Lymphocyte-derived and lipoprotein-derived inflammatory ratios as biomarkers in bipolar disorder type I: Characteristics, predictive values, and influence of current psychopharmacological treatments.

PURPOSE OF THIS RESEARCH: The purpose of this research was to investigate peripheral inflammation by analyzing lymphocyte and lipoprotein-derived inflammatory ratios in patients with bipolar disorder type I (BD-I) and healthy controls (HCs), considering mood stabilizer drug treatments, sex and clinical trajectories. METHODS: This was a cross-sectional case-control study of BD-I patients (n=252) and healthy controls (n=62). We investigated peripheral inflammation biomarkers through blood count values (CBCs), lipoproteins and a complex panel of inflammatory ratios, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-HDL ratio (NHR), monocyte-to-HDL ratio (MHR), platelet-to-HDL ratio (PHR) and lymphocyte-to-HDL ratio (LHR). Furthermore, we examined the effects of sex, drug treatment and clinical outcome on the inflammatory profile. RESULTS: We found that the monocyte-to-lymphocyte ratio (MLR) and lipoprotein-derived inflammatory ratio (NHR, MHR, PHR, and LHR) were significantly greater in BD-I patients than in control individuals. The monocyte-to-HDL ratio (MHR) showed acceptable accuracy as a disease predictor. Logistic regression analysis adjusted for sex, age and BMI indicated that the risk of having a BD-I diagnosis was greater for participants with MHR levels in quartiles 3 (OR= 5.2, p=0.001) and 4 (OR=13, p<0.001). There was a strong association between lithium treatment and increased inflammation represented by elevated lymphocyte-derived inflammatory ratios (NLR, MLR, PLR, SII, and SIRI) in lithium-treated BD-I patients compared to those in lithium-free or lithium treatment-naïve BD-I patients. The main limitations are the cross-sectional nature of the study and limited sample size of HCs. MAJOR CONCLUSIONS: Several CBCs, lipoproteins, and a complex panel of inflammatory ratios, including lymphocyte-derived inflammatory ratios (NLR, MLR, PLR, SII, and SIRI) and lipoprotein-derived inflammatory ratios (NHR, MHR, PHR, and LHR), are altered in individuals diagnosed with BD-I. The monocyte-to-HDL ratio (MHR) emerged as a disease predictor in our BD-I sample. A remarkable finding is the association of lithium and valproate treatment with the inflammatory state. Considering the study limitations, our results underscore the importance of pharmacological treatments when researching inflammation markers in mood disorders. Lymphocyte-derived and lipoprotein-derived inflammatory ratios are easy-to-implement and relevant biomarkers in BD-I patients.

Altered activation of the dorsal anterior cingulate cortex during oddball performance in individuals at risk for Alzheimer's disease.

INTRODUCTION: The neural mechanisms underlying neurodegenerative disorders in the elderly remain elusive, despite extensive neuroimaging research in recent decades. Amnestic type mild cognitive impairment (aMCI) and late-life major depressive disorder (MDD) are two such conditions characterized by intersecting cognitive and affective symptomatology, and they are at a higher risk for Alzheimer's disease. MATERIALS AND METHODS: This study analyzed the neural underpinnings of cognitive and depressive symptoms in a cohort comprising 12 aMCI subjects, 24 late-life MDD patients, and 26 healthy controls (HCs). Participants underwent a detailed neuropsychological assessment and completed a visual attentional oddball task during functional magnetic resonance imaging (fMRI), with evaluations at baseline and at 2-year follow-up. RESULTS: Initial findings showed that aMCI subjects had reduced dACC activation during oddball (target) stimulus detection, a pattern that persisted in longitudinal analyses and correlated with cognitive functioning measures. For HCs, subsequent dACC activation was linked to depression scores. Furthermore, in the affective-cognitive altered groups, later dACC activation correlated with oddball and memory performance. CONCLUSIONS: These findings enhance our comprehension of the neurobiological basis of cognitive and depressive disturbances in aging, indicating that dACC activation in response to a visual attentional oddball task could serve as a neural marker for assessing cognitive impairment and depression in conditions predisposing to Alzheimer's disease.

Effective connectivity of the locus coeruleus in patients with late-life Major Depressive Disorder or mild cognitive impairment.

INTRODUCTION: We compared effective connectivity from the locus coeruleus (LC) during the resting-state in patients with late-life Major Depressive Disorder (MDD), individuals with amnestic Mild Cognitive Impairment (aMCI), and Healthy Controls (HCs). PARTICIPANTS: 23 patients with late-life MDD, 22 patients with aMCI, and 28 HCs. MATERIAL AND METHODS: Participants were assessed in two time-points, 2 years apart. They underwent a resting-state functional magnetic resonance imaging and a high-resolution anatomical acquisition, as well as clinical assessments. Functional imaging data were analyzed with dynamic causal modeling, and parametric empirical Bayes model was used to map effective connectivity between 7 distinct nodes: 4 from the locus coeruleus and 3 regions displaying gray matter decreases during the two-year follow-up period. RESULTS: Longitudinal analysis of structural data identified three clusters of larger over-time gray matter volume reduction in patients (MDD+aMCI vs. HCs): the right precuneus, and the visual association and parahippocampal cortices. aMCI patients showed decreased effective connectivity from the left rostral to caudal portions of the LC, while connectivity from the left rostral LC to the parahippocampal cortex increased. In MDD, there was a decline in effective connectivity across LC caudal seeds, and increased connectivity from the left rostral to the left caudal LC seed over time. Connectivity alterations with cortical regions involved cross-hemisphere increases and same-hemisphere decreases. CONCLUSIONS: Our discoveries provide insight into the dynamic changes in effective connectivity in individuals with late-life MDD and aMCI, also shedding light on the mechanisms potentially contributing to the onset of neurodegenerative disorders.

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.

A systematic review and meta-analysis of suicidality in psychotic disorders: Stratified analyses by psychotic subtypes, clinical setting and geographical region.

We studied the prevalence of suicide attempts and cumulative incidence of completed suicide in schizophrenia (SZ), schizoaffective disorder (SZAF), delusional disorder (DD) and first-episode psychosis (FEP). A systematic review was performed using Scopus and PubMed databases (1990- July 2020). A random effects meta-analysis was conducted. Stratified analyses were conducted by diagnosis, clinical setting and geographical region. The prevalence of attempted suicide was 20.3% for SZ, 46.8% for SZAF, 11.1% for DD and 12.5% for FEP. Suicide attempts rates were higher for outpatient samples than for inpatient samples in SZ, SZAF and DD (but not FEP) studies. Analyses by geographical region in SZ showed greater prevalence of suicide attempts in North America and Northern Europe. The cumulative incidence of completed suicide was 2.0% for SZ, 2.4% for SZAF; 2.2% for DD and 1.9% for FEP. In schizophrenia and FEP studies, Northern European studies reported higher rates of completed suicide when compared to Western European countries. In conclusion, suicidal behaviour rates in psychoses differ by diagnoses, clinical setting and geographical region.

Diagnosis of late-life depression using structural equation modeling and dynamic effective connectivity during resting fMRI.

BACKGROUND: Late-life depression (LLD) is characterized by cognitive and social impairments. Determining neurobiological alterations in connectivity in LLD by means of fMRI may lead to a better understanding of the neural basis underlying this disorder and more precise diagnostic markers. The primary objective of this paper is to identify a structural model that best explains the dynamic effective connectivity (EC) of the default mode network (DMN) in LLD patients compared to controls. METHODS: Twenty-seven patients and 29 healthy controls underwent resting-state fMRI during a period of eight minutes. In both groups, jackknife correlation matrices were generated with six ROIs of the DMN that constitute the posterior DMN (pDMN). The different correlation matrices were used as input to estimate each structural equation model (SEM) for each subject in both groups incorporating dynamic effects. RESULTS: The results show that the proposed LLD diagnosis algorithm achieves perfect accuracy in classifying LLD patients and controls. This differentiation is based on three aspects: the importance of ROIs 4 and 6, which seem to be the most distinctive among the subnetworks; the shape that the specific connections adopt in their networks, or in other words, the directed connections that are established among the ROIs in the pDMN for each group; and the number of dynamic effects that seem to be greater throughout the six ROIs studied [t = 54.346; df = 54; p < .001; 95 % CI difference = 5.486-5.906]. LIMITATIONS: The sample size was moderate, and the participants continued their current medications. CONCLUSIONS: The network models that we developed describe a pattern of dynamic activation in the pDMN that may be considered a possible biomarker for LLD, which may allow early diagnosis of this disorder.

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.

Hormone Targets for the Treatment of Sleep Disorders in Postmenopausal Women with Schizophrenia: A Narrative Review.

While the early identification of insomnia in patients with schizophrenia is of clinical relevance, the use of specific compounds to treat insomnia has been studied less in postmenopausal women with schizophrenia. We aimed to explore the effects of melatonin, sex hormones, and raloxifene for the treatment of insomnia in these populations. Although melatonin treatment improved the quality and efficiency of the sleep of patients with schizophrenia, few studies have explored its use in postmenopausal women with schizophrenia. The estrogen and progesterone pathways are dysregulated in major psychiatric disorders, such as in schizophrenia. While, in the context of menopause, a high testosterone-to-estradiol ratio is associated with higher frequencies of depressive symptoms, the effects of estradiol and other sex hormones on sleep disorders in postmenopausal women with schizophrenia has not been sufficiently investigated. Raloxifene, a selective estrogen receptor modulator, has shown positive effects on sleep disorders in postmenopausal women. Future studies should investigate the effectiveness of hormonal compounds on insomnia in postmenopausal women with schizophrenia.

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.

The role of childhood trauma, HPA axis reactivity and FKBP5 genotype on cognition in healthy individuals.

Cognitive impairment has been associated with both childhood adversity and abnormalities of hypothalamic-pituitary-adrenal (HPA) axis function. An interaction exists between the functional polymorphism rs1360780 in the FKBP5 gene and childhood maltreatment, influencing a variety of clinical outcomes. Our goal was to study the relationship between different types of childhood trauma, HPA axis functionality, rs1360780 genotype and cognitive function in 198 healthy individuals who participated in the study. We obtained clinical data, childhood maltreatment scores and neurocognitive performance by clinical assessment; HPA negative feedback was analysed using the dexamethasone suppression test ratio (DSTR) after administration of 0.25 mg of dexamethasone; and the FKBP5 rs1360780 polymorphism was genotyped in DNA obtained from blood samples. The results showed a significant influence of physical neglect on measures of neurocognition as well as an interaction between the DSTR and physical and emotional neglect. Regarding social cognition, a significant association was found with sexual and physical abuse as well as with rs1360780 risk-allele carrier status. Moreover, an interaction between the rs1360780 genotype and the presence of physical abuse was significantly associated with social cognition results. Our results suggest a specific impact of different kinds of childhood maltreatment on measures of neurocognition and social cognition, which might be influenced by HPA axis reactivity and genetic variants in HPA axis-related genes such as FKBP5. Disentangling the relationship between these elements and their influence on cognitive performance might help identify susceptible individuals with higher stress vulnerability and develop preventive interventions.

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.

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.

First manic/hypomanic episode in obsessive-compulsive disorder patients treated with antidepressants: A systematic review.

High doses of antidepressants, particularly clomipramine and selective serotonin reuptake inhibitors (SSRIs), are the well-established treatment for obsessive-compulsive disorder (OCD), but manic/hypomanic episodes are potential adverse events associated with this treatment. A systematic literature review was performed on manic/hypomanic episodes in non-bipolar OCD patients. Clinical, sociodemographic and antidepressant characteristics during the manic/hypomanic switch were extracted using descriptive statistics. Data were obtained from 20 case reports and case series. Switching episodes mostly appeared in the first 12 weeks after antidepressant initiation and took place more frequently during SSRI use (mostly fluoxetine) in 64.3% of cases. Clomipramine and SSRI use differed non-significantly between the switching episodes that appeared during the first 12 weeks of antidepressant treatment and the episodes that appeared beyond 12 weeks. Switching episodes emerging before 12 weeks were associated with a lower defined daily dose of antidepressants than episodes emerging after 12 weeks. These findings suggest that there are two independent characteristics involved in manic/hypomanic switch in OCD: a) they appeared most frequently with SSRI use (fluoxetine) regardless of the time of it use, and b) episodes appeared in the first 12 weeks after SSRI or clomipramine initiation had a lower dose of antidepressant than episodes appeared after 12 weeks.

Lower Locus Coeruleus MRI intensity in patients with late-life major depression.

BACKGROUND: The locus coeruleus (LC) is the major noradrenergic source in the central nervous system. Structural alterations in the LC contribute to the pathophysiology of different neuropsychiatric disorders, which may increase to a variable extent the likelihood of developing neurodegenerative conditions. The characterization of such alterations may therefore help to predict progression to neurodegenerative disorders. Despite the LC cannot be visualized with conventional magnetic resonance imaging (MRI), specific MRI sequences have been developed to infer its structural integrity. METHODS: We quantified LC signal Contrast Ratios (LCCRs) in late-life major depressive disorder (MDD) (n = 37, 9 with comorbid aMCI), amnestic Mild Cognitive Impairment (aMCI) (n = 21, without comorbid MDD), and healthy controls (HCs) (n = 31), and also assessed the putative modulatory effects of comorbidities and other clinical variables. RESULTS: LCCRs were lower in MDD compared to aMCI and HCs. While no effects of aMCI comorbidity were observed, lower LCCRs were specifically observed in patients taking serotonin/norepinephrine reuptake inhibitors (SNRIs). CONCLUSION: Our results do not support the hypothesis that lower LCCRs characterize the different clinical groups that may eventually develop a neurodegenerative disorder. Conversely, our results were specifically observed in patients with late-life MDD taking SNRIs. Further research with larger samples is warranted to ascertain whether medication or particular clinical features of patients taking SNRIs are associated with changes in LC neurons.

Sleep disturbances in obsessive-compulsive disorder: influence of depression symptoms and trait anxiety.

BACKGROUND: Sleep disturbances have been reported in obsessive-compulsive disorder (OCD) patients, with heterogeneous results. The aim of our study was to assess sleep function in OCD and to investigate the relationship between sleep and the severity of obsessive-compulsive (OC) symptoms, depressive symptoms and trait anxiety. METHODS: Sleep quality was measured in 61 OCD patients and 100 healthy controls (HCs) using the Pittsburgh Sleep Quality Index (PSQI). Multiple linear regression was conducted to explore the association between sleep and psychopathological measures; a mediation analysis was also performed. RESULTS: OCD patients showed poor sleep quality and more sleep disturbances compared to HCs. The severity of depression, trait anxiety and OC symptomatology were correlated with poor sleep quality. Multiple linear regression analyses controlling for potential confounders revealed that the severity of depression and trait anxiety were independently related to poor sleep quality in OCD. A mediation analysis showed that both the severity of trait anxiety and depression mediate the relationship between the severity of OC symptoms and poor sleep quality among patients with OCD. CONCLUSIONS: Our findings support the existence of sleep disturbances in OCD. Trait anxiety and depression play a key role in sleep quality among OCD patients.