Risk factors for suicide reattempt: a systematic review and meta-analysis.

BACKGROUND: Suicide is one of the main external causes of death worldwide. People who have already attempted suicide are at high risk of new suicidal behavior. However, there is a lack of information on the risk factors that facilitate the appearance of reattempts. The aim of this study was to calculate the risk of suicide reattempt in the presence of suicidal history and psychosocial risk factors and to estimate the effect of each individual risk factor. METHODS: This systematic review and meta-analysis were conducted following the PRISMA-2020 guidelines. Studies on suicide reattempt that measured risk factors were searched from inception to 2022. The risk factors studied were those directly related to suicide history: history of suicide prior to the index attempt, and those that mediate the transition from suicidal ideation to attempt (alcohol or drug misuse, impulsivity, trauma, and non-suicidal self-injury). RESULTS: The initial search resulted in 11 905 articles. Of these, 34 articles were selected for this meta-analysis, jointly presenting 52 different effect sizes. The pooled effect size across the risk factors was significant (OR 2.16). Reattempt risk may be increased in presence of any of the following risk factors: previous history, active suicidal ideation, trauma, alcohol misuse, and drug misuse. However, impulsivity, and non-suicidal self-injury did not show a significant effect on reattempt. CONCLUSION: Most of the risk factors traditionally associated with suicide are also relevant when talking about suicide reattempts. Knowing the traits that define reattempters can help develop better preventive and intervention plans.

Anxious and depressive symptoms and health-related quality of life in a cohort of people who recently attempted suicide: A network analysis.

BACKGROUND: Suicide is an international health concern with immeasurable impact from the perspective of human and social suffering. Prior suicide attempts, anxious and depressive symptoms, and relatively lower health-related quality of life (HRQoL) are among the most replicated risk factors for suicide. Our goal was to visualize the distribution of these features and their interconnections with use of a network analysis approach in individuals who recently attempted suicide. METHODS: Individuals with a recent suicide attempt were recruited from nine University Hospitals across Spain as part of the SURVIVE cohort study. Anxious and depressive symptoms, and perceived HRQoL were included in the network analysis. Network structures were estimated with the EBICglasso model. Centrality measures and bridge symptoms connecting communities were explored. Subnetworks comparing younger and older individuals, and women and men were analyzed. RESULTS: A total of 1106 individuals with a recent suicide attempt were included. Depressed mood was the symptom with the greatest influence in the overall network, followed by anxiety symptoms such as feeling nervous, worrying, restless, and having difficulties to relax. Perceived general health was associated with increased suicidal ideation in the whole sample. Older people showed a specific connection between perceived general health and depressed mood. LIMITATIONS: The cross-sectional design does not allow determination of established causality. CONCLUSIONS: Depressed mood was the core network's symptom and, therefore, an important target in the management and prevention of suicide. HRQoL had more influence on the network of older populations, in which it should be a primary focus.

Psychiatric profiles in suicidal attempters: Relationships with suicide behaviour features.

BACKGROUND: Suicide constitutes a major health concern worldwide, being a significant contributor of death, globally. The diagnosis of a mental disorder has been extensively linked to the varying forms of suicidal ideation and behaviour. The aim of our study was to identify the varying diagnostic profiles in a sample of suicide attempters. METHODS: A sample of 683 adults (71.3% females, 40.10±15.74 years) admitted at a hospital emergency department due to a suicide attempt was recruited. Latent class analysis was used to identify diagnostic profiles and logistic regression to study the relationship between comorbidity profile membership and sociodemographic and clinical variables. RESULTS: Two comorbidity profiles were identified (Class I: low comorbidity class, 71.3% of attempters; Class II: high comorbidity class, 28.7% of attempters). Class I members were featured by the diagnosis of depression and general anxiety disorder, and low comorbidity; by contrast, the high comorbidity profile was characterized by a higher probability of presenting two or more coexisting psychiatric disorders. Class II included more females, younger, with more depressive symptoms and with higher impulsivity levels. Moreover, Class II members showed more severe suicidal ideation, higher number of suicide behaviours and a greater number of previous suicide attempts (p<.01, for all the outcomes), compared to Class I members. CONCLUSIONS: Psychiatric profiles may be considered for treatment provision and personalized psychiatric treatment in suicidal attempters as well as tackle suicide risk.

Reconsidering the Use of Population Health Surveys for Monitoring of Mental Health.

Monitoring of the mental health status of the population and assessment of its determinants are 2 of the most relevant pillars of public mental health, and data from population health surveys could be instrumental to support them. Although these surveys could be an important and suitable resource for these purposes, due to different limitations and challenges, they are often relegated to the background behind other data sources, such as electronic health records. These limitations and challenges include those related to measurement properties and cross-cultural validity of the tools used for the assessment of mental disorders, their degree of representativeness, and possible difficulties in the linkage with other data sources. Successfully addressing these limitations could significantly increase the potential of health surveys in the monitoring of mental disorders and ultimately maximize the impact of the relevant policies to reduce their burden at the population level. The widespread use of data from population health surveys, ideally linked to electronic health records data, would enhance the quality of the information available for research, public mental health decision-making, and ultimately addressing the growing burden of mental disorders.

Second victim experience in Spanish psychiatrists coping with patient suicide: A call for postvention.

BACKGROUND: Losing a patient by suicide may lead to psychological distress and mid/long-term personal and professional consequences for psychiatrists, becoming second victims. MATERIAL AND METHODS: The validated Spanish version of the Second Victim Experience and Support Tool (SVEST-E) questionnaire and a 30-item questionnaire created ad-hoc was administered online to psychiatrists from all over Spain to evaluate how patient suicide affects mental health professionals. RESULTS: Two hundred ninety-nine psychiatrists participated in the survey, and 256 completed the SVEST-E questionnaire. The results of the SVEST-E questionnaire revealed a negative impact of suicide on emotional and physical domains, although this seemed not to lead to work absenteeism. Most respondents desired peer support from a respected colleague and considered institutional support, although desirable, lacking. Almost 70% of surveyed stated that an employee assistance program providing free counseling to employees outside of work would be desirable. The ad-hoc questionnaire showed that up to 88% of respondents considered some suicides unavoidable, and 76% considered the suicide unexpected. Almost 60% of respondents reported no changes in the approach of patients with suicidal ideation/behavior, after losing a patient. However, up to 76% reported performing more detailed clinical evaluations and notes in the medical record. Up to 13% of respondents considered leaving or changing their job or advancing retirement after losing a patient by suicide. CONCLUSIONS: After a patient's suicide, psychiatrists often suffer the feelings of second victim, impacting personal and professional areas. The study results indicate the need for postvention strategies to mitigate the negative impact of patient suicide.

Reliability and cross-country equivalence of the 8-item version of the Patient Health Questionnaire (PHQ-8) for the assessment of depression: results from 27 countries in Europe.

Background: The 8-item version of the Patient Health Questionnaire (PHQ-8) is one of the self-reported questionnaires most frequently used worldwide for the screening and severity assessment of depression. However, in some European countries its reliability is unknown, and it is unclear whether its psychometric properties vary between European countries. Therefore, the aim of this study was to assess the internal structure, reliability and cross-country equivalence of the PHQ-8 in Europe. Methods: All participants from the 27 countries included in the second wave of the European Health Interview Survey (EHIS-2) between 2014 and 2015 with complete information on the PHQ-8 were included (n = 258,888). The internal structure of the PHQ-8 was assessed using confirmatory factor analyses (CFA) for categorical items. Additionally, the reliability of the questionnaire was assessed based on the internal consistency, Item Response Theory information functions, and item-discrimination (using Graded Response Models), and the cross-country equivalence based on multi-group CFA. Findings: The PHQ-8 shows high internal consistency for all countries. The countries in which the PHQ-8 was more reliable were Romania, Bulgaria and Cyprus and less reliable were Iceland, Norway and Austria. The PHQ-8 item with highest discrimination was item 2 (feeling down, depressed, or hopeless) in 24 of the 27 countries. Measurement invariance between countries in Europe was observed from multigroup CFA at the configural, metric and scalar levels. Interpretation: The results from our study, likely the largest study to the date assessing the internal structure, reliability and cross-country comparability of a self-reported mental health assessment measure, shows that the PHQ-8 has an adequate reliability and cross-country equivalence across the 27 European countries included. These results highlight the suitability of the comparisons of the PHQ-8 scores in Europe. They could be helpful to improve the screening and severity assessment of depressive symptoms at the European level. Funding: This work was partially funded by CIBER Epidemiology and Public Health (CIBERESP) as part of the Intramural call of 2021 (ESP21PI05).

The Suicide Prevention and Intervention Study (SURVIVE): Study protocol for a multisite cohort study with nested randomized-controlled trials.

INTRODUCTION: Suicide is one of the leading causes of avoidable death. Gathering national data on suicidal behaviour incidence is crucial to develop evidence-based public policies. The study has two primary objectives: (1) to determine the incidence of suicide attempts in Spain and related risk factors, and (2) to analyze the efficacy of secondary prevention programmes to prevent suicide re-attempting in comparison to treatment as usual (TAU). MATERIALS AND METHODS: Multisite, coordinated, cohort study with three nested randomized controlled trials. A cohort of 2000 individuals (age >=12) with suicidal behaviour will be recruited at ten sites distributed across Spain. Assessments will be conducted within 10 days of the suicide attempt (V0-baseline visit) and after 12 months (V4-last visit) and will include clinician reported and participant reported outcomes (PROs). Between V0 and V4, PROs will be collected remotely every three months (V1, V2 and V3). Optatively, cohort participants will participate in three nested randomized-controlled-trials (RCTs) evaluating different secondary prevention interventions: Participants aged 18 years and older will be randomly allocated to: Telephone-based Management+TAU vs. TAU or iFightDepression-Survive+TAU vs. TAU. Participants aged between 12 and 18 years will be allocated to a specific intervention for youths: Self Awareness of Mental Health+TAU vs. TAU. RESULTS: This study will provide interesting data to estimate suicide attempt incidence in Spain. and will provide evidence on three. CONCLUSIONS: Evidence on three potentially efficacious interventions for individuals at high risk of suicide will be obtained, and this could improve the treatment given to these individuals. TRIAL REGISTRATION: NCT04343703.

Clinical predictors and psychosocial risk factors of suicide attempt severity.

BACKGROUND: Suicide attempts are an important predictor of completed suicide and may differ in terms of severity of medical consequences or medical lethality. There is little evidence on serious suicide attempt (SSA) and very few studies have compared SSA with non-SSA. OBJECTIVE: The aim of this multisite, coordinated, cohort study was to analyze the role of clinical variables and the sociodemographic and psychological risk factors of SSA. METHOD: In this multisite, coordinated, cohort study, 684 participants (222 for the mild suicide attempt group, 371 for the moderate suicide attempt group and 91 for the SSA group) were included in the study. Ordinal regression models were performed to analyze the predictor variables of SSA. RESULTS: Early physical abuse (OR=1.231) and impulsivity (OR=1.036) were predictors of SSA, while depressive symptoms were associated with a lower risk of SSA. CONCLUSION: Environmental and psychological factors as physical abuse and impulsivity are related with severe suicide severity. These findings will help to develop strategies to prevent suicide and may be considered for the treatment and management of suicide.

Safety intervention for improving functioning in suicidal attempters (STRONG): A secondary prevention study. Study rationale and research protocol.

BACKGROUND: Suicide is one of the most largely preventable causes of death worldwide. The aim of the STRONG study is to assess the effectiveness of a specific intervention (an extended Safety Planning Intervention) called iFightDepression-SURVIVE (iFD-S) in suicidal attempters by changes in psychosocial functioning. As secondary outcomes, quality of life, cognitive performance, clinical state and neuroimaging correlates will be considered. OBJECTIVE: To describe the rationale and design of the STRONG study, an extension of the SURVIVE study, a national multicenter cohort about on prevention in suicidal attempters. METHODS: The STRONG study is a two-year clinical trial. A total sample of 60 patients will be randomly allocated to two arms: a group will receive a iFD-S and treatment as usual (TAU) (n=30 treatment group), while another group will exclusively receive TAU (n=30 control group). There will be three study points: baseline; 3-month; and 6-month follow-up assessments, all of which will include rater-blinded evaluation of psychosocial functioning, quality of life, clinical state, cognitive performance and neuroimaging acquisition. RESULTS: It is expected to obtain data on the efficacy of iFD-S in patients who have committed a suicide attempt. CONCLUSION: Results will provide insight into the effectiveness of IFD-S in suicidal attempters with respect to improvements in psychosocial functioning, quality of life, cognition, and neuroimaging correlates. CLINICAL TRIALS ID: NCT05655390.

Advancing the treatment of long-lasting borderline personality disorder: a feasibility and acceptability study of an expanded DBT-based skills intervention.

BACKGROUND: Long-term follow-up studies in patients with borderline personality disorder (BPD) consistently show persistent impairment in psychosocial adjustment, although symptoms tend to decrease over time. Consequently, it might be better to deemphasize symptom-oriented interventions and instead promote interventions that incorporate patient perspectives on recovery. In this study we aimed to examine the feasibility and acceptability of a novel intervention (dialectical behavioral therapy combined with positive psychology and contextual-based skills) in the clinical treatment of long-lasting BPD difficulties. METHODS: This was a qualitative study. We developed an initial 8-week group intervention for long-lasting BPD. Upon completion of the 8-week program, the participants were asked to participate in a group discussion to provide feedback. Based on that feedback, the intervention protocol was modified and then offered to a second group of patients, who also provided feedback. The protocol was revised again and administered to a third group. A total of 32 patients participated in the group interventions; of these, 20 provided feedback in the qualitative study. The main outcome measure was acceptability. RESULTS: The following overarching themes emerged from the group interviews: helpful, unhelpful and neutral practices; internal/external barriers; facilitators; and effects. Participants reported difficulties in imagining an optimal future and self-compassion. By contrast, positive skills were associated with an increase in positive emotions. The main internal barrier was facing difficult emotions. The main external barriers were language-related issues. The group format was perceived as a facilitator to success. Dropout rates, which were assessed as an additional measure of acceptability, decreased substantially in each successive group, from 60 to 40% and finally 20%. CONCLUSIONS: The intervention was feasible to implement in the clinical setting and participants rated the final set of skills highly. Most of the skills were considered useful. Participant feedback was invaluable to improve the intervention, as evidenced by the large increase in the retention rate from 40 to 80%. Randomized clinical trials are needed to test the efficacy of this intervention in promoting well-being in participants with long-lasting BPD.

Cognitive and quality-of-life related factors of body mass index (BMI) improvement after deep brain stimulation in the subcallosal cingulate and nucleus accumbens in treatment-refractory chronic anorexia nervosa.

BACKGROUND: Up to 20% of the cases of anorexia nervosa (AN) are chronic and treatment-resistant. Recently, the efficacy of deep brain stimulation (DBS) for severe cases of AN has been explored, with studies showing an improvement in body mass index and other psychiatric outcomes. While the effects of DBS on cognitive domains have been studied in patients with other neurological and psychiatric conditions so far, no evidence has been gathered in AN. METHODS: Eight patients with severe, chronic, treatment-resistant AN received DBS either to the nucleus accumbens (NAcc) or subcallosal cingulate (SCC; four subjects on each target). A comprehensive battery of neuropsychological and clinical outcomes was used before and 6-month after surgery. FINDINGS: Although Body Mass Index (BMI) did not normalise, statistically significant improvements in BMI, quality of life, and performance on cognitive flexibility were observed after 6 months of DBS. Changes in BMI were related to a decrease in depressive symptoms and an improvement in memory functioning. INTERPRETATION: These findings, although preliminary, support the use of DBS in AN, pointing to its safety, even for cognitive functioning; improvements of cognitive flexibility are reported. DBS seems to exert changes on cognition and mood that accompany BMI increments. Further studies are needed better to determine the impact of DBS on cognitive functions.

The Effectiveness of Mindfulness-Based Cognitive Therapy in Primary Care and the Role of Depression Severity and Treatment Attendance.

Objectives: Evidence suggests the efficacy of mindfulness-based cognitive therapy (MBCT) to prevent depression relapse and decrease depressive symptoms during the acute phase. However, the effectiveness of MBCT in real-world heterogeneous samples treated in clinical health settings, including primary care, has received little attention. This study had two aims: (1) to evaluate the effectiveness of MBCT delivered in primary care considering pre-treatment depression scores and (2) to explore the role of participants' characteristics on symptom improvement. Methods: Data were obtained from 433 individuals who received MBCT. Participants completed the Personality Inventory for ICD-11 (PiCD) pretreatment and the Beck Depression Inventory (BDI-II) pre- and post-treatment. Results: Sixty percent presented moderate-to-severe depression according to scores on the BDI-II, 18.1% presented mild depression, and 21.7% were in the non-depressed range. The severity of pre-treatment depressive symptoms was associated with outcomes. Most individuals who lacked depressive symptoms at baseline remained in the non-clinical range after the treatment. Those in the severe group benefited the most from the intervention, since 35.6% were considered recovered. Rates of deterioration ranged from 2.1 to 2.7%, depending on the depression-baseline scores. Depression severity at the entrance, attendance, and age, but not personality traits, appear to be related to symptom improvement. Conclusions: According to our results, MBCT can be effectively and safely delivered in primary care.

A Functional Connectivity Study to Investigate the Role of the Right Anterior Insula in Modulating Emotional Dysfunction in Borderline Personality Disorder.

OBJECTIVE: Previous imaging studies in patients with borderline personality disorder (BPD) have detected functional brain dysfunctions. Mindfulness training may improve the symptoms of BPD, although the neural mechanisms involved remain poorly understood. This study had several key aims: a) to investigate the role of right anterior insula (rAI) functional connectivity in modulating baseline emotional status in BPD, b) to compare differences in connectivity changes after mindfulness training versus interpersonal effectiveness intervention, and c) to explore the correlation between longitudinal changes in imaging data and clinical indicators. METHODS: Thirty-eight patients with BPD underwent resting-state functional magnetic resonance imaging. Participants completed self-report clinical scales and participated in a dialectical-behavioral therapy (mindfulness versus interpersonal effectiveness modules). Changes in clinical and imaging variables were evaluated longitudinally after completion of the first 10-week sessions of psychotherapeutic intervention. RESULTS: At baseline, the rAI was strongly connected with the other salience network nodes and anticorrelated with most core nodes of the default mode network (p < .05, corrected). The functional connectivity of the rAI correlated with emotional dysregulation and deficits in mindfulness capacities (p < .05, corrected). After completion of psychotherapeutic intervention, both groups (mindfulness and interpersonal effectiveness) showed divergent posttherapy functional connectivity changes, which were in turn associated with the clinical response. CONCLUSIONS: The functional connectivity of the rAI seems to play an important role in emotion dysregulation and deficits in mindfulness capacities in individuals with BPD. Psychotherapy seems to modulate this functional connectivity, leading to beneficial changes in clinical variables.

Ayahuasca may help to improve self-compassion and self-criticism capacities.

OBJECTIVE: Ayahuasca is a psychedelic brew that originated in the Amazon basin. The psychological effects of this drug are becoming better understood due to the growing research interest in identifying new potential therapeutic agents for the treatment of emotion dysregulation and other disorders. Previous studies suggest that ayahuasca enhances mindfulness-related capacities (decentering, non-judging, non-reacting and acceptance) and emotion regulation. The aim of the present exploratory study was to determine the effects of ayahuasca on self-compassion in a community sample. METHODS: We administered validated questionnaires (the Self-Compassion Scale-Short Form and Forms of Self-Criticism and Self-Reassurance) to evaluate pre-post changes in self-compassion and self-criticism/self-reassurance in 45 volunteers (27 women; 60%) before and after (≤24 h) an ayahuasca ceremony. Most participants (n = 29; 67.4%) had previously used ayahuasca. RESULTS: Ayahuasca resulted in significant improvements, with medium to large effect sizes (η2  = 0.184-0.276), in measures of self-compassion (p < 0.05), self-criticism (p < 0.01) and self-reassurance (p < 0.01). CONCLUSIONS: The findings of this study suggest that ayahuasca promotes well-being and self-compassion, which could have a therapeutic effect on individuals with negative affect and other psychopathological conditions. Large, controlled studies are needed to confirm these findings.

Mindfulness in Borderline Personality Disorder: Decentering Mediates the Effectiveness.

BACKGROUND: Mindfulness skills training is a core component of dialectical behavior therapy (DBT) that has proven to be an effective stand-alone treatment for the general symptoms commonly present in patients with borderline personality disorder (BPD). The aim of the present study was to compare the effectiveness of mindfulness-based DBT skills training (DBT-M) to interpersonal effectiveness-based DBT skills training (DBT-IE) in reducing BPD symptoms. We also evaluated the specific mechanism of action of these therapies through two proposed mediators: decentering and emotion dysregulation. METHOD: A total of 102 participants diagnosed with BPD were included in the study. Multivariate repeated-measures ANOVAs were performed followed by a multiple mediation analysis. RESULTS: The analyses showed that DBT-M was more effective than DBT-IE in reducing BPD symptoms, although both interventions were effective in reducing emotion dysregulation. We identified a serial mediation model in which DBT-M reduced BPD symptoms by increasing decentering ability, which in turn reduced emotion dysregulation. This mediation effect showed that changes in decentering preceded improvements in emotion dysregulation. CONCLUSIONS: These findings underscore the key role of decentering as a primary mechanism of action in DBT-M, suggesting that this skill is a main component for BPD treatment.

The clinical effectiveness of using a predictive algorithm to guide antidepressant treatment in primary care (PReDicT): an open-label, randomised controlled trial.

Depressed patients often do not respond to the first antidepressant prescribed, resulting in sequential trials of different medications. Personalised medicine offers a means of reducing this delay; however, the clinical effectiveness of personalised approaches to antidepressant treatment has not previously been tested. We assessed the clinical effectiveness of using a predictive algorithm, based on behavioural tests of affective cognition and subjective symptoms, to guide antidepressant treatment. We conducted a multicentre, open-label, randomised controlled trial in 913 medication-free depressed patients. Patients were randomly assigned to have their antidepressant treatment guided by a predictive algorithm or treatment as usual (TaU). The primary outcome was the response of depression symptoms, defined as a 50% or greater reduction in baseline score of the QIDS-SR-16 scale, at week 8. Additional prespecified outcomes included symptoms of anxiety at week 8, and symptoms of depression and functional outcome at weeks 8, 24 and 48. The response rate of depressive symptoms at week 8 in the PReDicT (55.9%) and TaU (51.8%) arms did not differ significantly (odds ratio: 1.18 (95% CI: 0.89-1.56), P = 0.25). However, there was a significantly greater reduction of anxiety in week 8 and a greater improvement in functional outcome at week 24 in the PReDicT arm. Use of the PReDicT test did not increase the rate of response to antidepressant treatment estimated by depressive symptoms but did improve symptoms of anxiety at week 8 and functional outcome at week 24. Our findings indicate that personalisation of antidepressant treatment may improve outcomes in depressed patients.

Structural brain abnormalities in borderline personality disorder correlate with clinical severity and predict psychotherapy response.

Although previous imaging studies in borderline personality disorder (BPD) have found brain abnormalities, the results have been inconsistent. This study aimed to investigate structural brain abnormalities using voxel-based morphometry (VBM) and cortical thickness (Cth) analyses in a large sample of patients with BPD. Additionally, we aimed to determine the correlation between structural abnormalities and clinical severity and to assess its potential value at predicting psychotherapeutic response. Sixty-one individuals with BPD and 19 healthy controls underwent magnetic resonance imaging. Participants with BPD completed several self-report clinical scales, received dialectical-behavioral therapy skills training and post-therapy changes in clinical scores were also recorded. Gray matter volume (GMV) and Cth differences between groups were compared. Within the BPD group, we further characterized the structural brain correlates of clinical severity and investigated the relationship between pre-therapy structural abnormalities and therapeutic response. As potential confounders we included age, sex, educational level, and total intracranial volume (the latter only in VBM analyses). Compared to controls, the BPD group showed a reduced GMV/Cth in prefrontal areas but increased GMV in the limbic structures (amygdala and parahippocampal regions). Prefrontal abnormalities correlated with higher baseline scores on impulsivity and general BPD severity. Increased GMV in the parahippocampal area correlated with a greater emotion dysregulation. Importantly, several baseline structural abnormalities correlated with worse response to psychotherapy. Patients with BPD showed a reduced GMV in the prefrontal areas but a greater GMV in the limbic structures. Several structural abnormalities (i.e. middle and inferior prefrontal areas, anterior insula, or parahippocampal area) correlated with clinical severity and could potentially be used as imaging biological correlates biomarkers to predict psychotherapy response.

A genome-wide methylation study reveals X chromosome and childhood trauma methylation alterations associated with borderline personality disorder.

Borderline personality disorder (BPD) is a severe and highly prevalent psychiatric disorder, more common in females than in males and with notable differences in presentation between genders. Recent studies have shown that epigenetic modifications such as DNA methylation may modulate gene × environment interactions and impact on neurodevelopment. We conducted an epigenome wide study (Illumina Infinium HumanMethylation450k beadchip) in a group of BPD patients with (N = 49) and without (N = 47) childhood traumas and in a control group (N = 44). Results were confirmed in a replication cohort (N = 293 BPD patients and N = 114 controls) using EpiTYPER assays. Differentially methylated CpG sites were observed in several genes and intragenic regions in the X chromosome (PQBP1, ZNF41, RPL10, cg07810091 and cg24395855) and in chromosome 6 (TAP2). BPD patients showed significantly lower methylation levels in these CpG sites than healthy controls. These differences seemed to be increased by the existence of childhood trauma. Comparisons between BPD patients with childhood trauma and patients and controls without revealed significant differences in four genes (POU5F1, GGT6, TNFRSF13C and FAM113B), none of them in the X chromosome. Gene set enrichment analyses revealed that epigenetic alterations were more frequently found in genes controlling oestrogen regulation, neurogenesis and cell differentiation. These results suggest that epigenetic alterations in the X chromosome and oestrogen-regulation genes may contribute to the development of BPD and explain the differences in presentation between genders. Furthermore, childhood trauma events may modulate the magnitude of the epigenetic alterations contributing to BPD.

A multicenter, observational study of pain and functional impairment in individuals with major depressive disorder in partial remission: the DESIRE study.

BACKGROUND: The study explores the association between pain and functional impairment in patients with partially remitted MDD, considering both clinician and patient reported outcomes. METHODS: Multicenter, observational, and cross-sectional study, with 583 outpatients with partially remitted MDD. Measures of pain intensity (VAS), functional impairment (SOFAS), depressive symptomatology (HAM-D6), and remission from MDD and functional status from a patient-centered perspective (RDQ) were collected. VAS scores (cut-off: 30) were used to divide the sample in two groups: no pain (n = 274) and pain (n = 309). Descriptive data, correlation and regression analyses were obtained. RESULTS: Functional impairment (SOFAS) and pain (VAS) were negatively and significantly correlated in the total sample, and in the group with pain. Lower pain predicted higher functioning. The pain sub-sample was older, less educated, with higher medical comorbidities, higher HAM-D6 scores, and lower functionality (SOFAS). In the RDQ, the pain group showed significantly higher scores in the symptom-related subscales, and lower scores in the subscales related to positive mental health, functioning and wellbeing. LIMITATIONS: Correlational and observational design. The criteria and instruments used to measure pain and to define a threshold might limit the generalizability of findings. CONCLUSIONS: Pain and functionality should be assessed and treated in patients with MDD in partial remission. Our results indicate that functionality should be assessed with a broader perspective, that also considers positive mental health features.