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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.
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Ideação Suicida , Tentativa de Suicídio , Humanos , Personalidade , Transtornos da Personalidade/diagnóstico , Transtornos da Personalidade/epidemiologia , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Symptoms of borderline personality disorder (BPD) were previously found to be associated with decreased work performance, even after controlling for depressive and anxiety disorders. Furthermore, co-occurrence of BPD and affective disorders is common. Therefore, we examined the effect of BPD symptoms on occupational functioning in workers with affective disorders. METHODS: Healthy workers (n = 287), workers with current depression/anxiety only (n = 195), workers with BPD symptoms only (n = 54), and workers with both depression/anxiety and BPD symptoms (n = 103) were selected from the Netherlands Study of Depression and Anxiety (NESDA). Both a categorical and dimensional approach were used to cross-sectionally study the effect of BPD symptoms on work performance and absenteeism. RESULTS: Compared to healthy controls, all symptomatic groups had impaired occupational functioning. Workers with current depression/anxiety had higher long-term absenteeism (OR = 3.59; 95%CI:1.83-7.02) and impaired work performance (OR = 7.81; 95%CI:4.44-13.73), workers with BPD symptoms only had higher impaired work performance (OR = 6.02 95%CI:2.76-13.09), and workers with both depression/anxiety and BPD symptoms had higher long-term absenteeism (OR = 3.66 95%CI:1.69-7.91) and impaired work performance (OR = 10.41 95%CI:5.38-20.15). No difference was found between the (symptomatic) groups. In the dimensional analysis, all associations between BPD symptoms and occupational measures disappeared when depressive symptoms were added. Depressive and BPD symptoms were highly correlated (r = .67). CONCLUSIONS: Our findings confirm that both affective disorders and BPD symptoms are associated with occupational dysfunction. The effect of BPD symptoms however, seems mediated by depressive symptoms. This would suggest that focusing on affective symptoms in occupational health may be effective to improve occupational functioning in persons with BPD.
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Transtorno da Personalidade Borderline , Desempenho Profissional , Absenteísmo , Ansiedade/epidemiologia , Transtorno da Personalidade Borderline/complicações , Transtorno da Personalidade Borderline/epidemiologia , Depressão/epidemiologia , Humanos , Países Baixos/epidemiologiaRESUMO
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.
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Transtorno da Personalidade Borderline/psicologia , Emprego/psicologia , Desempenho Profissional , Adolescente , Adulto , Transtorno da Personalidade Borderline/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Personalidade , Inquéritos e Questionários , Adulto JovemRESUMO
Post-traumatic stress disorder (PTSD) is a psychiatric disorder with traumatic memories at its core. Post-treatment sleep may offer a unique time window to increase therapeutic efficacy through consolidation of therapeutically modified traumatic memories. Targeted memory reactivation (TMR) enhances memory consolidation by presenting reminder cues (e.g., sounds associated with a memory) during sleep. Here, we applied TMR in PTSD patients to strengthen therapeutic memories during sleep after one treatment session with eye movement desensitization and reprocessing (EMDR). PTSD patients received either slow oscillation (SO) phase-targeted TMR, using modeling-based closed-loop neurostimulation (M-CLNS) with EMDR clicks as a reactivation cue (n = 17), or sham stimulation (n = 16). Effects of TMR on sleep were assessed through high-density polysomnography. Effects on treatment outcome were assessed through subjective, autonomic, and fMRI responses to script-driven imagery (SDI) of the targeted traumatic memory and overall PTSD symptom level. Compared to sham stimulation, TMR led to stimulus-locked increases in SO and spindle dynamics, which correlated positively with PTSD symptom reduction in the TMR group. Given the role of SOs and spindles in memory consolidation, these findings suggest that TMR may have strengthened the consolidation of the EMDR-treatment memory. Clinically, TMR vs. sham stimulation resulted in a larger reduction of avoidance level during SDI. TMR did not disturb sleep or trigger nightmares. Together, these data provide first proof of principle that TMR may be a safe and viable future treatment augmentation strategy for PTSD. The required follow-up studies may implement multi-night TMR or TMR during REM sleep to further establish the clinical effect of TMR for traumatic memories.
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Dessensibilização e Reprocessamento através dos Movimentos Oculares , Consolidação da Memória , Transtornos de Estresse Pós-Traumáticos , Transtornos de Estresse Pós-Traumáticos/terapia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Humanos , Dessensibilização e Reprocessamento através dos Movimentos Oculares/métodos , Adulto , Masculino , Consolidação da Memória/fisiologia , Feminino , Pessoa de Meia-Idade , Polissonografia , Sono/fisiologia , Memória/fisiologia , Adulto Jovem , Imageamento por Ressonância MagnéticaRESUMO
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.
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Exposure to an acute stressor can lead to unreliable remembrance of intrinsically neutral information, as exemplified by low reliability of eyewitness memories, which stands in contrast with enhanced memory for the stressful incident itself. Stress-sensitive neuromodulators (e.g., catecholamines) are believed to cause this low reliability by altering neurocognitive processes underlying memory formation. Using event-related functional magnetic resonance imaging, we investigated neural activity during memory formation in 44 young, healthy human participants while incidentally encoding emotionally neutral, complex scenes embedded in either a stressful or neutral context. We recorded event-related pupil dilation responses as an indirect index of phasic noradrenergic activity. Autonomic, endocrine, and psychological measures were acquired to validate stress manipulation. Acute stress during encoding led to a more liberal response bias (more hits and false alarms) when testing memory for the scenes 24 h later. The strength of this bias correlated negatively with pupil dilation responses and positively with stress-induced heart rate increases at encoding. Acute stress, moreover, reduced subsequent memory effects (SMEs; items later remembered vs forgotten) in hippocampus and midbrain, and in pupil dilation responses. The diminished SMEs indicate reduced selectivity and specificity in mnemonic processing during memory formation. This is in line with a model in which stress-induced catecholaminergic hyperactivation alters phasic neuromodulatory signaling in memory-related circuits, resulting in generalized (gist-based) processing at the cost of specificity. Thus, one may speculate that loss of specificity may yield less discrete memory representations at time of encoding, thereby causing a more liberal response bias when probing these memories.
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Hipocampo/fisiopatologia , Transtornos da Memória/etiologia , Transtornos da Memória/patologia , Mesencéfalo/fisiopatologia , Estresse Psicológico/complicações , Adulto , Análise de Variância , Área Sob a Curva , Mapeamento Encefálico , Estudos de Casos e Controles , Frequência Cardíaca , Hipocampo/irrigação sanguínea , Humanos , Hidrocortisona/metabolismo , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Masculino , Mesencéfalo/irrigação sanguínea , Testes Neuropsicológicos , Oxigênio/sangue , Medição da Dor , Estimulação Luminosa , Pupila/fisiologia , Saliva/química , Fatores de Tempo , Adulto JovemRESUMO
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 alpha2b-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.
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Tonsila do Cerebelo/fisiologia , Estresse Psicológico , Adolescente , Adulto , Genótipo , Humanos , Imageamento por Ressonância Magnética , Masculino , Receptores Adrenérgicos alfa 2/genética , Receptores Adrenérgicos alfa 2/metabolismo , Adulto JovemRESUMO
Although commonly used, the term memory strength is not well defined in humans. Besides durability, it has been conceptualized by retrieval characteristics, such as subjective confidence associated with retrieval, or objectively, by the amount of information accurately retrieved. Behaviorally, these measures are not necessarily correlated, indicating that distinct neural processes may underlie them. Thus, we aimed at disentangling neural activity at encoding associated with either a subsequent subjective sense of memory strength or with a subsequent objective amount of information remembered. Using functional magnetic resonance imaging (fMRI), participants were scanned while incidentally encoding a series of photographs of complex scenes. The next day, they underwent two memory tests, quantifying memory strength either subjectively (confidence on remembering the gist of a scene) or objectively (the number of details accurately remembered within a scene). Correlations between these measurements were mutually partialed out in subsequent memory analyses of fMRI data. Results revealed that activation in left ventral lateral prefrontal cortex and temporoparietal junction predicted subsequent confidence ratings. In contrast, parahippocampal and hippocampal activity predicted the number of details remembered. Our findings suggest that memory strength may reflect a functionally heterogeneous set of (at least two) phenomena. One phenomenon appears related to prefrontal and temporoparietal top-down modulations, resulting in the subjective sense of memory strength that is potentially based on gist memory. The other phenomenon is likely related to medial-temporal binding processes, determining the amount of information accurately encoded into memory. Thus, our study dissociated two distinct phenomena that are usually described as memory strength.
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Mapeamento Encefálico , Córtex Cerebral/fisiologia , Memória/fisiologia , Adulto , Córtex Cerebral/irrigação sanguínea , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Modelos Estatísticos , Testes Neuropsicológicos , Oxigênio/sangue , Reconhecimento Visual de Modelos , Estimulação Luminosa , Fatores de Tempo , Adulto JovemRESUMO
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.
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Devastating and persisting traumatic memories are a central symptom of post-traumatic stress disorder (PTSD). Sleep problems are highly co-occurrent with PTSD and intertwined with its etiology. Notably, sleep hosts memory consolidation processes, supported by sleep spindles (11-16 Hz). Here we assess the hypothesis that intrusive memory symptoms in PTSD may arise from excessive memory consolidation, reflected in exaggerated spindling. We use a newly developed spindle detection method, entailing minimal assumptions regarding spindle phenotype, to assess spindle activity in PTSD patients and traumatized controls. Our results show increased spindle activity in PTSD, which positively correlates with daytime intrusive memory symptoms. Together, these findings provide a putative mechanism through which the profound sleep disturbance in PTSD may contribute to memory problems. Due to its uniform and unbiased approach, the new, minimal assumption spindle analysis seems a promising tool to detect aberrant spindling in psychiatric disorders.
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Consolidação da Memória , Transtornos de Estresse Pós-Traumáticos , Humanos , Memória , Transtornos da Memória , Sono , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/psicologiaRESUMO
Neuroimaging studies have consistently linked depression to hyperactivation of a (para)limbic affective processing network centered around the amygdala. Recent studies have started to investigate how antidepressant drugs affect amygdala reactivity in healthy individuals, but the influence of their subchronic administration on the functional integrity of the affective neurocircuitry as a whole remains unknown. Therefore, we used functional magnetic resonance imaging in nineteen healthy volunteers to assess the effect of two weeks of administration of the combined serotonin and norepinephrine reuptake inhibitor duloxetine (60 mg) on reactivity and functional connectivity within the affective neurocircuitry in a double-blind, placebo-controlled, crossover design. Using an emotional face matching task we demonstrated that duloxetine reduced neural responses in affect processing regions including the amygdala, the anterior insula, the thalamus and the ventral aspect of the anterior cingulate cortex. Additionally, functional coupling between the amygdala and the anterior insula was enhanced by the drug. These results suggest that duloxetine attenuates the bottom-up processing of biologically salient information in an extended amygdala circuitry, while at the same time possibly potentiating the effective communication between its subparts. Since hyperactivation of the same affective neurocircuitry is thought to underlie emotional dysfunction in depression, these results suggest a putative neural mechanism through which duloxetine could normalize typical negativity biases in depression.
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Tonsila do Cerebelo/efeitos dos fármacos , Antidepressivos/farmacologia , Mapeamento Encefálico , Tiofenos/farmacologia , Adolescente , Adulto , Tonsila do Cerebelo/fisiologia , Estudos Cross-Over , Método Duplo-Cego , Cloridrato de Duloxetina , Emoções/fisiologia , Expressão Facial , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Estimulação Luminosa , Adulto JovemRESUMO
Acute psychological stress can trigger normal and abnormal motivated behaviors such as reward seeking, habitual behavior, and drug craving. Animal research suggests that such effects may result from actions of catecholamines and glucocorticoids that converge in brain regions that regulate motivated behaviors and incentive processing. At present, however, little is known about the acute effects of stress on these circuits in humans. During functional magnetic resonance imaging (fMRI), twenty-seven healthy young women performed a modified version of the monetary incentive delay (MID) task, which is known to robustly engage ventral striatal and medial prefrontal regions. To induce psychological stress, strongly aversive movie clips (versus neutral movie clips) were shown with the instruction to imagine being an eyewitness. Physiological (cortisol levels, heart rate frequency, and heart rate variability) and subjective measurements confirmed successful induction of moderate levels of acute psychological stress. Brain imaging data revealed that stress induction resulted in a significant decrease in reward-related responses in the medial prefrontal cortex (PFC) without affecting ventral striatal responses. Our results thus show that acute psychological stress induces regionally specific changes in functioning of incentive processing circuits. This regional specificity is in line with animal data showing inverted U-shaped relations between levels of stress-related neuromodulators and functioning of the PFC, a structure that is believed to be critical for coordinating behavior in accordance with higher order internal goals. Our findings thus suggest that stress-related increases in habitual and reward-seeking behaviors may be triggered primarily by an impairment of such PFC-dependent cognitive control mechanisms.
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Imageamento por Ressonância Magnética , Córtex Pré-Frontal/fisiopatologia , Recompensa , Estresse Psicológico/fisiopatologia , Adolescente , Adulto , Feminino , Humanos , Adulto JovemRESUMO
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.
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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.
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Apego ao Objeto , Transtornos da Personalidade , Adulto , Ansiedade , HumanosRESUMO
Recent neuroimaging studies investigating responses to stressful stimuli may importantly further our understanding of psychological trauma etiology. However, theory posits that sustained activation of these stress circuits after the stressful event may play an equally important role in the development of stress-related psychopathology. Importantly, such post-stress network changes remain poorly characterized. The amygdala with its connections is crucially positioned in the central stress circuitry that mediates the initial stress response. Hence, we investigated post-stress amygdala-centered connectivity patterns in order to characterize the aftermath of acute, experimentally-induced stress in healthy humans. We recorded resting-state functional MRI in 26 female participants following a period of moderate psychological stress induced by means of aversive (vs. emotionally neutral) movie watching with a self-referencing instruction. Next, we implemented a seedregion analysis calculating the voxel-wise correlation with the anatomically extracted time-series of the amygdala. Various stress measures confirmed successful stress induction. Moreover, we demonstrated enhanced functional coupling of the amygdala with dorsal anterior cingulate cortex, anterior insula, and a dorso-rostral pontine region, which appears to overlap with the anatomical location of the locus coeruleus (LC), when contrasting the stress with the control group. Thus, we show that the aftermath of acute stress is qualified by prolonged activation in an amygdala-connectivity network. This pattern of co-activation may indicate an extended state of hypervigilance that promotes sustained salience and mnemonic processing after stress. Characterization of the post-stress brain state may provide initial insight into the early phases of psychological trauma formation.
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Tonsila do Cerebelo/fisiopatologia , Relógios Biológicos , Descanso , Estresse Psicológico/fisiopatologia , Doença Aguda , Adolescente , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto JovemRESUMO
BACKGROUND: Borderline personality disorder (BPD) is associated with unemployment and impaired functioning. However, a comprehensive understanding of barriers and facilitators to employment from a multidisciplinary perspective is currently lacking. Therefore, the aim of this qualitative study was to explore barriers and facilitators in gaining and maintaining employment in BPD from the perspectives of patients, mental health practitioners (MHPs) and insurance physicians (IPs). METHODS: Fifteen semi-structured interviews were conducted in patients with BPD and two focus groups were carried out among MHPs (n = 7) and IPs (n = 6) following a thematic content analysis approach. RESULTS: All participants described barriers and facilitators relating to three overall themes: characteristics of BPD, stigma, and support to employment. Barriers to employment mainly related to characteristics of BPD, such as low self-image, difficulty posing personal boundaries, difficulty regulating emotions, and lack of structure. MHPs and IPs additionally mentioned externalization and overestimation of competencies on the part of patients. Enhancing emotion regulation and self-reflection by successful treatment was suggested as a facilitator to enhance employment. Increasing collaboration between mental health and vocational rehabilitation services, and increasing knowledge about BPD, were suggested to increase sustainable employment and decrease stigma. CONCLUSIONS: The present findings revealed that both facilitators and barriers are important in gaining and maintaining employment in BPD in which diminishing symptoms, examining stigma and increasing support to employment are key. As a next step, supported employment strategies that follow patient preferences and integrate employment and mental health services, should be studied in the context of BPD.
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Transtorno da Personalidade Borderline/psicologia , Emprego/psicologia , Pessoal de Saúde/psicologia , Pacientes/psicologia , Adulto , Transtorno da Personalidade Borderline/epidemiologia , Transtorno da Personalidade Borderline/reabilitação , Emprego/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Serviço Social em Psiquiatria/estatística & dados numéricosRESUMO
Brain function is fundamentally related in the most general sense to the richness of thalamocortical interconnectivity, and in particular to the rhythmic oscillatory properties of thalamocortical loops. Such rhythmicity is involved in the genesis of cognition, in the sleep-wake cycle, and in several neurological and psychiatric disorders. The role of GABA-mediated transmission in regulating these functional states is addressed here. At the cortical level, inhibition determines the spread of cortical activation by sculpting the precise activity patterns that underlie the details of cognition and motor control. At the thalamic level, GABA-mediated inhibition modulates and resets distribution of the ongoing thalamocortical rhythmic oscillations that bind multisensory inputs into a single cognitive experience and regulate arousal levels.
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Vias Neurais/fisiologia , Periodicidade , Transmissão Sináptica/fisiologia , Ácido gama-Aminobutírico/fisiologia , Animais , Mapeamento Encefálico , Cognição/fisiologia , Sincronização Cortical/métodos , Diagnóstico por Imagem/métodos , Estimulação Elétrica/métodos , Humanos , Interneurônios/fisiologia , Magnetoencefalografia/métodos , Inibição Neural/fisiologia , Redes Neurais de ComputaçãoRESUMO
A host of animal work demonstrates that the retention benefit for emotionally aversive over neutral memories is regulated by glucocorticoid action during memory consolidation. Particularly, glucocorticoids may affect systems-level processes that promote the gradual reorganization of emotional memory traces. These effects remain largely uninvestigated in humans. Therefore, in this functional magnetic resonance imaging study we administered hydrocortisone during a polysomnographically monitored night of sleep directly after healthy volunteers studied negative and neutral pictures in a double-blind, placebo-controlled, between-subjects design. The following evening memory consolidation was probed during a recognition memory test in the MR scanner by assessing the difference in brain activity associated with memory for the consolidated items studied before sleep and new, unconsolidated items studied shortly before test (remote vs. recent memory paradigm). Hydrocortisone administration resulted in elevated cortisol levels throughout the experimental night with no group difference at recent encoding or test. Behaviorally, we showed that cortisol enhanced the difference between emotional and neutral consolidated memory, effectively prioritizing emotional memory consolidation. On a neural level, we found that cortisol reduced amygdala reactivity related to the retrieval of these same consolidated, negative items. These findings show that cortisol administration during first post-encoding sleep had a twofold effect on the first 24h of emotional memory consolidation. While cortisol prioritized recognition memory for emotional items, it reduced reactivation of the neural circuitry underlying emotional responsiveness during retrieval. These findings fit recent theories on emotional depotentiation following consolidation during sleep, although future research should establish the sleep-dependence of this effect. Moreover, our data may shed light on mechanisms underlying potential therapeutic effects of cortisol administration following psychological trauma.
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Emoções/fisiologia , Hidrocortisona/farmacologia , Hidrocortisona/fisiologia , Memória/fisiologia , Nootrópicos/farmacologia , Reconhecimento Psicológico/efeitos dos fármacos , Sono/efeitos dos fármacos , Adulto , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiologia , Nível de Alerta , Método Duplo-Cego , Esquema de Medicação , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/análise , Hidrocortisona/metabolismo , Imageamento por Ressonância Magnética , Masculino , Nootrópicos/administração & dosagem , Polissonografia , Reconhecimento Psicológico/fisiologia , Saliva/química , Taxa Secretória , Sono/fisiologia , Adulto JovemRESUMO
Acute stress shifts the brain into a state that fosters rapid defense mechanisms. Stress-related neuromodulators are thought to trigger this change by altering properties of large-scale neural populations throughout the brain. We investigated this brain-state shift in humans. During exposure to a fear-related acute stressor, responsiveness and interconnectivity within a network including cortical (frontoinsular, dorsal anterior cingulate, inferotemporal, and temporoparietal) and subcortical (amygdala, thalamus, hypothalamus, and midbrain) regions increased as a function of stress response magnitudes. ß-adrenergic receptor blockade, but not cortisol synthesis inhibition, diminished this increase. Thus, our findings reveal that noradrenergic activation during acute stress results in prolonged coupling within a distributed network that integrates information exchange between regions involved in autonomic-neuroendocrine control and vigilant attentional reorienting.
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Encéfalo/fisiologia , Rede Nervosa/fisiologia , Neurotransmissores/fisiologia , Norepinefrina/fisiologia , Estresse Psicológico/fisiopatologia , Adolescente , Neurônios Adrenérgicos/fisiologia , Antagonistas Adrenérgicos beta/farmacologia , Adulto , Afeto , Atenção , Sistema Nervoso Autônomo/fisiologia , Mapeamento Encefálico , Feminino , Neuroimagem Funcional , Frequência Cardíaca , Humanos , Hidrocortisona/análise , Locus Cerúleo/fisiologia , Imageamento por Ressonância Magnética , Masculino , Metirapona/farmacologia , Sistemas Neurossecretores/fisiologia , Receptores Adrenérgicos beta/fisiologia , Saliva/química , Estresse Psicológico/psicologia , Adulto Jovem , alfa-Amilases/metabolismoRESUMO
BACKGROUND: A vital component of an organism's response to acute stress is a surge in vigilance that serves to optimize the detection and assessment of threats to its homeostasis. The amygdala is thought to regulate this process, but in humans, acute stress and amygdala function have up to now only been studied in isolation. Hence, we developed an integrated design using functional magnetic resonance imaging to investigate the immediate effects of controlled stress induction on amygdala function. METHODS: In 27 healthy female participants, we studied brain responses to emotional facial stimuli, embedded in an either acutely stressful or neutral context by means of adjoining movie clips. RESULTS: A variety of physiological and psychological measures confirmed successful induction of moderate levels of acute stress. More importantly, this context manipulation shifted the amygdala toward higher sensitivity as well as lower specificity, that is, stress induction augmented amygdala responses to equally high levels for threat-related and positively valenced stimuli, thereby diminishing a threat-selective response pattern. Additionally, stress amplified sensory processing in early visual regions and the face responsive area of the fusiform gyrus but not in a frontal region involved in task execution. CONCLUSIONS: A shift of amygdala function toward heightened sensitivity with lower levels of specificity suggests a state of indiscriminate hypervigilance under stress. Although this represents initial survival value in adverse situations where the risk for false negatives in the detection of potential threats should be minimized, it might similarly play a causative role in the sequelae of traumatic events.