Juckel G, Hegerl U, Mavrogiorgou P, Gallinat J, Mager T, Tigges
P, Dresel S, Schroter A, Stotz G, Meller I, Greil W, Moller HJ.
and biological findings in a case with 48-hour bipolar ultrarapid cycling before
and during valproate treatment.
J Clin Psychiatry 2000
"BACKGROUND: The rare cases of patients with 48-hour
ultrarapid cycling allow close investigation of mood cycles in affective disorders,
because rhythmic changes in psychopathologic state and biological parameters happen
very precisely. METHOD: A 67-year-old white man who had experienced bipolar 48-hour
ultrarapid cycling (DSM-IV 296.80) for several years was studied without any medication
and then again studied 4 weeks later during treatment with valproate (1800 mg/day).
RESULTS: Objective and self ratings revealed pronounced manic states 1 day and
depressed states the following day, which were found to be accompanied by rhythmic
fluctuations in behavior and electroencephalographic parameters, blood cortisol
and growth hormone levels (both elevated on depressive days), and urinary metanephrine
(dopamine metabolite) and norepinephrine levels (both elevated on manic days).
Using single photon emission computed tomography, regional blood flow in the left
thalamus was lower than in the right thalamus on the manic day, while symmetric
perfusion of the thalamus was found on the depressive day. Under valproate treatment,
the patient remitted completely, and significant rhythmic changes in most of the
biological parameters were no longer detectable. CONCLUSION: The biological findings
in this patient with bipolar 48-hour ultrarapid cycling, which correspond to those
in other types of affective disorders, suggest that disturbances in the diencephalon-pituitary
axis may be especially correlated to pathologic changes of mood." [Abstract]
Benke T, Kurzthaler I, Schmidauer Ch, Moncayo R, Donnemiller
Mania caused by a diencephalic lesion.
"We describe the case of a young male
patient, SN, who suffered a MR-documented ischaemic lesion of both dorsomedial
thalami and presented with a transient maniform syndrome. SN's neuropsychological,
structural and functional imaging findings are compared with similar reported
cases and are discussed in the framework of fronto-subcortical circuits and their
proposed behavioural disorders. SN's mania was characterized by restlessness,
mood elevation, a tendency for pleasurable activities, inflated self-esteem and
loss of disease awareness. Other symptoms were sexual disinhibition, tactlessness,
abnormal discourse, and reduced need for food and sleep. His neuropsychological
assessment revealed an anterograde amnesia, and an impairment of frontal-executive
functions. A SPECT-study showed diaschisis-related areas of hypoperfusion in both
prefrontal regions which were interpreted as equivalents of SN's frontal-dysexecutive
syndrome. In addition, there was a perfusion deficit in the right orbitofrontal
cortex, which was taken as the imaging correlate of SN's secondary mania and personality
disorder. These findings suggest that SN's mania and his other symptoms result
from the twofold disruption of fronto-subcortical connections, namely of the right
orbitofrontal loop which is concerned with mood regulation and socially appropriate
behaviour, and of the dorsolateral prefrontal loop which mediates executive cognitive
J, Ferrazzini M, Regli F, Assal G, Tanabe H, Delaloye-Bischof A.
delirium and frontal-like syndrome with paramedian infarction of the right thalamus.
J Neurol Neurosurg Psychiatry 1988 Jan;51(1):116-9
"A disinhibition syndrome
affecting speech (with logorrhoea, delirium, jokes, laughs, inappropriate comments,
extraordinary confabulations), was the main manifestation of a right-sided thalamic
infarct involving the dorsomedian nucleus, intralaminar nuclei and medial part
of the ventral lateral nucleus. Resolution of conflicting tasks was severely impaired,
suggesting frontal lobe dysfunction. These abnormalities correlated with the finding
on SPECT of a marked hypoperfusion in the overlying hemisphere predominating in
the frontal region. We suggest that this behavioural syndrome was produced by
disconnecting the dorsomedian nucleus from the frontal lobe and limbic system."
JL, Mendez MF.
Secondary mania with focal cerebrovascular lesions.
Am J Psychiatry 1984 Sep;141(9):1084-7
"The authors describe two patients
with secondary mania associated with right thalamic infarctions. Both patients
exhibited hemisensory loss, denial of illness, and amnesia for the manic episode.
One improved with lithium therapy and the other recovered without specific pharmacologic
intervention. A review of reported cases reveals that most focal lesions associated
with secondary mania involve the diencephalic region and that the majority of
lateralized lesions are on the right side." [Abstract]
Kromkamp M, Uylings HB, Smidt MP, Hellemons AJ, Burbach
JP, Kahn RS.
Decreased thalamic expression of the homeobox gene DLX1
Arch Gen Psychiatry. 2003 Sep;60(9):869-74.
A shared vulnerability to develop psychosis can be related to abnormalities in
thalamic circuits in schizophrenia and bipolar disorder and could be a genetic
link between these disorders. Homeobox genes involved in development and differentiation
of the brain could play an important role in these disorders. OBJECTIVE: To determine
whether patients with schizophrenia and bipolar disorder have different thalamic
expression patterns of 2 homeobox genes, DLX1 and SHOX2 (alias OG12X or SHOT)
compared with psychiatric and nonpsychiatric control subjects. DESIGN: Postmortem
sections containing the thalamic mediodorsal nucleus were subjected to in situ
hybridization with mouse Dlx1 and human SHOX2 RNA probes. The number of both DLX1-
and SHOX2-positive neurons relative to Nissl-stained neurons was estimated in
systematic randomly sampled volume probes.Patients Fifteen patients with schizophrenia,
15 with bipolar disorder with or without history of psychosis, 15 with major depressive
disorder, and 15 nonpsychiatric controls from the Stanley Foundation Brain Bank.
MAIN OUTCOME MEASURE: Relative numbers of DLX1- and SHOX2-positive neurons in
patients with schizophrenia and bipolar disorder with history of psychosis compared
with psychiatric and nonpsychiatric controls. RESULTS: Patients with a history
of psychosis showed significantly decreased relative numbers of DLX1-positive
neurons compared with patients without history of psychosis and nonpsychiatric
controls (P =.02), whereas no differences could be found in relative numbers of
SHOX2-positive neurons (P>.15). Results were obtained blind to diagnosis, symptoms,
or any other variable except hemisphere. CONCLUSION: Decreased thalamic expression
of DLX1 in schizophrenia and bipolar disorder with psychosis suggests shared genetic
deficits in expression of this homeobox gene." [Abstract]
A. Castro-Alamancos, and Maria E. Calcagnotto
of Corticothalamic Activity by Neuromodulators Released in the Thalamus During
Arousal: In Vitro and In Vivo
J Neurophysiol 85: 1489-1497,
"The thalamus is the principal relay station of sensory information
to the neocortex. In return, the neocortex sends a massive feedback projection
back to the thalamus. The thalamus also receives neuromodulatory inputs from the
brain stem reticular formation, which is vigorously activated during arousal.
We investigated the effects of two neuromodulators, acetylcholine and norepinephrine,
on corticothalamic responses in vitro and in vivo. Results from rodent slices
in vitro showed that acetylcholine and norepinephrine depress the efficacy of
corticothalamic synapses while enhancing their frequency-dependent facilitation.
This produces a stronger depression of low-frequency responses than of high-frequency
responses. The effects of acetylcholine and norepinephrine were mimicked by muscarinic
and alpha(2)-adrenergic receptor agonists and blocked by muscarinic and alpha-adrenergic
antagonists, respectively. Stimulation of the brain stem reticular formation in
vivo also strongly depressed corticothalamic responses. The suppression was very
strong for low-frequency responses, which do not produce synaptic facilitation,
but absent for high-frequency corticothalamic responses. As in vitro, application
of muscarinic and alpha-adrenergic antagonists into the thalamus in vivo abolished
the suppression of corticothalamic responses induced by stimulating the reticular
formation. In conclusion, cholinergic and noradrenergic activation during arousal
high-pass filters corticothalamic activity. Thus, during arousal only high-frequency
inputs from the neocortex are allowed to reach the thalamus. Neuromodulators acting
on corticothalamic synapses gate the flow of cortical activity to the thalamus
as dictated by behavioral state." [Full
Castro-Alamancos, Manuel A.
of Thalamocortical Sensory Suppression during Arousal: Focusing Sensory Inputs
J. Neurosci. 2002 22: 9651-9655
thalamus serves as a gate that regulates the flow of sensory inputs to the neocortex,
and this gate is controlled by neuromodulators from the brainstem reticular formation
that are released during arousal. We found recently that sensory-evoked responses
are suppressed in the neocortex during arousal. This sensory suppression results
from the activity-dependent depression of the thalamocortical connection caused
by increased tonic firing of thalamocortical cells during arousal. In the present
study, the functional consequences of thalamocortical suppression during arousal
were investigated using the vibrissae system of rodents. The results show that
thalamocortical suppression is associated with a strong reduction in the spread
of sensory inputs through the cortex, thus reducing the size of sensory representations.
In addition, when the responses of single cells to principal and adjacent whiskers
are compared, the response to the adjacent whiskers was found to be strongly suppressed,
much more so than that of principal whiskers. Consequently, the receptive fields
of cortical neurons become more focused to the principal whisker. The results
indicate that thalamocortical suppression during arousal serves to focus sensory
inputs to their appropriate representations in neocortex, which may be computationally
helpful for the spatial processing of sensory information." [Abstract]
Anatomical evidence concerning the role of the thalamus in corticocortical
communication: a brief review.
J Anat 1995 Dec;187 ( Pt
"Two distinct types of thalamic nucleus are proposed on the
basis of the afferent fibres that they receive from ascending pathways and from
the cerebral cortex. 'First order nuclei' receive primary afferent fibres, definable
on the basis of their origin and their intrathalamic synaptic relationships, from
ascending pathways. These nuclei receive corticothalamic afferents from pyramidal
cells in cortical layer 6, which also send branches to the thalamic reticular
nucleus and appear to have a modulatory function. 'Higher order nuclei' receive
most or all of their 'primary afferents' from pyramidal cells in cortical layer
5. These resemble the ascending primary afferents in the first order nuclei in
terms of fine structure, synaptic relationships and in lacking a branch to the
thalamic reticular nucleus. The higher order nuclei also receive modulatory afferents
from layer 6. It is proposed that the higher-order nuclei are largely concerned
with transmitting information about the output of one cortical area to another
cortical area, and that they are likely to play a key role in corticocortical
communication and higher cortical functions." [Abstract]
Blumberg HP, Martin A, Kaufman J, Leung HC, Skudlarski
P, Lacadie C, Fulbright RK, Gore JC, Charney DS, Krystal JH, Peterson BS.
abnormalities in adolescents with bipolar disorder: preliminary observations from
Am J Psychiatry. 2003 Jul;160(7):1345-7.
This study investigated whether the functional abnormalities in prefrontal systems
observed in adult bipolar disorder are manifested in adolescents with this illness.
METHOD: Ten adolescents with bipolar disorder and 10 healthy comparison subjects
participated in a color-naming Stroop task during event-related functional magnetic
resonance imaging. RESULTS: Signal increases in the left putamen and thalamus
were significantly greater in the bipolar disorder group than in the healthy group.
Age correlated positively with signal increases in the bilateral rostroventral
prefrontal cortex and the striatum in the healthy group but not in the bipolar
disorder group. In the bipolar disorder subjects, depressive symptoms correlated
positively with signal increases in the ventral striatum. CONCLUSIONS: These findings
suggest the presence of dysfunction in the subcortical portions of the frontostriatal
circuits in adolescents with bipolar disorder. The absence of the prefrontal abnormalities
that were observed previously in adults and the absence of the age-related increases
in prefrontal activity observed in normal comparison subjects suggest that a developmental
disturbance in prefrontal function may emerge in bipolar disorder over the course
of adolescence." [Abstract]
M, Friedman L, Jesberger J, Stuve TA, Findling RL, Swales TP, Schulz SC.
magnetic resonance imaging study of thalamic area in adolescent patients with
either schizophrenia or bipolar disorder as compared to healthy controls.
Psychiatry Res 1999 Oct 11;91(3):155-62
"The purpose of this study was
to compare thalamic size in adolescent patients with either schizophrenia or bipolar
disorder and healthy controls. T2-weighted axial magnetic resonance images were
used to manually define the area of the thalamus for 20 schizophrenia patients,
15 bipolar patients and 16 normal control subjects, all of whom were adolescents.
Two orthogonal planned contrasts were tested: Contrast 1, patients with schizophrenia
vs. patients with bipolar disorder; and Contrast 2, both patient groups taken
as a single group compared to controls. Contrast 1 was not statistically significant
for right or left thalamic area. Contrast 2 was statistically significant and
indicated reductions in thalamic area in the patients as compared to controls.
The same pattern of results emerged after adjustment for total brain volume. Our
results indicate that thalamic abnormalities reported in adult schizophrenic and
bipolar patients are also observed in adolescent patients. Our findings also add
to the evidence implicating the thalamus in the pathophysiology of schizophrenia
and bipolar disorder." [Abstract]
SC, Sassi R, Brambilla P, Harenski K, Nicoletti M, Mallinger AG, Frank E, Kupfer
DJ, Keshavan MS, Soares JC.
MRI study of thalamic volumes in bipolar
and unipolar patients and healthy individuals.
Res 2001 Dec 30;108(3):161-8
"The thalamus is a key structure in brain
anatomic circuits potentially involved in the pathophysiology of mood disorders.
Available findings from studies that examined this brain region in mood disorder
patients have been conflicting. To examine the hypothesis of anatomical abnormalities
in the thalamus in patients with mood disorders, we conducted a magnetic resonance
imaging (MRI) study in 25 bipolar patients (mean age+/-S.D.=34.4+/-9.8 years),
17 unipolar patients (mean age+/-S.D.=42.8+/-9.2 years), and 39 healthy control
subjects (mean age+/-S.D.=36.6+/-9.7 years). Thalamic volumes Gray Matter were
measured blindly with a semi-automated technique. Multivariate analysis of variance,
with age and gender as covariates, revealed no significant differences in left
or right thalamic volumes among bipolar patients, unipolar patients and healthy
individuals. There were no significant effects of gender, age at illness onset,
episode type, number of episodes, length of illness, or family history of mood
disorders on thalamic measurements. Although functional abnormalities in the thalamus
are likely to be implicated in the pathophysiology of mood disorders, no abnormalities
in thalamic size appear present in bipolar or unipolar individuals." [Abstract]
SE, Fedoroff P, Berthier ML, Robinson RG.
pure manic states after brain lesions.
1991 Jan 15;29(2):149-58
"Although mania is a rare complication of brain
lesions, recent reports have emphasized the importance of lesion location and
genetic predisposition in these patients. In the present study we compared patients
who developed a bipolar affective disorder (i.e., mania and depression) after
a brain lesion with patients who only developed mania. Although no significant
between-group differences were found on demographic variables, the manic-depressed
group showed significantly more impairments on the Mini Mental State Exam than
the mania only group. All the bipolar patients had subcortical lesions (mainly
right head of the caudate and right thalamus), while patients with unipolar mania
had significantly higher frequency of cortical involvement (mainly right orbitofrontal
and basotemporal cortices). It is suggested that subcortical and cortical right
hemisphere lesions may produce different neurochemical and/or remote metabolic
brain changes that may underlie the production of either a bipolar disease or
a unipolar mania." [Abstract]
JK, Huguelet P, Ohl LE, Koeppe RA, Kilbourn MR, Carr JM, Giordani BJ, Frey KA.
High vesicular monoamine transporter binding in asymptomatic bipolar
I disorder: sex differences and cognitive correlates.
J Psychiatry 2000 Oct;157(10):1619-28
"OBJECTIVE: It has been hypothesized
that anomalies in monoaminergic function underlie some of the manifestations of
bipolar disorder. In this study the authors examined the possibility that trait-related
abnormalities in the concentration of monoaminergic synaptic terminals may be
present in patients with asymptomatic bipolar disorder type I. METHOD: The concentration
of a stable presynaptic marker, the vesicular monoamine transporter protein (VMAT2),
was quantified with (+)[(11)C]dihydrotetrabenazine (DTBZ) and positron emission
tomography. Sixteen asymptomatic patients with bipolar I disorder who had a prior
history of mania with psychosis (nine men and seven women) and individually matched
healthy subjects were studied. Correlational analyses were conducted to examine
the relationship between regional VMAT2 binding, cognitive function, and clinical
variables. RESULTS: VMAT2 binding in the thalamus and ventral brainstem of the
bipolar patients was higher than that in the comparison subjects. VMAT2 concentrations
in these regions correlated with performance on measures of frontal, executive
function. In addition, sex differences in VMAT2 binding were detected in the thalamus
of the bipolar patients; the male patients had higher binding than the women.
No sex differences in binding were observed in the healthy comparison group. CONCLUSIONS:
These initial results suggest that higher than normal VMAT2 expression and, by
extension, concentration of monoaminergic synaptic terminals, may represent a
trait-related abnormality in patients with bipolar I disorder and that male and
female patients show different patterns. Also, VMAT2 concentrations may be associated
with some of the cognitive deficits encountered in euthymic bipolar disorder."
RF, Eliaz Y, Feiwell R, Schuff N.
Increased thalamic N-acetylaspartate
in male patients with familial bipolar I disorder.
Res 2001 Feb 28;106(1):35-45
"N-Acetylaspartate (NAA) in the anterior
and mediodorsal thalamic regions was measured using proton magnetic resonance
spectroscopic imaging (1H-MRSI) in 15 euthymic male patients with familial bipolar
I disorder and compared to values in 15 male control subjects to determine if
there was evidence for altered neuronal/axonal integrity. MRI tissue segmentation
methods were also utilized to obtain tissue-contribution estimates for each MRSI
voxel. Relative to the comparison group, the patients with bipolar I disorder
demonstrated significantly higher NAA and creatine in both the right and left
thalamus. NAA was also significantly higher in the left thalamus compared to the
right in both bipolar I patients and controls. There were no group or lateralized
differences in the percentages of different tissue types within the MRSI voxels,
suggesting that the thalamic NAA and creatine alterations were not an artifact
of variations in tissue type percentages in the MRSI voxels. There was also no
significant association between NAA or creatine and illness duration. The findings
of increased thalamic NAA bilaterally may represent neuronal hypertrophy or hyperplasia,
reduced glial cell density, or abnormal synaptic and dendritic pruning. Increased
thalamic creatine bilaterally may represent altered cellular energy metabolism
and is consistent with prior studies demonstrating changes in thalamic metabolism
in mood disorders." [Abstract]
J, Berthier ML, Gironell A, Pascual-Sedano B, Molet J, Pares P.
following deep brain stimulation for Parkinson's disease.
2002 Nov 12;59(9):1421-4.
"Three patients with PD developed manic behavior
after bilateral implantation of electrodes for deep-brain stimulation (DBS). Common
to all three patients were manic symptoms unremitting after levodopa reduction
or stimulation "off," lower electrodes positioning caudal to the subthalamic
nucleus area, postoperative DBS with the lower contacts (0) of the quadripolar
electrodes, and resolution of the manic episodes coinciding with stimulation through
higher contacts." [Abstract]
Romito LM, Raja M, Daniele A, Contarino MF, Bentivoglio
AR, Barbier A, Scerrati M, Albanese A.
Transient mania with hypersexuality
after surgery for high frequency stimulation of the subthalamic nucleus in Parkinson's
Mov Disord. 2002 Nov;17(6):1371-4.
30 Parkinson's disease patients who received high frequency stimulation of the
subthalamic nucleus, 5 developed remarkable disorders of mood or sexual behavior
after the implant. We describe 2 men who developed mania and hypersexuality a
few days after the implant that lasted for some months and then gradually disappeared