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Abstract Objective We investigated the associations between FKBP5 single‐nucleotide polymorphisms (SNPs) and functional seizures (FS). Methods Seventy patients with FS, 140 with major depressive disorder (MDD), and 140 healthy controls were studied. Their DNAs were analyzed for the rs1360780 in the 3′ region and rs9470080 in the 5′ region of the FKBP5. Childhood trauma questionnaire and hospital anxiety and depression scale were used. Results Patients with FS and those with MDD had less GG and more AA genotypes in both rs9470080 and rs1360780 SNPs compared with those in healthy controls. Similar results were observed for allelic frequencies. There were no significant differences between FS and MDD groups in terms of genotype and allelic frequencies for both SNPs. The results of multinomial logistic regression analysis showed that FKBP5 polymorphisms were not associated with the diagnosis. Significance Patients with FS and those with MDD had significantly different genotypes in both rs9470080 and rs1360780 SNPs compared with those in healthy controls. However, it seems that FKBP5 polymorphisms were not associated with FS in the absence of depression. Further genetic investigations of patients with FS may increase our understanding of the neurobiological underpinnings of this condition, but such studies should be large enough and very well designed; they should include a comparison group with depression in addition to a healthy control group.

Abstract Objective We searched for, from the FDA (Food and Drug Administration‐USA)‐approved drugs, inhibitors of FKBP5 with tolerable adverse effect profiles (eg, mild headache, sedation, etc.) and with the ability to cross the blood brain barrier (BBB), using bio‐informatics tools (in‐silico). This may pave the road for designing clinical trials of such drugs in patients with functional seizures (FS) and other stress‐associated disorders. Methods Several databases were used to find all the approved drugs that potentially have interactions with FKBP51 protein [ie, CTD gene‐chemical interaction section of FKBP51 protein of Harmonizome of Mayaanlab, DrugCenteral database, PDID (Protein Drug Interaction Database), DGIdb (the Drug Gene Interaction database)]. Other databases were also searched [eg, clinicaltrials.gov; DRUGBANK (the FASTA format of the FKBP51 protein was imported to the target sequencing section of the database to find the associated drugs), and the STITCH database (to find the related chemical interaction molecules)]. Results After a comprehensive search of the designated databases, 28 unique and approved drugs were identified. Fluticasone propionate and Mifepristone and Ponatinib, Mirtazapine, Clozapine, Enzalutamide, Sertraline, Prednisolone, Fluoxetine, Dexamethasone, Clomipramine, Duloxetine, Citalopram, Chlorpromazine, Nefazodone, and Escitalopram are inhibitors of FKBP5 and have BBB permeability. Significance While the current in‐silico repurposing study could identify potential drugs (that are already approved and are widely available) for designing clinical trials in patients with stress‐associated disorders (eg, FS), any future clinical trial should consider the pharmacological profile of the desired drug and also the characteristics and comorbidities of the patients in order to foster a success.

Background: Dissociative Identity Disorder (DID) is a rare condition that causes alternation of at least two separate personality states and has a prevalence of less than 1% in the general population. This study aims to appraise the social media platforms, YouTube and TikTok, as sources of medical information on DID. Methods: YouTube and TikTok were queried using the following search phrases: “Dissociative Identity Disorder,” “Multiple Personality Disorder,” and “Split Personality Disorder.” The top 60 videos by views for YouTube and likes for TikTok were selected from each search term on each platform. Videos were reviewed by four independent reviewers using a modified DISCERN (mDISCERN) Scale, Global Quality Scale (GQS), and they were further classified as useful, misleading, or neither useful or misleading. Results: Number of videos that met criteria were 60 YouTube videos and 97 TikTok videos. After classification, 51.7% of YouTube videos were useful while only 5.2% of TikTok videos were useful. A significant difference was found between (mDISCERN and GQS) score and the video source, type of content, and classification (α < 0.05). Limitations: This study focused exclusively on English videos. Additionally, it did not evaluate other social media platforms that are used worldwide. Conclusion: This results of this study show the need for healthcare professionals and organizations to not only create content of high quality but increase engagement on social media platforms, particularly TikTok, in order to educate users on DID.

Background: Evidence on the genetics of functional seizures is scarce, and the purpose of the current scoping systematic review is to examine the existing evidence and propose how to advance the field. Methods: Web of science and MEDLINE were searched, from their initiation until May 2023. The following key words were used: functional neurological disorder(s), psychogenic neurological disorder(s), functional movement disorder(s), psychogenic movement disorder(s), functional seizures(s), psychogenic seizure(s), nonepileptic seizure(s), dissociative seizure(s), or psychogenic nonepileptic seizure(s), AND, gene, genetic(s), polymorphism, genome, epigenetics, copy number variant, copy number variation(s), whole exome sequencing, or next-generation sequencing. Results: We identified three original studies. In one study, the authors observed that six (5.9%) patients with functional seizures carried pathogenic/likely pathogenic variants. In another study, the authors observed that, in functional seizures, there was a significant correlation with genes that are over-represented in adrenergic, serotonergic, oxytocin, opioid, and GABA receptor signaling pathways. In the third study, the authors observed that patients with functional seizures, as well as patients with depression, had significantly different genotypes in FKBP5 single nucleotide polymorphisms compared with controls. Conclusion: Future genetic investigations of patients with functional seizures would increase our understanding of the pathophysiological and neurobiological problems underlying this common neuropsychological stress-associated condition. [ABSTRACT FROM AUTHOR]

The present study aimed at assessing the effects of combining 20 mg/kg S(+) ketamine with 25 μg/kg dexmedetomidine and 0.4 mg/kg butorphanol on the physiological parameters and anesthetic recovery time and score of eight captive scarlet macaw (Ara macao) specimens. These specimens were captured at the Marabá Zoobotanic Foundation (Fundação Zoobotânica de Marabá), Pará, using butterfly and mist nets, and subsequently subjected to the proposed protocol. The following physiological parameters were evaluated: heart rate (HR), respiratory rate (RR), saturation of peripheral oxygen (SpO2), body temperature (BT), and non-invasive blood pressure 5 min after drug administration (M0) and every 10 min thereafter (M1‒M5), with a total of 55 min of analysis of anesthetic effects. Glycemia was measured 5 min after drug administration and every 30 min thereafter. Anesthetic induction and recovery times were also determined. Among the parameters evaluated in this study, both HR and BT significantly decreased throughout the anesthetic period, with the lowest levels at 55 min after drug administration (M5). In contrast, RR did not significantly differ, and all animals remained stable, maintaining an RR close to a mean of 20 ± 8 cpm. Throughout the anesthetic period, SpO2 was 92 ± 5%, with no significant difference. The birds remained under spontaneous ventilation and without oxygen supplementation. Systolic, diastolic, and mean blood pressures remained stable, with no significant differences in any of these measurements. At M0 and M3, the glycemia decreased slightly, albeit with no significant difference justifying an adverse effect or even hypoglycemia. The anesthetic induction time, from M0 to decubitus, was 2.4 ± 0.7 min. The anesthetic recovery time, from M0 to effortless bipedal position and adequate phalangeal flexion, was 99.3 ± 32.4 min. The sedation was assessed as intense, and the anesthetic recovery was rated excellent in 62.5% and good in 37.5% of the animals.

Objective: We searched for, from the FDA (Food and Drug Administration‐USA)‐approved drugs, inhibitors of FKBP5 with tolerable adverse effect profiles (eg, mild headache, sedation, etc.) and with the ability to cross the blood brain barrier (BBB), using bio‐informatics tools (in‐silico). This may pave the road for designing clinical trials of such drugs in patients with functional seizures (FS) and other stress‐associated disorders. Methods: Several databases were used to find all the approved drugs that potentially have interactions with FKBP51 protein [ie, CTD gene‐chemical interaction section of FKBP51 protein of Harmonizome of Mayaanlab, DrugCenteral database, PDID (Protein Drug Interaction Database), DGIdb (the Drug Gene Interaction database)]. Other databases were also searched [eg, clinicaltrials.gov; DRUGBANK (the FASTA format of the FKBP51 protein was imported to the target sequencing section of the database to find the associated drugs), and the STITCH database (to find the related chemical interaction molecules)]. Results: After a comprehensive search of the designated databases, 28 unique and approved drugs were identified. Fluticasone propionate and Mifepristone and Ponatinib, Mirtazapine, Clozapine, Enzalutamide, Sertraline, Prednisolone, Fluoxetine, Dexamethasone, Clomipramine, Duloxetine, Citalopram, Chlorpromazine, Nefazodone, and Escitalopram are inhibitors of FKBP5 and have BBB permeability. Significance: While the current in‐silico repurposing study could identify potential drugs (that are already approved and are widely available) for designing clinical trials in patients with stress‐associated disorders (eg, FS), any future clinical trial should consider the pharmacological profile of the desired drug and also the characteristics and comorbidities of the patients in order to foster a success. [ABSTRACT FROM AUTHOR]

Objective: We investigated the associations between FKBP5 single‐nucleotide polymorphisms (SNPs) and functional seizures (FS). Methods: Seventy patients with FS, 140 with major depressive disorder (MDD), and 140 healthy controls were studied. Their DNAs were analyzed for the rs1360780 in the 3′ region and rs9470080 in the 5′ region of the FKBP5. Childhood trauma questionnaire and hospital anxiety and depression scale were used. Results: Patients with FS and those with MDD had less GG and more AA genotypes in both rs9470080 and rs1360780 SNPs compared with those in healthy controls. Similar results were observed for allelic frequencies. There were no significant differences between FS and MDD groups in terms of genotype and allelic frequencies for both SNPs. The results of multinomial logistic regression analysis showed that FKBP5 polymorphisms were not associated with the diagnosis. Significance: Patients with FS and those with MDD had significantly different genotypes in both rs9470080 and rs1360780 SNPs compared with those in healthy controls. However, it seems that FKBP5 polymorphisms were not associated with FS in the absence of depression. Further genetic investigations of patients with FS may increase our understanding of the neurobiological underpinnings of this condition, but such studies should be large enough and very well designed; they should include a comparison group with depression in addition to a healthy control group. [ABSTRACT FROM AUTHOR]

Appropriate calculation and use of reference intervals have widespread clinical and research implications. Unfortunately, reference intervals for blood pressure in one of the most commonly used NHP species, rhesus macaques (Macaca mulatta), have never been calculated. Although anesthetic drugs and noninvasive methods of blood pressure measurement both have known effects on blood pressure values, their use provides the safest, fastest, and most widely used approach to clinical evaluation and blood pressure collection in this species. We analyzed noninvasive blood pressure measurements from 103 healthy, ketamine-sedated, adult (age, 8 to 16 y) rhesus macaques, representing both sexes, with various body condition scores by using 2 types of sphygmomanometers at 3 different anatomic locations. Reference intervals were calculated for each device, in each location, thus establishing normative data beneficial to clinical veterinarians assessing animal health and encouraging researchers to use noninvasive methods. Age, body condition score, sex, type of sphygmomanometer, and location of cuff placement were all found to influence blood pressure measurements significantly, providing important information necessary for the appropriate interpretation of noninvasive blood pressure values in rhesus macaques.

Ketamine is a glutamate N-methyl-D-aspartate receptor antagonist that is a rapid-acting dissociative anesthetic. It has been proposed as an adjuvant treatment along with other drugs (atropine, midazolam, pralidoxime) used in the current standard of care (SOC) for organophosphate and nerve agent exposures. Ketamine is a pharmaceutical agent that is readily available to most clinicians in emergency departments and possesses a broad therapeutic index with well-characterized effects in humans. The objective of this study was to determine the pharmacokinetic profile of ketamine and its active metabolite, norketamine, in F344 rats following single or repeated intramuscular administrations of subanesthetic levels (7.5 mg/kg or 30 mg/kg) of ketamine with or without the SOC. Following administration, plasma and brain tissues were collected and analyzed using a liquid chromatography-mass spectrometry method to quantitate ketamine and norketamine. Following sample analysis, the pharmacokinetics were determined using non-compartmental analysis. The addition of the current SOC had a minimal impact on the pharmacokinetics of ketamine following intramuscular administration and repeated dosing at 7.5 mg/kg every 90 minutes allows for sustained plasma concentrations above 100 ng/mL. The pharmacokinetics of ketamine with and without the SOC in rats supports further investigation of the efficacy of ketamine co-administration with the SOC following nerve agent exposure in animal models.

Application of metabolic magnetic resonance imaging measures such as cerebral blood flow in translational medicine is limited by the unknown link of observed alterations to specific neurophysiological processes. In particular, the sensitivity of cerebral blood flow to activity changes in specific neurotransmitter systems remains unclear. We address this question by probing cerebral blood flow in healthy volunteers using seven established drugs with known dopaminergic, serotonergic, glutamatergic and GABAergic mechanisms of action. We use a novel framework aimed at disentangling the observed effects to contribution from underlying neurotransmitter systems. We find for all evaluated compounds a reliable spatial link of respective cerebral blood flow changes with underlying neurotransmitter receptor densities corresponding to their primary mechanisms of action. The strength of these associations with receptor density is mediated by respective drug affinities. These findings suggest that cerebral blood flow is a sensitive brain-wide in-vivo assay of metabolic demands across a variety of neurotransmitter systems in humans.

Psychogenic nonepileptic seizures, also called Functional Seizures, are a highly disabling form of Functional Neurological Disorder. The diagnosis of PNES could be missed in clinical scenarios where patients exhibit concurrent musculoskeletal/neurological findings. Characterization of convulsions and judicious use of diagnostics are equally valuable in establishing the diagnosis. [ABSTRACT FROM AUTHOR]

Laboratory animals are commonly anesthetized to prevent pain and distress and to provide safe handling. Anesthesia procedures are well-developed for common laboratory mammals, but not as well established in reptiles. We assessed the performance of intramuscularly injected tiletamine (dissociative anesthetic) and zolazepam (benzodiazepine sedative) in fixed combination (2 mg/kg and 3 mg/kg) in comparison to 2 mg/kg of midazolam (benzodiazepine sedative) in ball pythons (Python regius). We measured heart and respiratory rates and quantified induction parameters (i.e., time to loss of righting reflex, time to loss of withdrawal reflex) and recovery parameters (i.e., time to regain righting reflex, withdrawal reflex, normal behavior). Mild decreases in heart and respiratory rates (median decrease of

A female rhesus macaque developed two episodes of generalized convulsions during transcutaneous spinal cord stimulation (TSCS) and urodynamic studies under ketamine anesthesia. The seizures took place in the absence of active TSCS and bladder pressure elevation. Ketamine anesthesia remains the primary risk factor for the convulsions during these experimental procedures.

OBJECTIVES: The aim of the study was to evaluate the effects of intramuscular (IM) injections of alfaxalone combined with butorphanol on echocardiographic (ECG) measurements in cats. METHODS: Client-owned adult domestic shorthair cats younger than 5 years of age were recruited. All cats that were considered healthy on the basis of physical examination, blood work, urinalysis, blood pressure measurement and baseline ECG underwent a second ECG under sedation. Cats were sedated with two separate IM injections of butorphanol at 0.2 mg/kg and alfaxalone at 2 mg/kg. ECG variables were analysed using a linear mixed model, and sedation scores were analysed using an ordinal mixed logistic model. The significance level was set at α = 0.05 and adjusted at α = 0.0017 for multiple comparisons of the ECG measurements. RESULTS: Ten healthy cats were included. Sedation was uneventful, and recovery was smooth and quick for all cats. The mean duration of lateral recumbency was 36.3 ± 4.37 mins. Reduction in heart rate following sedation approached statistical significance (P = 0.002). The thickness of the interventricular septum, the thickness of the left ventricular free wall, and the left ventricular internal dimensions in diastole and systole were not affected by the sedation. The changes in left atrium/aortic ratio and shortening fraction were statistically significant. Although the peak velocity of early diastolic transmitral flow (E) and late diastolic transmitral flow (A), the peak early diastolic (Ea) mitral valve annulus velocity, and the peak late diastolic (Aa) mitral valve annulus velocity changed after sedation, the ratios E/A, E/Ea and Ea/Aa were not significantly different after sedation. CONCLUSIONS AND RELEVANCE: IM injections of alfaxalone and butorphanol induced rapid, deep and short-lasting sedation. The mean differences after sedation were not clinically significant for most echocardiographic measurements.

BackgroundEmergency physicians regularly encounter agitated patients. In extremely agitated and violent patients, the onset of many traditional medications is relatively slow and often requires additional medication. Ketamine is frequently used in emergency departments (EDs) for procedural sedation and intubation, but has recently been suggested as a treatment for acute agitation.ObjectivesWe sought to examine the use of ketamine in the treatment of acute agitation in an ED setting, including vital sign changes as a result of this medication.MethodsThis is a structured review of an historical cohort of patients over 7 years at two university EDs. Patients were included if they received ketamine as treatment for acute agitation. Abstracted data included age, vital signs including hypoxia, any additional medications for agitation, and alcohol/drug intoxication.ResultsKetamine was administered for agitation on 32 visits involving 27 patients. Preadministration systolic blood pressure was 131 ± 20 mm Hg, with an average postadministration increase of 17 ± 25 mm Hg. The average baseline heart rate was 98 ± 23 beats/min, with an average increase of 8 ± 17 beats/min. No patients became hypoxic; 62.5% of patients required additional calming medication. Alcohol or drug intoxication was present in 40.6% of patients.ConclusionsWe found ketamine was used rarely, but had few major adverse effects on vital signs even in a population with 21.9% alcohol intoxication. However, a high proportion (62.5%) of patients required additional pharmacologic treatment for agitation, implying that administering ketamine is useful only for initial control of severe agitation.

[Display omitted] • Comparison of poly(propylene maleate) with poly(propylene fumarate) to produce dissociative CANs using multifunctional furan crosslinkers. • Networks comprising poly(propylene maleate) have higher dissociation temperatures than networks comprising poly(propylene fumarate). • The characteristics of the networks comprising furan-maleate cycloadducts are similar to networks based on furan-maleimide cycloadducts. • The unsaturated polyesters are commercially available in large quantities (currently used for thermosets), and the multifunctional furan crosslinkers are made with high atom efficiency. Unsaturated polyesters (UPEs) are a class of thermosetting resins which are prevalent in the polymer industry, offering excellent durability in many applications. However, their permanent crosslinks prevent re-use or recycling at their end-of-life. This problem is addressed using UPEs to generate dissociative covalent adaptable networks (CANs). Poly(propylene maleate) and poly(propylene fumarate) were copolymerised with furan-functionalised crosslinkers to form networks comprising reversible Diels-Alder cycloadducts. The thermal properties of each material were analysed by differential scanning calorimetry (DSC), showing that the furan-maleate networks dissociated at 130 °C compared to the furan-fumarate networks which dissociated at a significantly lower temperature (100 °C). The network formed from poly(propylene maleate) using a flexible trifunctional furan crosslinker provided the largest increase in T g and T rDA , producing the highest gel fraction (99 %) and a stable plateau modulus of 10 MPa by DMA. The networks reform at ambient temperature, although the rate of formation can be increased significantly by mild heating at 65 °C. Overall, the results indicate that furan-maleate CANs behave like reference furan-maleimide networks. Thermal analysis indicated that the furan-maleate cycloadduct was retained by heating to 150 °C, whereas isomerisation of maleate to fumarate was observed after repeated heating cycles to 180 °C. Mechanical testing showed that a bond strength of almost 10 MPa was achieved using these CANs as adhesives, which could be readily modified through changes in copolymer composition. [ABSTRACT FROM AUTHOR]

Objective: To determine whether patients who experienced their first psychogenic non-epileptic seizure (PNES) at 50 years or older differed from those who developed PNES at a younger age, in terms of demographic, social/clinical as well as psychological measures.Background: The typical age for PNES onset is roughly between 20 and 40 years of age. Only a handful of studies have examined samples with PNES onset at an older age and therefore information about these individuals is limited.Methods: This is a retrospective study of 75 consecutive individuals who developed (video EEG-confirmed diagnosis) PNES before age 50 years and 55 consecutive individuals who developed PNES at 50 years or more. Patients were examined on demographics (age, education, working and relationship status), clinical (seizure frequency, trauma type: sexual, multiple trauma, and health-related traumatic experiences), and self-report measures(Coping Inventory for Stressful Situations, Toronto Alexithymia Scale, and the Quality of Life Inventory in Epilepsy-31).Results: Patients who had experienced sexual trauma were likelier to develop PNES at an earlier age. Those who experienced "health problems pre-PNES onset" were likelier to develop PNES at an older age. On psychological measures, it was noted that after adjusting for the covariate effects, those with elevations in Avoidance (CISS) were likelier to develop PNES at an earlier age. and those with elevations in QOLIE31 cognitive complaints were likelier to be in the older cohort.Conclusions: No matter at what age PNES presented, patients reported markedly high rates of exposure to psychological trauma (single and multiple), similarly elevated unemployment rates and low quality of life.  The groups with different age of onset differed in the type of trauma experienced prior to the development of PNES. In addition, the younger onset group demonstrated a significantly higher use of avoidance as a stress-coping strategy. [ABSTRACT FROM AUTHOR]

Compartmentalization phenomena have been identified in somatoform symptoms such as seizures or paralysis seen in Functional Neurological Disorders, and also in psychoform symptoms such as amnesia, flashbacks, or pseudohallucinations (Brown, [6]). Keywords: dissociative; compartmentalization; psychosis; delusion; CBTp EN dissociative compartmentalization psychosis delusion CBTp N.PAG N.PAG 4 04/26/21 20210409 NES 210409 Introduction Recommended psychological treatments for psychosis [National Institute of Health and Care Excellence (NICE), [19]] have developed from innovative cognitive models of positive symptoms (Garety et al., [11]) which explain delusions as causal inferences that form in response to affective, perceptual, and cognitive anomalies (Newman-Taylor and Sambrook, [20]). Dissociative symptoms in schizophrenic patients with positive and negative symptoms. Dissociative symptoms in patients with schizophrenia: relationships with childhood trauma and psychotic symptoms. [Extracted from the article]

Distractions are often associated with negative outcomes however, distractions can also benefit people. Using the hypothesis of internal-external distractions in the competition for cue, this study examined the effects of an active (controlled) and passive (uncontrolled) distraction on three endurance tasks. Participants (N=42), aged 20 to 23 years were assigned to three groups. Tasks and conditions were counterbalanced across groups to minimize the residual effects of fatigue, learning an intervention and other confounding variables. Performance time, heart rate, ratings of perceived exertion and perceived fatigue were measured. Results showed that active distraction significantly improved performance and lowered Rate of Perceived Exertion in one task. As expected, the active distraction group was the least accurate for estimating time spent. Passive distraction caused minimal performance change. More investigation is needed to understand why an active distraction only affected one trial. Future studies should delve into means for better understanding the hypothesis of competition for cue.

Functional seizures (FS) are frequently encountered in neurology clinics, often affect young adults, and have significant negative impacts on many aspects of a person’s life. In the current narrative review, we searched the literature regarding some of the consequences of FS (i.e., psychiatric comorbidities, social consequences, costs that are associated with the condition, cognitive impairment in patients with FS, the quality of life of the people with FS, and the increased risk of mortality that is associated with FS). Evidence shows that FS have significant negative consequences, comparable in their magnitude to those affecting patients with epilepsy. The clinical and scientific communities should take steps to address these consequences through clinical care and research that prioritizes, facilitates, and expedites evidence-based diagnosis and treatment for FS.

Alcohol use disorders often co-occur with affective disorders, anxiety disorders and schizophrenia. The presence of dual diagnosis worsens the prognosis in patients. However comorbid patients rarely receive specialized treatment that addresses both conditions. This paper reviews currently available treatment options for patients with dual diagnosis, as well as addresses the issues of common neurobiological mechanisms converging on monoaminergic neurons originating from the brain stem. Particular emphasis is made on the updated role for dynorphin / kappa-opioid (KOP) receptor system modulation of the mesocorticolimbic dopaminergic circuitry - a neuronal hub playing a major role in the pathology of the majority of mental disorders and chemical addictions. The interest to the kappa-opioid system is caused by the role of endogenous opioid neuropeptide dynorphin being one of the most powerful endogenous depressants of monoaminergic (dopamine, norepinephrine, and serotonin) and glutamatergic neurotransmission in the cerebral cortex and subcortical limbic structures. This designates the strategic role for the kappa-subtype opioid receptor in regulation of mood, emotions, motivation, cognitive performance, perception and impulse control. Most of the KOP-antagonists are still being under clinical development and are not yet routinely available to clinicians. These agents are being developed for the treatment-resistant depression, bipolar, dissociative disorders and addictions. However, recently nalmefene - a new treatment for alcohol addiction, has been approved in Europe and Russia. Nalmefene is an opioid receptor antagonist with the preferential affinity to the KOP receptor. As this psychopharmacological agent carries therapeutic potential beyond substance abuse and addiction, possible clinical benefits of nalmefene in the treatment of complex comorbid patients are discussed. In comorbid schizophrenia patients the validity and necessity of the simultaneous therapy with antipsychotics and drugs used for the treatment of alcoholism (including opiate receptor blockers) were proved.

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Objectives: The aim of the current endeavor was to systematically review the existing evidence on brain connectivity abnormalities in patients with functional seizures (FS).Methods: This systematic review was prepared according to the instructions of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. MEDLINE (accessed from PubMed) and Scopus from inception to April 4, 2020 were systematically searched. The following search strategy was implemented and these key words (in the title/abstract) were used: "connectivity" OR "network" AND "psychogenic" OR "dissociative" OR "nonepileptic".Results: Through the search strategy, we could identify eighteen articles. These studies have applied various methodologies and they could identify a variety of brain connectivity abnormalities in people with FS. However, none of these studies provided a high level of evidence. They were all small studies (none had a sample size of more than 21 patients). In addition, most of the studies did not match their cases and their controls with respect to the psychiatric comorbidities and other significant confounders.Conclusion: Abnormal functional connectivity between emotion processing areas of the brain with regions involved in executive control and cognitive performance, and the functional connections of the anterior cingulate cortex are of major interest and may be involved in the pathophysiology of FS. Pursuing the concept of brain connectivity abnormalities in patients with FS and comparing the findings with well-matched controls in well-designed studies may result in a breakthrough in identifying the exact neurobiological origin of FS. [ABSTRACT FROM AUTHOR]

Objective: To determine the utility of suggestive seizure induction for inpatient work‐up of suspected psychogenic nonepileptic seizures (PNES). Methods: Prospective study of epilepsy center inpatient admissions with suspected PNES. Patients were randomized to undergo suggestive induction first (group A) and then, if necessary, long‐term video–electroencephalography (EEG) monitoring, or vice versa (group B). Diagnostic pathways were compared. Potential clinical predictors for diagnostic success were evaluated. Results: Length of in‐hospital stay did not significantly differ between groups. Suspicion of PNES was confirmed in 43 of 77 (56%) patients, evenly distributed between group A (22 of 39) and group B (21 of 38). In nine patients, recorded habitual seizures were epileptic and in 25 cases, no diagnostic event could be recorded. Diagnosis of PNES was ascertained primarily by recording a typical seizure through suggestive induction in 24 patients and through long‐term monitoring in 19 patients. In group A (induction first), monitoring was not deemed necessary in 21% of cases. In group B (monitoring first), 13% would have remained inconclusive without suggestive induction. Patients who reported triggers to their habitual seizures were not more likely to have spontaneous or provoked PNES during monitoring or suggestive inducion, respectively. Patients with subjective seizure prodromes (auras) were significantly more likely to have a PNES during suggestive induction than those without (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.1‐10.4). There was no significant difference in seizure frequency between patients with spontaneous PNES during long‐term monitoring and those with nondiagnostic monitoring sessions. Significance: Our results support the notion that suggestive seizure induction can reduce the number of inconclusive inpatient workups, and can obviate resource‐intensive long‐term monitoring in one fifth of cases. Patients who are aware of prodromes might have a higher chance of having seizures induced through suggestion. [ABSTRACT FROM AUTHOR]

• 1492 patients were studied (559 patients with IGE, 646 people with TLE, and 287 persons with FS). • 77 (5.2%) individuals had severe head injuries before the onset of their seizures [9 patients (1.6%) with IGE, 56 people (8.7%) with TLE, and 12 persons (4.2%) with FS; p = 0.0001]. • Compared to people with IGE, the odds ratio of having a premorbid history of severe head injury in the FS group was 2.67 [95% confidence interval (CI): 1.11–6.40; p = 0.0280]. • Compared to people with TLE, the odds ratio of having a premorbid history of severe head injury in the FS group was 0.46 (95% CI: 0.24–0.87; p = 0.0170). The aim of the current study was to compare the frequency of significant head injuries in three groups of people with seizures [idiopathic generalized epilepsies (IGE) vs. temporal lobe epilepsy (TLE) vs. functional seizures (FS)]. This was a retrospective study. All patients with a diagnosis of IGE, TLE, or FS were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2020. One thousand and four hundred ninety-two patients were studied (559 patients with IGE, 646 people with TLE, and 287 persons with FS). Overall, 77 (5.2%) individuals of the studied people reported experiencing severe head injuries before the onset of their seizures [9 patients (1.6%) with IGE, 56 people (8.7%) with TLE, and 12 persons (4.2%) with FS; p = 0.0001]. Compared to people with IGE, the odds ratio of having a premorbid history of severe head injury in the FS group was 2.67 [95% Confidence Interval (CI): 1.11–6.40; p = 0.0280]. Compared to people with TLE, the odds ratio of having a premorbid history of severe head injury in the FS group was 0.46 (95% CI: 0.24–0.87; p = 0.0170). Severe head injury is significantly associated with FS. However, since head injury is also a significant risk factor for focal epilepsies, it may be necessary to ascertain the diagnosis of post-traumatic seizures by obtaing a detailed clinical history and also by performing video-EEG monitoring in order to adopt an appropriate treatment strategy in these patients. [ABSTRACT FROM AUTHOR]

Introduction: Psychotic dissociative disorder is a mental process where a person disconnects from their own thoughts, feelings, memories or sense of identity. It usually occurs after the person experienced a traumatic event and it can serve as a defense mechanism against overwhelming emotions. Case Report: The purpose of this report is to present a rare case of psychotic dissociative disorder with serious damage of physical health. The 18 year old patient was brought to emergency service of psychiatric clinic due bizarre and chaotic behaviour, incomprehensible speech. This acute psychotic episode debuted four days prior and was characterized by autoand allopsychic disorientation, disjointed and tangential speech, echolalia, marked suggestibility and restlessness, purposeless movements. The patient's drug test came back negative and she doesn't have any history of psychiatric disorders. According to the patient's mother, symptoms debuted following a traumatic event at school and they worsened during those 4 days. Over the initial three weeks of hospitalization, the patient was noncooperative and did not respond to the prescribed treatment regimen. Her condition got gradually worse and she started manifesting muscle spasms, dysphonia, dysphagia and ultimately entering a catatonic state. Consequently, she was transferred to the ICU, where she remained for the next 2 weeks. Upon returning to the psychiatric clinic, her mental state had not improved, she continued to exhibit extreme agitation, aimless laughter, and peculiar behaviour. A revised treatment plan yielded success, leading to the patient's discharge after a month of care. Currently, there have been no recurrences of psychotic episodes, and the patient maintains a stable clinical course. Discussions : Considering the patient's established hysterical personality tendencies, the traumatic event had an even bigger impact on her. Due to the inclination to seek attention and the reduced capacity to tolerate stress and psychological trauma, the patient dissociated as a way of coping. Several examinations were conducted to ascertain the etiology of her physical deterioration, yet all results returned within normal parameters. This underscores the proposition that her catatonic state was solely precipitated by psychological factors. Conclusions: Psychotic dissociative disorder stands as a complex and multifaceted condition that requires a comprehensive and meticulous approach, because clearly this disorder poses significant challenges for both those affected and their caregivers, potentially even endangering the patient's life. [ABSTRACT FROM AUTHOR]

Ketamine binds non-competitive against a phencyclidine receptors bound N-methyl-D-aspartate (NMDA), a receptor that is involved in the pathophysiology of acute pain. Ketamine has been used as an intravenous anesthesia, analgesia for acute and chronic pain at a dose of subanaesthetic. Ketamine is a dissociative anesthetic produces a state with a characteristic strong analgesia, amnesia, and catalepsy. Dissociative components resulting from the effect on the limbic system and talamoneokortikal. Lowdose ketamine as known as analgesia dose ketamine or subanestesia dose is 0.2 to 0.75 mg / kg IV. At low doses, ketamine does not increase the effect psychomimetic like dissociation or deep sedation. The combination with midazolam provides satisfactory sedation, amnesia and analgesia without significant cardiovascular depression.

Intranasal anesthesia in birds is considered a safe, simple and efficient technique. The aim of this study was compare the anesthetic effects of midazolam (5 mg.kg-1) with racemic (R) or S+ (S) ketamine (15 mg.kg-1), administered intranasally (IN) or intramuscularly (IM) in budgerigars (Melopsittacus undulatus). Eight budgerigars were used in a crossover design with four treatments: INR, INS, IMR and IMS. Onset time, dorsal recumbency time duration, total anesthesia time, total recovery time, sedation degree and recovery quality were evaluated. Significant differences were observed in onset time between INS (40.25±10.55 sec) and IMR (74.32±21.77 sec); between administration vials for dorsal recumbency time, INS (23.93±7.51 min) and INR (28.68±16.13 min), which were different from IMS (60.08 ± 27.37 min) and IMR (74.3±21 min). In total anesthesia time, INS (45.48±17.94 min) and INR (39.24±15.62 min) were different from IMS (75.84±20.20 min) and IMR (20.73±79.4 min). The total recovery time was significantly higher in INS (21.55±18.43 min) compared to IMR (5.1±3.56 min). The results of this study indicated that both administration vials can be used for short time non-invasive procedures and the intranasal vial is preferable for fast procedures.

Purpose: We investigated the driving rate and the rate of road traffic accidents in patients with functional seizures. We hypothesized that road traffic accidents are common in these patients.Methods: In this long-term study, all patients with functional seizures, who were diagnosed at Shiraz Comprehensive Epilepsy Center, Iran, from 2008 until 2018, were investigated. In a phone call interview in February 2020, we obtained the following information: seizure outcome, driving a motor vehicle, experiencing any road traffic accidents in the past 12 months, and their drug regimen.Results: 100 patients participated; 41 patients were driving a motor vehicle in their routine daily lives. Seizure freedom [Odds Ratio (OR): 6.15; 95 % Confidence Interval (CI): 1.95-19.35; p = 0.002] and being employed (OR: 10.66; 95 % CI: 3.03-37.49; p = 0.0001) were significantly associated with driving a motor vehicle. Five patients reported experiencing road traffic accidents while driving a motor vehicle in the past 12 months. All these five patients reported being seizure-free.Conclusion: The majority of patients with functional seizures do not drive a motor vehicle; fear of seizures is a significant determinant. When patients with functional seizures achieve seizure freedom, the rate of driving a motor vehicle increases significantly. The rate of road traffic accidents in patients with functional seizures does not seem to be high. [ABSTRACT FROM AUTHOR]

Dissociative disorders have been present in our society since time immemorial, with culture, society, and spiritual beliefs playing a major part. It went through many changes from its name and what it constituted. Diagnosis can be made based on the International Classification of Diseases (ICD) 10, Diagnostic and Statistical Manual of Mental Disorders (DSM) 5, and now the current International Classification of Diseases (ICD) 11 criteria. One of its constituents is trance and possession disorder which is one of the main obstacles faced by psychiatrists in Indian society. Through this case, we can assume that there are many factors involved that lead to delays in diagnosing and managing a case of dissociative disorder, most importantly the social and cultural factors. Even now cultural-socio-spiritual beliefs add to the challenge of dissociative disorders. This case reveals that individuals first consult a general physician before visiting a psychiatrist; so, the need for consultation liaison psychiatry (CLP) and its role today in diagnosis and further management is emphasized. There still exists a need for awareness to be made regarding the mind-body relationship and psychosocial support to both patients and their relatives keeping in mind their beliefs., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Longkumer et al.)

Background: Ketamine attenuates morphine tolerance by antagonising N-methyl-d-aspartate receptors. However, a pharmacokinetic interaction between morphine and ketamine has also been suggested. The interaction between oxycodone and ketamine is unclear. We studied the effects of ketamine and norketamine on the attenuation of morphine and oxycodone tolerance focusing on both the pharmacodynamic and pharmacokinetic interactions.Methods: Morphine 9.6 mg day-1 or oxycodone 3.6 mg day-1 was delivered to Sprague-Dawley rats by subcutaneous pumps. Once tolerance had developed, the rats received subcutaneous injections of ketamine or norketamine. Tail-flick, hot-plate, and rotarod tests were performed. Drug concentrations were measured with high-performance liquid chromatography-tandem mass spectrometry.Results: Anti-nociceptive tolerance to morphine and oxycodone developed similarly by Day 6. Acute ketamine 10 mg kg-1 and norketamine 30 mg kg-1 attenuated morphine tolerance for 120 and 150 min, respectively, whereas in oxycodone-tolerant rats the effect lasted only 60 min. Both ketamine and norketamine increased the brain and serum concentrations of morphine, and inhibited its metabolism to morphine-3-glucuronide, whereas oxycodone concentrations were not changed. Morphine, but not oxycodone, pretreatment increased the brain and serum concentrations of ketamine and norketamine. Ketamine, but not norketamine, significantly impaired the motor coordination.Conclusions: Ketamine and norketamine attenuated morphine tolerance more effectively than oxycodone tolerance. Ketamine and norketamine increased morphine, but not oxycodone brain concentrations, which may partly explain this difference. Norketamine is effective in attenuating morphine tolerance with minor effects on motor coordination. These results warrant pharmacokinetic studies in patients who are co-treated with ketamine and opioids. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective: The aim of this study is to examine patients with suicide attempts in respect of mood disorders and dissociative symptoms and to understand the impact of these symptoms on suicide attempts. Method: Seventy participants who were directed to psychiatry outpatient department from the Kastamonu State Hospital crisis intervention unit between January 2009 and January 2010 and who agreed to participate in the study were included. All of the patients were evaluated by psychiatric interview. A detailed sociodemographic and clinical data form was filled for all included patients and present or past history of psychiatric illness were explored. The Mood Disorders Questionnaire (MDQ), Beck Depression Inventory (BDI), Beck Suicide Intention Scale (BSIS), Dissociative Experiences Scale (DES) were applied to all participants. Results: The mean score of DES was 39±21.3, of MDQ 7.5±2.5, of BDI 28±14 and of BSIS 15.3±5.8. Participants who scored higher than 7 in the MDQ had statistically more dissociative experiences than those who scored lower than 7 in MDQ. In addition, participants who scored higher than 5 points in the MDQ had more dissociative experiences than those who scored lower than 5 in the MDQ. Having higher scores on DES, MDQ and BDI was positively correlated with having higher scores on BSIS. Conclusion: The etiologies of suicides are complex. Suicide attempter might often have both mood symptoms and dissociative experiences. [JCBPR 2014; 3(1.000): 39-45]

Background: Research has shown that the therapeutic alliance plays an important role in enhancing treatment outcome among individuals with a variety of disorders, including posttraumatic stress disorder (PTSD). However, the therapeutic alliance and treatment outcome has not yet been studied in dissociative disorders (DD). Objectives: The current study sought to investigate the impact of alliance on treatment outcome for DD patients. Methods: Data from a naturalistic, longitudinal international treatment study of DD patients and their therapists were analyzed to determine if the alliance, as reported by patients and therapists, was associated with treatment outcome. Results: Patients with higher self-rated alliance had fewer symptoms of dissociation, PTSD, and general distress, as well as higher levels of therapist-rated adaptive functioning. Over time, self-rated alliance scores predicted better outcomes, after controlling for patient adaptive capacities including symptom management at the time when the alliance ratings were made. Patient-rated alliance was more strongly associated with outcome than therapist-rated alliance. Conclusion: Therapists who work with DD patients should understand the importance of the alliance on treatment outcome. These findings are consistent with previous literature demonstrating the importance of developing and maintaining a strong therapeutic alliance, although the effect sizes of individuals with DD were stronger than what has been found in many other patient groups. A greater understanding of the impact of the alliance in traumatized individuals may contribute to better outcomes for these individuals.