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.

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.

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.

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.

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.

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.

Sex differences in the association between obsessive-compulsive symptom dimensions and diurnal cortisol patterns.

Previous studies in non-clinical populations suggest that obsessive-compulsive symptoms are associated with hypothalamic-pituitary-adrenal (HPA) axis measures and that there are sex differences in these associations. We aimed to replicate these findings in a sample of 57 patients with obsessive-compulsive disorder (OCD) and 98 healthy subjects. Current and lifetime OCD symptom dimensions were assessed with the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS). Depressive symptoms and state and trait anxiety were also assessed. The following HPA axis measures were analysed in saliva: the diurnal cortisol slope (calculated using two formulas: [1] awakening to 11 p.m. [AWE diurnal slope] and [2] considering fixed time points [FTP diurnal slope] from 10 a.m. to 11 p.m.) and the dexamethasone suppression test ratio (DSTR) after 0.25 mg of dexamethasone. Multiple linear regression analyses were conducted to explore the contribution of OCD symptom dimensions to each HPA axis measure while adjusting for age, sex, BMI, smoking, trait anxiety and depressive symptoms. A sex-specific association between current ordering/symmetry symptoms and AWE diurnal cortisol slope (positive association [flattened slope] in men, inverse association [stepper slope] in women) was found. Two similar sex by OCD dimensions interactions were found for lifetime aggressive and ordering/symmetry symptoms and both (FTP, AWE) diurnal cortisol slopes. Current and lifetime hoarding symptoms were associated to a more flattened FTP diurnal cortisol slope in women. The DSTR was not associated with OCD symptoms. The lifetime interference in functionality was associated with a more flattened AWE diurnal cortisol slope. In conclusion, our study suggests that there are sex differences in the association between OCD subtypes and specific HPA axis measures.

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.

The Role of Sleep Quality, Trait Anxiety and Hypothalamic-Pituitary-Adrenal Axis Measures in Cognitive Abilities of Healthy Individuals.

Sleep plays a crucial role in cognitive processes. Sleep and wake memory consolidation seem to be regulated by glucocorticoids, pointing out the potential role of the hypothalamic-pituitary-adrenal (HPA) axis in the relationship between sleep quality and cognitive abilities. Trait anxiety is another factor that is likely to moderate the relationship between sleep and cognition, because poorer sleep quality and subtle HPA axis abnormalities have been reported in people with high trait anxiety. The current study aimed to explore whether HPA axis activity or trait anxiety moderate the relationship between sleep quality and cognitive abilities in healthy individuals. We studied 203 healthy individuals. We measured verbal and visual memory, working memory, processing speed, attention and executive function. Sleep quality was assessed with the Pittsburgh Sleep Quality Index. Trait anxiety was assessed with the State-Trait Anxiety Inventory. HPA axis measures included the cortisol awakening response (CAR), diurnal cortisol slope and cortisol levels during the day. Multiple linear regression analyses explored the relationship between sleep quality and cognition and tested potential moderating effects by HPA axis measures and trait anxiety. Poor sleep quality was associated with poorer performance in memory, processing speed and executive function tasks. In people with poorer sleep quality, a blunted CAR was associated with poorer verbal and visual memory and executive functions, and higher cortisol levels during the day were associated with poorer processing speed. Trait anxiety was a moderator of visual memory and executive functioning. These results suggest that subtle abnormalities in the HPA axis and higher trait anxiety contribute to the relationship between lower sleep quality and poorer cognitive functioning in healthy individuals.

Hypothalamic-pituitary-adrenal axis-related genes and cognition in major mood disorders and schizophrenia: a systematic review.

Hypothalamic-pituitary-adrenal (HPA) axis dysregulation and cognitive deficits are two well-characterized endophenotypes present in different serious mental illnesses (SMIs), including major depressive disorder, bipolar disorder and schizophrenia. Our aim was to study the influence of genetic and epigenetic variations in HPA axis-related genes on cognitive performance in clinical samples, including patients with major mood disorders and schizophrenia. A systematic search was performed using PubMed (Medline), PsycINFO and Scopus databases. The systematic review identified 12 studies dealing with HPA-related genes and cognition in samples including patients with SMIs, focusing on single nucleotide polymorphism (SNP) variants, while no studies analysing epigenetic variations were found. The results suggest different and specific effects on the cognitive performance of SNP variants in the HPA axis-related genes studied, as well as interactions with traumatic experiences. There was high heterogeneity in the studied samples, genes analysed, and cognitive tasks evaluated. The relationship between HPA-related genes and cognition in SMIs is still largely unknown, and further studies including larger samples and epigenetic variations are needed.

Sex-specific association between the cortisol awakening response and obsessive-compulsive symptoms in healthy individuals.

BACKGROUND: Previous studies have shown associations between obsessive-compulsive disorder (OCD) and hypothalamic-pituitary-adrenal axis activity (HPA). We aimed to investigate the association between obsessive-compulsive (OC) symptoms and HPA axis functionality in a non-clinical sample and to explore whether there are sex differences in this relationship. METHODS: One hundred eighty-three healthy individuals without any psychiatric diagnosis (80 men, 103 women; mean age 41.3 ± 17.9 years) were recruited from the general population. The Obsessive-Compulsive Inventory Revised (OCI-R) was used to assess OC symptoms. State-trait anxiety, perceived stress, and stressful life events were also assessed. Saliva cortisol levels were determined at 6 time points (awakening, 30 and 60 min post-awakening, 10:00 a.m., 23:00 p.m. and 10:00 a.m. the following day of 0.25 mg dexamethasone intake [that occurred at 23:00 p.m.]). Three HPA axis measures were calculated: cortisol awakening response (CAR), cortisol diurnal slope, and cortisol suppression ratio after dexamethasone (DSTR). Multiple linear regression analyses were used to explore the association between OC symptoms and HPA axis measures while adjusting for covariates. Our main analyses were focused on OCI-R total score, but we also explored associations with specific OC symptom dimensions. RESULTS: No significant differences were observed between males and females in OC symptoms, anxiety measures, stress, or cortisol measures. In the multiple linear regression analyses between overall OC symptoms and HPA axis measures, a female sex by OC symptoms significant interaction (standardized beta = - 0.322; p = 0.023) for the CAR (but not cortisol diurnal slope nor DSTR) was found. Regarding specific symptom dimensions, two other sex interactions were found: a blunted CAR was associated with obsessing symptoms in women, whereas a more flattened diurnal cortisol slope was associated with ordering symptoms in men. CONCLUSIONS: There are sex differences in the association between OC symptoms and HPA axis measures in healthy individuals.

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.

Actividad del eje hipotalámico-hipofisario-adrenal y rendimiento cognitivo en el anciano. El papel del estado de remisión de la depresión mayor / No disponible

El eje hipotalámico-hipofisario-adrenal (HHA) y su producto final, el cortisol, son elementos clave en la respuesta fisiológica de los seres humanos al estrés. El envejecimiento normal se ha relacionado con un aumento de los niveles basales de cortisol. La exposición a niveles elevados de cortisol juega un papel importante en el propio proceso de envejecimiento, dado que se ha asociado con atrofia del hipocampo y afectación de la memoria, también en ancianos sanos. Esto podría contribuir a explicar la génesis de los déficits de memoria en la población anciana. Por otra parte, el estrés crónico en personas mayores se ha asociado con el desarrollo de depresión, que se caracteriza frecuentemente por una hiperactividad del eje HHA y por alteraciones cognitivas que afectan a la calidad de vida y al funcionamiento psicosocial del individuo. Dichas alteraciones cognitivas pueden persistir tras la remisión de los síntomas afectivos. Se ha propuesto que una hiperactividad sutil del eje HHA podría estar relacionada con la disfunción cognitiva relacionada con la depresión, apuntando a la posibilidad que estas alteraciones del eje HHA representen un rasgo de disfunción neurobiológica subyacente ligada a la persistencia de déficits cognitivos en la depresión. En un momento en que los datos demográficos relativos a la población mundial en países desarrollados indican un envejecimiento creciente, es importante optimizar la detección de problemas relacionados con el estrés en nuestros ancianos, incluida la depresión. Ello permitiría el desarrollo de intervenciones individuales preventivas para, en última instancia, mejorar la funcionalidad y la calidad de vida de nuestros mayores

he hypothalamic-pituitary-adrenal (HPA) axis and cortisol, its final product, are relevant in the physiological response to stress. Normal aging has been linked to increased basal cortisol levels. Exposure to higher cortisol levels plays an important role in the aging process itself, since it is associated with atrophy of the hippocampus and memory impairment, even in the healthy elderly. This could help explain the genesis of memory deficits in old age. Besides, chronic stress in the elderly has been associated with the development of depression, which is frequently characterized by hyperactivity of the HPA axis and cognitive dysfunction that affect quality of life and psychosocial functioning. Cognitive dysfunction may persist after the remission of affective symptoms. It has been proposed that a subtle hyperactivity of the HPA axis could be related to these cognitive deficits, pointing to the possibility that HPA axis dysfunction represents a trait of underlying neurobiological dysfunction linked to the persistence of cognitive deficits in depression. At a time when the world population is aging, it is important to optimize the detection of problems related to stress in our elderly, including depression. This would allow the development of individual preventive interventions to, ultimately, improve the functionality and quality of life of our elders

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.

Psiconeuroinmunología de los trastornos mentales / Psychoneuroimmunology of mental disorders

El sistema inmunitario es una pieza fundamental en la defensa del organismo y participa en el mantenimiento de la homeostasis. Existe un interés creciente en las implicaciones etiopatogénicas y pronósticas del sistema inmunitario en los trastornos mentales, avalado por estudios previos que sugieren la existencia de una disregulación de la respuesta inmune y un estado proinflamatorio en pacientes con una enfermedad mental, así como la elevada prevalencia de síntomas neuropsiquiátricos en pacientes con enfermedades autoinmunes o que reciben tratamientos inmunológicos. En el presente trabajo se realiza una revisión narrativa de la literatura científica sobre el papel de la psiconeuroinmunología en los trastornos mentales, especialmente en aspectos diagnósticos, pronósticos y terapéuticos. El desarrollo de este cuerpo de conocimiento puede aportar en el futuro importantes avances en la vulnerabilidad, mecanismos etiopatogénicos, diagnóstico y tratamiento de algunos trastornos psiquiátricos

The immune system is a key element in the organism's defence system and participates in the maintenance of homeostasis. There is growing interest in the aetiopathogenic and prognostic implications of the immune system in mental disorders, as previous studies suggest the existence of a dysregulation of the immune response and a pro-inflammatory state in patients with mental disorders, as well as an increased prevalence of neuropsychiatric symptoms in patients suffering from autoimmune diseases or receiving immune treatments. This study aims to conduct a narrative review of the scientific literature on the role of Psychoneuroimmunology in mental disorders, with special focus on diagnostic, prognostic and therapeutic issues. The development of this body of knowledge may bring in the future important advances in the vulnerability, aetiopathogenic mechanisms, diagnosis and treatment of some mental disorders

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.

Psychoneuroimmunology of mental disorders. / Psiconeuroinmunología de los trastornos mentales.

The immune system is a key element in the organism's defence system and participates in the maintenance of homeostasis. There is growing interest in the aetiopathogenic and prognostic implications of the immune system in mental disorders, as previous studies suggest the existence of a dysregulation of the immune response and a pro-inflammatory state in patients with mental disorders, as well as an increased prevalence of neuropsychiatric symptoms in patients suffering from autoimmune diseases or receiving immune treatments. This study aims to conduct a narrative review of the scientific literature on the role of Psychoneuroimmunology in mental disorders, with special focus on diagnostic, prognostic and therapeutic issues. The development of this body of knowledge may bring in the future important advances in the vulnerability, aetiopathogenic mechanisms, diagnosis and treatment of some mental disorders.