Brain-to-Serum Lithium Ratio and Age: An In Vivo Magnetic Resonance Spectroscopy Study

Abstract

Objective-The authors' goal was to determine if there is an association between brain-to-serum lithium ratios and age.Method-Lithium-7 magnetic resonance spectroscopy was used to measure in vivo brain lithium levels in nine children and adolescents (mean age=13.4 years, SD=3.6) and 18 adults (mean age=37.3, SD=9.1) with bipolar disorder.Results-Serum and brain lithium concentrations were positively correlated. Younger subjects had lower brain-to-serum concentration ratios than adults: 0.58 (SD=0.24) versus 0.92 (SD=0.36). The brain-to-serum concentration ratio correlated positively with age.Conclusions-These observations suggest that children and adolescents may need higher maintenance serum lithium concentrations than adults to ensure that brain lithium concentrations reach therapeutic levels.Since children have a higher glomerular filtration rate than adults and lithium is eliminated by a renal route (1), children and adolescents receiving lithium treatment require larger doses of lithium in relation to their weight than adults to achieve therapeutic serum lithium levels (2). However, it is known that serum lithium levels are not always accurate in predicting therapeutic response or adverse effects (3).Few studies have looked at lithium pharmacokinetics in children and adolescents (4). Use of lithium-7 ( 7 Li) magnetic resonance spectroscopy (MRS) makes it possible to measure in vivo lithium brain levels (5). 7 Li MRS results have shown correlations (r 2 ) of 0.50 to 0.97 between brain and serum lithium levels (1, 5-7). Studies have suggested that brain lithium levels may provide a better measure of lithium efficacy than serum lithium levels (5). The purpose of the current study was to investigate the relationship between age and lithium levels in the brain and/or serum. MethodNine children and adolescents and 18 adults who were actively receiving lithium medication participated in this study. The mean age of the children was 13.4 years (SD=3.6); five were boys, and four were girls. All were interviewed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version (8). All had a diagnosis of bipolar I disorder. Additional diagnoses were attention deficit hyperactivity disorder (N=4), attention deficit disorder (N=2), oppositional defiant disorder (N=2), obsessive-compulsive disorder (N=1), and social adjustment disorder (N=1).Inclusion criteria for the children were an age range of 7-18 years and active treatment with lithium for at least 30 days with a current stable dose. Exclusion criteria were a history of drug or alcohol abuse within 4 months of study entry, a history of seizures or organic brain disorder, mental retardation (IQ<80), inability to comply with instructions or procedures of the study, and presence of metal pins or braces. The parents of children who were potential subjects for the study were capable of understanding the nature of this study as well as the discomforts and potential benefits, which were explained in full. The parents of all ...

Biomedical applications of7Li NMR

“…Most previous studies found average ratios of 0.5-0.8, although a recent study 20 found 0.92 for adult patients, a value very similar to that found by us for rats. Beyond the fact that our values are for rats and all previous values are for humans, the major difference is that in rats the reduced 7 Li MR visibility was taken into account in estimation of the brain Li concentrations.…”

“…Moore et al 20 measured steady-state brain and serum Li levels as a function of age in 27 children and adults. Consistent with most previous work, they found a weak but significant correlation of brain Li level with that of serum (r ¼ 0.60, p < 0.001).…”

Lithium attenuates stress-induced impairment of long-term potentiation induction

“…Moore et al [24] have reported the brain-to-serum lithium ratio of 0.92 in adult bipolar patients using magnetic resonance spectroscopy. Extrapolating from their results, lithium concentrations in artificial cerebrospinal fluid used in the present study are reflective of a therapeutically relevant serum lithium concentration.…”

Mood-Stabilizing Agents

“…Cerebral concentrations of lithium are lower than those in plasma by 20-40% and attain peak and nadir levels somewhat more slowly than blood. Brain/blood ratios tend to increase and to become less closely correlated at advanced ages, adding to the need for caution when using lithium with elderly patients [ 244 ] . Studies of the cerebral pharmacokinetics of lithium are facilitated by use of nuclear magnetic-resonance spectroscopy (NMS) technology, which can detect 7 Li in brain tissue in living patients [ 244,315 ] .…”