Neurological abnormalities in drug-free and drug-treated patients with bipolar affective disorder

Abstract Objective: To assess the effect of medication on neurological abnormalities in patients with bipolar affective disorder. Patients and Methods: Neurological abnormalities were examined in 30 drug-free patients and 30 drug-treated patients meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition diagnostic criteria for bipolar affective disorder, and 20 age- and sex-matched controls, using the Extended Standard Neurological Assessment Instrument. Mania and depression were assessed using the Young Mania Rating Scale and the Hamilton Rating Scale for Depression, respectively. Side effects of medications were assessed using the Udvalg for Kliniske Undersogelser Side Effect Rating Scale. Results: Patients with bipolar affective disorder had higher mean total scores on the Extended Standard Neurological Assessment Instrument (drug-free group 22.83 [+ or -] 11.04, drug-treated group 22.00 [+ or -] 10.23) than controls, who did not score on any items of the neurological battery. There was a significant excess of hard signs and involuntary movements in the drug-treated group compared with the drug-free group, and a significant positive correlation between hard signs and the involuntary movements score and the neurological subscore on Udvalg for Kliniske Undersogelser Side Effect Rating Scale in the drug-treated group. Conclusion: The presence of neurological signs in drug-free patients with bipolar affective disorder suggests that neurological abnormalities may occur independently of medication effects. Side effects of drug treatment for bipolar affective disorder may contribute to the prevalence of neurological abnormalities in this patient population. Key words: Bipolar disorder, Dyskinesia, drug-induced, Neurologic manifestations Introduction There has been a steady increase in interest and appreciation of the biological underpinnings of mood disorders. Bipolar disorder appears to be related to anatomic abnormalities in the medial temporal lobe, in particular the amygdala, prefrontal cortex and cerebellum. (1) Recent magnetic resonance imaging findings support a neurodevelopmental etiology for bipolar affective disorder, at least in a subgroup of patients, as for schizophrenia. The frequency of medial temporal lobe (hippocampus/amygdala complex) hypoplasia noted in patients with bipolar affective disorder was similar to that seen in schizophrenia, and correlated with the degree of cognitive impairment. (2) A meta-analysis by Videbech (3) showed an increased ventricle/brain ratio and other signs of cerebral atrophy, as well as an increased frequency of signal hyperintensity, in the frontal lobes and basal ganglia of patients with bipolar affective disorder. Shioiri et al (4) reported a higher incidence of cavum septum pellucidum in subjects with bipolar affective disorder than controls, but lower than in subjects with schizophrenia. Neurological soft signs (NSS) have been reported in minimal brain dysfunction, (5) emotionally unstable character, (6) heavy polydrug users, (7) borderline personality disorder, (8) obsessive compulsive disorder, (9) and consistently in individuals with schizophrenia. (10,11) Nasrallah et al (12) found that NSS are as common in individuals with mania as in those with schizophrenia. An excess of neurological signs in adults with bipolar affective disorder has also been reported by other researchers. (13-15) Basu et al (16) reported similar findings in adolescents with mania. These soft signs are thought to reflect diffuse brain dysfunction. However, it has been suggested that although diffuse, NSS may reflect selective dysfunction in areas of motor coordination, integrative sensory function, and complex motor task coordination. (17) One area of interest has been the role of medication in the expression of neurological abnormalities. Although few studies have been able to exclude the influence of medication in the appearance of neurological abnormalities, (6,18) a comprehensive review by Heinrichs and Buchanan (17) concluded that medications do not seem to alter neurological signs in most cases of schizophrenia. …