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.

Cardiac manifestations of cocaine abuse: a cross-sectional study of asymptomatic men with a history of long-term abuse of "crack" cocaine.

OBJECTIVES: The objective of this study was to evaluate the prevalence of cardiac abnormalities in young, asymptomatic long-term "crack" cocaine abusers. BACKGROUND: Although the cardiac complications of cocaine abuse have received widespread attention, the prevalence of cardiac abnormalities in asymptomatic long-term cocaine abusers is unknown. METHODS: History, physical examination, electrocardiogram (ECG) and echocardiogram were performed in 52 consecutive long-term cocaine abusers admitted to a drug rehabilitation program. Findings were compared with those in 14 age-matched normal volunteers and 14 age-matched normotensive patients admitted to a psychiatric service who had a pattern of smoking and alcohol consumption similar to that of the study patients. RESULTS: The ECG findings were abnormal in 29% of cocaine abusers, and included nonspecific ST-T wave changes in 15%, abnormal ST segment elevation in 10%, old inferior infarction in 2%, old anteroseptal infarction in 2% and abnormal precordial R wave progression in 10%. When compared with normal volunteers and control patients, cocaine abusers had increased left ventricular posterior wall thickness (1.12 vs. 0.76 and 0.85 cm, respectively, p < 0.0001), increased septal thickness (1.13 vs. 0.76 and 0.86 cm, p < 0.001) and higher left ventricular mass index (142 vs. 84 and 94 g/m2, p < 0.0001). Left ventricular diastolic filling variables did not differ significantly among the three groups. Diastolic filling variables were similar in cocaine abusers with and without left ventricular hypertrophy, and the prevalence of left ventricular hypertrophy did not differ significantly between those who used no alcohol or < 35 ml/week of alcohol and those who consumed > or = 500 ml/week of alcohol. Left ventricular segmental wall motion abnormalities were present in 11 subjects (21%) and the ejection fraction was decreased (< 0.45) in 2 (4%). CONCLUSIONS: Electrocardiographic and echocardiographic abnormalities are common in long-term cocaine abusers. Despite the frequent occurrence of left ventricular hypertrophy, Doppler-derived diastolic filling pattern was not altered. Concomitant alcohol use did not affect the prevalence of these abnormalities.

Electroencephalographic sleep in panic disorder. A focus on sleep-related panic attacks.

Sleep electroencephalograms were studied in 13 patients with panic disorder, six of whom experienced panic from sleep, and seven controls. Sleep was disturbed in the patients, as manifested by increased sleep latency, decreased sleep time, and decreased sleep efficiency. Rapid eye movement (REM) latencies were not reduced in the patient group. All six of the panic awakenings were preceded by non-REM sleep, which could be further characterized as a transition from stage II toward delta sleep. The overall degree of sleep disturbance (ie, sleep latency, sleep efficiency) did not appear to be influenced by the occurrence of sleep panic. There was also an association of increased REM latency with nights of sleep panic.

Behavioral and physiologic effects of short-term and long-term administration of clonidine in panic disorder.

We evaluated the behavioral and physiologic effects of clonidine hydrochloride, a centrally active alpha 2-adrenergic agonist, in two separate studies of patients with panic disorder. In the first study, intravenous clonidine (2 micrograms/kg) and placebo were administered on a blind basis to 12 patients with panic disorder and ten normal controls. Clonidine produced significantly greater decrements in anxiety at one hour in the patients with panic disorder than in the controls. The changes in pulse, blood pressure, and ratings of sleepiness did not differ significantly between patients and controls. In the second study, oral clonidine was administered to 18 patients in a double-blind, flexible-dose treatment trial averaging ten weeks in duration. While anxiolytic effects were noticed in some patients, these effects did not persist in the group as a whole. These two studies indicate that while clonidine has short-term anxiolytic effects in patients with panic disorder, these effects do not persist with long-term administration in most patients.

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.

Obsessive-compulsive symptoms in panic disorder.

Previous reports have noted an increased prevalence of obsessive-compulsive symptoms in patients with panic disorder. The authors found a prevalence of obsessive-compulsive symptoms in 19 (27%) of 70 patients with panic disorder. Compared to a subgroup of 25 patients with classic features of panic disorder and no obsessive-compulsive symptoms, the subgroup with obsessive-compulsive symptoms had an earlier onset of illness, were more likely to have personal and family histories of major depression and substance abuse, and showed a poorer outcome after treatment.

Withdrawal syndrome with gradual tapering of alprazolam.

The clinical and biological correlates of gradual alprazolam withdrawal were investigated in 10 patients in a double-blind, placebo-controlled trial. During gradual alprazolam withdrawal, anxiety and plasma cortisol levels were higher than during a postwithdrawal medication-free period.

Sleep panic attacks: new clinical findings and theoretical implications.

Forty-five panic disorder patients and 26 normal control subjects were surveyed regarding their histories of sleep panic attacks, insomnia, and vulnerability to exogenous panic stimuli. Sixty-nine percent (N = 31) of the patients reported having experienced sleep panic at some time in their lives, and 33% (N = 15) of the patients experienced recurrent sleep panic. The implications of these findings for the management of panic disorder are discussed.

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.

Phenomenology and course of psychiatric disorders associated with combat-related posttraumatic stress disorder.

OBJECTIVE: Studies indicate that chronic combat-related posttraumatic stress disorder (PTSD) is frequently associated with other psychiatric disorders. Questions regarding the nature and interrelationships of these conditions require clarification. The purpose of this study was to address primary and secondary illness relationships by focusing on the specific phenomenology and course of illness onset of PTSD comorbidity. METHOD: In order to minimize confounding factors, only outpatients without recent substance use disorders were included. Sixty subjects who had been exposed to severe combat stress including veterans of Vietnam and veterans of World War II or Korea, 15 of whom were former prisoners of war, received structured assessments over serial evaluations. RESULTS: PTSD was the most prevalent lifetime disorder followed by major depression, panic disorder, generalized anxiety disorder, and phobic disorder or symptoms. Endogenous-appearing features overlapping other clinical populations were common; however, some specific symptom patterns also were suggestive of traumatic influence. Unlike generalized anxiety disorder and past substance use, the mean onset of phobias, major depression, and panic disorder, respectively, occurred later than PTSD. CONCLUSIONS: These observations suggest that persistent conditions related to PTSD progress toward symptoms that are increasingly autonomous in their pattern of occurrence.

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.

Cerebral glucose metabolic differences in patients with panic disorder.

Regional glucose metabolic rates were measured in patients with panic disorder during the performance of auditory discrimination. Those regions examined by Reiman and colleagues in their blood flow study of panic disorder [Nature 310:683 (1984)] were examined with a higher resolution positron emission tomography (PET) scanner and with the tracer [F-18]-2-fluoro-2-deoxyglucose (FDG). In contrast to the blood flow findings of Reiman et al., we did not find global gray metabolic differences between patients with panic disorder and normal controls. Consistent with the findings of Reiman et al. [Nature; Am J Psychiatry 143:469 (1986)], we found hippocampal region asymmetry. We also found metabolic decreases in the left inferior parietal lobule and in the anterior cingulate (trend), as well as an increase in the metabolic rate of the medial orbital frontal cortex (trend) of panic disorder patients. It is unclear whether the continuous performance task (CPT) enhanced or diminished findings that would have been noted in a study performed without task.

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.

Combat-related flashbacks in posttraumatic stress disorder: phenomenology and similarity to panic attacks.

Combat veterans (N = 25) with posttraumatic stress disorder had flashbacks related to their combat stressors, which included major losses and exposure to danger. Certain affects, loud noises, fatigue, and personal stress tended to precipitate flashback episodes. Flashbacks began a year or more after exposure to combat in 50% of patients; 56% of patients experienced daily flashbacks. Flashback phenomenology met DSM-III criteria for panic attacks. The similarity of flashbacks to panic attacks suggests treatment trials with monoamine oxidase inhibitors or imipramine for these selected symptoms.

Patients with frequent sleep panic: clinical findings and response to medication treatment.

The authors present 12 cases of panic disorder patients whose sleep panic attacks represented their primary complaint at the time of admission. The patients averaged 18 sleep panic attacks per month before admission. Seven patients were treated with tricyclic antidepressants and demonstrated marked global clinical improvement and a reduction in the frequency of sleep panic attacks. The clinical and theoretical implications of these preliminary findings are discussed within the context of current theories regarding the spontaneous nature of panic attacks.

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.

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.

Night terrors in adults: phenomenology and relationship to psychopathology.

BACKGROUND: Night terrors have been classically described in children. Night terrors occurring in adults have been linked to psychopathology. Recent descriptions of sleep panic attacks have raised questions about their relationship to night terrors. METHOD: Evaluations from a medically affiliated sleep disorders program were reviewed to identify adult patients presenting with events consistent with night terrors. Eleven patients were identified, 10 of whom had polysomnographic evaluation, and their records were reviewed for information relevant to night terrors and psychiatric symptoms. Six of these patients were available for further assessment which included inquiry regarding sleep events, a Structured Clinical Interview (SCID) for psychiatric disorders, and the Millon Clinical Multiaxial Inventory II (MCMI-II) for personality-related measurements. RESULTS: In the original sample, night terror episodes featured confused behaviors, motor activity, and absent or fragmented recall. Polysomnography documented arousals from slow wave sleep in 9 of 10 patients. All of the original patients reported psychiatric symptoms. All 6 patients who received the subsequent structured evaluation met lifetime criteria for Axis I conditions (most commonly affective and substance use disorders) and had elevated scores on the personality scales of the MCMI-II. Night terrors were not limited to psychiatric episodes. CONCLUSION: Night terrors occur in adults that are similar to episodes described in children. While distinct from sleep panic attacks, night terrors appear to occur in adults with histories of psychopathology.

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.

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.