Cognitive impairment in remission in bipolar affective disorder

Rubinsztein, Judy S.; Michael, A.; Paykel, Eugene S.; Sahakian, Barbara J.

doi:10.1017/s0033291799002664

Cited by 272 publications

(271 citation statements)

References 63 publications

(80 reference statements)

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“…Cognitive impairments have previously been described in FH and also in manic, depressed, and euthymic BD patients (Sobczak et al, 2002c;Rossi et al, 2000;Martinez-Aran et al, 2000;Ferrier et al, 1999;Murphy et al, 1999;Rubinsztein et al, 2000). The cognitive deficits in BD may be partially explained by abnormalities in functional brain structures and/or metabolism (Stoll et al, 2000;Manji et al, 2000;van Gorp et al, 1999;Coffman et al, 1990).…”

Section: Discussionmentioning

confidence: 89%

“…The cognitive deficits in BD may be partially explained by abnormalities in functional brain structures and/or metabolism (Stoll et al, 2000;Manji et al, 2000;van Gorp et al, 1999;Coffman et al, 1990). As cognitive impairments are present in FH and persist during clinical remission in BD patients, they may be regarded as trait markers (Henry et al, 1973;van Gorp et al, 1998;Murphy et al, 1999;Coffman et al, 1990;Ferrier et al, 1999;Rubinsztein et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Manic patients showed impairments on planning and reaction time (RT) (Murphy et al, 1999). During remission, cognitive deficits may persist (van Gorp et al, 1998;Ferrier et al, 1999;Rubinsztein et al, 2000;Scott et al, 2000); euthymic BD patients showed impairments on visuospatial recognition, verbal and nonverbal memory and learning, retrieval of information from semantic memory an increased RT on a planning task (Coffman et al, 1990;Ferrier et al, 1999;Rubinsztein et al, 2000). The fact that cognitive deficits persist during remission suggests that they constitute a trait marker in BD.…”

Section: Introductionmentioning

confidence: 99%

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Pronounced Cognitive Deficits Following an Intravenous L-Tryptophan Challenge in First-Degree Relatives of Bipolar Patients Compared to Healthy Controls

Sobczak

Honig

Schmitt

et al. 2002

Neuropsychopharmacol

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Cognitive impairment has repeatedly been described in bipolar disorders (BD). Serotonin (5-hydroxytryptophan; 5-HT) is possibly involved in these cognitive processes, more particularly in executive functions, learning, memory, and attention. The aim of this study was to investigate serotonergic vulnerability and its relation to cognitive functioning in healthy first-degree relatives of BD patients. We investigated the effects of an intravenous (i.v.) tryptophan (Trp) challenge and placebo on cognitive performance in 30 healthy firstdegree relatives of bipolar patients (FH) and 15 matched controls in a double-blind crossover design. A distinction was made between relatives of type I BD patients (FH I) and type II BD patients (FH II). Performances on planning, memory, attention, and psychomotor tasks were assessed 3 h after Trp infusion. After Trp, planning and attention were impaired in FH subjects but not in controls. Independent of Trp, FH subjects showed cognitive deficits on memory, focused and divided attention, and psychomotor performance. FH I subjects showed more pronounced cognitive impairments then FH II and controls. In all groups, Trp impaired memory and psychomotor performance significantly. In conclusions, cognitive deficits in FH following Trp may reflect a central 5-HT vulnerability in frontal brain areas. Independent of Trp, cognitive deficits in FH provide evidence for a trait marker for BD.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pronounced Cognitive Deficits Following an Intravenous L-Tryptophan Challenge in First-Degree Relatives of Bipolar Patients Compared to Healthy Controls

Sobczak

Honig

Schmitt

et al. 2002

Neuropsychopharmacol

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“…A substantial number of studies have now confirmed that many patients with BD have cognitive impairment that persists into the euthymic state. [154][155][156][157][158][159] Impairment has been demonstrated in sustained attention, 160 working memory and executive function, 155 global cognitive functioning, 154 visuospatial recognition memory, 161 problem-solving strategies, 156 declarative memory, 157 and cognitive processing speed. 162 The fact that such impairment is detectable independent of clinical state is suggestive of a trait marker, but factors such as the neuropsychological deterioration secondary to acute episodes of illness, medication treatment, and/or withdrawal effects, long-term effects of comorbid conditions such as substance abuse, or the effect of unrecognized neurobiological changes such as dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis could all contribute to performance deficits in the euthymic state.…”

Section: Cognitive 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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“…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). Recent evidence suggests that deficits may persist into clinical remission (Abas et al, 1990;Rubinsztein et al, 2000;Austin et al, 2001).…”

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

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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.

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Cognitive impairment in remission in bipolar affective disorder

Cited by 272 publications

References 63 publications

Pronounced Cognitive Deficits Following an Intravenous L-Tryptophan Challenge in First-Degree Relatives of Bipolar Patients Compared to Healthy Controls

Pronounced Cognitive Deficits Following an Intravenous L-Tryptophan Challenge in First-Degree Relatives of Bipolar Patients Compared to Healthy Controls

The phenotypes of bipolar disorder: relevance for genetic investigations

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

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