Investigating the Role of Leukocyte Telomere Length in Treatment-Resistant Depression and in Response to Electroconvulsive Therapy.

Psychiatric disorders seem to be characterized by premature cell senescence. However, controversial results have also been reported. In addition, the relationship between accelerated aging and treatment-resistance has scarcely been investigated. In the current study, we measured leukocyte telomere length (LTL) in 148 patients with treatment-resistant depression (TRD, 125 with major depressive disorder, MDD, and 23 with bipolar disorder, BD) treated with electroconvulsive therapy (ECT) and analyzed whether LTL was associated with different response profiles. We also compared LTL between patients with TRD and 335 non-psychiatric controls. For 107 patients for which genome-wide association data were available, we evaluated whether a significant overlap among genetic variants or genes associated with LTL and with response to ECT could be observed. LTL was negatively correlated with age (Spearman's correlation coefficient = -0.25, p < 0.0001) and significantly shorter in patients with treatment-resistant MDD (Quade's F = 35.18, p < 0.0001) or BD (Quade's F = 20.84, p < 0.0001) compared to controls. Conversely, baseline LTL was not associated with response to ECT or remission. We did not detect any significant overlap between genetic variants or genes associated with LTL and response to ECT. Our results support previous findings suggesting premature cell senescence in patients with severe psychiatric disorders and suggest that LTL could not be a predictive biomarker of response to ECT.

Genetic determinants of circulating VEGF levels in major depressive disorder and electroconvulsive therapy response.

Alterations in peripheral vascular endothelial growth factor (VEGF) levels were observed in major depressive disorder and relative treatments and were shown to be influenced by genetic variants. The study objective was to explore, at a genome-wide level, possible interplaying effects between the genetic background and major depressive disorder in regulating VEGF levels. Moreover, we aimed to investigate the association between these variants and response to electroconvulsive therapy. A genome-wide association study was carried out both on controls and patients with major depressive disorder (n = 145; n = 121) in correlation with serum VEGF levels determined by ELISA. Five SNPs not included in SNP arrays were additionally genotyped. Seventy-one patients with treatment-resistant depression underwent electroconvulsive therapy and were evaluated as responders/nonresponders. An association between VEGF levels and a locus in 6p21.1, downstream the VEGF gene, was evidenced both in controls (best SNP: FDR-corrected p = 2.4 × 10-5 ) and in patients with major depressive disorder (best SNP: FDR-corrected p = 2.6 × 10-3 ). The alleles associated with lower VEGF concentrations in patients were also associated with nonresponse to electroconvulsive therapy (p = .01). These results confirm a role of SNPs in 6p21.1 locus as major influencers of circulating VEGF levels also in patients affected by major depressive disorder and indicate a possible implication in response to electroconvulsive therapy.

Seizure Adequacy Markers and the Prediction of Electroconvulsive Therapy Response.

OBJECTIVES: Electroconvulsive therapy (ECT) is the most effective therapy for patients with treatment-resistant depression; however, some patients do not respond or relapse in a short time. Electroconvulsive therapy stimulus parameters may be related to the outcome. We carried out a retrospective study review to investigate various ECT parameters in relation to the outcome, clinical variables, and pharmacological treatments. Our aim was to understand which factors could be considered putative seizure quality markers and which are relevant to clinical practice. METHODS: Two physicians evaluated the seizure length, the postictal suppression index, the wave amplitude, tachycardia, and hemispheric brain wave synchronicity in a double-blind manner for 45 treatment-resistant depression patients receiving ECT. RESULTS: The analysis showed a significant association between the outcome and the ECT seizure quality measured by the parameters (P = 9.9 × 10). Among patients with poor-quality seizures, 61.5% relapsed after approximately 1 month from the last ECT session. Particularly, there was an association between higher symptomatology decrease and higher quality of hemispheric brain wave synchronicity (P = 5.0 × 10), as well as a higher wave amplitude (P = 0.01). CONCLUSIONS: Our results confirm that ECT seizure quality was strongly correlated with the decrease of depressive symptomatology.

The role of the potassium channel gene KCNK2 in major depressive disorder.

Six single nucleotide polymorphisms (SNPs) of the KCNK2 gene were investigated for their association with major depressive disorder (MDD) and treatment efficacy in 590 MDD patients and 441 controls. The A homozygotes of rs10779646 were significantly more frequent in patients than controls whereas G allele of rs7549184 was associated with the presence of psychotic symptoms and the severity of disease. Evaluating the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) dataset, we confirmed our findings.