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.

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.

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.

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.

NATURALISTIC COURSE OF MAJOR DEPRESSIVE DISORDER PREDICTED BY CLINICAL AND STRUCTURAL NEUROIMAGING DATA: A 5-YEAR FOLLOW-UP.

BACKGROUND: Despite its high recurrence rate, major depression disorder (MDD) still lacks neurobiological markers to optimize treatment selection. The aim of this study was to examine the prognostic potential of clinical and structural magnetic resonance imaging (sMRI) in the long-term MDD clinical outcomes (COs). METHODS: Forty-nine MDD patients were grouped into one of four different CO categories according to their trajectory: recovery, partial remission, remission recurrence, and chronic depression. Regression models including baseline demographic, clinical, and sMRI data were used for predicting patients' COs and symptom severity 5 years later. RESULTS: The model including only clinical data explained 32.4% of the variance in COs and 55% in HDRS, whereas the model combining clinical and sMRI data increased up to 52/68%, respectively. A bigger volume of right anterior cingulate gyrus was the variable that best predicted COs. CONCLUSIONS: The findings suggest that the addition of sMRI brain data to clinical information in depressive patients can significantly improve the prediction of their COs. The dorsal part of the right anterior cingulate gyrus may act as a potential biomarker of long-term clinical trajectories.

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.

Cognitive-enhanced eHealth psychosocial stepped intervention for managing breast cancer-related cognitive impairment: Protocol for a randomized controlled trial.

Introduction: Breast cancer often leads to cancer-related cognitive impairment (CRCI), which includes both objective and subjective cognitive deficits. While psychosocial interventions benefit quality of life and distress reduction, their impact on cognitive deficits is uncertain. This study evaluates the integration of a cognitive module into a digital psychosocial intervention for breast cancer patients. Methods: In this randomized controlled trial (RCT), 88 recently diagnosed breast cancer (BC) patients will receive the ICOnnecta't program (control group) - a digital stepped intervention addressing a variety of psychosocial needs. The experimental group (n = 88) will receive ICOnnecta't plus a cognitive module. Assessments at baseline, 3, 6, and 12 months will measure the interventions' impact on cognition, emotional distress, medication adherence, quality of life, post-traumatic stress, work functioning and healthcare experience. Feasibility and cost-utility analyses will also be conducted. Results: The cognitive module includes three levels. The first level contains a cognitive screening using FACT-Cog Perceived Cognitive Impairment (PCI). Patients with PCI <54 progress to a cognitive psychoeducational campus (Level 2) with content on cognitive education, behavioural strategies and mindfulness. Patients with persistent or worsened PCI (≥6) after 3 months move to Level 3, an online cognitive training through CogniFit software delivered twice a week over 12 weeks. Conclusions: This study assesses whether integrating a cognitive module into a digital psychosocial intervention improves objective and subjective cognition in breast cancer patients. Secondary outcomes explore cognitive improvement's impact on psychosocial variables. The research will contribute to testing efficacious approaches for detecting and addressing cognitive dysfunction in breast cancer patients. Trial registration: ClinicalTrials.gov, NCT06103318. Registered 26 October 2023, https://classic.clinicaltrials.gov/ct2/show/NCT06103318?term=serra-blasco&draw=2&rank=4.

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.

Effects of illness duration and treatment resistance on grey matter abnormalities in major depression.

BACKGROUND: Findings of brain structural changes in major depressive disorder are still inconsistent, partly because some crucial clinical variables have not been taken into account. AIMS: To investigate the effect of major depressive disorder on grey matter volumes. METHOD: Voxel-based morphometry was used to compare 66 patients with depression at different illness stages (22 each with first-episode, remitted-recurrent and treatment resistant/chronic depression) with 32 healthy controls. Brain volumes were correlated with clinical variables. RESULTS: Voxel-based morphometry showed a significant group effect in right superior frontal gyrus, left medial frontal gyrus and left cingulate gyrus (P<0.05, family wise error-corrected). Patients whose condition was treatment resistant/chronic exhibited the smallest volumes in frontotemporal areas. Longer illness duration was negatively correlated with decreases in right medial frontal cortex and left insula. CONCLUSIONS: Frontotemporolimbic areas are smaller in the patients with severe depression and are associated with duration of illness, but not with medication patterns, suggesting negative effects of long-lasting major depressive disorder on grey matter.

Hippocampal abnormalities of glutamate/glutamine, N-acetylaspartate and choline in patients with depression are related to past illness burden.

BACKGROUND: Smaller hippocampal volumes in major depressive disorder (MDD) have been linked with earlier onset, previous recurrences and treatment refractoriness. The aim of our study was to investigate metabolite abnormalities in the hippocampus associated with past depressive illness burden. METHODS: Glutamate/glutamine (Glx), N-acetylaspartate (NAA) and choline (Cho), potential markers of glial/neuronal integrity and membrane turnover, respectively, were measured in adults with depression and healthy controls using a 3 T magnetic resonance spectroscopy scanner. Voxels were placed in the head of the right and left hippocampus. We controlled for systematic differences resulting from volume-of-interest (VOI) tissue composition and total hippocampal volume. RESULTS: Our final sample comprised a total of 16 healthy controls and 52 adult patients with depression in different stages of the illness (20 treatment-resistant/chronic, 18 remitted-recurrent and 14 first-episode), comparable for age and sex distribution. Patients with treatment-resistant/chronic and remitted-recurrent depression had significantly lower levels of Glx and NAA than controls, especially in the right hippocampal region (p ≤ 0.025). Diminished levels of Glx were correlated with longer illness duration (left VOI r = -0.34, p = 0.01). By contrast, Cho levels were significantly higher in patients with treatment-resistant/chronic depression than those with first-episode depression or controls in the right and left hippocampus (up to 19% higher; all p ≤ 0.025) and were consistently related to longer illness duration (right VOI r = 0.30, p = 0.028; left VOI r = 0.38, p = 0.004) and more previous episodes (right VOI r = 0.46, p = 0.001; left VOI r = 0.44, p = 0.001). LIMITATIONS: The cross-sectional design and the inclusion of treated patients are the main limitations of the study. CONCLUSION: Our results support that metabolite alterations within the hippocampus are more pronounced in patients with a clinical evolution characterized by recurrences and/or chronicity and add further evidence to the potential deleterious effects of stress and depression on this region.

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.

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.

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".

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.

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.

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.

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.