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.

Role of allelic variants of FK506-binding protein 51 (FKBP5) gene in the development of anxiety disorders.

BACKGROUND: Anxiety disorders exhibit remarkably high rates of comorbidity with major depressive disorder (MDD). Mood and anxiety disorders are considered stress-related diseases. Genetic variations in the co-chaperone FK506-binding protein 51, FKBP5, which modulates the function of glucocorticoid receptors, have been associated with an increased risk for the development of posttraumatic stress disorder, but data regarding its role in MDD are controversial. The aims of this study were to clarify the role of the FKBP5 gene in depression and anxiety disorders through a case-control study and an association study with personality traits using the Temperament and Character Inventory (TCI) in healthy subjects. METHODS: Six hundred fifty-seven MDD patients, with or without an anxiety disorder in comorbidity, and 462 healthy volunteers were enrolled in the study. Two hundred fifty-six controls agreed to fill out the TCI. RESULTS: The results showed that the T allele of rs1360780 was more frequent among the patients affected by MDD with a comorbidity of anxiety disorders, compared to those without (P < .001). Among the controls, we found that the T allele more often exhibited personality traits associated with an increased vulnerability to anxiety. CONCLUSIONS: These results support the hypothesis that allelic variants of FKBP5 are a risk factor for anxiety disorders. The identification of genetic variants involved in anxiety may have implications for the optimization of therapeutic interventions.

Serotonin transporter gene polymorphisms and treatment-resistant depression.

Major Depression Disorder (MDD) is a serious mental illness that is one of the most disabling diseases worldwide. In addition, approximately 15% of depression patients are defined treatment-resistant (TRD). Preclinical and genetic studies show that serotonin modulation dysfunction exists in patients with TRD. Some polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4) are likely to be involved in the pathogenesis/treatment of MDD; however, no data are available concerning TRD. Therefore, in order to investigate the possible influence of SLC6A4 polymorphisms on the risk of TRD, we genotyped 310 DSM-IV MDD treatment-resistant patients and 284 healthy volunteers. We analysed the most studied polymorphism 5-HTTLPR (L/S) and a single nucleotide substitution, rs25531 (A/G), in relation to different functional haplotype combinations. However the correct mapping of rs25531 is still debated whether it is within or outside the insertion. Our sequencing analysis showed that rs25531 is immediately outside of the 5-HTTLPR segment. Differences in 5-HTTLPR allele (p=0.04) and in L allele carriers (p<0.05) were observed between the two groups. Concerning the estimated haplotype analyses, L(A)L(A) homozygote haplotype was more represented among the control subjects (p=0.01, OR=0.64 95%CI: 0.45-0.91). In conclusion, this study reports a protective effect of the L(A)L(A) haplotype on TRD, supporting the hypothesis that lower serotonin transporter transcription alleles are correlated to a common resistant depression mechanism.

Electroconvulsive Therapy (ECT) increases serum Brain Derived Neurotrophic Factor (BDNF) in drug resistant depressed patients.

Several findings have suggested that the neurotrophin BDNF could contribute to clinical efficacy of antidepressant treatments. The purpose of this study was to analyse if ECT operates a modulation of serum BDNF levels in a sample of drug resistant depressed patients. The results obtained show significantly higher serum levels of BDNF following ECT. More specifically, while no change occurred in the whole sample between T0 (baseline) and T1 (after ECT) (p=0.543) a significant increase has been identified at T2, one month after the end of ECT (p=0.002). However, the BDNF augmentation was evident even between T0 and T1 in a subgroup of patients who has low baseline BDNF levels. Although future researches are needed, the results herein presented show for the first time that ECT is associated with changes in serum BDNF and further support the possible involvement of BDNF in antidepressant therapies.