Regional prefrontal gray and white matter abnormalities in bipolar disorder

Lopez-Larson, Melissa; DelBello, Melissa P.; Zimmerman, Molly E.; Schwiers, Michael; Strakowski, Stephen M.

doi:10.1016/s0006-3223(02)01350-1

Cited by 259 publications

(179 citation statements)

References 43 publications

Supporting

Mentioning

154

Contrasting

Unclassified

Order By: Relevance

“…44 Additionally, post-mortem investigations have shown decreased gray matter volume, lower DHA concentrations, and reduced neuronal and glial densities in the frontal cortex of bipolar disorder patients. 12,[45][46][47] Upon finding that BDNF, phosphorylated CREB and p38 MAPK were decreased in the rat frontal cortex after 15 weeks of dietary n-3 PUFA deprivation, we used rat primary cortical astrocytes to show that DHA induction of BDNF was blocked by a p38 MAPK inhibitor.…”

Section: Introductionmentioning

confidence: 99%

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

et al. 2006

Mol Psychiatry

257

151

View full text Add to dashboard Cite

Decreased docosahexaenoic acid (DHA) and brain-derived neurotrophic factor (BDNF) have been implicated in bipolar disorder. It also has been reported that dietary deprivation of n-3 polyunsaturated fatty acids (PUFAs) for 15 weeks in rats, increased their depression and aggression scores. Here, we show that n-3 PUFA deprivation for 15 weeks decreased the frontal cortex DHA level and reduced frontal cortex BDNF expression, cAMP response element binding protein (CREB) transcription factor activity and p38 mitogen-activated protein kinase (MAPK) activity. Activities of other CREB activating protein kinases were not significantly changed. The addition of DHA to rat primary cortical astrocytes in vitro, induced BDNF protein expression and this was blocked by a p38 MAPK inhibitor. DHA's ability to regulate BDNF via a p38 MAPK-dependent mechanism may contribute to its therapeutic efficacy in brain diseases having disordered cell survival and neuroplasticity.

show abstract

Section: Introductionmentioning

confidence: 99%

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

et al. 2006

Mol Psychiatry

257

151

View full text Add to dashboard Cite

show abstract

“…The etiology of this lack of functional activation remains unknown. Reduced gray matter in the IFC has been reported in several studies (Lopez-Larson et al, 2002;Lyoo et al, 2004;Foland-Ross et al, 2011), and reduced frontal gray matter density may provide an explanation for the functional abnormalities seen in patients with bipolar disorder across mood states. Alternatively, deficits in white matter tracts (Adler et al, 2004;Beyer et al, 2005) or white matter volume (Kieseppa et al, 2003) could also result in a disruption of normal activation in this frontal-striatal circuit.…”

Section: Discussionmentioning

confidence: 71%

Frontal lobe hypoactivation in medication-free adults with bipolar II depression during response inhibition

Penfold¹,

Vizueta²,

Townsend³

et al. 2015

Psychiatry Research: Neuroimaging

View full text Add to dashboard Cite

“…192 Regions of particular interest in BD, including the hippocampus and amygdala, for example, have been reported to be increased, decreased, and not changed. Some segmentation studies report decreased overall grey matter volumes, 193,194 but others have found no difference compared with control subjects. 195 No decreases in overall white matter volumes were apparent in several studies.…”

Section: Brain Imaging and Endophenotypesmentioning

confidence: 99%

“…212 Other studies, including a meta-analysis of available data, reported no change in total or prefrontal white matter, however. [193][194][195][247][248][249] Anterior cingulate In a recent study of patients with BD, schizophrenia, and their first-degree relatives, McDonald et al 245 examined associations between genetic liability and variations in grey or white matter volumes. Genetic risk for BD was specifically related to grey matter deficits in the right anterior cingulate gyrus and ventral striatum.…”

Section: Basal Gangliamentioning

confidence: 99%

The phenotypes of bipolar disorder: relevance for genetic investigations

2005

View full text Add to dashboard Cite

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...

show abstract

Regional prefrontal gray and white matter abnormalities in bipolar disorder

Cited by 259 publications

References 43 publications

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

Frontal lobe hypoactivation in medication-free adults with bipolar II depression during response inhibition

The phenotypes of bipolar disorder: relevance for genetic investigations

Contact Info

Product

Resources

About