Factor scores for cognitive performance allow the identification of intermediate cognitive phenotypes (ICPs) in bipolar disorder patients that may provide specific targets for the development of novel treatments, argue US scientists.

As many, but not all, patients with major depressive disorder, bipolar disorder, anxiety disorders, and schizophrenia have cognitive dysfunction, such dysfunction can be considered to be one of several possible intermediate phenotypes, which are likely to be underpinned by one or more genetic variants.

Noting that ICPs have been only rarely studied in bipolar disorder, Scott Langenecker and colleagues from the University of Michigan in Ann Arbor studied 34 healthy controls, 66 euthymic bipolar disorder patients, 43 depressed bipolar disorder patients, and 13 hypomanic/mixed bipolar disorder patients.

The participants were administered a neuropsychological battery covering the eight domains of auditory memory, visual memory, processing speed with interference resolution, verbal fluency and processing speed, conceptual reasoning and set-shifting, inhibitory control, emotion processing, and fine motor dexterity.

MANOVA analysis revealed that there was a significant group effect in the eight factor scores, such that controls outperformed euthymic patients on processing speed with interference resolution, visual memory, and fine motor dexterity.

In addition, controls outperformed depressed patients on all factors aside from inhibitory control, and outperformed hypomanic/mixed patients on inhibitory control, processing speed with interference resolution, fine motor dexterity, and auditory memory.

Focusing on euthymic patients, the team found that the number of psychiatric hospitalizations correlated with four of eight factor scores, while the number of years of illness was linked to five factor scores.

Both of these clinical variables were also significantly correlated with the sum of all eight factor scores. Antipsychotic medication was the only drug class associated with factor scores.

The researchers conclude in the Journal of Affective Disorders: “We and others argue that there may be common ICPs for bipolar disorder and related disorders that can be pursued in future studies of phenotypes with subsequent integration of genetic data.

“As a result there could be an expectation of earlier identification and preventative or ameliorative treatment, or development of specific targets for novel treatments.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

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Bipolar disorder patients who have high levels of anxiety during an episode are more likely to have greater long-term depressive morbidity, the results of a US study indicate.

It is known that there are differences between bipolar disorder patients with and without comorbid anxiety, but the long-term prognostic significance of comorbid anxiety is unclear, argue William Coryell, from University of Iowa Hospitals and Clinics in Iowa City, and colleagues.

The team therefore studied 427 participants from the National Institute of Mental Health Collaborative Depression Study who were followed-up prospectively for an average of 17.4 years. The manifestations of anxiety at baseline were characterized and related to the proportion of follow-up weeks in episodes of major depression and mania or hypomania.

Overall, 92 patients had mania only at baseline, while 168 had depression only and 167 were cycling. Using the Schedule for Affective Disorders and Schizophrenia, the researchers found that the patients’ somatic anxiety scores were 1.7, 3.2, and 2.8, respectively, while their psychic anxiety scores were 1.9, 4.0, and 3.5, respectively. The global anxiety level was 3.6, 7.2, and 6.3, respectively.

The percentage of weeks in depressive episodes was not predicted by gender, age at intake, age at illness onset, the presence of antisocial personality disorder, alcoholism, or drug dependence.

Patients with past or future manic episodes spent a smaller percentage of weeks in depressive episodes than those with only episodes of hypomania, at 27.4% and 36.5%, respectively. The proportion of weeks spent in depressive episodes was 13.2% for patients with purely manic episodes at baseline, 37.7% for those who had a purely depressive episode at baseline, and 33.0% for those who had a cycling episode.

Time spent in depressive episodes was not predicted by either panic attacks or any anxiety disorder. However, psychic anxiety was significantly associated with time in depressive episodes, while somatic anxiety had borderline significance.

Global anxiety was found to have a continuous relationship with number of weeks in depressive episodes, with no clear threshold for separating anxious and non-anxious patients.

However, the team was able to determine that patients with a purely manic index episode and a global anxiety level below the median value of 7 spent only 12.4% of weeks in depressive episodes, compared with 18.8% for patients with mania and an anxiety score ?7. The rates for patients with depressed or cycling index episodes were 29.7% and 40.4% depending on whether they had anxiety levels below or above the median, respectively.

The team writes in the American Journal of Psychiatry: “The combination of presenting phase and anxiety level appears to offer a potent clinical tool for predicting whether an individual is likely to follow a course dominated by depressive symptoms or one in which mania is more prominent.

“Such prediction is inherently valuable but may also have practical importance in the selection of a mood-stabilizer regimen designed to offer more protection against one or the other pole of bipolar illness.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

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The prevalence of suicidal ideation in bipolar disorder (BD) mainly depends on its definition and the type of measure used for its identification, with the Scale for Suicide Ideation (SSI) the most accurate measure, suggest study results.

“Different measures for ideation have the potential to cause inconsistency when correlates of suicidal ideation are investigated,” explain Erkki Isometsä (Helsinki University Central Hospital, Finland) and colleagues in the Journal of Affective Disorders.

To investigate how different definitions and measures for suicidal ideation influence its prevalence, correlates, and predictive validity in BD, the researchers measured suicidal ideation using different scales at baseline and at 6 months follow-up in 191 patients with BD who took part in the Jorvi Bipolar Study.

Measures included either having considered suicide, a Beck Depression Inventory (BDI) item 9 1 or 9 2, a Hamilton Depression Rating Scale (HAM-D) item 3 2 or 3 3, or a SSI sum score 6.

During the follow-up period, 15% of patients attempted suicide.

In total, 74% of patients were classified as presenting suicidal ideation by at least one of the measures. However, only 29% of these patients met the criteria for suicidal ideation under all definitions and agreement between definitions ranged from low to moderate, with the best agreement seen between SSI 6 and HAM-D item 3 2.

Furthermore, using a different cut-off as a threshold for ideation in BDI item 9 significantly affected the number of patients identified as having suicidal ideation, at 64% versus 9% when it was set at 1 versus 2, respectively.

BDI item 9 2 had the best positive predictive value for a suicide attempt during the next 6 months, but its sensitivity was quite low, at 33%.

The researchers determined that of the alternative definitions investigated, an SSI score of 8 provided an optimal combination of sensitivity (0.82) and specificity (0.69) for attempting suicide within the next few months.

Isometsä and team further found that the single common independent risk factor for suicidal ideation was the severity of depression and hopelessness.

They conclude: “The difference between the estimated prevalence of suicidal ideation based on different definition of suicidal ideation may be explained by different aspects and intensity of suicidal thoughts explored by these measurements.

“We recommend use of SSI for future studies evaluating suicidal ideation.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

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