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Forensic Science International Jan 2024Ketamine is primarily used as an anaesthetic or for analgesics in medical treatment, but due to its dissociative and hallucinogenic effects, abuse has increased in the...
INTRODUCTION
Ketamine is primarily used as an anaesthetic or for analgesics in medical treatment, but due to its dissociative and hallucinogenic effects, abuse has increased in the past years leading to several drug impaired driving cases.
METHODS
Eight DUID (driving under the influence of drugs) cases involving ketamine from two institutes of legal medicine over a period from January 2021 to January 2023 were evaluated. The cases were compared with regard to psychomotor impairments, adverse effects on driving performance and co-consumption of drugs. Analyses of ketamine were carried out by high performance liquid chromatography with diode array detection (HPLC-DAD). Other drugs of abuse were either detected via liquid chromatography with tandem mass spectromety (LC-MS/MS) and/or gas chromatography with (tandem) mass spectrometry (GC-MS(/MS)).
RESULTS
Ketamine plasma concentrations in a range of approx. 100-1200 ng/mL (mean: 510 ng/mL, median: 370 ng/mL) were detected. Co-consumption of at least one substance was ascertained in all cases. Besides driving impairments, recorded psychomotor impairments of the drivers comprised e.g. dilated pupils, missing or delayed pupil reactions, a slurred or decelerated speech, delayed reaction, lack of concentration, vertigo or agitation.
DISCUSSION
The observed peculiarities were in-line with literature data. However, the assessment and differentiation of ketamine-induced impairments was aggravated due to co-consumption of other drugs of abuse or pharmaceuticals in the herein investigated cases. Nevertheless, in two cases impairments can be attributed mainly to ketamine consumption since the co-consumed substances were only detected in low concentrations.
CONCLUSION
The presented cases provide additional data on psychomotor impairments observed in ketamine-related DUID cases. Limiting factors are co-consumption of substances, unknown habituation to drugs and the limited case number. Nevertheless, the results of this study are comparable with existing literature data. Since the abuse of ketamine has increased in the past years, these data will support forensic casework.
Topics: Humans; Gas Chromatography-Mass Spectrometry; Tandem Mass Spectrometry; Ketamine; Chromatography, Liquid; Substance Abuse Detection; Psychomotor Disorders; Automobile Driving
PubMed: 38064774
DOI: 10.1016/j.forsciint.2023.111905 -
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 -
European Journal of Psychotraumatology 2023Previous studies have demonstrated the high prevalence of dissociative symptoms and their association with considerable healthcare costs. However, there is a lack of...
Previous studies have demonstrated the high prevalence of dissociative symptoms and their association with considerable healthcare costs. However, there is a lack of studies that describe whether dissociative symptoms persist and lead to other clinical outcomes over time in the community. This study investigated the persistence, predictors, and consequences of dissociative symptoms in the community. We analyzed longitudinal data in a sample of community health service users in Hong Kong ( = 173). A relatively high proportion (63.6%) of participants with baseline dissociative symptoms continued to exhibit dissociative symptoms after approximately 9 months. Baseline non-betrayal trauma predicted subsequent dissociative symptoms (β = .141, = .024). Participants with baseline dissociative symptoms were more likely to have received subsequent emergency mental health services (9.1% vs 0.7%, = .005). Baseline dissociative symptoms significantly predicted subsequent post-traumatic symptoms (β = .165 to .191, < .05) and difficulty in social and occupational participation (β = -.152 to -.182, < .05) even after controlling for baseline scores, trauma exposure, and use of professional support. The predictive role of dissociative symptoms on subsequent disturbances in self-organization symptoms and social participation difficulty remained significant after applying the Bonferroni correction. This is one of the very few studies showing that dissociative symptoms are persistent to a certain degree and could predict other symptoms and subsequent impairments even in community settings. Factors that affect the trajectory of dissociative symptoms should be further investigated. Regular screening for dissociative symptoms is recommended. Considering its prevalence, persistence, and clinical and social consequences, dissociation should be given greater public health attention.
Topics: Humans; Hong Kong; Longitudinal Studies; Mental Health Services; Dissociative Disorders; Disease Progression
PubMed: 37902274
DOI: 10.1080/20008066.2023.2269695 -
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