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Neurobiology of Stress Jan 2024Adverse childhood experiences (ACE), which can be separated into abuse and neglect, contribute to the development of post-traumatic stress symptoms (PTSS). However,...
Cortical volume alteration in the superior parietal region mediates the relationship between childhood abuse and PTSD avoidance symptoms: A complementary multimodal neuroimaging study.
BACKGROUND
Adverse childhood experiences (ACE), which can be separated into abuse and neglect, contribute to the development of post-traumatic stress symptoms (PTSS). However, which brain structures are mainly affected by ACE as well as the mediating role these brain structures play in ACE and PTSS relationship are still being investigated. The current study tested the effect of ACE on brain structure and investigated the latter's mediating role in ACE-PTSS relationship.
METHODS
A total of 78 adults with self-reported ACE were included in this study. Participants completed the childhood trauma questionnaire (CTQ) and a Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) to ascertain ACE history and PTSS, respectively. T1w images and diffusion MRI scans were then acquired to assess cortical morphometry and white matter (WM) integrity in fibre tracts connecting key areas where ACE-related cortical volume alterations were observed.
RESULTS
The combined effect of ACE was negatively associated with total grey matter volume and local cortical area in the right superior parietal region (rSP). Childhood abuse was negatively related to right superior parietal volume after controlling for neglect and overall psychological burden. The right superior parietal volume significantly mediated the relationship between childhood abuse and avoidance-related PTSS. Post-hoc analyses showed that the indirect relation was subsequently moderated by dissociative symptoms. Lastly, a complementary examination of the WM tracts connected to abuse-associated cortical GM regions shows that abuse was negatively related to the normalised fibre density of WM tracts connected to the right superior parietal region.
CONCLUSION
We provide multimodal structural evidence that ACE in the first years of life is related to alterations in the right superior brain region, which plays a crucial role in spatial processing and attentional functioning. Additionally, we highlight that the cortical volume alteration in this region may play a role in explaining the relationship between childhood abuse and avoidance symptoms.
PubMed: 38045556
DOI: 10.1016/j.ynstr.2023.100586 -
Journal of Neurology, Neurosurgery, and... Apr 2024Differences in affective processing have previously been shown in functional neurological disorder (FND); however, the mechanistic relevance is uncertain. We tested the...
BACKGROUND
Differences in affective processing have previously been shown in functional neurological disorder (FND); however, the mechanistic relevance is uncertain. We tested the hypotheses that highly arousing affective stimulation would result in elevated subjective functional neurological symptoms (FNS), and this would be associated with elevated autonomic reactivity. The possible influence of cognitive detachment was also explored.
METHOD
Individuals diagnosed with FND (motor symptoms/seizures; n=14) and healthy controls (n=14) viewed Positive, Negative and Neutral images in blocks, while passively observing the stimuli ('Watch') or detaching themselves ('Distance'). The FND group rated their primary FNS, and all participants rated subjective physical (arousal, pain, fatigue) and psychological states (positive/negative affect, dissociation), immediately after each block. Skin conductance (SC) and heart rate (HR) were monitored continuously.
RESULTS
FNS ratings were higher after Negative compared with Positive and Neutral blocks in the FND group (p=0.002, η =0.386); however, this effect was diminished in the Distance condition relative to the Watch condition (p=0.018, η =0.267). SC and/or HR correlated with FNS ratings in the Negative-Watch and Neutral-Distance conditions (r values=0.527-0.672, p values=0.006-0.035). The groups did not differ in subjective affect or perceived arousal (p values=0.541-0.919, η =<0.001-0.015).
CONCLUSIONS
Emotionally significant events may exert an influence on FNS which is related to autonomic activation rather than altered subjective affect or perceived arousal. This influence may be modulated by cognitive detachment. Further work is needed to determine the relevance and neural bases of these processes in specific FND phenotypes.
Topics: Humans; Conversion Disorder; Dissociative Disorders; Arousal; Seizures
PubMed: 37963722
DOI: 10.1136/jnnp-2023-332364 -
Behavioural and Cognitive Psychotherapy Mar 2024Dissociation may be important across many mental health disorders, but has been variously conceptualised and measured. We introduced a conceptualisation of a common type...
BACKGROUND
Dissociation may be important across many mental health disorders, but has been variously conceptualised and measured. We introduced a conceptualisation of a common type of dissociative experience, 'felt sense of anomaly' (FSA), and developed a corresponding measure, the Černis Felt Sense of Anomaly (ČEFSA) scale.
AIMS
We aimed to develop a short-form version of the ČEFSA that is valid for adolescent and adult respondents.
METHOD
Data were collected from 1031 adult NHS patients with psychosis and 932 adult and 1233 adolescent non-clinical online survey respondents. Local structural equation modelling (LSEM) was used to establish measurement invariance of items across the age range. Ant colony optimisation (ACO) was used to produce a 14-item short-form measure. Finally, the expected test score function derived from item response theory modelling guided the establishment of interpretive scoring ranges.
RESULTS
LSEM indicated 25 items of the original 35-item ČEFSA were age invariant. They were also invariant across gender and clinical status. ACO of these items produced a 14-item short-form (ČEFSA-14) with excellent psychometric properties (CFI=0.992; TLI=0.987; RMSEA=0.034; SRMR=0.017; Cronbach's alpha=0.92). Score ranges were established based on the expected test scores at approximately 0.7, 1.25 and 2.0 theta (equivalent to standard deviations above the mean). Scores of 29 and above may indicate elevated levels of FSA-dissociation.
CONCLUSIONS
The ČEFSA-14 is a psychometrically valid measure of FSA-dissociation for adolescents and adults. It can be used with clinical and non-clinical respondents. It could be used by clinicians as an initial tool to explore dissociation with their clients.
Topics: Adult; Humans; Adolescent; Reproducibility of Results; Emotions; Surveys and Questionnaires; Psychotic Disorders; Psychometrics
PubMed: 37926868
DOI: 10.1017/S1352465823000498 -
Frontiers in Psychiatry 2023Severe self-harm leading to extensive hospitalization generates extreme challenges for patients, families, and health services. Controversies regarding diagnoses and...
Mental health disorders, functioning and health-related quality of life among extensively hospitalized patients due to severe self-harm - results from the Extreme Challenges project.
BACKGROUND
Severe self-harm leading to extensive hospitalization generates extreme challenges for patients, families, and health services. Controversies regarding diagnoses and health care often follow. Most evidence-based treatments targeting self-harm are designed for borderline personality disorder (BPD). However, current knowledge about mental health status among individuals with severe self-harm is limited.
OBJECTIVES
To investigate psychopathology among patients extensively hospitalized due to severe or frequent self-harming behaviors.
METHOD
A cross sectional study (period 2019-2021) targeting psychiatric inpatients (>18 years) with frequent (>5) or long (>4 weeks) admissions last year due to self-harm. The target sample ( = 42, from 12 hospitals across all Norwegian health regions) was compared to individuals admitted to outpatient personality disorder (PD) treatment within specialist mental health services in the same period ( = 389). Clinicians performed interviews on self-harm and psychopathology, supplemented by self-report.
RESULTS
The target sample were young adults, mainly female, with considerable hospitalization and self-harming behaviors, both significantly more extensive than the comparison group. The majority in both groups reported self-harm onset <18 years. The target sample reported increasing severity of self-harm acts and suicidal intention over time. Both samples had high levels of childhood trauma, impaired personality functioning, and a majority fulfilled criteria for PD. In the target sample, comorbid depression, PTSD, anxiety disorders, and substance use occurred more frequently and in 50%, psychosis/dissociative disorder/autism spectrum disorder/ADHD was reported (outpatient comparison sample: 9%). 35% in the target sample screened over cut-off for possible intellectual disability. The target sample reported poor psychosocial functioning and health-related quality of life - greater impairment than the outpatient comparison sample.
CONCLUSION
The study reveals that severe self-harm inpatients have complex psychopathology and highlights the importance of individualized and thorough assessment among patients with severe and/or repetitive self-harm.
PubMed: 37920539
DOI: 10.3389/fpsyt.2023.1258025 -
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 -
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