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Background Anorexia nervosa (AN) is a severe and disabling disorder, with relapse rates as high as 50% after the first episode, posing a significant challenge for clinicians. Most therapies excessively focus on nourishment, resulting in temporary weight restoration but with no improvements in general well-being and quality of life. Radically Open Dialectical Behavior Therapy (RO-DBT) is a transdiagnostic treatment designed to address overcontrol, a key aspect in the functioning of patients with AN. To date, no clinical trial (CT) has shown its efficacy in these patients or evaluated its neurobiological mechanism of action. Methods A randomized CT in weight restored adult AN patients will be conducted, with one group receiving treatment as usual (TAU) and the other TAU plus RO-DBT, with the main outcome being quality of life. Secondary variables will include eating disorders (EDs) symptoms, overcontrol characteristics, autistic traits, and neuroimaging changes. Discussion The results will address a gap in knowledge regarding AN treatment, with the expectation that patients receiving TAU with RO-DBT will exhibit improved quality of life and experience fewer relapses at the one-year follow-up. This is the first study examining neuroimaging changes in RO-DBT to better understand its underlying mechanisms. Trial registration The study has been registered in ClinicalTrials.gov in September 22, 2023. It can be found in https://classic.clinicaltrials.gov/ct2/show/NCT06050421 . Trial Registration Number: NCT06050421.

Although pharmacotherapy is considered the first-line treatment for bipolar disorders (BD), adjunctive psychoeducation has proven its effectiveness in improving self-management of the disease and reducing relapse rates. Few studies have evaluated the effect of brief group psychoeducation on pragmatic variables, such as the number of hospitalizations. The aim of the present study was to assess the mid-term effect of a four-session group psychoeducation on course-related variables in BD. Thirty-two individuals with BD were included in the study. Sixteen were exposed to psychoeducation and were matched to sixteen nonexposed individuals who received their usual treatment. Both groups were compared on insight, treatment adherence, change in the number of hospitalizations and visits to the emergency services, occurrence rate after intervention, and time to the first psychiatric hospitalization and the first urgent attendance. There was a significant reduction in the mean number of hospitalizations and urgent attendances in the exposed group in comparison to the nonexposed group. The first urgent attendance was significantly sooner in the nonexposed cohort. There were no differences between groups in any of the other variables. This intervention has shown benefits for pragmatic variables of the disease course and may be a feasible and cost-effective intervention to routinely implement in the management of BD.

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.

Objective Although no psychotropic drugs have been officially approved for the treatment of borderline personality disorder (BPD), medications are routinely prescribed for these patients. The primary aim of this study was to evaluate changes in the pharmacological management of patients with BPD treated in an outpatient specific unit in Spain over the past 20 years, while a secondary aim was to identify the factors associated with the prescription. Methods Observational and cross-sectional study of all patients with a primary diagnosis of BPD ( n  = 620) consecutively admitted to a BPD outpatient program in Barcelona, Spain, from 2001 through 2020. We examined trends in the prescription of antidepressants, benzodiazepines, mood stabilizers, and antipsychotics. For the analysis, prescription data were grouped into four 5-year periods (2001–2005, 2006–2010, 2011–2015, and 2016–2020). Logistic regression models were performed to identify sociodemographic and clinical variables associated with pharmacological prescription and polypharmacy. Results The percentage of patients receiving pharmacotherapy decreased over time. Antidepressant prescription rates remained high and stable over time (74% of patients), while benzodiazepine use decreased significantly during the study period (from 77 to 36%) and second-generation antipsychotic (SGA) use increased from 15 to 32%. Psychiatric comorbidity was the main factor associated with pharmacological treatment (odds ratio 2.5, 95% confidence interval 1.5-4.2) and polypharmacy, although a high percentage of patients without comorbidity were also taking medications. Conclusions Over the past 20 years, the pharmacological treatment of BPD outpatients has undergone important changes, most notably the decrease in benzodiazepines and increase in SGAs. The findings of this study demonstrate that pharmacotherapy is much more prevalent in patients with BPD than recommended in most clinical guidelines.

The aim of this prospective study was to expand previously reported evidence on the 10-year clinical and functional course of borderline personality disorder (BPD) in a Spanish sample. Participants diagnosed with BPD were assessed at baseline and at 10-year follow-up to evaluate BPD symptomatology and other relevant clinical measures, suicidal behavior, dimensional personality traits, Axis I and II comorbidity, use of mental health resources, and psychosocial functioning. At the 10-year follow up, significant improvements were observed on BPD domains, suicidal behavior, and other clinical measures. Neuroticism, impulsiveness, and aggression-hostility features trended toward normalization, whereas activity and sociability were impaired over time. Comorbidity with Axis I and personality disorders remained high. Social functioning and occupational functioning were largely unchanged. These findings confirm the tendency toward a symptomatic remission of BPD over the long term with regard to symptom criteria and characteristic dimensional traits. However, psychosocial functioning remains impaired.

Cognitive deficits are a core feature of serious mental illnesses such as major depression, bipolar disorder and schizophrenia and are a common cause of functional disability. However, the efficacy of pharmacological interventions for improving the cognitive deficits in these disorders is limited. As pro-cognitive pharmacological treatments are lacking, we aimed to review whether thyroid hormones or drugs that target prolactin may become potential candidates for ‘repurposing’ trials aiming to improve cognition. We conducted a narrative review focused on thyroid hormones and prolactin as potential targets for improving cognition in major mood disorders or schizophrenia. The role of thyroid hormones and prolactin on cognitive processes in non-psychiatric populations was also reviewed. Although clinical trials regarding these hormones are lacking, particularly in patients with schizophrenia, bipolar disorder or major depression, there is evidence from observational studies for the contribution of these hormones to cognitive processes. Patients with bipolar disorder and subclinical hypothyroidism show poorer cognitive function than euthyroid patients. In patients with early psychosis, lower free thyroxine concentrations have been associated with poorer attention whereas increased prolactin levels have been associated with poorer speed of processing. Only two small clinical trials tested the potential pro-cognitive effects of thyroid hormones, with positive findings for triiodothyronine (T3) treatment in patients receiving lithium or electroconvulsive therapy. In sum, thyroid hormones and prolactin might contribute to the cognitive performance of patients with major mood disorders and psychotic disorders. Thyroid hormones and prolactin-lowering drugs (e.g. cabergoline, aripiprazole) are candidate drugs to be tested in repurposing clinical trials aiming to improve the cognitive abilities of patients with major mood disorder and schizophrenia.

Intensive home treatment (IHT) has shown to be a feasible alternative to hospitalization for the management of acute psychiatric episodes, but there are no real-world studies assessing if patients with a first IHT use it again for the management of their recurrences. The objectives of this retrospective cohort study were to map the use ofacute treatment resources after the implementation of IHT in our territory through the establishment of trajectories of management, and to disentangle if there are profiles of patients who fit better each trajectory. We included the first 1000 episodes admitted to IHT, of which we selected those that corresponded to the first IHT of a patient (index admission). Trajectories after the index admission were: (T-A) absence of use of acute resources, (T-B) only IHT, and (T-C) at least one hospitalization. Follow-up ranged from 6 months to 6 years. We calculated the frequency of each trajectory and performed univariate analyses searching for associations between trajectory and clinical factors. Among those patients with psychiatric history (N = 659), 66.2% followedT-A, 11.2% T-B, and 22.6% T-C. The probability of following T-C was higher for patients with a psychotic disorder (p Bonf  = 0.018) and with previous hospitalizations (p Bonf  < 0.0001). Among those patients without psychiatric history (N = 168), 82.7% followed T-A, 6.6% T-B, and 10.7% T-C. The probability of following T-B was higher for those with a higher severity at the index admission (p Bonf  = 0.028). This study shows that some -or even all- recurrences of some subjects were successfully managed with IHT, providing real-world evidence for its use in acute psychiatric conditions.

Childhood maltreatment and temperamental traits play a role in the development of Borderline Personality Disorder (BPD). The aim of the present study was to assess the involvement and the interrelationship of both factors in the clinical severity of BPD. The self-reported history of childhood trauma, psychobiological temperamental traits, and severity of BPD symptoms were evaluated in 130 subjects with BPD. Approximately 70% of the sample reported some form of abuse or neglect. Childhood maltreatment inversely correlated with sociability, but no correlation was observed with the other temperamental traits. The regression model showed that neuroticism–anxiety and aggression–hostility traits, as well as emotional abuse, were risk factors independently associated with the severity of BPD. Sexual abuse was not associated with the severity of the disorder. Finally, the interaction between high neuroticism–anxiety traits and the presence of severe emotional abuse was associated with BPD severity. These results suggest that the interaction between temperamental traits and childhood emotional abuse has an influence not only on the development but also on the severity of BPD. Further studies are needed to identify more biological and environmental factors associated with the severity of the disorder.

Recent research suggests that deficits in the ability to be mindful may be related to core aspects of borderline personality disorder (BPD). Mindfulness plays a central role in BPD treatment, and evidence also indicates that mindfulness is the most commonly practiced of the skills taught in dialectical behavior therapy (DBT). The present study investigated whether a 10-week mindfulness training program would improve BPD symptoms and mindfulness-related capacities in a sample of individuals diagnosed with BPD. A total of 64 participants (mean age = 31.64, SD = 6.9; 86 % female) were randomized to 10 weeks of mindfulness ( n  = 32) or interpersonal effectiveness skills training (control group; n  = 32). BPD symptoms and mindfulness capacities were measured at pre- and post-intervention. Compared to the control group, participants assigned to mindfulness experienced a significantly greater reduction and increase, respectively, in BPD symptoms and decentering capacity. Treatment response rates (in reference to BPD symptoms) were higher for the mindfulness group (40 vs. 13 %). Interpersonal effectiveness alone did not result in improvements on any outcome measures. These findings suggest that mindfulness training may be a useful approach to decreasing BPD symptoms while simultaneously improving mindfulness capacities.

Structural imaging studies of borderline personality disorder (BPD) have found regions of reduced cortical volume, but these have varied considerably across studies. Reduced hippocampus and amygdala volume have also been a regular finding in studies using conventional volumetric measurement. How far comorbid major depression, which is common in BPD and can also affect in brain structure, influences the findings is not clear. Seventy-six women with BPD and 76 matched controls were examined using whole-brain voxel-based morphometry (VBM). The hippocampus and amygdala were also measured, using both conventional volume measurement and VBM within a mask restricted to these two subcortical structures. Lifetime history of major depression was assessed using structured psychiatric interview. At a threshold of p = 0.05 corrected, the BPD patients showed clusters of volume reduction in the dorsolateral prefrontal cortex bilaterally and in the pregenual/subgenual medial frontal cortex. There was no evidence of volume reductions in the hippocampus or amygdala, either on conventional volumetry or using VBM masked to these regions. Instead there was evidence of right-sided enlargement of these structures. No significant structural differences were found between patients with and without lifetime major depression. According to this study, BPD is characterized by a restricted pattern of cortical volume reduction involving the dorsolateral frontal cortex and the medial frontal cortex, both areas of potential relevance for the clinical features of the disorder. Previous findings concerning reduced hippocampus and amygdala volume in the disorder are not supported. Brain structural findings in BPD do not appear to be explainable on the basis of history of associated lifetime major depression.