Acute Dissociation and Ketamine's Antidepressant and Anti-Suicidal Ideation Effects in a Midazolam-Controlled Trial.

OBJECTIVE: We sought to explore relationships of acute dissociative effects of intravenous ketamine with change in depression and suicidal ideation and with plasma metabolite levels in a randomized, midazolam-controlled trial. METHODS: Data from a completed trial in suicidal, depressed participants (n = 40) randomly assigned to ketamine was used to examine relationships between ketamine treatment-emergent dissociative and psychotomimetic symptoms with pre/post-infusion changes in suicidal ideation and depression severity. Nonparametric correlational statistics were used. These methods were also used to explore associations between dissociative or psychotomimetic symptoms and blood levels of ketamine and metabolites in a subset of participants (n = 28) who provided blood samples immediately post-infusion. RESULTS: Neither acute dissociative nor psychotomimetic effects of ketamine were associated with changes in suicidal ideation or depressive symptoms from pre- to post-infusion. Norketamine had a trend-level, moderate inverse correlation with dissociative symptoms on Day 1 post-injection (P = .064; P =.013 removing 1 outlier). Dehydronorketamine correlated with Clinician-Administered Dissociative States Scale scores at 40 minutes (P = .034), 230 minutes (P = .014), and Day 1 (P = .012). CONCLUSION: We did not find evidence that ketamine's acute, transient dissociative, or psychotomimetic effects are associated with its antidepressant or anti-suicidal ideation actions. The correlation of higher plasma norketamine with lower dissociative symptoms on Day 1 post-treatment suggests dissociation may be more an effect of the parent drug.

The differential effects of PTSD, MDD, and dissociation on CRP in trauma-exposed women.

OBJECTIVE: C-reactive protein (CRP), a marker of systemic inflammation, has been associated with psychiatric disorders including major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). Some research suggests that exposure to trauma can trigger increased activity in the inflammatory system. Dissociation is associated with chronic trauma exposure and may be an important factor in understanding the risk for psychiatric outcomes associated with inflammation. The main objective of the current study was to understand how CRP was related to trauma, dissociation, PTSD and MDD in a sample of 55 traumatized African American women with type 2 diabetes mellitus recruited from an urban hospital. METHOD: High sensitivity CRP (hsCRP) was assayed through blood samples; psychiatric disorders were assessed with structured clinical interviews, dissociation was assessed with the Multiscale Dissociation Inventory, and exposure to trauma in childhood and adulthood was assessed with the Childhood Trauma Questionnaire and the Traumatic Events Inventory, respectively. RESULTS: Correlational results showed a significant association between higher concentrations of hsCRP and child abuse (p < 0.05), overall dissociation severity (p < 0.001), and PTSD symptoms (p < 0.01). ANOVA results showed significantly higher levels of hsCRP in those with current MDD, current PTSD, and remitted PTSD. A hierarchical linear regression model demonstrated a significant association between dissociation symptoms and greater hsCRP levels independent of childhood abuse, PTSD, and MDD (R2∆ = 0.11, p = 0.001) and independent of emotion dysregulation (p < 0.05). CONCLUSION: These findings suggest that dissociation symptoms among those with a history of trauma may be particularly associated with higher levels of inflammation.

Physiologic correlates of culture-bound dissociation: A comparative study of Brazilian spiritist mediums and controls.

Mediumship and spirit possession are cultural phenomena found in many societies worldwide. In Brazil, Spiritism (a tradition in which mediumship is emphasized) is the third largest religious denomination. The present study aimed to investigate physiologic correlates of nonpathological dissociative experiences by comparing 20 female spiritist mediums with several years of socially sanctioned practice to 20 female nonmedium control subjects from the same religious context. We measured plasma levels of hormones and neuroactive substances, as well as vital signs and heart rate variability (HRV) parameters, before and immediately after spirit communication. Although no between-group differences were noted in basal physiological parameters, in response to the possession experiences the groups differed in heart rate and in plasma concentrations of noradrenaline, thyroid-stimulating hormone (TSH), prolactin, and creatine phosphokinase (CPK). The changes in parameters indicated an arousal response in mediums and a relaxation response in control participants, and the same pattern of changes was observed in HRV parameters from each group during the possession experiences. However, the changes in physiologic parameters for mediums were mild and of short duration: 1 hour after the possession experiences, no difference in cardiac autonomic regulation was noted. No significant group effect was noted for melatonin. Cognitive control processes may explain the arousal associated with the dissociative state. Findings from this study suggest that pathological and nonpathological dissociation may have different physiological correlates.

Gestational and Postnatal Cortisol Profiles of Women With Posttraumatic Stress Disorder and the Dissociative Subtype.

OBJECTIVE: To test the hypothesis that women with posttraumatic stress disorder (PTSD) have greater salivary cortisol levels across the diurnal curve and throughout gestation, birth, and the postpartum period than women who do not have PTSD. DESIGN: Prospective, longitudinal, biobehavioral cohort study. SETTING: Prenatal clinics at academic health centers in the Midwest region of the United States. PARTICIPANTS: Women expecting their first infants who fit with one of four cohorts: a nonexposed control group, a trauma-exposed control group, a group with PTSD, and a group with the dissociative subtype of PTSD. METHODS: In the first half of pregnancy, 395 women provided three salivary cortisol specimens on a single day for diurnal data. A subsample of 111 women provided three salivary cortisol specimens per day, 12 times, from early pregnancy to 6 weeks postpartum for longitudinal data. Trauma history, PTSD, and dissociative symptoms were measured via standardized telephone diagnostic interviews with the use of validated epidemiologic measures. Generalized estimating equations were used to determine group differences. RESULTS: Generalized estimating equations showed that women with the dissociative subtype of PTSD had the highest and flattest gestational cortisol level curves. The difference was greatest in early pregnancy, when participants in the dissociative subtype group had cortisol levels 8 times greater in the afternoon and 10 times greater at bedtime than those in the nonexposed control group. CONCLUSION: Women with the dissociative subtype of PTSD, a complex form associated with a history of childhood maltreatment, may have toxic levels of cortisol that contribute to intergenerational patterns of adverse health outcomes.

Lipid levels in dissociative disorders: effects of psychodynamic psychotherapy.

Although there are several data suggesting a link between lower lipids levels and the risk of suicide, there are few data concerning lower lipids levels in patients with dissociative disorders (DD). This is the first longitudinal study investigating the evolution of the lipids levels during a specific 8 weeks of psychodynamic psychotherapy (PP) for patients with DD. 32 patients diagnosed with DD (SCID for DSMIVR) were assessed with Dissociative Experiences Scale (DES), Clinical Global Impression and Improvement Scale and their lipids levels (total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein and very low density lipoprotein) were measured at inclusion and after 3 and 8 weeks of PP. 30 patients finished the study. There is a significant positive (p < 0.05) link between lower lipids levels (total cholesterol, LDL, triglycerids) and a higher level of dissociation (DES scores) at the beginning and at the end of the study. Interestingly, we found a significant (p = 0.018) positive link between the reduction of the dissociation (DES) and the increase of the triglycerides levels after 8 weeks of treatment. While lower lipids seems related to a higher level of dissociation before and after the treatment, an increasing triglycerides level was observed after 8 weeks of PP in patients with a better outcome. Further studies are needed with larger samples and control groups, in order to confirm these preliminary data. These findings could open the way for hypothesis about the role of lipids in the pathophysiology of DD and raise the question of the patients with DD receiving antilipidemiants agents.

In search of an adult attachment stress provocation to measure effect on the oxytocin system: a pilot validation study.

BACKGROUND: Oxytocin is a promising biomarker for psychiatric conditions arising from early relational trauma, childhood maltreatment, and attachment dysregulation, including posttraumatic stress and dissociative disorders. OBJECTIVE: This exploratory pilot study examined plasma oxytocin as a biomarker for alterations in the attachment system. DESIGN: We used a single group, repeated-measures design with 15 women. The protocol used a film clip previously validated as a provocation to the hypothalamic-pituitary-adrenal axis. RESULTS: The repeated-measures ANOVA showed differences in oxytocin across the three time points. Correlations with oxytocin indicated that measures of dissociation and somatization correlated most strongly with higher levels of oxytocin measured during exposure to the film's bonding scene and posttraumatic stress disorder correlated most strongly with lower levels at the film's abandonment scene. Post hoc analyses revealed differences in oxytocin response related to psychopathology. CONCLUSION: Replication studies should characterize participants on a range of psychiatric conditions associated with attachment dysregulation.

Exploring dissociation and oxytocin as pathways between trauma exposure and trauma-related hyperemesis gravidarum: a test-of-concept pilot.

Posttraumatic stress disorder (PTSD) is associated with gastrointestinal and genitourinary comorbidities. These map onto the somatization disorder symptoms in the Diagnostic and Statistical Manual of Mental Disorders ( American Psychiatric Association, 1994 ) and the dissociative (conversion) disorders symptoms in the International Classification of Diseases taxonomy ( World Health Organization, 2007 ). Hyperemesis gravidarum (HG) is one of these symptoms and a gastrointestinal comorbidity of PTSD occurring in pregnancy. It is an idiopathic condition defined as severe vomiting with dehydration, metabolic imbalance, wasting, and hospital care seeking. HG is more severe than the normative phenomenon of nausea and vomiting of pregnancy. This test-of-concept pilot (N = 25) explored the hypothesis that there is a trauma-related subtype of HG characterized by (a) high levels of dissociative symptoms and (b) altered plasma concentrations of oxytocin. This hypothesis is informed by a theory of posttraumatic oxytocin dysregulation that posits altered oxytocin function as a mechanism of gut smooth muscle peristalsis dysfunction. A 4-group analysis compared controls with nausea and vomiting of pregnancy (NV only) and cases with HG only, NV and PTSD, or HG and PTSD. Oxytocin was correlated with the nausea and vomiting symptom severity score (r = .464, p = .019) and with the dissociation symptom score (r = .570, p = .003). Women in the group with both PTSD and HG (the trauma-related HG subtype) had the highest levels of dissociation and the highest levels of oxytocin. A linear regression model indicated that the independent association of the trauma-related HG subtype with oxytocin level was mediated by high levels of dissociative symptoms.

Depression, traumatic stress and interleukin-6.

BACKGROUND: Recent evidence indicates that various types of interactions between nervous and immune system are important in pathogenesis of depression. These findings show that a significant role in developing depression play pro-inflammatory cytokines that may mediate its psychological, and neurobiological manifestations. Great importance among these cytokine molecules plays interleukin-6 (IL-6). There is growing evidence that this inflammatory process related to depression may be influenced by psychological stress as well as organic inflammatory conditions. These findings suggest that specific influences related to traumatic stress and dissociation could be found in close relationship to increased level of cytokine IL-6. METHODS: In the present study we have performed psychometric measurement of depression (BDI-II), traumatic stress symptoms (TSC-40) and dissociation (DES, SDQ-20), and immunochemical measure of serum IL-6 in 40 inpatients with unipolar depression (mean age 42.3+/-6.8). RESULTS: The results show that IL-6 is significantly correlated to BDI-II (Spearman R=0.47, p<0.01), TSC-40 (Spearman R=0.32, p<0.05), SDQ-20 (Spearman R=0.34, p<0.05) but not to DES (Spearman R=0.25, p=0.11). CONCLUSION: The findings of the present study indicate that increased level of IL-6 in depression could be directly related to symptoms of traumatic stress and somatoform dissociation.

Relationships among plasma dehydroepiandrosterone and dehydroepiandrosterone sulfate, cortisol, symptoms of dissociation, and objective performance in humans exposed to underwater navigation stress.

BACKGROUND: A growing body of research has provided evidence that dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) are involved in an organism's response to stress and that it may provide beneficial behavioral and neurotrophic effects. METHODS: This study investigated plasma DHEA and DHEAS, cortisol, psychological symptoms of dissociation, and military performance in 41 healthy active duty subjects enrolled in the military Combat Diver Qualification Course (CDQC). RESULTS: Baseline values of DHEA and DHEAS were significantly and positively predictive of superior performance in the underwater navigation exam; in addition, DHEA and DHEAS were significantly and negatively related to stress-induced symptoms of dissociation during performance of the task. Similarly, participants who reported fewer symptoms of dissociation exhibited superior military performance and increased levels of DHEA after the test. CONCLUSIONS: These data provide prospective, empiric evidence that DHEA and DHEAS are associated with superior stress tolerance, fewer symptoms of dissociation, and superior, objectively assessed, military performance.

Dissociative symptoms and neuroendocrine dysregulation in depression.

BACKGROUND: Dissociative symptoms are traditionally attributed to psychological stressors that produce dissociated memories related to stressful life events. Dissociative disorders and dissociative symptoms including psychogenic amnesia, fugue, dissociative identity-disorder, depersonalization, derealization and other symptoms or syndromes have been reported as an epidemic psychiatric condition that may be coexistent with various psychiatric diagnoses such as depression, schizophrenia, borderline personality disorder or anxiety disorders. According to recent findings also the somatic components of dissociation may occur and influence brain, autonomic and neuroendocrine functions. At this time there are only few studies examining neuroendocrine response related to dissociative symptoms that suggest significant dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. The aim of the present study is to perform examination of HPA axis functioning indexed by basal cortisol and prolactin and test their relationship to psychic and somatoform dissociative symptoms. MATERIAL/METHODS: Basal cortisol and prolactin and psychic and somatoform dissociative symptoms were assessed in 40 consecutive inpatients with diagnosis of unipolar depression mean age 43.37 (SD=12.21). RESULTS: The results show that prolactin and cortisol as indices of HPA axis functioning manifest significant relationship to dissociative symptoms. Main results represent highly significant correlations obtained by simple regression between psychic dissociative symptoms (DES) and serum prolactin (R=0.55, p=0.00027), and between somatoform dissociation (SDQ-20) and serum cortisol (R=-0.38, p=0.015). CONCLUSIONS: These results indicate relationship between HPA-axis reactivity and dissociative symptoms in unipolar depressive patients that could reflect passive coping behavior and disengagement.

Depression, cortisol and somatoform dissociative symptoms.

OBJECTIVE: According to recent findings neuroendocrine response related to dissociative symptoms is related to dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis but HPA axis functioning as related to dissociation is only partially understood. METHOD: With the aim to test the relationship between basal serum cortisol and dissociative symptoms measured as somatoform and psychic dissociation we performed clinical testing and biochemical analysis in 30 inpatients with diagnosis of unipolar depression (mean age 41.46, SD=13.68). RESULTS: The results show that cortisol as an index of HPA axis functioning manifests significant relationship to somatoform dissociative symptoms (r=-0.40; p=0.014). CONCLUSIONS: The result indicates relationship between HPA-axis reactivity and somatoform dissociative symptoms in unipolar depressive patients and suggests that somatoform dissociation presents a defense mechanism related to a passive coping response.

Cortisol, dehydroepiandrosterone, and estradiol measured over 24 hours in women with childhood sexual abuse-related posttraumatic stress disorder.

Preclinical studies have shown long-term alterations in several hormonal systems including cortisol, dehydroepiandrosterone (DHEA) and DHEA-Sulfate, and estradiol. The purpose of this study was to assess cortisol, DHEA, and estradiol over a 24-hour period in women with early childhood sexual abuse and posttraumatic stress disorder (PTSD); with early abuse and without PTSD; and women without early abuse or PTSD. Forty-three women with early childhood sexual abuse and PTSD, early abuse without PTSD, and without abuse or PTSD, underwent a comprehensive assessment of hormones in plasma at multiple time points over a 24-hour period. Abused women with PTSD had lower concentrations of cortisol during the afternoon hours (12-8 p.m.) compared with women with abuse without PTSD and women without abuse or PTSD. DHEA-Sulfate was elevated throughout the 24-hour period in PTSD women, although this was of marginal statistical significance. There were no differences between groups in DHEA or estradiol. PTSD women also had increased cortisol pulsatility compared with the other groups. These findings suggest that a resting hypocortisolemia in the afternoon hours with increased cortisol pulsatility is associated with childhood abuse-related PTSD in women.

Depression, prolactin and dissociated mind.

OBJECTIVES: Usual neuroendocrinological manifestation of traumatic stress and dissociation is dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. The aim of the present study is to perform examination of HPA axis as indexed by basal serum prolactin and test its relationship to dissociative symptoms and symptoms of traumatic stress. PATIENTS AND METHODS: 25 inpatients treated at the university hospital with diagnosis of unipolar depression mean age 41.23 (SD=11.53) were assessed using psychometric measures of dissociation (DES) and traumatic symptoms (TSC-40), and using standard biochemical analytical methods basal serum prolactin levels were investigated. RESULTS: Data show that prolactin manifests significant relationship to dissociative symptoms (r=0.52, p=0.004). Significant correlation was not found between prolactin and traumatic symptoms measured by TSC-40 (r=0.31, p=0.07). CONCLUSIONS: The present data suggest that serum prolactin levels in unipolar depressive patients are related to dissociative symptoms that is likely caused by passive coping mechanisms leading to dissociation.

Hypothalamic-pituitary-adrenal axis function in dissociative disorders, post-traumatic stress disorder, and healthy volunteers.

BACKGROUND: This study investigated basal and stress-induced hypothalamic-pituitary-adrenal (HPA)-axis alterations in dissociative disorders (DDs). METHODS: Forty-six subjects with DD without lifetime post-traumatic stress disorder (PTSD), 35 subjects with PTSD, and 58 healthy comparison (HC) subjects, free of current major depression, were studied as inpatients. After a 24-hour urine collection and hourly blood sampling for ambient cortisol determination, a low-dose dexamethasone suppression test was administered, followed by the Trier Social Stress Test. RESULTS: The DD group had significantly elevated urinary cortisol compared with the HC group, which was more pronounced in the absence of lifetime major depression, whereas the PTSD and HC groups did not differ. The DD group demonstrated significantly greater resistance to, and faster escape from, dexamethasone suppression compared with the HC group, whereas the PTSD and HC groups did not differ. The three groups did not differ in cortisol stress reactivity, but both psychiatric groups demonstrated a significant inverse correlation between dissociation severity and cortisol reactivity, after controlling for all other symptomatology. The PTSD subgroup with comorbid DD tended to have blunted stress reactivity compared with the HC group. CONCLUSIONS: The study demonstrates a distinct pattern of HPA-axis dysregulation in DDs, emphasizing the importance of further study of stress-response systems in dissociative psychopathology.

Serum lipid levels in patients with dissociative disorder.

OBJECTIVE: There may be an association between a low serum cholesterol level and dissociative disorders. METHOD: The subjects of the study were 16 patients with dissociative disorder and 16 normal comparison subjects (two men and 14 women in each group). Total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, and very low density lipoprotein levels were compared. RESULTS: Patients with dissociative disorders had lower serum triglyceride, total cholesterol, low-density lipoprotein, and very low density lipoprotein levels than normal comparison subjects. CONCLUSIONS: Low serum lipid concentrations may be related to a high incidence of self-injurious behaviors and borderline features in patients with dissociative disorders.

Relationships among plasma dehydroepiandrosterone sulfate and cortisol levels, symptoms of dissociation, and objective performance in humans exposed to acute stress.

CONTEXT: Recently, a growing body of research has provided evidence that dehydroepiandrosterone sulfate (DHEA-S) is involved in an organism's response to stress and that it may provide beneficial behavioral and neurotrophic effects. OBJECTIVE: To investigate plasma DHEA-S and cortisol levels, psychological symptoms of dissociation, and military performance. DESIGN: Prospective study. SETTING AND PARTICIPANTS: Twenty-five healthy subjects enrolled in military survival school. RESULTS: The DHEA-S-cortisol ratios during stress were significantly higher in subjects who reported fewer symptoms of dissociation and exhibited superior military performance. CONCLUSIONS: These data provide prospective, empirical evidence that the DHEA-S level is increased by acute stress in healthy humans and that the DHEA-S-cortisol ratio may index the degree to which an individual is buffered against the negative effects of stress.

Catecholamines and opioid peptides increase in plasma in humans during possession trances.

Naturally induced possession trances have been observed in healthy people of many societies. The neurophysiological basis of this phenomenon remains unknown, however, because of the difficulty in accessing subjects in trances due to their sacred context. In the present study, we measured the plasma levels of several neuroactive substances from subjects exhibiting or lacking possession trance characteristics during Balinese dedicatory dramas under natural conditions. The trance group exhibited significant increases in plasma concentrations of noradrenaline, dopamine and beta-endorphin, compared with controls who performed the same actions as the trance group. The present finding suggests that catecholamines and opioid peptides are involved in possession trances.

Relationship among plasma cortisol, catecholamines, neuropeptide Y, and human performance during exposure to uncontrollable stress.

OBJECTIVE: Although many people are exposed to trauma, only some individuals develop posttraumatic stress disorder; most do not. It is possible that humans differ in the degree to which stress induces neurobiological perturbations of their threat response systems, which may result in a differential capacity to cope with aversive experiences. This study explored the idea that differences in the neurobiological responses of individuals exposed to threat are significantly related to psychological and behavioral indices. METHODS: Individual differences in neurohormonal, psychological, and performance indices among 44 healthy subjects enrolled in US Army survival school were investigated. Subjects were examined before, during, and after exposure to uncontrollable stress. RESULTS: Stress-induced release of cortisol, neuropeptide Y, and norepinephrine were positively correlated; cortisol release during stress accounted for 42% of the variance in neuropeptide Y release during stress. Cortisol also accounted for 22% of the variance in psychological symptoms of dissociation and 31% of the variance in military performance during stress. CONCLUSIONS: Because dissociation, abnormalities in the hypothalamic-pituitary-adrenocortical axis, and catecholamine functioning have all been implicated in the development of stress disorders such as posttraumatic stress disorder, these data suggest that some biological differences may exist before index trauma exposure and before the development of stress-related illness. The data also imply a relationship among specific neurobiological factors and psychological dissociation. In addition, the data provide clues about the way in which individuals' psychobiological responses to threat differ from one another.

Uso de la lidocaína en pacientes con enfermedad bronco pulmonar obstructiva crónica / Use of the lidocaine in patients with bronchopulmonary obstructive chronic disease

El presente estudio fue realizado en el Departamento de Neumonología y Cirugía de Tórax del Hospital Militar "Dr. Carlos Arvelo" específicamente en el laboratorio para el estudio del "Funcionamiento pulmonar" fundado y dirigido hasta el año 1995 por el Dr. Eduardo Carvallo. El mismo busca demostrar dos hipótesis que se plantean ante un fenómeno observado en un estudio previo donde se administró lidocaína 2 por ciento en forma nebulizada, como premedicación antes de la realización de las broncofibroscópias, en el que se pudo apreciar que aquellos pacientes que recibieron el medicamento presentaban un aumento de la diferencial de la Pa02 arterial posterior a la práctica del mismo. De todo esto surge la posibilidad que el medicamento se comporte como un broncodilatador por su acción indirecta sobre los canales de calcio, o puede tener un efecto directo sobre la superficie de intercambio de gases (alvéolo), logrando así este fenómeno. Nuestro estudio se realiza para el período julio de 1995 a junio de 1996, con una muestra al azar de pacientes con EBPOC leve, moderada y severa; de ambos sexos, para una muestra mínima de 41 pacientes en un estudio a doble ciego. Al llegar el paciente, el técnico le realiza medición de los flujos (espirometría) y toma de muestras para gasometría de sangre arterial, luego se nebuliza el paciente con la droga y después se vuelven a medir los flujos y se toma otra muestra para medición de gases arteriales, para seguidamente proceder a tabular los datos obtenidos de cada paciente y se concluye con el análisis de los resultados, posterior a ruptura de los sellos. Nuestros resultados evidencian el efecto de la lidocaína nebulizada sobre la PaO2 de manera evidente, pero sin demostrar un significativo efecto broncodilatador, los que nos hace pensar en un posible efecto directo sobre el intercambio gaseoso a nivel alvéolar