Sleep-disordered breathing and nocturnal hypoxemia in young adults with sickle cell disease.

Sleep-disordered breathing (SDB) is reported in up to 69% of adolescents and children with sickle cell disease (SCD) [1], but data regarding the prevalence of SDB in adults with SCD are limited. In order to obtain a preliminary assessment of the frequency and degree of sleep-related hypoxemia and potential associations with cardiovascular function in adults with SCD, we conducted overnight sleep studies, 6-min walk tests, echocardiograms, and hematologic and chemistry panels, calculated the Pittsburgh sleep quality index (PSQI), and conducted fatigue- and health-related quality-of-life measurement in 20 young adults with SCD visiting a sickle cell clinic for routine care. Sleep apnea, defined as an apnea-hypopnea index (AHI) > 5 events/h, was found in 50% of patients. Traditional clinical indicators, such as obesity, the presence of snoring, and reported sleep complaints, did not reliably differentiate them. The patients with AHI > 5 had higher mean systolic blood pressure (p = 0.03), evidence of impaired left ventricular diastolic function (i.e., increased mitral valve E/A ratio, p = 0.05), a trend toward higher reduction in 6-min walk distances (p = 0.06), and lower health-related quality-of-life scores (p ≤ 0.01). Three of nine patients with more severe anemia (total Hb < 9.0) showed nocturnal hypoxemia in the absence of sleep apnea. As prolonged and frequent hypoxemic episodes likely increase risks for vaso-occlusive, cardiovascular, and neurologic complications of SCD, these results suggest that the prevalence and severity of SDB should be investigated further in studies of larger patient populations. If confirmed, these findings could identify opportunities to prevent or reduce nocturnal hypoxia and improve outcomes.

A pilot study testing a medication algorithm to reduce polypharmacy.

BACKGROUND: Polypharmacy is common in the treatment of persons with severe mental illness, yet it is not an evidence-based practice. To address this, an attempt was made to reduce medications for patients already receiving polypharmacy during an episode of acute psychiatric hospitalization. METHODS: A medication-reduction algorithm was developed , based on the best available evidence regarding indications for and efficacy of medications and principles of collaborative care. A feasibility pilot study was conducted using a matched case-control design for 12 patients treated with the algorithm and 12 patients treated as usual. RESULTS: The intervention patients were discharged on significantly fewer medications than controls; symptom reduction and length of stay did not differ significantly. CONCLUSION: A collaborative approach to reducing polypharmacy may reverse the trend to add medications during hospitalization.

Predictors of post-traumatic stress disorder following severe injury.

The chronicity and morbidity of established post-traumatic stress disorder (PTSD) has stimulated interest in recognizing and understanding the early development of the disorder. Acute stress disorder, a new diagnosis intended to facilitate early case detection, rests on the occurrence of dissociative reactions. It remains uncertain whether dissociation is a universal or unique early predictor of subsequent PTSD. Traumatic injury is an important and relatively understudied antecedent of PTSD. The objective of this study was to preliminarily identify which previously implicated early reactions and risk factors would apply to the prediction of PTSD following severe traumatic injury. Patients admitted to a regional Level I trauma center following life threatening events who had recall of the incident and did not have signs of traumatic brain injury or recent psychopathology were enrolled. Comprehensive assessments were conducted during hospitalization and after discharge approximately 2 months after the traumatic event. At follow-up, 24% of the available 50 subjects met full criteria for PTSD and an additional 22% met criteria for two of three symptom clusters. Early symptoms of heightened arousal and coping with disengagement were independent predictors of PTSD severity at follow-up. Relationships to initial dissociative reactions and a diagnosis of ASD were not significant. These early predictors found in a setting of severe injury only partially overlap findings from previous PTSD studies.

Dreams and exposure therapy in PTSD.

Exposure therapy is a well-established treatment for PTSD that requires the patient to focus on and describe the details of a traumatic experience. Nightmares that refer to or replicate traumatic experiences are prominent and distressing symptoms of PTSD and appear to exacerbate the disorder. With this apparent paradox in mind, exposure therapy and the literature on sleep and PTSD are reviewed in the context of the relationship between therapeutic exposure and exposure to trauma-related stimuli that occurs in dreams. It is concluded that nightmares that replay the trauma and disrupt sleep do not meet requirements for therapeutic exposure, whereas other dreaming may aid in the recovery from trauma.

Evidence-based pharmacologic treatment for people with severe mental illness: a focus on guidelines and algorithms.

Medication treatment of severe mental illness has been advanced and complicated by the introduction of numerous therapeutic agents. Practice guidelines based on research evidence have been developed to help clinicians make complex decisions. Studies of usual care suggest an important potential role for guidelines in improving the quality of medication treatment for people with severe mental illness. The authors review current evidence-based guidelines for medication treatment of persons with severe mental illness. Four categories of guidelines are described: recommendations, comprehensive treatment options, medication algorithms, and expert consensus. The authors note that more research is needed on optimal next-step strategies and the treatment of patients with comorbidity and other complicating problems. They discuss barriers to the implementation of guidelines, and they observe that the potential of guidelines and algorithms to promote evidence-based medication treatment for persons with severe mental illness depends on refinement of tools, progress in research, and cooperation of physicians, nonphysician clinicians, administrators, and consumers and family members.

Cognitive functioning and the early development of PTSD.

Cross-sectional studies of chronic PTSD reveal deficits in verbal memory. We studied cognitive functioning and its relationship to current and subsequent PTSD severity during an early phase of trauma response. Thiry-eight participants with traumatic injuries and only posttrauma incident psychopathology were evaluated shortly after admission to a Level I Trauma Center Neuropsychological measures were obtained at baseline and assessment of PTSD and other psychiatric disorders was conducted at baseline and follow-up, 6 weeks later. Significant negative correlations were found for follow-up PTSD severity with delayed recall and retroactive interference. These relationships were not significant for and were independent of baseline PTSD severity. Relative deficits in select areas of verbal memory after a trauma may confer greater risk for developing PTSD.

Psychophysiological alterations in post-traumatic stress disorder.

Psychophysiological research in trauma-exposed populations has provided objective data supporting the validity of the post-traumatic stress disorder (PTSD) diagnostic concept. Consistent with a conditioning model, PTSD patients show specific increased peripheral physiological responding to audio-visually and imaginally presented stimuli symbolizing or resembling the etiologic traumatic event. PTSD patients respond to startling stimuli with larger autonomic and electromyographic responses, especially under threat conditions. Electroencephalographic event-related potential (ERP) response abnormalities in PTSD include reduced P2 amplitude at high stimulus intensities, impaired P1 habituation, and attenuated P3 amplitude to target auditory stimuli. However, larger P3 and N1 amplitude responses and shorter P3 and N1 latencies have been reported in PTSD subjects in response to trauma-related stimuli. These ERP findings suggest sensory, cognitive, and affective processing abnormalities in PTSD. Polysomnographic sleep studies have revealed increased awakenings, reduced sleep time, and increased motor activity, or in some cases, paradoxical deepening of sleep. There is also evidence for increased phasic eye movement activity during rapid eye movement (REM) sleep and disrupted REM continuity in PTSD. Psychophysiological studies are offering valuable insights into the pathophysiology of this important neuropsychiatric condition.

Psychotic symptoms in combat-related posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is known often to be comorbid with other anxiety, mood, and substance use disorders. Psychotic symptoms have also been noted in PTSD and have been reported to be more common in Hispanic veterans. However, the occurrence of psychotic symptoms, including the degree to which they are accounted for by comorbid disorders, have received limited systematic investigation. Our study objectives were to assess psychotic symptoms according to DSM-III-R criteria in patients with a primary diagnosis of combat-related PTSD and determine the associations of those symptoms with psychiatric comorbidity and ethnicity. METHOD: Fifty-three male combat veterans consecutively admitted to a PTSD rehabilitation unit were assessed for psychotic symptoms and Axis I disorders. Ninety-one percent were Vietnam veterans; 72% were white, 17% were Hispanic, and 11% were black. Associations between psychotic symptoms and comorbid depression, substance use disorders, and minority status were compared by chi-square analyses; associations between psychotic symptoms and both PTSD and dissociative symptom severity were compared by t test analysis. RESULTS: Forty percent of patients reported a psychotic symptom or symptoms in the preceding 6 months. These symptoms featured auditory hallucinations in all but 1 case. The psychotic symptoms typically reflected combat-themes and guilt, were nonbizarre, and were not usually associated with formal thought disorder or flat or inappropriate affect. Psychotic symptoms were significantly associated with current major depression (p < .02), but not with alcohol or drug abuse or with self-rated PTSD and dissociation severity. Psychotic symptoms and current major depression were more common in minority (black and Hispanic) than white veterans (p < .002). CONCLUSION: Psychotic symptoms can be a feature of combat-related PTSD and appear to be associated with major depression. The association with minority status may be a function of comorbidity.

Pilot evaluation of hypnotic medication during acute traumatic stress response.

Early intervention aimed at secondary prevention is a high priority for posttraumatic stress disorder (PTSD) research. Disrupted sleep may have a role in the initiation and maintenance of PTSD. Three of the participants were recruited from a surgical trauma service, and one had sought treatment in a psychiatric setting. All were within 1-3 weeks of trauma exposure and had acute PTSD symptoms that included disturbed sleep. Temazepam, a benzodiazepine hypnotic, was administered for 5 nights, tapered for 2 nights, and then discontinued. Evaluations 1-week after the medication had been discontinued revealed improved sleep and reduced PTSD severity. These observations suggest an approach that may be clinically useful and a need for more systematic trials.

Psychobiology of sleep disturbances in posttraumatic stress disorder.

Sleep disturbances are prominent complaints of PTSD patients. Some, but not all, of the polysomnographic studies support the occurrence of sleep disruption. The main dimensions of sleep disturbance in the disorder relate to arousal regulation and REM-related functions of dreaming and memory processing. Both of these issues are relevant to the pathogenesis of PTSD and manifestations of the disorder during wake states. Studies elucidating the effects of treatment on sleep parameters are an important direction for future research.

A polysomnographic comparison of veterans with combat-related PTSD, depressed men, and non-ill controls.

Post-traumatic stress disorder (PTSD) overlaps major depression (MD) clinically, but differs with respect to treatment response and some biological markers. Sleep disturbances represent core features of PTSD and are also common in MD. Rapid eye movement sleep (REM) has been postulated to be involved in the pathophysiology of PTSD, and REM abnormalities occur in MD. Twenty-five patients with combat-related PTSD, 16 men with a principal diagnosis of MD, and 10 asymptomatic male controls were compared by polysomnography (PSG) under medication and substance-free conditions. Data were obtained from recordings made after an accommodation night. One subject from each group was excluded for significant apnea or limb movements. Sleep efficiency was decreased in the PTSD group compared to the MD and control groups. REM density was comparably increased in PTSD and MD groups, while the amount of REM sleep was reduced in PTSD compared to MD groups. These sleep measures were not significantly associated with co-morbid depression, substance-use disorder histories, or subclinical sleep apnea or limb movements within the PTSD group. These findings support sleep maintenance being impaired in chronic PTSD patients. Increased REM density in PTSD patients was replicated and was comparable to increases in the MD group. Divergence of REM time between these clinical groups suggests the possibility of different underlying mechanisms.

Psychiatric morbidity following Hurricane Andrew.

The nature of psychiatric morbidity in previously non-ill subjects from the area most affected by Hurricane Andrew was investigated at 6-12 months posthurricane. Preliminary associations of morbidity with personal and event-related risk factors were also determined. Fifty one percent (31/61) met criteria for a new-onset disorder, including posttraumatic stress disorder (PTSD) in 36%, major depression (MD) in 30%, and other anxiety disorders in 20%. Thirty four subjects (56%) had significant symptoms persisting beyond 6 months. Having sustained "severe damage" was the risk factor most strongly associated with outcome. Our data underscore the range of psychiatric morbidity related to a natural disaster, and suggest a relationship to chronic stressors.

A double-blind, randomized, placebo-controlled, multi-center study of brofaromine in the treatment of post-traumatic stress disorder.

A large multi-center, double-blind, parallel trial to assess the efficacy of brofaromine in the treatment of post traumatic stress disorder (PTSD) failed to show a significant difference between the brofaromine and placebo treatment groups. The placebo response rate in this study was higher than that in previously published double-blind, placebo-controlled studies of PTSD.

Sleep disturbance and its relationship to psychiatric morbidity after Hurricane Andrew.

OBJECTIVE: Sleep disturbance is an important dimension of posttraumatic stress disorder (PTSD), but most of the limited available data were obtained years after the original traumatic event. This study provides information on sleep disturbance and its relationship to posttraumatic morbidity from evaluations done within a year after the trauma. METHOD: Sleep and psychiatric symptoms of 54 victims (12 men and 42 women) of Hurricane Andrew who had no psychiatric illness in the 6 months before the hurricane were evaluated. A subset of hurricane victims with active psychiatric morbidity (N = 10) and nine comparison subjects who were unaffected by the hurricane were examined in a sleep laboratory. RESULTS: A broad range of sleep-related complaints were rated as being greater after the hurricane, and psychiatric morbidity (which was most commonly PTSD, followed by depression) had a significant effect on most of the subjective sleep measures. In addition, subjects with active morbidity endorsed greater frequencies of "bad dreams" and general sleep disturbances before the hurricane. Polysomnographic results for the hurricane victims revealed a greater number of arousals and entries into stage 1 sleep. REM density correlated positively with both the PTSD symptom of reexperiencing trauma and global distress. CONCLUSIONS: Subjects affected by Hurricane Andrew reported sleep disturbances, particularly those subjects with psychiatric morbidity. Tendencies to experience bad dreams and interrupted sleep before a trauma appear to mark vulnerability to posttraumatic morbidity. Results of sleep laboratory evaluations suggested brief shifts toward higher arousal levels during sleep for PTSD subjects and a relationship of REM phasic activity and symptom severity.

Nocturnal/daytime urine noradrenergic measures and sleep in combat-related PTSD.

Prominent heightened arousal symptoms and clinical/laboratory findings implicate the central noradrenergic system in posttraumatic stress disorder (PTSD). Heightened arousal frequently manifests in relation to sleep in PTSD. Central noradrenergic systems have a role in regulating arousal levels during sleep. We therefore evaluated noradrenergic production via urinary excretion in relation to sleep/wake activity in PTSD patients and controls. Twenty patients--all Vietnam veterans diagnosed with combat-related PTSD--and eight non-ill, non-combat-exposed controls had overnight sleep studies under medication and substance-free conditions. In association with sleep recording, subjects saved their urine for 24 hours in three 8-hour collections in order to obtain "daytime" (8:00 AM to 4:00 PM, 4:00 PM to MN) and "nocturnal" (MN to 8:00 AM) catecholamine measures. PTSD patients had decreased sleep efficiency relative to controls and increased REM density; 24-hour norepinephrine and MHPG (the more centrally derived metabolite) did not differ between patients and controls. "Nocturnal" excretion of MHPG minus the average of the two "daytime" values was negative in the controls, slightly positive in the patients, and differed significantly between the two groups. "Nocturnal minus daytime" MHPG also correlated negatively with total sleep time in the PTSD patients (R = -.45, p < .05). Our data support a relationship of nondiminished central noradrenergic activity at night, and sleep disturbance, in chronic, combat-related PTSD.

Panic-phobic patients and developmental trauma.

BACKGROUND: Several studies suggest high rates of developmental trauma among adult anxiety disorder patients. We attempted to replicate these findings in patients with panic disorder, agoraphobia, and/or social phobia in comparison with a nonclinical population and to evaluate possible relationship of traumas and phobic subtypes. METHOD: Fifty-one patients with panic disorder with agoraphobia and/or social phobia were assessed for lifetime diagnoses using interviews and rating scales and for developmental trauma by the Life Experience Questionnaire (LEQ). Fifty-one demographically similar nonclinical subjects completed a questionnaire that included the LEQ and screening questions for lifetime psychopathology. RESULTS: Childhood trauma was reported by 63% (N = 32) of the patients (vs. 35% or 18 of comparison subjects and 24% or 9 of subjects negative for lifetime psychopathology; chi 2 = 7.7, df = 1, p < .01). Sexual and/or physical abuse histories (and not separation and/or loss) were significantly increased in the patient group and were most specifically associated with social phobia. CONCLUSION: We find a similar, increased rate of childhood trauma as has been reported in previous studies of anxiety disorder patients. In our findings, this most specifically represents an association of social phobia and sexual/physical abuse histories.

Sleep events among veterans with combat-related posttraumatic stress disorder.

OBJECTIVE: Sleep disturbances are important features of posttraumatic stress disorder (PTSD); however, the published data characterizing PTSD sleep phenomena are limited. The authors report on the phenomenology and physiological correlates of symptomatic sleep events in PTSD. METHOD: The study data included survey results that addressed sleep symptoms during the past month in combat veterans with and without PTSD (N = 58), sleep diary records of awakenings from combat veterans with PTSD hospitalized on an inpatient rehabilitation unit (N = 52), and overnight polysomnography recordings obtained from 21 medication-free combat veterans with PTSD and eight healthy comparison subjects not exposed to combat. RESULTS: Recurrent awakenings, threatening dreams, thrashing movements during sleep, and awakenings with startle or panic features represented the most prevalently reported sleep-related symptoms. Laboratory findings of longer time awake, micro-awakenings, and a trend for patients to exhibit body and limb movements during sleep are consistent with the subjectively reported symptom profile. Prospectively assessed symptomatic awakenings featured startle or panic symptoms or anxiety related to threatening dreams. Laboratory findings revealed a trend for the symptomatic awakenings (with and without dream recall) to be disproportionately preceded by REM sleep, and the two recorded awakenings with objective physiological arousal were preceded by REM. CONCLUSIONS: PTSD features intrusions into sleep of more highly aroused behaviors and states, which appear partially conditioned to REM sleep.