Study results suggest that anxiety state and trait are heritable and share some genetic factors in bipolar disorder (BD), with trait anxiety showing a stair-step distribution in family members based on their genetic proximity to the affected individual.

“If this trait is proven to be an endophenotype, it will be of help in diagnosing and treating bipolar I patients in a more reliable and biologically valid manner than our current classification allows,” say Javier Contreras (University of Texas Health Science Center at San Antonio, Texas, USA) and colleagues.

The localization of genes that predispose to BD has been difficult as some of these genes may be transmitted without expression of the categorical clinical phenotype.

“One strategy to overcome this obstacle is the use of quantitative endophenotypes, as has been done for other medical disorders,” explain the researchers in the Journal of Affective Disorders.

Contreras and team therefore computed heritability and genetic correlation of the state and trait scale from the Anxiety State and Trait Inventory in 30 bipolar I extended families, with an average family size of 10 members, and 20 unrelated healthy controls from a Costa Rican sample.

Of the 300 individuals from the extended families, 63 had BD type I, 74 major depressive disorder, 101 had no axis I disorder, with the remainder presenting other disorders.

The study showed that anxiety symptoms were underdiagnosed, with 14.4% meeting criteria for a DSM-IV categorical anxiety diagnosis compared with 26.0% of 274 individuals with no categorical anxiety diagnosis that were over the 75th percentile of the anxiety trait scale.

“This finding strongly encourages the use of anxiety quantitative measures in psychiatric genetics research,” says the team.

Patients with BD showed the highest trait anxiety scores, followed by relatives with other psychiatric disorders, healthy relatives, and healthy unrelated controls. The researchers note that although both state and trait showed significant heritability, state was less heritable and stable.

Furthermore, only anxiety trait showed normal distribution in healthy individuals, current mood status independence, and significant liability for BD type I.

“Further research is needed to evaluate if anxiety traits are specially related to bipolar I disorder in comparison with other traits such as anger, attention, or response inhibition deficit, pathological impulsivity or low self-directedness,” conclude the researchers.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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Older bipolar disorder patients have a similar cognitive profile to that of younger patients with the disease, say Swiss scientists, who suggest that processing speed and episodic memory are two core deficits in elderly patients.

Previous studies have indicated that bipolar disorder patients have impairments in processing speed, working memory, episodic memory, and executive function. However, these investigations have largely focused on young and middle-aged patients and all have shown that the severity of cognitive deficits increase with illness duration.

To examine cognitive deficits in older patients, Christophe Delaloye, from University Hospitals of Geneva in Chêne-Bourg, and colleagues administered a comprehensive neuropsychological battery to 22 euthymic elderly bipolar disorder patients with an average age of 68.45 years and 22 gender-, age-, and education-matched controls.

In comparison with controls, bipolar disorder patients were found to have significantly slower processing speed, lower working memory scores, lower episodic memory scores, and verbal fluency scores, at r-value effect sizes of 0.44, 0.44, 0.48, and 0.38, respectively.

There were no significant differences between the two groups in terms of executive function, and duration of illness had no impact on cognitive performance.

Processing speed was found to explain 19% of the variance in working memory scores, 14% of the verbal fluency composite scores, and 23% of the variance in episodic memory scores in hierarchical regression analysis. After controlling for processing speed, only episodic memory had a persistent group effect, explaining 10% of the variance in scores.

The team writes in the journal Bipolar Disorders: “Euthymic elderly BD patients had reduced performance in measures of processing speed, working memory, verbal fluency, and episodic memory compared to controls. This pattern of cognitive deficits is largely comparable to the one reported in younger BD cohorts.

“Moreover, the length of illness was not associated with cognitive performance in our elderly BD group, suggesting that longstanding BD is not associated with an increase in cognitive decline.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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The auditory event-related P300 amplitude appears to be an endophenotype for schizophrenia, but it is also affected in bipolar disorder patients and may be a marker for psychosis in general, conclude UK researchers.

Decreased P300 positive event-related potential component amplitude, which requires the detection of rare target stimuli, is associated with alcoholism and schizophrenia, and studies have shown that the potential is genetically influenced. However, such studies have different and more complex tasks than those used in clinical studies.

Patricia Bestelmeyer, from the University of Glasgow, and colleagues therefore initially examined the genetic influence on the P300 potential in 14 pairs of healthy monozygotic twins and 14 pairs of healthy dizygotic twins. The team measured the P300 amplitude response to one auditory and one visual paradigm, each of which consisted of 150 stimuli in two blocks, with oddball stimuli appearing at a probability of 20%.

Participants made significantly more errors when reacting to visual than to auditory stimuli on univariate analysis, while a mixed design analysis of variance showed that individuals reacted significantly faster to oddball trials. On multivariate analysis, there were no significant effects of zygosity for reaction time and error rate.

The results, published in the journal Psychiatry Research, indicate that the auditory P300 amplitude was significantly intraclass correlated in monozygotic twins, and the correlation was significantly larger than that seen in dizygotic twins. No significant correlations were seen for auditory P300 latency, or for visual P300 amplitude or latency.

In a second experiment, the team used the same paradigms, procedure, recording condition, and analysis to study visual and auditory P300 in 21 schizophrenia patients, 19 bipolar disorder patients, and 35 healthy unmedicated controls.

Healthy controls made significantly fewer errors in response to auditory stimuli than schizophrenia patients but not compared with bipolar disorder patients. In contrast, healthy controls reacted significantly faster to oddball stimuli than individuals from both patient groups, a pattern that was repeated with standard stimuli. In response to visual stimuli, the only significant difference was between healthy controls and bipolar disorder patients on reaction times, with the former being faster.

Interestingly, while schizophrenia and bipolar disorder patients had significantly lower auditory P300 amplitudes than controls, there were no significant differences between patient groups. A similar pattern was seen for visual P300 amplitudes the centro-parietal electrode site (Pz), although the reduction in bipolar disorder patients versus controls had only a non-significant trend for difference. There were no significant differences in auditory or visual P300 latencies.

The team concludes: “Taken together, our findings imply that the auditory P300 amplitude at Pz may be an endophenotype for psychosis in general rather than specifically for schizophrenia.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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