P.0887 Extended prefrontal cortex recruitment in euthymic bipolar patients during a self-referential task

Bipolar disorder is a chronic multifactorial psychiatric illness that affects the mood, cognition, and functioning of about 1–2% of the world’s population. Its biological basis is unknown, and its treatment is unsatisfactory. The α1, α2, and α3 isoforms of the Na+, K+-ATPase, an essential membrane transporter, are vital for neuronal and glial function. The enzyme and its regulators, endogenous cardiac steroids like ouabain and marinobufagenin, are implicated in neuropsychiatric disorders, bipolar disorder in particular. Here, we address the hypothesis that the α isoforms of the Na+, K+-ATPase and its regulators are altered in the prefrontal cortex of bipolar disease patients. The α isoforms were determined by Western blot and ouabain and marinobufagenin by specific and sensitive immunoassays. We found that the α2 and α3 isoforms were significantly higher and marinobufagenin levels were significantly lower in the prefrontal cortex of the bipolar disease patients compared with those in the control. A positive correlation was found between the levels of the three α isoforms in all samples and between the α1 isoform and ouabain levels in the controls. These results are in accordance with the notion that the Na+, K+-ATPase-endogenous cardiac steroids system is involved in bipolar disease and suggest that it may be used as a target for drug development.

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Normal Metabolic Levels in Prefrontal Cortex in Euthymic Bipolar I Patients with and without Suicide Attempts

Neural Plasticity ◽

10.1155/2015/165180 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Marlos Vasconcelos Rocha ◽

Fabiana Nery-Fernandes ◽

José Luiz Guimarães ◽

Lucas de Castro Quarantini ◽

Irismar Reis de Oliveira ◽

...

Keyword(s):

Prefrontal Cortex ◽

Healthy Subjects ◽

Rating Scale ◽

Suicide Attempts ◽

Resonance Spectroscopy ◽

Type I ◽

Young Mania ◽

Suicide Attempters ◽

Axis I ◽

Bipolar Patients

Introduction/Objective. Evidence suggests that the prefrontal cortex has been implicated in the pathophysiology of bipolar disorder (BD), but few neurochemical studies have evaluated this region in bipolar patients and there is no information from BD suicide attempters using Proton Magnetic Resonance Spectroscopy (H+MRS). The objective was to evaluate the metabolic function of the medial orbital frontal cortex in euthymic BD type I suicide and nonsuicide attempters compared to healthy subjects by H+MRS.Methods. 40 euthymic bipolar I outpatients, 19 without and 21 with history of suicide attempt, and 22 healthy subjects were interviewed using the Structured Clinical Interview with the DSM-IV axis I, the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Barratt Impulsiveness Scale-11 and underwent H+MRS.Results. We did not find any metabolic abnormality in medial orbital frontal regions of suicide and nonsuicide BD patients and BD patients as a group compared to healthy subjects.Conclusions. The combined chronic use of psychotropic drugs with neuroprotective or neurotrophic effects leading to a euthymic state for longer periods of time may improve neurometabolic function, at least measured by H+MRS, even in suicide attempters. Besides, these results may implicate mood dependent alterations in brain metabolic activity. However, more studies with larger sample sizes of this heterogeneous disorder are warranted to clarify these data.

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Brain functional changes in first-degree relatives of patients with bipolar disorder: evidence for default mode network dysfunction

Psychological Medicine ◽

10.1017/s0033291716001148 ◽

2016 ◽

Vol 46 (12) ◽

pp. 2513-2521 ◽

Cited By ~ 7

Author(s):

S. Alonso-Lana ◽

M. Valentí ◽

A. Romaguera ◽

C. Sarri ◽

S. Sarró ◽

...

Keyword(s):

Bipolar Disorder ◽

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Default Mode Network ◽

Healthy Controls ◽

Whole Brain ◽

Default Mode ◽

Functional Changes ◽

Significant Difference ◽

Bipolar Patients

BackgroundRelatively few studies have investigated whether relatives of patients with bipolar disorder show brain functional changes, and these have focused on activation changes. Failure of de-activation during cognitive task performance is also seen in the disorder and may have trait-like characteristics since it has been found in euthymia.MethodA total of 20 euthymic patients with bipolar disorder, 20 of their unaffected siblings and 40 healthy controls underwent functional magnetic resonance imaging during performance of the n-back working memory task. An analysis of variance (ANOVA) was fitted to individual whole-brain maps from each set of patient–relative–matched pair of controls. Clusters of significant difference among the groups were used as regions of interest to compare mean activations/de-activations between them.ResultsA single cluster of significant difference among the three groups was found in the whole-brain ANOVA. This was located in the medial prefrontal cortex, a region of task-related de-activation in the healthy controls. Both the patients and their siblings showed significantly reduced de-activation compared with the healthy controls in this region, but the failure was less marked in the relatives.ConclusionsFailure to de-activate the medial prefrontal cortex in both euthymic bipolar patients and their unaffected siblings adds to evidence for default mode network dysfunction in the disorder, and suggests that it may act as a trait marker.

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CACNB2 rs11013860 polymorphism correlates of prefrontal cortex thickness in bipolar patients with first-episode mania

Journal of Affective Disorders ◽

10.1016/j.jad.2020.02.007 ◽

2020 ◽

Vol 268 ◽

pp. 82-87

Author(s):

Jianshan Chen ◽

Jiuwei Tan ◽

Andrew J Greenshaw ◽

Jeff Sawalha ◽

Yang Liu ◽

...

Keyword(s):

Prefrontal Cortex ◽

First Episode ◽

Bipolar Patients

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Dorsolateral prefrontal N-acetyl-aspartate concentration in male patients with chronic schizophrenia and with chronic bipolar disorder

European Psychiatry ◽

10.1016/j.eurpsy.2007.07.006 ◽

2007 ◽

Vol 22 (8) ◽

pp. 505-512 ◽

Cited By ~ 43

Author(s):

V. Molina ◽

J. Sánchez ◽

J. Sanz ◽

S. Reig ◽

C. Benito ◽

...

Keyword(s):

Bipolar Disorder ◽

Prefrontal Cortex ◽

Chronic Schizophrenia ◽

The Other ◽

Resonance Spectroscopy ◽

Dorsolateral Prefrontal ◽

Prefrontal Region ◽

Healthy Control ◽

Male Patients ◽

Bipolar Patients

AbstractObjectivesA study of N-acetyl-aspartate (NAA) can provide data of interest about cortical alterations in psychotic illnesses. Although a decreased NAA level in the cerebral cortex is a replicated finding in chronic schizophrenia, the data are less consistent for bipolar disease. On the other hand, it is likely that NAA values in schizophrenia may differ in men and women.MethodsWe used proton magnetic resonance spectroscopy (1H MRS) to examine NAA levels in the prefrontal cortex in two groups of male patients, one with schizophrenia (n = 11) and the other with bipolar disorder (n = 13) of similar duration, and compared them to a sample of healthy control males (n = 10). Additionally, we compared the degree of structural deviations from normal volumes of gray matter (GM) and cerebrospinal fluid (CSF) in the dorsolateral prefrontal cortex.ResultsCompared to controls, schizophrenia and bipolar patients presented decreased NAA to creatine ratios, while only the schizophrenia group showed an increase in CSF in the dorsolateral prefrontal region. There were no differences in choline to creatine ratios among the groups.ConclusionsThese data suggest that the decrease in NAA in the prefrontal region may be similar in schizophrenia and bipolar disorder, at least in the chronic state. However, cortical CSF may be markedly increased in schizophrenia patients.

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Anatomical MRI Abnormalities in Bipolar Disorder: Do They Exist and Do They Progress?

Australian & New Zealand Journal of Psychiatry ◽

10.1080/j.1440-1614.2005.01571.x ◽

2005 ◽

Vol 39 (4) ◽

pp. 222-226 ◽

Cited By ~ 3

Author(s):

E. Serap Monkul ◽

Gin S. Malhi ◽

Jair C. Soares

Keyword(s):

Bipolar Disorder ◽

Prefrontal Cortex ◽

Brain Imaging ◽

Grey Matter ◽

Brain Structures ◽

Brain Regions ◽

Anterior Cingulate ◽

Imaging Studies ◽

Neuroprotective Effects ◽

Bipolar Patients

Aim: Morphometric brain imaging studies have revealed regional brain abnormalities in patients with bipolar disorder, which may play a role in illness pathophysiology. It is not known whether such changes are of neurodevelopmental, neurodegenerative, or combined origin. We reviewed the anatomical brain imaging literature in bipolar disorder, in an attempt to determine whether there is evidence to suggest that such abnormalities are progressive. Method: Literature searches were conducted using MEDLINE for the period from 1966 to June 2004, using specific key words; bipolar disorder and the names of the individual brain structures. Papers were selected according to their salience in relation to whether reported changes are progressive. Results: Available findings suggest reduced grey matter in prefrontal brain regions such as anterior cingulate and subgenual prefrontal cortex, and abnormalities in amygdala size in adult and paediatric bipolar patients. White matter hyperintensities, which are non-specific abnormalities, are also common in bipolar patients. Bipolar patients may lose more brain grey matter by ageing. There is also evidence for impaired myelination of the corpus callosum in bipolar disorder. Lithium may reverse or prevent grey matter prefrontal cortex abnormalities in bipolar patients by its neuroprotective effects. Conclusions: Both early developmental and later neurodegenerative processes may play a role in the pathophysiology of bipolar disorder. Findings from anatomical brain imaging studies implicate key regions involved in mood regulation. The evidence for the progressive nature of this illness is tentative, as no follow-up study with bipolar patients has been reported to this date.

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Low Levels of N-Acetyl Aspartate in the Left Dorsolateral Prefrontal Cortex of Pediatric Bipolar Patients

Journal of Child and Adolescent Psychopharmacology ◽

10.1089/cap.2007.0102 ◽

2007 ◽

Vol 17 (4) ◽

pp. 461-473 ◽

Cited By ~ 32

Author(s):

Rene L. Olvera ◽

Sheila C. Caetano ◽

Manoela Fonseca ◽

Mark Nicoletti ◽

Jeffrey A. Stanley ◽

...

Keyword(s):

Prefrontal Cortex ◽

Dorsolateral Prefrontal Cortex ◽

Dorsolateral Prefrontal ◽

Low Levels ◽

Bipolar Patients

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A functional MRI study of verbal fluency in adults with bipolar disorder and their unaffected relatives

Psychological Medicine ◽

10.1017/s0033291710000127 ◽

2010 ◽

Vol 40 (12) ◽

pp. 2025-2035 ◽

Cited By ~ 40

Author(s):

M. P. G. Allin ◽

N. Marshall ◽

K. Schulze ◽

M. Walshe ◽

M.-H. Hall ◽

...

Keyword(s):

Bipolar Disorder ◽

Prefrontal Cortex ◽

Verbal Fluency ◽

Retrosplenial Cortex ◽

Control Group ◽

Verbal Fluency Task ◽

Easy Condition ◽

Bipolar Patients ◽

Mri Study ◽

Fluency Task

BackgroundIndividuals with a history of bipolar disorder demonstrate abnormalities of executive function, even during euthymia. The neural architecture underlying this and its relationship with genetic susceptibility for illness remain unclear.MethodWe assessed 18 remitted individuals with bipolar disorder, 19 of their unaffected first degree relatives and 19 healthy controls using functional magnetic resonance imaging (fMRI) and a paced verbal fluency task with two levels of difficulty.ResultsBipolar patients made significantly more errors in the easy level of the verbal fluency task than their relatives or controls. Analysis of variance of fMRI data demonstrated a significant main effect of group in a large cluster including retrosplenial cortex and adjacent precuneate cortex (x=7, y=−56, x=15). All three groups showed deactivation in these areas during task performance relative to a neutral or rest condition. Group differences comprised a lesser amount of deactivation in unaffected relatives compared with controls in the easy condition [F(2, 55)=3.42, p=0.04] and in unaffected relatives compared with bipolar patients in the hard condition [F(2, 55)=4.34, p=0.018]. Comparison with the control group indicated that both bipolar patients and their relatives showed similar deficits of deactivation in retrosplenial cortex and reduced activation of left prefrontal cortex.ConclusionsBipolar disorder may be associated with an inherited abnormality of a neural network incorporating left prefrontal cortex and bilateral retrosplenial cortex.

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