Mindfulness-based cognitive therapy neurobiology in treatment-resistant obsessive-compulsive disorder: A domain-related resting-state networks approach.

Mindfulness-based cognitive therapy (MBCT) stands out as a promising augmentation psychological therapy for patients with obsessive-compulsive disorder (OCD). To identify potential predictive and response biomarkers, this study examines the relationship between clinical domains and resting-state network connectivity in OCD patients undergoing a 3-month MBCT programme. Twelve OCD patients underwent two resting-state functional magnetic resonance imaging sessions at baseline and after the MBCT programme. We assessed four clinical domains: positive affect, negative affect, anxiety sensitivity, and rumination. Independent component analysis characterised resting-state networks (RSNs), and multiple regression analyses evaluated brain-clinical associations. At baseline, distinct network connectivity patterns were found for each clinical domain: parietal-subcortical, lateral prefrontal, medial prefrontal, and frontal-occipital. Predictive and response biomarkers revealed significant brain-clinical associations within two main RSNs: the ventral default mode network (vDMN) and the frontostriatal network (FSN). Key brain nodes -the precuneus and the frontopolar cortex- were identified within these networks. MBCT may modulate vDMN and FSN connectivity in OCD patients, possibly reducing symptoms across clinical domains. Each clinical domain had a unique baseline brain connectivity pattern, suggesting potential symptom-based biomarkers. Using these RSNs as predictors could enable personalised treatments and the identification of patients who would benefit most from MBCT.

Impact of Stress on Brain Morphology: Insights into Structural Biomarkers of Stress-related Disorders.

Exposure to acute and chronic stress has a broad range of structural effects on the brain. The brain areas commonly targeted in the stress response models include the hippocampus, the amygdala, and the prefrontal cortex. Studies in patients suffering from the so-called stress-related disorders -embracing post-traumatic stress, major depressive and anxiety disorders- have fairly replicated animal models of stress response -particularly the neuroendocrine and the inflammatory models- by finding alterations in different brain areas, even in the early neurodevelopment. Therefore, this narrative review aims to provide an overview of structural neuroimaging findings and to discuss how these studies have contributed to our knowledge of variability in response to stress and the ulterior development of stress-related disorders. There are a gross number of studies available but neuroimaging research of stress-related disorders as a single category is still in its infancy. Although the available studies point at particular brain circuitries involved in stress and emotion regulation, the pathophysiology of these abnormalities -involving genetics, epigenetics and molecular pathways-, their relation to intraindividual stress responses -including personality characteristics, self-perception of stress conditions…-, and their potential involvement as biomarkers in diagnosis, treatment prescription and prognosis are discussed.

If you feel you can't, you won't: the role of subjective and objective cognitive competence on psychosocial functioning in depression.

BACKGROUND: The purpose of this exploratory study is to examine the role of sociodemographic, clinical, and cognitive - both objective and subjective - factors in overall and in specific domains of psychosocial functioning, in patients with depression at different clinical states of the disease (remitted and non-remitted). METHODS: A sample of 325 patients with major depressive disorder, 117 in remission and 208 in non-remission, were assessed with a semi-structured interview collecting sociodemographic, clinical, cognitive (with neuropsychological tests and the Perceived Deficit Questionnaire), and functional (Functioning Assessment Short Test) characteristics. Backward regression models were conducted to determine associations of global and specific areas of functioning with independent factors, for both clinical states. RESULTS: Residual depressive symptomatology and self-appraisal of executive competence were significantly associated with psychosocial functioning in remitted patients, in overall and some subdomains of functioning, particularly cognitive and interpersonal areas. While depressive symptoms, executive deficits and self-appraisal of executive function were significantly related to functional outcomes in non-remitted patients, both in overall functioning and in most of subdomains. DISCUSSION: This study evidences the strong association of one's appraisal of executive competence with psychosocial functioning, together with depressive symptoms, both in remitted and non-remitted patients with depression. Therefore, to achieve full recovery, clinical management of patients should tackle not only the relief of core depressive symptoms, but also the cognitive ones, both those that are objectified with neuropsychological tests and those that are reported by the patients themselves.

An eHealth ecosystem for stepped and early psychosocial care in advanced lung cancer: Rationale and protocol for a randomized control trial.

Background: Receiving a diagnosis of lung cancer is an emotional event, not least because it is usually diagnosed at advanced stages with limited life expectancy. Although evidence-based educational, emotional, and social interventions exist, they reach few patients and usually when it is too late. Objective: This project will be carried out in a comprehensive center for cancer care and health research, aiming to study the efficacy, costs, and utility of an eHealth ecosystem to meet the psychosocial needs of patients with advanced lung cancer. Method: We will enroll 76 patients with advanced lung cancer into an eHealth ecosystem of stepped and personalized psychosocial care for 9 months. These patients will be compared with another 76 receiving usual care in a non-inferiority randomized controlled trial. The following main outcomes will be measured every 3 months: emotional distress, spirituality, demoralization, quality of life, and medication adherence. Secondary outcomes will include symptomatology, health education, cost-utility analyses, usability and satisfaction with the platform, and time to detect emotional needs and provide care. Baseline differences between groups will be measured with the Student t-test or chi-square test, as appropriate. We will then compare the main outcomes between groups over time using multilevel linear models, report effect sizes (Hedges' g), and assess non-inferiority. The cost-utility of both interventions will be considered in terms of quality adjusted life years and quality of life given the costs of providing each treatment. Discussion: This randomized controlled trial should provide new evidence on the efficacy and cost-utility of an eHealth ecosystem to deliver personalized and timely psychosocial care to patients with advanced lung cancer. Trial registration: ClinicalTrials.gov ID "NCT05497973".

Effectiveness of enhancing cognitive reserve in children, adolescents and young adults at genetic risk for psychosis: Study protocol for a randomized controlled trial.

BACKGROUND: Offspring of patients diagnosed with bipolar disorder and schizophrenia (Off-BDSZ) have a high genetic risk of developing a mental illness. The aim of this project is to develop and investigate the efficacy of an intervention aimed at this population, based on the concept of cognitive reserve. METHODS: This is a multicenter randomized trial with an experimental test-retest design study with control group. Two groups will be included: a community comparison group (CC) and a Off-BDSZ group. A total of 108 Off-BDSZ and 65 CC aged between 6 and 25 years will be recruited. Off-BDSZ participants will be randomized to receive either Cognitive Reserve EnhAncement ThErapy (CREATE) (n=54), or a supportive approach (n=54). The CC group will be assessed at baseline. The duration of the intervention will be 3 months, with 12 weekly group sessions. The primary outcome will be the improvement in CR measured according to change in the Cognitive Reserve Assessment Scale in Health (CRASH) and Cognitive Reserve scale for Adolescents (CORE-A). All participants will be blindly evaluated using clinical, cognitive and neuroimaging measures at baseline, at three months (after the psychological intervention), and at twelve-month follow-up after treatment completion. DISCUSSION: The results will provide insight into whether the CREATE-Offspring version may enhance cognitive reserve (CR) in child, adolescent and young adult Off-BDSZ as well as advance knowledge about changes in clinical manifestations, neuropsychological performance and brain structure and function associated with improving CR. This novel and cost-effective intervention represents an advance in the framework of preventive interventions in mental health. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03722082. Registered on 26 October 2018.

A Digital Cancer Ecosystem to Deliver Health and Psychosocial Education as Preventive Intervention.

Health education and psychosocial interventions prevent emotional distress, and the latter has been shown to have an impact on survival. In turn, digital health education interventions may help promote equity by reaching a higher number of cancer patients, both because they avoid journeys to the hospital, by and having a better efficiency. A total of 234 women recently diagnosed with breast cancer in a comprehensive cancer center used the digital ecosystem ICOnnecta't from March 2019 to March 2021. ICOnnecta't consists of four care levels, provided to patients according to their level of distress. The second level of this intervention consists of an educational campus, which was analyzed to track users' interests and their information-seeking behavior. Overall, 99 out of 234 women (42.3%) used the educational campus. There were no significant differences in sociodemographic and clinical variables between the campus users and non-users. Among users, the median number of resources utilized per user was four (interquartile range: 2−9). Emotional and medical resources were the contents most frequently viewed and the audiovisual format the most consulted (p < 0.01). Resources were used mainly within the first three months from enrolment. Users who were guided to visit the virtual campus were more active than spontaneous users. Offering an early holistic health educational platform inside a digital cancer ecosystem, with health professionals involved, can reach more patients, promoting equity in the access of cancer information and prevention, from the very beginning of the disease.

Stressful Life Events and Distress in Breast Cancer: A 5-Years Follow-Up.

Background/Objective: Environmental factors such as psychosocial stress have demonstrated to have an impact on the breast cancer (BC) course. This study aims to explore the impact of psychotherapy and stressful life events (SLE) on BC survivors' illness trajectories. Method: 68 women with BC underwent Positive Psychotherapy or Cognitive-Behavioral Stress Management and 37 patients were included as a control group. The effects of distress reduction and SLE on their 5-year recurrence were investigated. Additional analyses examined the effect of receiving vs. not receiving psychotherapy and of the type of therapy on survival and disease-free interval, DFI. Results: A one-point decrease of the Hospital Anxiety and Depression Scale (HADS) after psychotherapy predicted a lower risk of 5-year recurrence, OR = 0.84, p = .037, 95% CI = 0.71-0.99). Also, a one point-increase in the number threatening SLE (OR = 1.92; p = .028, 95% CI = 1.07-3.43) was related to higher 5-year recurrence. Conclusions: The findings highlight the necessity of studying not only a given situation (i.e., psychotherapy, SLE) but its specific impact on individuals.

Antecedentes/Objetivo: El estrés psicosocial ha demostrado tener un impacto en la evolución del cáncer de mama (CM). Este estudio tiene como objetivo explorar el impacto de la psicoterapia y de los acontecimientos vitales estresantes (AVE) en la supervivencia de pacientes con CM. Método: 113 mujeres con CM recibieron psicoterapia positiva o terapia cognitivo-conductual para manejar el estrés y 37 se incluyeron como grupo control. Se analizaron los efectos de la reducción de la Escala de Ansiedad y Depresión Hospitalaria (HADS) y de los AVE sobre la recurrencia a los cinco años, así como el efecto de recibir psicoterapia y del tipo de enfoque d esta sobre la supervivencia. Resultados: La reducción de un punto en la HADS después de recibir psicoterapia predijo un menor riesgo de recurrencia, OR = 0,84, p = 0,037, IC 95% = 0,71-0,99. Además, cada aumento en el número de AVE vividos como amenazantes (OR = 1,92; p = 0,028, 95% CI = 1,07-3,43) se relacionó con una mayor recurrencia. Conclusiones: Los resultados indican la necesidad de estudiar no solo la presencia de un evento potencialmente impactante en la conducta (psicoterapia o AVE) sino el efecto especifico que ha tenido en cada individuo.

Randomized clinical trial of integral cognitive remediation program for major depression (INCREM).

BACKGROUND: Despite achieving clinical remission, patients with depression encounter difficulties to return to their premorbid psychosocial functioning. Cognitive dysfunction has been proposed to be a primary mediator of functional impairment. Therefore, the new non-pharmacological procognitive strategy INtegral Cognitive REMediation for Depression (INCREM) has been developed with the aim of targeting cognitive and psychosocial functioning. METHODS: This is a single-blind randomized controlled clinical trial with three treatment arms. Fifty-two depressed patients in clinical remission, with psychosocial difficulties and cognitive impairment, were randomly assigned to receive INCREM intervention, Psychoeducation programme, or treatment as usual. Patients were assessed before and after the study period, and six months after. The primary outcome was the change from baseline of patients' psychosocial functioning. Changes in cognitive functioning and other variables were considered secondary outcomes. RESULTS: The analysis showed a significant improvement in psychosocial functioning in the INCREM group, especially six months after the intervention, compared to patients who received the psychoeducation programme. An improvement in cognitive performance was also observed in the INCREM group. LIMITATIONS: This study includes a small sample size due to the anticipated end of the clinical trial because of the COVID-19 pandemic. DISCUSSION: These results provide preliminary evidence on the feasibility and potential efficacy of the INCREM program to improve not only cognitive performance but also psychosocial functioning in clinically remitted depressed patients, and such improvement is maintained six months after. It can be speculated that the maintenance is mediated by the cognitive enhancement achieved with INCREM.

Stressful Life Events and Distress in Breast Cancer: A 5-Years Follow-Up / Acontecimientos vitales estresantes y malestar emocional en cáncer de mama: seguimiento a 5 años

AbstractBackground/Objective: Environmental factors such as psychosocial stress have demonstrated to have an impact on the breast cancer (BC) course. This study aims to explore the impact of psychotherapy and stressful life events (SLE) on BC survivors’ illness trajectories. Method: 68 women with BC underwent Positive Psychotherapy or Cognitive-Behavioral Stress Management and 37 patients were included as a control group. The effects of distress reduction and SLE on their 5-year recurrence were investigated. Additional analyses examined the effect of receiving vs. not receiving psychotherapy and of the type of therapy on survival and disease-free interval, DFI. Results: A one-point decrease of the Hospital Anxiety and Depression Scale (HADS) after psychotherapy predicted a lower risk of 5-year recurrence, OR = 0.84, p = .037, 95% CI = 0.71-0.99). Also, a one point-increase in the number threating SLE (OR = 1.92; p = .028, 95% CI = 1.07-3.43) was related to higher 5-year recurrence. Conclusions: The findings highlight the necessity of studying not only a given situation (i.e., psychotherapy, SLE) but its specific impact on individuals.

ResumenAntecedentes/Objetivo: El estrés psicosocial ha demostrado tener un impacto en la evo-lución del cáncer de mama (CM). Este estudio tiene como objetivo explorar el impacto de la psicoterapia y de los acontecimientos vitales estresantes (AVE) en la supervivencia de pacientes con CM. Método: 113 mujeres con CM recibieron psicoterapia positiva o terapia cognitivo-conductual para controlar el estrés y 37 se incluyeron como grupo con-trol. Se analizaron los efectos de la reducción de la Escala de Ansiedad y Depresión Hos-pitalaria (HADS) y de los AVE sobre la recurrencia a los cinco años, así como el efecto de recibir psicoterapia y del tipo de enfoque sobre la supervivencia. Resultados: La reduc-ción de un punto en la HADS después de recibir psicoterapia predijo un menor riesgo de recurrencia, OR = 0,84, p = 0,037, IC 95% = 0,71-0,99. Además, cada aumento en el nú-mero de AVE vividos como amenazantes (OR = 1,92; p = 0,028, 95% CI = 1,07-3,43) se relacionó con una mayor recurrencia. Conclusiones: Los resultados indican la necesidad de estudiar no solo la presencia de un evento potencialmente impactante en la conducta (psicoterapia o AVE) sino el efecto específico que ha tenido en cada individuo.

Efficacy and fMRI-based response predictors to mindfulness-based cognitive therapy in obsessive-compulsive disorder: Study protocol for a randomised clinical trial.

BACKGROUND: Around 40-50% of patients with obsessive-compulsive disorder (OCD) suffer from obsessions and compulsions after receiving first-line treatments. Mindfulness-based cognitive therapy (MBCT) has been proposed as a reasonable augmentation strategy for OCD. MBCT trains to decentre from distressful thoughts and emotions by focusing on them voluntarily and with consciousness. This practice develops alternative ways to deal with obsessions, which could increase non-reactivity behaviours and, in turn, reduce compulsions. This study aims to investigate the efficacy of MBCT to improve OCD symptoms. Secondly, it pursues to investigate which socio-demographic, clinical, and neurobiological characteristics mediate or moderate the MBCT response; and identify potential biomarkers of positive/negative response. METHODS: This study is a randomised clinical trial (RCT) of 60 OCD patients who do not respond to first-line treatments. Participants will be randomised to either an MBCT program or treatment as usual. The MBCT group will undergo 10 weekly sessions of 120min. Principal outcome: change in OCD severity symptoms using clinician and self-reported measures. Also, participants will undergo a comprehensive evaluation assessing comorbid clinical variables, neuropsychological functioning and thought content. Finally, a comprehensive neuroimaging protocol using structural and functional magnetic resonance imaging will be acquired in a 3T scanner. All data will be obtained at baseline and post-intervention. DISCUSSION: This study will assess the efficacy of mindfulness in OCD patients who do not achieve clinical recovery after usual treatment. It is the first RCT in this subject examining clinical, neuropsychological and neuroimaging variables to examine the neural patterns associated with the MBCT response. CLINICAL TRIALS REGISTRATION: NCT03128749.

Higher order theory of mind in patients with bipolar disorder and schizophrenia/schizoaffective disorder.

Some evidence suggests that patients with bipolar disorder (BD) have better Theory of Mind (ToM) skills than patients with schizophrenia/schizoaffective disorder (SCH). However, this difference is not consistently reported across studies, so rather than being global, it may be restricted to specific aspects of ToM. Our primary objective was to compare higher order ToM performance between BD and SCH patients using the Hinting Task (HT). Ninety-four remitted patients were recruited (BD = 47, SCH = 47). Intelligence quotient (IQ), attention, memory, executive functions, and processing speed were also assessed. Patients with BD performed better on the HT than patients with SCH, even when the analysis was adjusted for IQ and neurocognition (p < 0.001, [Formula: see text] = 0.144). Regression analysis in the total sample showed that a diagnosis of SCH and lower IQ were associated with lower HT scores (R2 = 0.316, p < 0.001). In the BD group, verbal memory and processing speed were the main predictors of HT performance (R2 = 0.344, p < 0.001). In the SCH group, no variable was significant in explaining HT performance. In the context of previous studies that found no significant differences in the most basic aspects of ToM (e.g., understand other people's thoughts/beliefs), our results suggest that differences between the two disorders might be limited to the more challenging aspects (e.g., understand the intended meaning of indirect requests). No causal inferences can be made in this cross-sectional study. However, regression analyses show that whereas in BD patients, ToM functioning would be partially modulated by neurocognitive performance, in SCH patients, it could be largely independent of the well-known neurocognitive impairment.

Group and sex differences in social cognition in bipolar disorder, schizophrenia/schizoaffective disorder and healthy people.

BACKGROUND: Impairment of social cognition is documented in bipolar disorder (BD) and schizophrenia/schizoaffective disorder (SCH). In healthy individuals, women perform better than men in some of its sub-domains. However, in BD and SCH the results are mixed. Our aim was to compare emotion recognition, affective Theory of Mind (ToM) and first- and second-order cognitive ToM in BD, SCH and healthy subjects, and to investigate sex-related differences. METHODS: 120 patients (BD = 60, SCH = 60) and 40 healthy subjects were recruited. Emotion recognition was assessed by the Pictures of Facial Affect (POFA) test, affective ToM by the Reading the Mind in the Eyes Test (RMET) and cognitive ToM by several false-belief stories. Group and sex differences were analyzed using parametric (POFA, RMET) and non-parametric (false-belief stories) tests. The impact of age, intelligence quotient (IQ) and clinical variables on patient performance was examined using a series of linear/logistic regressions. RESULTS: Both groups of patients performed worse than healthy subjects on POFA, RMET and second-order false-belief (p < 0.001), but no differences were found between them. Instead, their deficits were related to older age and/or lower IQ (p < 0.01). Subthreshold depression was associated with a 6-fold increased risk of first-order false-belief failure (p < 0.001). Sex differences were only found in healthy subjects, with women outperforming men on POFA and RMET (p ≤ 0.012), but not on first/second-order false-belief. LIMITATIONS: The cross-sectional design does not allow for causal inferences. CONCLUSION: BD and SCH patients had deficits in emotion recognition, affective ToM, and second-order cognitive ToM, but their performance was comparable to each other, highlighting that the differences between them may be subtler than previously thought. First-order cognitive ToM remained intact, but subthreshold depression altered their normal functioning. Our results suggest that the advantage of healthy women in the emotional and affective aspects of social cognition would not be maintained in BD and SCH.

Structural brain correlates in major depression, anxiety disorders and post-traumatic stress disorder: A voxel-based morphometry meta-analysis.

The high comorbidity of Major Depressive Disorder (MDD), Anxiety Disorders (ANX), and Posttraumatic Stress Disorder (PTSD) has hindered the study of their structural neural correlates. The authors analyzed specific and common grey matter volume (GMV) characteristics by comparing them with healthy controls (HC). The meta-analysis of voxel-based morphometry (VBM) studies showed unique GMV diminutions for each disorder (p < 0.05, corrected) and less robust smaller GMV across diagnostics (p < 0.01, uncorrected). Pairwise comparison between the disorders showed GMV differences in MDD versus ANX and in ANX versus PTSD. These results endorse the hypothesis that unique clinical features characterizing MDD, ANX, and PTSD are also reflected by disorder specific GMV correlates.

Focusing on Comorbidity-A Novel Meta-Analytic Approach and Protocol to Disentangle the Specific Neuroanatomy of Co-occurring Mental Disorders.

BACKGROUND: In mental health, comorbidities are the norm rather than the exception. However, current meta-analytic methods for summarizing the neural correlates of mental disorders do not consider comorbidities, reducing them to a source of noise and bias rather than benefitting from their valuable information. OBJECTIVES: We describe and validate a novel neuroimaging meta-analytic approach that focuses on comorbidities. In addition, we present the protocol for a meta-analysis of all major mental disorders and their comorbidities. METHODS: The novel approach consists of a modification of Seed-based d Mapping-with Permutation of Subject Images (SDM-PSI) in which the linear models have no intercept. As in previous SDM meta-analyses, the dependent variable is the brain anatomical difference between patients and controls in a voxel. However, there is no primary disorder, and the independent variables are the percentages of patients with each disorder and each pair of potentially comorbid disorders. We use simulations to validate and provide an example of this novel approach, which correctly disentangled the abnormalities associated with each disorder and comorbidity. We then describe a protocol for conducting the new meta-analysis of all major mental disorders and their comorbidities. Specifically, we will include all voxel-based morphometry (VBM) studies of mental disorders for which a meta-analysis has already been published, including at least 10 studies. We will use the novel approach to analyze all included studies in two separate single linear models, one for children/adolescents and one for adults. DISCUSSION: The novel approach is a valid method to focus on comorbidities. The meta-analysis will yield a comprehensive atlas of the neuroanatomy of all major mental disorders and their comorbidities, which we hope might help develop potential diagnostic and therapeutic tools.

Dealing with heterogeneity of cognitive dysfunction in acute depression: a clustering approach.

BACKGROUND: Heterogeneity in cognitive functioning among major depressive disorder (MDD) patients could have been the reason for the small-to-moderate differences reported so far when it is compared to other psychiatric conditions or to healthy controls. Additionally, most of these studies did not take into account clinical and sociodemographic characteristics that could have played a relevant role in cognitive variability. This study aims to identify empirical clusters based on cognitive, clinical and sociodemographic variables in a sample of acute MDD patients. METHODS: In a sample of 174 patients with an acute depressive episode, a two-step clustering analysis was applied considering potentially relevant cognitive, clinical and sociodemographic variables as indicators for grouping. RESULTS: Treatment resistance was the most important factor for clustering, closely followed by cognitive performance. Three empirical subgroups were obtained: cluster 1 was characterized by a sample of non-resistant patients with preserved cognitive functioning (n = 68, 39%); cluster 2 was formed by treatment-resistant patients with selective cognitive deficits (n = 66, 38%) and cluster 3 consisted of resistant (n = 23, 58%) and non-resistant (n = 17, 42%) acute patients with significant deficits in all neurocognitive domains (n = 40, 23%). CONCLUSIONS: The findings provide evidence upon the existence of cognitive heterogeneity across patients in an acute depressive episode. Therefore, assessing cognition becomes an evident necessity for all patients diagnosed with MDD, and although treatment resistant is associated with greater cognitive dysfunction, non-resistant patients can also show significant cognitive deficits. By targeting not only mood but also cognition, patients are more likely to achieve full recovery and prevent new relapses.

Is cognitive dysfunction involved in difficult-to-treat depression? Characterizing resistance from a cognitive perspective.

BACKGROUND: This study aimed to identify clinical and cognitive factors associated with increased risk for difficult-to-treat depression (DTD) or treatment-resistant depression (TRD). METHODS: A total of 229 adult outpatients with major depression were recruited from the mental health unit at a public hospital. Participants were subdivided into resistant and nonresistant groups according to their Maudsley Staging Model score. Sociodemographic, clinical, and cognitive (objective and subjective measures) variables were compared between groups, and a logistic regression model was used to identify the factors most associated with TRD risk. RESULTS: TRD group patients present higher verbal memory impairment than the nonresistant group irrespective of pharmacological treatment or depressive symptom severity. Logistic regression analysis showed that low verbal memory scores (odds ratio [OR]: 2.02; 95% confidence interval [CI]: 1.38-2.95) together with high depressive symptom severity (OR: 1.29; CI95%: 1.01-1.65) were associated with TRD risk. CONCLUSIONS: Our findings align with neuroprogression models of depression, in which more severe patients, defined by greater verbal memory impairment and depressive symptoms, develop a more resistant profile as a result of increasingly detrimental neuronal changes. Moreover, our results support a more comprehensive approach in the evaluation and treatment of DTD in order to improve illness course. Longitudinal studies are warranted to confirm the predictive value of verbal memory and depression severity in the development of TRD.

Childhood maltreatment and risk for suicide attempts in major depression: a sex-specific approach.

Background: Childhood maltreatment increases the risk of suicide attempts in the general population, possibly having similar effects among patients with major depressive disorder (MDD). The few studies that have addressed this association have been restricted to specific populations (e.g. treatment-resistant depression, personality disorders) and have rarely taken sex into account. Objective: To examine the impact of childhood maltreatment on suicide attempts among MDD patients above and beyond other risk factors and potential confounders, while considering potential sex-specific effects. Methods: The study assessed 165 patients with a principal diagnosis of MDD. Neurological alterations, psychiatric comorbidities, and drug abuse were reasons for exclusion. Logistic regressions using the whole sample, and divided by sex, were run to test the association between childhood maltreatment and history of suicide attempts, controlling for symptom severity, comorbidities, and treatment-resistant depression. Results: There was a significant and clinically relevant association between childhood maltreatment and history of suicide attempts in the total sample. Patients with childhood maltreatment were 3.01 times more likely to present a history of suicide attempts than patients without childhood maltreatment. A family history of psychiatric disorders also contributed to the variance of attempted suicide, but its interaction with childhood maltreatment was not statistically significant. When testing the model separately, the effect of childhood maltreatment on suicide attempts remained for females, whereas for males, age of MDD onset and Childhood Trauma Questionnaire minimization-denial scale were predictive variables. Conclusions: Childhood maltreatment is a clear predictor of suicidal behaviour among MDD patients, and this effect remains significant after controlling for potential confounders. Also, the sex of patients emerges as a relevant factor that may model the mechanisms underlying the prediction of suicide attempts. Since suicide is the main cause of premature death among MDD patients, interventions targeting childhood maltreatment should be included in preventive and clinical strategies.

Planteamiento: el maltrato infantil aumenta el riesgo de intentos de suicidio en la población general, y podría tener efectos similares en pacientes con trastorno depresivo mayor (TDM). Los escasos estudios que han abordado este tema se han restringido a poblaciones específicas (p.ej. depresión resistente al tratamiento, trastornos de personalidad) y rara vez tienen en cuenta el sexo.Objetivo: evaluar el impacto del maltrato infantil en las tentativas de suicidio en pacientes con TDM, considerando potenciales factores de riesgo y de confusión, al tiempo que se estudian los posibles efectos del sexo.Método: se evaluó una muestra de 165 pacientes con diagnóstico principal de TDM. Las alteraciones neurológicas, las comorbilidades psiquiátricas y el abuso de drogas fueron motivos de exclusión. Para explorar la asociación entre el maltrato infantil y el historial de intentos de suicidio (controlando por la gravedad de los síntomas, la comorbilidad y la resistencia al tratamiento), se realizaron regresiones logísticas con la muestra completa, así como en hombres y mujeres por separado.Resultados: existe una asociación significativa y clínicamente relevante entre el maltrato infantil y la historia de intentos de suicidio en el total de la muestra. Las personas con maltrato infantil tenían 3,01 veces más probabilidades de presentar historia de tentativas de suicidio que aquellas sin maltrato infantil. Los antecedentes familiares de trastorno psiquiátrico también contribuyeron a la varianza de los intentos de suicidio, pero su interacción con el maltrato infantil no resultó estadísticamente significativa. Al analizar el modelo por separado, el efecto del maltrato infantil en las tentativas suicidas se mantuvo en las pacientes mujeres, mientras que en los pacientes hombres la edad de inicio del TDM y la escala de minimización-negación del CTQ fueron las variables explicativas.Conclusiones: el maltrato infantil predice el comportamiento suicida en pacientes con TDM, persistiendo este efecto después de controlar posibles factores de confusión. Además, el sexo de las personas modelaría los mecanismos subyacentes en cuanto a predecir las tentativas de suicidio. Dado que el suicidio es la principal causa de muerte prematura entre pacientes con TDM, las intervenciones dirigidas al maltrato infantil deberían incluirse dentro de las estrategias tanto preventivas como terapéuticas.

Testing the efficacy of INtegral Cognitive REMediation (INCREM) in major depressive disorder: study protocol for a randomized clinical trial.

BACKGROUND: Given the limitation of pharmacological treatments to treat cognitive symptoms in patients with Major Depressive Disorder (MDD), cognitive remediation programs has been proposed as a possible procognitive intervention but findings are not conclusive. This study investigates the efficacy of an INtegral Cognitive REMediation (INCREM) that includes a combination of a Functional Remediation (FR) strategy plus a Computerized Cognitive Training (CCT) in order to improve not only cognitive performance but also the psychosocial functioning and the quality of life. METHODS: A single blind randomized controlled clinical trial in 81 patients with a diagnosis of MDD in clinical remission or in partial remission. Participants will be randomized to one of three conditions: INCREM (FR + CCT), Psychoeducation plus online games and Treatment As Usual (TAU). Intervention will consist in 12 group sessions, of approximately 110 min once a week. The primary outcome measure will be % of change in psychosocial functioning after treatment measured by the Functional Assessment Short Test (FAST); additionally, number of sick leaves and daily activities will also be recorded as pragmatic outcomes. DISCUSSION: To our knowledge, this is the first randomized controlled clinical trial using a combination of two different approaches (FR + CCT) to treat the present cognitive deficits and to promote their improvements into a better psychosocial functioning. TRIAL REGISTRATION: Clinical Trials NCT03624621 . Date registered 10th of August 2018 and last updated 24th August 2018.

Discrepancy between objective and subjective cognition in major depressive disorder.

Objective and subjective cognitive measures are altered in major depressive disorder (MDD), but there is a poor correlation between them. This study aims to explore such discrepancy and the characteristics explaining this phenomenon. 229 patients with MDD subdivided into remitted (n = 57), partially remitted (n = 90) and acute (n = 82) underwent a clinical interview, completed self-report questionnaires and a neuropsychological assessment. The association between objective and subjective cognition was evaluated in the areas of attention and memory. Also, dependent measures of concordance and self-appraisal were calculated for each patient. Potential predictors of these outcomes were evaluated through regression analysis. Depressive symptoms correlated negatively with objective but especially with subjective cognition. Patients in an acute episode showed a significant correlation between objective and subjective attention/memory measures, but also the greatest underestimation of their cognitive performance. In those with fewer depressive symptoms, objective and subjective cognition showed poor correspondence between them. In the regression analyses with the full MDD sample, higher scores on depressive symptoms, intelligence quotient and executive functions predicted lower self-appraisal. Objective and subjective cognition show poor concordance in MDD patients, especially in those with residual mood symptoms. Higher executive functions also explain this discrepancy. Assessments of both subjective cognitive complaints and objective performance seem necessary as they may be measuring different aspects of cognitive functioning.

Cognición en remisión / Cognitive remission

Las alteraciones cognitivas son comunes en el contexto del trastorno depresivo mayor. En la actualidad, existe una creciente evidencia que demuestra que la presencia de estas alteraciones no sólo se limita al episodio depresivo agudo o activo, sino que transciende y persiste de forma significativa tras la remisión de la sintomatología depresiva en un porcentaje importante de pacientes que han sufrido depresión. El objetivo de este trabajo es revisar la literatura que ha abordado este aspecto con el fin de definir el perfil y patrón sintomático de las disfunciones cognitivas en la depresión en remisión y establecer su repercusión clínica y funcional. Distintos estudios han evaluado la alteración del funcionamiento cognitivo tras la remisión y han objetivado alteraciones de distintos dominios cognitivos; entre ellos destacan las alteraciones en la atención, la memoria y las funciones ejecutivas como los más relevantes. La presencia de estas alteraciones están relacionadas con un impacto significativo en el rendimiento funcional del paciente, así como en la calidad de vida del mismo e incrementa el riesgo de nuevas recaídas depresivas. Es necesario incrementar los esfuerzos en aras de evaluar de forma adecuada la presencia de estas alteraciones en los pacientes que hayan padecido un cuadro depresivo y el desarrollo de estrategias adecuadas para su abordaje terapéutico efectivo (AU)

Cognitive impairments are common in the context of major depressive disorder. Nowadays, there is growing evidence confirming that these alterations are present not only during acute or active depressive episodes, but that they persist for some time after significant remission of depressive symptoms in a substantial percentage of patients who have suffered from this disorder. This study reviews the literature that has addressed this issue with a view to defining the profile and pattern of cognitive dysfunction in remitted depression and establishing its clinical and functional impact. Various studies have assessed impaired cognitive functioning after remission and have demonstrated alterations in distinct cognitive domains; the most important of these alterations involve dysfunctions in attention, memory and executive function. The presence of these alterations significantly affects the patient’s functional performance and quality of life and increases the risk of further depressive relapses. There is a need for increased efforts to adequately assess the presence of these alterations in patients who have had depressive symptoms and to develop appropriate therapeutic strategies for their effective management (AU)