title: Prophylactic lithium treatment and cognitive performance in patients with a long history of bipolar illness: no simple answers in complex disease-treatment interplay.
abstract: Cognitive impairment in patients with bipolar disorder (BD) is not restricted to symptomatic phases. It is also present in euthymia. There is evidence of differences in the brain's structure between bipolar patients and healthy individuals, as well as changes over time in patients. Lithium constitutes the gold standard in long-term prophylactic treatment. Appropriate therapy that prevents new episodes improves the disease's course and reduces the frequency of harmful outcomes. Interestingly, preclinical data suggest that lithium has a (additional) neuroprotective effect. There is limited data on its related effects in humans and even less on its long-term application. In this multi-center cross-sectional study from the International Group for the Study of Lithium-treated Patients (IGSLi), we compared three groups: bipolar patients without long-term lithium treatment (non-Li group; <3 months cumulative lithium exposure, ≥24 months ago), bipolar patients with long-term lithium treatment (Li group, ongoing treatment ≥24 months), and healthy subjects (controls). Strict inclusion and exclusion criteria were defined; the inclusion criteria for patients were diagnosis of BD types I or II, duration of illness ≥10 years, ≥5 episodes in patient's history and a euthymic mood state. Neurocognitive functioning was assessed using the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the California Verbal Learning Test (CVLT), and a visual backward masking (VBM) task. A total of 142 subjects were included, 31 in the non-Li and 58 in the Li group, as well as 53 healthy controls. Treated patients with long-standing BD and controls did not differ significantly in overall cognitive functioning and verbal learning, recall, and recognition; regardless of whether lithium had been part of the treatment. Patients, however, demonstrated poorer early visual information processing than healthy controls, with the lithium-treated patients performing worse than those without. Our data suggest that bipolar patients with a long illness history and effective prophylactic treatment do not reveal significantly impaired general cognitive functioning or verbal learning and memory. However, they are worse at processing early visual information. Accompanying volumetric and spectroscopic data suggest cell loss in patients not treated with lithium that may be counterbalanced by long-term lithium treatment.
authors.affiliation: Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany ; International Group for the Study of Lithium-Treated Patients (IGSLi), Berlin, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pfennig
authors.affiliation: Department of Psychiatry, Dalhousie University, Halifax, Canada ; International Group for the Study of Lithium-Treated Patients (IGSLi), Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Alda
authors.affiliation: Department of Psychiatry, University of British Columbia Faculty of Medicine, Vancouver, Canada ; International Group for the Study of Lithium-Treated Patients (IGSLi), Berlin, Germany.
authors.forename: Trevor
authors.initials: T
authors.lastname: Young
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Calgary, Calgary, Canada ; International Group for the Study of Lithium-Treated Patients (IGSLi), Berlin, Germany.
authors.forename: Glenda
authors.initials: G
authors.lastname: MacQueen
authors.affiliation: Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland ; International Group for the Study of Lithium-Treated Patients (IGSLi), Berlin, Germany.
authors.forename: Janusz
authors.initials: J
authors.lastname: Rybakowski
authors.affiliation: Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland ; International Group for the Study of Lithium-Treated Patients (IGSLi), Berlin, Germany.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Suwalska
authors.affiliation: Department of Psychiatry, Hospital Neunkirchen, CS now: Bipolar Centre, Vienna, Austria ; International Group for the Study of Lithium-Treated Patients (IGSLi), Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Simhandl
authors.affiliation: Department of Psychiatry, Hospital Neunkirchen, CS now: Bipolar Centre, Vienna, Austria ; International Group for the Study of Lithium-Treated Patients (IGSLi), Berlin, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: König
authors.affiliation: Department of Psychiatry, Dalhousie University, Halifax, Canada ; International Group for the Study of Lithium-Treated Patients (IGSLi), Berlin, Germany.
authors.forename: Tomas
authors.initials: T
authors.lastname: Hajek
authors.affiliation: Department of Psychiatry, Dalhousie University, Halifax, Canada ; International Group for the Study of Lithium-Treated Patients (IGSLi), Berlin, Germany.
authors.forename: Claire
authors.initials: C
authors.lastname: O'Donovan
authors.affiliation: Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Wittekind
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Berlin, Campus Mitte, Berlin, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: von Quillfeldt
authors.affiliation: Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Ploch
authors.affiliation: Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Sauer
authors.affiliation: Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany ; International Group for the Study of Lithium-Treated Patients (IGSLi), Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bauer
keywords: Bipolar disorder; Cognition; Lithium