The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review

Bearden, Carrie E.; Hoffman, Kathleen M; Cannon, Tyrone D.

doi:10.1034/j.1399-5618.2001.030302.x

Cited by 505 publications

(429 citation statements)

References 193 publications

(287 reference statements)

Supporting

Mentioning

371

Contrasting

Unclassified

Order By: Relevance

“…195 No decreases in overall white matter volumes were apparent in several studies. 193 A number of investigators have reported increased occurrence of WMHs in patients with BD, however, [196][197][198][199] including in adolescents with BD. 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.…”

Section: Brain Imaging and Endophenotypesmentioning

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

Section: Brain Imaging and Endophenotypesmentioning

confidence: 99%

The phenotypes of bipolar disorder: relevance for genetic investigations

2005

View full text Add to dashboard Cite

show abstract

“…Neuropsychological studies of bipolar patients consistently report decrements in sustained attention during affective episodes (reviewed in Bearden et al, 2001). These observations are not particularly surprising since both experiential and experimental evidence support the notion that strong emotional states interfere with attention (Mayberg et al, 1999;Yamasaki et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

A Preliminary fMRI Study of Sustained Attention in Euthymic, Unmedicated Bipolar Disorder

Strakowski

Adler

Holland

et al. 2004

Neuropsychopharmacol

225

180

View full text Add to dashboard Cite

The symptoms of bipolar disorder suggest dysfunction of anterior limbic networks that modulate emotional behavior and that reciprocally interact with dorsal attentional systems. Bipolar patients maintain a constant vulnerability to mood episodes even during euthymia, when symptoms are minimal. Consequently, we predicted that, compared with healthy subjects, bipolar patients would exhibit abnormal activation of regions of the anterior limbic network with corresponding abnormal activation of other cortical areas involved in attentional processing. In all, 10 unmedicated euthymic bipolar patients and 10 group-matched healthy subjects were studied with fMRI while performing the Continuous Performance Task-Identical Pairs version (CPT-IP). fMRI scans were obtained on a 3.0 T Bruker system using an echo planar imaging (EPI) pulse sequence, while subjects performed the CPT-IP and a control condition to contrast group differences in regional brain activation. The euthymic bipolar and healthy subjects performed similarly on the CPT-IP, yet showed significantly different patterns of brain activation. Specifically, bipolar patients exhibited increased activation of limbic, paralimbic, and ventrolateral prefrontal areas, as well as visual associational cortices. Healthy subjects exhibited relatively increased activation in fusiform gyrus and medial prefrontal cortex. In conclusion, these differences suggest that bipolar patients exhibit overactivation of anterior limbic areas with corresponding abnormal activation in visual associational cortical areas, permitting successful performance of an attentional task. Since the differences occurred in euthymia, they may represent trait, rather than state, abnormalities of brain function in bipolar disorder.

show abstract

“…Moreover, in elderly humans, there is also a recognized decline in memory function (Golomb et al, 1996;Mayeux et al, 2001). Interestingly, patients with affective disorders have also been shown to exhibit cognitive deficits including in mnemonic processing (for reviews see Christensen et al, 1997;Bearden et al, 1998). These impairments, in particular those in visuospatial memory, have been most consistently observed in severe unipolar depression (including melancholic and psychotic subtypes) as well as in bipolar disorder (Austin et al, 2001;Quraishi and Frangou, 2002).…”

Section: Introductionmentioning

confidence: 99%

Flattening the Glucocorticoid Rhythm causes Changes in Hippocampal Expression of Messenger RNAs Coding Structural and Functional Proteins: Implications for Aging and Depression

Gartside

Leitch

McQuade

et al. 2002

Neuropsychopharmacol

View full text Add to dashboard Cite

Subtle changes in glucocorticoid levels, including a flattening of the diurnal rhythm with raised nadir, are prevalent, being characteristic of both aging and major depression. Both these conditions are also associated with deficits in hippocampally mediated cognitive functions. We hypothesized that this profile of glucocorticoid levels causes structural and functional changes in the hippocampus, which in turn may engender cognitive deficits. We implanted slow-release corticosterone pellets into adrenally intact adult male rats to produce a flattened glucocorticoid rhythm with levels clamped midway between the normal nadir and zenith. Using density profile analysis we measured hippocampal expression of messenger RNAs encoding structural and functional proteins. In rats with a flattened glucocorticoid rhythm, the expression of the mRNA coding for microtubule associated protein-2b (MAP2b) was reduced in CA3 relative to sham-operated controls, but unchanged in dentate gyrus and CA1. In contrast, the expression of the mRNA coding the alpha subunit of calciumcalmodulin dependent kinase (CAMKIIa) was reduced in dentate gyrus in animals with a flattened glucocorticoid rhythm, but unchanged in CA3. The expression of the mRNA coding the synaptic vesicle protein synaptophysin was unchanged in both CA3 and dentate gyrus. The data indicate that a flattening of the normal diurnal glucocorticoid rhythm decreases the hippocampal expression of mRNAs coding key structural and functional proteins, and does so in a regionally selective manner. The data may have relevance for cognitive deficits characteristic of aging and depression.

show abstract

The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review

Cited by 505 publications

References 193 publications

The phenotypes of bipolar disorder: relevance for genetic investigations

The phenotypes of bipolar disorder: relevance for genetic investigations

A Preliminary fMRI Study of Sustained Attention in Euthymic, Unmedicated Bipolar Disorder

Flattening the Glucocorticoid Rhythm causes Changes in Hippocampal Expression of Messenger RNAs Coding Structural and Functional Proteins: Implications for Aging and Depression

Contact Info

Product

Resources

About