Three Prospective Case Studies Examining Mifepristone's Efficacy in Patients with Treatment-Resistant PTSD

Despite the availability of various treatment approaches for patients with posttraumatic stress disorder (PTSD), some patients do not respond to these therapies, and novel treatment approaches are needed. This study investigated the efficacy of mifepristone, a glucocorticoid receptor antagonist, in treatment-resistant PTSD patients. Three patients with PTSD who were resistant to standard psychological and pharmacological treatments were prescribed mifepristone (600-1,200 mg/day) for 1 week. A baseline-controlled single-case design was used, involving a 2-week baseline phase (no intervention), a 1-week intervention phase (mifepristone), and a 2-week postintervention phase. The primary outcome measure, self-reported PTSD symptom severity (PCL-5), was assessed daily, with participants providing their own control condition. Two of the three patients experienced a significant reduction in PTSD symptom severity after the intervention phase and no longer met the diagnostic criteria for PTSD. These positive results were maintained during long-term follow-up. These findings support the potential effectiveness of mifepristone in the treatment of patients with treatment-resistant PTSD. However, our findings must be interpreted with caution, and further studies with larger sample sizes and more rigorous designs are necessary to confirm the promising results

The thalamus and its subnuclei—a gateway to obsessive-compulsive disorder

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T-1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered (https://osf.io/73dvy) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = -0.15 to -0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status

Disturbed Sleep in PTSD: Thinking Beyond Nightmares

Sleep disturbances frequently co-occur with posttraumatic stress disorder (PTSD). Insomnia and nightmares are viewed as core symptoms of PTSD. Yet, relations between disturbed sleep and PTSD are far more complex: PTSD is linked to a broad range of sleep disorders and disturbed sleep markedly affects PTSD-outcome. This article provides a concise overview of the literature on prevalent comorbid sleep disorders, their reciprocal relation with PTSD and possible underlying neurophysiological mechanisms. Furthermore, diagnostic procedures, standard interventions—particularly first choice non-pharmacological therapies—and practical problems that often arise in the assessment and treatment of sleep disturbances in PTSD are described. Finally, we will present some perspectives on future multidisciplinary clinical and experimental research to develop new, more effective sleep therapies to improve both sleep and PTSD

The effect of distress on the balance between goal-directed and habit networks in obsessive-compulsive disorder

The classical cognitive-behavioral theory of obsessive-compulsive disorder (OCD) holds that compulsions are performed to reduce distress that is evoked by obsessions, whereas a recent neuroscience-inspired theory suggests that compulsivity results from a disbalance between goal-directed and habit-related neural networks. To bridge these theories, we investigated whether the balance between goal-directed and habit networks in patients with OCD was affected during psychological distress. Twenty-three OCD patients and twenty-three healthy controls participated in a controlled stress induction paradigm using the socially evaluated cold-pressor test in a crossover design. Stress responses were evaluated through cortisol levels, blood pressure, and anxiety ratings. Functional connectivity of the caudate nucleus and posterior putamen was assessed using seed region analysis of resting-state functional magnetic resonance imaging data, which are hubs of the goal-directed and habit network, respectively. Stress induction increased blood pressure and psychological stress measures across groups and resulted in blunted cortisol responses in patients. Furthermore, patients showed a blunted reduction in connectivity between the caudate nucleus and precuneus during psychological distress, which was positively correlated with compulsivity but not obsession severity. The posterior putamen showed no significant group differences in distress-induced connectivity. These results suggest that compulsivity in OCD is associated with altered connectivity between the goal-directed and default mode networks during psychological distress

Cluster B versus Cluster C Personality Disorders: A Comparison of Comorbidity, Suicidality, Traumatization and Global Functioning

A general clinical assumption states that cluster B personality disorders (PDs) represent a more severe form of PD than cluster C PDs. Consequently, most PD research is centered on cluster B PDs (especially borderline PD). Yet, prevalence ratings of cluster C PDs exceed those of cluster B PDs. In this explorative, cross-sectional study, we compared cluster B and C PD patients (N = 94) on a wide range of clinically-relevant severity measures, including comorbidity, suicidality, (childhood) traumatization and global functioning. Results showed that, although cluster B PD patients suffered more often from substance use disorders and lifetime suicide attempts, no difference could be established between groups for all other severity measures, including trauma variables. In our study, we additionally included a group of combined cluster B and C PDs, who were largely similar to both other groups. Although our study is insufficiently powered to claim a significant non-difference, these findings emphasize that high rates of comorbidity, suicidality, childhood traumatization and functional impairment apply to both cluster B and C patients. As such, our findings encourage more research into cluster C PDs, ultimately leading to more evidence-based treatments for this prevalent patient group. In addition, the high level of traumatization across groups calls for a routine trauma screening, especially since PD treatment may benefit from concurrent trauma treatment

Associations between personality traits and suicidal ideation and suicide attempts in patients with personality disorders

Introduction: People with personality disorders (PDs) have an elevated suicide risk. However, correlates of suicidal ideation (SI) and suicide attempts (SA) remain largely unknown in this population. A growing body of literature highlights the contribution of the Big Five personality traits in suicide-outcomes. Therefore, the present study investigates the association between the Big Five personality traits and SI and SA in people with PDs while applying the ideation-to-action framework. Method: Data were obtained from 105 treatment-seeking individuals diagnosed with PDs participating in the Trauma tO Personality Spectrum Study (TOPSS). Multinomial logistic regression analyses were used to analyze the association between the NEO Five-Factor Inventory and the three category suicide-outcome: non-suicidal, SI, and SA. Results: After controlling for age, gender, a comorbid depressive disorder, the severity of borderline manifestations, and other personality traits from the Big Five taxonomy, significantly lower levels of extraversion were observed in participants with SI compared to non-suicidal participants (OR = 0.27, 95% CI 0.10–0.72) but not in SA participants. In contrast, higher levels of extraversion were associated with SA when compared to SI (OR = 3.52, 95% CI 1.33–9.32). Other Big Five traits were not independently associated with suicide-outcomes. Conclusions: Of the Big Five traits, the introversion-extraversion dimension most clearly distinguishes individuals with SI from non-suicidal individuals, as well as those with a SA in the past from those with SI only. Prospective studies are required to investigate if this personality trait can predict the progression from being non-suicidal to having SI and from having SI to performing an attempt

Acute stress modulates genotype effects on amygdala processing in humans

Probing gene–environment interactions that affect neural processing is crucial for understanding individual differences in behavior and disease vulnerability. Here, we tested whether the current environmental context, which affects the acute brain state, modulates genotype effects on brain function in humans. We manipulated the context by inducing acute psychological stress, which increases noradrenergic activity, and probed its effect on tonic activity and phasic responses in the amygdala using two MRI techniques: conventional blood oxygen level–dependent functional MRI and arterial spin labeling. We showed that only carriers of a common functional deletion in ADRA2B, the gene coding for the α2b-adrenoreceptor, displayed increased phasic amygdala responses under stress. Tonic activity, reflecting the perfusion of the amygdala, increased independently of genotype after stress induction. Thus, when tonic activity was heightened by stress, only deletion carriers showed increased amygdala responses. Our results demonstrate that genetic effects on brain operations can be state dependent, such that they only become apparent under specific, often environmentally controlled, conditions

The Association Between Childhood Trauma and Attachment Functioning in Patients With Personality Disorders

Attachment (mal)functioning and a history of childhood trauma (CT) are both considered psychological determinants of personality disorders (PDs). Their interaction, however, remains largely uninvestigated. In this study, the authors assessed adult and childhood attachment style in a sample of patients with diverse PDs (N = 75) and determined the relation with both occurrence and severity of CT. The authors found that the sample was characterized by severe attachment malfunctioning and high levels of CT. Using cross-tabulations and analysis of variance, the authors showed that patients with a fearful or dismissive attachment style experienced more severe CT than patients with a preoccupied attachment style. Patients reporting an affectionless control bonding style to either parent suffered frequent and severe CT. Although temporal causality cannot be determined, these findings stress the necessity to screen for CT in PDs and suggest that attachment-centered psychotherapy for these patients may benefit from preceding or concurrent trauma treatment

Borderline personality symptoms and work performance: a population-based survey

BACKGROUND: This study aims to elucidate the interplay between borderline personality symptoms and working conditions as a pathway for impaired work performance among workers in the general population. METHODS: Cross-sectional data from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2) were used, including 3672 workers. Borderline personality symptoms were measured with the International Personality Disorder Examination (IPDE) questionnaire. Working conditions (decision latitude, psychological job demands, job security and co-worker support) were assessed with the Job Content Questionnaire (JCQ). Impaired work performance was assessed as total work loss days per month, defined as the sum of days of three types of impaired work performance (inability to work, cut-down to work, and diminished quality at work). These were assessed with the WHO Disability Assessment Schedule (WHO-DAS). Common mental disorders (CMD) were assessed with the Composite International Diagnostic Interview (CIDI). RESULTS: Number of borderline personality symptoms was consistently associated with impaired work performance, even after controlling for type or number of adverse working conditions and co-occurrence of CMD. Borderline personality symptoms were associated with low decision latitude, job insecurity and low co-worker support. The relationship between borderline personality symptoms and work performance diminished slightly after controlling for type or number of working conditions. CONCLUSIONS: The current study shows that having borderline personality symptoms is a unique determinant of work performance. This association seems partially explained through the impact of borderline personality symptoms on working conditions. Future studies are warranted to study causality and should aim at diminishing borderline personality symptoms and coping with working conditions

Borderline personality symptoms and work performance: a population-based survey

Abstract Background This study aims to elucidate the interplay between borderline personality symptoms and working conditions as a pathway for impaired work performance among workers in the general population. Methods Cross-sectional data from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2) were used, including 3672 workers. Borderline personality symptoms were measured with the International Personality Disorder Examination (IPDE) questionnaire. Working conditions (decision latitude, psychological job demands, job security and co-worker support) were assessed with the Job Content Questionnaire (JCQ). Impaired work performance was assessed as total work loss days per month, defined as the sum of days of three types of impaired work performance (inability to work, cut-down to work, and diminished quality at work). These were assessed with the WHO Disability Assessment Schedule (WHO-DAS). Common mental disorders (CMD) were assessed with the Composite International Diagnostic Interview (CIDI). Results Number of borderline personality symptoms was consistently associated with impaired work performance, even after controlling for type or number of adverse working conditions and co-occurrence of CMD. Borderline personality symptoms were associated with low decision latitude, job insecurity and low co-worker support. The relationship between borderline personality symptoms and work performance diminished slightly after controlling for type or number of working conditions. Conclusions The current study shows that having borderline personality symptoms is a unique determinant of work performance. This association seems partially explained through the impact of borderline personality symptoms on working conditions. Future studies are warranted to study causality and should aim at diminishing borderline personality symptoms and coping with working conditions