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ABSTRACT: The pathways to increased cardiovascular risk in bipolar disorder include health behaviors, psychosocial stress and long-term medication exposure. However, the evidence that the association between cardiovascular risk factors and bipolar disorder remains significant after controlling for these co-factors suggests that additional important risk factors have yet to be identified. Our hypothesis is that disturbances in the sleep-wake cycle are an important and under-recognized pathway through which affective disorders lead to increased cardiovascular risk.
In patients with bipolar disorder type 1 in clinical remission, we: 1) explored whether sleep disturbance predicted the endorsement of NCEP ATP-III criteria for dyslipidemia, independent of other lifestyle factors and 2) tested the association between low HDL (NCEP-ATP III) and sleep duration measured with actigraphy over an eight-day period.
Median sleep duration is significantly associated with low HDL. The risk of having low HDL increases by 1.23 with every 30 minutes of reduced sleep time.
Since sleep patterns in patients with bipolar disorder are variable and irregular, it is possible that other sleep characteristics, not present during the span of our study, or the variability itself may be what drives the increased cardiovascular risk.
Sleep characteristics of patients with bipolar disorder in clinical remission are associated with cardiovascular risk. More specifically, sleep duration was associated with low HDL. Clinicians should pay special attention to sleep hygiene in treating individuals with bipolar disorder, even when they are in clinical remission.
Journal of affective disorders 05/2012; 141(2-3):484-7. · 3.76 Impact Factor
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ABSTRACT: One aim of personalized medicine is to determine which treatment is to be preferred for an individual patient, given all patient information available. Particularly in mental health, however, there is a lack of a single objective, reliable measure of outcome that is sensitive to crucial individual differences among patients.
We examined the feasibility of quantifying the total clinical value provided by a treatment (measured by both harms and benefits) in a single metric. An expert panel was asked to compare 100 pairs of patients, one from each treatment group, who had participated in a randomized clinical trial (RCT) involving interpersonal psychotherapy (IPT) and escitalopram, selecting the patient with the preferred outcome considering both benefits and harms.
From these results, an integrated preference score (IPS) was derived, such that the differences between any two patients' IPSs would predict the clinicians' preferences. This IPS was then computed for all patients in the RCT. A second set of 100 pairs was rated by the panel. Their preferences were highly correlated with the IPS differences (r=0.84). Finally, the IPS was used as the outcome measure comparing IPT and escitalopram. The 95% confidence interval (CI) for the effect size comparing treatments indicated clinical equivalence of the treatments.
A metric that combines benefits and harms of treatments could increase the value of RCTs by making clearer which treatments are preferable and, ultimately, for whom. Such methods result in more precise estimation of effect sizes, without increasing the required sample size.
Psychological Medicine 08/2011; 42(4):865-73. · 6.16 Impact Factor
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E Frank,
G B Cassano,
P Rucci,
W K Thompson,
H C Kraemer,
A Fagiolini,
L Maggi, D J Kupfer,
M K Shear,
P R Houck,
S Calugi,
V J Grochocinski,
P Scocco,
J Buttenfield,
R N Forgione
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ABSTRACT: Although many studies suggest that, on average, depression-specific psychotherapy and antidepressant pharmacotherapy are efficacious, we know relatively little about which patients are more likely to respond to one versus the other. We sought to determine whether measures of spectrum psychopathology are useful in deciding which patients with unipolar depression should receive pharmacotherapy versus depression-specific psychotherapy.
A total of 318 adult out-patients with major depression were randomly assigned to escitalopram pharmacotherapy or interpersonal psychotherapy (IPT) at academic medical centers at Pittsburgh, Pennsylvania and Pisa, Italy. Our main focus was on predictors and moderators of time to remission on monotherapy at 12 weeks.
Participants with higher scores on the need for medical reassurance factor of the Panic-Agoraphobic Spectrum Self-Report (PAS-SR) had more rapid remission with IPT and those with lower scores on the psychomotor activation factor of the Mood Spectrum Self-Report (MOODS-SR) experienced more rapid remission with selective serotonin reuptake inhibitor (SSRI) pharmacotherapy. Non-specific predictors of longer time to remission with monotherapy included several panic spectrum and mood spectrum factors and the Social Phobia Spectrum (SHY) total score. Higher baseline scores on the 17- and 25-item Hamilton Depression Rating Scales (HAMD-17 and HAMD-25) and the Work and Social Adjustment Scale (WSAS) also predicted a longer time to remission, whereas being married predicted a shorter time to remission.
This exploratory study identified several non-specific predictors but few moderators of psychotherapy versus pharmacotherapy outcome. It offers useful indicators of the characteristics of patients that are generally difficult to treat, but only limited guidance as to who benefits from IPT versus SSRI pharmacotherapy.
Psychological Medicine 04/2010; 41(1):151-62. · 6.16 Impact Factor
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ABSTRACT: Cognitive impairment in bipolar disorder has been associated with poor functional outcomes. We examined the relation of self-reported cognitive problems to employment trajectory in patients diagnosed with bipolar I disorder.
154 bipolar I disorder patients were followed for 15-43months at the Bipolar Disorders Center for Pennsylvanians. Using a multinomial logistic regression we examined predictors of employment group including self-reported cognitive problems, mood symptoms, education and age. Cognitive functioning was measured via 4 self-report items assessing memory/concentration at baseline and termination. Employment status was recorded at baseline and termination. Employment was categorized as working (full-time, part-time, homemaker, volunteer) or not working (leave of absence, disability, unemployed, no longer volunteering) at each time point. Patients were categorized as good stable, improving, worsening and poor stable.
Baseline self-reported concentration problems and years of education significantly predicted employment trajectory.
Post-hoc analyses of existing clinical data.
Self-reported concentration problems assessed in the context of specific areas of functioning may serve as a sensitive predictor of functional outcome in patients diagnosed with bipolar I disorder.
Journal of affective disorders 11/2009; 124(3):324-8. · 3.76 Impact Factor
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G B Cassano,
M Mula,
P Rucci,
M Miniati,
E Frank, D J Kupfer,
A Oppo,
S Calugi,
L Maggi,
R Gibbons,
A Fagiolini
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ABSTRACT: The observation that bipolar disorders frequently go unrecognized has prompted the development of screening instruments designed to improve the identification of bipolarity in clinical and non-clinical samples. Starting from a lifetime approach, researchers of the Spectrum Project developed the Mood Spectrum Self-Report (MOODS-SR) that assesses threshold-level manifestations of unipolar and bipolar mood psychopathology, but also atypical symptoms, behavioral traits and temperamental features. The aim of the present study is to examine the structure of mania/hypomania using 68 items of the MOODS-SR that explore cognitive, mood and energy/activity features associated with mania/hypomania.
A data pool of 617 patients with bipolar disorders, recruited at Pittsburgh and Pisa, Italy was used for this purpose. Classical exploratory factor analysis, based on a tetrachoric matrix, was carried out on the 68 items, followed by an Item Response Theory (IRT)-based factor analytic approach.
Nine factors were initially identified, that include Psychomotor Activation, Creativity, Mixed Instability, Sociability/Extraversion, Spirituality/Mysticism/Psychoticism, Mixed Irritability, Inflated Self-esteem, Euphoria, Wastefulness/Recklessness, and account overall for 56.4% of the variance of items. In a subsequent IRT-based bi-factor analysis, only five of them (Psychomotor Activation, Mixed Instability, Spirituality/Mysticism/Psychoticism, Mixed Irritability, Euphoria) were retained.
Our data confirm the central role of Psychomotor Activation in mania/hypomania and support the definitions of pure manic (Psychomotor Activation and Euphoria) and mixed manic (Mixed Instability and Mixed Irritability) components, bearing the opportunity to identify patients with specific profiles for a better clinical and neurobiological definition.
Journal of Affective Disorders 07/2008; 112(1-3):59-70. · 3.52 Impact Factor
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ABSTRACT: Little is known about sleep and the effects of total sleep loss in the ‘old old’ (i.e., 80-year-olds). We investigated sleep, mood, and performance responses to acute sleep deprivation in healthy 80-year-olds (n–10) and 20-year-olds (n = 14). The protocol consisted of three nights of baseline sleep, one night of total sleep deprivation, and two nights of recovery sleep. Mood and vigilance were tested using visual analog scales and a Mackworth clock procedure in the morning and evening of each study day. Daytime sleepiness was measured by five naps on the days following the third and sixth nights. Old subjects had lower sleep efficiency and less delta sleep than young subjects. However, sleep continuity and delta sleep were enhanced in both groups on the first recovery night, indicating that sleep changes in old subjects are at least partially reversible by this procedure. Surprisingly, young subjects had shorter daytime sleep latencies than the old, suggesting a greater unmet sleep need in the former group. Mood and performance were disturbed by sleep loss in both groups, but to a greater extent among the young. This suggests that acute total sleep loss is a more disruptive procedure for the young than for the old.
Psychophysiology 01/2007; 27(6):677 - 685. · 3.29 Impact Factor
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ABSTRACT: We hypothesize that circadian dysfunction could underlie, at least partially, the liability for bipolar 1 disorder (BD1). Our hypothesis motivated tests for the association between the polymorphisms of genes that mediate circadian function and liability for BD1. The US Caucasian patients with BD1 (DSM-IV criteria) and available parents were recruited from Pittsburgh and surrounding areas (n = 138 cases, 196 parents) and also selected from the NIMH Genetics Collaborative Initiative (n = 96 cases, 192 parents). We assayed 44 informative single-nucleotide polymorphisms (SNPs) from eight circadian genes in the BD1 samples. A population-based sample, specifically cord blood samples from local live births, served as community-based controls (n = 180). It was used as a contrast for genotype and haplotype distributions with those of patients. US patients with schizophrenia/schizoaffective disorder (SZ/SZA, n = 331) and available parents from Pittsburgh (n = 344) were assayed for a smaller set of SNPs based on the results from the BD1 samples. Modest associations with SNPs at ARNTL (BmaL1) and TIMELESS genes were observed in the BD1 samples. The associations were detected using family-based and case-control analyses, albeit with different SNPs. Associations with TIMELESS and PERIOD3 were also detected in the Pittsburgh SZ/SZA group. Thus far, evidence for association between specific SNPs at the circadian gene loci and BD1 is tentative. Additional studies using larger samples are required to evaluate the associations reported here.
Genes Brain and Behavior 04/2006; 5(2):150-7. · 3.48 Impact Factor
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A Sbrana,
L Dell'Osso,
A Benvenuti,
P Rucci,
P Cassano,
S Banti,
C Gonnelli,
M R Doria,
L Ravani,
S Spagnolli,
L Rossi,
F Raimondi,
M Catena,
J Endicott,
E Frank, D J Kupfer,
G B Cassano
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ABSTRACT: This study evaluates the validity and the reliability of a new instrument developed to assess the psychotic spectrum: the Structured Clinical Interview for the Psychotic Spectrum (SCI-PSY). The instrument is based on a spectrum model that emphasizes soft signs, low-grade symptoms, subthreshold syndromes, as well as temperamental and personality traits comprising the clinical and subsyndromal psychotic manifestations. The items of the interview include, in addition to a subset of the DSM-IV criteria for psychotic syndromes, a number of features derived from clinical experience and from a review of the phenomenological descriptions of psychoses. Study participants were enrolled at 11 Italian Departments of Psychiatry located at 9 sites and included 77 consecutive patients with schizophrenia or schizoaffective disorder, 66 with borderline personality disorder, 59 with psychotic mood disorders, 98 with non-psychotic mood disorders and 57 with panic disorder. A comparison group of 102 unselected controls was enrolled at the same sites. The SCI-PSY significantly discriminated subjects with any psychiatric diagnosis from controls and subjects with from those without psychotic disorders. The hypothesized structure of the instrument was confirmed empirically.
Schizophrenia Research 07/2005; 75(2-3):375-87. · 4.75 Impact Factor
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ABSTRACT: Empirical data on the impact of personality pathology on acute treatment outcome for depression are mixed, in part because of challenges posed by assessing trait-like personality patterns while patients are in an active mood episode. To our knowledge, no previous study has examined the effect of personality pathology on maintenance treatment outcome. By maintenance treatment we refer to long-term treatment provided to prevent depression recurrence among remitted patients.
Structured Clinical Interviews for the DSM-III-R Personality Disorders (SCID-II) were obtained on a sample of 125 recurrently depressed women following sustained remission of the acute mood episode and prior to entering maintenance treatment. SCID-II interviews were then repeated following 1 and 2 years of maintenance interpersonal psychotherapy.
At the pre-maintenance assessment, 21.6% of the sample met SCID-II personality disorder criteria. Co-morbid personality pathology was related to an earlier age of onset, more previous depressive episodes, and a greater need for adjunctive pharmacotherapy to achieve remission of the acute mood episode. Co-morbid personality pathology predicted both higher rates of depression recurrence and a shorter time to recurrence over the 2-year course of maintenance treatment. Notably, among those patients who remained depression-free, continuous levels of personality pathology steadily declined over the 2-year course of maintenance therapy.
Results highlight the need for early and effective intervention of both episodic mood disorder and inter-episode interpersonal dysfunction inherent to the personality disorders. Future maintenance treatment trials are needed to clarify the relationship between episodic mood disorder and personality function over time.
Psychological Medicine 06/2004; 34(4):659-69. · 6.16 Impact Factor
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ABSTRACT: Current guidelines provide little practical information on the clinical characteristics of bipolar I patients who are likely to benefit from the combination of a mood stabilizer and an antidepressant. Rather, guidelines simply state that an adjunctive antidepressant is recommended in cases of 'severe' depression. Our objective was to evaluate the clinical and demographic differences between patients who remitted on a mood stabilizer alone and patients who subsequently required an adjunctive antidepressant to achieve stabilization.
We retrospectively compared the pharmacological treatment strategies of 39 patients with bipolar I disorder who were in a current depressive episode. Patients who did not respond to mood stabilizer monotherapy were prescribed an adjunctive antidepressant. We evaluated the clinical differences at baseline and week 1, 2 and 3 of treatment between patients stabilizing on a mood stabilizer alone and patients that did not remit until they subsequently received an adjunctive antidepressant.
Patients who required an adjunctive antidepressant had significantly higher total Hamilton Depression Rating (HRS-D) scores at week 1, 2 and 3 of treatment, but not at baseline. Patients who remitted on mood stabilizer monotherapy were more likely to be married, achieved stabilization in less time, presented with higher Young Mania Rating Scale (YMRS) scores, and experienced the previous episode of depression more recently than patients who required an antidepressant.
Our findings suggest that rapid improvement after achieving a therapeutic dose of a mood stabilizer is clinically significant and represents a surrogate endpoint in the treatment of bipolar I depression. Larger, prospective, and controlled studies are needed to verify our results and to identify additional indicators for a mood stabilizer and antidepressant combination treatment strategy.
Bipolar Disorders 11/2002; 4(5):277-82. · 5.29 Impact Factor
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ABSTRACT: The reliability of telephone interviews for rating 25 selected individual items of the Diagnostic Interview for Genetic Studies (DIGS) was assessed among persons with remitted bipolar disorder I (BPD I, n = 20).
The Diagnostic Interview for Genetic Studies (DIGS) was administered directly (with two raters present) and by telephone in random order to 20 adults with bipolar disorder I.
Telephone interviews achieved reliability comparable to direct interviews for 16 items (64%), but were considered unsatisfactory for seven others (28%). Two other items, which evaluated the overlap between substance abuse and mood disorder, were considered unreliable for both methods of interview.
The presence of two interviewers for the in-person interview may have led to over-estimation of in-person reliability. Investigator bias in favor of phone interviews and a relatively small sample may have confounded the results.
Telephone interviews may be used to evaluate individuals with BPD I in remission, provided the limitations of this method are recognized. They have limited reliability for dissecting overlap between mood abnormalities and psychotic phenomena or substance abuse.
Journal of Affective Disorders 10/2002; 71(1-3):221-7. · 3.52 Impact Factor
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ABSTRACT: The treatment of bipolar depression remains a major clinical challenge. The effectiveness and safety of adjunctive citalopram were evaluated in DSM-IV-diagnosed bipolar depressed patients in a 5-site study.
The treatment strategy consisted of an open-label add-on design in which patients received 8 weeks of acute treatment with citalopram adjunctive to their ongoing treatment with mood stabilizers. Ongoing treatment with 1 antipsychotic, 1 anxiolytic, and 1 hypnotic agent was permitted. Responders to the 8-week trial then received 16 weeks of additional treatment with citalopram.
Forty-five subjects entered the trial; 12 dropped out before the end of the acute treatment phase. Of the 33 patients who completed the acute treatment phase, 64% (N = 21) were responders and 36% (N = 12) were nonresponders. In the continuation phase of the study, 14 patients achieved sustained remission, 3 patients did not achieve remission before completing 16 weeks of continuation treatment, 2 patients experienced a relapse, and 2 patients dropped out of the study and did not have a chance to remit. In spite of the extensive concomitant medication usage allowed in this study, citalopram treatment was well tolerated and the level of reported adverse events (including headache, nausea, diarrhea, and sexual dysfunction) relatively low.
The high response rate, the high rate of sustained remission, and the low rate of adverse events strongly support the use of citalopram as a treatment for bipolar I or II depression. These findings should stimulate a controlled double-blind trial to demonstrate even more clearly the usefulness of this drug in the therapeutic regimen for bipolar disorder.
The Journal of Clinical Psychiatry 01/2002; 62(12):985-90. · 5.80 Impact Factor
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ABSTRACT: The thalamus is a key structure in brain anatomic circuits potentially involved in the pathophysiology of mood disorders. Available findings from studies that examined this brain region in mood disorder patients have been conflicting. To examine the hypothesis of anatomical abnormalities in the thalamus in patients with mood disorders, we conducted a magnetic resonance imaging (MRI) study in 25 bipolar patients (mean age+/-S.D.=34.4+/-9.8 years), 17 unipolar patients (mean age+/-S.D.=42.8+/-9.2 years), and 39 healthy control subjects (mean age+/-S.D.=36.6+/-9.7 years). Thalamic volumes Gray Matter were measured blindly with a semi-automated technique. Multivariate analysis of variance, with age and gender as covariates, revealed no significant differences in left or right thalamic volumes among bipolar patients, unipolar patients and healthy individuals. There were no significant effects of gender, age at illness onset, episode type, number of episodes, length of illness, or family history of mood disorders on thalamic measurements. Although functional abnormalities in the thalamus are likely to be implicated in the pathophysiology of mood disorders, no abnormalities in thalamic size appear present in bipolar or unipolar individuals.
Psychiatry Research 01/2002; 108(3):161-8. · 2.52 Impact Factor
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ABSTRACT: Patients with bipolar disorder are often prescribed lithium in combination with a selective serotonin reuptake inhibitor. Doubts still remain, however, about the safety of the combination, particularly with regard to the risk of developing a serotonin syndrome. The authors retrospectively evaluated the safety of the combination of lithium and paroxetine when the two medications were sequentially prescribed in patients with bipolar disorder. The authors examined a sample of 17 patients with bipolar disorder who were treated with lithium during a depressive episode and who required paroxetine as an adjunctive antidepressant to ongoing lithium treatment. Averaging across all subjects, no statistically significant increase was found for any of the somatic symptoms that were assessed before and after paroxetine was added to ongoing lithium therapy. Examining the clinical records of each patient in detail; however, four patients who developed significant adverse events, possibly related to an emerging serotonin syndrome were identified. Clinicians should be aware of the possible development of a serotonin syndrome among patients in whom paroxetine is added to ongoing lithium treatment.
Journal of Clinical Psychopharmacology 11/2001; 21(5):474-8. · 4.10 Impact Factor
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ABSTRACT: Neuroendocrinologic investigations in bipolar disorder have suggested abnormalities in pituitary function. However, few imaging studies have evaluated possible anatomical differences in this brain structure in mood disorder patients. Our aim was to examine potential abnormalities in pituitary volume in patients with bipolar and in a comparison group of patients with unipolar disorder.
We measured the volumes of the pituitary gland in 23 patients with bipolar disorder (mean +/- s.d. = 34.3 +/- 9.9 years) and 13 patients with unipolar disorder (41.2 +/- 9.6 years), and 34 healthy control subjects (36.6 +/- 9.6 years) using 1.5 mm thick T1-weighted coronal 1.5 T MRI images. All measurements were done blindly by a trained rater.
Patients with bipolar disorder had significantly smaller pituitary volumes than healthy control subjects (mean volume +/- s.d. = 0.55 +/- 0.15 ml and 0.68 +/- 0.20 ml, respectively; ANCOVA, F = 8.66, p = 0.005), and than patients with unipolar disorder (0.70 +/- 0.12 ml, F = 5.98, p = 0.02). No differences were found between patients with unipolar disorder and healthy control subjects (F = 0.01, p = 0.91).
To our knowledge, this is the first study that reports smaller pituitary volumes in bipolar disorder. Our findings suggest that detectable abnormalities in pituitary size are present in patients with bipolar disorder, which may reflect a dysfunctional HPA axis.
Biological Psychiatry 09/2001; 50(4):271-80. · 8.28 Impact Factor
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ABSTRACT: This study examined quantitative measures of sleep electroencephalogram (EEG) and phasic rapid eye movements (REM) as correlates of remission and recovery in depressed patients. To address correlates of remission, pre-treatment EEG sleep studies were examined in 130 women outpatients with major depressive disorder treated with interpersonal psychotherapy (IPT). To address correlates of recovery, baseline and post-treatment EEG sleep studies were examined in 23 women who recovered with IPT alone and 23 women who recovered with IPT+fluoxetine. Outcomes included EEG power spectra during non-rapid eye movement (NREM) sleep and REM sleep and quantitative REMs. IPT non-remitters had increased phasic REM compared with remitters, but no significant differences in EEG power spectra. IPT+fluoxetine recoverers, but not IPT recoverers, showed increases in phasic REM and REM percentage from baseline to recovery. In NREM sleep, the IPT+fluoxetine group showed a decrease in alpha power from baseline to recovery, while the IPT group showed a slight increase. The number of REMs was a more robust correlate of remission and recovery than modeled quantitative EEG spectra during NREM or REM sleep. Quantitative REMs may provide a more direct measure of brainstem function and dysfunction during REM sleep than quantitative sleep EEG measures.
Psychiatry Research 09/2001; 103(1):51-67. · 2.52 Impact Factor
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ABSTRACT: Although active maintenance treatments appear superior to placebo in preventing depression recurrence in older adults, few data are available to guide maintenance modality selection to maximize the probability of continued wellness for a given patient. Patients' temporal patterns of acute treatment response may predict who requires which maintenance therapy to remain well.
Depression levels were observed over 16 weeks of combined nortriptyline (NT) and interpersonal psychotherapy (IPT) in 140 persons aged >or=60 years with recurrent major depression. Subjects were empirically classified into four groups: rapid, sustained responders; delayed, sustained responders; mixed responders without sustained improvement; prolonged nonresponders. Groups were compared on subsequent recovery rates and on time to depression recurrence after randomization to 3 years of combined maintenance therapy (monthly IPT with NT), monotherapy (either IPT or NT alone), or medication clinic with placebo. Pretreatment psychosocial and clinical variables were controlled.
Initial response profile predicted ultimate recovery rates, as well as who remained well, given the maintenance treatment received. Rapid initial responders showed lower recurrence risk with either combined or monotherapy, relative to placebo. Specific types of monotherapy appeared equally effective in rapid responders. In initially mixed responders, only combined therapy was superior to placebo. It was marginally superior to monotherapy. For delayed responders, combined therapy was superior to placebo; monotherapy did not differ from the other maintenance conditions. Prolonged nonresponders did not benefit from maintenance treatment.
Subjects had only recurrent, unipolar depression. Initial response profile groups were established empirically and require replication. Sample sizes in initial response profile by maintenance treatment cells were small.
The ability to match patients to maintenance treatments more likely to prevent recurrence may be enhanced by considering the temporal profile of initial response to acute treatment.
Journal of Affective Disorders 08/2001; 65(2):155-66. · 3.52 Impact Factor
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ABSTRACT: There is increasing interest on the part of investigators and the public at large in finding ways to study and improve treatments for the seriously mentally ill without exposing such individuals to unnecessary risks. One group of particular interest in this regard are patients suffering from acute mania. We set out to define "exit" criteria or novel clinical endpoints that might help to assess the efficacy of antimanic compounds. We sought a method that would be safer, more economical, and less sensitive to nonspecific factors in the clinical environment while still allowing unambiguous assessment of efficacy.
From a pool of subjects being screened for or already participating in intervention studies, we retrospectively identified 76 admissions of patients with a manic or mixed episode according to DSM-IV. We fit a mixed-effects regression model to all available data obtained using the Bech-Rafaelsen Mania Scale from admission to day 28 of treatment. Using the estimated model coefficients, we obtained empirical Bayes (EB) estimates of each subject's trend coefficients based on (1) all available data and (2) data through day 11 of treatment for mania.
We found a high correlation (r = .67) between EB estimates of final response at day 28 and actual day 28 scores on the Bech-Rafaelsen scale based on scores through day 11. When subjects were categorized as full, partial, or nonresponders according to their final Bech-Rafaelsen score, we were able to show that only 2 of the 23 predicted nonresponders became full responders, 27 of the 31 predicted full responders became full responders, and 16 of the 22 predicted partial responders became partial or full responders.
We conclude on the basis of this chart review study that it should be possible to define exit criteria for trials assessing the efficacy of antimanic compounds on the basis of relatively short duration exposure to experimental treatment.
The Journal of Clinical Psychiatry 07/2001; 62(6):421-5. · 5.80 Impact Factor
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ABSTRACT: The effects of age and gender on sleep EEG power spectral density were assessed in a group of 100 subjects aged 20 to 60 years. We propose a new statistical strategy (mixed-model using fixed-knot regression splines) to analyze quantitative EEG measures. The effect of gender varied according to frequency, but no interactions emerged between age and gender, suggesting that the aging process does not differentially influence men and women. Women had higher power density than men in delta, theta, low alpha, and high spindle frequency range. The effect of age varied according to frequency and across the night. The decrease in power with age was not restricted to slow-wave activity, but also included theta and sigma activity. With increasing age, the attenuation over the night in power density between 1.25 and 8.00 Hz diminished, and the rise in power between 12.25 and 14.00 Hz across the night decreased. Increasing age was associated with higher power in the beta range. These results suggest that increasing age may be related to an attenuation of homeostatic sleep pressure and to an increase in cortical activation during sleep.
Psychophysiology 04/2001; 38(2):232-42. · 3.29 Impact Factor
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ABSTRACT: This study examined possible anatomical abnormalities in basal ganglia structures in bipolar disorder patients. Caudate and putamen gray matter volumes, and globus pallidus total volume were measured with magnetic resonance imaging (MRI) in 22 DSM-IV bipolar patients (age+/-S.D.=36+/-10 years; eight drug-free and 14 lithium monotherapy patients) and 22 matched healthy control subjects (age+/-S.D.=38+/-10 years). No significant differences were found between bipolar patients and healthy control subjects for any of the basal ganglia measures (t-tests, P>0.05). Age was inversely correlated with left putamen volumes in patients (R=-0.44, P=0.04), but not in healthy control subjects (R=-0.33, P=0.14). Older patients (>36 years old) had a significantly larger left globus pallidus than younger ones (< or =36 years old) (ANOVA, P=0.01). In a multiple regression analysis, after entering age as independent variable, the length of illness predicted smaller left putamen volumes, explaining 10.4% of the variance (F=4.07, d.f.=2, P=0.03). No significant effects of episode type, number of prior episodes, or gender were found in any basal ganglia measurements (ANOVA, P>0.05). In conclusion, our findings indicate that the basal ganglia may be anatomically preserved in bipolar patients. This is in contrast to available findings for unipolar disorder. However, our findings also suggest that age and length of illness may have significant effects on basal ganglia structures in bipolar patients, which may be more pronounced among bipolar I patients, and of relevance for the pathophysiology of the disorder.
Psychiatry Research 04/2001; 106(2):65-80. · 2.52 Impact Factor
