Personality traits and escitalopram treatment outcome in major depression.

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.

Whole-genome expression analysis reveals genes associated with treatment response to escitalopram in major depression.

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.

Polymorphisms of IKBKE gene are associated with major depressive disorder and panic disorder.

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.

Whole-exome sequencing identifies a polymorphism in the BMP5 gene associated with SSRI treatment response in major depression.

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.

Obstructive sleep apnea syndrome (OSAS): Pathophysiology in Estonians.

The aim of the study was to clarify the roles of age, obesity, smoking, alcohol, pathoanatomy and -physiology in Estonian's OSAS. For this 164 randomly chosen such patients were selected in different regions of Estonia. They underwent naso-oropharyngeal examination, physical examination of craniofacial abnormalities, and polysomnography. They also completed a self-reported questionnaire about smoking, alcohol use, excessive daytime sleepiness, hypertension, cardiac disorders, headaches, concentration disorders, and recurrent upper-airway diseases. The patients (129 men; 35 women) aged between 19 and 75 years (mean 47+/-12), BMI between 21 and 49 (mean 30.5+/-5.15), AHI between 5 and 105 (33+/-22). The results showed that there was a high percentage of naso-oropharyngeal disorders, such as: recurrent upper-airway diseases (54.2%), nasal breathing disorders (63.5%), and hypertrophy of tonsils (57%). There was also a high percentage of general characteristics, such as alcohol use (64%), excessive daytime sleepiness (85.5%), overweight (63%), and hypertension (51.2%). The regression summary for the dependent variable AHI if p-level=0.0042 (R=0.63347013) included age, BMI, hypertension, cardiac disorders, headaches, nasal obstruction, hypertrophy of pharyngeal muscles, tongue level, submental fat and slow-wave sleep (S3+S4%). In conclusion recurrent upper-airway diseases, nasal obstruction, and hypertrophy of tonsils in combination with smoking and alcohol caused the changes in the pharyngeal and lingual muscles. The latter gives rise to such sleep apnea-related problems as heart complaints, hypertension, headache and shortage of slow-wave sleep (SWS).

Thyroid autoimmunity and treatment response to escitalopram in major depression.

BACKGROUND: There is evidence that immune alterations play an important part in the pathogenesis of major depression. Thyroid autoimmunity has been found in association with major depression in several studies. AIM: 1) to examine whether the prevalence of anti-thyroid peroxidase autoantibodies (anti-TPO) in depressive patients differs from that in healthy controls; 2) to investigate the possible relationship between thyroid autoimmunity, total T3, free T3, free T4, thyroid-stimulating hormone (TSH), clinical status and treatment outcome in depression. METHOD: The study group consisted of 129 outpatients (69.8% female; mean age 31.7+/-12.0 years) with major depressive disorder with a Montgomery-Azsberg Depression Rating Scale total score of 22 or higher and 72 healthy controls (62.5% female; mean age 31.7+/-13.1 years). The patients were treated with escitalopram 10-20 mg/day for 12 weeks using open-label placebo non-controlled design. Anti-TPO, total T3, free T3, free T4 and TSH were measured before the treatment. RESULTS: The anti-TPO was found in eight (8.9%) depressive and two (4.8%) healthy females without statistical difference between these groups. Since anti-TPO was not seen in males, all further statistical analyses were carried out in females. At the end of week 12 of the treatment, 60 female patients (66.7%) were defined as responders and 30 depressive females (33.3%) showed insufficient response to treatment. Although there were no significant differences in the measurements between responders and non-responders, the last group showed a trend for a higher prevalence of anti-TPO compared with responders. CONCLUSION: Thyroid autoimmunity might be a factor predicting treatment response to antidepressants in depressive patients.

Interleukin 10 family gene polymorphisms are not associated with major depressive disorder and panic disorder phenotypes.

Genetic regulation of immune system and inflammatory response may be related to the pathogenesis and manifestations of mood and anxiety disorders. In the present study we examined a range of single-nucleotide polymorphisms (SNP) in chromosomal region 1q32, the locus of interleukin 10 (IL10) gene, in patients with major depressive disorder (n=312) and panic disorder (n=210), and matched healthy controls (n=356). We found no significant associations of the SNPs in IL10 family genes with either diagnostic group. Haplotype analysis revealed seven haplotype blocks, but their frequencies did not differ between patients and controls. Significant associations were detected for SNP rs1539243 in IKBKE (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon) gene showing different allelic and genotypic distributions in the total as well as in separate diagnostic groups as compared to controls. IKBKE emerged as a candidate for further studies of genetic factors associated with panic disorder and major depressive disorder.

The role of IL-2 and soluble IL-2R in depression and antidepressant response.

Cytokines are widely studied in the context of the pathogenesis and treatment of major depression. This review focuses on the potential importance of IL-2 and soluble IL-2R in major depression, as well as on their role in the mediation of the effects of antidepressant treatment. In general, there has been no consistent pattern in the associations observed between cytokine concentration, or changes thereof, and clinical indices of major depression. One intriguing question is whether pretreatment levels of immune system markers, such as IL-2R alpha, can be used to predict responses to antidepressant treatment. Based on the currently available data, this issue remains unresolved. This review also highlights certain methodological problems pertaining to the measurement of IL-2 and IL-2R in the context of depression and presents ideas for further research in this field.

Serotonin transporter promoter region polymorphisms do not influence treatment response to escitalopram in patients with major depression.

Several studies and meta-analyses have implicated a polymorphism in the promoter region of the serotonin transporter (5-HTT) gene, 5-HTTLPR in treatment outcomes of selective serotonin re-uptake inhibitors in patients with major depression. In this study we investigated the impact of 5-HTTLPR and a functional SNP rs25531 on the treatment outcomes to escitalopram in depressive patients. The study sample consisted of 135 outpatients with major depressive disorder (mean age 31.1+/-11.6 years, 68% females) treated with escitalopram 10-20 mg/day for 12 weeks. There were no significant associations between 5-HTT promoter region polymorphisms and response rate or mean change of depressive symptoms during escitalopram treatment. However we showed that patients carrying S allele of 5-HTTLPR may have increased risk for some side effects, including headache, induced by escitalopram medication.