Margaret Knutelska

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.

Factors associated with resilience in healthy adults

Mature defenses comprise one well-validated indicator of resilience. We investigated the relationships of resilience to trauma, attachment, temperament, cortisol, and cognitive performance in adult healthy volunteers. Participants were administered the Defense Style Questionnaire; the Relationship Questionnaire; the Childhood Trauma Questionnaire, and the Tridimensional Personality Questionnaire. Cortisol determinations included 24-h urinary, mean hourly plasma, response to low-dose dexamethasone suppression, and reactivity to the Trier social stress test (TSST). Mathematical performance during the TSST was quantified. Twenty-five women and 29 men participated. Resilience was significantly negatively correlated with childhood interpersonal trauma and with harm avoidance. Resilience was significantly positively correlated with urinary cortisol, secure attachment, reward dependence, and superior performance. In a linear regression analysis, the strongest predictor of resilience was childhood trauma, followed by math performance under stress and harm avoidance. We conclude that in young adults without manifest psychiatric disorder, resilience was associated with developmental, biological, and cognitive measures which merit further investigation.

A preliminary study of cortisol and norepinephrine reactivity to psychosocial stress in borderline personality disorder with high and low dissociation

The goal of the current study was to investigate subjective and neurohormonal reactivity to acute psychosocial stress in borderline personality disorder (BPD) as a function of dissociative symptoms. Five BPD subjects with high dissociation, 8 BPD subjects with low dissociation, and 11 healthy control subjects were compared in basal urinary cortisol and norepinephrine, as well as in plasma cortisol and norepinephrine reactivity to the Trier Social Stress Test (TSST). Subjective stress rating and emotional response to the TSST were also measured. The three groups differed significantly in cortisol stress reactivity, with the high-dissociation BPD group demonstrating the most robust response. The three groups did not significantly differ in norepinephrine stress reactivity. In the combined BPD sample, dissociation severity tended to be inversely correlated with basal urinary norepinephrine, was positively correlated with norepinephrine stress reactivity. Childhood trauma was inversely correlated with basal urinary cortisol. In conclusion, despite its small sample size this pilot study suggests that dissociative symptomatology may be a marker of heightened biological vulnerability to stress in BPD, and merits further study.

Basal norepinephrine in depersonalization disorder.

In contrast to the noradrenergic dysregulation described in PTSD, little is known regarding noradrenergic function in dissociative disorders. The purpose of this preliminary study was to investigate basal norepinephrine in depersonalization disorder (DPD). Nine subjects with DSM-IV DPD, without lifetime PTSD, were compared to nine healthy comparison (HC) subjects. Norepinephrine was measured via 24-h urine collection and three serial plasma determinations. Groups did not differ significantly in plasma norepinephrine levels. Compared to the HC group, the DPD group demonstrated significantly higher urinary norepinephrine, only prior to covarying for anxiety. The DPD group also demonstrated a highly significant inverse correlation between urinary norepinephrine and depersonalization severity (r=-0.88). Norepinephrine and cortisol levels (reported in a prior study) were not intercorrelated. We concluded that although dissociation accompanied by anxiety was associated with heightened noradrenergic tone, there was a marked basal norepinephrine decline with increasing severity of dissociation. The findings are in concordance with the few reports on autonomic blunting in dissociation and merit further investigation.

Cognitive Functioning in Depersonalization Disorder

Depersonalization disorder (DPD) is a dissociative disorder characterized by a subjective sense of unreality and detachment, and has been associated with deficits in perception and short-term memory. In this study, 21 DPD and 17 healthy comparison participants free of psychiatric disorders were administered a comprehensive neuropsychologic battery. The groups did not differ in full-scale, verbal, and performance IQ (Wechsler Adult Intelligence Scale), in working memory (Paced Auditory Serial Addition Test), or in selective attention (Digit Span with Distracters). The DPD group performed significantly worse on immediate visual and verbal recall (Wechsler Memory Scale, Revised), but not on delayed recall. Dissociation severity was significantly correlated with processing slowness and distractibility. We conclude that DPD is associated with cognitive disruptions in early perceptual and attentional processes.

An open trial of naltrexone in the treatment of depersonalization disorder.

Abstract: Depersonalization disorder (DPD) remains one of the few disorders in modern psychiatry for which no treatments are established that are even partially effective, whether pharmacological or psychotherapeutic. Depersonalization disorder is a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition dissociative disorder characterized by a pervasive subjective sense of unreality and detachment with intact reality testing. Two recent controlled medication trials, one with lamotrigine and one with fluoxetine, failed to show efficacy. There is some evidence for dysregulation of endogenous opioid systems in depersonalization, and a few studies have suggested that opioid antagonists may have efficacy in the treatment of dissociation and depersonalization symptoms. In this prospective open treatment trial, 14 subjects were recruited and treated with naltrexone for 6 weeks to a maximum dose of 100 mg/d (first 7 subjects) or 10 weeks to a maximum dose of 250 mg/d (next 7 subjects). Mean naltrexone dose was 120 mg/d. There was an average 30% reduction of symptoms with treatment, as measured by 3 validated dissociation scales. Three patients were very much improved, and 1 patient was much improved with naltrexone treatment. These findings are potentially promising in a highly treatment-refractory disorder for which no treatment guidelines exist and warrant a randomized controlled trial.

Examination of the pathological dissociation taxon in depersonalization disorder.

In recent years, the pathologic dissociation taxon developed by Waller, Putnam, and Carlson (Psychological Methods 1:300–321, 1996) from a Dissociative Identity Disorder (DID) sample has been increasingly used in studies of dissociation in general. However, the taxon’s convergence with dissociative diagnoses other than DID, as well as the taxon’s central premise that pathologic dissociation is a categorical rather than a dimensional construct, remain areas of exploration. This report examines the applicability of the pathologic dissociation taxon to Depersonalization Disorder (DPD). The Dissociative Experiences Scale was administered to 100 consecutively recruited DPD subjects diagnosed by semistructured clinical interview and by the SCID-D. Taxon membership probability was calculated using the recommended SAS scoring program. Approximately 2/3 of subjects (N = 64) had a very high probability (> .80) of belonging to the taxon, while 1/3 of subjects had a very low probability (<.10) of belonging to the taxon. A taxon cutoff score of 13 yielded an 81% sensitivity in detecting the presence of DPD. The modest convergence between taxonic membership and clinical dissociative disorder diagnosis suggests that the taxon may have important limitations in its use, at least when applied to DPD in its current form. As previously, we continue to recommend a low taxon cutoff score (13) for the sensitive detection of depersonalization disorder. The inference that pathologic dissociation is a unitary and categorical entity is also discussed.

Alexithymia, absorption, and cognitive failures in depersonalization disorder: a comparison to posttraumatic stress disorder and healthy volunteers.

Alexithymia, absorption, and cognitive failures are traits that have been implicated in dissociative psychopathology. Forty-six participants with depersonalization disorder (DPD), 21 with posttraumatic stress disorder, and 35 healthy controls completed measures of dissociation, alexithymia, absorption, cognitive failures, and childhood trauma. The DPD and posttraumatic stress disorder groups had significantly and comparably elevated absorption and cognitive failures scores. Only the DPD group had significantly elevated alexithymia scores, specifically in “difficulty identifying feelings.” Regression analyses revealed that “alexithymia—difficulty identifying feelings” was predictive of both DPD diagnosis and depersonalization scores. In contrast, amnesia scores were predicted by childhood trauma and absorption. In conclusion, the link between depersonalization and alexithymia appeared to be specific rather than broadly related to early trauma or to trauma-spectrum psychopathology.

Hypothalamic-pituitary-adrenal Axis Dysregulation in Depersonalization Disorder

Background: The purpose of this preliminary study was to investigate HPA axis function in dissociation. Methods: Nine subjects with DSM-IV depersonalization disorder (DPD), without lifetime Posttraumatic Stress Disorder (PTSD) or current major depression, were compared to nine healthy comparison (HC) subjects of comparable age and gender. Results: DPD subjects demonstrated significant hyposuppression to low-dose dexamethasone administration and significantly elevated morning plasma cortisol levels when covaried for depression scores, but no difference in 24-hour urinary cortisol excretion. Dissociation scores powerfully predicted suppression whereas depression scores did not contribute to the prediction. Conclusions: Primary dissociative conditions, such as depersonalization disorder, may be associated with a pattern of HPA axis dysregulation that differs from PTSD and merits further study.

Dissociation versus posttraumatic stress: cortisol and physiological correlates in adults highly exposed to the World Trade Center attack on 9/11.

Nine months on average after the World Trade Center (WTC) attack, 21 highly exposed adults and 10 healthy controls without major exposure did not differ in cortisol and physiologic measures. Dissociation and posttraumatic stress symptoms were quantified in the exposed group. Dissociation was associated with greater peritraumatic dissociation and, marginally, childhood trauma, lower plasma cortisol levels at 08.00h, and blunted heart rate reactivity to psychosocial stress. Posttraumatic stress was associated with exposure, peritraumatic distress, and early posttraumatic stress, and marginally associated with peritraumatic dissociation; it was not associated with cortisol or physiologic measures. Urinary cortisol differed significantly in its relationship to dissociation versus posttraumatic stress. This small study emphasizes the importance of dissecting the neurobiology of posttraumatic stress versus dissociative traumatic responses.