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Background: Cognitive impairment has been reported in patients with Major Depressive Disorder (MDD). This study aims to explore the association between lifestyle habits and health-related factors and the presence of cognitive symptoms in MDD patients. Methods: Demographic, clinical, health-related variables and cognitive scores measured with the Cambridge Neuropsychological Test Automated Battery (CANTAB) were compared between 74 patients with current MDD and 68 healthy controls (HC). To test the hypothesis of associated factors to cognitive symptoms, multivariate backward stepwise linear regression models were run. Results: Significant neuropsychological deficits were evident in MDD compared with HC in the global cognitive index (F=8.29; df=1, 140; p=0.005). In the regression analysis performed on MDD and HC, years of schooling (β=-0.11; p=

Major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) have both been linked to abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. Polymorphisms in the genes involved in HPA axis activity, such as FKBP5, and their interactions with childhood trauma have been associated with stress-related mental disorders. Our goal was to study the role of FKBP5 genetic variants in HPA axis negative feedback regulation as a possible risk factor for different mental disorders such as MDD and OCD, while controlling for childhood trauma, anxiety and depressive symptoms. The sample included 266 participants divided into three groups: 1) MDD (n = 89 [n = 73 melancholic; n = 3 atypical]), 2) OCD (n = 51; 39% with comorbid MDD [n = 13 melancholic; n = 7 atypical]) and 3) healthy controls (n = 126). Childhood trauma, trait anxiety and depressive symptoms were assessed. HPA negative feedback was analyzed using the dexamethasone suppression test ratio (DSTR) after administration of 0.25 mg of dexamethasone. Twelve SNPs in the FKBP5 gene were selected for genotyping. Multiple linear regressions, after adjusting for the covariates considered, showed a reduced DSTR in individuals with the rs9470079-A variant that was significant after correction for multiple testing. Childhood trauma did not moderate the association between the rs9470079 and DSTR. Our results support the evidence that FKBP5 genetic variation could lead to abnormal HPA axis negative feedback independent of diagnosis. Therefore, this association can be identified as a transdiagnostic feature, offering an interesting opportunity to identify patients with higher stress vulnerability. Further studies focusing on the influence of FKBP5 on measurable biological endophenotypes are needed.

Background Early improvement to antidepressant drugs predicts remission, but the predictive value of early improvement to electroconvulsive therapy (ECT) is still unclear. The main aim of this study was to determine the optimal definition of early improvement in the treatment of major depressive disorder (MDD) with ECT, by analyzing its value as a predictor of remission. Methods A naturalistic study was conducted in 87 adult MDD patients treated with acute ECT. ROC curves were generated to identify the best time point (week 1 or 2 of treatment) predicted remission. Sensibility, specificity, and predictive values were calculated for several definitions of early improvement previously proposed in the literature (20%, 25%, 30%, and 35%). Complementary, time to remission was analyzed and a logistic regression model was performed to further characterize the impact of the optimal definition of early improvement on remission while adjusting for other clinically relevant variables. Results A 30% reduction in the HAM-D score after 2 weeks was identified as the optimal definition of early improvement, with acceptable sensitivity (76%), and specificity (67%). Complementary analyses provided further support for this definition showing a shorter time to remission and a significant effect adjusted for the rest of variables. Limitations Relatively small sample size, ECT restricted to brief bilateral treatment. Conclusions Early improvement, defined as a 30% of reduction in the HAM-D21 score at week 2, is a good predictor of remission in MDD patients treated with bilateral ECT, with potential clinical impact. Lack of early improvement could indicate a need for further changes in treatment strategies.

Major depressive disorder (MDD) is the most common psychiatric comorbidity in patients with obsessive–compulsive disorder (OCD). Hypothalamic-pituitary-adrenal (HPA) axis abnormalities have been described in both disorders and might play a role in the association between them. We aimed to study the role of HPA axis activity in the comorbidity between OCD and MDD, while controlling for psychopathological dimensions such as anxiety and depressive symptoms. We studied 324 participants belonging to four diagnostic groups: 1) MDD (n = 101), 2) OCD with comorbid MDD (n = 33), 3) OCD without MDD (n = 52), and 4) healthy subjects (n = 138). State anxiety, trait anxiety and depressive symptoms were assessed. Three HPA axis measures were analyzed in saliva: cortisol awakening response (CAR), diurnal cortisol slope (calculated using two formulas: [1] awakening to 11 p.m. [AWE diurnal slope]; [2] considering fixed time points [FTP diurnal slope] from 10 a.m. to 11 p.m.), and dexamethasone suppression test ratio after 0.25 mg of dexamethasone (DSTR). Multiple linear regression analyses were conducted to explore the contribution of clinical diagnosis and symptom dimensions to each HPA axis measure. A more flattened FTP diurnal cortisol slope was observed for OCD patients with comorbid MDD. Regarding the CAR and DSTR, a significant interaction was found between trait anxiety and OCD, as OCD patients with greater trait anxiety showed an increased CAR and reduced cortisol suppression after dexamethasone administration. Our results suggest that trait anxiety plays an important role in the relationship between HPA axis measures and OCD/MDD comorbidity.

Background Hyperventilation has been proposed as an augmentation strategy in electroconvulsive therapy (ECT) in accordance with its proconvulsant effect. Objective This study reviews the existing literature on the application of hyperventilation in ECT, its efficacy, and tolerance. Methods A systematic search was performed in PubMed and EMBASE databases. Search terms (‘electroconvulsive therapy’ and ‘hyperventilation’, ‘ventilation’, ‘hyperoxygenation’, ‘hyperoxia’, ‘hypocapnia’) were used to retrieve works from 1966 to June 2016. Works that described hyperventilation manoeuvres in ECT settings and their clinical repercussion were included in the review. Results A total of 17 observational and experimental studies were selected. An important heterogeneity in study designs, samples and ECT conditions, was detected. Findings support a positive influence of hyperventilation on seizure duration, which is the main study variable across different works. Effects of hyperventilation on seizure threshold and quality parameters have been less thoroughly studied. Systematic recording of clinical outcomes and adverse effects of hyperventilation is uncommon. Conclusions The literature suggests that hyperventilation may be an effective and safe technique to enhance ECT, but many aspects remain to be studied. Further investigations, especially controlled clinical trials, are necessary and should result in a specific and reliable hyperventilation protocol for ECT settings.

Background Hyperventilation is recommended in electroconvulsive therapy (ECT) to enhance seizures and to increase patients’ safety. However, more evidence is needed regarding its effects and the optimum method of application. Methods This prospective study involving 21 subjects compared two procedures, protocolized hyperventilation (PHV) and hyperventilation as usual (HVau), applied to the same patient in two consecutive sessions. Transcutaneous partial pressure of carbon dioxide (TcPCO2) was measured throughout all sessions. Ventilation parameters, hemodynamic measures, seizure characteristics, and side effects were also explored. Results PHV resulted in lower TcPCO2 after hyperventilation (p=.008) and over the whole session (p=.035). The lowest TcPCO2 was achieved after voluntary hyperventilation. Changes in TcPCO2 from baseline showed differences between HVau and PHV at each session time-point (all p s factors were statistically significant in a general linear model. Seizure duration was greater in PHV sessions (p=.028), without differences in other seizure quality parameters or adverse effects. Correlations were found between hypocapnia induction and seizure quality indexes. Limitations Secondary outcomes could be underpowered. Conclusions PHV produces hypocapnia before the stimulus, modifies patients’ TcPCO2 values throughout the ECT session and lengthens seizure duration. Voluntary hyperventilation is the most important part of the PHV procedure with respect to achieving hypocapnia. A specific ventilation approach, CO2 quantification and monitoring may be advisable in ECT. PHV is easy to apply in daily clinical practice and does not imply added costs. Ventilation management has promising effects in terms of optimizing ECT technique.

Resumen Introduccion La hiperventilacion en las sesiones de terapia electroconvulsiva se ha relacionado con el umbral convulsivo, las caracteristicas de la convulsion y los efectos cognitivos. No existe consenso sobre el procedimiento optimo de aplicacion de las maniobras de hiperventilacion durante la terapia electroconvulsiva. Material y metodos Evaluacion prospectiva de los efectos del uso sistematizado de maniobras de hiperventilacion con mascarilla facial y capnografia (hiperventilacion reglada [HVr]) en los parametros ventilatorios y de la convulsion. Muestra de 130 sesiones (65 realizadas con hiperventilacion segun la practica habitual y 65 sucesivas con HVr) de 35 pacientes en un periodo de 10 semanas. Resultados Las maniobras de HVr disminuyeron el CO2 espirado e incrementaron la saturacion de O2 significativamente (p Conclusiones Las maniobras de HVr propuestas modifican de forma relevante los parametros ventilatorios. La hipocapnia y la hiperoxia obtenidas al aplicar estas maniobras alargan la duracion de las convulsiones sin empeorar la calidad del trazado electroencefalografico. El uso de protocolos de HVr es generalizable y puede mejorar el procedimiento de la terapia electroconvulsiva sin anadir costes.

BACKGROUND: Although current models of depression suggest that a sequential modulation of limbic and prefrontal connectivity is needed for illness recovery, neuroimaging studies of electroconvulsive therapy (ECT) have focused on assessing functional connectivity (FC) before and after an ECT course, without characterizing functional changes occurring at early treatment phases. OBJECTIVE: To assess sequential changes in limbic and prefrontal FC during the course of ECT and their impact on clinical response. METHODS: Longitudinal intralimbic and limbic-prefrontal networks connectivity study. We assessed 15 patients with treatment-resistant depression at four different time-points throughout the entire course of an ECT protocol and 10 healthy participants at two functional neuroimaging examinations. Furthermore, a path analysis to test direct and indirect predictive effects of limbic and prefrontal FC changes on clinical response measured with the Hamilton Rating Scale for Depression was also performed. RESULTS: An early significant intralimbic FC decrease significantly predicted a later increase in limbic-prefrontal FC, which in turn significantly predicted clinical improvement at the end of an ECT course. CONCLUSIONS: Our data support that treatment response involves sequential changes in FC within regions of the intralimbic and limbic-prefrontal networks. This approach may help in identifying potential early biomarkers of treatment response.