Rapid Communications
Bipolar Rapid Cycling: Focus on Depression as its Hallmark
JR Calabrese, MD Shelton, Case Western Reserve University School of
Medicine, Cleveland, U.S.A.
The phenomenon of frequent cycling in bipolar disorder was first recognized by
Emil Kraepelin in 1913. More recently, rapid cycling has been reported to be a
predictor of non-response to treatment. At the time of presentation, most
patients with rapid cycling appear to present in the depressed phase of their
illness. Frequent and more severe episodes of depression appear to be the
hallmark of rapid cycling. Reported here are recent preliminary data (n = 233)
suggesting that combination of lithium and divalproex administered continuously
over six months appears to result in marked acute and continuation antimanic
efficacy in 85% of patients, but marked antidepressant efficacy in only 60%.
However, only one-half of patients experience bimodal stabilization. Comorbid
alcohol/drug abuse did not appear to directly affect the spectrum of efficacy of
lithium and divalproex or response rates in compliant patients. Comorbidity
appeared to alter prognosis by increasing the prevalence of poor compliance. The
majority of patients on lithium and divalproex that required additional
treatment were depressed, suggesting that the frequent recurrence of depression
is the primary unmet need in patients with rapid cycling. The use of
antidepressants in this population has been discouraged because of concerns over
the possibility of cycle acceleration. There exists a need for a pharmacotherapy
that not only possesses marked acute antidepressant properties, but one that
does so without causing cycle acceleration. To explore the efficacy of
lamotrigine, a recent rapid cycling multicenter study (n=182) has examined
lamotrigine as a maintenance therapy for this population and will be summarized.
Key words: rapid cycling, depression, prophylaxis.
Reference
Calabrese JR, Suppes T, Bowden CL et al : A double-blind,
placebo-controlled, prophylaxis study of lamotrigine in rapid cycling bipolar
disorder. J Clin Psychiatry. 2000;61:841-850.
Cognitive Therapy for
Bipolar Affective Disorder – A Randomised Controlled Study
D. Lam, E. Watkins, P. Hayward, J Bright, P. Sham
Institute of Psychiatry, London, U.K.
One hundred and three patients suffering from
bipolar 1 affective disorder were recruited in a randomised controlled trial of
cognitive therapy (CT) specifically designed for bipolar affective disorder. The
study targeted bipolar patients who are vulnerable to relapses. They had to have
had at least two episodes in the last three years or three episodes in the last
five years despite the prescription of mood stabilisers. All subjects had to be
taking a mood stabiliser on recruitment. The control group received minimal
psychiatric input, i.e. mood stabilisers and outpatients follow-up. The therapy
group received up to twenty sessions of CT plus minimal psychiatric input. There
were no significant differences between the two groups in terms of demographics
or the number of previous bipolar episodes. At the end of therapy, intention to
treat analysis revealed that the therapy group had significantly fewer bipolar
episodes, number of days when subjects were in bipolar episodes and better
medication compliance. Moreover, subjects in the therapy group had fewer
episodes of bipolar depression and number of days hospitalised. The therapy
group also had significantly less fluctuation according to the Activation
subscale of the Internal State Scale that subjects returned monthly. The therapy
group had significantly reduction in BDI scores over the six months. When the
therapy dropouts (fewer than six sessions) were excluded, the therapy group also
had significantly fewer hospital admissions and fewer hypomanic episodes. This
study replicated our earlier pilot study.
Key words: cognitive therapy, bipolar illness, outcome.
ICD-10 versus DSM-IV Diagnostic Criteria for Bipolar Mania:
A Clinical Comparison
R.W. Licht; M. Bysted; H. Christensen; P.Vestergaard, Mood Disorders
Research Unit, Aarhus University Psychiatric Hospital, Risskov, Denmark.
Introduction: The diagnostic criteria for bipolar mania according to the
DSM-IV is well established although not fully validated. In the ICD-10 criteria
for research, the algorithm for the diagnosis of mania is the same as in the
DSM-IV regarding duration of illness and requirements to mood change and to the
number of additional manic symptoms. However, the total number of additional
manic symptoms (items) is different in the 2 systems, i.e. 9 in the ICD-10 as
compared with 7 in the DSM-IV, and furthermore, a few of the symptoms differ
across the 2 systems. The present study compared the 2 sets of items in
consecutively admitted manic patients. Methods: By clinical interviews
based on the Present State Examination, 42 patients (20 men and 22 women) with
mean age (SD) of 43.4 (10.7) years fulfilling either the DSM-IV or the ICD-10
criteria for bipolar mania were identified and the presence or absence of each
symptom from the 2 systems was recorded. The patients were also rated with the
Bech-Rafaelsen Mania Rating Scale (MAS). The frequencies and patterns of manic
symptoms were analyzed. Results: Only one patient fulfilled one set of
criteria (ICD-10) without fulfilling the other (DSM-IV). The mean MAS score was
20.5 (6.1). Based on the analyses, it is suggested that a future revision of
the ICD-10 and the DSM-IV should converge toward an identical set of manic
items. A modified shared version based on the DSM-IV criteria with the addition
of item 4 from the ICD-10, covering loss of social inhibitions, will seemingly
improve the content validity. The number of positive items according to this
proposed modified set of items was positively correlated to the MAS score
(P<0.01).
Key words: bipolar disorder, classification, validation.
Using fMRI to Study Euthymic Bipolar Patients:
Investigating Word Generation
PJ Monks1, JM Thompson2, AJ Lloyd2, CL Harrison2, ET Bullmore1, MJ
Brammer1, SCR Williams1, A Simmons1, RM Murray1, IN Ferrier2, AH Young2, VA
Curtis1.
1Division of Psychological Medicine, Institute of Psychiatry, London, England.
2Stanley Bipolar Research Foundation, Department of Psychiatry, University of
Newcastle
Introduction: Functional imaging studies in bipolar disorder have shown
inconsistent patterns of frontal lobe response during word generation tasks
which could be explained by confounding effects of psychopathology, medication
and task demands. Using fMRI we explored the cerebral responses to 6 overlapping
cognitive activation tasks: Repetition (baseline condition), Word form analysis,
Phonetic and Semantic Categorization, Phonetic (PVF) and Semantic Verbal Fluency
(SVF). We present preliminary data from the verbal fluency tasks.
Methods: Four dextral male bipolar subjects and 4 dextral controls matched
for demographic variables and premorbid I.Q. (NART) were recruited. Established
tools for rating psychopathology were administered. All bipolar subjects were
prospectively euthymic (including normal salivary cortisol) and either
unmedicated (n=1) or receiving Lithium monotherapy. Images were acquired on a
1.5T GE system using a sparse T2* BOLD sequence (16 slices, TR 6000ms). Visual
stimuli were presented every 6 seconds and subjects articulated responses during
scanner silence. Data analysis comprised motion correction, coregistration with
a structural image, regression to a model of haemodynamic response and
non-parametric hypothesis testing of each VF condition versus baseline, then
transformation to standard (Talairach) space. Generic activation maps were
generated for each group from the median magnitudes of activation at each voxel.
Between–group differences were tested using ANOVA. Results:
Compared with controls, bipolar subjects showed robust frontal activations
during PVF with reductions in both temporal and midline responses. During SVF
bipolar subjects’ frontal activation was accompanied by greater response in the
left superior temporal and supramarginal gyri and reduced amplitude of midline
response. Discussion: These studies emphasise the intimate
relationship between precise task demands and cerebral response. Small sample
size limits interpretation but the data suggest that even in euthymia different
patterns of cerebral activation persist in bipolar subjects which may serve as
markers for neuropsychological deficits. Patient studies continue.
Key words: verbal fluency, functional MRI, eutkymia.
Acute Tryptophan Depletion in First-Degree Relatives of
Bipolar Patients: Effects on Mood, Cognition and Cortisol Release
S.Sobczak, W.J. Riedel, A.H. Honig, M. Maes, Experimental
Psychopharmacology Unit, Brain & Behaviour Institute, European Graduate School
of Neuroscience (EURON), University Hospital Maastricht, The Netherlands
Acute Tryptophan Depletion (ATD) has become a popular paradigm to investigate
the involvement of serotonin in mood, psychopathology and cognition. ATD induces
a transient decrease of central serotonergic turnover by depleting the
availability of the serotonergic precursor, tryptophan (TRP). These effects will
occur after consuming an amino acid (AA) mixture, rich in large neutral amino
acids (LNAAs) but deficient in TRP. The effects of ATD are maximal 5-7 hours
after consumption.
Forty-five physically and mentally healthy subjects (aged 19-63 yr; mean
41, SD 14) were included, 30 subjects had a first-degree relative with bipolar
disorder (FH+ group) and 15 subjects had no psychiatric family history (FH-
group). Thirty-three subjects were female and all were tested in the follicular
phase of their menstrual cycle. The treatment consisted of a 75g amino acid
mixture with or without TRP. All subjects received TRP depletion and placebo
depletion according to a double blind, order-balanced cross-over design.
Cognitive performance was assessed with respect to memory (Visual Verbal
Learning Task, VVLT; Picture Learning Task, PLT; Memory Scanning Task, MST),
attention (Stroop Color Word Task, SCWT; Dichotic Listening Task, DLT). Mood was
assessed using a bimodal profile of Mood States (POMS). Mood and cognitive
performance were assessed before and 5 and 7 hours after ATD. Beside, cortisol
samples in saliva were taken, at baseline, 5 hours after ATD and subsequently
after a stress-inducing paradigm, the Stress Inducing Speaking Task (SIST). The
VVLT and POMS measurements were repeated after the SIST.
The results showed that ATD significantly impaired delayed recall
performance on the VVLT and PLT, independent of family history. No significant
effects were found on attentional capacity. ATD decreased cortisol release only
in subjects vulnerable for bipolar disorder. The decrease in cortisol was
independent of stress-induced cortisol release. There were no differences in
mood changes following ATD between subjects in the FH+ group and FH- group. But
adding Type bipolar disorder (type I or type II) as a between subjects’ factor,
reveilled a significant increase in mood only in relatives of patients having a
type II bipolar disorder diagnosis. This is the first tryptophan depletion study
in first-degree relatives of bipolar patients. The results demonstrated an ATD
induced lowering of cortisol secretion, in subjects vulnerable for bipolar
disorder. A mood response in relatives of type II bipolar patients only reflects
a postulated serotonergic vulnerability in this group. Furthermore, the results
confirm and extend earlier findings implicating serotonin in memory
consolidation, independent of family history. These results taken in combination
are indicative of serotonins’ influence on cognition at the level of the
temporal cortex.
Key words: first-degree relatives of bipolar patients, acute
tryptaphan depletion, mood, cortisol, cognition.
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