Biomedical subjects

M H Rapaport

Publications and source records attributed to M H Rapaport.

At least 19 recordsLinked to original sources

PubMed2001

The effects of lithium on ex vivo cytokine production.

BACKGROUND: Studies suggest that lithium may have profound immunomodulatory effects in animal models as well as in humans. METHODS: In this study, whole blood cultures from normal control subjects were established for 5 days and the effects of lithium on cytokine production were investigated. Because many of lithium's actions have been postulated to be modulated through phosphoinositide (PI), protein kinase C (PKC) and cyclic adenosine monophosphate (c-AMP) signaling pathways, the effects of myo-inositol and prostaglandin E(2), alone or in combination with lithium, were also investigated. RESULTS: We found that lithium caused an increase in interleukin-4 and interleukin-10 levels, traditionally classified as T-helper lymphocyte type-2 cytokines, and a decrease in interleukin-2 and interferon-gamma levels, traditionally classified as T-helper lymphocyte type-1 (TH-1) cytokines. This shift cannot be fully explained by lithium's actions on the PI, PKC, or c-AMP messenger systems. CONCLUSIONS: Monocytes exposed to lithium in the presence of a mitogen for 5 days produced a shift toward the production of TH-2 cytokines and away from the production of TH-1 cytokines. The study suggests that lithium may have complex time-dependent effects on immune function.

Adult↗

PubMed2001

A genome survey indicates a possible susceptibility locus for bipolar disorder on chromosome 22.

Bipolar disorder or manic depressive illness is a major psychiatric disorder that is characterized by fluctuation between two abnormal mood states. Mania is accompanied by symptoms of euphoria, irritability, or excitation, whereas depression is associated with low mood and decreased motivation and energy. The etiology is currently unknown; however, numerous family, twin, and adoption studies have argued for a substantial genetic contribution. We have conducted a genome survey of bipolar disorder using 443 microsatellite markers in a set of 20 families from the general North American population to identify possible susceptibility loci. A maximum logarithm of odds score of 3.8 was obtained at D22S278 on 22q. Positive scores were found spanning a region of nearly 32 centimorgans (cM) on 22q, with a possible secondary peak at D22S419. Six other chromosomal regions yielded suggestive evidence for linkage: 3p21, 3q27, 5p15, 10q, 13q31-q34, and 21q22. The regions on 22q, 13q, and 10q have been implicated in studies of schizophrenia, suggesting the possible presence of susceptibility genes common to both disorders.

Bipolar Disorder↗

PubMed2001

Trait contributions of complex dysregulated behavioral organization in schizophrenic patients.

BACKGROUND: The "temporal architecture" of behavior is a construct that can be used to quantify the structure of behavioral sequences in the temporal domain-for example, by using a two-choice prediction task to investigate how past responses, stimuli, and outcomes influence the decision-making process. Using this task, previous investigations of the temporal architecture of the behavior in schizophrenic patients have identified an increased frequency of alternating highly predictable and highly unpredictable response sequences in the same test session in the same patient. Here, the hypothesis is tested that this dysregulation is stable over time and independent of psychosocial factors and symptomatic fluctuations. METHODS: Ninety-one schizophrenic patients were tested on a 128 trial version of the two-choice prediction task; of those, 58 subjects completed a retest session 40 days later. Three sets of measures were obtained: simple response biases, dynamical entropy, and mutual information functions. These measures were subjected to a factor analysis, and the reliability of the resulting factors was examined. RESULTS: First, three factors were obtained, which quantify 1) the level of dysregulation on this task; 2) the extent to which a win-stay/lose-shift strategy was used; and 3) the amount of simple response perseveration. Second, Crohnbach alpha for these factors was .699, .721, and .458, respectively. Third, there were no significant differences in the level of these factors within individual patients at the two time points. Fourth, neither symptom measures (Scale for the Assessment of Positive Symptoms and Scale for the Assessment of Negative Symptoms subscale scores) nor psychosocial or clinical variables (age, gender, illness duration, medication status) were able to predict the level of these factors at test or at retest. CONCLUSIONS: These results support the hypothesis that the fundamental dysregulation of the temporal architecture of behavior in schizophrenic patients is stable across time and independent of symptomatic status. Future studies will examine the heritability of this dysfunction.

Adult↗

PubMed2001

Sleep and sleep electroencephalogram in depressed patients treated with phenelzine.

BACKGROUND: The beneficial effect of antidepressant interventions has been proposed to depend on suppression of rapid eye movement (REM) sleep or inhibition of electroencephalographic (EEG) slow-wave activity (SWA) in non-REM sleep. Use of the monoamine oxidase inhibitor phenelzine sulfate can eliminate REM sleep. We studied the relation between REM sleep suppression and antidepressant response and the effect of phenelzine therapy on sleep EEG power spectra. METHODS: Open-labeled prescriptions of 30 to 90 mg of phenelzine were given to 11 patients with major depressive disorder (6 men and 5 women; mean age, 41.4 years); all were physically healthy. Mood, dream recall, sleep, sleep EEG, and ocular and muscular activity during sleep were studied before treatment and during the third and fifth weeks of pharmacotherapy. RESULTS: Six patients remitted from depression, 2 responded partially, and 3 showed no antidepressant response. Independent from clinical response, REM sleep was dramatically suppressed. On average, only 4.9 minutes of REM sleep was observed in treatment week 5, and it was completely absent in 6 patients. This effect was compensated for by increased stage 2 sleep. In non-REM sleep, EEG power was higher than at baseline between 16.25 and 25 Hz. Slow-wave activity (power within 0.75-4.5 Hz) and the exponential decline of SWA during sleep were not affected. CONCLUSIONS: Antidepressant response to phenelzine treatment does not depend on elimination of REM sleep or inhibition of SWA in non-REM sleep. In depressed patients, REM sleep is regulated independently from non-REM sleep and can be manipulated without altering the dynamics of SWA.

Adult↗

PubMed2001

Panic disorder.

In this article, the authors review the most recent advances in the pharmacotherapy, psychotherapy, and combined therapy for panic disorder. The authors focus on peer-reviewed data and on pragmatic clinical approaches that may help patients suffering from panic disorder.

Anti-Anxiety Agents↗

PubMed2001

Depression, visual acuity, comorbidity, and disability associated with age-related macular degeneration.

OBJECTIVE: To examine (1) the prevalence of depressive disorders in community-dwelling adults with advanced age-related macular degeneration (AMD) and (2) the relationship in this population between depression, visual acuity, the number of comorbid medical conditions, disability caused by vision loss as measured by the National Eye Institute-Vision Function Questionnaire (NEI-VFQ) and the vision-specific Sickness Impact Profile (SIPV), and disability caused by overall health status as measured by the Sickness Impact Profile-68 (SIP). DESIGN: Analysis of cross-sectional baseline data from a randomized clinical trial. PARTICIPANTS: Participants were 151 adults aged 60 and older (mean age, 80 years) with advanced macular degeneration whose vision was 20/60 or worse in their better eye. METHODS: Subjects were interviewed using measures of depression, disability, and chronic medical conditions. Visual acuity was obtained. Nonparametric correlation analyses and linear regression analyses were performed. MAIN OUTCOME MEASURES: Structured Clinical Interview for DSM-IV (SCID-IV), Geriatric Depression Scale (GDS), NEI-VFQ, SIPV, and SIP. RESULTS: Of the participants, 32.5% (n = 49) met SCID-IV criteria for depressive disorder, twice the rate observed in previous studies of community-dwelling elderly. Over and above depression (GDS), visual acuity aided in prediction of the level of vision-specific disability (NEI-VFQ and SIPV). CONCLUSIONS: Depressive disorder is a significant problem for the elderly afflicted with advanced macular degeneration. Further research on psychopharmacologic and psychotherapeutic interventions for depressed AMD patients is warranted to improve depression and enhance functioning. Over and above depression, visual acuity aided in predicting vision-specific disability. Treatment strategies that teach patients to cope with vision loss should be developed and evaluated.

Aged↗

PubMed2001

An abbreviated review of immune abnormalities in schizophrenia.

Initial investigations of the possible interaction between schizophrenia and the immune system began in the early 1900s and have proceeded in a rather halting fashion because of the methodological challenges faced by investigators. However, a confluence of recent data suggests that activation of the inflammatory response system, the cellular immune system, and the humoral immune system may be present in some patients with schizophrenia. Some of the most compelling data support the hypothesis that minor levels of immune activation may be associated with acute psychotic exacerbations. However, a second body of evidence suggests that some individuals with schizophrenia may have chronic, evolving autoimmune processes. This article is an overview of the history, rationale, and some of the recent findings on the interaction between schizophrenia and the immune system.

Journal Article↗

PubMed2001

Sertraline treatment of panic disorder: results of a long-term study.

OBJECTIVE: To investigate the long-term efficacy, prevention of relapse and safety of sertraline in the treatment of panic disorder. METHOD: This study consisted of 52 weeks of open-label sertraline treatment (n=398) followed by a 28 weeks of a double-blind, placebo-controlled discontinuation trial (n=183). RESULTS: Ninety-three patients were randomized to sertraline and 90 were randomized to placebo. Discontinuation due to insufficient clinical response occurred in 23.6% of placebo-treated patients and 12.0% of sertraline-treated patients (log-rank test, P=0.040). Thirty-three per cent of placebo-treated patients had an exacerbation of panic symptomatology, versus 13% of sertraline-treated patients (log-rank test, P=0.005). Abrupt cessation of sertraline resulted in dizziness (4.3% sertraline vs. 16.9% placebo; P=0.007) and insomnia (4.3% sertraline vs. 15.7% placebo; P=0.013) occurring at significantly higher rates. CONCLUSION: Long-term sertraline treatment was effective in preventing relapse of panic disorder, well tolerated and associated with minimal discontinuation symptoms.

Adult↗

PubMed2001

Panic disorder and response to sertraline: the effect of previous treatment with benzodiazepines.

More than 50% of patients who seek psychiatric care for panic disorder have previously received prescriptions for a benzodiazepine (BZ). Research on the treatment of generalized anxiety suggests that a history of BZ exposure might decrease the efficacy and tolerability of treatment with a serotonergic anxiolytic. This study examines the effect of prior BZ treatment on the efficacy and tolerability of sertraline treatment for panic disorder. Data were pooled (N = 705) from four double-blind, placebo-controlled studies of the efficacy of sertraline for the treatment of panic. Two of the studies were 12-week fixed-dose studies with starting doses of 50 mg, whereas 2 were flexible-dose studies of 10-week duration with starting doses of 25 mg. The effect of study treatment on the frequency of panic attacks, Clinical Global Impressions (CGI) Improvement Scale, and tolerability was examined for patients with or without prior BZ treatment. The efficacy of sertraline was not affected by prior treatment with BZs. The mean endpoint reduction in panic attack frequency was identical in patients with or without prior BZ use: 79% vs. 80% (not significant). A history of good versus poor response to prior BZ treatment did not significantly influence CGI responder rates for sertraline-treated patients (67% vs. 61%, respectively). Sertraline CGI responder rates were significantly greater than placebo response, which was 47% for the good-response prior-BZ subgroup (p = 0.007), and 36% for the poor-response BZ subgroup (p = 0.013). Placebo response was lower in patients with any prior BZ use by 10% on an intent-to-treat last-observation-carried-forward analysis (p = 0.106) and by 15% on a completer analysis (p = 0.045). Prior BZ use did not influence either rates of adverse events or discontinuation rates within the first 3 weeks in patients treated with either sertraline or placebo. Sertraline is both well-tolerated and has significant efficacy in patients with panic disorder, including the subset of patients with panic disorder who have previously been treated with BZs.

Adolescent↗

PubMed2001

Absence of neuropsychologic deficits in patients receiving long-term treatment with alprazolam-XR for panic disorder.

Studies to date on the effects of benzodiazepines on neuropsychologic function have yielded conflicting data with respect to the type, severity, and duration of deficits that may be induced by these agents. As part of a placebo-controlled trial of alprazolam-XR (extended release) administered in combination with cognitive-behavioral therapy in patients with panic disorder, a battery of tests was used to measure neuropsychologic function. Thirty-eight outpatients were randomly assigned to receive either alprazolam-XR or placebo. Dosages were titrated up so that the alprazolam group (N = 18) received a mean dose of 4 mg/day (reduced in two patients because of sedative side effects). Neuropsychologic function after 6 weeks of therapy at the target dosage was compared with baseline assessments in each group. Both groups showed a statistically significant improvement from baseline to repeated assessments on measures of attention, executive functioning, psychomotor speed, and visual memory (p < 0.001); these gains were attributed to a practice effect. No significant changes were noted in measures of learning, verbal memory, or reaction time, and neither group showed any deterioration from baseline to retesting in any aspect of neuropsychologic function. These findings call into question the assumption that long-term benzodiazepine therapy produces significant neuropsychologic deficit in patients with diagnosed anxiety disorders.

Adult↗

PubMed2001

An open-label, 12-week clinical and sleep EEG study of nefazodone in chronic combat-related posttraumatic stress disorder.

BACKGROUND: We examined the effects of nefazodone on polysomnographic sleep measures and subjective reports of sleep quality and nightmares. as well as other symptoms, in patients with chronic combat-related posttraumatic stress disorder (PTSD) during a 12-week, open-label clinical trial. To our knowledge, this is the first polysomnographic study of treatment in patients with PTSD. METHOD: The subjects were 12 male veterans (mean age = 54 years) who met DSM-IV diagnostic criteria for PTSD (mean duration = 30 years). All but I patient also met DSM-IV criteria for major depressive disorder. Patients were evaluated weekly with clinical ratings in an open-label clinical trial. Polysomnographic recordings for 2 consecutive nights were obtained before treatment and at 2, 4, 8, and 12 weeks. The dose of nefazodone was adjusted according to individual clinical needs. Final mean daily dose was 441 mg. RESULTS: The patients reported significantly fewer nightmares and sleep problems during treatment. Nevertheless, contrary to studies in depressed patients, nefazodone did not significantly affect polysomnographic sleep measures compared with baseline. In addition, the patients showed significant improvement in the Clinical Global Impressions of PTSD symptoms (global score, hyperarousals and intrusions subscales), the Clinician-Administered PTSD Scale (global, hyperarousal, and intrusions subscales), the Hamilton Rating Scale for Depression (HAM-D). and the Beck Depression Inventory (BDI). CONCLUSION: These patients with chronic, treatment-resistant, combat-related PTSD showed significant improvement of subjective symptoms of nightmares and sleep disturbance, as well as depression and PTSD symptoms. in this 12-week open-label clinical trial. Nevertheless, objective polysomnographic sleep measures did not change. Further studies, including double-blind. placebo-controlled trials, are needed to extend these findings and to understand the relationships between the physiology of sleep and symptoms of poor sleep and nightmares.

Arousal↗

PubMed2001

Prevalence, recognition, and treatment of comorbid depression and anxiety.

The management of depression is often complicated by comorbid psychiatric illness. Incomplete diagnoses or inadequate treatment can severely limit a patient's improvement. However, careful diagnosis and straightforward treatment can relieve suffering and restore function. This article will examine recent research investigating the coexistence of depression with a number of different anxiety disorders and review literature on the prevalence and recognition of depression with comorbid anxiety disorders. Finally, current data on treatment will be discussed, with a focus on optimal treatment approaches and duration of treatment.

Adolescent↗

PubMed2000

Preliminary evidence of an association between increased REM density and poor antidepressant response to partial sleep deprivation.

BACKGROUND: One night of total sleep deprivation or of late-night partial sleep deprivation (PSD) produces a temporary remission in approximately 40-60% of patients with major depressive disorder; however, little is known about polysomnography (PSG) characteristics of responders to these types of sleep deprivation (SD). METHODS: Twenty-three unmedicated unipolar patients (17-item Hamilton Depression Rating Scale (HDRS17) >16) and 14 normal controls underwent 1 night of late-night PSD (awake after 3 a.m.) Subjects underwent baseline PSG and received the HDRS17 at standard times before and after PSD. Clinical response was defined as a reduction of >30% in the modified HDRS17 (omitting sleep and weight loss items) following PSD. RESULTS: The 12 responders and 11 nonresponders did not differ from each other significantly on baseline HDRS17 or PSG variables. The only PSG variable correlating with percent decrease in modified HDRS17 was baseline REM density (Pearson's r=-0.52, n=23, P=0.01.) In other words, the lower the baseline REM density, the more robust the antidepressant response was. LIMITATIONS: Subject numbers are relatively small. CONCLUSIONS: Increased REM density, which reflects the number of rapid eye movements per epoch of REM sleep, may be a physiological marker for severity or poor prognosis in a variety of psychiatric disorders, including relapse in recovering alcoholics, suicidality in schizophrenia, and poor response to PSD or interpersonal psychotherapy in depression.

Adult↗

PubMed2000

Evaluating the parent-of-origin effect in bipolar affective disorder. Is a more penetrant subtype transmitted paternally?

BACKGROUND: Numerous genetic mechanisms and modes of transmission underlying bipolar affective disorder (BPAD) have been postulated. Recently, the discovery of genomic imprinting and mitochondrial transmission of illness in humans has stimulated study of parent-of-origin effects in the transmission of BPAD. METHODS: We examined a large sample of families from an associated linkage study to search for a possible parent-of-origin effect. Selecting for unilineal families with at least one offspring and/or parent diagnosed with BPAD after structured interview, we conducted three analyses: (1) the rates of illness among mothers and fathers of offspring affected with BPAD; (2) the observed frequency of transmission and rates of illness among maternal and paternal lineages; and (3) the rates of affective illness among offspring of parents affected with BPAD. RESULTS: Our results indicate no significant differences in the rates of illness among mothers and fathers of offspring affected with BPAD. Also, the frequency of transmission and rates of illness among maternal and paternal lineages did not differ significantly. However, the rate of BPAD among the offspring of fathers affected with BPAD was significantly higher than for mothers with the illness. LIMITATIONS: Substantially more women than men, and maternal than paternal relatives were studied - introducing possible gender biases. CONCLUSIONS: These results suggest a possible paternal parent-of-origin effect.

Bipolar Disorder↗

PubMed2000

Is placebo response the same as drug response in panic disorder?

OBJECTIVE: The authors used seven definitions of response in panic disorder to compare patient-rated improvements in quality of life between patients with panic disorder who responded to sertraline and those who responded to placebo. METHOD: They combined and examined data from two multicenter, randomized, double-blind, parallel-group, flexible-dose studies of panic disorder (N=302). RESULTS: Significant differences in quality of life between patients who responded to sertraline and those who responded to placebo were apparent across all the definitions of clinical response. CONCLUSIONS: Patients who respond to placebo in panic disorder treatment studies may show symptom relief but may not experience improvement in quality of life. Determinations of quality of life should be included as components of both standard clinical assessment and clinical treatment studies of patients with panic disorder.

Attitude to Health↗

PubMed2000

Sertraline treatment of panic disorder: response in patients at risk for poor outcome.

BACKGROUND: More than one third of panic disorder patients have a chronic and/or recurrent form of the disorder, accounting for much of the individual and societal cost associated with the illness. Six clinical variables have been most consistently identified as high-risk predictors of poor outcome: (1) panic severity, (2) presence of agoraphobia, (3) comorbid depression, (4) comorbid personality disorder, (5) duration of illness, and (6) female sex. No published research has systematically examined the differential antipanic efficacy of selective serotonin reuptake inhibitors in patients at high risk for poor outcome. METHOD: Data were pooled (N = 664) from 4 double-blind, placebo-controlled studies of the efficacy of sertraline for the treatment of DSM-III-R panic disorder. Two of the studies were 12-week fixed-dose studies with starting daily doses of sertraline, 50 mg, and 2 were 10-week flexible-dose studies with starting daily doses of sertraline, 25 mg. All other study design features were the same, except for the exclusion of women of childbearing potential in the 2 fixed-dose studies. Exclusion of patients with marked personality disorders and depression meant that only 4 of the poor-outcome variables could be evaluated. RESULTS: Clinical improvement was similar for patients treated with sertraline whether or not they carried an agoraphobia diagnosis, had a duration of illness > 2 years, or were female. Patients with high baseline panic severity had significantly (p = .01) less improvement on the endpoint Clinical Global Impressions-Improvement (CGI-I) scale than patients with moderate severity, although the Clinical Global Impressions-Severity of Illness scale change score was higher in the patients with high severity (-2.00 vs. -1.31). For patients with 3 or more high-risk variables, there was a modest, but statistically significant, tendency for reduced global improvement (endpoint CGI-I score of 2.7 for the high-risk vs. 2.4 for the non-high-risk group; p = .017), although the high-risk group actually had a similar endpoint reduction in frequency of panic attacks (82%) compared with the non-high-risk group (78%). CONCLUSION: Treatment of panic disorder with sertraline was generally effective, even in the presence of baseline clinical variables that have been associated with poor treatment response. The main limitations of the analysis were the reliance on pooled data from 4 studies (even if the designs were similar) and our inability to examine the impact of depression and personality disorders on response to treatment because of the exclusion criteria of the clinical trials.

Adult↗

PubMed1999

Analysis of GNAZ gene polymorphism in bipolar affective disorder.

Evidence for a bipolar disorder (BPD) susceptibility locus on chromosome 22q11 has been provided in several studies. One candidate gene that maps to this region is the G-protein alpha subunit gene Galphaz (GNAZ). We have identified a common silent polymorphism in GNAZ exon 2 by single strand conformation polymorphism analysis. The frequency of this polymorphism was determined in a control population (n=84) and in patients with BPD (n=88). The data showed a statistical trend toward a difference in the distribution of alleles in patients with BPD compared with control subjects (chi square=3.2, 1 df, P=0.073, two-tailed). No significant difference was detected when the GNAZ polymorphism was analyzed in control subjects and schizophrenia patients (n=63, P=0.92). These data continue to provide some support for a BPD susceptibility gene on 22q11, possibly in linkage disequilibrium with the GNAZ 309 polymorphism.

Adult↗

PubMed1999

Neonaticide in the city of Rio de Janeiro: forensic and psycholegal perspectives.

This is a retrospective study of mothers charged with killing their children within 24 h of birth in the city of Rio de Janeiro, Brazil. Characteristics of the mothers and the victims, the circumstances surrounding the offense, the mothers' motivation and state of mind at the time of the offense, the legal process, and follow-up data were investigated. We analyzed our cohort as two sub-groups: 26 offenses that occurred between 1900 and 1939 and were dealt with under the Brazilian Penal Code of 1890, and 27 offenses that were committed between 1940 and 1995 and were dealt with under the Penal Code of 1940. The mothers were young (mean 22.5 +/- 5.3 years), unmarried (88.2%), non-Caucasian (73.8%), and had limited formal education. They usually kept the pregnancy a secret (94.1%) and gave birth in a classified way (100%). Most victims were killed through wounding violence (77.4%). Offenders identified between the years of 1940-1995 had increased rates of literacy (chi 2 = 6.80, d.f. = 1, p = .009), a higher incidence of reported psychiatric symptoms (chi 2 = 11.82, d.f. = 1, p < .001), increased referral for psychiatric assessment (chi 2 = 3.85, d.f. = 1, p = .05), and greater frequency of cases where statute of limitations was expired (chi 2 = 3.88, d.f. = 1, p = .049).

Adolescent↗