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RESÚMENES JUNIO 2004 |
Mood - Anxiety Disorders & Antidepressants – Mood Stabilizers
Neuropsychological Dysfunction in Antipsychotic-Naive First-Episode Unipolar Psychotic Depression
S. Kristian Hill, Matcheri S. Keshavan, Michael E. Thase,
and John A. Sweeney
Am J Psychiatry 161:996-1003, June 2004
OBJECTIVE: The
profile of neuropsychological impairment associated with unipolar
psychotic depression remains unclear. The authors used a
neuropsychological test battery to characterize the neuropsychiatric profile
of patients with unipolar psychotic depression, relative to that of
patients with nonpsychotic unipolar depression, patients with
schizophrenia, and healthy comparison subjects. METHOD: Study
subjects included antipsychotic-naive patients with a first episode
of psychotic unipolar depression (N=20), antipsychotic-naive and unmedicated
patients with nonpsychotic unipolar depression (N=14),
antipsychotic-naive patients with first-episode schizophrenia (N=86),
and healthy volunteers (N=81). Groups were matched on age, sex,
race, education, parental socioeconomic status, and estimated
premorbid intelligence. Psychotic patients were followed clinically
for 2 years to confirm diagnosis. All participants completed a
standard neuropsychological battery, including tests of general
intelligence, executive function, attention, verbal memory, motor
skills, and visual-spatial perception. RESULTS: Patients with
psychotic depression had a pattern of neuropsychological dysfunction
that was similar to but less severe than that of patients with
schizophrenia. In contrast, patients with nonpsychotic unipolar
depression had a neuropsychological profile that was similar to that
of healthy individuals but that included mild dysfunction on tests
of attention. Neuropsychological test performance was generally
independent of acute clinical symptoms, but some pairwise group
differences were attenuated by covariation for symptom severity.
CONCLUSIONS: The similar neuropsychological profiles for
schizophrenia and psychotic depression suggest that these psychotic
disorders may have common pathophysiological features. The dramatic
differences in performance between the patients with psychotic
depression and those with nonpsychotic depression point to a marked
distinction in neurocognitive function associated with the
expression of psychosis in depressed patients.
Brain Structural Abnormalities in Psychotropic Drug-Naive Pediatric Patients With Obsessive-Compulsive Disorder
Philip R. Szeszko, Shauna MacMillan, Marjorie McMeniman,
Steven Chen, Keith Baribault, Kelvin O. Lim, Jennifer Ivey, Michelle Rose, S. Preeya
Banerjee, Rashmi Bhandari, Gregory J. Moore, and David R. Rosenberg
Am J Psychiatry 161:1049-1056, June 2004
OBJECTIVE: The
authors investigated structural abnormalities in brain regions
comprising cortical-striatal-thalamic-cortical loops in pediatric
patients with obsessive-compulsive disorder (OCD). METHOD: Volumes
of the caudate nucleus, putamen, and globus pallidus and gray and
white matter volumes of the anterior cingulate gyrus and superior
frontal gyrus were computed from contiguous 1.5-mm magnetic
resonance images from 23 psychotropic drug-naive pediatric patients
with OCD (seven male patients and 16 female patients) and 27 healthy
volunteers (12 male subjects and 15 female subjects). RESULTS:
Patients had smaller globus pallidus volumes than healthy
volunteers, but the two groups did not differ in volumes of the
caudate nucleus, putamen, or frontal white matter regions. Compared
to healthy volunteers, patients had more total gray matter in the
anterior cingulate gyrus but not the superior frontal gyrus. Total
anterior cingulate gyrus volume correlated significantly and
positively with globus pallidus volume in the healthy volunteers but
not in patients. CONCLUSIONS: These findings provide evidence of
smaller globus pallidus volume in patients with OCD without the
potentially confounding effects of prior psychotropic drug exposure.
Volumetric abnormalities in the anterior cingulate gyrus appear
specific to the gray matter in OCD, at least at the gross anatomic
level, and are consistent with findings of functional neuroimaging
studies that have reported anterior cingulate hypermetabolism in
the disorder.
Rapid Antimanic Effect of Risperidone Monotherapy: A 3-Week Multicenter, Double-Blind, Placebo-Controlled Trial
Robert M.A. Hirschfeld, Paul E. Keck, Jr., Michelle Kramer,
Keith Karcher, Carla Canuso, Marielle Eerdekens, and Fred Grossman
Am J Psychiatry 161:1057-1065, June 2004
OBJECTIVE: This
study evaluated the efficacy and safety of risperidone monotherapy
in the treatment of acute bipolar mania. METHOD: Patients with
DSM-IV bipolar I disorder experiencing an acute manic episode
(baseline Young Mania Rating Scale score 
20)
were randomly assigned to 3 weeks of treatment with risperidone (flexible
dose: 1–6 mg/day) or placebo. The primary efficacy measure was the
mean baseline-to-endpoint change in total score on the Young Mania
Rating Scale. Secondary efficacy measures included the Clinical
Global Impression (CGI) severity rating and scores on the
Montgomery-Åsberg Depression Rating Scale, Positive and Negative
Syndrome Scale, and Global Assessment Scale (GAS). Safety
assessments consisted of monitoring adverse events, vital signs,
electrocardiogram and laboratory results, and scores on the
Extrapyramidal Symptom Rating Scale. RESULTS: Subjects (N=259)
received treatment with either risperidone (N=134) or placebo
(N=125). The mean modal dose of risperidone was 4.1 mg/day.
Improvement in mean Young Mania Rating Scale total score (adjusted
for covariates) was significantly greater in the risperidone than in
the placebo group at endpoint (mean change=–10.6 [SD=9.5] versus
–4.8 [SD=9.5], respectively), with significant between-group
differences seen as early as 3 days after start of treatment (change
with risperidone: mean=–6.8 [SD=5.8]; change with placebo: mean=–4.0
[SD=5.8]) and continuing throughout all time points. Improvements in
CGI severity ratings and scores on the Montgomery-Åsberg Depression
Rating Scale, Positive and Negative Syndrome Scale, and GAS were
also significantly greater among patients receiving risperidone than
those given placebo. The most common adverse event reported among
risperidone patients was somnolence. While Extrapyramidal Symptom
Rating Scale scores were significantly greater in patients receiving
risperidone, mean total and subscale scores were low. CONCLUSIONS:
Risperidone monotherapy was significantly more efficacious than
placebo in the treatment of acute mania and demonstrated a rapid
onset of action. Risperidone was well tolerated by patients in this
study.
A Randomized, Placebo-Controlled Trial of Citalopram for the Treatment of Major Depression in Children and Adolescents
Karen Dineen Wagner,
Am J Psychiatry 161:1079-1083, June 2004
OBJECTIVE:
Open-label trials with the selective serotonin reuptake inhibitor
citalopram suggest that this agent is effective and safe for the
treatment of depressive symptoms in children and adolescents. The
current study investigated the efficacy and safety of citalopram
compared with placebo in the treatment of pediatric patients with
major depression. METHOD: An 8-week, randomized, double-blind, placebo-controlled
study compared the safety and efficacy of citalopram with placebo in
the treatment of children (ages 7–11) and adolescents (ages 12–17)
with major depressive disorder. Diagnosis was established with the
Schedule for Affective Disorders and Schizophrenia for School-Age Children—Present
and Lifetime Version. Patients (N=174) were treated initially with
placebo or 20 mg/day of citalopram, with an option to increase the
dose to 40 mg/day at week 4 if clinically indicated. The primary
outcome measure was score on the Children’s Depression Rating
Scale—Revised; the response criterion was defined as a score of 
28.
RESULTS: The overall mean citalopram dose was approximately 24
mg/day. Mean Children’s Depression Rating Scale—Revised scores
decreased significantly more from baseline in the citalopram treatment
group than in the placebo treatment group, beginning at week 1 and
continuing at every observation point to the end of the study
(effect size=2.9). The difference in response rate at week 8 between
placebo (24%) and citalopram (36%) also was statistically
significant. Citalopram treatment was well tolerated. Rates of
discontinuation due to adverse events were comparable in the placebo
and citalopram groups (5.9% versus 5.6%, respectively). Rhinitis,
nausea, and abdominal pain were the only adverse events to occur
with a frequency exceeding 10% in either treatment group.
CONCLUSIONS: In this population of children and adolescents, treatment
with citalopram reduced depressive symptoms to a significantly greater
extent than placebo treatment and was well tolerated.
Lithium facilitates apoptotic signaling induced by
activation of the Fas death domain-containing receptor
Ling
Song, Tong Zhou and Richard S Jope
BMC
Neuroscience 2004, 5:20
Background
Lithium,
a mood stabilizer widely used to treat bipolar disorder, also is a
neuroprotectant, providing neurons protection from apoptosis induced by a broad
spectrum of toxic conditions. A portion of this neuroprotection is due to
lithium's inhibition of glycogen synthase kinase-3. The present investigation
examined if the neuroprotection provided by lithium included apoptosis induced
by stimulation of the death domain-containing receptor Fas.
Results
Instead
of providing protection, treatment with 20 mM lithium significantly increased
apoptotic signaling induced by activation of Fas, and this occurred in both
Jurkat cells and differentiated immortalized hippocampal neurons. Other
inhibitors of glycogen synthase kinase-3, including 20 microM
indirubin-3'-monoxime, 5 microM kenpaullone, and 5 microM rottlerin, also
facilitated Fas-induced apoptotic signaling, indicating that the facilitation
of apoptosis by lithium was due to inhibition of glycogen synthase kinase-3.
Conclusions
These
results demonstrate that lithium is not always a neuroprotectant, and it has
the opposite effect of facilitating apoptosis mediated by stimulation of death
domain-containing receptors.
Adrian J. Lloyd,
The British Journal of Psychiatry (2004)
184: 488-495
Background
Evidence for structural hippocampal change in depression is limited
despite reports of neuronal damage due to hypercortisolaemia and
vascular pathology.
Aims To
compare hippocampal and white matter structural change in
demographically matched controls and participants with early-onset and
late-onset depression.
Method
High-resolution volumetric magnetic resonance imaging (MRI) and
rating of MRI hyperintensities.
Results
Atotal of 51 people with depression and 39 control participants were
included. Participants with late-onset depression had bilateral hippocampal
atrophy compared with those with early-onset depression and
controls. Hippocampal volumes did not differ between control participants
and those with early-onset depression. Age of depression onset
correlated (negatively) with hippocampal volume but lifetime
duration of depression did not. Hyperintensity ratings did not
differ between groups.
Conclusions
Results suggest that acquired biological factors are of greater
importance in late-than in early-onset illness and that pathological
processes other than exposure to hypercortisolaemia of depression
underlie hippocampal atrophy in depression of late life.
Hypothalamic-pituitary-adrenal axis function in patients with bipolar
disorder
Stuart Watson, James C. Ritchie,
The British Journal of Psychiatry (2004)
184: 496-502
Background
Hypothalamic-pituitary-adrenal (HPA) axis function, as variously
measured by the responses to the combined
dexamethasone/corticotrophin-releasing hormone (dex/CRH) test, the
dexamethasone suppression test (DST) and basal cortisol levels, has
been reported to be abnormal in bipolar disorder.
Aims To
test the hypothesis that HPA axis dysfunction persists in patients
in remission from bipolar disorder.
Method
Salivary cortisol levels and the plasma cortisol response to the DST
and dex/CRH test were examined in 53 patients with bipolar disorder,
27 of whom fulfilled stringent criteria for remission, and in 28
healthy controls. Serum dexamethasone levels were measured.
Results
Patients with bipolar disorder demonstrated an enhanced cortisol
response to the dex/CRH test compared with controls (P=0.001). This
response did not differ significantly between remitted and
non-remitted patients. These findings were present after the
potentially confounding effects of dexamethasone levels were
accounted for.
Conclusions
The dex/CRH test is abnormal in both remitted and non-remitted
patients with bipolar disorder. This measure of HPA axis dysfunction
is a potential trait marker in bipolar disorder and thus possibly
indicative of the core pathophysiological process in this illness.
The effect of duloxetine on painful physical symptoms in depressed patients:
do improvements in these symptoms result in higher remission rates?
Fava M,
Mallinckrodt CH, Detke MJ, Watkin JG, Wohlreich MM.
Journal
of clinical psychiatry 2004;65(4):521-530.
BACKGROUND:
Depression is a chronic disease consisting of emotional/psychological and
physical symptoms. Emotional symptoms have been shown to respond to currently
available antidepressants; however, physical symptoms may not be as responsive.
It was hypothesized that resolution of both psychological and physical symptoms
of depression would predict a higher percentage of patients achieving remission.
METHOD: Efficacy data were pooled from 2 identical, but independent, 9-week
randomized, double-blind clinical trials of duloxetine 60 mg q.d. (N = 251) and
placebo (N = 261). All patients met diagnostic criteria for DSM-IV major
depressive disorder, which was confirmed by the Mini-International
Neuropsychiatric Interview. Efficacy measures included the 17-item Hamilton
Rating Scale for Depression (HAM-D-17) total score, the HAM-D-17 Maier
subscale, the Clinical Global Impressions-Severity of Illness (CGI-S) scale,
the Patient Global Impression of Improvement (PGI-I) scale, the Somatic Symptom
Inventory, the Quality of Life in Depression Scale, and Visual Analog Scales
(VAS) for pain (overall pain, headaches, back pain, shoulder pain, interference
with daily activities, and time in pain while awake). RESULTS:
Duloxetine-treated patients demonstrated significantly greater improvement in
overall pain (p =.016), back pain (p =.002), and shoulder pain (p =.021) at
week 9 compared with patients receiving placebo. When treatment effects were
pooled over all visits, patients receiving duloxetine, 60 mg q.d., exhibited
significantly greater improvement than placebo-treated patients in 5 of the 6
assessed VAS pain measures. Approximately 50% of the improvement in overall
pain was independent of improvement in HAM-D-17 total score. Assuming the same
level of improvement in core emotional symptoms of depression (Maier subscale),
improvement in overall pain severity was associated with higher estimated
probabilities of remission (p <.001). The week 9 means for VAS overall pain
severity were 13.0 for remitters (last observed value for HAM-D-17 was < or
= 7) compared with 22.7 for nonremitters (p <.001), respectively,
representing a greater than 3-fold improvement from baseline in remitters. The
remission rate for pain responders (improvement in VAS overall pain from
baseline to last observation > or = 50%) was twice that observed for pain
nonresponders (36.2% vs. 17.8%, p <.001). Greater improvements in pain outcomes
were associated with more favorable endpoint outcomes on the CGI-S and PGI-I
scales. In addition, early favorable responses in VAS overall pain severity
were associated with favorable endpoint outcomes. CONCLUSIONS: Treatment with
duloxetine, 60 mg q.d., significantly reduced pain compared with placebo.
Improvements in pain severity were attributable equally to the direct effect of
duloxetine and to associated changes in depression severity. Improvement in
painful physical symptoms was associated with higher remission rates even after
accounting for improvement in core emotional symptoms.
Single photon emission computed tomography in
posttraumatic stress disorder before and after treatment with a selective
serotonin reuptake inhibitor.
Seedat S,
Warwick J, van Heerden B, Hugo C, Zungu-Dirwayi N, Van Kradenburg J, Stein DJ.
J Affect Disord. 2004 May;80(1):45-53.
BACKGROUND: Posttraumatic stress disorder (PTSD) is recognized as a disorder
mediated by specific neurobiological circuits. Functional imaging studies using
script-driven trauma imagery and pharmacological challenges have documented
altered cerebral function (activation and deactivation) in several brain
regions, including the amygdala, hippocampus, prefrontal cortex and anterior
cingulate. However, the neural substrates of PTSD remain poorly understood and
the effect of selective serotonin reuptake inhibition on regional cerebral
activity is deserving of further investigation. METHODS: Eleven adult patients
(seven men, four women) (mean age+S.D.=33.6+/-9.2 years) with a DSM-IV
diagnosis of PTSD, as determined by the Structured Clinical Interview for
DSM-IV (SCID-I) and the Clinician-Administered PTSD Scale (CAPS), underwent
single photon emission computed tomography (SPECT) with Tc-99m HMPAO pre- and
post-8 weeks of treatment with the selective serotonin reuptake inhibitor,
citalopram. Symptoms were assessed at baseline and at 2-week intervals with the
Clinician-Administered PTSD Scale (CAPS), Montgomery-Asberg Depression Rating
Scale (MADRS), and the Clinical Global Impression Scale (CGI). Image analysis
of baseline and post-treatment scans was performed using Statistical Parametric
Mapping (SPM). RESULTS: Treatment with citalopram resulted in significant
deactivation in the left medial temporal cortex irrespective of clinical
response. On covariate analysis, a significant correlation between CAPS score
reduction and activation in the left paracingulate region (medial prefrontal
cortex) was observed post-treatment. No significant pre-treatment differences were
observed between responders and non-responders in anterior cingulate perfusion.
CONCLUSIONS: These preliminary findings are consistent with clinical data
indicating temporal and prefrontal cortical dysfunction in PTSD and preclinical
data demonstrating serotonergic innervation of these regions. However, further
studies, in particular in vivo receptor imaging studies, are needed to confirm
whether these regional abnormalities correlate with clinical features and
treatment response.
Treatment
and response in refractory depression: results from a specialist affective
disorders service
N.
Kennedy and E. S. Paykel
Journal of Affective Disorders .Volume 81, Issue 1 , July 2004, Pages 49-53
Background:
The best treatment approaches for chronic severe refractory depression remain
uncertain. This study aimed to identify short-term outcome and most successful
somatic treatments of severe refractory depressives referred to an affective
disorders service. Methods: Patients with chronic refractory depression
referred to a specialist affective disorders service over a 10-year period were
studied. Using detailed case records of the index episode, courses of treatment
and outcome were examined. Results: Patients were predominantly middle-aged
females with few prior episodes but long index episodes. Patients received
higher antidepressant doses and more combinations on the specialist service.
Very-high-dose antidepressants (tricyclics, velafaxine or tricyclic–MAOI
combinations), usually augmented with lithium and often combined with ECT, were
the most effective somatic treatments. Most subjects improved substantially,
but few reached premorbid levels. Limitations: The study was retrospective.
Treatment courses were sequential rather than random. Conclusions: Refractory
depression is responsive to vigorous somatic therapy, although most patients
continue with some symptoms.
Gabriel
Rubio, Luis San, Francisco López-Muñoz and Cecilio Alamo
Journal of Affective Disorders .Volume 81, Issue 1 , July 2004, Pages 67-72
Background:
To investigate the usefulness of the combination therapy with two
antidepressants from different pharmacological families in treatment-resistant
depressive patients. Methods: In this prospective 6 weeks open-label study, we
assessed the effectiveness of the addition of reboxetine to 61 depressive
patients that had previously not responded, or had done so only in a partial
way, to conventional treatment, in monotherapy, with selective serotonin
reuptake inhibitors (SSRIs), venlafaxine or mirtazapine. Data were analyzed on
an intent-to-treat basis, using the last-observation-carried-forward (LOCF)
method. Results: Mean decrease on the 21-item Hamilton Depression Rating Scale
(HDRS) score was 48.9% and on the Clinical Global Impressions Scale (CGI),
38.9%. At the end of the treatment, 62.3% of the patients were evaluated as
improvement (CGI<4), 54.1% as responders (HDRS≤50%) and 45.9% in
remission (HDRS≤10). No serious side effects were observed during
combination therapy, being more frequent increased sweating (8.2%) and dry
mouth (6.6%). Conclusions: These findings suggest that the strategy of
combination with reboxetine may be an effective and well-tolerated tool in
treatment-resistant patients who have failed to adequately respond to
monotherapy with SSRIs, venlafaxine or mirtazapine.
The
selective serotonin reuptake inhibitor citalopram increases fear after acute
treatment but reduces fear with chronic treatment: a comparison with tianeptine
Nesha S.
Burghardt, Gregory M. Sullivan, Bruce S. McEwen, Jack M. Gorman and Joseph E.
LeDoux
Biological Psychiatry .Volume 55, Issue 12 , 15 June 2004, Pages
1171-1178
Background
Selective
serotonin reuptake inhibitors (SSRIs) are efficacious in the treatment of a
variety of fear or anxiety disorders. Although they inhibit the reuptake of
serotonin within hours of administration, therapeutic improvement only occurs
after several weeks. In this study, we used fear conditioning to begin to
understand how acute and chronic SSRI treatment might differentially affect
well-characterized fear circuits.
Methods
We
evaluated the effects of acute and chronic treatment with the SSRI citalopram
on the acquisition of auditory fear conditioning. To further understand the
role of serotonin in modulating fear circuits, we compared these effects with
those of acute and chronic administration of the antidepressant tianeptine, a
purported serotonin reuptake enhancer.
Results
We found
that acute administration of the SSRI citalopram enhanced acquisition, whereas
chronic treatment reduced the acquisition of auditory fear conditioning. In
comparison, treatment with tianeptine had no effect acutely but also reduced
the acquisition of tone conditioning when administered chronically.
Conclusions
Our
findings with citalopram are consistent with the clinical effects of SSRI
treatment seen in patients with anxiety disorders, in which anxiety is often
increased during early stages of treatment and decreased after several weeks of
treatment. The findings also indicate that auditory fear conditioning can be a
useful tool in understanding differences in the effects of short-term and
long-term antidepressant treatment with serotonergic medications.
One
year cumulative incidence of depression following myocardial infarction and
impact on cardiac outcome
Jacqueline
J. M. H. Strik, Richel Lousberg, Emile C. Cheriex and Adriaan Honig
Journal of Psychosomatic Research .Volume 56, Issue 1 , January 2004, Pages
59-66
Background
Major
depression has been identified as an independent risk factor for increased
morbidity and mortality in mixed patients populations with first and recurrent
myocardial infarction (MI). The aim of this study was to evaluate whether
incidence of major and minor depression is as high in a population with merely
first-MI patients as in recurrent MI populations. Furthermore, it was evaluated
whether in first-MI patients major and minor depression, and depressive
symptoms, had an impact on cardiac mortality and morbidity up to 3 years post
MI.
Methods
A
consecutive cohort of 206 patients with a first MI were included in this study.
One month following MI, all patients were interviewed using the Structured
Clinical Interview for DSM-IV (SCID-I-R). Three, six, nine and twelve months
following MI, patients filled out three psychiatric self-rating scales for
depression, the Beck Depression Inventory (BDI), the Hospital Anxiety and
Depression Scale (HADS), and the 90-item Symptom Checklist (SCL-90). Patients,
exceeding a previously defined cut-off value on at least one of these scales,
were reinterviewed using the SCID. The BDI was applied to assess depressive
symptoms in relation to cardiac outcome as the SCL-90 and HADS showed similar
results. Cardiac outcome was defined as major cardiac event, i.e., death or
recurrent MI, and health care consumption, i.e., cardiac rehospitalisation
and/or frequent visits at the cardiac outpatient clinic. Depression outcome was
assessed from 1 month post MI up to 1 year post MI whereas cardiac outcome was
assessed between 1 month and 3 years post MI.
Results
A 1-year
incidence of 31% of major and minor depression was found in first-MI patients.
The highest incidence rate for both major and minor depression was found in the
first month after MI. Compared with nondepressed patients, depressed patients
were younger (P=.001), female (P=.04) and were known with a previous depressive
episode (P=.002). Neither major/minor depression nor depressive symptoms
significantly predicted major cardiac events, but did predict health care
consumption (P=.04 and P<.001, respectively).
Conclusions
Incidence
of major and minor depression is similar in this first-MI patients population
as in recurrent MI populations. Major/minor depressive disorder nor depressive
symptoms predicted neither mortality nor reinfarction.
Mani N.
Pavuluri, Ellen S. Herbener and John A. Sweeney
Journal of Affective Disorders .Volume 80, Issue 1 , May 2004, Pages 19-28
Background:
There is under-recognition or misdiagnosis of pediatric bipolar disorder with
psychotic features. It is of major public health importance to recognize
psychosis in bipolar disorder. Method: Original research on phenomenological
description of psychosis and external validators including family history,
longitudinal course and treatment effects are systematically reviewed. Age
differences, sampling, and interview methods of the studies on pediatric
bipolar disorder that reported psychotic features are compared. Critical
differentiating features between pediatric bipolar disorder and pediatric
schizophrenia are summarized given the presence of overlapping psychotic
features. Results: Prevalence of psychotic features in pediatric bipolar
disorder ranged from 16 to 87.5% based on age and methodological differences.
The most common psychotic features are mood congruent delusions, mainly
grandiose delusions. Psychotic features appear in the context of affective
symptoms in pediatric bipolar disorder as opposed to schizophrenia where
psychotic symptoms are independent of them. Family history of affective psychosis
aggregated in probands with bipolar disorder. Limitations: There is discrepancy
in clinical appraisal of what constitutes psychosis and pediatric bipolar
disorder, apart from the differences in methodology and nature of the samples.
Conclusion: Clinicians must be vigilant in identifying psychosis in pediatric
bipolar disorder, especially when there is a positive family history of
psychosis.
Differential
response of bipolar and normal control lymphoblastoid cell sodium pump to
ethacrynic acid
Rena Li
and Rif S. El-Mallakh
Journal of Affective Disorders .Volume 80, Issue 1 , May 2004, Pages 11-17
Background:
While the pathogenesis of manic-depressive, or bipolar, illness is unknown, an
excess of intracellular sodium and calcium concentrations is thought to
contribute to the development of the illness. Previous work has demonstrated a
reduced adaptive response of the sodium pump to ethacrynic acid in lymphocytes
obtained from bipolar subjects compared to psychiatrically normal controls.
Methods: To further examine this phenomenon, we investigated several aspects of
sodium pump response (transcription, translation, activity, and intracellular
ion concentration) in lymphoblastoid cell lines derived from bipolar subjects
and matched normal controls. Cells were treated with ethacrynic acid 100 
M
for 3 days. Results:
Single
photon emission computed tomography in posttraumatic stress disorder before and
after treatment with a selective serotonin reuptake inhibitor
Soraya
Seedat, James Warwick, Barend van Heerden, Charmaine Hugo, Nompumelelo
Zungu-Dirwayi, Jeanine Van Kradenburg, and Dan J. Stein
Journal of Affective Disorders .Volume 80, Issue 1 , May 2004, Pages 45-53
Background:
Posttraumatic stress disorder (PTSD) is recognized as a disorder mediated by
specific neurobiological circuits. Functional imaging studies using
script-driven trauma imagery and pharmacological challenges have documented
altered cerebral function (activation and deactivation) in several brain
regions, including the amygdala, hippocampus, prefrontal cortex and anterior
cingulate. However, the neural substrates of PTSD remain poorly understood and
the effect of selective serotonin reuptake inhibition on regional cerebral
activity is deserving of further investigation. Methods: Eleven adult patients
(seven men, four women) (mean age+S.D.=33.6±9.2 years) with a DSM-IV diagnosis
of PTSD, as determined by the Structured Clinical Interview for DSM-IV (SCID-I)
and the Clinician-Administered PTSD Scale (CAPS), underwent single photon
emission computed tomography (SPECT) with Tc-99m HMPAO pre- and post-8 weeks of
treatment with the selective serotonin reuptake inhibitor, citalopram. Symptoms
were assessed at baseline and at 2-week intervals with the
Clinician-Administered PTSD Scale (CAPS), Montgomery–Asberg Depression Rating
Scale (MADRS), and the Clinical Global Impression Scale (CGI). Image analysis
of baseline and post-treatment scans was performed using Statistical Parametric
Mapping (SPM). Results: Treatment with citalopram resulted in significant
deactivation in the left medial temporal cortex irrespective of clinical
response. On covariate analysis, a significant correlation between CAPS score
reduction and activation in the left paracingulate region (medial prefrontal
cortex) was observed post-treatment. No significant pre-treatment differences
were observed between responders and non-responders in anterior cingulate
perfusion. Conclusions: These preliminary findings are consistent with clinical
data indicating temporal and prefrontal cortical dysfunction in PTSD and
preclinical data demonstrating serotonergic innervation of these regions.
However, further studies, in particular in vivo receptor imaging studies, are
needed to confirm whether these regional abnormalities correlate with clinical
features and treatment response.
Correlation
between cerebral blood flow and items of the
Ariel Graff-Guerrero,
Jorge González-Olvera, Yazmín Mendoza-Espinosa, Víctor Vaugier and Juan Carlos
García-Reyna
Journal of Affective Disorders .Volume 80, Issue 1 , May 2004, Pages 55-63
Background:
The purpose of this study was to correlate the basal cerebral blood flow (CBF)
in patients with major depressive disorder (MDD) with the score for each of the
21 questions in the Hamilton Rating Scale for Depression (HRSD), in order to
determine the cerebral regions associated with each item. Methods: Fourteen
antidepressant-naive patients with unipolar depression (DSM-IV criteria for MDD)
participated in this study with a HRSD score of ≥20 points. CBF images
obtained by SPECT were analyzed by SPM99 software. The significant correlation
threshold for a priori regions (frontocortical and limbic regions) was a Z
value of at least 2.25 and clusters formed by more than 10 voxels. Results:
Items 1, 6, 11 and 20 were positively correlated with right medial frontal
gyrus; item 7 was negatively correlated with bilateral medial frontal gyrus.
Items 2 and 10 were positively correlated with right anterior and medial
cingulate, respectively. Item 5 was negatively correlated with the left
amygdala. Item 9 was negatively correlated with bilateral insula, and item 16
with right insula. Items 12 and 14 were positively correlated with right and
left precentral frontal gyrus, respectively. Limitations: The small sample size
and only out-patients included in the study. Conclusions: The frontal cortex
plays an important role in the expression of MDD symptoms. Not all the symptoms
evaluated correlated with one single structure, which may explain the diverse
results reported in the literature. These preliminary results support the
necessity of further analyses by symptoms that could provide more specific
information on the pathophysiology of MDD.
Measurement of Brain Regional 
-[11C]Methyl-L-Tryptophan
Trapping as a Measure of Serotonin Synthesis in Medication-Free Patients With
Major Depression
Pedro Rosa-Neto, Mirko Diksic, Hidehiko Okazawa,
Marco Leyton, Nayyer Ghadirian, Shadreck Mzengeza, Akio Nakai, Guy Debonnel,
Pierre Blier, Chawki Benkelfat
Arch Gen Psychiatry. 2004;61:556-563.
Context The serotonin hypothesis of
depression invokes a relative or absolute deficit of serotonin
neurotransmission. Reduced synthesis of serotonin in the brain
pathways mediating the expression of mood (ie, the limbic cortex) is
a plausible candidate mechanism.
Objectives To measure and compare, using the 
-[11C]methyl-L-tryptophan/positron
emission tomography method, the brain trapping constant of -[11C]methyl-L-tryptophan
(K*, milliliters per gram per minute), an index of serotonin synthesis,
in brain areas involved in the regulation of mood in patients with
major depression (MD) and age- and sex-matched controls.
Design Between-group comparison.
Setting Department of Psychiatry and
Participants Seventeen medication-free
outpatients with a current episode of MD (9 women: mean ± SD age, 41
± 11 years; 8 men: mean ± SD age, 41 ± 11 years) and 17
controls (9 women: mean ± SD age, 37 ± 15 years; 8 men: mean ± SD
age, 32.5 ± 9.9 years).
Main Outcome Measure Normalized K*,
normalized to the global mean, was measured in the dorsolateral
prefrontal, anterior cingulate, and mesial temporal cortices; the
thalamus; and the caudate nucleus.
Results Compared with age- and sex-matched
controls, normalized K* was significantly decreased bilaterally in
female patients with MD in the anterior cingulate cortex, in the
left anterior cingulate cortex in male patients with MD, and in the
left mesial temporal cortex in male and female patients with MD
(P<.001 for all). Exploratory analyses identified additional
patient-control differences for normalized K* (eg, inferior frontal
gyrus and superior parietal lobule), most of which, once corrected
for 38 multiple comparisons, lost their significance. Morphometric
measurements of the cingulate cortex divisions confirmed that the
reduction of normalized K* in depressed patients was not attributable
to a reduction in gray matter volume. Normalized K* in the anterior
cingulate cortex did not correlate with ratings of depression
severity collected at the time of scan.
Conclusions Reduction of normalized K*, an
index of serotonin synthesis, in parts of the limbic and paralimbic
cortices may contribute to the biochemical alterations associated
with MD.
Distinct Neural Correlates of
Washing, Checking, and Hoarding Symptom Dimensions in Obsessive-compulsive
Disorder
David Mataix-Cols, Sarah Wooderson, Natalia
Lawrence, Michael J. Brammer, Anne Speckens, Mary L. Phillips
Arch Gen Psychiatry. 2004;61:564-576.
Context Obsessive-compulsive disorder (OCD)
is clinically heterogeneous, yet most previous functional
neuroimaging studies grouped together patients with mixed symptoms,
thus potentially reducing the power and obscuring the findings of
such studies.
Objective To investigate the neural
correlates of washing, checking, and hoarding symptom dimensions in
OCD.
Design Symptom provocation paradigm,
functional magnetic resonance imaging, block design, and
nonparametric brain mapping analyses.
Setting University hospital.
Participants Sixteen patients with OCD (11
inpatients, 5 outpatients) with mixed symptoms and 17 healthy
volunteers of both sexes.
Intervention All subjects participated in 4
functional magnetic resonance imaging experiments. They were scanned
while viewing alternating blocks of emotional (washing-related,
checking-related, hoarding-related, or aversive, symptom-unrelated)
and neutral pictures, and imagining scenarios related to the content
of each picture type.
Main Outcome Measure Blood oxygenation
level–dependent response.
Results Both patients and control subjects
experienced increased subjective anxiety during symptom provocation
(patients significantly more so) and activated neural regions
previously linked to OCD. Analyses of covariance, controlling for
depression, showed a distinct pattern of activation associated with
each symptom dimension. Patients demonstrated significantly greater
activation than controls in bilateral ventromedial prefrontal regions
and right caudate nucleus (washing); putamen/globus pallidus,
thalamus, and dorsal cortical areas (checking); left precentral
gyrus and right orbitofrontal cortex (hoarding); and left
occipitotemporal regions (aversive, symptom-unrelated). These
results were further supported by correlation analyses within
patients, which showed highly specific positive associations between
subjective anxiety, questionnaire scores, and neural response in
each experiment. There were no consistently significant differences
between patients with (n = 9) and without (n = 7) comorbid
diagnoses.
Conclusions The findings suggest that
different obsessive-compulsive symptom dimensions are mediated by
relatively distinct components of frontostriatothalamic circuits
implicated in cognitive and emotion processing. Obsessive-compulsive
disorder may be best conceptualized as a spectrum of multiple,
potentially overlapping syndromes rather than a unitary nosologic
entity.
Update on neurosurgical treatment for obsessive compulsive disorder.
LOPES, Antonio Carlos, MATHIS, Maria Eugênia de, CANTERAS, Miguel Montes et al.
Rev. Bras. Psiquiatr., Mar. 2004, vol.26, no.1,
p.62-66.
Responses
to pharmacotherapy and psychotherapy in obsessive-compulsive disorder (OCD)
range from 60 to 80% of cases. However, a subset of OCD patients do not respond
to adequately conducted treatment trials, leading to severe psychosocial
impairment. Stereotactic surgery can be indicated then as the last resource.
Five surgical techniques are available, with the following rates of global
post-operative improvement: anterior capsulotomy (38-100%); anterior
cingulotomy (27-57%); subcaudate tractotomy (33-67%); limbic leucotomy
(61-69%), and central lateral thalamotomy/anterior medial pallidotomy (62.5%).
The first technique can be conducted as a standard neurosurgery, as
radiosurgery or as deep brain stimulation. In the standard neurosurgery neural
circuits are interrupted by radiofrequency. In radiosurgery, an actinic lesion
is provoked without opening the brain. Deep brain stimulation consists on
implanting electrodes which are activated by stimulators. Literature reports a
relatively low prevalence of adverse events and complications.
Neuropsychological and personality changes are rarely reported. However, there
is a lack of randomized controlled trials to prove efficacy and adverse
events/complication issues among these surgical procedures. Concluding, there is
a recent development in the neurosurgeries for severe psychiatric disorders in
the direction of making them more efficacious and safer. These surgeries, when
correctly indicated, can profoundly alleviate the suffering of severe OCD
patients.
Implication of the hypothalamic–pituitary–adrenal
axis in the physiopathology of depression
Nicholas Barden
J Psychiatry
Neurosci. 2004 May; 29 (3): 185–193
Major alterations of the
hypothalamic–pituitary–adrenocortical (HPA) system that can be reversed by
successful antidepressant therapy are often seen in depressed patients.
Persuasive evidence points to the involvement of a dysfunctional glucocorticoid
receptor (GR) system in these changes. Support for this also comes from studies
of transgenic mice that express an antisense RNA, complementary to the GR mRNA,
and have numerous neuroendocrine characteristics of human depression as well as
altered behaviour. Many of these neuroendocrine and behavioural characteristics
of the transgenic mice can be reversed by antidepressants. A possible
explanation for this is that the antidepressant-induced increase in GRs renders
the HPA axis more sensitive to glucocorticoid feedback. This new insight into
antidepressant drug action suggests a novel approach to the development of antidepressant
drugs.
Implications of adult hippocampal
neurogenesis in antidepressant action
Jessica E. Malberg
J Psychiatry
Neurosci. 2004 May; 29 (3): 196–205
In the dentate gyrus of the hippocampus, cell birth and maturation into neurons, or neurogenesis, occur throughout the lifetime of animals and humans. Multiple factors have been shown to regulate adult neurogenesis, and a number of findings in this fi