisting of members of the World Federation of Societies for Biological Psychiatry Task Force on Biological Markers and of the European College of Neuropsychopharmacology Anxiety Disorders Research Network. RESULTS: The present article (Part I) summarises findings on potential biomarkers in neuroimaging studies, including structural brain morphology, functional magnetic resonance imaging and techniques for measuring metabolic changes, including positron emission tomography and others. Furthermore, this review reports on the clinical and molecular genetic findings of family, twin, linkage, association and genome-wide association studies. Part II of the review focuses on neurochemistry, neurophysiology and neurocognition. CONCLUSIONS: Although at present, none of the putative biomarkers is sufficient and specific as a diagnostic tool, an abundance of high-quality research has accumulated that will improve our understanding of the neurobiological causes of anxiety disorders, OCD and PTSD.


Assuntos
Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/genética , Neuroimagem , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/genética , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/genética , Transtornos de Ansiedade/terapia , Biomarcadores , Encéfalo/patologia , Terapia Combinada , Comorbidade , Humanos , Transtorno Obsessivo-Compulsivo/terapia , Fatores de Risco , Fatores Sexuais , Transtornos de Estresse Pós-Traumáticos/terapia
12.
Eur Neuropsychopharmacol ; 26(9): 1475-1483, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27461515

RESUMO

The reasons for variability in treatment response in major depressive disorder (MDD) are not fully understood, but there is accumulating evidence suggesting that therapeutic outcomes of antidepressants can be influenced by genetic factors. In the present study we applied the microarray Illumina platform for whole genome expression profiling in depressive patients treated with escitalopram medication in order to identify genes underlying response to antidepressant treatment. The initial study sample consisted of 135 outpatients with major depressive disorder (mean age 31.1±11.6 years, 68% females) treated with escitalopram 10-20mg/day for 12 weeks, from which 87 patients (55 females) were included in gene expression analyzing. The gene expression profiles were measured on peripheral blood cells at baseline, at week 4 and at the end of treatment (week 12) using BeadChips Illumina. The fold change was used to demonstrate rate of changes in average gene expressions between studied groups. Statistical analyses were performed using the false discovery rate (FDR). The most interesting gene, which showed the predictive effect on treatment outcome by delineating low dose responders and treatment-resistant patients at the beginning of medication, was NLGN2, belonging to a family of neuronal cell surface proteins and involving in synapse formation. In addition, the several gene clusters, related to immune response, signal transduction and neurotrophin pathway, have distinguished responders from non-responders at the week 4 of treatment. After 4 weeks of escitalopram treatment (10mg/day), the YWHAZ gene has showed the highest transcriptional change in responders as compared with non-responders. Finally, at the end of the treatment we noticed that at least three genes (NR2C2, ZNF641, FKBP1A) have been strongly associated with resistance to escitalopram. Thus the results of this study support that exploration of peripheral gene expression is a useful tool in the further identification of novel genetic biomarkers for antidepressant treatment response.


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Citalopram/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Adulto , Feminino , Perfilação da Expressão Gênica , Genoma , Humanos , Masculino , Análise em Microsséries , Escalas de Graduação Psiquiátrica , Receptores de Esteroides/genética , Receptores dos Hormônios Tireóideos/genética , Proteínas de Ligação a Tacrolimo/genética , Transativadores/genética , Resultado do Tratamento
14.
J Psychopharmacol ; 30(1): 33-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26645207

RESUMO

Recent functional magnetic resonance (fMRI) imaging studies have revealed that subchronic medication with escitalopram leads to significant reduction in both amygdala and medial frontal gyrus reactivity during processing of emotional faces, suggesting that escitalopram may have a distinguishable modulatory effect on neural activation as compared with other serotonin-selective antidepressants. In this fMRI study we aimed to explore whether short-term medication with escitalopram in healthy volunteers is associated with reduced neural response to emotional processing, and whether this effect is predicted by drug plasma concentration. The neural response to fearful and happy faces was measured before and on day 7 of treatment with escitalopram (10mg) in 15 healthy volunteers and compared with those in a control unmedicated group (n=14). Significantly reduced activation to fearful, but not to happy facial expressions was observed in the bilateral amygdala, cingulate and right medial frontal gyrus following escitalopram medication. This effect was not correlated with plasma drug concentration. In accordance with previous data, we showed that escitalopram exerts its rapid direct effect on emotional processing via attenuation of neural activation in pathways involving medial frontal gyrus and amygdala, an effect that seems to be distinguishable from that of other SSRIs.


Assuntos
Citalopram/farmacologia , Emoções/efeitos dos fármacos , Imagem por Ressonância Magnética/métodos , Inibidores de Captação de Serotonina/farmacologia , Adulto , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Citalopram/administração & dosagem , Expressão Facial , Feminino , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/metabolismo , Humanos , Masculino , Adulto Jovem
15.
Dialogues Clin Neurosci ; 17(3): 305-17, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26487811

RESUMO

At least one third of patients with anxiety disorders do not adequately respond to available pharmacological treatment. The reason that some patients with anxiety disorders respond well, but others not, to the same classes of medication is not yet fully understood. It is suggested that several biological factors may influence treatment mechanisms in anxiety and therefore could be identified as possible biomarkers predicting treatment response. In this review, we look at current evidence exploring different types of treatment predictors, including neuroimaging, genetic factors, and blood-related measures, which could open up novel perspectives in clinical management of patients with anxiety disorders.


Assuntos
Ansiolíticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/fisiopatologia , Biomarcadores , Transtornos de Ansiedade/sangue , Transtornos de Ansiedade/genética , Biomarcadores/sangue , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Humanos , Neuroimagem , Valor Preditivo dos Testes
16.
Brain Behav ; 5(4): e00314, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25798331

RESUMO

BACKGROUND: The immune system has been increasingly implicated in the development of mood and anxiety disorders. Inhibitor of kappa light polypeptide gene enhancer in B cells, kinase epsilon (IKBKE) gene encodes IKKε protein that is involved in innate immunity, predominantly antiviral response generation. It also bears pro-inflammatory properties that could affect psychiatric outcomes. In order to investigate the possible role of IKBKE gene in major depressive disorder (MDD) and panic disorder (PD), we conducted a case-control genetic association study concerning these disorders. METHODS: In all, 14 SNPs of IKBKE gene were genotyped in groups of 391 patients with MDD and 190 patients with PD together with respective 389 and 371 healthy control individuals. The given groups were further divided by gender for additional analyses. RESULTS: Substantial genetic associations were revealed between IKBKE SNPs and MDD (multiple testing adjusted P < 0.05) and suggestive associations in case of PD (P(adj) > 0.05). In addition, two SNPs that were only associated with PD among males, also displayed significantly different allele frequencies compared to PD females. This may indicate a specific role of these SNPs in male PD, but caution should be applied here due to the small size of the studied PD males group. CONCLUSIONS: The results of this study confirm our initial findings and indicate a possible role of IKBKE gene in mood and anxiety disorders.


Assuntos
Transtorno Depressivo Maior/genética , Quinase I-kappa B/genética , Transtorno de Pânico/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Adulto Jovem
17.
Ann Gen Psychiatry ; 12(1): 28, 2013 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-24025191

RESUMO

BACKGROUND: The Subjective Well-Being Under Neuroleptic Treatment Scale short form (SWN-K) is a self-rating scale developed to measure mentally ill patients' well-being under the antipsychotic drug treatment. This paper reports on adaptation and psychometric properties of the instrument in an Estonian psychiatric sample. METHODS: In a naturalistic study design, 124 inpatients or outpatients suffering from the first psychotic episode or chronic psychotic illness completed the translated SWN-K instrument. Item content analysis, internal consistency analysis, exploratory principal components analysis, and confirmatory factor analysis were used to construct the Estonian version of the SWN-K (SWN-K-E). Additionally, socio-demographic and clinical data, observer-rated psychopathology, medication side effects, daily antipsychotic drug dosages, and general functioning were assessed at two time points, at baseline and after a 29-week period; the associations of the SWN-K-E scores with these variables were explored. RESULTS: After having selected 20 items for the Estonian adaptation, the internal consistency of the total SWN-K-E was 0.93 and the subscale consistencies ranged from 0.70 to 0.80. Good test-retest reliabilities were observed for the adapted scale scores, with the correlation of the total score over about 6 months being r = 0.70. Confirmatory factor analysis replicated the presence of a higher-order factor (general well-being) and five first-order factors (mental functioning, physical functioning, social integration, emotional regulation, and self-control); the model fitted the data well. The results indicated a moderate-high correlations r = 0.54 between the SWN-K-E total score and the evaluation how satisfied patients were with their lives in generally. No significant correlations were found between the overall subjective well-being score and age, severity of the psychopathology, drug adverse effects, or prescribed drug dosage. CONCLUSION: Taken together, the results demonstrated that the Estonian version of the SWN-K is a reliable and valid instrument with psychometric properties similar to the original English version. The potential uses of the scale in both research and clinical settings are considered.

18.
J Psychopharmacol ; 27(10): 915-20, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23926243

RESUMO

Although antidepressants are widely used in the pharmacotherapy of major depressive disorder (MDD), their efficacy is still insufficient as approximately one-third of the patients do not fully recover even after several treatment trials. Inter-individual genetic differences are thought to contribute to the variability in antidepressant response; however, current findings from pharmacogenetic studies are uncertain or not clearly replicated. Here we report the first application of full exome sequencing for the analysis of pharmacogenomics on antidepressant treatment. After 12 weeks of treatment with the selective serotonin re-uptake inhibitor escitalopram, we selected five clear responders and five clear non-responders for exome sequencing. By comparing the allele counts of previously known single nucleotide polymorphisms and novel polymorphisms we selected 38 markers for further genotyping in two independent patient samples treated with escitalopram (n=116 and n=394). The A allele, carried by approximately 30% of the patients with MDD, of rs41271330 in the bone morphogenetic protein (BMP5) gene showed strong association with worse treatment response in both sample sets (p=0.001), indicating that this is an promising pharmacogenetic marker for prediction of antidepressant therapeutic outcome.


Assuntos
Proteína Morfogenética Óssea 5/genética , Citalopram/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Exoma/genética , Adulto , Alelos , Feminino , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Análise de Sequência de DNA , Inibidores de Captação de Serotonina/uso terapêutico , Resultado do Tratamento
19.
NMR Biomed ; 26(11): 1353-62, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23696182

RESUMO

Short-TE MRS has been proposed recently as a method for the in vivo detection and quantification of γ-aminobutyric acid (GABA) in the human brain at 3 T. In this study, we investigated the accuracy and reproducibility of short-TE MRS measurements of GABA at 3 T using both simulations and experiments. LCModel analysis was performed on a large number of simulated spectra with known metabolite input concentrations. Simulated spectra were generated using a range of spectral linewidths and signal-to-noise ratios to investigate the effect of varying experimental conditions, and analyses were performed using two different baseline models to investigate the effect of an inaccurate baseline model on GABA quantification. The results of these analyses indicated that, under experimental conditions corresponding to those typically observed in the occipital cortex, GABA concentration estimates are reproducible (mean reproducibility error, <20%), even when an incorrect baseline model is used. However, simulations indicate that the accuracy of GABA concentration estimates depends strongly on the experimental conditions (linewidth and signal-to-noise ratio). In addition to simulations, in vivo GABA measurements were performed using both spectral editing and short-TE MRS in the occipital cortex of 14 healthy volunteers. Short-TE MRS measurements of GABA exhibited a significant positive correlation with edited GABA measurements (R = 0.58, p < 0.05), suggesting that short-TE measurements of GABA correspond well with measurements made using spectral editing techniques. Finally, within-session reproducibility was assessed in the same 14 subjects using four consecutive short-TE GABA measurements in the occipital cortex. Across all subjects, the average coefficient of variation of these four GABA measurements was 8.7 ± 4.9%. This study demonstrates that, under some experimental conditions, short-TE MRS can be employed for the reproducible detection of GABA at 3 T, but that the technique should be used with caution, as the results are dependent on the experimental conditions.


Assuntos
Espectroscopia de Ressonância Magnética , Lobo Occipital/metabolismo , Ácido gama-Aminobutírico/metabolismo , Simulação por Computador , Creatinina/metabolismo , Feminino , Humanos , Lipídeos/análise , Substâncias Macromoleculares/análise , Masculino , Metaboloma , Reprodutibilidade dos Testes , Marcadores de Spin , Fatores de Tempo , Adulto Jovem
20.
Artigo em Inglês | MEDLINE | ID: mdl-25225016

RESUMO

Presently available clinical genetic studies point to a considerable heritability of anxiety disorders (30-67%), with multiple vulnerability genes such as 5-HT1A, 5-HTT, MAO-A, COMT, CCK-B, ADORA2A, CRHR1, FKBP5, ACE, RGS2/7 and NPSR1 suggested by molecular genetic association studies. These genes have been shown to partially interact with each other as well as with environmental factors to shape the overall disease risk in a complex genetic model. Additionally, recent studies have pointed out the crucial role of epigenetic signatures such as methylation patterns in modifying environmental influences as well as in driving the functional impact of anxiety disorder risk genes. On a systems level, vulnerability genes of anxiety disorders seem to confer some of the disease risk via intermediate phenotypes like behavioral inhibition, anxiety sensitivity or several neurobiological traits such as increased startle reactivity or dysfunctional corticolimbic activity during emotional processing. Finally, first pharmaco- and psychotherapy-genetic studies provide evidence for certain risk genes to confer interindividual variability in response to a pharmacological or psychotherapeutic intervention in anxiety disorders. Genetic research in anxiety disorders will be discussed regarding its potential to foster innovative and individually tailored therapeutic approaches for patients with anxiety disorders.


Assuntos
Transtornos de Ansiedade/genética , Ligação Genética , Predisposição Genética para Doença/genética , Antiarrítmicos/uso terapêutico , Transtornos de Ansiedade/etiologia , Transtornos de Ansiedade/terapia , Interação Gene-Ambiente , Humanos , Psicoterapia/métodos , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...