|
Anand A, Shekhar A.
Brain imaging studies in mood
and anxiety disorders: special emphasis on the amygdala.
Ann
N Y Acad Sci. 2003 Apr;985:370-88.
"Human studies attempting to elucidate
brain functioning in health and disease are crucial for our understanding of neuropsychiatric
disorders. In the past, scientists relied heavily on neurological lesion studies
to understand the functional roles of brain areas. In the last few decades, brain
imaging research has made it possible to investigate the molecular and synaptic
neuronal events as well as the functioning of neuronal networks in vivo, in patients
with neuropsychiatric illnesses. In this context, the functional role of the amygdala
has been a focus of neuroimaging studies by leading researchers. Several of these
researchers presented papers at a conference, entitled The Amygdala in Brain Function:
Basic and Clinical Approaches, that provided the basis for this volume. These
papers follow this review in the current volume. The present paper briefly summarizes
the highlights of the different presentations, focusing on the functional diversity
of the amygdala and its role in different neuropsychiatric disorders; reviews
the various brain imaging technologies currently available; and discusses the
major findings on the pathophysiology and treatment of depression, bipolar disorder,
and anxiety disorders." [Abstract]
Brambilla P, Harenski K, Nicoletti M, Sassi RB, Mallinger
AG, Frank E, Kupfer DJ, Keshavan MS, Soares JC.
MRI investigation
of temporal lobe structures in bipolar patients.
J Psychiatr
Res. 2003 Jul-Aug;37(4):287-95.
"Previous anatomical MRI studies have
suggested abnormalities in amygdala volumes in bipolar disorder, whereas hippocampus,
temporal lobe (TL), and superior temporal gyri (STG) measures have been reported
to be normal. This study further investigated the existence of anatomical abnormalities
in these brain structures in bipolar subjects, to attempt to replicate previously
reported findings. Twenty-four DSM-IV bipolar patients (mean age+/-S.D.=35+/-10
years) and 36 healthy controls (mean age+/-S.D.=37+/-10 years) were studied. 3D
SPGR images were obtained with a 1.5T-GE Signa magnet (TR=25 ms, TE=5 ms, FOV=24
cm, slice-thickness=1.5 mm, matrix-size=256 x 192). Volumetric measurements of
TL, hippocampus, amygdala, and STG were performed blindly, with a semi-automated
software. Bipolar patients had significantly larger left amygdala volumes compared
with controls (mean volumes+/-S.D.=2.57+/-0.69 vs. 2.17+/-0.58 ml, respectively;
ANCOVA, age, gender, ICV as covariates; F=4.42, df=1/55, P=0.04). The volumes
of the other temporal lobe structures did not differ significantly between the
two groups (ANCOVA, age, gender, and ICV as covariates, P>0.05). Our findings
of enlarged left amygdala in bipolar patients are in agreement with prior MRI
studies, suggesting that abnormalities in this brain structure may be implicated
in pathophysiology of the illness. Longitudinal studies in high-risk offspring
and first-episode patients will be needed to examine whether such abnormalities
precede the appearance of symptoms, or whether they may appear subsequently as
a result of illness course." [Abstract] Drevets
WC, Price JL, Bardgett ME, Reich T, Todd RD, Raichle ME.
Glucose
metabolism in the amygdala in depression: relationship to diagnostic subtype and
plasma cortisol levels.
Pharmacol Biochem Behav 2002 Mar;71(3):431-47
"In a previous positron emission tomography (PET) study of major depression,
we demonstrated that cerebral blood flow was increased in the left amygdala in
unipolar depressives with familial pure depressive disease (FPDD) relative to
healthy controls [J. Neurosci. 12 (1992) 3628.]. These measures were obtained
from relatively low-resolution PET images using a stereotaxic method based upon
skull X-ray landmarks. The current experiments aimed to replicate and extend these
results using higher-resolution glucose metabolism images and magnetic resonance
imaging (MRI)-based region-of-interest (ROI) analysis. The specificity of this
finding to FPDD was also investigated by assessing depressed samples with bipolar
disorder (BD-D) and depression spectrum disease (DSD). Finally, the relationship
between amygdala metabolism and plasma cortisol levels obtained during the scanning
procedure was assessed. Glucose metabolism was measured using PET and 18F-fluorodeoxyglucose
(18FDG) in healthy control (n=12), FPDD (n=12), DSD (n=9) and BD-D (n=7) samples
in the amygdala and the adjacent hippocampus. The left amygdala metabolism differed
across groups (P<.001), being increased in both the FPDD and BD-D groups relative
to the control group. The left amygdala metabolism was positively correlated with
stressed plasma cortisol levels in both the unipolar (r=.69; P<.005) and the
bipolar depressives (r=0.68;.1<P<.05). In contrast, neither significant
main effects of diagnosis nor significant relationships with plasma cortisol were
evident in post hoc analyses of metabolism in the right amygdala or the hippocampus.
Preliminary assessment of BD subjects imaged during remission suggested that amygdala
metabolism is also elevated in remitted subjects who are not taking mood-stabilizing
drugs, but within the normal range in subjects taking mood stabilizers. These
data confirm our previous finding that neurophysiological activity is abnormally
increased in FPDD, and extend it to BD-D. These abnormalities were not accounted
for by spilling in of radioactivity from the adjacent hippocampus. The correlation
between left amygdala metabolism and stressed plasma cortisol levels may conceivably
reflect either the effect of amygdala activity on corticotropin-releasing hormone
(CRH) secretion or the effect of cortisol on amygdala function." [Abstract] Altshuler
LL, Bartzokis G, Grieder T, Curran J, Jimenez T, Leight K, Wilkins J, Gerner R,
Mintz J.
An MRI study of temporal lobe structures in men with bipolar
disorder or schizophrenia.
Biol Psychiatry 2000 Jul 15;48(2):147-62
"BACKGROUND: Hippocampal atrophy has been described in postmortem and magnetic
resonance imaging studies of schizophrenia. The specificity of this finding to
schizophrenia remains to be determined. The neuropathology of bipolar disorder
is understudied, and temporal lobe structures have only recently been evaluated.
METHODS: Twenty-four bipolar, 20 schizophrenic, and 18 normal comparison subjects
were evaluated using magnetic resonance brain imaging. Image data were acquired
using a three-dimensional spoiled GRASS sequence, and brain images were reformatted
in three planes. Temporal lobe structures including the amygdala, hippocampus,
parahippocampus, and total temporal lobe were measured to obtain volumes for each
structure in the three subject groups. Severity of symptoms in both patient groups
was assessed at the time the magnetic resonance images were obtained. RESULTS:
Hippocampal volumes were significantly smaller in the schizophrenic group than
in both bipolar and normal comparison subjects. Further, amygdala volumes were
significantly larger in the bipolar group than in both schizophrenic and normal
comparison subjects. CONCLUSIONS: The results suggest differences in affected
limbic structures in patients with schizophrenia and bipolar disorder. These specific
neuroanatomic abnormalities may shed light on the underlying pathophysiology and
presentation of the two disorders." [Abstract] Blumberg
HP, Kaufman J, Martin A, Whiteman R, Zhang JH, Gore JC, Charney DS, Krystal JH,
Peterson BS.
Amygdala and hippocampal volumes in adolescents and
adults with bipolar disorder.
Arch Gen Psychiatry. 2003
Dec;60(12):1201-8.
"BACKGROUND: The purported functions of medial temporal
lobe structures suggest their involvement in the pathophysiology of bipolar disorder
(BD). Previous reports of abnormalities in the volume of the amygdala and hippocampus
in patients with BD have been inconsistent in their findings and limited to adult
samples. Appreciation of whether volumetric abnormalities are early features of
BD or whether the abnormalities represent neurodegenerative changes associated
with illness duration is limited by the paucity of data in juvenile samples. OBJECTIVE:
To investigate amygdala and hippocampal volume in adults and adolescents with
BD.Setting and PARTICIPANTS: Subjects included 36 individuals (14 adolescents
and 22 adults) in outpatient treatment for BD type I at a university hospital
or Veterans Affairs medical center or in the surrounding community, and 56 healthy
comparison subjects (23 adolescents and 33 adults).Design and MAIN OUTCOME MEASURES:
Amygdala and hippocampal volumes were defined and measured on high-resolution
anatomic magnetic resonance imaging scans. We used a mixed-model, repeated-measures
statistical analysis to compare amygdala and hippocampal volumes across groups
while covarying for total brain volume, age, and sex. Potential effects of illness
features were explored, including rapid cycling, medication, alcohol or other
substance dependence, duration, and mood state. RESULTS: For both the amygdala
and hippocampal regions, we found an overall significant volume reduction in the
BD compared with the control group (P<.0001). Amygdala volume reductions (15.6%)
were highly significant (P<.0001). We observed a nonsignificant trend (P =.054)
toward reductions in hippocampal volumes of lesser magnitude (5.3%). Effects of
illness features were not detected. CONCLUSIONS: These results suggest that BD
is associated with decreased volumes of medial temporal lobe structures, with
greater effect sizes in the amygdala than in the hippocampus. These abnormalities
are likely manifested early in the course of illness, as they affected adolescent
and adult subjects similarly in this sample." [Abstract] Ketter
TA, Kimbrell TA, George MS, Dunn RT, Speer AM, Benson BE, Willis MW, Danielson
A, Frye MA, Herscovitch P, Post RM.
Effects of mood and subtype
on cerebral glucose metabolism in treatment-resistant bipolar disorder.
Biol Psychiatry 2001 Jan 15;49(2):97-109
"BACKGROUND: Functional brain
imaging studies in unipolar and secondary depression have generally found decreased
prefrontal cortical activity, but in bipolar disorders findings have been more
variable. METHODS: Forty-three medication-free, treatment-resistant, predominantly
rapid-cycling bipolar disorder patients and 43 age- and gender-matched healthy
control subjects had cerebral glucose metabolism assessed using positron emission
tomography and fluorine-18-deoxyglucose. RESULTS: Depressed bipolar disorder patients
compared to control subjects had decreased global, absolute prefrontal and anterior
paralimbic cortical, and increased normalized subcortical (ventral striatum, thalamus,
right amygdala) metabolism. Degree of depression correlated negatively with absolute
prefrontal and paralimbic cortical, and positively with normalized anterior paralimbic
subcortical metabolism. Increased normalized cerebello-posterior cortical metabolism
was seen in all patient subgroups compared to control subjects, independent of
mood state, disorder subtype, or cycle frequency. CONCLUSIONS: In bipolar depression,
we observed a pattern of prefrontal hypometabolism, consistent with observations
in primary unipolar and secondary depression, suggesting this is part of a common
neural substrate for depression independent of etiology. In contrast, the cerebello-posterior
cortical normalized hypermetabolism seen in all bipolar subgroups (including euthymic)
suggests a possible congenital or acquired trait abnormality. The degree to which
these findings in treatment-resistant, predominantly rapid-cycling patients pertain
to community samples remains to be established." [Abstract] Strakowski
SM, DelBello MP, Sax KW, Zimmerman ME, Shear PK, Hawkins JM, Larson ER.
Brain
magnetic resonance imaging of structural abnormalities in bipolar disorder.
Arch Gen Psychiatry 1999 Mar;56(3):254-60
"BACKGROUND: The neuropathogenesis
of bipolar disorder remains poorly described. Previous work suggests that patients
with bipolar disorder may have abnormalities in neural pathways that are hypothesized
to modulate human mood states. We examined differences in brain structural volumes
associated with these pathways between patients with bipolar disorder hospitalized
with mania and healthy community volunteers. METHODS: Twenty-four patients with
bipolar disorder and mania were recruited from hospital admission records. Twenty-two
healthy volunteers were recruited from the community who were similar to the patients
in age, sex, race, height, handedness, and education. All subjects were scanned
using a 3-dimensional radio-frequency-spoiled Fourier acquired steady state acquisition
sequence on a 1.5-T magnetic resonance imaging scanner. Scans were analyzed using
commercial software. Prefrontal, thalamic, hippocampal, amygdala, pallidal, and
striatal volumetric measurements were compared between the 2 groups. RESULTS:
Patients with bipolar disorder demonstrated a significant (A = 0.64; F6,37 = 3.4;
P = .009) overall difference in structural volumes in these regions compared with
controls. In particular, the amygdala was enlarged in the patients. Brain structural
volumes were not significantly associated with duration of illness, prior medication
exposure, number of previous hospital admissions, or duration of substance abuse.
Separating patients into first-episode (n = 12) and multiple-episode (n = 12)
subgroups revealed no significant differences in any structure (P>.10). CONCLUSION:
Patients with bipolar disorder exhibit structural abnormalities in neural pathways
thought to modulate human mood." [Abstract]
Benes FM, Berretta S.
GABAergic interneurons:
implications for understanding schizophrenia and bipolar disorder.
Neuropsychopharmacology 2001 Jul;25(1):1-27
"A core component to corticolimbic
circuitry is the GABAergic interneuron. Neuroanatomic studies conducted over the
past century have demonstrated several subtypes of interneuron defined by characteristic
morphological appearances in Golgi-stained preparations. More recently, both cytochemical
and electrophysiological techniques have defined various subtypes of GABA neuron
according to synaptic connections, electrophysiological properties and neuropeptide
content. These cells provide both inhibitory and disinhibitory modulation of cortical
and hippocampal circuits and contribute to the generation of oscillatory rhythms,
discriminative information processing and gating of sensory information within
the corticolimbic system. All of these functions are abnormal in schizophrenia.
Recent postmortem studies have provided consistent evidence that a defect of GABAergic
neurotransmission probably plays a role in both schizophrenia and bipolar disorder.
Many now believe that such a disturbance may be related to a perturbation of early
development, one that may result in a disturbance of cell migration and the formation
of normal lamination. The ingrowth of extrinsic afferents, such as the mesocortical
dopamine projections, may "trigger" the appearance of a defective GABA
system, particularly under stressful conditions when the modulation of the dopamine
system is likely to be altered. Based on the regional and subregional distribution
of changes in GABA cells in schizophrenia and bipolar disorder, it has been postulated
that the basolateral nucleus of the amygdala may contribute to these abnormalities
through an increased flow of excitatory activity. By using "partial"
modeling, changes in the GABA system remarkably similar to those seen in schizophrenia
and bipolar disorder have been induced in rat hippocampus. In the years to come,
continued investigations of the GABA system in rodent, primate and human brain
and the characterization of changes in specific phenotypic subclasses of interneurons
in schizophrenia and bipolar disorder will undoubtedly provide important new insights
into how the integration of this transmitter system may be altered in neuropsychiatric
disease." [Abstract] |
Malhi GS, Lagopoulos J, Ward PB, Kumari V, Mitchell
PB, Parker GB, Ivanovski B, Sachdev P.
Cognitive generation of affect
in bipolar depression: an fMRI study.
Eur J Neurosci. 2004
Feb;19(3):741-54.
"Individuals with bipolar disorder manifest the full
spectrum of emotions ranging from depression to mania. In attempting to understand
the functional substrates of mood we attempted to identify brain regions associated
with the cognitive generation of affect in bipolar depressed patients. We therefore
examined ten depressed female subjects with bipolar affective disorder, and ten
age-matched and sex-matched healthy comparison subjects using functional magnetic
resonance imaging (fMRI) while viewing alternating blocks of captioned pictures
designed to evoke negative, positive or no affective change. The activation paradigm
involved the presentation of the same visual materials over three experiments
alternating (experiment 1) negative and reference; (experiment 2) positive and
reference and (experiment 3) positive and negative captioned pictures. The stimuli
produced activation in both patients and comparison subjects in brain regions
previously implicated in the generation and modulation of affect, in particular
the prefrontal and anterior cingulate cortices. The activation in patients, when
compared with healthy subjects, involved additional subcortical regions, in particular
the amygdala, thalamus, hypothalamus and medial globus pallidus. Patients and
comparison subjects displayed differential sensitivity to affective change with
negative (experiment 1) and positive (experiment 2) affect induction producing
converse patterns of activation. We conclude that bipolar depressed patients perhaps
recruit additional subcortical limbic systems for emotional evaluation and this
may reflect state-related or trait-related dysfunction. The differential patterns
of activation inform us about bipolar depression and have potential diagnostic
and therapeutic significance." [Abstract] Yurgelun-Todd
DA, Gruber SA, Kanayama G, Killgore WD, Baird AA, Young AD.
fMRI
during affect discrimination in bipolar affective disorder.
Bipolar Disord 2000 Sep;2(3 Pt 2):237-48
"OBJECTIVE: It has been hypothesized
that disturbances in affect may represent distinct etiologic factors for bipolar
affective disorder. The neural mechanisms mediating affective processes and their
relationship to brain development and the pathophysiology of bipolar affective
disorder remain to be clarified. Recent advances in neuroimaging techniques have
made possible the non-invasive examination of specific brain regions during cortical
challenge paradigms. This study reports findings based on fMRI data acquired during
fearful and happy affect recognition paradigms in patients with bipolar affective
disorder and in healthy adult subjects. METHODS: Prior to the scan, subjects were
instructed to view the stimuli and to identify the type of facial expression presented.
Echo planar scanning was performed on a 1.5 Tesla scanner which had been retrofitted
with a whole body echo planar coil, using a head coil. RESULTS: The data indicate
that in adult subjects with bipolar affective disorder, there is a reduction in
dorsolateral prefrontal cortex activation and an increase in amygdalar activation
in response to fearful facial affect. In a healthy comparison group, signal intensity
changes were not found in these regions. In addition, although the patients with
bipolar affective disorder completed the task demands, they demonstrated an impaired
ability to correctly identify fearful facial affect but not the happy facial affect
displayed. CONCLUSION: These findings are consistent with the hypothesis that
in some patients with bipolar affective disorder, there may be a reduction of
frontal cortical function which may be associated with affective as well as attentional
processing deficits." [Abstract] Drevets
WC.
Prefrontal cortical-amygdalar metabolism in major depression.
Ann N Y Acad Sci 1999 Jun 29;877:614-37
"Functional neuroimaging studies
of the anatomical correlates of familial major depressive disorder (MDD) and bipolar
disorder (BD) have identified abnormalities of resting blood flow (BF) and glucose
metabolism in depression in the amygdala and the orbital and medial prefrontal
cortical (PFC) areas that are extensively connected with the amygdala. The amygdala
metabolism in MDD and BD is positively correlated with both depression severity
and "stressed" plasma cortisol concentrations measured during scanning.
During antidepressant drug treatment, the mean amygdala metabolism decreases in
treatment responders, and the persistence of elevated amygdala metabolism during
remission is associated with a high risk for the development of depressive relapse.
The orbital C metabolism is also abnormally elevated during depression, but is
negatively correlated with both depression severity and amygdala metabolism, suggesting
that this structure may be activated as a compensatory mechanism to modulate amygdala
activity or amygdala-driven emotional responses. The posterior orbital C and anterior
cingulate C ventral to the genu of the corpus callosum (subgenual PFC) have more
recently been shown in morphometric MRI and/or post mortem histopathological studies
to have reduced grey matter volume and reduced glial cell numbers (with no equivalent
loss of neurons) in familial MDD and BD. These data suggest a neural model in
which dysfunction of limbic PFC structures impairs the modulation of the amygdala,
leading to abnormal processing of emotional stimuli. Antidepressant drugs may
compensate for this dysfunction by inhibiting pathological limbic activity."
[Abstract] DelBello
MP, Zimmerman ME, Mills NP, Getz GE, Strakowski SM
Magnetic
resonance imaging analysis of amygdala and other subcortical brain regions in
adolescents with bipolar disorder.
Bipolar Disord.
2004 Feb;6(1):43-52.
OBJECTIVES: Few studies have examined the abnormalities
that underlie the neuroanatomy of bipolar disorder in youth. The aim of this study
was to evaluate brain regions that are thought to modulate mood utilizing quantitative
analyses of thin-slice magnetic resonance imaging (MRI) scans of adolescents with
bipolar disorder. We hypothesized that adolescents with bipolar disorder would
exhibit abnormalities in brain regions that are involved in the regulation of
mood including the amygdala, globus pallidus, caudate, putamen, and thalamus.
METHODS: Bipolar adolescents (n = 23) and healthy subjects (n = 20) matched for
age, race, sex, socioeconomic status, IQ, education and Tanner stage, were evaluated
using the Washington University at St Louis Kiddie-Schedule for Affective Disorders
and Schizophrenia (WASH-U K-SADS). Contiguous 1 mm axial T1-weighted MRI slices
were obtained using a GE 1.5 T MR scanner. Regions of interest (ROI) included
total cerebral volume, amygdala, globus pallidus, caudate, putamen, and thalamus.
RESULTS: Total cerebral volume was smaller in bipolar adolescents than in healthy
adolescents. A MANCOVA revealed a significant group difference in overall ROI
volumes after adjusting for total cerebral volume. Specifically, adolescents with
bipolar disorder exhibited smaller amygdala and enlarged putamen compared with
healthy subjects. CONCLUSIONS: Our findings indicate that adolescents with bipolar
disorder exhibit abnormalities in some of the brain regions that are thought to
be involved in the regulation of mood. Additional structural and functional neuroimaging
investigations of children, adolescents, and adults with bipolar disorder are
necessary to clarify the role of these brain regions in the neurophysiology of
adolescent bipolar disorder. [Abstract] Strakowski
SM, Adler CM, DelBello MP.
Volumetric MRI studies of mood disorders:
do they distinguish unipolar and bipolar disorder?
Bipolar
Disord 2002 Apr;4(2):80-8
"The authors reviewed magnetic resonance imaging
volumetric imaging results in major mood disorders, particularly comparing similarities
and differences from studies of bipolar disorder and unipolar major depression.
Abnormalities of cerebral brain regions appear inconsistently in mood disorders
and, when present, typically consist of decreased frontal or prefrontal cortical
volumes in both unipolar depression and bipolar disorder. In contrast, subcortical
and medial temporal abnormalities are more commonly observed and are different
between these two major classes of affective illness. Specifically, whereas structural
enlargement of the basal ganglia and amygdala have been observed in bipolar disorder,
in unipolar depression, these structures appear to be smaller in patients than
healthy subjects. These findings suggest that affective illnesses may share in
common an underdeveloped or atrophied prefrontal region, leading to loss of cortical
modulation of limbic emotional networks. The effect of this loss results in unipolar
depression or cycling (mania with depression) depending on the abnormalities of
the subcortical structures involved. The cerebellum may also play a role in the
presentation of mood disorders. This hypothesis remains speculative as much more
research is needed to specifically examine how morphometric brain abnormalities
translate into the neurophysiologic deficits that produce mood disorders."
[Abstract] Kennedy
SH, Javanmard M, Vaccarino FJ.
A review of functional neuroimaging
in mood disorders: positron emission tomography and depression.
Can J Psychiatry 1997 Jun;42(5):467-75
"OBJECTIVE: To examine the progress
of positron emission tomography (PET) as a tool for understanding the psychobiology
of mood disorders, particularly major depression and bipolar disorder. METHOD:
Review of the literature on functional imaging of mood disorders. RESULTS: Functional
imaging techniques have been used in psychiatric research as a noninvasive method
to study the behaviour and function of the brain. Techniques used so far have
involved the manipulation of emotion in healthy volunteers, the evaluation of
depressed (unipolar and bipolar as well as secondary depression), manic, and normal
subjects under resting and various activation conditions, such as cognitive activation,
acute pharmacological challenge, and chronic thymoleptic treatments. As a result,
functional imaging studies tend to support abnormalities in specific frontal and
limbic regions. CONCLUSION: Different PET methods demonstrate consistent abnormalities
in the prefrontal, cingulate, and amygdala regions. These findings are in agreement
with past animal and clinical anatomical correlates of mood and emotions."
[Abstract]
Hurd YL.
Subjects with major depression or
bipolar disorder show reduction of prodynorphin mRNA expression in discrete nuclei
of the amygdaloid complex.
Mol Psychiatry 2002;7(1):75-81
"The dynorphin system has been associated with the regulation of mood. The
expression of the prodynorphin mRNA was currently studied in the amygdaloid complex,
a brain region critical for emotional processing, in subjects (14-15 per group)
diagnosed with major depression, bipolar disorder, or schizophrenia and compared
to normal controls. In situ hybridization histochemistry was used to characterize
the anatomical distribution and expression levels of the prodynorphin mRNA within
the amygdaloid complex. High prodynorphin mRNA levels were expressed in the parvicellular
division of the accessory basal, posterior cortical, periamygdaloid cortex, and
amygdalohippocampal area in normal subjects. Individuals with major depression
had significantly reduced (41-68%) expression of the prodynorphin mRNA in the
accessory basal (both parvicellular and magnocellular divisions; P < 0.01)
and amygdalohippocampal area (P < 0.001) as compared to controls. The bipolar
disorder group also showed a significant reduction (37-38%, P < 0.01) of the
mRNA expression levels in the amygdalohippocampal area and in the parvicellular
division of the accessory basal. No other amygdala nuclei studied showed any significant
differences for the prodynorphin mRNA levels measured in the major depression
and bipolar disorder subjects. Additionally, the prodynorphin mRNA expression
levels did not differ significantly between the schizophrenic and normal control
subjects in any of the amygdala areas examined. These findings indicate specific
prodynorphin amygdala impairment in association with mood disorder." [Abstract] Bowley
MP, Drevets WC, Ongur D, Price JL.
Low glial numbers in the amygdala
in major depressive disorder.
Biol Psychiatry. 2002 Sep
1;52(5):404-12.
"BACKGROUND: Functional imaging studies implicate the
prefrontal cortex and amygdala in major depressive disorder and bipolar disorder,
and glial decreases have been reported in the prefrontal cortex. Here, glia and
neurons were counted in the amygdala and entorhinal cortex in major depressive
disorder, bipolar disorder, and control cases. METHODS: Tissue blocks from major
depressive disorder (7), bipolar disorder (10), and control (12) cases, equally
divided between right and left, were cut into 50 microm sections and stained with
the Nissl method. One major depressive disorder and all but two bipolar disorder
cases had been treated with lithium or valproate. Neurons and glia were counted
using stereological methods. RESULTS: Glial density and the glia/neuron ratio
were substantially reduced in the amygdala in major depressive disorder cases.
The reduction was mainly accounted for by counts in the left hemisphere. No change
was found in neurons. Average glia measures were not reduced in bipolar disorder
cases; however, bipolar disorder cases not treated with lithium or valproate had
significant glial reduction. Similar but smaller changes were found in the entorhinal
cortex. CONCLUSIONS: Glia are reduced in the amygdala in major depressive disorder,
especially on the left side. The results suggest that lithium and valproate may
moderate the glial reduction." [Abstract] Hamidi
M, Drevets WC, Price JL
Glial reduction in amygdala
in major depressive disorder is due to oligodendrocytes.
Biol
Psychiatry. 2004 Mar 15;55(6):563-9.
BACKGROUND: A previous study reported
reductions in glial density and glia/neuron ratio in the amygdala of individuals
with major depressive disorder (MDD), without a change in neuronal density. It
is not known, however, whether this glial loss is due to astrocytes, oligodendrocytes,
or microglia. METHODS: Tissue samples, equally from the right and left hemispheres,
were obtained from subjects diagnosed with MDD (n = 8), bipolar disorder (BD)
(n = 9), or no psychiatric disorders (n = 10). Sections were stained immunohistochemically
for S-100beta (for astrocytes) and human leukocyte antigen (for microglia), and
with the Nissl method. In Nissl-stained sections, oligodendrocytes have more compact,
darker-stained nuclei, whereas astrocytes and microglia have larger, lighter-stained
nuclei, with more granular chromatin. Neurons are larger, with a nucleolus and
stained cytoplasm. The density of glia was determined with stereologic methods.
RESULTS: The density of total glia and oligodendrocytes in the amygdala was significantly
lower in MDD than in control subjects, but not significantly lower in BD compared
with control subjects. The decreases were largely accounted for by differences
in the left hemisphere. There was no significant decrease in astrocyte or microglia
density in MDD or BD subjects. CONCLUSIONS: The glial cell reduction previously
found in the amygdala in MDD is primarily due to oligodendrocytes. [Abstract] Young
LT, Bezchlibnyk YB, Chen B, Wang JF, MacQueen GM
Amygdala
cyclic adenosine monophosphate response element binding protein phosphorylation
in patients with mood disorders: effects of diagnosis, suicide, and drug treatment.
Biol
Psychiatry. 2004 Mar 15;55(6):570-7.
BACKGROUND: Signal transduction abnormalities
have been identified in patients with bipolar (BD) and major depressive (MDD)
disorders and are targets for lithium and antidepressant drugs. A key downstream
target for signal transduction pathways is the transcription factor cyclic adenosine
monophosphate (cAMP) response element binding protein (CREB). Therefore, we measured
the levels of phosphorylated CREB (pCREB) in the amygdala, a region critical to
emotional processing and important in the pathophysiology of both BD and MDD.
METHODS: Human postmortem amygdala sections were generously provided by the Stanley
Foundation Neuropathology Consortium. Samples consisted of subjects with MDD,
BD, schizophrenia (SCZ), and nonpsychiatric-nonneurologic comparison subjects
(n = 15 per group). Levels of pCREB were measured by immunohistochemistry, relative
to total cell number. RESULTS: There were no differences between diagnostic groups--control
subjects and subjects with BD, MDD, or SCZ--but increased numbers of pCREB stained
cells were found in several amygdalar nuclei in subjects who had died by suicide.
In contrast, patients treated with lithium at the time of death had significantly
lower pCREB levels in the same region. CONCLUSIONS: These results suggest that
CREB activity may be an important factor in the neurobiology of suicide and the
well-documented antisuicidal effect of lithium. [Abstract] |
