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Brain Lithium Levels and Effects on Cognition and Mood in Geriatric Bipolar Disorder: A Lithium-7 Magnetic Resonance Spectroscopy Study

https://doi.org/10.1097/JGP.0b013e318172b3d0Get rights and content

Objectives:

The authors investigated the relationship between brain lithium, serum lithium and age in adult subjects treated with lithium. In addition, the authors investigated the association between brain lithium and serum lithium with frontal lobe functioning and mood in a subgroup of older subjects.

Design:

Cross-sectional assessment.

Setting:

McLean Hospital's Geriatric Psychiatry Research Program and Brain Imaging Center; The Division of Psychiatry, Boston University School of Medicine.

Participants:

Twenty-six subjects, 20 to 85 years, with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition–TR bipolar disorder (BD), currently treated with lithium.

Measurements:

All subjects had measurements of mood (Hamilton Depression Rating Scale [HDRS] and Young Mania Rating Scale) and serum and brain lithium levels. Brain lithium levels were assessed using lithium Magnetic Resonance Spectroscopy. Ten subjects older than 50 years also had assessments of frontal lobe functioning (Stroop, Trails A and B, Wis. Card Sorting Task).

Results:

Brain lithium levels correlated with serum lithium levels for the group as a whole. However, this relationship was not present for the group of subjects older than 50. For these older subjects elevations in brain (but not serum) lithium levels were associated with frontal lobe dysfunction and higher HDRS scores. The higher HDRS were associated with increased somatic symptoms.

Conclusion:

Frontal lobe dysfunction and elevated depression symptoms correlating with higher brain lithium levels supports conservative dosing recommendations in bipolar older adults. The absence of a predictable relationship between serum and brain lithium makes specific individual predictions about the “ideal” lithium serum level in an older adult with BD difficult.

Section snippets

METHODS

The Institutional Review Boards at McLean Hospital and Boston University School of Medicine approved this study. Subjects were recruited through a) the McLean Hospital Mood Disorders Division, Geriatric Psychiatry Research Program and through referrals from the McLean Hospital Geriatric Psychiatry Inpatient Service, Partial Hospital Program and Outpatient Clinic; and b) the Division of Psychiatry, Boston University School of Medicine. Subjects were also recruited through flyers posted around

RESULTS

Table 1 gives a description of the subjects' demographics, mean lithium dose, use of extended release lithium, and the number of other psychotropic medications they were receiving. Table 2 shows the subjects' age, duration of illness, and daily dose of lithium. For the older subjects (50–85 years), serum lithium levels were acquired on two occasions, on the day of the neurocognitive testing (serum lithium level = 0.68 ± 0.15 meq/L [N = 10]), and on the day of the MRS examination (serum lithium

CONCLUSIONS

This study supported previous reports,10, 28, 30 of the presence of a correlation between serum lithium levels and brain lithium levels in younger adults. Our findings did not, however, find evidence to support the hypothesis that advancing age beyond midlife is associated with an elevation in the brain to serum lithium ratio. Furthermore, we found evidence that elevations in brain, but not serum, lithium levels were associated with executive dysfunction and higher depression rating scores in a

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  • Cited by (0)

    This study was supported by an NARSAD (National Alliance for Research in Schizophrenia and Affective Disorders); National Institute of Mental Health (MH58681 (PFR) and MH001978 (CMM)); Commonwealth Research Center of Harvard Medical School; Harvard Research Center for Excellence; The National Center for Research Resources (M01RR00533); National Institute on Alcohol Abuse and Alcoholism (K23AA13149 to CCS); and Gennaro Acampora Charity Trust to the Division of Psychiatry, Boston Medical Center. Disclosures: Brent Forester: Speakers Bureau: Pfizer, Eli Lilly, AstraZeneca, Abbot, Novartis, Janssen; Grant Support: NARSAD, Abbott, GlaxoSmithKlein, Pfizer, Rogers Family Foundation; Clinical Investigator Training Program: Harvard MIT Health Sciences and Technology–Beth Israel Deaconess Medical Center, in collaboration with Pfizer and Merck & Co.; Chris C. Streeter: Risk Management Foundation of the Harvard Medical Institutions, Inc., Karns law Group, Trustees of Boston University, Norcal Mutual Insurance Company, Deluca and Weizenbaum, LTD, UCB Pharma, Bristol Myers Squibb, National Institute of Alcohol Abuse and Alcoholism; Consultant: Janssen Pharmaceuticals; Research Support: NIH, GSK; Perry F. Renshaw: Consultant: GSK, Novartis, Kyowa Hakko. Grant Support: Eli Lilly.

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