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Background: Participants who received ketamine at the NIMH were among the first to receive ketamine for depression in controlled clinical trials, providing a unique opportunity to assess long-term outcomes. This analysis evaluated the relationship between participating in a ketamine clinical trial and subsequent ketamine/esketamine use after leaving the research setting., Methods: Participants seen within the NIMH Experimental Therapeutics and Pathophysiology Branch from 2002 to 2022 (n = 1000) were contacted for follow-up assessment. Participants reported whether they had used ketamine/esketamine, sought non-prescribed ketamine, attempted suicide, or been psychiatrically hospitalized since discharge. Information regarding their recent depressive symptoms, dissociative symptoms, and hallucinations was also collected., Results: Of the 203 participants in follow-up assessments (55 % female, average time since leaving NIMH = 9.04 years), 52 (25.6 %) had originally received ketamine at the NIMH, and the rest had participated in non-ketamine studies. Individuals who had received ketamine at the NIMH were more likely to have received ketamine/esketamine post-discharge than those who did not receive ketamine at the NIMH (OR = 0.25, p < .001). Participants who reported using ketamine/esketamine post-discharge reported more depressive symptoms than those who had not (p < .001). Receiving ketamine at the NIMH was not associated with differences in suicide attempts, psychiatric hospitalizations, dissociation, hallucinations, or attempt to obtain non-prescribed ketamine., Limitations: Low follow-up study participation rate; varying time since discharge., Conclusions: Participants who received ketamine in an NIMH clinical trial were more likely to receive ketamine/esketamine post-discharge, but none reported symptoms indicating abuse. Results underscore the critical need for long-term follow-up of individuals receiving these and other rapid-acting antidepressants., Clinical Trials Identifier: NCT04877977., Competing Interests: Declaration of competing interest Dr. Zarate is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydroxylated and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. All other authors have no conflict of interest to disclose, financial or otherwise., (Published by Elsevier B.V.)

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 d  = 1.46 (95% CI: 0.62-2.31)]. However, the studies we included were very heterogeneous [Q = 66.89 ( p  < .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.

The Clinician-Administered Dissociative States Scale (CADSS) is a structured clinical interview to assess state dissociation rated by clinicians. The current study aimed to validate the German version of CADSS by comparing it to the established self-report measures for dissociation and exploring its underlying factor structure. Severity of within-session state dissociation was assessed directly following a standard psychotherapy session in a trauma-exposed patient sample ( N = 105; 81.9% female). Internal consistency, convergent validity with other dissociation measures, and the factorial structure of the instrument were analyzed. The German version exhibited excellent internal consistency (Cronbach's α = .94) and correlated significantly with self-report measures of state dissociation ( r = .86) and trait dissociation ( r = .77) indicative of high convergent validity. Exploratory factor analysis revealed a three-factor solution with the factors (1) Depersonalization/Derealization, (2) Identity Confusion/Alteration, and (3) Amnesia. Results support the CADSS as a useful instrument to assess state dissociation, conceptualized as a multidimensional construct, in clinical practice.

Background: Dissociation is a treatment-emergent adverse event commonly associated with IV ketamine, often measured using the 23-item Clinician-Administered Dissociative States Scale (CADSS). The objective of this study was to develop a short form version of the CADSS for easier clinical use., Methods: Retrospective data of 260 patients with treatment-resistant depression (TRD) receiving IV ketamine were randomly divided into two datasets. The first dataset (n = 130) was leveraged to develop a brief 6-item version of the CADSS (CADSS-6) based on items most sensitive to ketamine-induced dissociation. The CADSS-6 questions were then applied to the second dataset (n = 130) and the Spearman's correlation between the full-length CADSS and the CADSS-6 were assessed., Results: The CADSS-6 was developed from questions 1, 2, 6, 7, 15, and 22 from the full length CADSS. There was a strong significant correlation between the CADSS-6 total score and the CADSS total score at infusions 1 (rs(106) = 0.92, p < 0.001), 2 (rs(100) = 0.91, p < 0.001), 3(rs(99) = 0.95, p < 0.001) and 4 (rs(102) = 0.94, p < 0.001)., Limitations: The CADSS-6 was developed using a retrospective data; therefore, the scale remains unvalidated in this population., Conclusions: The CADSS-6 presented herein was sensitive to dissociation experienced by patients receiving IV ketamine. Overall, the CADSS-6 was strongly correlated at each infusion with the full-length CADSS. While future studies should look to validate the CADSS-6 in a TRD sample, this scale offers clinicians a brief assessment that can be used to characterize symptoms of dissociation., (Copyright © 2020. Published by Elsevier B.V.)

Background: Ketamine produces significant rapid-onset and robust antidepressant effects in patients with major depressive disorder. However, this drug also has transient cardiovascular stimulatory effects, and there are limited data about potential predictors of these cardiovascular effects., Methods: A total of 135 patients with unipolar and bipolar depression received a total of 741 ketamine infusions (0.5 mg/kg over 40 min). Blood pressure and pulse were monitored every 10 min during the infusions and 30 min after the infusions. Depressive, psychotomimetic and dissociative symptom severity was assessed at baseline and 4 hours after each infusion., Results: The maximum blood pressure and pulse values were observed at 30-40 min during infusions. The largest mean systolic/diastolic blood pressure increases were 7.4/6.0 mmHg, and the largest mean pulse increase was 1.9 beats per min. No significant change in blood pressure and pulse was found in the second to sixth infusions compared with the first infusion. Patients who were older (age⩾50 years), hypertensive and receiving infusions while exhibiting dissociative symptoms showed greater maximal changes in systolic and diastolic blood pressure than patients who were younger (age<50 years), normotensive and without dissociative symptoms (all p < 0.05). Hypertensive patients had less elevation of pulse than normotensive patients ( p < 0.05). Ketamine dosage was positively correlated with changes in systolic and diastolic blood pressure (all p < 0.05)., Conclusions: Blood pressure and pulse elevations following subanaesthetic ketamine infusions are transient and do not cause serious cardiovascular events. Older age, hypertension, large ketamine dosage and dissociative symptoms may predict increased ketamine-induced cardiovascular effects.

Background: Sub-anesthetic ketamine administration may be helpful for substance use disorders. Converging evidence suggests that the efficacy of ketamine for certain conditions may implicate a subset of its psychoactive effects., Aims: The aim of this analysis is to evaluate whether the mystical-type effects of ketamine are critical for clinical efficacy in alcohol-dependent individuals. In this secondary analysis, we determine if a subset of the psychoactive effects of ketamine, the so-called mystical-type experience, mediates the effect of ketamine, when combined with motivational enhancement therapy, on at-risk drinking behavior in alcohol-dependent individuals interested in treatment., Methods: Forty alcohol dependent adults were randomized to either a 52-minute infusion of ketamine or midazolam, which they received on a designated quit-day during the second week of a five-week motivational enhancement therapy regimen. Psychoactive effects were assessed following the infusion, and alcohol use was monitored for the subsequent 3 weeks at each twice-weekly visit., Results: We found that ketamine leads to significantly greater mystical-type effects (by Hood Mysticism Scale) and dissociation (by Clinician Administered Dissociative States Scale) compared to the active control. Ketamine also led to significant reduction in at-risk drinking. The Hood Mysticism Scale, but not Clinician Administered Dissociative States Scale score, was found to mediate the effect of ketamine on drinking behavior., Conclusions: This trial adds evidence to the literature on the importance of mystical-type experiences in addiction treatment. Future research should continue to investigate the relationship between the psychoactive effects of psychedelic therapeutics and clinical outcomes for other substance use and mental health disorders.

Ketamine produces immediate antidepressant effects and has inspired research into next-generation treatments. Ketamine also has short term dissociative effects, in which individuals report altered consciousness and perceptions of themselves and their environment. However, whether ketamine's dissociative side effects are necessary for its antidepressant effects remains unclear. This perspective examines the relationship between dissociative effects and acute and longer-lasting antidepressant response to ketamine and other N-methyl-D-aspartate (NMDA) receptor antagonists. Presently, the literature does not support the conclusion that dissociation is necessary for antidepressant response to ketamine. However, further work is needed to explore the relationship between dissociation and antidepressant response at the molecular, biomarker, and psychological levels.

Objective: Recent theory has proposed that a dysfunction of the opioid system modulates mood, reward and pain; seems to be unstable in people with Borderline Personality Disorder. Our purpose is to analyze the evidence on the efficacy of the use of buprenorphine, nalmefene, naloxone and naltrexone, in the treatment of dissociative symptoms, self-mutilation and suicidal behavior of these patients., Method: We conducted a systematic search of MEDLINE and LILACS databases, to retrieve relevant articles. Included studies were experimental and observational designs of borderline personality samples in which dissociative symptoms, self mutilation or suicidal behavior was reported as an outcome and evaluated with some impact measures., Results: A total of eight studies were reviewed. These provided interesting expectations about posible treatment lines in Borderline Personality Disorder using opioid antagonists. The subgroup most benefited was the one who has analgesia and highest number of diagnostic criteria., Conclusions: Studies of higher methodological quality are needed, in larger population samples and using control of confounding variables that allow us to estimate a value power calculation, and thus be able to support firm conclusions., Competing Interests: The authors have no conflicts of interest to declare.

Objective: The relationship between ketamine's hallucinogenic- and dissociative-type effects and antidepressant mechanism of action is poorly understood. This paper reviewed the correlation between subjective effects defined by various psychometric scales and observed clinical outcomes in the treatment of patients with Major Depressive Disorder (MDD)., Methods: Based on PRISMA guidelines, we reviewed the dissociative and psychotomimetic mental state induced with ketamine during MDD treatment. Our selected studies correlated depression rating with validated scales collected at regular intervals throughout the study period such as the Clinician-Administered Dissociative States Scale (CADSS), Brief Psychiatric Rating Scale (BPRS), and the 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC). We excluded studies with bipolar depression or with repeated dosing and no single-dose phase. We included 8 of 556 screened reports., Results: Two of five CADSS studies found significant negative correlations between increases in CADSS scores and depression scores. One of six BPRS studies demonstrated correlations between BPRS scores and depression scores. The 5D-ASC's one study found no correlation with the MADRS., Conclusions: Ketamine's dissociative and psychotomimetic effects were correlated with depression changes in 37.5% of studies, but most studies did not examine this relationship and future studies should consider this association since it appears important for MDMA and psilocybin therapies., Competing Interests: Declaration of Competing Interest Dr. Storch has received consulting fees from Levo Therapeutics. The authors alone are responsible for the content and writing of this paper., (Copyright © 2019. Published by Elsevier B.V.)

Background: Dissociative Disorder (DD) is a large group of disorders that shares common psychopathology. Psychopharmacological agents have sparse evidence in the treatment of DD in general. Multiple pharmacotherapy options have been used without conclusive evidence., Methods: We conducted a systematic review of data in English language from 1967 to 2019 the protocol of which was registered under PROSPERO (Study ID CRD42019127235). Using PRISMA guidelines, 5 RCTs reporting data on 214 participants providing data on response to pharmacotherapy in dissociative disorder were included., Results: The treatment response rate of pharmacotherapy group as measured in reduction in dissociative symptoms was 68.42% (n = 65/95), significantly higher than that of 39.49% (n = 47/119) in the control group. And, the pooled RR was 1.59 (95% CI, 0.76-3.30; P = 0.21). The overall effect estimates are favourable to pharmacotherapy group over placebo., Conclusion: It would be apt to conclude that Paroxetine and Naloxone are the only pharmacological agents studied through RCTs and found to have modest evidence for controlling depersonalization symptoms and dissociative symptoms that are comorbid with PTSD and BPD. Results of this meta-analysis should be interpreted with caution in view of high heterogeneity and scanty literature on RCTs on various subtypes of DD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The reflexive startle- and orienting-response have been widely studied in psychiatric disorders. Existing evidence in patients with borderline personality disorder (BPD) is mixed, and limited to adults. The present study addressed clinical correlates of the psychophysiological orienting response in adolescents with BPD., Methods: Female adolescents (13-19 years) with BPD (n = 30), healthy controls (HC; n = 34), and psychiatric clinical controls (CC; n = 53) participated in the trial. Orienting response was induced using acoustic startle-probes (sinus tones) while heart rate (HR) and skin conductance (SCR) were continuously recorded. Besides clinical interviews, the assessment included self-reports on depressive symptoms, anxiety, dissociation and psychopathological distress., Results: On a group level, relative habituation of the HR-response (regression slope) significantly differed between groups (F (2,114)  = 3.74, p = 0.027), with significant contrasts (p = 0.026, Sidak corrected) comparing CC (slope 0.04 ± 0.41) and BPD (slope 0.28 ± 0.40). On a dimensional level, relative HR habituation was significantly correlated with the number of BPD diagnostic criteria endorsed (r (117)  = 0.183, p = 0.049) and symptoms of dissociation (r (116)  = 0.193, p = 0.038), indicating that delayed HR habituation across probes was associated with greater BPD symptom severity. Analyses of SCR showed no significant findings., Conclusion: Findings provide preliminary support for altered habituation of the HR orienting response in adolescent BPD, associated with BPD severity - in particular dissociative experiences. Dissociative experiences may alter the automatic defensive response early in the course of BPD, providing a potential pathway to exaggerated emotional responding in BPD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Ketamine induces rapid and robust antidepressant effects, and many patients also describe dissociation, which is associated with antidepressant response. This follow-up study investigated whether antidepressant efficacy is uniquely related to dissociative symptom clusters., Methods: Treatment-resistant patients with major depressive disorder (MDD) or bipolar disorder (BD) (n = 126) drawn from three studies received a single subanesthetic (0.5 mg/kg) ketamine infusion. Dissociative effects were measured using the Clinician-Administered Dissociative States Scale (CADSS). Antidepressant response was measured using the 17-item Hamilton Depression Rating Scale (HAM-D). A confirmatory factor analysis established the validity of CADSS subscales (derealization, depersonalization, amnesia), and a general linear model with repeated measures was fitted to test whether subscale scores were associated with antidepressant response., Results: Factor validity was supported, with a root mean square error of approximation of .06, a comparative fit index of .97, and a Tucker-Lewis index of .96. Across all studies and timepoints, the depersonalization subscale was positively related to HAM-D percent change. A significant effect of derealization on HAM-D percent change was observed at one timepoint (Day 7) in one study. The amnesia subscale was unrelated to HAM-D percent change., Limitations: Possible inadequate blinding; combined MDD/BD datasets might have underrepresented ketamine's antidepressant efficacy; the possibility of Type I errors in secondary analyses., Conclusions: From a psychometric perspective, researchers may elect to administer only the CADSS depersonalization subscale, given that it was most closely related to antidepressant response. From a neurobiological perspective, mechanistic similarities may exist between ketamine-induced depersonalization and antidepressant response, although off-target effects cannot be excluded., (Published by Elsevier B.V.)

Symptoms of dissociation, including dissociative amnesia, depersonalization, and derealization, commonly develop in individuals subject to chronic and repeated trauma during development. This includes the trauma of environmental inability to facilitate development of adequate cognitive strategies for coping with strong negative emotions. Dissociation likely involves dysregulated balance of prefrontal inhibition of limbic structures and inadequate regulation of attentional bias by both prefrontal and limbic systems. There is currently no established psychopharmacologic treatment for dissociative symptoms. Here the case of a woman with severe dissociative symptoms that were markedly improved with the administration of mixed amphetamine salts is discussed. Potential neurobiologic mechanisms for dissociative symptom improvement with psychostimulants are discussed.

Dissociative convulsions or pseudoseizures are a difficult to treat common psychiatric condition. In a subset of these patients, the chief complaint is clenching of teeth with apparent nonresponsiveness alone. Neither drugs nor psychotherapeutic interventions have been found to be of much help in its management. Report of two such subsets of cases is presented, in which patients with dissociative convulsions showed sudden, dramatic, and sustained good response to the addition of a muscle relaxant eperisone., Competing Interests: There are no conflicts of interest.

Complex trauma involves multiple exposures to adverse events over the lifespan. Such experiences are associated with a variety of psychological outcomes, including a decreased threshold for the development of posttraumatic stress disorder as well as self-capacity problems and dysfunctional behaviors. Psychological interventions that increase affect regulation, support titrated processing of memories and cognitions, and emphasize the therapeutic relationship seem to be most helpful for complex trauma effects. Pharmacologic treatments have some efficacy in the treatment of the posttraumatic stress components of complex posttraumatic outcomes but are generally less successful in reducing self-related problems and symptoms., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Despite widespread awareness of their frequent co-occurrence, little is known about treatment of individuals with comorbid posttraumatic stress disorder (PTSD) and dissociative disorders. Patients with dissociative disorders do not respond well to standard exposure therapy, and few psychopharmacologic trials exist. Fluoxetine proved ineffective for depersonalization disorder, but paroxetine showed efficacy in decreasing dissociative symptoms in PTSD patients., (© Copyright 2015 Physicians Postgraduate Press, Inc.)

Background: Following the hypothesis that blocking opioid receptors leads to a decline in opiate-modulated dissociative phenomena, experiences with naltrexone as medication for dissociative symptoms have been gained since 1999 (mainly in doses of 25-100 mg/day)., Patients and Methods: In this study patients with severe trauma-related and dissociative disorders were treated with naltrexone in doses of 2-6 mg/day (0.06 mg/kg body weight)., Results: The low dose treatment with naltrexone proved to be effective whereby 11 out of 15 patients reported immediate positive effects and 7 described a lasting helpful effect. The majority of patients who felt positive effects reported a clearer perception of both their surroundings and their inner life. Assessment of reality and dealing with it improved as did the perception of their own body and affects as well as self-regulation. The treatment was very low in side effects., Conclusion: Treatment with low-dose naltrexone may be a helpful element in the treatment of patients with complex posttraumatic stress disorder. However, it has to be realized that the decrease of dissociation may lead patients to a not yet resolvable challenge, in as much as dissociation had previously been a necessary mechanism of self-protection.

Typical and atypical antipsychotics have been shown to alleviate N-methyl-D-aspartate (NMDA) receptor antagonist-induced BOLD signals in healthy humans and animals to differing degrees; factors that might relate to their different molecular mechanisms and clinical profiles. Recent studies have also extended these investigations to the analysis of resting state functional connectivity measures of BOLD signals in different brain regions. Using constant potential amperometry, we examined the effects of the NMDA receptor antagonist S-(+)-ketamine on tissue oxygen levels in medial prefrontal cortex (mPFC) and medial ventral striatum (mVS), and temporal coherence of low-frequency oxygen fluctuations between these regions in freely moving rats. Furthermore, we assessed the extent to which the atypical antipsychotic clozapine and the typical antipsychotic haloperidol could modulate the effects of S-(+)-ketamine on these measures. Acute S-(+)-ketamine (5-25 mg/kg) produced dose-dependent increases in both tissue O2 levels and coherence. Although effects of clozapine and haloperidol alone were relatively minor, their effects on ketamine-induced signals were markedly more distinct. Clozapine dose-dependently attenuated the absolute S-(+)-ketamine (25 mg/kg) O2 signal in both regions, and also attenuated ketamine-induced increases in regional coherence. Haloperidol had no effect on the absolute ketamine O2 signal yet potentiated increases in regional coherence. The dissociable effects of haloperidol and clozapine on ketamine-induced hyperoxygenation and mPFC-mVS coherence elucidate potentially important mechanistic differences between these classes of pharmacology. This study demonstrates for the first time that in vivo amperometry can measure both regional brain tissue O2 levels and inter-regional coherence, advancing BOLD-like measurements of functional connectivity into awake, unconstrained animals.

Reported findings indicate that attentional narrowing is related to decreased complexity and increased inhibition of neural assemblies. These findings suggest that analysis of electroencephalogram (EEG) complexity could present a useful method for research of attentional changes related to dissociation. To examine this model we used a case study to test the two hypotheses: (1) that successful anticonvulsant medication would result in dissociative symptom alleviation, improvement of inhibitory neural functions, and decreased EEG complexity, and (2) that cognitive conflict, related to aversive events in the patient's past experience, during reliving of a dissociative state would lead to greater allocation of attention and decreased EEG complexity. Three EEG studies recorded in the eyes closed non-drowsy state were performed: (1) at baseline, (2) post-induction of dissociative state, and (3) post-anticonvulsant medication following induction of dissociative state. A dissociative state was achieved following an interview regarding the patient's aversive past experiences through use of the Peritraumatic Dissociative Experiences Questionnaire (PDEQ). The patient's level of dissociation was measured using the Dissociative Experiences Scale-II (DES-II). The PDEQ interview and DES-II assessment were also used one hour following the oral consumption of an anticonvulsant medication (clonazepam 2mg). Analysis of the data revealed that complexity values (PD2) are significantly lower following the oral consumption of clonazepam (2mg) in the majority of EEG channels. Additionally, complexity during the reliving of a dissociative state was statistically significantly lower than both the baseline and post-medication conditions in all but two EEG channels. Results of the case study suggest that changes in attentional processes linked to dissociation are related to: (1) decreased complexity when attention is extremely focused because of attentional narrowing to the disturbing past experience, and (2) increased complexity during ordinary experiences when attention is less narrowly focused.

Objectives: Alarming somatic symptoms and in particular the cardiovascular symptoms, are the characteristic features of panic attacks. Increased cardiac mortality and morbidity have been proposed in these patients. Power spectral analysis of electrocardiogram R-R intervals is known to be a particularly successful tool in the detection of autonomic instabilities in various clinical disorders. Heart rate variability (HRV) has been found to be the outcome of rapidly reacting cardiovascular control systems. The aim of our study is to measure very low frequency band (VLF), low frequency band (LF) and high frequency band (HF) components of R-R interval during orthostatic experiment in patients with panic disorder before and after treatment and compares it with healthy controls., Methods: We assessed heart rate variability in 19 patients with panic disorder before and after 6-weeks treatment with antidepressants combined with cognitive behavioral therapy (CBT) and in 18 healthy controls. Diagnosis was done according to the ICD-10 research diagnostic criteria confirmed with MINI (MINI international neuropsychiatric interview). Patients were treated with CBT and psychotropics. They were regularly every week assessed using CGI (Clinical Global Impression), BAI (Beck Anxiety Inventory) and BDI (Beck Depression Inventory). Heart rate variability was assessed during 3 positions (1st - 5 min supine; 2nd - 5 min standing; 3rd - 5 min supine) before and after the treatment. Power spectra were computed for very low frequency - VLF (0.0033-0.04 Hz), low-frequency - LF (0.04-0.15 Hz) and high frequency - HF (0.15-0.40 Hz) bands using fast Fourier transformation., Results: Nineteen panic disorder patients resistant to pharmacological treatment entered a 6-week open-label treatment study with combination of SSRI and CBT. The combination of CBT and pharmacotherapy proved to be an effective treatment in these patients. The patients significantly improved during the study period in all rating scales. There were highly statistical significant differences between panic patients and control group in all components of power spectral analysis in 2nd (VLF, LF and H in standing) and in two component of 3rd (LF and HF in supine) positions. There was also a statistically significant difference between these two groups in LF/HF ratio in standing position (2nd). During therapy there was a tendency increasing values in all three positions in components of HRV power spectra, but HF in 1st supine position was the only component where the increase reached the level os statistical significance., Conclusions: These findings demonstrate a lower autonomic activity in panic disorder patients measured during the changes of postural position in comparison with healthy controls and tendency to increase this autonomic power during the treatment.

Early views of borderline personality disorder (BPD) were based on the idea that patients with this pathology were "on the border" of psychosis. However, more recent studies have not supported this view, although they have found evidence of a malevolent interpersonal evaluation and a significant proportion of BPD patients showing psychotic symptoms. For example, in one study, 24% of BPD patients reported severe psychotic symptoms and about 75% had dissociative experiences and paranoid ideation. Thus, we start with an overview regarding the prevalence of psychotic symptoms in BPD patients. Furthermore, we report findings of studies investigating the role of comorbidity (eg, post-traumatic stress disorder) in the severity and frequency of psychotic symptoms in BPD patients. We then present results of genetic and neurobiological studies comparing BPD patients with patients with schizophrenia or nonschizophrenic psychotic disorders. In conclusion, this review reveals that psychotic symptoms in BPD patients may not predict the development of a psychotic disorder but are often permanent and severe and need careful consideration by clinicians. Therefore, adequate diagnosis and treatment of psychotic symptoms in BPD patients is emphasized.

This study evaluated the efficacy of paroxetine for symptoms and associated features of chronic posttraumatic stress disorder (PTSD), interpersonal problems, and dissociative symptoms in an urban population of mostly minority adults. Adult outpatients with a primary DSM-IV diagnosis of chronic PTSD received 1 week of single-blind placebo (N = 70). Those not rated as significantly improved were then randomly assigned to placebo (N = 27) or paroxetine (N = 25) for 10 weeks, with a flexible dosage design (maximum 60 mg by week 7). Significantly more patients treated with paroxetine were rated as responders (14/21, 66.7%) on the Clinical Global Impression-Improvement Scale (CGI-I) compared to patients treated with placebo (6/22, 27.3%). Mixed effects models showed greater reductions on the Clinician-Administered PTSD Scale (CAPS) total score (primary plus associated features of PTSD) in the paroxetine versus placebo groups. Paroxetine was also superior to placebo on reduction of dissociative symptoms [Dissociative Experiences Scale (DES) score] and reduction in self-reported interpersonal problems [Inventory of Interpersonal Problems (IIP) score]. In a 12-week maintenance phase, paroxetine response continued to improve, but placebo response did not. Paroxetine was well tolerated and superior to placebo in ameliorating the symptoms of chronic PTSD, associated features of PTSD, dissociative symptoms, and interpersonal problems in the first trial conducted primarily in minority adults.

Over two thirds of people suffering from depression complain of pain with or without reporting psychological symptoms. Physical symptoms are more prevalent among the women, the elderly, the poor, and in children population. Successful treatment of depression in children complicated by pain symptoms constitutes a great clinical challenge. Duloxetine has already emerged as a safe and effective treatment option for adult depressed patients with painful physical symptoms. However, no data exist in literature which suggests use of duloxetine in childhood and adolescent population for the same clinical indication. We report a case documenting successful use of duloxetine in a depressed girl child who also had severe pain and dissociative symptoms.

Background: States of strong aversive inner tension and dissociative symptoms are clinical hallmarks of borderline personality disorder and major reasons for self-injurious behavior, a severe clinical condition for which there are no established pharmacologic treatment options., Method: The acute effect of 75 and 150 microg of clonidine administered orally in acute states of strong aversive inner tension and urge to commit self-injurious behavior was examined in 14 female patients meeting DSM-IV criteria for borderline personality disorder. Before and 30, 60, and 120 minutes after administration of clonidine, aversive inner tension and dissociative symptoms were assessed using a self-rating instrument for aversive inner tension and dissociation (Dissociation-Tension-Scale acute), and the urge to commit self-injurious behavior and suicidal ideations were assessed using self-rating Likert scales. Blood pressure and heart rate were monitored during the trial., Results: Aversive inner tension and urge to commit self-injurious behavior before administration of clonidine were strong. After administration of clonidine in both doses, aversive inner tension, dissociative symptoms, urge to commit self-injurious behavior, and suicidal ideations significantly decreased. The strongest effects were seen between 30 and 60 minutes after drug intake and correspond to the pharmacokinetics of clonidine with maximum plasma concentrations after 1 hour. Blood pressure and aversive inner tension and dissociative symptoms were positively correlated before and after administration of clonidine., Conclusion: Orally given clonidine may be effective for treatment of acute states of aversive inner tension, dissociative symptoms, and urge to commit self-injurious behavior in female patients with borderline personality disorder. Further placebo-controlled studies with larger populations are needed to confirm this finding.

Background: Acute dissociative states are common in patients with borderline personality disorder (BPD). However, there are no established pharmacotherapeutic treatment options for this severe clinical condition., Methods: The effect of 0.4 mg naloxone administered intravenously in acute dissociative states was examined as compared to placebo in a double-blind crossover study in nine patients who met DSM-IV-criteria for BPD. Dissociative symptoms before and 15 min after a single dose of naloxone or saline placebo were assessed using a self-rating instrument for dissociation and aversive inner tension (DSS) and the observer-based items of the Clinician Administered Dissociative States Scale (CADSS)., Results: Dissociative symptoms before treatment with naloxone or saline placebo were moderate to severe. After injection of either naloxone or placebo, dissociative symptoms significantly decreased on the DSS (p < 0.01) and the CADSS (p < 0.05). However, there were no significant differences between naloxone and placebo in the reduction of symptoms. Patients who showed the most prominent response to naloxone fulfilled the highest number of DSM-IV-criteria for BPD., Conclusions: Although it is difficult to draw definite conclusions from this small sample of patients, this study does not support the assumption that naloxone in a single dose of 0.4 mg is superior to placebo in acute dissociative states in patients with BPD. Further studies will investigate whether patients benefit from naloxone in a higher dose or whether subgroups of patients with BPD profit from naloxone in acute dissociative states.

Objective: To review the case of Anna O in light of perspectives offered by Dr Kaplan in his paper 'O Anna: being Bertha Pappenheim--historiography and biography' and to compare it with a contemporary case, that of Hanna Q., Conclusions: Josef Breuer's initial diagnoses do not need revision. However, the aetiology of such diagnoses is informed by subsequent research and by comparison with contemporary cases that can quite closely resemble that of Anna O's. Her symptomatology was not unique.

The two international systems of diagnostic classification for psychiatric disorders, ICD-10 and DSM-IV, differentiate a variety of disorders or syndromes characterized by the common feature of the presence of physical symptoms without "organic correlate." Conversion disorders (DSM) or dissociative disorders (ICD) are historically related to the concept of hysteria. Like psychoanalytical theories, the DSM and ICD refer to a psychological conflict preceding the onset of physical symptoms, although in a purely descriptive manner. The etiology of these disorders is still not very well understood. This article summarizes present knowledge from clinical and epidemiological studies. Functional neuroimaging studies on conversion disorders, although still very rare, allow testing of hypotheses about neuronal mechanisms. Such studies question the traditional and often misinterpreted dichotomy between organic and psychogenic diseases.

Existent neurocognitive models of schizophrenia converge towards a core of impairments involving working memory, context processing, action planning, controlled and intentional processing. However, the emergence of this core remains itself difficult to explain and more specific hypotheses do not explain the heterogeneity of schizophrenia. To overcome these limits, we propose a new paradigm based on representational theory from cognitive science. Some recent developments of this theory enable us to describe a subjective universe as a representational space which is displayed from memory. We outline a conceptual framework to construct such a representational space from analogical -representations that can be activated in working memory and are connected to a network of symbolic structures. These connections are notably made through an analytic process of the analogical fragments, which involves the attentional focus. This framework allows us to define rigorously some defense processes in response to traumatic tensions that are expressed on the representational space. The fragmentation of representational space is a consequence of a defensive denial based on an impairment of the analytic process. The fragmentation forms some parasitic areas in memory which are excluded from the main part of the representational space and disturb information processing. The key clinical concepts of paranoid syndromes can be defined in this conceptual framework: mental automatism, delusional intuition, acute destructuration, psychotic dissociation, and autistic withdrawal. We show that these syndromes imply each other, which in return increases the fragmentation of the representational space. Some new concepts emerge naturally in this framework, such as the concept of "suture" which is defined as a link between a parasitic area and the main representational space. Schizophrenia appears as a borderline case of fragmentation of the representational space. This conceptual framework is compatible with numerous etiological factors. Multiple clinical forms can be differentiated in accordance with the persistence of parasitic areas, the degree of fragmentation, and the formation of sutures. We use this approach to account for an empirical study concerning the analysis of analogical representations in schizophrenia. We used the Parallel Visual Information Processing Test (PVIPT) which assesses the analysis of interfering visual information. Subjects were asked to connect several small geometric figures printed on a transparency. The transparency was displayed above four photographs which were the interfering material. Then, subjects completed three tasks concerning the photographs: a recognition task, a recall task, and an affective qualification task. Using a case-by-case study, this test allows us to access the defense processes of the subjects, which is not possible with the usual methods in cognitive psychopathology. Twelve clinically-stable schizophrenic subjects participated in the study which also included a self-assessment of alexithymia by the Toronto Alexithymia Scale. We obtained 2 main results: (a) creation of items in recall or false recognition by 8 subjects, and (b) lack of the usual -negative correlations between the alexithymia score and the recall, recognition and affective qualification scores in the PVIPT. These 2 results contrast with what has been previously observed for alexithymia using the same methodology. The result (a) confirms an interfering activation in schizophrenic memory, which can be interpreted in our framework as indicative of parasitic areas. The creation of items suggests the formation of sutures between the semantic content of photographs and some delusional fragments. The result (b) suggests that the apparent alexithymia in schizophrenia is a defense against interfering activation in parasitic areas. We underline the interest of individual protocols to exhibit the dynamic interplay between an interfering activity in memory and a defensive flattening of affects.

Objective: Not until one year ago has it become more and more known in German speaking countries, that the treatment of borderline and posttraumatic disorders benefits from the use of opiate receptor antagonists. Prerequisite is, that psychotherapeutic approaches, pharmacotherapy and brain physiological research are integrated in an overall concept., Methods: We report on the current standing of scientific research and moreover our own clinical experiences with opiate antagonists are explained., Conclusions: Our achieved knowledge permits our to present criteria how to combine these drugs and psychotherapy successfully.

Objective: To compare the opinions of Canadian psychiatrists regarding dissociative disorder diagnoses with those of previously surveyed American psychiatrists., Method: We sent a 1-page questionnaire to a stratified representative sample of 550 Canadian psychiatrists., Results: Eighty percent of Canadian psychiatrists responded. Fewer than one-third replied that dissociative amnesia and dissociative identity disorder should be included without reservations in the DSM-IV; fewer than 1 in 7 felt that the validity of these diagnoses was supported by strong scientific evidence. French- and English-speaking Canadians had similar opinions. Overall, Canadians were significantly less accepting than Americans., Conclusion: Both Canadian and American psychiatrists show little consensus regarding the diagnostic status or scientific validity of dissociative amnesia and dissociative identity disorder.

Background: Dissociative phenomena, including flashbacks, are common in patients with borderline personality disorder and posttraumatic stress disorder (PTSD). Although dissociative symptoms can be severe and may interfere with psychotherapy, there is no established pharmacotherapy for these symptoms. Evidence suggests that alterations of the endogenous opiate system contribute to dissociative symptoms in patients with borderline personality disorder and PTSD., Method: We treated 2 groups of female borderline personality disorder patients (N = 13, with an overlap of 5 patients between the 2 groups; all met the diagnostic criteria of DSM-IV and the revised Diagnostic Interview for Borderline Patients) who experienced prominent dissociative phenomena including flashbacks with the nonselective opiate receptor antagonist naltrexone, 25 to 100 mg q.i.d., for at least 2 weeks. A self-rated questionnaire measuring dissociation, analgesia, tonic immobility, and tension (DAISS) was applied to 9 patients, who completed it for 7 consecutive days before and during treatment with naltrexone. In addition, 9 patients (with an overlap of 5 patients from the other group) completed a flashback protocol., Results: DAISS scores reflected a highly significant reduction of the duration and the intensity of dissociative phenomena and tonic immobility as well as a marked reduction in analgesia during treatment with naltrexone. Six of 9 patients reported a decrease in the mean number of flashbacks per day., Conclusion: These observations support the hypothesis that an increased activity of the opioid system contributes to dissociative symptoms, including flashbacks, in borderline personality disorder and suggest that these symptoms may respond to treatment with opiate antagonists. In view of these results, a placebo-controlled, double-blind study to assess the potential benefit of naltrexone in a more rigorous way appears justified.

Background: An Indian man now in Britain explained his criminal behaviour as episodic ghost possession. Traditional exorcisms failed to help., Method: A 'Western' diagnosis of dissociative state or paranoid schizophrenia was made. Treatment commenced using trifluoperazine and clopenthixol., Results: The patient underwent remission during neuroleptic treatment, despite previous evidence of genuine possession., Conclusions: Many cultures give rise to apparently genuine cases of ghost possession. Neuroleptics may relieve symptoms of exorcism-resistant possession.

Histories of childhood trauma have been reported previously in bulimic subjects but no study to date has assessed how these experiences may affect response to fluoxetine. Thirty outpatient subjects in a placebo-controlled trial of 60 mg of fluoxetine for the treatment of bulimia nervosa completed the Dissociative Experiences Scale and a self-report instrument assessing trauma. Response to treatment was measured with the Hamilton Depression Scale-17 (HAMD-17), the CGI, the PGI, and the change in number of binges per day. Subjects taking fluoxetine with histories of physical abuse showed a significantly greater drop in HAMD-17 scores than those without such histories. No relationship between a reported history of abuse and the response of binging to fluoxetine was found. A history of abuse does not appear to predict the response of binging to fluoxetine but may predict a greater response of nonspecific symptoms like depression.

Dissociative Experiences Survey scores were compared between bulimics with and without depression, and among depressed patients with and without bulimia. An association is noted between depression and dissociation, confounding the previously noted relationship between bulimia nervosa and dissociation.

The current state of the data concerned with psychopharmacologic interventions for multiple personality disorder (MPD) is reviewed. Common sense guidelines are provided for drug treatment of MPD. An overview is given for use of medications for specific symptoms commonly found in MPD patients, such as affective, posttraumatic stress disorder, and sleep disorder symptoms.