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Biomedicines Oct 2023The present review aimed to identify the means through which neurologic injury can predispose individuals to Post-Traumatic Stress Disorder (PTSD). In recent years,... (Review)
Review
The present review aimed to identify the means through which neurologic injury can predispose individuals to Post-Traumatic Stress Disorder (PTSD). In recent years, comprehensive studies have helped to clarify which structures in the central nervous system can lead to distinct PTSD symptoms-namely, dissociative reactions or flashbacks-when damaged. Our review narrowed its focus to three common neurologic injuries, traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and stroke. We found that in each of the three cases, individuals may be at an increased risk of developing PTSD symptoms. Beyond discussing the potential mechanisms by which neurotrauma may lead to PTSD, we summarized our current understanding of the pathophysiology of the disorder and discussed predicted associations between the limbic system and PTSD. In particular, the effect of noradrenergic neuromodulatory signaling on the hypothalamic pituitary adrenal (HPA) axis as it pertains to fear memory recall needs to be further explored to better understand its effects on limbic structures in PTSD patients. At present, altered limbic activity can be found in both neurotrauma and PTSD patients, suggesting a potential causative link. Particularly, changes in the function of the limbic system may be associated with characteristic symptoms of PTSD such as intrusive memories and acute psychological distress. Despite evidence demonstrating the correlation between neurotrauma and PTSD, a lack of PTSD prognosis exists in TBI, SAH, and stroke patients who could benefit from early treatment. It should be noted that PTSD symptoms often compound with pre-existing issues, further deteriorating health outcomes for these patients. It is ultimately our goal to clarify the relationship between neurotrauma and PTSD so that earlier diagnoses and appropriate treatment are observed in clinic.
PubMed: 37893106
DOI: 10.3390/biomedicines11102732 -
Psychopharmacology Feb 2024A subanesthetic dose of ketamine, a non-competitive N-methyl-D-aspartate glutamate receptor (NMDAR) antagonist, elicits dissociation in individuals with posttraumatic... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of a dissociative drug on fronto-limbic resting-state functional connectivity in individuals with posttraumatic stress disorder: a randomized controlled pilot study.
RATIONALE
A subanesthetic dose of ketamine, a non-competitive N-methyl-D-aspartate glutamate receptor (NMDAR) antagonist, elicits dissociation in individuals with posttraumatic stress disorder (PTSD), who also often suffer from chronic dissociative symptoms in daily life. These debilitating symptoms have not only been linked to worse PTSD trajectories, but also to increased resting-state functional connectivity (RSFC) between medial prefrontal cortex (mPFC) and amygdala, supporting the conceptualization of dissociation as emotion overmodulation. Yet, as studies were observational, causal evidence is lacking.
OBJECTIVES
The present randomized controlled pilot study examines the effect of ketamine, a dissociative drug, on RSFC between mPFC subregions and amygdala in individuals with PTSD.
METHODS
Twenty-six individuals with PTSD received either ketamine (0.5mg/kg; n = 12) or the control drug midazolam (0.045mg/kg; n = 14) during functional magnetic resonance imaging (fMRI). RSFC between amygdala and mPFC subregions, i.e., ventromedial PFC (vmPFC), dorsomedial PFC (dmPFC) and anterior-medial PFC (amPFC), was assessed at baseline and during intravenous drug infusion.
RESULTS
Contrary to pre-registered predictions, ketamine did not promote a greater increase in RSFC between amygdala and mPFC subregions from baseline to infusion compared to midazolam. Instead, ketamine elicited a stronger transient decrease in vmPFC-amygdala RSFC compared to midazolam.
CONCLUSIONS
A dissociative drug did not increase fronto-limbic RSFC in individuals with PTSD. These preliminary experimental findings contrast with prior correlative findings and call for further exploration and, potentially, a more differentiated view on the neurobiological underpinning of dissociative phenomena in PTSD.
Topics: Humans; Stress Disorders, Post-Traumatic; Ketamine; Midazolam; Pilot Projects; Amygdala; Magnetic Resonance Imaging
PubMed: 37872291
DOI: 10.1007/s00213-023-06479-4 -
European Journal of Psychotraumatology 2023The clinical guidelines for the treatment of dissociation focus primarily on psychotherapy. However, different psychoactive drugs are used in clinical practice. The use... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The clinical guidelines for the treatment of dissociation focus primarily on psychotherapy. However, different psychoactive drugs are used in clinical practice. The use of opioid antagonists has been proposed as a therapeutic option based on the theory that dissociation might be a phenomenon mediated by dysregulation of the endogenous opioid system.
OBJECTIVE
To review and meta-analyse the available evidence on the efficacy of the opioid antagonists naltrexone, naloxone, and nalmefene as treatments for dissociative symptoms and disorders.
METHOD
The PRISMA guidelines were followed, and this review was registered in Prospero with reference number CRD42021280976. The search was performed in the PubMed, Scopus, Web of Science, EMBASE, PsycINFO, and PubPsych databases.
RESULTS
1,798 citations were obtained. After removing duplicates and applying inclusion and exclusion criteria, we included 5 comparative studies with 9 dissociation measures that had included a total of 154 participants, of whom 134 had been treated with an opioid antagonist. The results of the meta-analysis showed a treatment effect for dissociation when using opioid antagonists [pooled = 1.46 (95% CI: 0.62-2.31)]. However, the studies we included were very heterogeneous [Q = 66.89 ( < .001)] and there may have been publication bias.
CONCLUSIONS
Although more research is needed and the results must be interpreted with caution because of the limited amount of data and heterogeneity in the studies and their methodological qualities, opioid antagonists (particularly naltrexone) are promising candidates for the treatment of dissociative symptoms and showed a moderate - large effect size in reducing these symptoms.
Topics: Humans; Narcotic Antagonists; Naltrexone; Naloxone; Dissociative Disorders
PubMed: 37860852
DOI: 10.1080/20008066.2023.2265184 -
European Journal of Psychotraumatology 2023Dysfunctional cognitions play a central role in the development of post-traumatic stress disorder (PTSD). However the role of specific dissociation-related beliefs about...
OBJECTIVE
Dysfunctional cognitions play a central role in the development of post-traumatic stress disorder (PTSD). However the role of specific dissociation-related beliefs about memory has not been previously investigated. This study aimed to investigate the role of dissociation-related beliefs about memory in trauma-focused treatment. It was hypothesized that patients with the dissociative subtype of PTSD would show higher levels of dissociation-related beliefs, dissociation-related beliefs about memory would decrease after trauma-focused treatment, and higher pre-treatment dissociation-related beliefs would be associated with fewer changes in PTSD symptoms.
METHOD
Post-traumatic symptoms, dissociative symptoms, and dissociation-related beliefs about memory were assessed in a sample of patients diagnosed with PTSD (= 111) or the dissociative subtype of PTSD ( = 61). They underwent intensive trauma-focused treatment consisting of four or eight consecutive treatment days. On each treatment day, patients received 90 min of individual prolonged exposure (PE) in the morning and 90 min of individual eye movement desensitization and reprocessing (EMDR) therapy in the afternoon. The relationship between dissociation-related beliefs about memory and the effects of trauma-focused treatment was investigated.
RESULTS
Dissociation-related beliefs about memory were significantly associated with PTSD and its dissociative symptoms. In addition, consistent with our hypothesis, patients with the dissociative subtype of PTSD scored significantly higher on dissociation-related beliefs about memory pre-treatment than those without the dissociative subtype. Additionally, the severity of these beliefs decreased significantly after trauma-related treatment. Contrary to our hypothesis, elevated dissociation-related beliefs did not negatively influence treatment outcome.
CONCLUSION
The results of the current study suggest that dissociation-related beliefs do not influence the outcome of trauma-focused treatment, and that trauma-focused treatment does not need to be altered specifically for patients experiencing more dissociation-related beliefs about memory because these beliefs decrease in association with treatment.
Topics: Humans; Dissociative Disorders; Stress Disorders, Post-Traumatic; Treatment Outcome; Eye Movement Desensitization Reprocessing
PubMed: 37846662
DOI: 10.1080/20008066.2023.2265182 -
Pharmacopsychiatry Jan 2024Predictors of treatment response to intravenous ketamine remain unclear in patients with treatment-resistant depression (TRD); therefore, this study aimed to clarify... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
Factors Associated with Antidepressant Effects of Ketamine: A Reanalysis of Double-Blind Randomized Placebo-Controlled Trial of Intravenous Ketamine for Treatment-Resistant Depression.
INTRODUCTION
Predictors of treatment response to intravenous ketamine remain unclear in patients with treatment-resistant depression (TRD); therefore, this study aimed to clarify these predictors using the US National Institutes of Health database of clinical trials.
METHODS
Data from a placebo-controlled, double-blind, randomized controlled trial were used to assess the efficacy of intravenous ketamine in adult patients with TRD (NCT01920555). For the analysis, data were used from the participants who had received therapeutic doses of intravenous ketamine (i. e., 0.5 and 1.0 mg/kg). Logistic and multivariable regression analyses were conducted to explore the demographic and clinical factors associated with response to treatment or changes in the Hamilton Depression Rating Scale 6 items (HAM-D-6) total score.
RESULTS
This study included 31 patients with TRD (13 women; mean±standard deviation age, 48.4±10.9 years). Logistic regression analysis showed that the age of onset was positively correlated with treatment response after three days of ketamine administration (β=0.08, p=0.037); however, no association was observed between treatment response and age, sex, baseline HAM-D-6 total score, or dissociative score assessed with the Clinician-Administered Dissociative States Scale 40 min after ketamine infusion. Multiple regression analysis showed that no factors were correlated significantly with the percentage change in the HAM-D-6 total score three days after ketamine administration.
DISCUSSION
Later disease onset correlates with a better treatment response three days after ketamine infusion in patients with TRD. Glutamatergic signal transmission may be impaired in patients with an earlier onset of depression, resulting in decreased neuroplasticity, which diminishes ketamine response.
Topics: Adult; Humans; Female; Middle Aged; Infant, Newborn; Ketamine; Depression; Antidepressive Agents; Depressive Disorder, Treatment-Resistant; Double-Blind Method; Treatment Outcome; Infusions, Intravenous
PubMed: 37846462
DOI: 10.1055/a-2179-8884 -
Epilepsy & Behavior : E&B Nov 2023The disease course of psychogenic nonepileptic seizures (PNES) over a prolonged period of time remains unclear. The aims of the study were: 1. to describe the course of...
BACKGROUND
The disease course of psychogenic nonepileptic seizures (PNES) over a prolonged period of time remains unclear. The aims of the study were: 1. to describe the course of illness with a median follow-up time of 4 years and a range of 2-15 years; and 2. to identify distinguishing features between participants regarding seizure cessation, functional level and health-related quality of life.
METHODS
Formerly, inpatients of an epileptic ward diagnosed with PNES between 2000 and 2013 were contacted via mail. They were asked by questionnaire about illness characteristics, i.e., age at onset, PNES status at onset and in the course, treatments, psychosocial situation, and quality of life status.
RESULTS
Two-thirds of the N = 63 formerly inpatients were female, their age at onset was 26.7 years. Seizure frequency decreased significantly over time, 31.7% were currently seizure-free, but still only 37% were regularly employed. Only 48% had a satisfying health-related quality of life. The remitted participants had a shorter duration of illness and higher health-related quality of life. Participants with a good level of functioning were more likely to be male, took fewer medications, and had a higher health-related quality of life. Those participants with higher quality of life were more frequently employed and had fewer seizures.
CONCLUSIONS
As participants continue to be severely limited in their functional level and quality of life over the period under review, enhanced treatment approaches that address experiential avoidance seem to be needed.
Topics: Humans; Male; Female; Adult; Quality of Life; Psychogenic Nonepileptic Seizures; Seizures; Epilepsy; Conversion Disorder; Electroencephalography
PubMed: 37839244
DOI: 10.1016/j.yebeh.2023.109463 -
Journal of Psychiatric Research Nov 2023There is ample evidence showing that childhood maltreatment increases two to three fold the risk of victimization in adulthood. Various risk factors, including...
There is ample evidence showing that childhood maltreatment increases two to three fold the risk of victimization in adulthood. Various risk factors, including posttraumatic stress disorder (PTSD) symptoms, dissociation, self-blame, and alcohol abuse are related to revictimization. Although previous research examined associations between risk factors for revictimization, the evidence is limited and the proposed models mostly include a handful of risk factors. Therefore, it is critical to investigate a more comprehensive model explaining the link between childhood maltreatment and adulthood (re)victimization. Accordingly, this study tested a data-driven theoretical path model consisting of 33 variables (and their associations) that could potentially enhance understanding of factors explaining revictimization. Cross-sectional data derived from a multi-wave study were used for this investigation. Participants (N = 2156, age = 19.94, SD = 2.89) were first-year female psychology students in the Netherlands and New Zealand, who responded to a battery of questionnaires and performed two computer tasks. The path model created by structural equation modelling using modification indices showed that peritraumatic dissociation, PTSD symptoms, trauma load, loneliness, and drug use were important mediators. Attachment styles, maladaptive schemas, meaning in life, and sex motives connected childhood maltreatment to adulthood victimization via other factors (i.e., PTSD symptoms, risky sex behavior, loneliness, emotion dysregulation, and sex motives). The model indicated that childhood maltreatment was associated with cognitive patterns (e.g., anxious attachment style), which in turn were associated with emotional factors (e.g., emotion dysregulation), and then with behavioral factors (e.g., risky sex behavior) resulting in revictimization. The findings of the study should be interpreted in the light of the limitations. In particular, the cross-sectional design of the study hinders us from ascertaining that the mediators preceded the outcome variable.
Topics: Humans; Female; Crime Victims; Young Adult; Adult; Adult Survivors of Child Abuse; Cross-Sectional Studies; Adolescent; Stress Disorders, Post-Traumatic; Netherlands; New Zealand; Models, Psychological; Dissociative Disorders
PubMed: 37832203
DOI: 10.1016/j.jpsychires.2023.10.007 -
European Journal of Psychotraumatology 2023Recent studies found that post-traumatic and dissociative symptoms are common in people with depressive symptoms. Although a trauma-related subtype of depression has...
BACKGROUND
Recent studies found that post-traumatic and dissociative symptoms are common in people with depressive symptoms. Although a trauma-related subtype of depression has been proposed, little is known about the persistence and clinical consequences of these symptoms.
OBJECTIVE
This one-year follow-up study investigated the persistence and clinical consequences of post-traumatic and dissociative symptoms in people with depressive symptoms.
METHODS
We analyzed longitudinal data from an international sample of people self-reporting depressive emotions ( = 152) (mean Patient Health Questionnaire-9 score = 17.27; SD = 6.31).
RESULTS
More than half (58.4%) of participants with baseline post-traumatic stress disorder (PTSD) still met the criteria for PTSD after one year. Participants with dissociative symptoms at baseline were significantly more likely to report lifetime psychiatric hospitalization (31.2% vs 14.7%), past-year use of psychiatric hospitalization (10.4% vs 0%) and emergency services (16.9% vs 4%) than those without dissociative symptoms. All post-traumatic and dissociative symptom clusters were cross-sectionally ( = .286 to .528, < .001) and longitudinally ( = .181 to .462, < .001) correlated with depressive symptoms. A sense of current threat ( = .146, < .05) and negative self-concept ( = .173, < .05) at baseline significantly predicted depressive symptoms after one year.
CONCLUSIONS
These findings contribute to the increasing body of knowledge regarding the PTSD/dissociation-depression comorbidity. Given their persistence and clinical consequences, we recommend that post-traumatic and dissociative symptoms be regularly screened for in clinical settings. The existence of a possible trauma-related subtype of depression should receive more attention in both research and clinical practice.
Topics: Humans; Follow-Up Studies; Depression; Stress Disorders, Post-Traumatic; Comorbidity; Dissociative Disorders
PubMed: 37818716
DOI: 10.1080/20008066.2023.2263314 -
Frontiers in Neurology 2023Spinal cord infarction secondary to ankylosing spondylitis is a rare but severe disorder.
INTRODUCTION
Spinal cord infarction secondary to ankylosing spondylitis is a rare but severe disorder.
CASE PRESENTATION
Here we present a case of acute spinal cord infarction in a 54 years-old man with a medical history of ankylosing spondylitis, scoliosis, and hypotension. The patient complained of a sudden onset of lower limb weakness. A physical examination showed that he suffered from a dissociative sensory disorder, paralysis, and concomitant sphincter disturbances. After undergoing a whole-spine MRI, he was diagnosed with an acute ischemic injury from T2 to T5. As he did not treat his ankylosing spondylitis, it later caused a spinal deformity, making the lumbar puncture technically challenging. However, using Taylor's approach, a CSF sample was successfully obtained. A CSF biochemical test ruled out myelitis, NMOSD, and MS. After receiving treatment with low-molecular-weight heparin, atorvastatin calcium, and methylprednisolone, his sphincter function gradually recovered, but his strength was only partially restored.
CONCLUSION
Although this is a rare entity, it is necessary for physicians to consider it when evaluating patients with a sudden loss of sensation and strength in their lower limbs.
PubMed: 37808493
DOI: 10.3389/fneur.2023.1221810 -
Epilepsy & Behavior : E&B Nov 2023A history of adverse life events (ALE) is a risk factor for functional seizures (FS). Their influence on long-term outcome remains unclear. International guidelines...
BACKGROUND
A history of adverse life events (ALE) is a risk factor for functional seizures (FS). Their influence on long-term outcome remains unclear. International guidelines recommend assessing ALE in patients presenting with associated disorders. It is not clear to what extent patients evaluated for FS are regularly asked about ALE.
OBJECTIVES
We hypothesised that the presence of ALE would relate to worse outcome at follow-up and, that the rate of detection of ALE in clinical work-up would be inferior to that based on self-report questionnaires.
METHODS
53 patients with FS from the National Centre for Epilepsy in Norway, aged 16-62 years were included. Symptom severity, health-related quality of life (HRQoL), and antecedent ALE were assessed at baseline. Medical records were examined for disclosure of ALE. At a mean of 70.45 (SD 29.0, range 22-130) months after inclusion, participants were inquired about FS status, FS-related health care utilization and HRQoL.
FINDINGS
A history of emotional abuse documented in the medical record was an independent risk factor for worse HRQoL at follow-up. Prevalence of ALE documented in medical records was lower compared with rates measured by a self-report questionnaire.
CONCLUSIONS
These findings indicate an association between antecedent ALE and HRQoL years after diagnosis. A substantial proportion of the adverse life events by a self-report questionnaire had not been documented in the clinical records.
CLINICAL IMPLICATIONS
The supplemental use of a self-report questionnaire in the diagnostic work-up of patients with FS may be valuable for detecting ALE.
Topics: Humans; Quality of Life; Seizures; Epilepsy; Surveys and Questionnaires; Self Report
PubMed: 37804600
DOI: 10.1016/j.yebeh.2023.109456