Effects of Lithium on Saccadic Eye Movements in Healthy Subjects in a Ten-Day Double-Blind Placebo-Controlled Cross-Over Pilot Study

Introduction: Although previous studies have shown that lithium modifies eye movements or psychomotor speed, no studies have ever explored the predictive saccades or memory guided saccades during lithium administration. We took the objective to determine the influence of lithium in pseudo-random, predictive or memory-guided saccades in healthy subjects with a view to detect reduced psychomotor speed, inability to anticipate incoming events, or working memory deficits. Methods: A ten day lithium-placebo randomized double-blind cross-over pilot study was carried out with 12 healthy male volunteers. The cognitive assessment included pseudo-random, predictive and memory guided saccades before and after lithium and placebo periods. A biological assay substantiated the lithium effect on TSH and thyroid hormones. Results: There was no change in pseudo-random or memory guided saccades when comparing lithium or placebo administration. However the ratio of anticipated saccades decreased under the lithium sequence while it remained stable under placebo. Also, subjects having lithium serum levels of > 0.5 meq/l had longer latencies in anticipated saccades. Conclusion: The findings do not support a major effect of lithium on alertness or on working memory, although the dosage and duration of lithium was sufficient to modify TSH blood level. Nevertheless, lithium treatment was associated with decreased anticipation in predictive saccades, suggesting this could reflect a reduced ability to anticipate quick motor movements and could be related to the well-known effect of lithium as an anti-impulsive medication.

References

• 1 Britton P G, Savage R D. A short form of the WAIS for use with age.  Br J Psychiatry. 1966;  112 417-418
• 2 Flechtner K M, Mackert A, Thies K, Frick K, Müller-Oerlinghausen B. Lithium effect on smooth pursuit eye movements of healthy volunteers.  Biol Psychiatry. 1992;  32 932-938
• 3 Glue P W, Nutt D J, Cowen P J, Broadbent D. Selective effect of lithium on cognitive performance in man.  Psychopharmacology. 1987;  91 109-111
• 4 Gooding D C, Iacono W G, Katsanis J, Beiser M, Grove W M. The association between lithium carbonate and smooth pursuit eye tracking among first-episode patients with psychotic affective disorders.  Psychophysiology. 1993;  30 3-9
• 5 Grunze H. Reevaluating therapies for bipolar depression.  J Clin Psychiatry. 2005;  66(S5) 17-25
• 6 Hegerl U, Herrman W M, Ulrich G. Müller-Oerlinghausen.  Biol Psychiatry. 1990;  27 555-560
• 7 Holzman P S, O’Brian C, Waternaux C. Effects of lithium treatment on eye movements.  Biol Psychiatry. 1991;  29 1001-1015
• 8 Iacono W G, Peloquin L J, Lumry A E, Valentine R H, Tuason V B. Eye tracking in patients with unipolar and bipolar affective disorders in remission.  J Abnormal Psych. 1982;  91 35-44
• 9 Ishihara S. Tests for blindness Tokyo; Kanehara Shuppan 1979
• 10 Karniol I G, Dalton J, Lader M H. Acute and chronic effects of lithium chloride on physiological and psychological measures in normals.  Psychopharmacology. 1978;  57 289-294
• 11 Kolk A, Kathmann N, Greil W. No short term changes of cognitive performance and mood after single doses of two different lithium retard preparations.  Pharmacopsychiatry. 1993;  26 235-239
• 12 Krebs M O, Gut-Fayand A, Amado I, Daban C, Bourdel M C, Poirier M F, Berthoz A. Impairment of predictive saccades in schizophrenia.  Neuroreport. 2001;  12 465-469
• 13 Kropf D, Muller-Oerlinghausen B. Changes in learning, memory and mood during lithium treatment.  Acta Psychiatr Scand. 1979;  59 97-124
• 14 Levy D L, Donus E, Shaughnerry R, Yarilb N J. Pharmacologic evidence for specificity of pursuit dysfunction to schizophrenia: Lithium carbonate associated with abnormal pursuit.  Arch Gen Psychiatry. 1985;  42 335-341
• 15 Linnoila M, Saarie I, Make M. Effect of treatment with diazepam or lithium and alcohol on psychomotor skills related to driving.  Eur J Clin Pharmacol. 1974;  39 337
• 16 Opgenoorth E, Kral G, Wolf R. Visually stimulated saccadic eye movements in patients treated with lithium.  Acta Psychiatr Scand. 1986;  73 54-59
• 17 Pachet A K, Wisniewski A M. The effect of lithium on cognition: an updated review.  Psychopharmacology. 2003;  170 225-234
• 18 Paykel E S. The interview for recent life events.  Psychol Med. 1997;  27 301-310
• 19 Piketty M L, Poirier E, Galinowski A, Bourdel M C, Lancelin F, Poirier M F. Effect of short time Lithium treatment on Thyrotropin and free thyroxin concentration: a double blind study on healthy volunteers. Communication, 12th International Thyroid Congress Kyoto; December 2000
• 20 Ramdane Cherif Z, Naît Ali A, Motsch J F, Krebs M O. Recording and analysing an eye movment during ocular fixation in schizophrenic subjects. Proceeding of the IEEE 28th Annual Northeast Bioengineering Conference 2002: 217-218
• 21 Ross S M, Ross L E. Children’s and adults predictive saccades to square wave targets.  Vision Res. 1987;  27 2177-2180
• 22 Stip E, Dufresne J, Lussier I, Lakshmi Y. A double-blind, placebo-controlled study of the effects of lithium on cognition in healthy subjects: mild and selective effects on learning.  J Affect Disord. 2000;  60 147-157
• 23 Weingartner H, Rudorfer M V, Linnoila M. Cognitive effects treatment in normal volunteers.  Psychopharmacology. 1985;  86 472-474