Importance of immunometabolic markers for the classification of patients with major depressive disorder using machine learning.

BACKGROUND: Although there is scientific evidence of the presence of immunometabolic alterations in major depression, not all patients present them. Recent studies point to the association between an inflammatory phenotype and certain clinical symptoms in patients with depression. The objective of our study was to classify major depression disorder patients using supervised learning algorithms or machine learning, based on immunometabolic and oxidative stress biomarkers and lifestyle habits. METHODS: Taking into account a series of inflammatory and oxidative stress biomarkers (C-reactive protein (CRP), tumor necrosis factor (TNF), 4-hydroxynonenal (HNE) and glutathione), metabolic risk markers (blood pressure, waist circumference and glucose, triglyceride and cholesterol levels) and lifestyle habits of the participants (physical activity, smoking and alcohol consumption), a study was carried out using machine learning in a sample of 171 participants, 91 patients with depression (71.42% women, mean age = 50.64) and 80 healthy subjects (67.50% women, mean age = 49.12). The algorithm used was the support vector machine, performing cross validation, by which the subdivision of the sample in training (70%) and test (30%) was carried out in order to estimate the precision of the model. The prediction of belonging to the patient group (MDD patients versus control subjects), melancholic type (melancholic versus non-melancholic patients) or resistant depression group (treatment-resistant versus non-treatment-resistant) was based on the importance of each of the immunometabolic and lifestyle variables. RESULTS: With the application of the algorithm, controls versus patients, such as patients with melancholic symptoms versus non-melancholic symptoms, and resistant versus non-resistant symptoms in the test phase were optimally classified. The variables that showed greater importance, according to the results of the area under the ROC curve, for the discrimination between healthy subjects and patients with depression were current alcohol consumption (AUC = 0.62), TNF-α levels (AUC = 0.61), glutathione redox status (AUC = 0.60) and the performance of both moderate (AUC = 0.59) and vigorous physical exercise (AUC = 0.58). On the other hand, the most important variables for classifying melancholic patients in relation to lifestyle habits were past (AUC = 0.65) and current (AUC = 0.60) tobacco habit, as well as walking routinely (AUC = 0.59) and in relation to immunometabolic markers were the levels of CRP (AUC = 0.62) and glucose (AUC = 0.58). In the analysis of the importance of the variables for the classification of treatment-resistant patients versus non-resistant patients, the systolic blood pressure (SBP) variable was shown to be the most relevant (AUC = 0.67). Other immunometabolic variables were also among the most important such as TNF-α (AUC = 0.65) and waist circumference (AUC = 0.64). In this case, sex (AUC = 0.59) was also relevant along with alcohol (AUC = 0.58) and tobacco (AUC = 0.56) consumption. CONCLUSIONS: The results obtained in our study show that it is possible to predict the diagnosis of depression and its clinical typology from immunometabolic markers and lifestyle habits, using machine learning techniques. The use of this type of methodology could facilitate the identification of patients at risk of presenting depression and could be very useful for managing clinical heterogeneity.

The relationship between sex, personality traits, and the hypothalamic-pituitary-adrenocortical axis.

The aim of our study was to examine whether there are sex-based differences in the relationship between personality traits and hypothalamic-pituitary-adrenal (HPA) axis measures. A total of 106 healthy volunteers (56.6% women; age: 48.0 ± 15.8 years) were studied. The revised temperament and character inventory (TCI-R) and the Childhood Trauma Questionnaire (CTQ) were administered. HPA axis function was assessed using three dynamic measures: the cortisol awakening response (CAR), the diurnal cortisol slope, and the cortisol suppression ratio with 0.25 mg of dexamethasone (DSTR). Female sex was associated with an increased CAR and a more flattened diurnal cortisol slope, although a negative significant interaction between harm avoidance and female sex was found. Regarding the DSTR, perseverance was associated with increased cortisol suppression after dexamethasone; sex did not affect this association. Our study suggests that the relationship between specific personality traits (harm avoidance) and HPA axis measures (CAR, diurnal slope) differs according to sex.

Cultural adaptation to Spanish of the “Patient Satisfaction Survey” to assess satisfaction with electroconvulsive therapy (ECT).

The degree of satisfaction of patients and their relatives with electroconvulsive therapy (ECT) is considered an important treatment goal; however there is no scale in Spanish to quantify it. The aim of the study was to translate and adapt into Spanish the “Patient Satisfaction Survey” (PSS) for its use in patients and their relatives.

Adaptación cultural al español de laencuesta “Patient Satisfaction Survey”para valorar la satisfacción con laterapia electroconvulsiva (TEC) / Cultural adaptation to spanish of the “patient satisfaction survey” to assess satisfaction with electroconvulsive therapy (ECT)

Introducción. El grado de satisfacción de pacientes y familiares con la terapia electroconvulsiva (TEC) es un resultado importante del tratamiento, pero no existe ningún instrumento en español que lo cuantifique. El objetivo del estudio es traducir y adaptar culturalmente al español el instrumento “Patient Satisfaction Survey” (PSS)1 para pacientes y familiares. Metodología. La traducción inicial la realizaron dos traductores y la retrotraducción un tercer traductor. Se obtuvouna encuesta de consenso adaptada por el comité investigador y revisada por los autores del instrumento original. Para la adaptación cultural se valoró la equivalencia entre el instrumento original y la retrotraducción, la legibilidad de la encuesta y se ensayó la versión española en una muestra de pacientes, de familiares y de expertos en TEC. Se realizó el mismo proceso para la encuesta de satisfacción de los familiares o cuidadores. Resultados. Las encuestas finales en español se obtuvieron de forma consensuada tras completarse el proceso de traducción e identificarse ítems problemáticos que se modificaron satisfactoriamente. La legibilidad de las encuestas fue muy accesible a la población española. La prueba piloto realizada en pacientes, familiares y expertos permitió detectar y modificar ítems confusos. Con los comentarios y los cambios realizados en esta prueba piloto se obtuvo la versión final de la traducción adaptada al español. Conclusiones. La traducción y adaptación realizada de la PSS para pacientes y familiares o cuidadores podría proporcionar unas escalas adecuadas de satisfacción con la TEC para su uso en español.(AU)

Introduction. The degree of satisfaction of patients and their relatives with electroconvulsive therapy (ECT) is considered an important treatment goal; however there is no scale in Spanish to quantify it. The aim of the study was to translate and adapt into Spanish the “Patient Satisfaction Survey” (PSS) for its use in patients and their relatives. Methodology. Two translators performed the initial translation and a third translator did the back translation. The research committee obtained a consensus survey; the authors of the original instrument reviewed and accepted this survey. The equivalence between the original instrument with the back translation and the readability of the survey were analyzed. The Spanish version was tested on a sample of patients, relatives and experts in ECT. The same process was carried out for the satisfaction survey of relatives or caregivers. Results. The Spanish surveys were obtained after completing the translation process and identifying the problematic items that were successfully modified. The readability of the surveys was very accessible to the Spanish population. The pilot test carried out on patients, relatives and experts allowed detection and changes of confusing items. The final Spanish surveys were obtained after this pilot test. Conclusions. The adaptation of the PSS for Spanish patients and relatives provide suitable satisfaction scale for its use in Spanish population.(AU)

Psychopathological and Personality Pro file in Chronic Nononcologic Nociceptive and Neuropathic pain: Cross-sectional Comparative Study.

Introduction: Adaptation to chronic non-oncologic pain is associated with the development of psychopathology and personality disorders, creating severity, chronicity, poorer treatment response, and exacerbations in patients with neuropathy. Objective: To identify the psychopathological and personality profiles of patients with chronic nociceptive and neuropathic pain and their association with pain progression and intensity. Method: A cross-sectional, descriptive and comparative study was conducted in the Pain Treatment Unit of Hospital Universitari Sagrat Cor, with systematic randomized recruitment for 25 months; 115 patients were evaluated using the Hamilton Depression and Anxiety Rating Scale (HAM-D, HAM-A) and the Millon Clinical MultiaxialInventory-III (MCMI-III). Results: The neuropathic group achieved significantly higher scores for pain intensity and depressive and anxiety symptoms. With greater magnitude and frequency, the neuropathic group related pain intensity and progression with depressive/anxiety symptoms, clinical syndromes, and personality patterns. Both groups revealed tendencies towards a compulsive personality pattern, followed by narcissistic, histrionic, and schizoid patterns. Conclusions: When treating chronic pain, the presence of various psychopathological indicators requires an individualized strategy.

Introducción: La adaptación al dolor crónico no oncológico se asocia al desarrollo de psicopatología y afectaciones de la personalidad, generando severidad, cronicidad, menor respuesta al tratamiento y agravándose ante la neuropatía. Objetivo: Identificar perfiles psicopatológicos y de personalidad en pacientes con dolor crónico nociceptivo y neuropático, y su relación con la evolución e intensidad del dolor. Método: Estudio transversal, descriptivo y comparativo, realizado en la Unidad de Tratamiento del Dolor del Hospital Universitari Sagrat Cor, con reclutamiento aleatorio sistemático durante 25 meses; 115 pacientes fueron evaluados mediante la Escala de Hamilton para la Depresión y Ansiedad (HAM-D, HAM-A) y el Inventario Clínico Multiaxialde Millon III (MCMI-III). Resultados: El grupo neuropático obtuvo puntuaciones significativamente mayores en intensidad del dolor, sintomatología depresiva y ansiosa. Con más magnitud y frecuencia, relacionó la intensidad y evolución del dolor con sintomatología depresiva, ansiosa, síndromes clínicos y patrones de la personalidad. Ambos grupos revelaron tendencia al patrón de personalidad compulsiva, seguido del narcisista, histriónico y esquizoide. Conclusiones: En el tratamiento del dolor crónico, la presencia de distintos indicadores psicopatológicos requiere una estrategia individualizada.

Relationship between immunometabolic status and cognitive performance among major depression disorder patients.

BACKGROUND: Alterations in cognitive performance have been described in patients with major depressive disorder (MDD). However, the specific risk factors of these changes are not yet known. This study aimed to explore whether inmunometabolic parameters are related to cognitive performance in MDD in comparison to healthy controls (HC) METHODS: Sample consisted of 84 MDD patients and 78 HC. Both groups were compared on the results of cognitive performance measured with the Cambridge Neuropsychological Test Automated Battery (CANTAB), the presence of metabolic syndrome (MetS) and an inflammatory/oxidative index calculated by a principal component analysis of peripheral biomarkers (tumor necrosis factor, C-reactive protein and 4-hydroxynonenal). A multiple linear regression was carried out, to study the relationship between inmunometabolic variables and the global cognitive performance, being the latter the dependent variable. RESULTS: Significant differences were obtained in the inflammatory/oxidative index between both groups (F(1157)= 12.93; p < .001), also in cognitive performance (F(1157)= 56.75; p < .001). The inmunometabolic covariate regression model (i.e., condition (HC/MDD), sex, age and medication loading, MetS, inflammatory/oxidative index and the interaction between MetS and inflammatory/oxidative index) was statistically significant (F(7157)= 11.24; p < .01) and explained 31% of variance. The condition, being either MDD or HD, (B=-0.97; p < .001), age (B=-0.28; p < .001) and the interaction between inflammatory/oxidative index and MetS (B=-0.38; p = .02) were factors associated to cognitive performance. LIMITATIONS: Sample size was relatively small. The cross-sectional design of the study limits the possibilities of analysis. CONCLUSIONS: Our results provide evidence on the conjoint influence of metabolic and inflammatory dysregulation on cognitive dysfunction in MDD patients. In this way, our study opens a line of research in immunometabolic agents to deal with cognitive decline associated with MDD.

Can the Addition of Maintenance Electroconvulsive Therapy to Pharmacotherapy Improve Relapse Prevention in Severe Major Depressive Disorder? A Randomized Controlled Trial.

Few systematic evaluations have been performed of the efficacy of electroconvulsive therapy (ECT) as a relapse prevention strategy in major depressive disorder (MDD). This is a single-blind, multicenter, randomized controlled trial to compare the efficacy and tolerability of pharmacotherapy plus maintenance ECT (M-Pharm/ECT) versus pharmacotherapy alone (M-Pharm) in the prevention of MDD relapse. Subjects with MDD who had remitted with bilateral acute ECT (n = 37) were randomly assigned to receive M-Pharm/ECT (n = 19, 14 treatments) or M-Pharm (n = 18) for nine months. The subjects were followed up for 15 months. The main outcome was relapse of depression, defined as a score of 18 or more on the Hamilton Depression Rating Scale. At nine months, 35% of the subjects treated with M-Pharm/ECT relapsed as compared with 61% of the patients treated with M-Pharm. No statistically significant differences between groups were indicated by either Kaplan-Meier or Cox proportional hazards regression analyses. The subjects without psychotic features were at higher risk of relapse. There were no statistically significant differences in the MMSE scores of the two groups at the end of the study. Further studies are needed to better define the indications for M-ECT in order to improve its efficacy as a relapse prevention strategy.

Factors Predicting Ictal Quality in Bilateral Electroconvulsive Therapy Sessions.

In electroconvulsive therapy (ECT), ictal characteristics predict treatment response and can be modified by changes in seizure threshold and in the ECT technique. We aimed to study the impact of ECT procedure-related variables that interact during each session and might influence the seizure results. Two hundred and fifty sessions of bilateral ECT in forty-seven subjects were included. Seizure results were evaluated by two different scales of combined ictal EEG parameters (seizure quality index (SQI) and seizure adequacy markers sum (SAMS) scores) and postictal suppression rating. Repeated measurement regression analyses were performed to identify predictors of each session's three outcome variables. Univariate models identified age, physical status, hyperventilation, basal oxygen saturation, days between sessions, benzodiazepines, lithium, and tricyclic antidepressants as predictors of seizure quality. Days elapsed between sessions, higher oxygen saturation and protocolized hyperventilation application were significant predictors of better seizure quality in both scales used in multivariate models. Additionally, lower ASA classification influenced SQI scores as well as benzodiazepine use and lithium daily doses were predictors of SAMS scores. Higher muscle relaxant doses and lower applied stimulus intensities significantly influenced the postictal suppression rating. The study found several modifiable procedural factors that impacted the obtained seizure characteristics; they could be adjusted to optimize ECT session results.

Ventilation Adjustment in ECT During COVID-19: Voluntary Hyperventilation is an Effective Strategy.

PURPOSE: Airway management is a key objective in adapted electroconvulsive therapy (ECT) protocols during the COVID-19 pandemic to prevent infection. The objective of this study was to describe the effectiveness of a modified ventilation procedure designed to reduce aerosol-generating bag-mask ventilation (BMV) and isolate possible droplets while maintaining adequate respiratory gas values in ECT sessions. MATERIALS AND METHODS: This prospective study analyzed the results of the modified protocol applied over a month. Adaptations entailed preoxygenation and extension of the voluntary hyperventilation (VHV) time for two minutes before anesthesia induction, asking patients to hyperventilate with oxygen therapy via nasal cannula and while wearing a face mask. Thereafter, vigorous hyperventilation was avoided, and patients were only assisted with tightly sealed BMV until emergence from anesthesia, isolating the ventilation by using a single-use plastic device. Oxygen saturation (SpO2) and transcutaneous partial pressure of carbon dioxide (TcPCO2) were recorded throughout the session. RESULTS: The study included 74 sessions of bilateral ECT with the modified ventilation protocol in 15 subjects. After VHV, the mean SpO2 increase was 2.12±2.14%, and the mean TcPCO2 decrease was 4.05±2.98 mmHg. TcPCO2 values at the moment of stimulus administration were 2.22±3.07 mmHg below pre-ECT values. The mean EEG seizure was 38.70±17.03 s, and postictal suppression was 68.31± 34.58% and 2.13±0.75 on a 0-3 scale. Brief desaturation (SpO2 <90) of 4-5 seconds duration was observed in 4 sessions. CONCLUSION: This modified ventilation protocol was effective during COVID-19, and it did not elicit significant side effects. In addition to avoiding vigorous BMV, it induced moderate hypocapnia, which has been tied to seizure optimization and less hypercapnia during the apnea period.

Childhood maltreatment interacts with hypothalamic-pituitary-adrenal axis negative feedback and major depression: effects on cognitive performance.

Background: Childhood maltreatment (CM) is associated with impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback and cognitive dysfunction, resembling those abnormalities linked to major depressive disorder (MDD). Objectives: We aimed to assess the potential modulating effects of MDD diagnosis or HPA axis function in the association between different types of CM and cognitive performance in adulthood. Methods: Sixty-eight MDD patients and 87 healthy controls were recruited. CM was assessed with the Childhood Trauma Questionnaire. We obtained three latent variables for neuropsychological performance (verbal memory, visual memory and executive function/processing speed) after running a confirmatory factor analysis with cognitive tests applied. Dexamethasone suppression test ratio (DSTR) was performed using dexamethasone 0.25 mg. Results: Different types of CM had different effects on cognition, modulated by MDD diagnosis and HPA axis function. Individuals with physical maltreatment and MDD presented with enhanced cognition in certain domains. The DSTR differentially modulated the association between visual memory and physical neglect or sexual abuse. Conclusions: HPA axis-related neurobiological mechanisms leading to cognitive impairment might differ depending upon the type of CM. Our results suggest a need for early assessment and intervention on cognition and resilience mechanisms in individuals exposed to CM to minimize its deleterious and lasting effects.

Antecedentes: El maltrato infantil (MI) se asocia con una alteración en la retroalimentación negativa del eje hipotalámico-hipofisario-adrenal (HHA) y disfunción cognitiva, que se asemejan a las anomalías vinculadas al trastorno depresivo mayor (TDM).Objetivos: Nuestro objetivo fue evaluar los posibles efectos moduladores del diagnóstico de TDM y de la función del eje HHA en la asociación entre diferentes tipos de MI y el rendimiento cognitivo en la edad adulta.Métodos: Se reclutaron 68 pacientes con TDM y 87 controles sanos. El MI se evaluó con el Cuestionario de trauma infantil. Se obtuvieron tres variables latentes para el rendimiento neuropsicológico (memoria verbal, memoria visual y función ejecutiva/velocidad de procesamiento) tras realizar un análisis factorial confirmatorio con las pruebas cognitivas aplicadas. La ratio de supresión de cortisol en el test de supresión con dexametasona (DSTR) se realizó usando dexametasona 0,25 mg.Resultados: Los diferentes tipos de MI tuvieron diferentes efectos sobre la cognición, modulados por el diagnóstico de TDM y la función del eje HHA. Los individuos con maltrato físico y TDM presentaron una cognición mejorada en ciertos dominios. El DSTR moduló diferencialmente la asociación entre memoria visual y negligencia física o abuso sexual.Conclusiones: Los mecanismos neurobiológicos relacionados con el eje HHA que conducen al deterioro cognitivo pueden diferir según el tipo de MI. Nuestros resultados sugieren la necesidad de una evaluación e intervención tempranas sobre la cognición y los mecanismos de resiliencia en individuos expuestos a MI para minimizar sus efectos nocivos y duraderos.

Childhood Maltreatment and Its Interaction with Hypothalamic-Pituitary-Adrenal Axis Activity and the Remission Status of Major Depression: Effects on Functionality and Quality of Life.

Relationships among childhood maltreatment (CM), hypothalamic-pituitary-adrenal (HPA) axis disturbances, major depressive disorder (MDD), poor functionality, and lower quality of life (QoL) in adulthood have been described. We aimed to study the roles of the remission status of depression and HPA axis function in the relationships between CM and functionality and QoL. Ninety-seven patients with MDD and 97 healthy controls were included. The cortisol awakening response, cortisol suppression ratio in the dexamethasone suppression test, and diurnal cortisol slope were assessed. Participants completed measures of psychopathology, CM, functionality, and QoL. Multiple linear regression analyses were performed to study the relationships between CM and functionality and QoL. Only non-remitted MDD patients showed lower functionality and QoL than controls, indicating that depressive symptoms may partly predict functionality and QoL. Cortisol measures did not differ between remitted and non-remitted patients. Although neither HPA axis measures nor depression remission status were consistently associated with functionality or QoL, these factors moderated the effects of CM on functionality and QoL. In conclusion, subtle neurobiological dysfunctions in stress-related systems could help to explain diminished functionality and QoL in individuals with CM and MDD and contribute to the persistence of these impairments even after the remission of depressive symptoms.

Similar clinical improvement of depression using 0.5-ms and 1-ms pulse widths in bilateral electroconvulsive therapy.

There is a lack of research regarding 0.5-ms pulse width (PW) in bilateral electroconvulsive therapy (ECT). The aim of this study was to compare the efficacy and number of treatment sessions between groups receiving 0.5-ms and 1-ms PW ECT. Ninety-four patients with unipolar major depression treated with acute bilateral ECT were analysed retrospectively, grouped as consecutive patients treated with 0.5-ms PW ECT (n = 47), and age- and sex-matched patients treated with 1-ms PW ECT. Clinical and ECT data were extracted from clinical records. Symptom evaluations and global cognitive screening at baseline and post-ECT were administered by trained psychiatrists. The Hamilton Rating Scale for Depression (HDRS-21) was rated weekly. Efficacy and number of treatment sessions were compared between groups. PW was explored as a predictor of mean decrease in HDRS and number of treatment sessions by regression models. Group characteristics did not differ at baseline. The mean decrease in HDRS in the 0.5- and 1-ms PW [25.85 (7.79) vs. 24.33 (6.99), respectively], response (95.7% vs. 97.9%), remission (87.2% vs. 80.9%) and mean number of treatment sessions [11.28 (3.85) vs. 11.34 (3.36)] were not significantly different. Episode duration and severity, and previous ECT predicted HDRS decrease. Severity at baseline and the 6th session, the dosing method and the last ECT treatment dose predicted the number of treatment sessions needed. PW was not significant in the regressions models. The results suggest that both PWs perform similarly in bilateral ECT for depression, resulting in equivalent antidepressant efficacy and number of treatment sessions needed.

Age at illness onset and physical activity are associated with cognitive impairment in patients with current diagnosis of major depressive disorder.

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 (ß=-0.11; p=<0.001), job status (ß=-0.50; p=0.016), physical activity (ß=-0.25; p=0.04) and age at illness onset (ß=0.17; p=0.017) were statistically significant factors associated to cognitive impairment. The regression model ran in HC showed that only years of schooling were significant (ß=-0.07; p=<0.001) in this group. LIMITATIONS: Sample size was relatively small. Everyday cognitive skills were not evaluated. CONCLUSIONS: MDD patients have cognitive deficits. These deficits are linked with the years of education, job status, age of onset of the disease and the performance of physical activity. These results support the importance of the implementation of interventions targeting the cognitive reserve and lifestyle habits of MDD patients, in addition to the conventional therapeutic approach focused on symptoms control.

BDNF genetic variants and methylation: effects on cognition in major depressive disorder.

Brain-derived neurotrophic factor (BDNF) gene regulation has been linked to the pathophysiology of major depressive disorder (MDD). MDD patients show cognitive deficits, and altered BDNF regulation has a relevant role in neurocognitive functions. Our goal was to explore the association between BDNF genetic and epigenetic variations with neurocognitive performance in a group of MDD patients and healthy controls considering possible modulating factors. The sample included 134 subjects, 64 MDD patients, and 70 healthy controls. Clinical data, childhood maltreatment, and neurocognitive performance were assessed in all participants. Eleven single nucleotide polymorphisms (SNPs) and two promoter regions in the BDNF gene were selected for genotype and methylation analysis. The role of interactions between BDNF genetic and epigenetic variations with MDD diagnosis, sex, and Childhood Trauma Questionnaire (CTQ) scores was also explored. We observed significant associations between neurocognitive performance and two BDNF SNPs (rs908867 and rs925946), an effect that was significantly mediated by methylation values at specific promoter I sites. We identified significant associations between neurocognitive results and methylation status as well as its interactions with MDD diagnosis, sex, and CTQ scores. Our results support the hypothesis that BDNF gene SNPs and methylation status, as well as their interactions with modulating factors, can influence cognition. Further studies are required to confirm the effect of BDNF variations and cognitive function in larger samples.

FKBP5 polymorphisms and hypothalamic-pituitary-adrenal axis negative feedback in major depression and obsessive-compulsive disorder.

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.

Early improvement as a predictor of final remission in major depressive disorder: New insights in electroconvulsive therapy.

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.

Hypothalamic-pituitary-adrenal axis activity in the comorbidity between obsessive-compulsive disorder and major depression.

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.