Background
The neurochemical effects of lithium in adolescents with bipolar disorder largely
are unknown. This study used proton magnetic resonance spectroscopy (1H MRS) to identify the in vivo effects of lithium on myo-inositol (mI) concentrations
in adolescent bipolar depression.
Methods
Twenty-eight adolescents (12–18 years old) with bipolar I disorder, current episode
depressed, received open-label lithium 30 mg/kg, adjusted to achieve serum levels
of 1.0–1.2 mEq/L. The mI concentrations in the medial as well as the left and right
lateral prefrontal cortices were measured at baseline, day 7, and day 42 of treatment.
Changes in mI concentrations over time were analyzed.
Results
Significant main effects of time were observed for mI concentrations in the medial
(p = .03) and right lateral (p = .05) prefrontal cortices. Baseline concentrations of mI were not significantly
different from day 7 or day 42 concentrations. However, mI concentrations on day 42
were significantly higher than those on day 7 (p = .02) in both regions.
Conclusions
This study demonstrates that prefrontal mI concentrations do not significantly change
from baseline after acute and chronic lithium treatment in adolescents with bipolar
depression. Further investigation of the effect of lithium on mI is warranted to better
understand possible mechanisms by which lithium exerts antidepressant activity.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- The Albert Lasker Medical Awards.JAMA. 1989; 262: 1834-1841
- Medication use in children and adolescents treated in the community for bipolar disorder.J Child Adolesc Psychopharmacol. 2003; 13: 515-522
- Frontal lobe differences in bipolar disorder as determined by proton MR spectroscopy.Bipolar Disord. 2002; 4: 357-365
- Inositol as an add-on treatment for bipolar depression.Bipolar Disord. 2000; 2: 47-55
- Statistical Power Analysis for the Behavioral Sciences. Erlbaum, Hillsdale, NJ1988
- Brain metabolic alterations in medication-free patients with bipolar disorder.Arch Gen Psychiatry. 2004; 61: 450-458
- Decreased anterior cingulate myo-inositol/creatine spectroscopy resonance with lithium treatment in children with bipolar disorder.Neuropsychopharmacology. 2001; 24: 359-369
- Proton magnetic resonance spectroscopy of bipolar disorder versus intermittent explosive disorder in children and adolescents.Am J Psychiatry. 2003; 160: 1442-1452
- Neurochemical effects of olanzapine in first-hospitalization manic adolescents: A proton magnetic resonance spectroscopy study.Neuropsychopharmacology. 2006; 31: 1264-1273
- Prior stimulant treatment in adolescents with bipolar disorder: Association with age at onset.Bipolar Disord. 2001; 3: 53-57
- Glycine: A possible role in lithium’s action and affective illness.Neuropsychobiology. 1983; 9: 215-218
- Fluoxetine for acute treatment of depression in children and adolescents: A placebo-controlled, randomized clinical trial.J Am Acad Child Adolesc Psychiatry. 2002; 41: 1205-1215
- A proton magnetic resonance spectroscopy investigation of the dorsolateral prefrontal cortex in acute mania.Hum Psychopharmacol. 2005; 20: 133-139
- Myo-inositol in depressive and healthy subjects determined by frontal 1H-magnetic resonance spectroscopy at 1.5 tesla.J Psychiatr Res. 1998; 32: 411-420
- Lithium and valproic acid treatment effects on brain chemistry in bipolar disorder.Biol Psychiatry. 2004; 56: 340-348
- Reliability of the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) mania and rapid cycling sections.J Am Acad Child Adolesc Psychiatry. 2001; 40: 450-455
- Move over ANOVA: Progress in analyzing repeated-measures data and its reflection in papers published in the Archives of General Psychiatry.Arch Gen Psychiatry. 2004; 61: 310-317
- The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain.J Biol Chem. 1980; 255: 10896-10901
- Increased inositol-monophosphatase activity by lithium treatment in bipolar patients.Prog Neuropsychopharmacol Biol Psychiatry. 2004; 28: 521-527
- Treatment guidelines for children and adolescents with bipolar disorder.J Am Acad Child Adolesc Psychiatry. 2005; 44: 213-235
- Double-blind, controlled trial of inositol treatment of depression.Am J Psychiatry. 1995; 152: 792-794
- Choline, myo-inositol and mood in bipolar disorder: A proton magnetic resonance spectroscopic imaging study of the anterior cingulate cortex.Bipolar Disord. 2000; 2: 207-216
- Temporal dissociation between lithium-induced changes in frontal lobe myo-inositol and clinical response in manic-depressive illness.Am J Psychiatry. 1999; 156: 1902-1908
- Effect of bipolar disorder on lymphocyte inositol monophosphatase mRNA levels.Int J Neuropsychopharmacol. 1999; 2: 25-29
- Effects of chronic lithium and sodium valproate on concentrations of brain amino acids.Eur Neuropsychopharmacol. 2003; 13: 220-227
- Regional changes in rat brain inositol monophosphatase 1 (IMPase 1) activity with chronic lithium treatment.Prog Neuropsychopharmacol Biol Psychiatry. 2003; 27: 55-60
- Open-label lithium for the treatment of adolescents with bipolar depression.J Am Acad Child Adolesc Psychiatry. 2006; 45: 289-297
- Children’s Depression Rating Scale-Revised. Western Psychological Services, Los Angeles, CA1995
- Estimation of metabolite concentrations from localized in vivo proton NMR spectra.Magn Reson Med. 1993; 30: 672-679
- Chronic dietary lithium induces increased levels of myo-inositol-1-phosphatase activity in rat cerebral cortex homogenates.Brain Res. 1986; 380: 401-404
- Proton magnetic resonance spectroscopy of the brain in schizophrenic and affective patients.Schizophr Res. 1992; 8: 43-49
- Bipolar disorder and myo-inositol: A review of the magnetic resonance spectroscopy findings.Bipolar Disord. 2005; 7: 1-10
- Chronic treatment with both lithium and sodium valproate may normalize phosphoinositol cycle activity in bipolar patients.Hum Psychopharmacol. 2002; 17: 321-327
- Modification of the Clinical Global Impressions (CGI) Scale for use in bipolar illness (BP): The CGI-BP.Psychiatry Res. 1997; 73: 159-171
- A rating scale for mania: Reliability, validity and sensitivity.Br J Psychiatry. 1978; 133: 429-435
Article info
Publication history
Accepted:
July 13,
2006
Received in revised form:
July 11,
2006
Received:
November 4,
2005
Identification
Copyright
© 2006 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
