Thursday, June 12, 2003
"Concurrent Rapid Communications Sessions"
Session A - Chair: Samuel Gershon, M.D.
Bibliography
Familial Relationship Between Bipolar Disorder Alcohol and Heroin
Dependence
Video | Audio
(Length: 22 min.)
M. Preisig1,
F. Ferrero2
1Psychiatric University Department, Lausanne,
Switzerland,
2University
Hospital, Department of Psychiatry, Geneva, Switzerland
Background: Clinical and epidemiological studies have consistently
revealed an association between bipolar disorders and both alcohol and heroin
dependence. However, the evidence regarding the nature of these associations is
unclear.
Methods: The familial patterns of alcohol and affective disorders were
examined using data from a study of 118 treated bipolar-I, 32 alcohol and 33
heroin dependent probands as well as 88 normal controls recruited in orthopedic
departments. These probands had 1073 first degree relatives. Probands and all
available first-degree relatives who agreed to participate were assessed using
the Diagnostic Interview for Genetic Studies (DIGS).
Results: The major findings are that 1) bipolar-I disorder was associated
with alcohol (OR = 2.1) and heroin dependence (OR = 6.0) in the relatives; 2)
there was a strong degree of familial aggregation of bipolar-I disorder (OR =
7.1), alcohol (OR = 2.3) and heroin dependence (OR = 4.0); 3) there was evidence
of cross-aggregation between bipolar-I disorder and alcohol dependence (i.e.,
increased risk of alcohol dependence among relatives of probands with bipolar
disorder without alcohol dependence, but not the converse); 4) there was no
evidence of cross-aggregation between bipolar-I disorder and heroin dependence.
Conclusion: Our data suggest different mechanisms underlying the
associations between bipolar-I disorder and alcohol dependence and bipolar
disorder and heroin dependence. The independent familial aggregation of bipolar
disorder and heroin dependence and the finding that the onset of bipolar
disorder tended to precede that of heroin dependence are compatible with a
self-medication hypothesis as the explanation for the frequent co-occurrence of
these disorders. In contrast, the finding of cross- aggregation between
bipolar-I disorder and alcohol dependence could be either an artifact and result
from undetected bipolar disorder in alcoholic probands or indicate shared
etiological factors between bipolar-I disorder and alcohol dependence.
An fMRI Study of Altered Load-Response Characteristics During Verbal Working
Memory Task Performance in Euthymic Bipolar I Disorder
Video
| Audio
(Length: 24 min.)
P.J. Monks1, J.M. Thompson2,
N. Giles1,
J. Suckling3,
E.T. Bullmore3,
M.J. Brammer1,
S.C.R. Williams1,
A. Simmons1,
R.M. Murray1,
I.N. Ferrier2,
A.H. Young2,
V.A. Curtis1
1Division of
Psychological Medicine, Institute of Psychiatry, London,
2Stanley Bipolar
Research Foundation, Psychiatry Department, Newcastle University,
3Department
of Psychiatry, University of Cambridge School of Clinical Medicine, Addenbrookes
Hospital, Cambridge, UK
Introduction: We used fMRI to investigate load-dependent neural
network engagement during executive and mnemonic function in Bipolar Disorder.
Methods: 12 euthymic dextral male Bipolar I subjects receiving Lithium
monotherapy were matched with 12 controls. We utilized a “Sternberg” task with a
parametric design incorporating variable working memory load, and a “two-back”
task contrasting a single memory load with a baseline recognition condition.
Data were fitted to haemodynamic response models convolved with experimental
design: Two-back, active-versus-baseline contrast and, Sternberg, overall
activation versus baseline. Group difference maps were produced for each of
these pairs of group maps by ANOVA. 4 regions of interest were identified in the
Sternberg group-difference map and load-response (LR) curves were plotted for
activation data at each.
Results: No significant group-differences in accuracy or response time
were observed. In the Two-back experiment, the Bipolar subjects were hypofrontal
compared with Controls. During the Sternberg task both groups engaged similar
fronto-temporal networks. There was greater activation (p=0.05): for Bipolars at
right cerebellar, caudate, occipital, superior frontal and left insular,
hippocampal and paracentral loci; for Controls at right cerebellar, temporal,
lingual, medial frontal, parietal, precentral and left putamen, anterior
cingulate, lateral frontal and bilateral hippocampal loci. Both groups showed
negative LR relationships at right medial frontal gyrus and left temporo-occipital
junction. Within right caudate nucleus and right hippocampus, the groups showed
different LR relationships. In Bipolars, it was positive (increasing recruitment
with increasing load) whilst in controls it was negative.
Discussion: We have demonstrated differing neural network activation in
Bipolar and Control subjects performing verbal working memory tasks. The Bipolar
group shows evidence of both hypofrontality and increasing recruitment with load
of right caudate and hippocampus. This may represent enhanced recruitment of
normally functioning regions to compensate for abnormalities elsewhere or
abnormal function of these specific regions.
Keywords: functional MRI, working memory, frontal lobe function.
Changes in Brain Activation in Bipolar Patients with Increasing Number of
Depressive Episodes
Video | Audio
(Length: 26 min.)
C.M. Adler, S.M. Strakowski
University of Cincinnati College of Medicine, Cincinnati, OH, USA
Background: We have previously found that bipolar patients demonstrate
significant deficits in working memory, an aspect of short-term memory essential
to function, in comparison with healthy volunteers. These deficits are
accompanied by patterns of increased neuronal activation within the working
memory “network.” Functional deficits may reflect the neuropathologic
consequences of repeated episodes of affective symptomatology. We followed up
our previous findings by utilizing functional magnetic resonance imaging (fMRI)
to examine changes in neuronal activation with increasing number of affective
episodes in bipolar patients.
Methods: Bipolar patients performed “zero-back” and “two-back” tasks in a
boxcar design during fMRI scanning; the “zero-back” served as contrast condition
for the “two-back” task. All scans were normalized to Talairach space.
Voxel-by-voxel Spearman correlation coefficients were calculated between changes
in blood flow and history of affective symptomatology. Cluster analysis
technique was employed to control for Type I error. In a secondary analysis,
individual voxel t-statistics were averaged across regions-of-interest (ROIs)
within the medial temporal cortex, and mean Spearman correlation coefficients
determined. Cognitive data were analyzed by discriminability and correlation
coefficients determined between performance and affective history.
Results: Working memory performance inversely correlated to number of
depressive episodes. On voxel-by-voxel analysis, patients demonstrated increased
activation of anterior cingulate with increased number of affective episodes. In
addition, ROI analysis demonstrated decreased left hippocampal activation with
increased occurrence of depression.
Conclusions: These data are consistent with suggestions that depressive
episodes in bipolar patients are associated with decrements in cognition.
Activation changes may reflect underlying neuropathology leading to cognitive
decline. Hippocampus has been demonstrated to be acutely sensitive to a variety
of stimuli, including increased stress-related hormones. The anterior cingulate
has been observed to act as a mediating element in cognitive networks and
increased activation may represent efforts to compensate for decrements in
performance elsewhere in the working memory network.
Keywords: bipolar disorder, depression, fMRI.
Session B - Chair: Lauren Marangell, M.D.
Bibliography
Effectiveness of a Population-Based Care Management Program for People
with Bipolar Disorder
Video | Audio
(Length: 15 min.)
G.E. Simon, E.J. Ludman, J. Unutzer, M.S. Bauer, C. Rutter, B.
Operskalski
Center for Health Studies, Group Health Cooperative, Seattle, WA, USA
Background: Care of bipolar disorder in everyday practice often falls
short of that proven efficacious in clinical trials.
Objective: Evaluate the effectiveness of a multi-component care
management program for bipolar disorder based on the chronic care model of by
Wagner and Von Korff.
Design: Randomized control trial with concealed assignment and blinded
outcome assessment.
Setting: 4 Behavioral health clinics of group-model managed care
organization during 1999 to 2001.
Patients: A population-based sample of 441 patients treated for bipolar
disorder during the prior year. Willingness to accept treatment was not
required.
Intervention: Participants were randomly assigned to continued usual care
or a systematic care management program including: initial assessment and care
planning, monthly telephone monitoring including structured assessment of
symptoms and medication use, feedback to and coordination with the mental health
treatment team, and a structured group psychoeducational program (Bauer and
McBride’s Life Goals Program) – all provided by a dedicated nurse care manager.
Main Outcome Measures: Weekly ratings of severity of depression and mania
symptoms using the Longitudinal Interval Follow-Up Evaluation.
Results: Of those randomized to the intervention, 95% participated in
telephone monitoring and 65% in the psychoeducational group. Based on intent to
treat, intervention patients had significantly lower mean mania ratings averaged
across the 12-month follow-up period (Z=2.44, p=.015) and approximately
one-third less time in full hypomanic or manic episode (2.59 weeks vs. 1.69
weeks, p=). Mean depression ratings over 12 months did not differ significantly
between groups, but intervention participants showed a greater decline in
depression over time (Z statistic for group-by-time interaction = 1.98, p=.048).
Conclusions: A systematic care program proved feasible and well-accepted
in a population-based sample. Compared to usual care, the program significantly
reduced risk of mania over 12 months. Preliminary results suggest a growing
effect on depression over time, but longer follow-up will be needed.
Keywords: randomized trial, group psychotherapy, care management.
Efficacy and Acceptability of Valproate in Acute Mania
Video |
Audio
(Length: 17 min.)
J.R. Geddes, K. Macritchie
University of Oxford, Warneford Hospital, Oxford, UK
Objectives: To determine the efficacy and acceptability of valproate
in the treatment of acute episodes of bipolar disorder.
Design: Systematic review and meta-analysis of randomized controlled
trials.
Search strategy: The search included the Cochrane Collaboration
Depression, Anxiety and Neurosis Controlled Trials Registrar (CCDANCTR), the
Cochrane Controlled Clinical Trials Register (CCTR), reference lists of relevant
papers and books, and contact with authors of trials, experts and pharmaceutical
companies.
Results: Ten randomized controlled trials were found comparing valproate
with other interventions in mania. None was found examining its use in
depression or mixed affective episodes. Valproate was more efficacious than
placebo (RRR 38%; RR 0.62; 95% C.I. 0.51 to 0.77) in the treatment of mania.
There was no significant difference between valproate and lithium (RRI 5%; RR
1.05; 95% C.I. 0.74-1.50) or between valproate and carbamazepine (RRR 34%; RR
0.66; 95% C.I. 0.38 to 1.16). Valproate was less effective than olanzapine
(failure to achieve clinical response; RRI 25%; RR 1.25, 95% C.I. 1.01 to 1.54;
average of 2.8 point less change on the Mania Rating Scale (95% CI 0.83 to
4.79). There were no significant differences in acceptability as measured by
total number of subjects withdrawing from the study. There were significant
differences in the side effect profiles of valproate and olanzapine, with more
sedation and weight gain on olanzapine.
Conclusions: There is consistent, if limited, evidence to suggest that
valproate is an efficacious treatment for acute mania. Valproate appears to be
less effective than olanzapine but may cause less sedation and weight gain. More
well designed, randomized controlled trials investigating the relative efficacy
and acceptability of valproate in the treatment of the full range of acute
affective episodes occurring in bipolar disorder are required.
Keywords: valproate, bipolar disorder, mania.
Divalproex Sodium verses Lithium Carbonate in the Treatment of Children and
Adolescents with Bipolar Disorder
Video |
Audio
(Length: 23 min.)
R.L. Findling, J.R. Calabrese, E.A. Youngstrom
University Hospitals of Cleveland/Case Western Reserve University, Cleveland,
OH, USA
Introduction: The primary objective of this study was to compare lithium
(Li+) and divalproex (DVPX) monotherapy as a maintenance treatment for
clinically stable children and adolescents.
Methods: Medically healthy youths ages 5-17 years with a lifetime history
of BP-I or BP- II were eligible to participate. Those that achieved syndromal
remission for four consecutive weeks with combination Li+ and DVPX
treatment were then eligible for study randomization. Subjects were randomized
to receive up to 76 weeks of Li+
or DVPX monotherapy treatment in a double-blind fashion. Serum blood levels were
maintained at therapeutic levels by an unblinded medical monitor. Survival
analyses examined differences in time to discontinuation due to a mood event and
discontinuation for any reason. Cox regression examined predictors of length of
survival time in the study.
Results: Sixty youths (39 males, 21 females) with an average age of 10.7
(3.6) years were randomized to receive either Li+
(n=30) or DVPX (n=30). The treatment groups did not differ in terms of survival
time until a mood event: Li+
median 112 days, S.E.+ 67.0 days versus DVPX median 84 days, S.E.+
58.6 days; Log Rank (1 df) = 0.33, p = 0.563. Also, median survival times until
discontinuation for any reason did not differ between Li+
(83 days, S.E.+ 41.0 days) and DVPX (56 days, S.E.+ 13.9 days);
Log Rank (1 df) = 0.28, p = 0.597. Post hoc analyses found that youths with the
rapid cycling form of bipolarity obtained more sustained treatment response with
lithium.
Conclusions: Overall, Li+
and DVPX appear to have similar efficacy as monotherapy for maintenance
treatment of children and adolescents with bipolar disorder. For young patients
with rapid cycling, it appears lithium may be a superior maintenance therapy.
Keywords: children, adolescents, treatment.
A Case Control Study in the Use of Telemedicine for
Treatment Adherence and Improved Outcomes in Remote and Rural Patients with
Bipolar Disorder
Video |
Audio
(Length: 31 min.)
R. Dsouza, D. Rich
Mental Health Research Institute, Box Hill Hospital, Melbourne, Australia
Objectives: To study retrospectively the outcomes of remote and rural
patients with a bipolar disorder admitted to a tertiary psychiatric center.
Patients and significant other received continuing discharge planning and CERRPM
Model of Psycho-education (Illness Management Skills Enhancement Programme)
through telemedicine were compared with the outcomes of a matched sample of
patients from the unit, who were discharged using conventional discharge
summaries to their primary care physician.
Method: 20 rural inpatients who had received Telemedicine for discharge
plans, continuing care and follow up over a 12 month period (TMG) and 21 rural
inpatients who had discharge summaries sent to their primary care physician with
ongoing care from the primary care physician (CG) were selected after matching
for age, sex and axis I diagnosis. A questionnaire, which studied 1.
Satisfaction with the medication prescribed 2. Adverse affects of medication 3.
Compliance with treatment. 4. Satisfaction with their case managers 5.
Satisfaction with psychiatric management. 6. Rehospitalization data case records
were studied. Case managers were consulted.
Results: Response rate higher with TM group. (TMG 90% CG 70%)
Significantly higher scores with the TMG in areas of satisfaction with
medication and case managers. TMG had higher compliance with treatment and
significantly lower side effects with medication prescribed. TMG had
significantly lower rehospitalization than CG. Thus better outcomes and quality
of life. Both groups were satisfied with their diagnosis and treatment at the
tertiary center.
Conclusion: This model of use of Telemedicine for remote and rural
patients with bipolar disorder can enhance treatment adherence and improve
outcomes. Telemedicine established and maintained therapeutic alliance with the
rural case managers. Over all there were improved longitudinal outcomes, thus
resulting in improved quality of life and a significant positive impact on the
health economics for the service and the bipolar patient.
Keywords: telemedicine, bipolar disorder, treatment adherence.
Top of Page
|
