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Fulltext Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

Amare AT, Schubert KO, Hou L, Clark SR, Papiol S, Cearns M, et al.

Mol Psychiatry, 2021 Jun;26(6):2457-2470.
PMID: 32203155 DOI: 10.1038/s41380-020-0689-5

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18-2.01) and European sample: OR = 1.75 (95% CI: 1.30-2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61-4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.

Matched MeSH terms: Lithium/therapeutic use
Fulltext Variant GADL1 and response to lithium in bipolar I disorder

Consortium on Lithium Genetics, Hou L, Heilbronner U, Rietschel M, Kato T, Kuo PH, et al.

N Engl J Med, 2014 05 08;370(19):1857-9.
PMID: 24806176 DOI: 10.1056/NEJMc1401817
Matched MeSH terms: Lithium/therapeutic use*
Fulltext Long term lithium therapy in Malaysia

Ngen CC, Cheong IK

Med J Malaysia, 1989 Sep;44(3):199-203.
PMID: 2626134

Ten patients on long term lithium therapy (mean four years, range 1-10.5 years) were subjected to various renal, thyroid, haematological, cardiac and endocrine tests. There was impaired urinary concentrating ability in seven subjects, which was not responsive to vasopressin stimulation, suggesting a partial nephrogenic diabetes insipidus. Nine subjects had metabolic acidosis with higher urinary pH than expected suggesting presence of acidification defect in the kidney. No significant change in renal function, thyroid function, ECG or haematological parameters were detected. Our findings concur with previous reports from the West regarding the safety of lithium administration.

Matched MeSH terms: Lithium/therapeutic use
Pharmacoepidemiology and Clinical Correlates of Lithium Treatment for Bipolar Disorder in Asia

Shuy YK, Santharan S, Chew QH, Lin SK, Ouyang WC, Chen CK, et al.

J Clin Psychopharmacol, 2024 01 16;44(2):117-123.
PMID: 38230861 DOI: 10.1097/JCP.0000000000001813

BACKGROUND: As clinical practices with lithium salts for patients diagnosed with bipolar disorder (BD) are poorly documented in Asia, we studied the prevalence and clinical correlates of lithium use there to support international comparisons.
METHODS: We conducted a cross-sectional study of use and dosing of lithium salts for BD patients across 13 Asian sites and evaluated bivariate relationships of lithium treatment with clinical correlates followed by multivariate logistic regression modeling.
RESULTS: In a total of 2139 BD participants (52.3% women) of mean age 42.4 years, lithium salts were prescribed in 27.3% of cases overall, varying among regions from 3.20% to 59.5%. Associated with lithium treatment were male sex, presence of euthymia or mild depression, and a history of seasonal mood change. Other mood stabilizers usually were given with lithium, often at relatively high doses. Lithium use was associated with newly emerging and dose-dependent risk of tremors as well as risk of hypothyroidism. We found no significant differences in rates of clinical remission or of suicidal behavior if treatment included lithium or not.
CONCLUSIONS: Study findings clarify current prevalence, dosing, and clinical correlates of lithium treatment for BD in Asia. This information should support clinical decision-making regarding treatment of BD patients and international comparisons of therapeutic practices.

Matched MeSH terms: Lithium/therapeutic use
Monitoring of lithium therapy

Aishah AB, Foo YN

Malays J Pathol, 1995 Jun;17(1):43-5.
PMID: 8907005

Results of serum lithium performed in the Chemical Pathology Laboratory, Universiti Kebangsaan Malaysia, Kuala Lumpur, over a years' period (June 1991 till May 1992) formed the subject of study. A total of 277 tests were carried out on 148 patients, giving a frequency of about 23.1 tests per month. Complete data regarding age, sex and ethnic group was available for 140 subjects. There were 74 males and 66 females. Racial distribution was 72 Malays, 42 Chinese and 26 Indians. Their ages ranged from 15 to 80 years. One hundred and twenty-three subjects (87.6%) were within the 3rd to 5th decade of life. 136/277 (49.1%) of serum lithium levels were less than 0.6 mmol/l and 24/277 (8.7%) gave results greater than 1.0 mmol/l. Only 6 tests gave values which exceeded 2 mmol/l. This study reveals the need to conduct a prospective study to determine the underlying cause of the high incidence of low serum lithium levels and whether this situation is associated with a satisfactory treatment response in the said population.

Matched MeSH terms: Lithium/therapeutic use
Fulltext Hypertensive bipolar: chronic lithium toxicity in patients taking ACE inhibitor

Masiran R, Abdul Aziz MF

BMJ Case Rep, 2017 Aug 28;2017.
PMID: 28847993 DOI: 10.1136/bcr-2017-220631

A patient with bipolar I disorder has been treated with lithium and haloperidol for the last 20 years and received an ACE inhibitor for his hypertension since 9 years ago. Despite regular clinic follow-ups and blood monitoring, he recently developed tremors and delirium. On hospital admission, serum level of lithium was far above toxic level. Mental state examination revealed an anxious and disorientated man with irrelevant speech. Immediate discontinuation of lithium resulted in slow reduction of serum lithium levels and gradual resolution of tremor but his delirium persisted for 2 weeks. His condition took a turn for the worse when he developed acute renal failure and arm abscess. We discussed about lithium toxicity and the vulnerability factors which have induced delirium and renal failure in this patient.

Matched MeSH terms: Lithium/therapeutic use