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Persistent Neuropsychological Deficit in Euthymic Bipolar Patients: Executive Function as a Core Deficit

J Clin Psychiatry 2007;68:1078-1086

Objective: To characterize neuropsychological deficits during the euthymic phase in a sample of bipolar outpatients treated with lithium as the principal mood-stabilizer medication. We sought to determine cognitive functioning of typical bipolar outpatients treated in clinical settings.

Method: Forty-four stable outpatients, fulfilling criteria of bipolar disorder (DSM-IV), were consecutively recruited from a defined catchment area and compared with 46 healthy matched controls in 2003. Patients were remitted for at least 3 months and euthymic (Hamilton Rating Scale for Depression score < 8 and Young Mania Rating Scale score < 6 for at least 3 months). They were receiving lithium as monotherapy (45.5%) or combined with other psychotropic medication (54.5%). Neuropsychological assessment was performed by means of a neuropsychological test battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory, and visual memory).

Results: Multivariate analysis of variance showed that euthymic bipolar patients performed significantly worse than controls in measures of executive function (F = 2.57, df = 4,82; p = .04) and inhibition (F = 3.83, df = 2,84; p = .03), after controlling for subclinical symptomatology, years of education, and premorbid intelligence quotient. Processing speed also differed significantly between groups (F = 3.73, df = 2,84; p = .03). The subgroup of patients on lithium monotherapy (45.5%) differed significantly from healthy matched controls on tasks of lack of inhibition (F = 5.8, df = 2,36; p = .007). Executive tasks showed between-subject effects.

Conclusions: These results suggest that impaired executive function and loss of inhibition might be an important feature of bipolar disorder regardless of the severity of the disease or the effects of medication. Also, these executive-type cognitive traits may constitute an endophenotype for further studies on the etiology of bipolar disorder.