Anatomical MRI findings in mood and anxiety disorders

Brambilla, Paolo; Barale, Francesco; Caverzasi, Edgardo; Soares, Jair C.

doi:10.1017/s1121189x00005558

Cited by 95 publications

(55 citation statements)

References 145 publications

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“…First, the effect of structurally different antimanic agents (such as lithium or VPA) had a common effect on GluR1/2 synaptic localization. Second, the attenuation of synaptic GluR1/2 by lithium or VPA occurred in the hippocampus, which is a brain region known to involve neuronal circuits critical for affective disorders (Brambilla et al, 2002;Velakoulis et al, 2006;Atmaca et al, 2007). Third, the effect of lithium or VPA on synaptic GluR1/2 occurred at therapeutically relevant concentrations both in vivo and in Figure 5.…”

Section: Regulation Of Ampa Receptor Trafficking By Antimanic Agents mentioning

confidence: 99%

“…Accumulating evidence suggests an association between the hippocampal region and bipolar disorder (Brambilla et al, 2002;Velakoulis et al, 2006;Atmaca et al, 2007). For instance, functional MRI has identified hippocampal morphological abnormalities in bipolar patients (Brambilla et al, 2002;Velakoulis et al, 2006;Atmaca et al, 2007).…”

Section: Regulation Of Ampa Receptor Trafficking By Antimanic Agents mentioning

confidence: 99%

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The Role of Hippocampal GluR1 and GluR2 Receptors in Manic-Like Behavior

Du¹,

Creson²,

Ren³

et al. 2008

J. Neurosci.

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The cellular basis underlying the complex clinical symptomatology of bipolar disorder and the mechanisms underlying the actions of its effective treatments have not yet been fully elucidated. This study investigated the role of hippocampal synaptic AMPA receptors. We found that chronic administration of the antimanic agents lithium and valproate (VPA) reduced synaptic AMPA receptor GluR1/2 in hippocampal neurons in vitro and in vivo. Electrophysiological studies confirmed that the AMPA/NMDA ratio was reduced in CA1 regions of hippocampal slices from lithium-treated animals. Reduction in GluR1 phosphorylation at its cAMP-dependent protein kinase A site by the synthetic peptide TAT-S845, which mimics the effects of lithium or VPA, was sufficient to attenuate surface and synaptic GluR1/2 levels in hippocampal neurons in vitro and in vivo. Intrahippocampal infusion studies with the AMPA-specific inhibitor GYKI [4-(8-methyl-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepin-5-yl)-benzenamine hydrochloride], a GluR1-specific TAT-S845 peptide, showed that GluR1/2 was essential for the development of manic/hedonic-like behaviors such as amphetamine-induced hyperactivity. These studies provide novel insights into the role of hippocampal GluR1/2 receptors in mediating facets of the manic syndrome and offer avenues for the development of novel therapeutics for these disorders.

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Section: Regulation Of Ampa Receptor Trafficking By Antimanic Agents mentioning

confidence: 99%

Section: Regulation Of Ampa Receptor Trafficking By Antimanic Agents mentioning

confidence: 99%

The Role of Hippocampal GluR1 and GluR2 Receptors in Manic-Like Behavior

Du¹,

Creson²,

Ren³

et al. 2008

J. Neurosci.

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“…200 Possible explanations for the discrepant nature of the reports are discussed in detail in several reviews and include not only variability in scan parameters, but also heterogeneity of patients along dimensions such as chronicity of illness, comorbidity, and medication exposure. 191,201,202 Several investigators have attempted to identify subgroups of patients for study, such as those with familial vs nonfamilial BD. Two groups found significant reductions in grey matter volume in the subgenual prefrontal cortex in family history-positive subjects, suggesting that studying more homogenous patient groups may result in more consistent findings as further studies emerge.…”

Section: Brain Imaging and Endophenotypesmentioning

confidence: 99%

The phenotypes of bipolar disorder: relevance for genetic investigations

2005

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The search for susceptibility genes for bipolar disorder (BD) depends on appropriate definitions of the phenotype. In this paper, we review data on diagnosis and clinical features of BD that could be used in genetic studies to better characterize patients or to define homogeneous subgroups. Clinical symptoms, long-term course, comorbid conditions, and response to prophylactic treatment may define groups associated with more or less specific loci. One such group is characterized by symptoms of psychosis and linkage to 13q and 22q. A second group includes mainly bipolar II patients with comorbid panic disorder, rapid mood switching, and evidence of chromosome 18 linkage. A third group comprises typical BD with an episodic course and favourable response to lithium prophylaxis. Reproducibility of cognitive deficits across studies raises the possibility of using cognitive profiles as endophenotypes of BD, with deficits in verbal explicit memory and executive function commonly reported. Brain imaging provides a more ambiguous data set consistent with heterogeneity of the illness. Keywords: bipolar disorder; genetics; endophenotype; neurocognitive function; brain imaging Bipolar disorder (BD) has a genetic basis with heritability of at least 80%. 1 A number of studies have attempted to map the susceptibility loci giving evidence of linkage in multiple genomic regions. In particular, findings in 4p, 4q, 8q, 10p, 12q24, 13q, 18p, 18q, 21q, and 22q have been supported by more than one study. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] However, these studies have not identified any specific genes, and a recent metaanalysis of available genome scans showed no regions with a conclusive evidence of linkage. 20 The relatively slow progress of gene-mapping efforts is often explained by the 'complex' nature of the illness and of the genotype-phenotype relation. The complexity most likely includes heterogeneity, interactions of multiple loci, incomplete penetrance, as well as phenotypes resulting from environmental effects-either alone or in interaction with the genetic predisposition. The goal of psychiatric genetic research is identification of (heritable) variations in DNA sequence or function that influence behaviour or give rise to mental illness. By definition, in complex (multifactorial) traits, this link is not unique and specific. That is, a particular change in gene sequence does not necessarily lead to a specific behaviour, and similar behaviours (symptoms) may be due to distinct (sets of) genes. Moreover, we must consider the possibility that the path between the genotype and behaviour is not unidirectional. Emerging examples point not only to general effects of environment, for instance stress, on behaviour, but also to specific behaviours influencing gene function that can be transmitted onto the next generation. 21 No single method is considered clearly superior in identifying susceptibility genes for complex traits such as BD. Most researchers agree that a combination of strategies is most lik...

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“…Therefore, it is of great interest to examine the dorsolateral prefrontal cortex (DLPFC; ie, Brodmann's areas 9 and 46) of healthy individuals with 1 H MRS before and after lithium administration. The DLPFC was chosen as our target region as in recent years, structural, functional, and neurochemical brain imaging studies have implicated abnormalities in prefrontal cortex circuits in the pathophysiology of mood disorders (Brambilla et al, 2002b;Morice, 1990;Sax et al, 1999;Soares and Mann, 1997). The DLPFC is an important area of the prefrontal cortex receiving projections from higher order association centers and playing a key role in cognitive and executive brain functions (Nauta, 1971;Quintana and Fuster, 1999).…”

Section: Introductionmentioning

confidence: 99%

1H MRS Study of Dorsolateral Prefrontal Cortex in Healthy Individuals before and after Lithium Administration

Brambilla

Stanley

Sassi

et al. 2004

Neuropsychopharmacol

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The mechanism of action of lithium is still largely unknown. However, recent animal and human studies suggested the possible neuroprotective effects of this medication. In particular, a recent magnetic resonance spectroscopy (MRS) study showed the increase of cortical brain levels of N-acetyl-aspartate (NAA), a putative marker of neuronal integrity/functioning, in both bipolar patients and normal controls after 4 weeks of lithium administration. We investigated the effects of lithium on NAA levels in a sample of healthy individuals using in vivo 1 H MRS in dorsolateral prefrontal cortex (DLPFC), a region likely implicated in the pathophysiology of bipolar disorder. In vivo short echo-time 1 H-MRS measurements of 8 cm 3 single voxels placed bilaterally in the DLPFC were conducted at baseline and after 4 weeks of lithium administration on 12 healthy individuals (mean age7SD ¼ 25.079.8 years; six males). After lithium administration, no significant differences in NAA, phosphocreatine plus creatine, glycerophosphocholine plus phosphocholine (or choline-containing molecules), and myo-inositol absolute levels or ratios were found in DLPFC (paired t-tests, p40.05). Contrary to prior MRS reports in bipolar patients, we found that lithium administration did not significantly increase NAA levels in the DLPFC of healthy individuals. Future longitudinal studies will be needed to further investigate whether chronic lithium treatment increases NAA levels in other brain regions in healthy individuals, and whether it promotes changes in these levels in specific brain regions in bipolar patients.

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Anatomical MRI findings in mood and anxiety disorders

Cited by 95 publications

References 145 publications

The Role of Hippocampal GluR1 and GluR2 Receptors in Manic-Like Behavior

The Role of Hippocampal GluR1 and GluR2 Receptors in Manic-Like Behavior

The phenotypes of bipolar disorder: relevance for genetic investigations

1H MRS Study of Dorsolateral Prefrontal Cortex in Healthy Individuals before and after Lithium Administration

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